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Clusterin: the missing link in the calcium-dependent resistance of cancer cells to apoptogenic stimuli.
The resistance of cancer cells to artificially induced apoptosis comprises a major pitfall in contemporary chemotherapy. In recent years, a wide range of molecular mechanisms was revealed that allow cancer cells to overcome apoptosis. In prostate, breast, and colorectal cancers, a protein named clusterin was identified with anti- or proapoptotic activity regulated by calcium homeostasis. Reports so far suggest "two faces" of clusterin activity: the calcium-dependent cellular retention of clusterin positively correlates with cell survival, whereas nuclear translocation of this protein promotes cell death in calcium-deprived cells. Better understanding of the proprieties of clusterin isoforms and the molecular mechanisms which regulate its activity provide the prospect of breaking down cancer cells' resistance to apoptosis. Thus one might expect such dual benefits as overcoming the "immune escape" of neoplastic cells and reducing the doses of cytostatic drugs, with a concomitant reduction in the side effects of chemotherapy. | {
"pile_set_name": "PubMed Abstracts"
} |
Distribution and Frequency of Fusarium Species Associated with Soybean Roots in Iowa.
A 3-year survey was conducted in Iowa to characterize the distribution and frequency of species of Fusarium associated with soybean roots. Ten plants were collected from each of 40 to 57 fields each year at V2 to V5 and R3 to R4 soybean growth stages. Fusarium colonies were isolated from symptomatic and symptomless roots and identified to species based on cultural and morphological characteristics. Species identification was confirmed by amplification and sequencing of the translation elongation factor (EF1-α) gene. Fifteen species were identified; Fusarium oxysporum was isolated most frequently, accounting for more than 30% of all isolates. F. acuminatum, F. graminearum, and F. solani were also among the most frequent and widespread species. Eleven other species were recovered from few fields, accounting for less than 10% of all isolates in a given year. No consistent trends were observed in geographic distribution of species. Variability in species frequency was found between soybean growth stages. Fusarium oxysporum was recovered at higher frequency during vegetative stages (40%) than reproductive stages (22%). Conversely, species such as F. acuminatum, F. graminearum, and F. solani were recovered more often from reproductive-stage plants. No significant differences in species composition were observed among fields differing in tillage practices and row spacing. | {
"pile_set_name": "PubMed Abstracts"
} |
Decreased blood level of beta 2-microglobulin in the employees of a factory which produced polychlorinated biphenyls.
Under the project of evaluating the health status of the employees of CHEMKO factory (East Slovakia) which produced PCBs between 1955 and 1985, the level of beta 2-microglobulin (beta 2-m) was measured in the serum of 242 subjects from CHEMKO (Group A) and two control groups from much less polluted areas: 1,277 females from a small mountainous village (Group B), 2,179 adults from the area of a large city of Kosice (Group C). The level of thymidine kinase (TK) was measured in the groups A and B only. In addition, age-matched groups of 155 women each from all areas were evaluated. In both the whole group and the age-matched group from CHEMKO the level of beta 2-m was significantly lower (P < 0.001) than that in the respective control groups, while no difference was found in the level of TK. In conclusion, it is suggested that the decrease of beta 2-m in CHEMKO employees might be related to the immunotoxic effects of organochlorines. | {
"pile_set_name": "PubMed Abstracts"
} |
[Hepatic psittacosis: a case of liver abnormality diagnosed by ultrasonography].
Psittacosis marked by liver and spleen involvement and minimal pericarditis was observed in an 18-year-old patient hospitalized for fever of 1 month duration. At admission, there was no other clinical manifestation and the chest X-ray showed no sign of pulmonary involvement. Liver tests revealed cholestasis. Ultrasonography of the abdomen revealed multiple nodular formations in the liver and spleen, images confirmed on computed tomography. Liver biopsy showed granulomatous with hyperplasia of the Kupffer cells surrounded by healthy tissue. Complement fixation to psittacosis antigen was positive and increased significantly over a 15-day interval. Treatment with tetracycline led to rapid remission of the fever and normalization of the liver tests and hepatic images. Liver involvement in psittacosis is not uncommon, but this is apparently the first case reporting echographic anomalies. The absence of pulmonary involvement has been reported earlier in a few cases. The diagnosis is usually suggested on the basis of epidemiologic criteria and confirmed by complement fixation. | {
"pile_set_name": "PubMed Abstracts"
} |
[Rh, Du phenotype in the pregnant woman].
The Rh, Du blood phenotype occurs rarely in the white population (0.23-0.60%). Its clinical significance is whether it should be considered it as Rh positive or negative. A pregnant woman with blood type Rh, Du (+), who delivered an Rh D (+) baby and was not given Rh immune globulin is presented. The Du antigen is manifested by weak expression of the D gene on the RBC envelope, and therefore Rh Du (+) is considered Rh (D) positive. An exception to this rule is the occurrence of transplacental fetomaternal bleeding in an Rh negative mother carrying an Rh positive fetus, when blood is typed close to the time of hemorrhage. In addition, there are other rare phenotypes, such as the D variant and the Du variant, in which there is alloanti-D present in the serum of Rh (D) positive or Rh Du positive patients, causing mild hemolytic disease of the newborn in rare instances. | {
"pile_set_name": "PubMed Abstracts"
} |
Chloroperoxidase-catalyzed oxidation of N-methyl-4-chloroaniline.
Chloroperoxidase catalyzed the H2O2 oxidative conversion of N-methyl-4-chloroaniline to 4-chloronitrosobenzene, 4-chloroaniline and a mixture of complex products. | {
"pile_set_name": "PubMed Abstracts"
} |
Molecular pathology of gastric carcinoma.
Gastric carcinoma (GC) is a biologically heterogeneous disease involving numerous genetic and epigenetic alterations. A very small proportion of GCs can be caused by a specific germ-line mutation of the E-cadherin gene (CDH1). Sporadic GC is developed through multistep processes that begin with Helicobacter pylori-induced atrophic gastritis. Epstein-Barr virus is another infectious cause of GC, and the above two infection-associated GCs are characterized by global CpG island methylation in the promoter region of cancer-related genes. Mutations of tumor protein p53 (TP53) and β-catenin (CTNNB1) genes occur early in the development of GC and contribute to gastric carcinogenesis. Furthermore, significant numbers of GCs show loss of Runx3 due to hemizygous deletion and hypermethylation of the promoter region. Aberrant Cdx2 expression has been shown in precancerous lesions as well as GC. However, it remains unclear whether Cdx2 plays an oncogenic role in gastric carcinogenesis. GC with microsatellite instability is also a well-defined subset exhibiting distinctive clinicopathologic features. Targeted therapy against GC with ERBB2 amplification recently improved the prognosis of patients with advanced GC. In addition, epigenetic changes in GC could be attractive targets for cancer treatment with modulators. A genome-wide search has been undertaken to identify novel methylation-silenced genes in GC, which will help us understand the overall molecular features of GC and further provide novel opportunities in the treatment of GC. | {
"pile_set_name": "PubMed Abstracts"
} |
An assessment of emergent tardive dyskinesia and existing dyskinesia in patients receiving long-acting, injectable risperidone: results from a long-term study.
Treatment-emergent tardive dyskinesia (TD) can be a serious side effect of antipsychotic treatment. Atypical antipsychotics are associated with a lower risk for TD than are conventional agents. A long-acting atypical antipsychotic, with more stable blood levels and lower peak blood levels than an oral formulation, may provide differential benefit regarding side effects, including movement disorders. This analysis assessed TD by defined research criteria in patients receiving long-acting, injectable risperidone. Clinically stable subjects with schizophrenia or schizoaffective disorder participated in a 50-week, open-label trial of long-acting, injectable risperidone. TD was studied by defined research criteria (Schooler, N.R., Kane, J.M., 1982. Research diagnosis for tardive dyskinesia. Arch. Gen. Psychiatry. 39, 486-487; Americal Psychiatric Association, 2000. Diagnostic and Statistical Manual of Mental Disorders, fourth ed. American Psychiatric Association, Washington, DC). The severity of dyskinesia and other movement disorders were rated by the Extrapyramidal Symptom Rating Scale (ESRS). ESRS dyskinesia data were available for 662 patients. Five of 530 subjects without dyskinesia at baseline (0.94%) met the predefined criteria for emergent persistent TD during therapy. Based on either exposure to study medication or Kaplan-Meier analysis, the 1-year rate was 1.19%. Among the 132 subjects with dyskinesia at baseline, the mean score on the ESRS physician's exam for dyskinesia improved significantly at endpoint (-2.77; P<0.0001), regardless of anticholinergic drug use. (P=0.243 for patients with versus without anticholinergic drug use.) In this open-label study, treatment with long-acting risperidone was associated with a low rate of emergent persistent TD. Significant improvement in existing dyskinesias was noted. The TD rate reported here is consistent with other reports of atypical antipsychotics and substantially lower than with conventional antipsychotics. | {
"pile_set_name": "PubMed Abstracts"
} |
Control of renal and extrarenal salt and water excretion by plasma angiotensin II in the kelp gull (Larus dominicanus).
The osmoregulatory effects of intravenously (i.v.) administered angiotensin II (AII) at dose rates of 5, 15 and 45 ng.kg-1.min-1 were examined in kelp gulls utilizing salt gland and/or kidneys as excretory organs. In birds given i.v. infusion of 1200 mOsmolal NaCl at 0.3 ml.min-1 and utilizing only the salt glands to excrete the load, infusion of AII for 30 min consistently inhibited salt gland function in a dose-dependent manner. In birds given i.v. infusion of 500 mOsmolal NaCl at 0.72 ml.min-1 and utilizing both salt glands and kidneys to excrete the load, each dose of AII given for 2 h inhibited salt gland function but stimulated the kidney, so that the overall outputs of salt and water were enhanced and showed significant (2P less than 0.01) positive correlations with plasma AII. In birds given i.v. infusion of 200 mOsmolal glucose at 0.5 ml.min-1 and utilizing only the kidneys to excrete the load, low doses of AII (5 and 15 ng.kg-1.min-1) caused renal salt and water retention, whereas a high dose (45 ng.kg-1.min-1) stimulated salt and water output. The actions of plasma AII in kelp gulls support the concept that this hormone plays a vital role in avian osmoregulation, having effects on both salt gland and kidney function. Elevation of plasma AII consistently inhibits actively secreting salt glands, but its effects upon renal excretion depend primarily on the osmotic status as well as on the plasma AII concentration. In conditions of salt and volume loading doses of AII stimulate sodium and water excretion. With salt and volume depletion, the action of AII is bi-phasic with low doses promoting renal sodium and water retention but high circulating levels causing natriuresis and diuresis. | {
"pile_set_name": "PubMed Abstracts"
} |
Synthesis, structural and magnetic properties of a series of copper(II) complexes containing a monocarboxylated perchlorotriphenylmethyl radical as a coordinating open-shell ligand.
A series of complexes of copper(II)-containing a perchlorotriphenylmethyl radical functionalized with a carboxylic group as a new ligand is reported. The compounds [Cu(PTMMC)(2)(L)(3)](PTMMC = (tetradecachloro-4-carboxytriphenyl)methyl radical; L =(1) H(2)O, (2) pyrimidine and ethanol or (3) pyridine), [Cu(2)(PTMMC)(2)(MeCOO)(2)(H(2)O)(2)](4) and [Cu(HPTMMC)(2)(L)(3)](HPTMMC =alpha-H-(tetradecachlorotriphenyl)methane-4-carboxylic acid; L = pyridine)(5) were structurally characterized. In complexes 1, 2, 3, and 5, the copper(II) ion is coordinated to two PTMMC (or HPTMMC) units in a slightly distorted square planar surrounding, while 4 shows a paddle-wheel copper(II) dimer structure, where each Cu metal ion has four O atoms of different carboxylate groups, two of them belonging to two PTMMC radicals. The copper(II)-radical exchange couplings are antiferromagnetic for complexes 1, 2 and 3. A linear three-spin model was applied to complexes 1, 2 and 3 to give J/k(B)=-24.9, -15.0 and -20.7 K, respectively. Magnetic properties of 4 show that it is one of the scarce examples of a spin-frustrated system composed of organic radicals and metal ions. In this case, experimental data were fitted to a magnetic model based on a symmetrical butterfly arrangement to give a copper(II)-copper(II) exchange coupling of J/k(B)=-350.0 K and a copper(II)-radical exchange coupling of J/k(B)=-21.3 K, similar to that observed for the copper(II)-radical interactions in complexes, and. | {
"pile_set_name": "PubMed Abstracts"
} |
Factors associated with acute and late dysphagia in the DAHANCA 6 & 7 randomized trial with accelerated radiotherapy for head and neck cancer.
Dysphagia is a common and debilitating side effect in head and neck radiotherapy (RT). Prognostic factors are numerous and their interrelationship not well understood. The aim of this study was to establish a multivariate prognostic model for acute and late dysphagia after RT, based on information from a prospective trial. The DAHANCA 6&7 randomized study included 1476 patients with head and neck cancer eligible for primary RT alone. Patients were randomized between 5 and 6 weekly fractions of conventional RT, and received 62-70 Gy in 31-35 fractions. Patients were scored for dysphagia weekly during treatment and at regular intervals until five years after treatment. Dysphagia scores were available from 1461 patients. Acute dysphagia according to DAHANCA grades 1, 2, 3 and 4 occurred in 83%, 71%, 43% and 23%, respectively. Severe dysphagia occurred in 47% and 38% of patients receiving accelerated or conventional radiotherapy, respectively (p = 0.001). At one, two, three, four and five years the prevalence of chronic dysphagia above grade 0, was 46%, 32%, 29%, 24%, 23%, respectively with no difference between 5 and 6 fractions. In multivariate analysis, the following parameters were independent factors for severe acute dysphagia: T3-T4 tumors, N-positive disease, non-glottic cancer, age> median, baseline dysphagia > 1 and accelerated radiotherapy. The following factors were prognostic factors for late dysphagia: non-glottic cancer, T3-T4, N-positive disease and baseline dysphagia > 1. The data confirmed previously published predictive models, as it was possible to separate patients in groups with low, medium and high risk of dysphagia, respectively, based on pre-treatment risk scores. Prognostic models were established to characterize patients at risk of developing acute or late dysphagia in the DAHANCA 6&7 trial. The results may be useful to identify patients at risk of dysphagia and thus candidates for prophylactic measures against swallowing dysfunction. | {
"pile_set_name": "PubMed Abstracts"
} |
[Subchronic oral toxicity study of calcium lactate in F344 rats].
A subchronic toxicity study of calcium lactate was carried out in male and female F344 rats to estimate the maximum tolerated dose for a subsequent long-term toxicity/carcinogenicity study. Experiment I: Rats were divided into 6 groups, each consisting of 5 males and 5 females. Calcium lactate was dissolved in water at concentrations of 5, 2.5, 1.25, 0.6, 0.3 and 0%, each animal group was given one of these solutions as the drinking water for 13 wk. In all groups, basic diet (CRF-1) was given ad libitum. No fatalities occurred. In all treated groups, including the 5% group, a less than 10% depression of body-weight gain as compared with the control group was observed. Some parameters in the hematological and biochemical data demonstrated change in the treated groups. On histological examination, however, no severe toxicological findings were found in any of the treated groups. Experiment II: Rats were fed synthetic diet B, containing 30, 20, 10, 5 or 0% calcium lactate. In the highest dose group, body weight-gain was strongly reduced as compared with the control group. Histological examination revealed nephrocalcinosis in all groups, including the control group, and adverse dose-effect relation was observed with regard to degree of its development. Females exhibited this lesion to a greater extent than males. Experiment III: Rats were given CRF-1 or synthetic diet B for 8 wk. Nephrocalcinosis was found only in the group given synthetic diet. It was ascertained that the nephrocalcinosis observed in Exp. II and III was dependent on the low Ca/P ratio (Ca/P: less than 1) of the synthetic diet B.(ABSTRACT TRUNCATED AT 250 WORDS) | {
"pile_set_name": "PubMed Abstracts"
} |
Lack of evidence for small vessel disease in a patient with "slow dye progression" in the coronary arteries.
A patient with chest pain of recent onset, suggestive for angina pectoris, was referred for diagnostic coronary angiography, which showed the typical phenomenon of "slow dye progression" in the absence of any significant coronary artery stenosis. While intracoronary Doppler measurements confirmed the extremely slow blood flow velocity, the coronary flow reserve and the calculated coronary blood flow proved to be within normal range. The present findings suggest that, in contrast with a previous hypothesis, the phenomenon of slow dye progression may not always be due to a microvascular cause. Epicardial artery disease, as suggested by the marked coronary artery ectasia, may be linked to the slow dye progression and predispose to coronary artery thrombosis. | {
"pile_set_name": "PubMed Abstracts"
} |
[HOME AND AMBULATORY ARTIFICIAL NUTRITION (NADYA) GROUP REPORT, HOME PARENTERAL NUTRITION IN SPAIN, 2014].
to communicate the results of the Spanish Home Parenteral Nutrition (HEN) registry of the NADYASENPE group for the year 2014. data was recorded online by NADYA group collaborators that were responsible of the HPN follow-up from 1st January to 31st December 2014. a total of 220 patients and 229 episodes of HPN were registered from 37 hospitals that represents a rate of 4.7 patients/million habitants/year 2014. The most frequent disease in adults was other diseases (23.3%), neoplasm (20.4%) followed by radical active neoplasm (11.8%) and mesenteric ischemia (10.9%). The most frequent diagnosis for children were the congenital intestinal disorders (33.3%) followed by traumatic short bowel and other diagnosis. the number of participating centers and registered patients increased progressively respect to preceding years. We consider that the HPN should be regulated by the Sanitary Administration within the framework of the National Health Service Interregional Council. And its inclusion in the portfolio of health services of the different Autonomous Comunities would be beneficial for patients and professionals. | {
"pile_set_name": "PubMed Abstracts"
} |
Screening for bioactive natural products from a 67-compound library of Glycyrrhiza inflata.
Licorice shows a variety of pharmacological activities. This work aims to discover bioactive natural products from one botanical source of licorice, Glycyrrhiza inflata. A total of 67 free phenolics were isolated to form a compound library. Based on the bioactivities of licorice, these compounds were screened using cell- or enzyme-based bioassay methods. A total of 11 compounds exhibited potent cytotoxic activities against three human cancer cell lines (HepG2, SW480 and MCF7), while showed little toxicity on human normal cell lines LO2 and HEK293T. A number of chalcones showed remarkable anti-inflammatory activities. Among them, 2 (licochalcone B, IC50 8.78μM), 10 (licoagrochalcone C, IC50 9.35μM) and 13 (licochalcone E, IC50 9.09μM) exhibited the most potent inhibitory activities on LPS-induced NO production, whereas 1, 8, 10, 12 and 13 (IC50 13.9, 7.27, 2.44, 6.67 and 3.83μM) showed potent inhibitory activities on NF-κB transcription. Nine prenylated phenolics were found to be PTP1B inhibitors. Particularly, licoagrochalcone A (4), kanzonol C (7), 2'-hydroxyisolupalbigenin (35), gancaonin Q (45), glisoflavanone (50) and glabrol (53) showed IC50 values of 0.31-0.97μM. Compounds 24 (semilicoisoflavone B, IC50 0.25μM), 26 (allolicoisoflavone B, IC50 0.80μM) and 64 (glabridin, IC50 0.10μM) showed noticeable tyrosinase inhibitory activities. Most of the above bioactive compounds were reported for the first time. | {
"pile_set_name": "PubMed Abstracts"
} |
Slow magnetic relaxation in trigonal-planar mononuclear Fe(II) and Co(II) bis(trimethylsilyl)amido complexes--a comparative study.
Alternating current magnetic investigations on the trigonal-planar high-spin Co(2+) complexes [Li(15-crown-5)] [Co{N(SiMe3)2}3], [Co{N(SiMe3)2}2(THF)] (THF = tetrahydrofuran), and [Co{N(SiMe3)2}2(PCy3)] (Cy = -C6H13 = cyclohexyl) reveal that all three complexes display slow magnetic relaxation at temperatures below 8 K under applied dc (direct current) fields. The parameters characteristic for their respective relaxation processes such as effective energy barriers Ueff (16.1(2), 17.1(3), and 19.1(7) cm(-1)) and relaxation times τ0 (3.5(3) × 10(-7), 9.3(8) × 10(-8), and 3.0(8) × 10(-7) s) are almost the same, despite distinct differences in the ligand properties. In contrast, the isostructural high-spin Fe(2+) complexes [Li(15-crown-5)] [Fe{N(SiMe3)2}3] and [Fe{N(SiMe3)2}2(THF)] do not show slow relaxation of the magnetization under similar conditions, whereas the phosphine complex [Fe{N(SiMe3)2}2(PCy3)] does, as recently reported by Lin et al. (Lin, P.-H.; Smythe, N. C.; Gorelsky, S. I.; Maguire, S.; Henson, N. J.; Korobkov, I.; Scott, B. L.; Gordon, J. C.; Baker, R. T.; Murugesu, M. J. Am. Chem. Soc. 2011, 135, 15806.) Distinctly differing axial anisotropy D parameters were obtained from fits of the dc magnetic data for both sets of complexes. According to density functional theory (DFT) calculations, all complexes possess spatially nondegenerate ground states. Thus distinct spin-orbit coupling effects, as a main source of magnetic anisotropy, can only be generated by mixing with excited states. This is in line with significant contributions of excited determinants for some of the compounds in complete active space self-consistent field (CASSCF) calculations done for model complexes. Furthermore, the calculated energetic sequence of d orbitals for the cobalt compounds as well as for [Fe{N(SiMe3)2}2(PCy3)] differs significantly from the prediction by crystal field theory. Experimental and calculated (time-dependent DFT) optical spectra display characteristic d-d transitions in the visible to near-infrared region. Energies for lowest transitions range from 0.19 to 0.35 eV; whereas, for [Li(15-crown-5)][Fe{N(SiMe3)2}3] a higher value is found (0.66 eV). Zero-field (57)Fe Mößbauer spectra of the three high-spin iron complexes exhibit a doublet at 3 K with small and similar values of the isomer shifts (δ), ranging between 0.57 and 0.59 mm/s, as well as an unusual small quadrupole splitting (ΔEQ = 0.60 mm/s) in [Li(15-crown-5)][Fe{N(SiMe3)2}3]. | {
"pile_set_name": "PubMed Abstracts"
} |
Dietary rescue of fumble--a Drosophila model for pantothenate-kinase-associated neurodegeneration.
Hallervorden-Spatz syndrome (HSS) is a devastating neurological disease, characterized by iron accumulation in the globus pallidus in the basal ganglia. Most HSS cases are caused by mutations in one of the four human pantothenate kinases (PANK2). This PANK2-caused subgroup of HSS is sometimes referred as PKAN (pantothenate-kinase-associated neurodegeneration). No effective treatment for PKAN or HSS is currently available. fumble, a Drosophila mutant that carries a mutation in Drosophila Pank, has many features similar to those of PKAN patients. In this study, we used fumble as a model to evaluate various compounds or nutritional products for their possible therapeutic efficacy. While no product was found to dramatically improve the symptoms, GKE (containing Ginkgo biloba extract and flavone) and vitamin E showed statistically significant beneficial effects. Our studies indicate that pantothenate is of limited value in alleviating fumble phenotypes and also suggest that some compounds might have deleterious effects. | {
"pile_set_name": "PubMed Abstracts"
} |
Cholesteryl ester transfer in hypercholesterolaemia: fasting and postprandial studies with and without pravastatin.
Subjects with hypercholesterolaemia (HC) have increased fasting cholesteryl ester transfer protein (CETP) activity and accelerated cholesteryl ester transfer (CET) from HDL to apo B-containing lipoproteins. The aim of this study was to examine the effects of postprandial lipaemia and pravastatin treatment on plasma triglycerides (TG) and CETP activity and on CET and LDL Stokes' diameter in primary HC (n = 19, total cholesterol > or =6.5, LDL-cholesterol > or =4.5, TG <4.0 mmol/l). Samples were collected fasting and 6 h after an oral fat load (0.88 g/kg body weight) after 6 weeks therapy with placebo or pravastatin 40 mg nocte according to a double-blind randomized cross-over study. Apart from significant reductions in plasma total cholesterol, LDL-cholesterol apo B and TG. pravastatin significantly reduced CETP activity in both the fasting (mean +/- SD, 37.9+/-12.2 to 32.0+/-10.3 nmol/ml plasma per h) and postprandial state (35.5+/-11.3 to 31.3+/-9.5 nmol/ml plasma per h) compared to equivalent placebo phases. CETP activity did not change during postprandial lipaemia despite a significant 45-55% increase in CET to triglyceride-rich lipoproteins (TRL) of d <1.006 g/ml. LDL Stokes' diameter was unchanged postprandially or by pravastatin. The mass of TRL was the strongest contributor to variation in CET in both fasting and postprandial plasma, accounting for at least 77% of the variance of CET. Postprandial TRL-TG was the strongest contributor to variation in fasting LDL Stokes' diameter in untreated HC (54%) whilst HDL-cholesterol was the strongest fasting contributor to variation (45%) for placebo- and pravastatin-treated HC. We conclude that pravastatin may reduce the atherogenicity of the lipoprotein profile in HC by reducing CETP activity. Furthermore, CET is strongly influenced by postprandial lipaemia which may have a cumulative effect on LDL size. | {
"pile_set_name": "PubMed Abstracts"
} |
Fused ring construction around pyrrole, indole, and related compounds via palladium-catalyzed oxidative coupling with alkynes.
The selective synthesis of 1,2,3,4-tetrasubstituted carbazoles can be performed effectively through the palladium-catalyzed oxidative coupling reactions of N-substituted indoles or their carboxylic acid derivatives with alkynes. Unsymmetrically octasubstituted carbazoles can also be obtained by the stepwise couplings of 1-methylpyrrole-2-carboxylic acid with two different alkynes. In addition, the present coupling procedure is applicable to the synthesis of other various heteroarenes possessing di-, tri-, and tetracyclic cores. Some of the products exhibit intense fluorescence in the solid state. | {
"pile_set_name": "PubMed Abstracts"
} |
A lesion categorized between ghost cell odontogenic carcinoma and dentinogenic ghost cell tumor with CTNNB1 mutation.
Ghost cell odontogenic carcinoma (GCOC) is a rare malignant neoplasm characterized by the presence of ghost cells. It is considered to arise either de novo or from a preexisting benign precursor, calcifying odontogenic cyst (COC), or dentinogenic ghost cell tumor (DGCT). We report a case of a 44-year-old Japanese male with a left maxillary tumor. The patient received treatment to resect the left maxillary cyst 25 years prior; however, the details were uncertain. The tumor was resected with clear margins. Taken together with the results of histological and immunohistochemical examinations, the tumor was categorized between GCOC and DGCT, and we diagnosed the tumor as GCOC suggesting similarity to DGCT. Further, we focused on CTNNB1, which encodes β-catenin and is frequently mutated in COCs. In this tumor, we identified CTNNB1 Ser33Cys, one of the mutations typically found in COCs. This finding suggests that CTNNB1 is a common target for the pathogenesis of tumors accompanied by ghost cells. | {
"pile_set_name": "PubMed Abstracts"
} |
Pancreatic retransplantation is associated with poor allograft survival: an update of the United Network for Organ Sharing database.
The aim of the study was to assess outcomes of pancreas retransplantation versus primary pancreas transplantation. Data from the United Network for Organ Sharing database on all adult (age, ≥18 years) subjects who received pancreas and kidney-pancreas transplants between 1996 and 2012 were analyzed (n = 20,854). The subjects were analyzed in the following 2 groups: retransplant (n = 1149) and primary transplant (n = 19,705). Kaplan-Meier analysis demonstrated significantly different patient survival (P < 0.0001) and death-censored graft survival (P < 0.0001) between the primary transplant versus retransplant subjects. Allograft survival was significantly poorer in the retransplantation group. Patient survival was greater in the retransplant group. The results of our study differ from previous studies, which showed similar allograft survival in primary and secondary pancreas transplants. Further studies may elucidate specific patients who will benefit from retransplantation. At the present time, it would appear that pancreas retransplantation is associated with poor graft survival and that retransplantation should not be considered for all patients with primary pancreatic allograft failure. | {
"pile_set_name": "PubMed Abstracts"
} |
Understanding glycemic control in the critically ill: 2011 update.
Intensive monitoring of blood glucose concentrations in critically ill patients has become a standard of care in intensive care units over the past 10 years, following the publication of a single-center randomized trial targeting euglycemia in postoperative patients. This article summarizes the literature describing the relationship between hyperglycemia and mortality in the critically ill, the main findings of the major interventional trials of intensive insulin therapy, the association between hypoglycemia and increased glycemic variability with adverse outcomes, and the impact of a preexisting diagnosis of diabetes. A framework for understanding dysglycemia in the critically ill, an approach that recognizes disturbances in the "3 domains" of glycemic control--hyperglycemia, hypoglycemia, and increased glycemic variability--is presented. Finally, practical considerations relating to the implementation of glycemic management protocols are discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Topical preparations for the treatment of psoriasis: a systematic review.
There is clinical uncertainty about the appropriate use of first-line topical treatments for psoriasis. To assess the relative effectiveness and tolerability of topical treatments for psoriasis suitable for use both in primary and secondary care. All major medical databases of published literature were searched electronically; references of trial reports and recent reviews were searched; authors and companies were contacted for missing data from published reports. The study selection comprised: (1) randomized placebo-controlled trials of topical treatments for psoriasis; and (2) randomized head-to-head studies of the new vitamin D3 derivative treatments for psoriasis that reported clinical outcome using a Total Severity Score (TSS), Psoriasis Area Severity Index or Investigator Assessment of Global Improvement. Eligibility and validity were assessed and data extracted independently by two authors. Clinical outcomes were pooled using a random effect standardized weighted mean difference (SWMD) metric, including 3380 patients randomized in 41 placebo (vehicle)-controlled trials and 4898 patients randomized in 28 head-to-head studies. There was a significant benefit in favour of active treatments against vehicle, SWMD: -1.06 (95% confidence interval [CI]: -1.26 to -0.86), approximately a 2-point improvement on a 12-point TSS after 6-8 weeks of treatment. The only significantly different benefit was for very potent corticosteroids: SWMD: -1.51 (95% CI: -1.76 to -1.25), approximately a 3-point improvement on a 12-point TSS. Head-to-head studies support these findings, except that calcipotriol was estimated to be more effective than dithranol, coal tar and other vitamin D3 derivatives. Polytherapy, using a potent steroid and calcipotriol, was more effective than calcipotriol alone: SWMD 0.42 (95% CI: 0.12-0.72 ) approximately a 0.8-point improvement on a 12-point TSS. No important differences in withdrawal or reporting of adverse events were identified. Trials of short duration neither adequately inform the management of chronic disease nor describe the sequelae of treatment. The evidence base for long-term care, reflecting the disease pathway, should be improved. Combination therapy with topical vitamin D analogues and steroids, and maintenance therapy following treatment response merit further investigation. | {
"pile_set_name": "PubMed Abstracts"
} |
Fertility maintenance and 5-fluorouracil timing within the mammalian fertility cycle.
The mammalian fertility cycle is responsible for tight coordination of molecular, biochemical and cellular events. We have investigated whether timing of 5-fluorouracil (5-FU) chemotherapy within this cycle affects its reproductive toxicology. When this very short half-life, largely S-phase active cytotoxic antimetabolite is administered during the estrous phase (immediate postovulatory) of the fertility cycle, female mice suffer greater subsequent loss of fertility (decreased successful pregnancy rate) than those mice receiving 5-FU during the metestrous, diestrous, or proestrous stages. Pups subsequently born to mothers given 5-FU during the estrous and metestrous stages are of lower weight compared with those born to mothers treated with 5-FU during diestrus or proestrus. Acute lethality is similarly affected by the fertility cycle timing of 5-FU administration. Treatment during estrus is associated with the greatest overall lethal toxicity. This finding indicates that the 5-FU susceptibility of nonreproductive tissues, the integrity of which is essential for survival, may also be coordinated by the mammalian fertility cycle. It is concluded that optimizing the fertility cycle timing of 5-FU (e.g., during the periovulatory, proestrous stage) diminishes the frequency and severity of long-term reproductive damage. | {
"pile_set_name": "PubMed Abstracts"
} |
Monobloc distraction osteogenesis in pediatric patients with severe syndromal craniosynostosis.
The management of the hypoplastic midface in syndromic craniosynostosis remains a great challenge. Frequently, patients have to be operated on numerous times to achieve a satisfactory end result, partially because of the limited skeletal advancement possible when using traditional surgical techniques. During the last decade, however, methods for gradual midfacial distraction have been presented, whereby greater advancements can be obtained. We present four children aged 17 months to 15 years with severe syndromal craniosynostosis in need of midface advancements because of severe respiratory obstruction or severe exophthalmos. These patients were complex cases with several previous craniofacial surgeries (mean of three times, range of two to six times) that yielded insufficient skeletal advancements. They were operated on with gradual monobloc advancements using the Modular Internal Distraction System. The mean length of operations was 370 minutes (range: 240-455 minutes), and the mean amount of perioperative blood transfusion needed was 1,300 ml (range: 280-2,700 ml) or 66.9 ml/kg (range: 31.1-94.9 ml/kg). The patient with the greatest number of previous operations also had the longest operation time as well as the most blood loss. The average midface advancement obtained was 25 mm (range: 20-30 mm), resulting in cessation or a significant decrease of preoperative respiratory problems, reduced exophthalmos, and improved facial profile. Apart from a local infection in one patient with a connective tissue disorder and several previous wound infections, no major postoperative complications were recorded. Distraction osteogenesis has become a versatile and safe technique that allows for large advancements of the midface. | {
"pile_set_name": "PubMed Abstracts"
} |
Laparoscopic repair of Morgagni-Larrey hernia in a child.
Primary laparoscopic repair of Morgagni-Larrey hernia has been described in adult patients but not in children. This is the first report of primary laparoscopic correction in the pediatric age group without using a prosthesis. A Morgagni-Larrey hernia was found incidentally in a 3-year-old-girl. Laparoscopic correction of the defect was performed. After 6 months the patient is doing well. The chest radiograph shows complete resolution of the hernia. The laparoscopic approach allowed repair the hernia with minimal invasiveness. Laparoscopic correction is not difficult except for those hernias in which dense adhesions are present. | {
"pile_set_name": "PubMed Abstracts"
} |
A gene showing sequence similarity to pectin esterase is specifically expressed in developing pollen of Brassica napus. Sequences in its 5' flanking region are conserved in other pollen-specific promoters.
Differential screening of a Brassica napus genomic library led to the isolation of the clone named Bp 19 containing a gene which is highly expressed during microspore development. The accumulation of Bp19 mRNA starts in uninucleate microspores, increases during development reaching a peak in the late stages but declines considerably in mature pollen. The nucleotide sequence of the entire coding region and of extended portions of the 5' and 3' flanking regions was determined. Several homologous cDNA clones were also isolated and sequenced. The Bp 19 gene contains a single intron of 137 bp and gives origin to a mRNA of ca. 1.9 kb which codes for a polypeptide of 584 amino acids. Bp 19 protein has an estimated molecular weight of 63 kilodaltons and has a highly hydrophobic amino terminal region which shows features of a signal peptide. The carboxy half of the Bp 19 protein, starting at amino acid 269, has striking sequence similarity to the pectin esterases of tomato and of the plant pathogen Erwinia chrysanthemi. Four short domains are extremely well conserved in all the three proteins and therefore could represent catalytic sites responsible for enzyme activity. Comparison of the 5' flanking region of the Bp 19 gene with the sequence of other pollen-specific promoters revealed the presence of several conserved regions. These short promoter sequences could correspond to regulatory elements responsible for pollen-specific gene expression. | {
"pile_set_name": "PubMed Abstracts"
} |
Goos-Hänchen induced vector eigenmodes in a dome cavity.
We demonstrate numerically calculated electromagnetic eigenmodes of a 3D dome cavity resonator that owe their shape and character entirely to the Goos-Hänchen effect. The V-shaped modes, which have purely TE or TM polarization, are well described by a 2D billiard map with the Goos-Hänchen shift included. A phase space plot of this augmented billiard map reveals a saddle-node bifurcation; the stable periodic orbit that is created in the bifurcation corresponds to the numerically calculated eigenmode, dictating the angle of its 'V.' A transition from a fundamental Gaussian to a TM V mode has been observed as the cavity is lengthened to become nearly hemispherical. | {
"pile_set_name": "PubMed Abstracts"
} |
[Crystal and molecular structure of the antimalarial agent alpha-(dibutylaminomethyl)-2, 7-dichloro-9-(p-chlorobenzylidene)-4- fluorenemethanol(benflumetol)].
The three-dimensional crystal and molecular structure of benflumetol(I), alpha-(dibutylaminomethyl)-2, 7-dichloro-9-(p-chlorobenzylidene)-4-fluorenemethanol, was determined by X-ray crystallography and compared with the crystal structures of the cinchona alkaloids. The aromatic rings of fluorene-phenyl system of benflumetol are twisted from each other by 52.8 degrees. The torsion angle of N-C-C-O of benflumetol is 47.6 degrees. The intramolecular aliphatic N-O distance in benflumetol is 2.709A, which is close to the N-O distance found in antimalarial cinchona alkaloids. Benflumetol contains an intramolecular hydrogen bond between the aliphatic nitrogen and oxygen atoms, no intermolecular hydrogen bond was found, which is different from the known amino alcohol antimalarials. | {
"pile_set_name": "PubMed Abstracts"
} |
A study of the breast cancer dynamics in North Carolina.
This work is concerned with the study of breast cancer incidence in the State of North Carolina. Methodologically, the current analysis illustrates the importance of spatiotemporal random field modelling and introduces a mode of reasoning that is based on a combination of inductive and deductive processes. The composite space/time analysis utilizes the variability characteristics of incidence and the mathematical features of the random field model to fit it to the data. The analysis is significantly general and can efficiently represent non-homogeneous and non-stationary characteristics of breast cancer variation. Incidence predictions are produced using data at the same time period as well as data from other time periods and disease registries. The random field provides a rigorous and systematic method for generating detailed maps, which offer a quantitative description of the incidence variation from place to place and from time to time, together with a measure of the accuracy of the incidence maps. Spatiotemporal mapping accounts for the geographical locations and the time instants of the incidence observations, which is not usually the case with most empirical Bayes methods. It is also more accurate than purely spatial statistics methods, and can offer valuable information about the breast cancer risk and dynamics in North Carolina. Field studies could be initialized in high-rate areas identified by the maps in an effort to uncover environmental or life-style factors that might be responsible for the high risk rates. Also, the incidence maps can help elucidate causal mechanisms, explain disease occurrences at a certain scale, and offer guidance in health management and administration. | {
"pile_set_name": "PubMed Abstracts"
} |
The health-related utility and health-related quality of life of hospital-treated subjects with type 1 or type 2 diabetes with particular reference to differing severity of peripheral neuropathy.
We characterised symptom severity of diabetic peripheral neuropathy (DPN) in people with diabetes, and correlated this with health-related utility and health-related quality of life. The study was undertaken in Cardiff and the Vale of Glamorgan, Wales. A postal survey was mailed to a random sample of subjects identified as having diabetes. Data were collected on the symptoms of neuropathy using the Neuropathic Total Symptom Score (self-administered) (NTSS-6-6A) and on quality of life using the Quality of Life in Diabetes Neuropathy Instrument (QoL-DN), EueroQoL five dimensions (EQ5D) and Short Form 36 (SF36). Other information, such as demographics and self-reported drug use, was also collected. The anonymised data were linked to routine inpatient and outpatient healthcare data. Responses were received from 1,298 patients. For patients with a clinically confirmed diagnosis of DPN, the mean NTSS-6-SA score was 6.16 vs 3.19 in patients without DPN (p<0.001). Four categories of severity were defined, ranging from none to severe. All quality of life measures showed a deterioration between these groups: the EQ5D(index) fell from an average of 0.81 in those without symptoms to 0.25 in those with severe symptoms, the SF36 general health profile fell from 59.9 to 25.5 (p<0.001) and the QoL-DN increased from 25.8 to 48.1 (p<0.001). Multivariate models also demonstrated that this relationship remained after controlling for other factors. This study demonstrated that severity of DPN symptoms was predictive of poor health-related utility and decreased quality of life. Furthermore, it provides detailed utility data for economic evaluation of treatment of typical diabetes-related morbidity states. Reducing DPN morbidity should be a priority. | {
"pile_set_name": "PubMed Abstracts"
} |
A novel device for the automatic decellularization of biological tissues.
Decellularized biological scaffolds represent a promising solution for tissue engineering. They offer a good substrate for cells in terms of biochemical composition, ultrastructure and mechanical properties without generating an immunogenic response. The aim of this study was to design and develop a device for the automatic decellularization of biological tissues to overcome manual operation limits, toward a good manufacturing practice-compliant process. A versatile, modular and easy-to-use device was designed, able to automatically exchange decellularization fluids and to provide mechanical shaking according to a user-defined protocol. Preliminary decellularization tests were made on porcine abdominal aortas comparing results between conventional process and device-operated process using water, sodium deoxycholate and DNase. Vessels were processed up to 4 cycles of the protocol and after each decellularization cycle histological analyses (hematoxylin-eosin, Movat pentachrome and DAPI stainings) were observed. Preliminary mechanical tests were also performed to compare the mechanical behavior of blood vessels processed with the 2 methods mentioned above. Briefly, the device consists of decellularization chambers, a shaking system and hydraulic modules for the exchange of fluids. The device was bench-tested for functionality and reliability with positive outcomes. The protocol used revealed to be effective, with a progressive tissue decellularization through repeated cycles. No difference between manual and automated operation was observed in histological or mechanical analyses. The developed device is able to automate the decellularization process lowering operator-related risks, and is a reliable and functional tool for clinical use. | {
"pile_set_name": "PubMed Abstracts"
} |
Prevalence of newly diagnosed endometriosis in women attending the general practitioner.
To investigate the prevalence of newly diagnosed endometriosis in premenopausal women who requested a consultation with their general practitioner because of non-gynecological problems. Participants in the study were invited to complete a questionnaire investigating the presence of pain symptoms and infertility. On the basis of the characteristics of these symptoms, some patients underwent gynecological examination and transvaginal ultrasound. Radiological examinations were performed when bowel or bladder endometriosis were suspected. A total of 1291 women without a previous diagnosis of endometriosis were included in the study. On the basis of the symptoms, 108 women were referred to a gynecologist. After gynecological examination and transvaginal ultrasound, endometriosis was suspected in 51 women (47.2%). The diagnosis of endometriosis was confirmed by radiological investigations and/or surgery in 46 patients; the diagnosis of endometriosis was presumed in 2 other women but it was not confirmed by radiological investigations and/or surgery. The prevalence of endometriosis diagnosed by magnetic resonance imaging and/or surgery was 3.6% (46/1291). The prevalence of newly diagnosed symptomatic endometriosis in this study was at least 3.6%. A simple evaluation of symptoms (pain and infertility) that can be performed by a general practitioner facilitates the diagnosis of endometriosis. | {
"pile_set_name": "PubMed Abstracts"
} |
Knudsen vapor pressure measurements on pure materials and solutions dispersed in porous media: molded nitroglycerin tablets.
The gravimetric Knudsen method for vapor pressure measurement may be subject to serious systematic errors when the sample: (a) consists of the volatile component dispersed in an inert porous matrix and/or (b) contains a dissolved polymeric solute. Vaporization of water present as an impurity in the matrix may result in an appreciable "background" mass loss, and "nonequilibrium effects" may be present; i.e., The vapor of interest may be unable to escape from the sample rapidly enough to maintain the equilibrium vapor pressure in the Knudsen cell. Methods for eliminating the interference due to background effects are described, and a theoretical analysis of nonequilibrium effects is presented. The essential validity of the theories for nonequilibrium effects and the effectiveness of the methods for circumventing background effects were verified by experimental studies with molded nitroglycerin tablets. With nitroglycerin tablets, accurate Knudsen vapor pressure data may be obtained using the modified procedures and data analysis presented in this report. | {
"pile_set_name": "PubMed Abstracts"
} |
Heparin-associated thrombocytopenia: nursing implications.
Because of the potential severity of the associated complications, nurses have an essential role in the care of patients with HAT. Bedside nurses have the opportunity to report information that may indicate a change in a patient's condition after administration of heparin. This information could lead to diagnosis of heparin sensitivity and prompt treatment to decrease the associated thrombotic complications. Once HAT is diagnosed, a variety of resources are available as the patient's condition evolves. Primary concerns include determining effective strategies to provide appropriate skin care, educating the patient and the patient's family members, and providing effective continuity of care. Continuity of care is essential to maintain the patient's physical and emotional status and should be provided by a multidisciplinary team that includes physical and occupational therapists, skin care specialists, and clinical nurse specialists. Future topics for nursing research on HAT include the education of nurses, patients, and families about HAT; the most effective nursing interventions; and appropriate treatment for ischemic extremities. By knowing how to respond safely and effectively to a patient's sensitivity to heparin, critical care nurses can have a beneficial impact on the patient's care. | {
"pile_set_name": "PubMed Abstracts"
} |
Identification and crystallisation of a heat- and protease-stable fragment of the bacteriophage T4 short tail fibre.
Irreversible binding of T-even bacteriophages to Escherichia coli is mediated by the short tail fibres, which serve as inextensible stays during DNA injection. Short tail fibres are exceptionally stable elongated trimers of gene product 12 (gp12), a 56 kDa protein. The N-terminal region of gp12 is important for phage attachment, the central region forms a long shaft, while a C-terminal globular region is implicated in binding to the bacterial lipopolysaccharide core. When gp12 was treated with stoichiometric amounts of trypsin or chymotrypsin at 37 degrees C, an N-terminally shortened fragment of 52 kDa resulted. If the protein was incubated at 56 degrees C before trypsin treatment at 37 degrees C, we obtained a stable trimeric fragment of 3 x 33 kDa lacking residues from both the N- and C-termini. Apparently, the protein unfolds partially at 56 degrees C, thereby exposing protease-sensitive sites in the C-terminal region and extra sites in the N-terminal region. Well-diffracting crystals of this fragment could be grown. Our results indicate that gp12 carries a stable central region, consisting of the C-terminal part of the shaft and the attached N-terminal half of the globular region. Implications for structure determination of the gp12 protein and its folding are discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Predicting outcome after cardiac surgery in patients with cirrhosis: a comparison of Child-Pugh and MELD scores.
This study aims to quantify the risk of cardiac surgery in patients with cirrhosis. Records of all adult patients with cirrhosis undergoing cardiac surgery using cardiopulmonary bypass at the Cleveland Clinic (Cleveland, OH) from January 1992 to June 2002 were analyzed for any relationship of Child-Pugh class and/or score and Model for End-Stage Liver Disease (MELD) score with outcome measures of hepatic decompensation and death during the first 3 months after surgery. Forty-four patients underwent coronary artery bypass grafting (16 patients), valve surgery (16 patients), a combination of the 2 procedures (10 patients), or pericardiectomy (2 patients). Twelve patients (27%) developed hepatic decompensation, and 7 patients (16%) died. Proportions of hepatic decompensation were 3 of 31, 8 of 12, and 1 of 1 patients, and death, 1 of 31, 5 of 12, and 1 of 1 patients in Child-Pugh classes A, B, and C, respectively. The association of hepatic decompensation and mortality with Child-Pugh class, Child-Pugh score, and MELD score was significant (P < 0.005). Areas under the receiver operating characteristic curves for mortality were similar for Child-Pugh (0.84 +/- 0.09) and MELD scores (0.87 +/- 0.09). A cutoff Child-Pugh score >7 was found to have a sensitivity and specificity of 86% and 92% for mortality, with a negative predictive value of 97% (95% confidence interval [CI], 83-99) and positive predictive value of 67% (95% CI, 31-91), respectively. However, a similar cutoff value for MELD score could not be established. Child-Pugh score and/or class and MELD score are significantly associated with hepatic decompensation and mortality after cardiac surgery using cardiopulmonary bypass in patients with cirrhosis. Such surgery can be conducted safely in patients with a Child-Pugh score </=7. Patients with a Child-Pugh score >/=8 have a significant risk for mortality. | {
"pile_set_name": "PubMed Abstracts"
} |
The association of selective serotonin reuptake inhibitors use and stroke in geriatric population.
Selective serotonin reuptake inhibitor (SSRI) exposure has controversial results in increasing the stroke risk. With the risk of stroke increased with age, the safety of SSRI use among older adults attracts much concern. We analyzed 28,145 subjects older than 65 years from a subset of a 9-year cohort database from the National Health Insurance Research Database, Taiwan. The survival analysis showed a greater probability of stroke in subjects with SSRI exposure after adjusting other covariates. Compared with other variables, SSRI exposure had the strongest effect (hazard ratio: 2.66, 95% confidence interval: 2.21-3.20). The risk was independent to depression-related stroke risk. The use of SSRIs independently increases the risk of stroke among older patients. SSRIs are still practically safe to most users, providing precautionary measures are taken. | {
"pile_set_name": "PubMed Abstracts"
} |
Identification of TSC-22 as a potential tumor suppressor that is upregulated by Flt3-D835V but not Flt3-ITD.
Transforming growth factor-beta (TGF-beta)-stimulated clone-22 (TSC-22) was originally isolated as a TGF-beta-inducible gene. In this study, we identified TSC-22 as a potential leukemia suppressor. Two types of FMS-like tyrosine kinase-3 (Flt3) mutations are frequently found in acute myeloid leukemia: Flt3-ITD harboring an internal tandem duplication in the juxtamembrane domain associated with poor prognosis and Flt3-TKD harboring a point mutation in the kinase domain. Comparison of gene expression profiles between Flt3-ITD- and Flt3-TKD-transduced Ba/F3 cells revealed that constitutive activation of Flt3 by Flt3-TKD, but not Flt3-ITD, upregulated the expression of TSC-22. Importantly, treatment with an Flt3 inhibitor PKC412 or an Flt3 small interfering RNA decreased the expression level of TSC-22 in Flt3-TKD-transduced cells. Forced expression of TSC-22 suppressed the growth and accelerated the differentiation of several leukemia cell lines into monocytes, in particular, in combination with differentiation-inducing reagents. On the other hand, a dominant-negative form of TSC-22 accelerated the growth of Flt3-TKD-transduced 32Dcl.3 cells. Collectively, these results suggest that TSC-22 is a possible target of leukemia therapy. | {
"pile_set_name": "PubMed Abstracts"
} |
Neural Network Model of the Visual System: Binding Form and Motion.
We propose a neural network model of the visual system of the brain which processes different kinds of attributes such as form and motion in parallel. The model has two separate channels: a channel processing form and a channel processing motion. Each channel has both forward and backward connections, and exhibits selective attention. The selective attention mechanism, however, does not work independently because of the interaction of the two channels, which occurs at their lower layers. Both channels always focus attention on the same object even when many objects are presented simultaneously to the input layer of the model. The model was simulated on a computer: several objects made of moving random dots were applied to the input layer. At first the model focused attention on one of the objects, and detected its form and motion. It then processed the rest of the objects in turn by switching attention. Copyright 1996 Elsevier Science Ltd. | {
"pile_set_name": "PubMed Abstracts"
} |
A multimethod analysis of families with a polydrug-dependent or normal adolescent daughter.
We compared behavioral interactions and perceived relationships in families of drug-dependent and normal adolescent girls. A total of 29 family triads including father, mother, and teenage daughter participated. L. S. Benjamin's (1974) structural analysis of social behavior model and methodology were used to code videotaped interactions and to rate self and other in perceived relationships. Observations of parental behavior toward their daughters did differentiate families of drug abusers from control families, but daughters' behavior did not. Parents communicated a conflictual message of both greater affirmation and condemnation of their daughter's autonomy. Both parents and daughters in the drug-dependent group blamed the daughters, despite their actual behavior, for the family's problems. The findings are interpreted as consistent with social-developmental and psychoanalytic theories of adolescent substance abuse as derailed individuation from the family. | {
"pile_set_name": "PubMed Abstracts"
} |
The roles of experience and domain of expertise in using numerical and verbal probability terms in medical decisions.
Verbal probability terms are frequently used in medical practice. In the present experiment the use of verbal and numerical probability terms in medical decisions was investigated. Interns, residents in surgery and internal medicine, surgeons, and internists were asked to make treatment decisions for three different cases (acute appendicitis, angina pectoris, and an imaginary disease) and were also asked to give numerical interpretations of a series of verbal probability terms. In the second stage of the experiment the respondents received the same cases, but with numerical probability terms. The results showed no effect of context or of domain experience on the interpretation of verbal terms. Residents and experienced surgeons more often agreed on treatment decisions when chance information was presented in numerical terms as compared with verbal terms. Physicians were less confident when verbal terms were presented, but only for the less familiar decision problems. Finally, physicians turned out to be better in Bayesian reasoning when numerical terms were used. Experienced physicians were quite accurate in estimating the posterior probability in the appendicitis case, but not in the imaginary-disease case. | {
"pile_set_name": "PubMed Abstracts"
} |
Relationship between E1A binding to cellular proteins, c-myc activation and S-phase induction.
We recently showed that p300/CREB-binding protein (CBP) plays an important role in maintaining cells in G0/G1 phase by keeping c-myc in a repressed state. Consistent with this, adenovirus E1A oncoprotein induces c-myc in a p300-dependent manner, and the c-myc induction is linked to S-phase induction. The induction of S phase by E1A is dependent on its binding to and inactivating several host proteins including p300/CBP. To determine whether there is a correlation between the host proteins binding to the N-terminal region of E1A, activation of c-myc and induction of S phase, we assayed the c-myc and S-phase induction in quiescent human cells by infecting them with Ad N-terminal E1A mutants with mutations that specifically affect binding to different chromatin-associated proteins including pRb, p300, p400 and p300/CBP-associated factor (PCAF). We show that the mutants that failed to bind to p300 or pRb were severely defective for c-myc and S-phase induction. The induction of c-myc and S phase was only moderately affected when E1A failed to bind to p400. Furthermore, analysis of the E1A mutants that fail to bind to p300, and both p300 and PCAF suggests that PCAF may also play a role in c-myc repression, and that the two chromatin-associated proteins may repress c-myc independently. In summary, these results suggest that c-myc deregulation by E1A through its interaction with these chromatin-associated proteins is an important step in the E1A-mediated cell cycle deregulation and possibly in cell transformation. | {
"pile_set_name": "PubMed Abstracts"
} |
[Role of breast feeding in providing the newborn infant with thyroid hormones].
Radioimmunoassay was conducted to study the content of triiodothyronine and thyroxine in the human milk and in the blood serum of mature and premature newborns. It was established that with the growth of the lactation period the content of triiodothyronine and thyroxine rose; it was, respectively, 0.5 +/- 0.12 and 100.3 +/- 8.4 nmol/l in colostrum, 9.2 +/- 0.7 and 271.3 +/- 14.1 nmol/l in transient milk, 11.1 +/- 1.07 and 405.0 +/- 21.4 nmol/l in fully formed milk. Fully formed milk contains three times more triiodothyronine and thyroxine than the blood serum of newborns. The mature newborns have a sufficiently formed thyroid function. The level of thyroid hormones in the blood serum of premature newborns is decreased in proportion to the stage of their prematurity. They receive the deficient hormones through the human milk. The authors recommend that the nutrition of premature newborns receiving mixed and artificial feeding should be supplemented with thyroid hormones. | {
"pile_set_name": "PubMed Abstracts"
} |
Buthionine sulfoximine induced growth inhibition in human lung carcinoma cells does not correlate with glutathione depletion.
Treatment of A549 human lung carcinoma cells with L-buthionine-[S,R]-sulfoximine (BSO) results concomitantly in cellular glutathione (GSH) depletion and growth inhibition. The nature of BSO effects on cell growth and the relationships between BSO inhibition of cell growth and BSO effects on cellular GSH levels were determined in this study. A dose dependent effect of BSO on cell growth was observed, but this effect was found not to correlate with BSO effects on cellular GSH levels. Treatment with BSO for 60 h at concentrations of 5 and 10 mM was found to deplete cellular GSH at similar rates and to an undetectable level (below 0.5 nmol/mg protein). However, cessation of growth occurred in 10 mM BSO whereas growth continued at better than one half the control rate in 5 mM BSO. The results suggest there may be a distinct threshold level of intracellular GSH (on the order of or less than 0.5 nmol/mg protein) required for cell growth and for cells to protect themselves from the antiproliferative effects of BSO. At a concentration of 10 mM, BSO inhibited both DNA and protein synthesis and arrested growth of A549 cells throughout rather than at a specific phase of the cell cycle. BSO inhibition of growth was not, as indicated by colony-forming efficiency (CFE) and electron microscopy studies, accompanied by indications of cytotoxic effects. A stimulatory effect of 0.1 mM BSO on the growth of A549 cells was found also. | {
"pile_set_name": "PubMed Abstracts"
} |
Cytotoxic T lymphocytes recognize determinants on the BALB/c-H-2Ld molecule controlled by alpha 1 and alpha 2 but not alpha 3 external domains.
We have shown that cytotoxic T lymphocytes (CTL) raised in H-2d mice use H-2Ld but not H-2Dd or H-2Kd antigens as restricting elements in lymphocytic choriomeningitis virus (LCMV) and vesicular stomatis virus (VSV) infections. To localize the regions of H-2Ld protein recognized by CTL, we constructed a recombinant H-2Ld/Dd gene encoding a hybrid antigen with alpha 1 and alpha 2 external domains of H-2Ld and alpha 3, transmembrane and cytoplasmic domains of H-2Dd. The recombinant gene was transfected into mouse cells and the hybrid molecules were characterized serologically, biochemically and functionally. In all assays, H-2Ld/Dd molecules were recognized by LCMV-and VSV-specific H-2Ld-restricted CTL in a manner similar to that of wild-type H-2Ld antigens. Analogous results were obtained with alloreactive CTL. Hybrid antigens containing the alpha 3 domain of H-2Ld fused to alpha 1 and alpha 2 domains of a Qa-2,3 region-encoded antigen were not used as restricting elements by LCMV-specific CTL. These results suggest that H-2Ld-restricted CTL directed against LCMV and VSV recognize determinants controlled by the alpha 1 and/or alpha 2 domains of the H-2Ld molecule. | {
"pile_set_name": "PubMed Abstracts"
} |
Bovine IL-18 ELISA: detection of IL-18 in sera of pregnant cow and newborn calf, and in colostrum.
In this study, we examined the concentration of bovine IL-18 in the sera of pregnant cows, their fetuses and newborn calves, and in colostrum in order to examine the role of IL-18 in bovine pregnancy and the neonatal period. A sandwich-ELISA to quantify bovine IL-18 was established using anti-porcine IL-18 monoclonal antibodies, which cross-reacted with bovine IL-18, and used it to measure the concentration of bovine IL-18 in the sera of pregnant cows, their fetuses and newborn calves, and in colostrum. Significant levels of IL-18 were detected in the sera of pregnant cows, but not in the sera obtained from the corresponding fetuses, umbilical arteries and veins. After birth, IL-18 levels in the sera of 1-day and 1-week old calves were low, and significantly increased in the sera of 1-month and 4-month old calves. IL-18 was also detected in colostrum, with the concentration of IL-18 in the first colostrum produced after delivery being the highest, and then decreasing depending on the number of milkings. Furthermore, the serum IL-18 concentration of newborn calves was increased after the oral administration of colostrum. These results suggest that IL-18 during bovine pregnancy and in the newborn period may play important roles in the maintenance of pregnancy and in the maturation of neonatal immunity. | {
"pile_set_name": "PubMed Abstracts"
} |
[Eight Cases of Primary Carcinoma of the Vermiform Appendix].
Primary carcinoma of the vermiform appendix is a rare neoplasm, and its treatment strategy has not yet been established. We retrospectively analyzed 8 cases of primary carcinoma of the vermiform appendix from 2007 to 2017. Six cases were male and two were female, with a median age of 60.5 years. Ileocecal resection and right hemicolectomy were performed in 7 cases and 1 case, respectively. Regarding pathological staging, 5 cases were of pStage Ⅱ, 2 were of pStage Ⅲa, and 1 was of pStage Ⅳ. Three cases had recurrences after curative resection. The postoperative median overall survival time was 45 months. Three cases with a tumor diameter of 20mm were alive without any recurrence; however, 3 of 5 cases with a tumor diameter of B21mm had recurrences. Although only 1 of 3 cases with adjuvant chemotherapy(pStage Ⅲa case)had recurrence, 2 of 4 cases without adjuvant chemotherapy, including a pStage Ⅱ case, had recurrences. Early diagnosis, surgery, and adjuvant chemotherapy could improve the long-term outcomes of patients with primary carcinoma of the vermiform appendix. | {
"pile_set_name": "PubMed Abstracts"
} |
Esophageal disease in progressive systemic sclerosis.
Progressive systemic sclerosis (PSS) or scleroderma is characterized by fibrosis of the skin and visceral organs. Gastrointestinal disease occurs in up to 90% of patients, with the esophagus being the most commonly affected organ. Heartburn, dysphagia, and regurgitation occur in most patients. Esophageal manometry aids in diagnosing PSS. Endoscopy rules out complications, such as Barrett's esophagus, Candida esophagitis, and cancer. Lifestyle modifications should be implemented, including avoidance of alcohol, nicotine, and NSAIDs. Proton pump inhibitor therapy should be instituted, although it is unclear whether the dose should be adjusted according to symptoms or to 24-hour pH monitoring. Prokinetic agents are useful in the early stages of PSS when gastrointestinal musculature is still intact. Metoclopramide improves reflux, lower esophageal sphincter pressure, and gastric emptying but has an inconsistent effect on esophageal peristalsis. A decision on when to perform antireflux surgery, if at all, is controversial. Esophageal disease in PSS is a common and difficult-to-treat problem. | {
"pile_set_name": "PubMed Abstracts"
} |
Type II collagen in mixed tumors of the skin. An immunohistochemical study and new speculations concerning histogenesis.
We studied 11 cases of mixed tumor of the skin with a polyclonal antibody against human type II collagen. Two of the cases were of the eccrine type, six were apocine, and three were malignant. In all of the benign cases of mixed tumor and in some of the malignant type, "chondroid" and mucinous portions stained. The clearly epithelial portions of the tumor stained as well, and staining was most intense in the eccrine types and least intense in the malignant types. The positive staining in mixed tumors may help elucidate the histogenesis of these unusual tumors as well as help differentiate among the various subtypes. | {
"pile_set_name": "PubMed Abstracts"
} |
The nature of cationic adsorption sites in alkaline zeolites--single, dual and multiple cation sites.
Gas adsorption on zeolites constitutes the base of many technological applications of these versatile porous materials. Quite often, especially when dealing with small molecules, individual extra-framework (exchangeable) cations are considered to be the adsorption site on which molecules coming from a gas phase form the corresponding adsorption complex. Nonetheless, while that can be the case in some instances, recent research work that combines variable temperature infrared spectroscopy with periodic DFT calculations showed that some types of adsorption sites involve two or more cations, which constitute dual and multiple cation sites, respectively. Adsorption complexes formed on these cationic adsorption sites differ in both structure and stability from those formed on a single cation alone. Examples concerning CO, CO(2) and H(2) adsorption on alkali and alkaline-earth metal exchanged zeolites are reviewed, with the double purpose of clarifying concepts and highlighting their relevance to practical use of zeolites in such fields as gas separation and purification, gas storage and heterogeneous catalysis. | {
"pile_set_name": "PubMed Abstracts"
} |
Transient prealbumin-associated hyperthyroxinemia in TSH-producing pituitary adenoma.
This case report describes a 38-year-old male who was hospitalized for further clarification of clinically mild hyperthyroidism. His increased total hormone levels, the elevated free thyroid hormones and the elevated basal TSH with blunted response to TRH strongly suggested a pituitary adenoma with inappropriate TSH incretion. Transmission computed tomography showed an intrasellar expansion, 16 mm in diameter. The neoplastic TSH production was confirmed by an elevated alpha-subunit and a raised molar alpha-sub/TSH ratio. However, T4 distribution on prealbumin (PA, TTR), albumin (A) and thyroxine binding globulin (TBG) showed a clearly increased binding to PA (39%), indicating additional prealbumin-associated hyperthyroxinemia. The absolute values of PA, A and TBG were within the normal range. After removal of the TSH-producing adenoma, basal TSH, the free thyroid hormones and T4 binding to prealbumin returned to normal. Therefore, the prealbumin-associated hyperthyroxinemia had to be interpreted as a transitory phenomenon related to secondary hyperthyroidism (T4 shift from thyroxine binding globulin to prealbumin) rather than a genetically conditioned anomaly of protein binding. | {
"pile_set_name": "PubMed Abstracts"
} |
Tailoring Structure and Field-Effect Characteristics of Ultrathin Conjugated Polymer Films via Phase Separation.
A phase-separation method has been developed to control the semiconductor thickness and molecular arrangement via the semiconducting/insulating polymer blend system. The thickness of the poly(3-hexylthiophene) film has been regulated from 10.5 ± 1.4 nm down to 1.9 ± 0.8 nm with a favorable self-assembly degree and the mobility ranging from 0.21 to 0.03 cm2 V-1 s-1. The ultrathin films show high bias stability and weak decay after 24 days with a bottom-gate configuration. Benefited from a good molecular order, the films have low activation energy and a 2D charge transport profile in semiconductor layers. Moreover, this blending process can be used as a general strategy of thickness control in flexible low-voltage devices and donor-acceptor-conjugated polymers. | {
"pile_set_name": "PubMed Abstracts"
} |
[Immunohistochemical studies on neuronal changes in brain stem nucleus of forensic autopsied cases. I. Various cases of asphyxia and respiratory disorder].
Several nuclei in brain stem are well known to play an important role in supporting human life. However, the connection between neural changes of brain stem and the cause of death is not yet fully understood. To investigate the correlation of brain stem damage with various cause of respiratory disorders, neural changes of the arcuate nucleus (ARC), the hypoglossal nucleus (HN) and the inferior olivary nucleus (IO) were examined using immunohistochemical technique. Based on the cause of death, the forensic autopsy cases were divided into 5 groups as follows. Group I: hanging, ligature strangulation and manual strangulation, Group II: smothering and choking, Group III: drowning, Group IV: respiratory failure, control group: heat stroke and sun stroke. Brain was fixed with phosphate-buffer formalin, and the brain stem was horizontally dissected at the level of apex, then embedded in paraffin. The sections were stained with the antibodies against microtubule-associated protein 2 (MAP2), muscalinic acetylcholine receptor (mAChR), c-fos gene product (c-Fos) and 72 kD heat-shock protein (HSP70). Three nuclei showed no obvious morphological changes in all examined groups. However, in case of asphyxia (Group I to III), neurons in HN were positively stained with both HSP70 and c-Fos antibodies. This may indicate that the occlusion of upper airway results in the neuronal damage of HN without their morphological changes. Positive staining of HSP70 and c-Fos in IO was more frequently observed in Group III than other 4 groups. Since IO is involved in maintaining body balance which is often disturbed by drowning, it seems possible that neuronal damage in IO observed in drowning may be related to the disturbance of body balance. These observations indicate that immunohistochemical study on the damage to neurons in brain stem nuclei can provide useful information for determining the cause of death. | {
"pile_set_name": "PubMed Abstracts"
} |
Proteolysis during in vitro-maturation of rabbit reticulocytes.
We investigated the ATP-dependent proteolysis, cytochrome oxidase and the succinate-cytochrome c-oxidoreductase in reticulocytes under different conditions of incubation in vitro at 37 degrees C. Under standard conditions the proteolysis virtually stops after 4 h. The degradation of the stroma proteins amounted to 30-65% depending on the percentage of reticulocytes. The decrease of the cytochrome oxidase amounted to 70% after 20 h of incubation. Inhibition of the cytosolic reticulocyte lipoxygenase (LOX) by the reversible inhibitor salicylhydroxamate (SHAM) leads to an inhibition of both proteolysis and cytochrome oxidase activity by about two-thirds after 20 h of incubation. In the presence of a Ca++-ionophore the rate of proteolysis was increased by 33%, while the cytochrome oxidase and succinate-cytochrome c-oxidoreductase activities both decreased more rapidly than in the control experiments. | {
"pile_set_name": "PubMed Abstracts"
} |
[A case of deep cerebral venous thrombosis with sudden convulsion after delivery].
A 25-year-old woman was admitted to our hospital because of convulsions after delivering a baby. Her neurological examination revealed a disturbance of consciousness and weakness in both arms. A brain magnetic resonance imaging scan (MRI) showed thrombosis of the left transverse sinus and many patchy high signals at bilateral basal ganglia and subcortical areas. A digital subtraction angiogram (DSA) of the brain revealed a defect at the left transverse sinus, congestion of the cerebral venous flow at the vein of Galen and vasospastic changes at both posterior cerebral arteries. After treating the patient with a venous infusion of heparin, nicardipine and phenytoin, her neurological deficits improved within a day. When MRI and DSA were repeated 2 weeks later, the abnormal lesions had disappeared. These findings suggest that venous thrombosis and vasospasm had the pathogenesis of eclampsia in this case. | {
"pile_set_name": "PubMed Abstracts"
} |
Fosfomycin penetration into the cerebrospinal fluid of patients with bacterial meningitis.
A comparative study was made of the penetration of fosfomycin, penicillin G, ampicillin and chloramphenicol into the cerebrospinal fluid of patients with meningitis treated with combinations of fosfomycin and one of the other three antibiotics. Minimal inhibitory concentrations and in vitro interaction of these antibiotics against Streptococcus pneumoniae and Neisseria meningitidis strains were determined. 90-96.5% of these strains were sensitive to penicillin G, 95-96.5% to ampicillin, 85-100% to chloramphenicol and 90-100% to fosfomycin. Fosfomycin shows a more marked synergism with penicillin G or ampicillin than with chloramphenicol against both bacterial species. The percentages of penetration into the cerebrospinal fluid were: chloramphenicol, 32%; fosfomycin, 25.7%; ampicillin, 15.9%, and penicillin G, 7.9%. The clinical results show that the combination of fosfomycin + penicillin G or fosfomycin + ampicillin can be an alternative in the treatment of meningitis produced by moderately susceptible strains of S. pneumoniae and N. meningitidis to penicillin G and ampicillin. | {
"pile_set_name": "PubMed Abstracts"
} |
[Numerus clausus at the end of the third year of medical school].
Owing to the establishment of a procedure aiming at a reduction of the medical supply (numerus clausus), the French Community of Belgium had decided to introduce, at the end of the third year of medical studies (third candidature), a procedure of selective attribution of the certificate allowing for a unlimited medical practice. We assessed the predictive value of the results obtained during and at the end of the first candidature (first year of medicine) for the attribution of this certificate. We studied the results of the 225 students enrolled in the first candidature in medicine at the University of Liège during the academic year 1997-1998, and we correlated them to the subsequent attribution (1999-2000- and 2000-2001) of the certificate. The success of the first candidature in the first or second session is an important predicting factor towards the reception of the certificate. A non-authorization to continue the studies in medicine in case of failure in the first session or a non-authorization to repeat the first candidature in case of failure in the second session would have, respectively, a negative predictive value (NPV) of 91.9% and 97.4% and would allow to restream 111 students at the end of the first session or 39 students at the end of the first candidature. The results of the preliminary assessments mode during the month of January are also highly predictive of the chances to get the certificate. Among the 160 students who have not successfully passed a minimum of 3 exams, only 14 students obtained the certificate. The restreaming of those students would correspond to a NPV of 91.2%. Students who were not successful in a minimum of 2 exams would have less than 5% chance to obtain the certificate. In this case, 109 students would be restreamed (NPV = 95.4%). In conclusion, the selection of the students who will obtain, at the end of the third year of medicine, the certificate allowing them for an unlimited medical practice is obtained, in a large proportion, during the first candidature and especially after the session of January. In view of those results and considering the decree abolishing the selection at the end of the third year of medical studies, one could argue about the appropriateness of the current procedure, chosen by the French Community of Belgium, compared to other solutions prioritising an earlier selection of the future doctors. | {
"pile_set_name": "PubMed Abstracts"
} |
Enhanced in vivo sensitivity of vanadyl-treated diabetic rats to insulin.
Vanadium has been reported to have insulin-like properties and has recently been demonstrated to be beneficial in the treatment of diabetic animals. In the present study, concentration dependence of the therapeutic effects of vanadium and the nature of interaction under in vivo conditions between vanadium and insulin were examined in streptozotocin-diabetic rats. During a 2-week period, blood glucose levels in all treated animals were decreased. At higher concentrations of vanadyl this decrease was greater and more rapid, and remained consistently lower for the entire treatment period. Daily intake of vanadyl, however, reached a similar steady state in all groups. Acute administration of submaximal doses of insulin, which had minimal effects in untreated diabetic rats, lowered blood glucose concentrations in vanadyl-treated and vanadyl-withdrawn animals to control levels. Chronic treatment of streptozotocin-diabetic rats with submaximal levels of vanadyl and insulin, ineffective alone, also produced significant decreases in blood glucose levels when used in combination. Finally, the insulin dosage required to maintain a nonglycosuric state in spontaneously diabetic (BB) rats was reduced in the presence of vanadyl. These studies indicate that chronic oral vanadyl treatment (a) produces a concentration-related lowering of blood glucose in diabetic rats, (b) potentiates the in vivo glucose lowering effects of acute and chronic administrations of insulin in streptozotocin-diabetic rats, and (c) substitutes for, or potentiates, the effects of chronic insulin therapy in spontaneously diabetic BB rats. | {
"pile_set_name": "PubMed Abstracts"
} |
Hepatitis C virus genotypes in Tirana, Albania.
Hepatitis C virus (HCV) infection is a worldwide concern. Knowledge of the HCV genotype is clinically important because it predicts the rate of response to therapy and guides the treatment duration. Moreover, it allows molecular epidemiology to be performed. To our knowledge, the prevalence of HCV genotypes has been assessed only once in Albania, using a line probe genotyping assay. We determined HCV genotypes by population sequencing of HCV-infected patients in Tirana, Albania. HCV genotype and sequence analyses were performed for serum samples collected from January 2011 through May 2012 from 61 HCV-seropositive patients using population sequencing of the NS3 protease gene and alternatively the NS5b gene and the 5' untranslated region (UTR). HCV RNA was retrieved from the blood samples of 50 patients. The HCV NS3 protease gene was sequenced for 28 patients and NS5b and/or 5'UTR fragments were sequenced for an additional 22 patients. The predominant genotype was 1b in 25 patients (50%), followed by genotypes 2c, 4a, 3a, and 1a in 18%, 14%, 8%, and 6% of cases, respectively. Best matches for these HCV RNAs in GenBank were obtained in different countries worldwide. One NS3 protease naturally harbored an amino acid conferring minor drug resistance to newly available HCV protease inhibitors. In conclusion, HCV-1b was predominant in the present Albanian population, as in southeastern Europe. | {
"pile_set_name": "PubMed Abstracts"
} |
Inhibition of cellular uptake of folate by blocking synthesis of the membrane folate receptor.
The folate receptor, bound to the plasma membrane through a glycosylphosphatidylinositol anchor, requires both sphingolipids and cholesterol in the membrane for full activity. In recent studies, treatment of cells in culture with the mycotoxin fumonisin B1, which inhibits sphingolipid synthesis, virtually abolished uptake of 5-methyltetrahydrofolate. | {
"pile_set_name": "PubMed Abstracts"
} |
Presence of immunoglobulin binding factor on human sperm surface as sperm coating antigen.
The presence of IgBF as a sperm-coating antigen was demonstrated by showing that anti-IgBF antibodies agglutinate and immobilize human sperm and by localizing IgBF on sperm surface by immunofluorescence staining. Several components interacting with sperm immobilizing antibodies, known to be involved in infertility, are sperm-coating antigens. Anti-IgBF antibody in vitro did not block the ability of human sperm to penetrate human zona pellucida and zona-free hamster egg. Anti-IgBF activity of sera obtained from infertile women did not correlate with the titers of anti-sperm antibodies measured by the sperm immobilization test. IgBF is a sperm-coating antigen and may play a role in suppressing antibody production against alloantigenic sperm in the female reproductive tract. | {
"pile_set_name": "PubMed Abstracts"
} |
[The Correlation between the Size of Vocal Polyps, Vocal Nodules and Vocal Dysfunction, before and after Laryngeal Microsurgery].
When we operate on a vocal polyp or a vocal nodule with laryngeal microscopy, we always carefully measure their length and width then multiply the length by the width to get the area. We examined whether there is a correlation between the area of these lesions and the acoustic analysis of voice. Before the surgery and one month post-operation, we checked five acoustic parameters, maximum phonation time (MPT), range of voice, mean air flow rate (MFR) and acoustic analyses (jitter% and shimmer%). By doing this, we could arrive at the improvement rate of each of the five acoustic parameters. We examined whether there was a correlation between the lesion area and acoustic parameters before surgery and the improvement rates of these acoustic parameters. Examinations of polyps showed a correlation between the size and range of voice and Jitter% pre-operation, and showed a correlation between the size and improvement rate of range of voice, MFR, Jitter% and Shimmer% post-operation. On the other hand, examination of nodules showed a correlation only between the size and range of voice pre-operation. Next we examined the correlation between the size and these acoustic parameters in the Elite vocal performer (EVP) group and extra EVP group. In the examinations of polyps, the EVP group showed a lower correlation between the size and acoustic parameters than in the extra EVP group. On the other hand, in the examinations of nodules, correlation between the size and acoustic parameters was low in both the EVP and extra EVP group. | {
"pile_set_name": "PubMed Abstracts"
} |
Compound-Specific Chlorine Isotope Analysis of the Herbicides Atrazine, Acetochlor, and Metolachlor.
A gas chromatography-single quadrupole mass spectrometry method was developed and validated for compound-specific chlorine isotope analysis (Cl-CSIA) of three chlorinated herbicides, atrazine, acetochlor, and metolachlor, which are widespread contaminants in the environment. For each compound, the two most abundant ions containing chlorine (202/200 for atrazine, 225/223 for acetochlor, and 240/238 for metolachlor) and a dwell time of 30 ms were determined as optimized MS parameters. A limit of precise isotope analysis for ethyl acetate solutions of 10 mg/L atrazine, 10 mg/L acetochlor, and 5 mg/L metolachlor could be reached with an associated uncertainty between 0.5 and 1‰. To this end, samples were measured 10-fold and bracketed with two calibration standards that covered a wide range of δ37Cl values and for which amplitudes matched those of the samples within 20% tolerance. The method was applied to investigate chlorine isotope fractionation during alkaline hydrolysis of metolachlor, which showed a shift in δ37Cl of +46‰ after 98% degradation, demonstrating that chlorine isotope fractionation could be a sensitive indicator of transformation processes even when limited degradation occurs. This method, combined with large-volume solid-phase extraction (SPE), allowed application of Cl-CSIA to environmentally relevant concentrations of widespread herbicides (i.e., 0.5-5 μg/L in water before extraction). Therefore, the combination of large-volume SPE and Cl-CSIA is a promising tool for assessing the transformation processes of these pollutants in the environment. | {
"pile_set_name": "PubMed Abstracts"
} |
Development of high-resolution melting (HRM) analysis for population studies of Fascioloides magna (Trematoda: Fasciolidae), the giant liver fluke of ruminants.
The high-resolution melting (HRM) technique was successfully optimized as fast and effective method for population study of digenetic fluke, Fascioloides magna (Trematoda: Fasciolidae), originally North American liver parasite of free-living and domestic ruminants. Previously selected variable region (439 bp) of mitochondrial cytochrome c oxidase subunit I (cox1) of 249 fluke individuals from enzootic European and North American regions were sequenced and mutually compared. The sequence analysis of partial cox1 revealed presence of seven structurally different haplotypes. Based on the sequence structure and alignments of six of them (Ha1-Ha6), three internal probes were designed and applied in HRM-based haplotype determination of all F. magna specimens. HRM analysis, performed with three designed probes, resulted in classification of samples into the seven haplogroups, equally with their assortment according to the sequence analysis. The representative of the haplotype, which was not involved in probe design (Ha7), was characterized by a unique melting curve shape as well. This provided an evidence of optimally settled conditions in HRM assay and indicated a probability of successful discrimination of novel haplotypes in future population studies on F. magna. The successful optimization of HRM method stands for an opportunity of detection of genetically unknown North American variants of F. magna and promises its application as fast and cheap screening technique for phylogeography studies of the giant liver fluke on its original continent. | {
"pile_set_name": "PubMed Abstracts"
} |
Neuropeptidergic mediators of spontaneous physical activity and non-exercise activity thermogenesis.
Lean individuals have high levels of spontaneous physical activity (SPA) and the energy expenditure derived from that activity, termed non-exercise activity thermogenesis or NEAT, appears to protect them from obesity. Conversely, obesity in different human populations is characterized by low levels of SPA and NEAT. Like in humans, elevated SPA in rats appears to protect against obesity: obesity-resistant rats have significantly greater SPA and NEAT than obesity-prone rats. We review the literature on brain mechanisms important in mediating SPA and NEAT. The focus is on neuropeptides, including cholecystokinin, corticotropin-releasing hormone (also known as corticotropin-releasing factor), neuromedin U, neuropeptide Y, leptin, agouti-related protein, orexin-A (also known as hypocretin-1), and ghrelin. We also review information regarding interactions between these neuropeptides and dopamine, a neurotransmitter important in mediating motor function. Finally, we present evidence that elevated signaling of pathways mediating SPA and NEAT may protect against weight gain and obesity. | {
"pile_set_name": "PubMed Abstracts"
} |
[Bone density in idiopathic hypercalciuria in men. Study by dual photon absorptiometry, X-ray computed tomography and histomorphometry].
Lumbar bone mineral density (BMD) of the L3 vertebra was evaluated by double photon absorptiometry or tomodensitometry (TDM) in 55 hypercalciuric individuals in two separate studies. In the first, in a department of nephrology, 29 lithiasis patients were studied by TDM of L3. By this technique, trabecular density was 75 +/- 23% of normal. It was lower in the 17 patients in whom hypercalciuria persisted after calcium restriction (66 +/- 15% of normal and below the "fracture threshold" in 9 cases) than in the 12 patients in whom it disappeared after the prescription of such a diet (88 +/- 26%, below the "fracture threshold" in 3 cases), this difference being significant (p less than 0.01). In another 26 patients, seen in a department of rheumatology, three of whom had osteoporosis with vertebral fracture, density was measured in 21 cases by double photon absorptiometry (mean Z score -1.9 +/- 1.0) and in 5 cases by TDM (mean BMD of L3 69 +/- 21% of normal). Mean iliac trabecular volume, measured in 8 cases only, was 70 +/- 25% of normal and was below the "fracture threshold" in 3 cases. Comparison of the two study groups was not possible because of differences in recruitment and methods of investigation. These two studies nevertheless show the existence of significant vertebral bone rarefaction during hypercalciuria in the young man. Confirmed and quantified in patients in whom the metabolic disturbance was discovered as a result of radiological abnormalities, this quantitative abnormality was also seen in patients in whom hypercalciurie was found because of renal lithiasis.(ABSTRACT TRUNCATED AT 250 WORDS) | {
"pile_set_name": "PubMed Abstracts"
} |
Social capital: implications from an investigation of illegal anabolic steroid networks.
Numerous studies have linked the constructs of social capital with behaviours that are health enhancing. The factors of social trust, social cohesion, sense of belonging, civic involvement, volunteer activity, social engagement and social reciprocity are all associated with social capital and their existence is often linked with communities or settings where health enhancement is high. Utilizing an interpretive perspective, this paper demonstrates how the existence of social capital may enhance the transition into drug use, the experience of using an illegal drug and decrease the risk of detection. It highlights how social capital may contribute to behaviours which are not health enhancing. Using a variety of data, including participant observation of 147 male anabolic steroid users and 98 semi-structured in-depth interviews with male anabolic steroid users, dealers and distributors it was found that social capital facilitated the operation of the illegal anabolic steroid distribution network. The subcultural norms and social trust that existed within the network allowed anabolic steroid dealers to sell the drug to others with reduced risk of detection. It is argued that social capital facilitates the distribution of illegal anabolic steroids and that social capital is a non-discriminatory concept, that may enhance both negative and positive health-related behaviours. | {
"pile_set_name": "PubMed Abstracts"
} |
Identification of a macrophage-specific cell surface antigen.
A mouse-specific macrophage antigen (MSMA) was identified in NP-40 extracts of 125I-radiolabeled mouse preitoneal macrophages by using a rabbit anti-mouse macrophage serum (AMS) and SDS-polyacrylamide gel electrophoresis. The antigen was shown to have a m.w. of 83,000 daltons and was present on both normal and "activated" peritoneal macrophages. MSMA was also present on syngeneic adherent spleen cells, allogeneic peritoneal macrophages, a mouse macrophage cell line (P388D1), and exhibited some cross-reactivity with peritoneal macrophages from closely related species (rats and hamsters). MSMA was not present on nonadherent peritoneal exudate cells, spleen cells, erythrocytes, thymocytes, or bone marrow cells. Extensive absorptions of AMS with thymocytes and erytrocytes from mice were necessary to remove other antibodies that reacted with other mouse membrane antigens. An antiserum directed against a specific membrane antigen has great potential in elucidating structure-function relationships with regard to a number of macrophage activities. | {
"pile_set_name": "PubMed Abstracts"
} |
Necessary but not sufficient: motion perception is required for perceiving biological motion.
Researchers have argued that biological motion perception from point-light animations is resolved from stationary form information. To determine whether motion is required for biological motion perception, we measured discrimination thresholds at isoluminance. Whereas simple direction discriminations falter at isoluminance, biological motion perception fails entirely. However, when performance is measured as a function of contrast, it is apparent that biological motion is contrast-dependent, while direction discriminations are contrast invariant. Our results are evidence that biological motion perception requires intact motion perception, but is also mediated by a secondary mechanism that may be the integration of form and motion, or the computation of higher-order motion cues. | {
"pile_set_name": "PubMed Abstracts"
} |
Additive manufacturing for in situ repair of osteochondral defects.
Tissue engineering holds great promise for injury repair and replacement of defective body parts. While a number of techniques exist for creating living biological constructs in vitro, none have been demonstrated for in situ repair. Using novel geometric feedback-based approaches and through development of appropriate printing-material combinations, we demonstrate the in situ repair of both chondral and osteochondral defects that mimic naturally occurring pathologies. A calf femur was mounted in a custom jig and held within a robocasting-based additive manufacturing (AM) system. Two defects were induced: one a cartilage-only representation of a grade IV chondral lesion and the other a two-material bone and cartilage fracture of the femoral condyle. Alginate hydrogel was used for the repair of cartilage; a novel formulation of demineralized bone matrix was used for bone repair. Repair prints for both defects had mean surface errors less than 0.1 mm. For the chondral defect, 42.8+/-2.6% of the surface points had errors that were within a clinically acceptable error range; however, with 1 mm path planning shift, an estimated approximately 75% of surface points could likely fall within the benchmark envelope. For the osteochondral defect, 83.6+/-2.7% of surface points had errors that were within clinically acceptable limits. In addition to implications for minimally invasive AM-based clinical treatments, these proof-of-concept prints are some of the only in situ demonstrations to-date, wherein the substrate geometry was unknown a priori. The work presented herein demonstrates in situ AM, suggests potential biomedical applications and also explores in situ-specific issues, including geometric feedback, material selection and novel path planning techniques. | {
"pile_set_name": "PubMed Abstracts"
} |
Diagnosing Distensible Venous Malformations of the Orbit With Diffusion-weighted Magnetic Resonance Imaging.
To compare the diffusion-weighted imaging of nonthrombosed distensible venous malformations of the orbit with that of other histologically-proven orbital tumors. Retrospective case-control study. Patients with nonthrombosed distensible venous malformations of the orbit and patients with other histologically-proven orbital tumors were selected for chart review. The main outcome measure was the apparent diffusion coefficient of these lesions. Sixty-seven patients qualified for chart review; 9 patients had nonthrombosed distensible venous malformations and 58 patients had other histologically-proven tumors. Three of the 9 patients with nonthrombosed distensible venous malformations were initially misdiagnosed as having had solid orbital tumors. The mean apparent diffusion coefficient of distensible venous malformations was 2.80 ± 0.48 × 10-3 mm2/s, whereas the mean apparent diffusion coefficient of other histologically-proven tumors was 1.18 ± 0.39 × 10-3 mm2/s (P < .001). The mean apparent diffusion coefficient ranged from 2.42 to 3.94 × 10-3 mm2/s in the distensible venous malformation group, whereas other histologically-proven tumors ranged from 0.53 to 2.08 × 10-3 mm2/s. Therefore, in this single-institution series, a threshold value of 2.10 × 10-3 mm2/s was 100% sensitive and 100% specific for distensible venous malformations. Certain nonthrombosed distensible venous malformations can evade diagnostic suspicion and mimic solid orbital tumors on standard magnetic resonance imaging sequences. In this single-institution series, diffusion-weighted imaging effectively distinguished these nonthrombosed distensible venous malformations from other orbital tumors. | {
"pile_set_name": "PubMed Abstracts"
} |
Association of angiotensin II receptor 1 and lectin-like oxidized low-density lipoprotein receptor-1 mediates the cardiac hypertrophy induced by oxidized low-density lipoprotein.
To date the molecular mechanism of cardiac hypertrophy has not been completely elucidated. Since oxidized low-density lipoprotein (ox-LDL) is considered a risk marker for early ventricular remodeling, we speculated that ox-LDL may be related to cardiac hypertrophy. We observed the significantly upregulation of plasma ox-LDL and hypertrophic responses, such as cardiomyocyte size and specific gene expressions in Apo E-/- mice fed with high fat diet, accompanied by the upregulation of AT1-R and lectin-like oxidized low-density protein receptor 1 (LOX-1). Ox-LDL treatment with neonatal rat cardiomyocyte for 24 h significantly induced similar hypertrophic responses and also upregulation of AT1-R and LOX-1. The analysis of co-immunoprecipitation and the bimolecular fluorescence complementation assay proved that LOX-1 and AT1-R could directly bind together in the presence of ox-LDL, suggesting a critical role of the association between LOX-1 and AT1-R in ox-LDL-induced cardiac hypertrophy. Furthermore, we found that the AT1-R blocker Losartan and LOX-1 neutralizing antibody through inhibiting AT1-R or LOX-1 could both decline ox-LDL-induced hypertrophic responses whereas angiotensin converting enzyme inhibitor Enalapril only partially inhibited the responses stimulated by ox-LDL. These findings suggested that ox-LDL could induce cardiac hypertrophy through the direct association of AT1-R and LOX-1. | {
"pile_set_name": "PubMed Abstracts"
} |
Solid-phase microextraction Arrow for the volatile organic compounds in soy sauce.
A novel solid-phase microextraction Arrow was used to separate volatile organic compounds from soy sauce, and the results were verified by using gas chromatography with mass spectrometry. Solid-phase microextraction Arrow was optimized in terms of three extraction conditions: type of fiber used (polydimethylsiloxane, polyacrylate, carbon wide range/polydimethylsiloxane, and divinylbenzene/polydimethylsiloxane), extraction temperature (40, 50, and 60°C), and extraction time (10, 30, and 60 min). The optimal solid-phase microextraction Arrow conditions were as follows: type of fiber = polyacrylate, extraction time = 60 min, and extraction temperature = 50°C. Under the optimized conditions, the solid-phase microextraction Arrow was compared with conventional solid-phase microextraction to determine extraction yields. The solid-phase microextraction Arrow yielded 6-42-fold higher levels than in solid-phase microextraction for all 21 volatile organic compounds detected in soy sauce due to the larger sorption phase volume. The findings of this study can provide practical guidelines for solid-phase microextraction Arrow applications in food matrixes by providing analytical methods for volatile organic compounds. | {
"pile_set_name": "PubMed Abstracts"
} |
POLLEN DISCOUNTING AND THE SPREAD OF A SELFING VARIANT IN TRISTYLOUS EICHHORNIA PANICULATA: EVIDENCE FROM EXPERIMENTAL POPULATIONS.
Floral traits that increase self-fertilization are expected to spread unless countered by the effects of inbreeding depression, pollen discounting (reduced outcross pollen success by individuals with increased rates of self-fertilization), or both. Few studies have attempted to measure pollen discounting because to do so requires estimating the male outcrossing success of plants that differ in selfing rate. In natural populations of tristylous Eichhornia paniculata, selfing variants of the mid-styled morph are usually absent from populations containing all three style morphs but often predominate in nontrimorphic populations. We used experimental garden populations of genetically marked plants to investigate whether the effects of population morph structure on relative gamete transmission by unmodified (M) and selfing variants (M') of the mid-styled morph could explain their observed distribution. Transmission through ovules and self and outcross pollen by plants of the M and M' morphs were compared under trimorphic, dimorphic (S morph absent), and monomorphic (L and S morphs absent) population structures. Neither population structure nor floral morphology affected female reproductive success, but both had strong effects on the relative transmission of male gametes. The frequency of self-fertilization in the M' morph was consistently higher than that of the M morph under all morph structures, and the frequency of self-fertilization by both morphs increased as morph diversity of experimental populations declined. In trimorphic populations, total transmission by the M and M' morphs did not differ. The small, nonsignificant increase in selfing by the M' relative to the M morph was balanced by decreased outcross siring success, particularly on the S morph. In populations lacking the S morph, male gamete transmission by the M' morph was approximately 1.5 times greater than that by the M morph because of both increased selfing and increased success through outcross pollen donation. Therefore, gamete transmission strongly favored the M' morph only in the absence of the S morph, a result consistent with the distribution of the M' morph in nature. This study indicates that floral traits that alter the selfing rate can have large and context-dependent influences on outcross pollen donation. | {
"pile_set_name": "PubMed Abstracts"
} |
The regulation of protein kinase C by chenodeoxycholate, deoxycholate and several structurally related bile acids.
There is increasing evidence that the enzyme protein kinase C (PKC) mediates the action of phorbol ester tumor promoters and also the action of certain growth factors. The present studies indicate that the bile acids chenodeoxycholate and deoxycholate inhibit the Ca2+-phosphatidylserine (PS)-dependent activity of PKC in the presence of 1 mM Ca2+, whereas seven structurally related bile acids do not detectably inhibit the enzyme under these conditions. Chenodeoxycholate and deoxycholate appear to inhibit PKC by interactions with both Ca2+ and PS, since their inhibitory potencies are reduced at an elevated PS concentration and since both of these bile acids actually enhance PKC activity, approximately 2-fold, when assayed at an elevated Ca2+ concentration (2 mM). Seven related bile acids also caused an approximately 2-fold enhancement of PKC activity in the presence of 2 mM Ca2+. Chenodeoxycholate and deoxycholate also caused an approximately 1.3-fold enhancement of PKC activity in the presence of 12-O-tetradecanoyl phorbol 13-acetate (TPA) and PS, and the absence of added Ca2+. Thus, depending on the reaction conditions, specific bile acids can act directly to inhibit or enhance PKC activity. There is evidence that during colon cancer formation, both in rodents and in humans, bile acids may act as tumor promoters. Thus the mediation of tumor promotion by bile acids in vivo may involve direct activation of PKC by the bile acids themselves. The present results suggest that the relative extents of absorption of Ca2+ and bile acids by the colonic mucosa may alter the activity of PKC in the mucosa, and thus alter the growth properties of this tissue. The present studies also suggest that lipophilic anionic compounds may provide a new approach to developing therapeutic agents that act by modulating PKC. | {
"pile_set_name": "PubMed Abstracts"
} |
Protective effect of telmisartan on rats with renal failure and its mechanism.
To study the protective effect of telmisartan on rats with renal failure and its mechanism. 60 Wistar rats were chosen as study objective, and were divided into 4 groups randomly: 15 in group A (sham operation group), 15 in group B (model group), 15 in group C (telmisartan group) and 15 in group D (telmisartan + GW9962 group). The difference of survival rate, blood-urine biochemical indexes, renal pathological change, and the expression level of PPARγ and nNOS were compared. After 12 weeks, the survival rate of group A was 93.33% (14/15), that of group B was 46.67% (7/15), that of group C was 86.67% (13/15), that of group D was 60.00% (9/15), and the difference among 4 groups had statistical significance (P < 0.05). After 1 week, the difference of Scr, that of BUN and that of 24 h protein urine among 4 groups was not statistical significant (P > 0.05); after 3 weeks, 6 weeks and 12 weeks, these difference was statistical significant (P < 0.05). The difference of blood-urine biochemical indexes, that of renal pathological change, and that of the expression level of PPARγ and nNOS was statistical significant (P < 0.05). Telmisartan has protective effect on renal failure caused by 5/6 nephrectomy, which might be relative to the expression level of PPARγ and nNOS. | {
"pile_set_name": "PubMed Abstracts"
} |
Synthesis, bioconversion, pharmacokinetic and pharmacodynamic evaluation of N-isopropyl-oxy-carbonyloxymethyl prodrugs of CZh-226, a potent and selective PAK4 inhibitor.
We have previously disclosed compound 3 (CZh-226), a potent and selective PAK4 inhibitor, but its development was delayed due to poor oral pharmacokinetics. In an attempt to improve this issue, we synthesised a series of prodrugs by masking its terminal nitrogen of the piperazine moiety. Most synthesised prodrugs of 3 have low or no inhibition of PAK4 activity. The stability of synthetic prodrugs was evaluated in PBS, SGF, SIF, rat plasma and liver S9 fraction. Of these, prodrug 19 was not only stable under both acidic and neutral conditions but also could be quickly converted to parent drug 3 in rat plasma and liver S9 fraction. Such effective conversion into parent drug 3 was observed in rats, providing higher exposure of 3 compared to its direct administration. When given via oral route at daily doses of 25 and 50 mg/kg, the prodrug 19 was effective and well tolerated in mouse model of HCT-116 and B16F10. | {
"pile_set_name": "PubMed Abstracts"
} |
Quantum computation with cold bosonic atoms in an optical lattice.
We analyse an implementation of a quantum computer using bosonic atoms in an optical lattice. We show that, even though the number of atoms per site and the tunnelling rate between neighbouring sites is unknown, one may operate a universal set of gates by means of adiabatic passage. | {
"pile_set_name": "PubMed Abstracts"
} |
The postoperative occurrence or worsening of diabetes mellitus may increase the risk of recurrence in resected pancreatic neuroendocrine tumors.
The goal of this retrospective study was to investigate the potential link between diabetes mellitus (DM) and the recurrence of pancreatic neuroendocrine tumors (PanNET) following curative intent surgery. We included patients who underwent surgical resection of non-metastatic well-differentiated PanNET. Exacerbation of DM was defined as the postoperative occurrence of DM or worsening of preexisting DM. We explored the variables associated with PanNET recurrence-free survival (RFS). RFS was compared in a subset of patients with and without DM operated on by anatomical resection, after matching for the main prognostic factors. The impact of antidiabetic therapy on RFS was assessed. A total of 268 patients (median age 54.7, 40% men) were included. Most PanNET were sporadic (85%), G1 (61%), pT1/pT2 (79%) and pN0 (76%). Postoperative DM exacerbation occurred in 38 patients (14%), including 27 with new-onset DM. On multivariable analysis, DM exacerbation was independently associated with an increased risk of PanNET recurrence (HR 2.35, 95% CI [1.24-4.47], p=0.009) after adjustment for age, multiplicity of tumors, grade, pT and pN stages. Similar results were found when 27 patients with and 48 patients without DM exacerbation, matched for grade, pT stage and pN stage were compared (HR 3.03, 95% CI [1.05-8.77], p=0.032). The postoperative use of metformin tended to decrease the risk of recurrence (HR 0.59, 95% CI 0.24-1.47, p=0.26). Patients with postoperative DM exacerbation may have an increased risk of PanNET recurrence. Closer follow-up might be beneficial in these patients. The protective role of metformin should be further explored. | {
"pile_set_name": "PubMed Abstracts"
} |
[Usefulness of examining the vaginal ecosystem and its importance in threatening premature labor].
The aim of the study was to examine whether, and in what extend bacterial vaginosis (BV) might be the cause of threatening premature labor. Vaginal ecosystem was examined in the group of 225 pregnant women with the symptoms of threatening premature labor. The control group consisted of women with physiologically proceeding pregnancies. Bacterial vaginosis was confirmed in 14.2% of pregnant women with the symptoms of premature labor, whereas BV was found in 10.2% of women in the control group. The examination of BV seems to be useful in all pregnant women, especially in those with threatening premature labor. | {
"pile_set_name": "PubMed Abstracts"
} |
Microsomal mixed-function amine oxidase. Oxidation products of piperazine-substituted phenothiazine drugs.
Oxidation products of fluphenazide, thioproperazine, and trifluoperazine obtained in reactions catalyzed by homogeneous preparations of the microsomal mixed-function amine oxidase have been isolated and identified. Approximately 0.5 g of metabolite of each piperazine-substituted phenothiazine drug was prepared in reactors containing, as catalyst, the purified oxidase covalently attached to glass beads. Nuclear magnetic resonance spectra of the isolated products indicated that with all three substrates the enzyme preferentially catalyzes N-oxidation of the piperazine nitrogen furthest from the phenothiazine nitrogen atom. The enzyme-catalyzed oxidation is quite specific and oxidation of the sulfur or nitrogen atoms in the phenothiazine ring could not be detected. Concentrations of piperazine-substituted phenothiazines required to half-saturate the amine oxidase were in the micromolar range and at pH 8.3 and 37 degrees C, all those tested were oxidized at approximately 2 mumol/min/mg of enzyme. Kinetic constants for the piperazine-substituted phenothiazines were very similar to those obtained with phenothiazines containing a dimethylaminopropyl sidechain. | {
"pile_set_name": "PubMed Abstracts"
} |
Frequencies of polymorphisms in CYP2C9 and VKORC1 genes influencing warfarin metabolism in Slovak population: implication for clinical practice.
The study was aimed at establishing an effective molecular-genetic method for detecting polymorphisms in genes CYP2C9 and VKORC1, which affect the pharmacogenetics of warfarin, and at determining their prevalence in Slovak population. Warfarin, derivative of coumarin, belongs to the most commonly prescribed oral anticoagulants with narrow therapeutic index. An insufficient dose of warfarin can result in failure to produce the antithrombotic effect, whereas an overdose increases the risk of bleeding. It was proven that genetic variability in two genes, CYP2C9 a VKORC1, has a significant influence on the individual's response to the dosage of warfarin. In a control group of 112 randomly selected individuals, we tested the frequency of selected single nucleotide polymorphisms including CYP2C9*2 (430C>T), CYP2C9*3 (1075A>C), VKORC1*2 (1173C>T) by allele-specific Real-Time PCR and VKORC1*2 (-1639G>A) by using PCR-RFLP. Due to the combination of frequent alleles CYP2C9*2, CYP2C9*3 and VKORC1*2 in Slovak population we determine that 25% of population need a standard 5-mg daily dose of warfarin, while 44%, 23%, and 8% need 4 mg, 3 mg and 2 mg of warfarin per day. Slovak population is in Hardy-Weinberg equilibrium and frequencies of SNPs were in accordance with other published results in European populations (Tab. 5. Fig. 3, Ref. 51). | {
"pile_set_name": "PubMed Abstracts"
} |
Flow-induced delayed Freedericksz transition.
We demonstrate that a compact manometer experiment allows direct observation of a delay to the classical electric-field-induced Freedericksz transition produced by flow in a highly dispersive nematic liquid crystal layer. The Ericksen-Leslie equations are used to show that a flow aligning torque generated in the nematic layer under Poiseuille flow competes with the orthogonal electric-field reorientation torque. This model fully reproduces the experimental results using only self-consistently determined viscosity values, and predicts a more generally applicable expression for the dependence of the delay E(c)∝sqrt[ζ/Δχ(e)] on the shear rate ζ and on the electric susceptibility anisotropy Δχ(e). | {
"pile_set_name": "PubMed Abstracts"
} |
Anatomical correction of vaginal vault prolapse by uterosacral ligament fixation in women who also require a pubovaginal sling.
We describe the anatomical and functional outcome in patients who underwent vaginal vault fixation to the proximal uterosacral ligaments for the treatment of vault prolapse and who also required a concomitant pubovaginal sling for associated stress urinary incontinence as well as the repair of other sector defects. We retrospectively analyzed the records of 33 patients who underwent such repairs between November 1998 and December 2001. Endopelvic fascial defects were described using the pelvic organ prolapse quantitative system (POPQ). Outcome measures included anatomical and functional assessment of pelvic floor defects and urinary incontinence. Preoperatively all patients complained of a vaginal bulge and stress urinary incontinence, while 17 of the 33 had urge incontinence, and 24 and 9 had POPQ stage III or IV and stage II prolapse, respectively. Mean followup was 28 months (range 6 to 43). There was significant improvement in all POPQ measurements (p <0.05). Most notably vaginal cuff support improved by a mean of 7 cm. Stages IIAp (rectocele) and IIC (cuff) prolapse developed in 4 and 2 failed cases, respectively. Stress urinary incontinence was cured in all 33 patients and urge incontinence was cured in 14 of 17, while in 27 vaginal prolapse symptoms resolved and most had improved defecation dysfunction. No patients had urinary obstructive symptoms. There were no ureteral, bladder or rectal complications but 1 patient required blood transfusion. Suspension of the vaginal cuff to the proximal uterosacral ligaments with site specific repair of other associated endopelvic fascial defects provides excellent anatomical and functional correction of vault prolapse. Furthermore, a concomitant pubovaginal sling is a compatible repair for associated stress urinary incontinence. It did not compromise vaginal repair and prolapse repair did not jeopardize the outcome of the sling. | {
"pile_set_name": "PubMed Abstracts"
} |
Predictors of mercury spatial patterns in San Francisco Bay forage fish.
Pollution reduction efforts should be targeted toward those sources that result in the highest bioaccumulation. For mercury (Hg) in estuaries and other complex water bodies, carefully designed biosentinel monitoring programs can help identify predictors of bioaccumulation and inform management priorities for source reduction. This study employed a probabilistic forage fish Hg survey with hypothesis testing in San Francisco Bay (California, USA). The goal was to determine what pollution sources, regions, and landscape features were associated with elevated Hg bioaccumulation. Across 99 sites, whole-body Hg concentrations in Mississippi silversides (Menidia audens) and topsmelt (Atherinops affinis) followed a broad spatial gradient, declining with distance from the Guadalupe River (Pearson's r = -0.69 and -0.42, respectively), which drains historic mining areas. Site landscape attributes and local Hg sources had subtle effects, which differed between fish species. Topsmelt Hg increased in embayment sites (i.e., enclosed sites including channels, creek mouths, marinas, and coves) and sites with historic Hg-contaminated sediment, suggesting an influence of legacy industrial and mining contamination. In 2008, Mississippi silverside Hg was reduced at sites draining wastewater-treatment plants. Fish Hg was not related to abundance of surrounding wetland cover but was elevated in some watersheds draining from historic Hg-mining operations. Results indicated both regional and site-specific influences for Hg bioaccumulation in San Francisco Bay, including legacy contamination and proximity to treated wastewater discharge. | {
"pile_set_name": "PubMed Abstracts"
} |
An Experimental Comparison of Quality Models for Health Data De-Identification.
When individual-level health data are shared in biomedical research, the privacy of patients must be protected. This is typically achieved by data de-identification methods, which transform data in such a way that formal privacy requirements are met. In the process, it is important to minimize the loss of information to maintain data quality. Although several models have been proposed for measuring this aspect, it remains unclear which model is best suited for which application. We have therefore performed an extensive experimental comparison. We first implemented several common quality models into the ARX de-identification tool for biomedical data. We then used each model to de-identify a patient discharge dataset covering almost 4 million cases and outputs were analyzed to measure the impact of different quality models on real-world applications. Our results show that different models are best suited for specific applications, but that one model (Non-Uniform Entropy) is particularly well suited for general-purpose use. | {
"pile_set_name": "PubMed Abstracts"
} |
Bayesian analysis of folding and unfolding time series of single-forced RNAs.
On the basis of a coarse-grain physical model of the folding and unfolding of single-forced RNAs conducted in light tweezer experiments, we theoretically investigate the feasibility of inferring the RNA's intrinsic kinetic parameters from the noisy time series of the molecule's extension. A Bayesian approach using Monte Carlo Markov Chain is proposed. We prove that this statistical approach is efficient and accurate in inferring the molecule's physical parameters, even if the experimental data are yielded under a narrow range of forces. | {
"pile_set_name": "PubMed Abstracts"
} |
Secular trends in hospital-acquired Clostridium difficile disease in the United States, 1987-2001.
We reviewed Clostridium difficile-associated disease (CDAD) data from the intensive care unit (ICU) and hospital-wide surveillance components of the National Nosocomial Infections Surveillance System hospitals during 1987-2001. ICU CDAD rates increased significantly only in hospitals with >500 beds (P<.01) and correlated with the duration of ICU stay (r=0.82; P<.05). Hospital-wide (non-ICU) rates increased only in hospitals with <250 beds (P<.01) and in general medicine patients versus surgery patients (P<.0001). CDAD predominated in general hospitals versus other facility types, and rates were significantly higher during winter versus nonwinter months (P<.01). Thus, prevention efforts should be targeted to high-risk groups in these settings. | {
"pile_set_name": "PubMed Abstracts"
} |
Objective measurement of visual acuity by optokinetic response determination in patients with ocular diseases.
To investigate the efficacy of optokinetic nystagmus (OKN) suppression and induction methods for the objective estimation of visual acuities in patients with various ocular diseases. Prospective, descriptive study. One hundred seventy-three eyes of 89 patients aged between 27 and 75 years who registered at our institution from January to December 2004 were prospectively enrolled onto this study. Ocular diseases included generalized retinal diseases (47 eyes), media opacity (32 eyes), refractive errors (31 eyes), glaucoma (27 eyes), maculopathies (26 eyes), and optic neuropathies (10 eyes). Horizontal optokinetic stimuli were presented on a 17-inch monitor screen at a distance of 40 cm from the subject in a dark room. Horizontal eye movements were recorded in each eye separately by infrared oculography. Objective visual acuities measured by using OKN suppression or induction methods were compared with subjective visual acuity assessments. The logarithm of minimal angle of resolution visual acuity was 1.03, and ranged from -0.08 to hand movement. Linear regression identified minimum stripe stimuli required to induce OKN by using the OKN induction method, and the minimum dot size required to suppress OKN was found to be correlated with subjective visual acuity (P<.01). The induction method was useful in patients with visual acuities of 20/60 or worse, and the suppression method was useful in patients with visual acuities of 20/200 or better. Combined use of the OKN induction and suppression methods provides a satisfactory means of determining objective visual acuity. | {
"pile_set_name": "PubMed Abstracts"
} |
Isolation and partial characterization of normal and defective bacteriophages of gram-negative hydrogen bacteria.
Widespread defective lysogeny was detected in Alcaligenes eutrophus by electron microscopic analysis of cultures. Mitomycin C treatment of the cultures resulted in the production of defective (inco-) particles. Polysheaths were produced both with and without induction. With the simultaneous isolation technique six phages were isolated for hydrogen-oxidizing strains of the new species Pseudomonas pseudoflava. The phages were able to replicate under autotrophic conditions and were found to have a very restricted host range. Electron microscopic analysis allowed classification into two structural groups. Group I contained phages with contractile tails; group II contained phages with flexible, noncontractile tails. All but one (gb) of the new phages were shown to be temperate by isolation of lysogens and induction with mitomycin C. | {
"pile_set_name": "PubMed Abstracts"
} |
Pore Shape Changes and Apatite Formation on Zn and Si Ion-Doped HA Films of Ti-6Al-4V After Plasma Electrolytic Oxidation Treatment.
In this study, pore shape changes and apatite formation on zinc (Zn) and silicon (Si) ion-doped hydroxyapatite (HA) films of Ti-6Al-4V by plasma electrolytic oxidation (PEO) treatment has been investigated by several techniques. The PEO films and the Ti-6Al-4V surface after immersion in SBF were observed by X-ray spectroscopy, field-emission scanning electron microscopy, and energy dispersive X-ray spectroscopy. The number of pores decreased as Zn ion concentration increased from 5Zn to 10Zn. The maximum size of pores were increased from 5Zn to 20Zn concentration, whereas, the minimum size of pores decreased. The amount of bone-like apatite formation for the 5Zn/5Si sample was higher than those of other samples immersed in SBF. | {
"pile_set_name": "PubMed Abstracts"
} |
A radical approach to cancer.
Reactive oxygen species are known to be potentially dangerous, but are also needed for signal-transduction pathways. Tumor cells have relatively low amounts of superoxide dismutase (SOD), which quenches superoxide anion (O2(-*)), and as a result of a higher level of aerobic metabolism, higher concentrations of O2(-*) , compared to normal cells. But this may not be true of all tumor cells. Some tumor cells have relatively higher amounts of vitamin E, a potent anti-oxidant, and a higher level of anaerobic metabolism, resulting in a balance that is tilted more towards higher anti-oxidant capacity. In both instances of higher aerobic and anaerobic metabolism methods designed to augment free radical generation in tumor cells can cause their death. It is suggested that free radicals and lipid peroxides suppress the expression of Bcl-2, activate caspases and shorten telomere, and thus inducing apoptosis of tumor cells. Ionizing radiation, anthracyclines, bleomycin and cytokines produce free radicals and thus are useful as anti-cancer agents. But they also produce many side-effects. 2-methoxyoestradiol and polyunsaturated fatty acids (PUFAs) inhibit SODs and cause an increase of O2(-*) in tumor cells leading to their death. In addition, PUFAs (especially gamma-linolenic acid), 2-methoxyoestradiol and thalidomide may possess anti-angiogenic activity. This suggests that free radicals can suppress angiogenesis. Limited clinical studies done with gamma-linolenic acid showed that it can regress human brain gliomas without any significant side-effects. Thus, PUFAs, thalidomide and 2-methoxyoestradiol or their derivatives may offer a new radical approach to the treatment of cancer. | {
"pile_set_name": "PubMed Abstracts"
} |
Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study.
In randomized trials the combination of cisplatin and paclitaxel was superior to cisplatin and cyclophosphamide in advanced-stage epithelial ovarian cancer. Although in nonrandomized trials, carboplatin and paclitaxel was a less toxic and highly active combination regimen, there remained concern regarding its efficacy in patients with small-volume, resected, stage III disease. Thus, we conducted a noninferiority trial of cisplatin and paclitaxel versus carboplatin and paclitaxel in this population. Patients with advanced ovarian cancer and no residual mass greater than 1.0 cm after surgery were randomly assigned to receive cisplatin 75 mg/m2 plus a 24-hour infusion of paclitaxel 135 mg/m2 (arm I), or carboplatin area under the curve 7.5 intravenously plus paclitaxel 175 mg/m2 over 3 hours (arm II). Seven hundred ninety-two eligible patients were enrolled onto the study. Prognostic factors were similar in the two treatment groups. Gastrointestinal, renal, and metabolic toxicity, as well as grade 4 leukopenia, were significantly more frequent in arm I. Grade 2 or greater thrombocytopenia was more common in arm II. Neurologic toxicity was similar in both regimens. Median progression-free survival and overall survival were 19.4 and 48.7 months, respectively, for arm I compared with 20.7 and 57.4 months, respectively, for arm II. The relative risk (RR) of progression for the carboplatin plus paclitaxel group was 0.88 (95% confidence interval [CI], 0.75 to 1.03) and the RR of death was 0.84 (95% CI, 0.70 to 1.02). In patients with advanced ovarian cancer, a chemotherapy regimen consisting of carboplatin plus paclitaxel results in less toxicity, is easier to administer, and is not inferior, when compared with cisplatin plus paclitaxel. | {
"pile_set_name": "PubMed Abstracts"
} |
Adverse drug reactions of psycopharmacs.
The objective of analysis of ADRs caused by drugs that pertain to the ATC group N (nervous system), as reported to the Croatian Agency for Medicinal Products and Medical Devices for the period from March 2005 to December 2008, was to examine the types of ADRs collected in said period, the profile of reporters and the possible impacts this could have on prescribing this group of medicinal products in the future. A retrospective observational study of ADRs was performed. Drugs causing ADRs were grouped according to the ATC drug classification, and subsequently entered into a database. Data were analyzed in respect of total number, gender, age, type, seriousness, expectedness, outcome, system organ class, suspected drug and reporter. The findings showed that 15% of all reported ADRs were caused by drugs from the ATC group N. 60% of these were caused by drugs belonging to the ATC subgroups N05 (psycholeptics) and N06A (antidepressants). A significant increase in the percentage of serious ADRs in the examined groups of medicinal products was observed. Analysis of expectedness showed that the share of unexpected ADRs is very high. The distribution of reporters is not satisfactory. The Agency, as regulatory authority, cannot undertake certain measures to improve the safe use of medicinal products without having reports. Only reporting of ADRs can result in changes to benefit all patient populations. Our joint aim should be avoiding a great number of ADRs and maintaining overall safe use of medicinal products. | {
"pile_set_name": "PubMed Abstracts"
} |
Extraocular muscles in congenital strabismus: muscle fiber and nerve ending ultrastructure according to different regions.
The ultrastructure of the extraocular muscles of patients affected by congenital strabismus is not completely known, and the structures responsible of the pathogenesis of this condition are still to be determined. Specimens obtained from patients suffering from congenital strabismus were studied and compared with specimens obtained from patients enucleated for various pathologies and not affected by any disorder in the oculomotor system. The scleral myotendinous junction, where the occurrence of an altered proprioceptive innervation was already reported, was examined, and findings obtained were compared with those observed in the muscle body (venter), where motor innervation is prominent and usually described as normal. Only a small number of damaged muscle fibers was found everywhere. The damage consisted in alterations of both contractile structures and mitochondria and resulted in severer lesions in the scleral myotendinous junction rather than in the muscle body. The normal muscle fibers were innervated by motor nerve endings with normal features and by few altered proprioceptors. The less damaged muscle fibers were innervated by normal motor nerve endings and severely damaged proprioceptors. The most severely damaged muscle fibers did not receive any type of innervation. These data seem to imply that the most important functional alteration in strabismus regards the scleral myotendinous junction. It is the authors' opinion that these findings might have a clinical importance in choosing the treatment to be pursued in patients with a squint. | {
"pile_set_name": "PubMed Abstracts"
} |
[The gastroduodenal peptic ulcerous disease (author's transl)].
After a brief history of gastroduodenal ulcer since the 19th century, the authors discuss the question of its uniqueness. Upon clinical, biological and genetic grounds, it seems possible to distinguish two different kinds of ulcers. Ulcers situated above the junction between fundic and antropyloric mucosae could possibly be the consequence of biliary reflux, while ulcers situated below this junction would be associated with hyperchlorhydria. Some properties of gastrin, which is responsible for Zollinger-Ellison syndromes I and II, are cited. Presently, gastrin cannot be considered as the primary cause of duodenal ulcer. | {
"pile_set_name": "PubMed Abstracts"
} |
The pathologist and managed care. Integration into the new health care delivery system.
As the health care system evolves, managed care plans are expanding rapidly, and pathologists face radical changes in contractual relationships and payment methodology. As a result, entirely new relationships will often need to be negotiated to adapt successfully. The experience of pathologists in areas where there is already high market penetration by managed care plans can be used in strategic planning, learning to gain entry to negotiations, and planning what and how to negotiate. Proper preparation is critical to successful negotiations in our new health care system and requires an understanding of capitation, contracting risks, and opportunities. | {
"pile_set_name": "PubMed Abstracts"
} |
Distribution of two forms of somatostatin and peptides belonging to the pancreatic polypeptide family in tissues of larval lampreys, Petromyzon marinus L.: an immunohistochemical study.
Immunohistochemistry on tissues of larval lampreys, Petromyzon marinus L., was used to determine the distribution of invariant somatostatin-14 (SST-14) and lamprey somatostatin-34 (SST-34) in the brain while antisera against porcine peptide tyrosine tyrosine (PYY), human neuropeptide Y (NPY), anglerfish peptide YG (aPY), salmon glucagon-like peptide (GLP), SST-14, and SST-34 were used in studies of the pancreas and anterior intestine. In the brain, SST-14 is the major form of somatostatin. SST-14- and SST-34-immunoreactive nerve fibers are distributed throughout the telencephalon, diencephalon, and mesencephalon. In the latter region SST-14 immunoreactivity is concentrated in nerve tracts in the nucleus interpeduncularis. Nerve cells within the olfactory bulbs are immunoreactive only to anti-SST-34. Cells immunostained with anti-SST-14 were localized within the ependymal and subependymal layers of the pars ventralis hypothalami and the subependymal layers of the pars dorsalis thalami. SST-14-immunoreactive perikarya are also distributed within the tegmentum mesencephali. Nerve fibers and cells immunoreactive to anti-SST-34 are detected in the pars ventralis hypothalami but these cells do not colocalize SST-14. Pancreatic islets, distributed within the epithelium and in the submucosal connective tissue at the esophageal-intestinal junction, are only immunoreactive to anti-insulin. The antisera revealed three distinct cell types in the intestinal epithelium: type 1 colocalizes aPY, NPY, and PYY; type 2 colocalizes SST-14 and SST-34; and type 3 demonstrates immunoreactivity only to anti-SST-34. Immunoreactivity to anti-GLP is absent. | {
"pile_set_name": "PubMed Abstracts"
} |
Oral clonidine prolongs lidocaine spinal anesthesia in human volunteers.
Premedication with oral clonidine may improve the quality and duration of lidocaine spinal anesthesia, but this effect has not been examined in a quantitative fashion. Eight volunteers received 50 mg lidocaine (1.5% dextrose free) both with and without 0.2 mg oral clonidine 1.5 h before spinal anesthesia in a randomized, double-blind, placebo-controlled, crossover fashion. Sensory block was assessed by pinprick, transcutaneous electric stimulation equivalent to surgical incision, and duration of tolerance to pneumatic thigh tourniquet. Motor block at the quadriceps and gastrocnemius muscles was assessed by isometric force dynamometry. Episodes of bradycardia, hypotension, and sedation were recorded. Regression of pinprick was unchanged with clonidine. However, duration of tolerance to electric stimulation was increased at the knee (28 +/- 24 min) and ankle (31 +/- 28 min) with clonidine (P < 0.05). The duration of tolerance to tourniquet-induced pain was increased with clonidine (14 +/- 12 min; P < 0.05). The duration of motor block was increased at the quadriceps (20 +/- 13 min) and gastrocnemius (33 +/- 24 min) muscle groups with clonidine (P < 0.05). Although clonidine decreased systolic blood pressure (13 +/- 4 mmHg, P < 0.003) and heart rate (13 +/- 5 beats/min; P = 0.02), no subjects had hypotension or bradycardia. The incidence of sedation was greater with clonidine than with plain lidocaine (50% vs. 0%, P < 0.04). Premedication with oral clonidine prolonged sensory and motor block from lidocaine spinal anesthesia. The exact mechanism whereby oral clonidine prolongs spinal anesthesia remains to be determined. | {
"pile_set_name": "PubMed Abstracts"
} |
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