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pubmed_1061_11614
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The outcomes of an intensive, preoperative smoking cessation program in patients undergoing lung resection were evaluated. Of 340 patients undergoing resection, 82 were currently smoking. Sixty-one were involved in our smoking cessation program, and 45 patients (73.7%) in the program were able to quit by surgery. At the 6-month and 1-year follow-up, 29 (64.4%) and 22 patients (48.9%) abstained from smoking. An intensive smoking cessation program in the perioperative period demonstrated a high success rate, with good results up to 1 year postoperatively for those able to quit before surgery.
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10.1016/j.athoracsur.2019.08.075
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pubmed_5_16862
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The thyromimetic compound SK&F L-94901 shows more potent thyromimetic activity in the liver than in the pituitary gland or heart when administered to rats. The mechanisms of liver-selectivity of SK&F L-94901 were examined using cultured rat hepatoma cells (dRLH-84) and rat pituitary tumor cells (GH3), both of which showed saturable cellular uptake of tri-iodothyronine (T(3)). When isolated nuclei with partial disruption of the outer nuclear membrane were used, SK&F L-94901 competed for [(125)I]T(3) binding to nuclear receptors almost equally in dRLH-84 and GH3 cells. SK&F L-94901 also did not discriminate thyroid hormone receptors (TR) alpha1 and beta1 in terms of binding affinity and activation of the thyroid hormone responsive element. In intact cells, however, SK&F L-94901 was a more potent inhibitor of nuclear [(125)I]T(3) binding in dRLH-84 cells than in GH3 cells at an early phase of the nuclear uptake process and after binding equilibrium. These data suggest that SK&F L-94901 is more effectively transported to nuclear TRs in hepatic cells than in pituitary cells and therefore shows liver-selective thyromimetic activity. In conclusion, SK&F L-94901 discriminates hepatic cells and pituitary cells at the nuclear transport process. The cellular transporters responsible for this discrimination were not evident.
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10.1677/joe.0.1650391
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pubmed_1060_9387
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Clones for human prothymosin alpha have been identified in cDNA libraries from staphylococcal enterotoxin A-stimulated normal human lymphocytes and from simian virus 40-transformed fibroblasts. The 1198-base-pair fibroblast clone has been sequenced. The encoded protein is highly acidic (54 residues out of 111) and shares greater than 90% sequence homology with rat prothymosin alpha. The peptide "hormone" thymosin alpha 1 appears at positions 2-29 of the prothymosin alpha amino acid sequence. There is no N-terminal signal peptide. Examination of mouse and human tissues revealed the presence of prothymosin alpha mRNA in kidney, liver, spleen, normal lymphocytes (predominantly T cells), human T-cell leukemia virus-infected T cells, and myeloma cells (B-cell lineage). Prothymosin alpha mRNA is inducible; upon mitogen stimulation it increased greater than 15-fold above the level found in resting lymphocytes. Similarly, serum-deprived NIH 3T3 cells responded to serum restitution with an increase in prothymosin alpha mRNA. Characterization of human genomic DNA by Southern blot analysis disclosed a complicated pattern consistent with genetic polymorphism. These data suggest that prothymosin alpha plays an intracellular role tied to cell proliferation. There is no evidence that it serves as a precursor for secreted thymic peptides. However, given the complexity at the genomic level, multiple functions, including a putative secretory capability, cannot be excluded.
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10.1073/pnas.83.24.9403
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pubmed_825_17946
|
Single graded doses of 1,25-dihydroxycholecalciferol of 2 and 4 micrograms were added intraperitoneally into the overnight 1.5% glucose dialysate of 6 patients on continuous ambulatory peritoneal dialysis. The effect on peritoneal macrophage chemotaxis and random migration was studied and compared with the baseline when no 1,25-(OH)2D3 was added. No consistent effect on peritoneal macrophage chemotaxis was observed. Random migration was significantly depressed at 4 micrograms when compared with baseline (5.4 +/- 1.9 vs. 12.2 +/- 3.7 cells/high-power field, p less than 0.05). The potential clinical role of 1,25-(OH)2D3 as an immune modulator requires further study.
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10.1159/000186604
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pubmed_646_15371
|
OBJECTIVE
Nateglinide, a new short-acting D-phenylalanine derivative for treating type 2 diabetes, reduces mealtime blood glucose excursions by physiologic regulation of insulin secretion. This study evaluated the pharmacokinetic and pharmacodynamic interactions of nateglinide and metformin in subjects with type 2 diabetes.
RESEARCH DESIGN AND METHODS
A total of 12 type 2 diabetic subjects with the following baseline characteristics were enrolled: age, 56 +/- 13 years; BMI, 28.7 +/- 4.5 kg/m2; HbA1c, 8.4 +/- 1.3%; and fasting plasma glucose 13 +/- 2.8 mmol/l. All subjects had been previously treated with glyburide and were switched to metformin monotherapy for 3 weeks before study start. Subjects then randomly received, in combination with 500 mg metformin, either 120 mg nateglinide or placebo before meals for 1 day, followed by the alternate treatment 7 days later. After 1 week of washout from both drugs, subjects received 1 day of open-label nateglinide treatment. Plasma concentrations of glucose, insulin, nateglinide, and metformin were assessed frequently during inpatient periods.
RESULTS
Postmeal plasma glucose levels were significantly lower in subjects treated with nateglinide plus metformin than in those treated with either drug alone (P < 0.001), especially after lunch and dinner. Coadministration of nateglinide and metformin did not affect the pharmacokinetics of either drug. All treatments were safe and well tolerated.
CONCLUSIONS
Combination therapy with nateglinide and metformin was more effective than either treatment alone and did not result in any pharmacokinetic interactions. Coadministration of nateglinide and metformin appears to be an excellent option for treating patients with type 2 diabetes not controlled with monotherapy.
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10.2337/diacare.23.3.349
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pubmed_275_5932
|
PURPOSE OF REVIEW
To provide an overview of recent clinical trials with monoclonal antibodies targeting epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) in head and neck cancer (HNC) and in other tumors. To discuss future therapeutic strategies.
RECENT FINDINGS
Cetuximab, a chimeric monoclonal antibody targeting EGFR, has induced improved locoregional control and survival in combination with radiotherapy in a phase III study in locally advanced inoperable HNC. The recent Bowel Oncology with Cetuximab Antibody (BOND) study has shown that the combination of irinotecan and cetuximab yields a better response rate and a longer time to progression with respect to cetuximab monotherapy in irinotecan-refractory metastatic colorectal cancer, pointing to both a cetuximab single-agent activity and a cetuximab potential for reversal of irinotecan resistance. Non-small cell lung cancer and pancreatic cancer represent further areas for cetuximab development. Bevacizumab is a humanized monoclonal antibody that targets VEGF. It is the first antiangiogenic drug to have induced a survival advantage in cancer therapy, within a randomized trial of irinotecan, 5-fluorouracil, leucovorin (IFL) combined with bevacizumab or placebo in metastatic colorectal cancer. The use of bevacizumab in HNC is supported by preclinical evidence of an angiogenic loop; a few clinical trials are exploring the feasibility and the therapeutic potential of a combination of bevacizumab and EGFR-targeted drugs.
SUMMARY
Monoclonal antibodies targeting EGFR and VEGF represent exciting therapeutic strategies that should be further evaluated both in combination with drugs acting on the same target at a different level and in combination with other antisignaling agents acting on different pathways.
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10.1097/01.cco.0000159623.68506.cf
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pubmed_230_5905
|
Drooling (saliva loss) is a frequently reported symptom in patients with Parkinson's disease (PD), but an accurate estimate of the prevalence of drooling is lacking. The aim of this study was to systematically review the prevalence of drooling in published research papers. A systematic PubMed and CINAHL search was done, including studies published until January 2009. Eight studies were found, presenting prevalence rates of drooling based on responses of PD patients to questionnaires. The statistical heterogeneity was highly significant (P < 0.0001), with prevalence rates ranging from 32 to 74%. The pooled prevalence estimate with random effect analysis was of 56% (95% CI 44-67) for PD patients and 14% (95% CI 3-25) for healthy controls; the pooled relative risk (RR) with random effect analysis was 5.5 (95% CI 2.1-14.4). All studies reported data of community dwelling idiopathic PD patients, with a mean age around 65 years and mild PD in 50-60% of the cases. Heterogeneity was mainly caused by differences in definition or frequency of drooling. The highest prevalence rates included nocturnal drooling where others noted only diurnal drooling. Analysis of the data of two studies showed that drooling is reported frequently by 22-26% of the patients. Prevalence rates were lower in milder PD patients. The summarized findings demonstrate that drooling can be present in half of all PD patients. In about a quarter of PD patients, drooling appears to be a frequently occurring problem. We recommend to report drooling in future studies with more detailed consideration of severity, frequency and nocturnal versus diurnal complaints.
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10.1007/s00415-009-5098-2
|
pubmed_516_13662
|
BACKGROUND
Radiocontrast-induced nephropathy (CIN) remains an important iatrogenic cause of acute renal failure in high-risk patients, despite the development of safer contrast media, the improvement of hydration protocols, and the introduction of additional preventive strategies. Erythropoietin (EPO) pretreatment may confer protection against acute renal failure through the induction of stress response genes.
METHODS
The effect of EPO has been evaluated in a rat model of CIN, induced by iothalamate, following the inhibition of nitric oxide- and prostaglandin-synthesis with indomethacin and N(omega) nitro-L-arginine methyl ester (L-NAME). Twenty-two male Sprague-Dawley rats were subjected to saline (CTR) or EPO injections (3000 U/kg and 600 U/kg, 24 and 2 h before the induction of CIN, respectively).
RESULTS
The decline in creatinine clearance in CTR animals from 0.38 +/- 0.03 to 0.28 +/- 0.03 mL/min/100 g (p < 0.005), was prevented by EPO pretreatment (from 0.34 +/- 0.02 to 0.32 +/- 0.03 mL/min/100 g, NS). The extent of medullary thick ascending limb- and S3-tubular damage in the outer medulla, however, was comparable in the two experimental groups.
CONCLUSIONS
EPO pretreatment prevents renal dysfunction in a rat model of CIN. Further experimental and clinical studies are required to confirm these preliminary conclusions regarding a potential protective potency of EPO against CIN.
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10.1080/08860220600591420
|
pubmed_789_15639
|
Metastasis to the bones of the hand and wrist is not common, and its discovery may reveal an advanced primary tumor located centrally. Clinically, hand metastasis is hard to differentiate from other more common hand pathologies. Its rarity, coupled with a lack of unique clinical manifestations, makes hand and wrist metastasis difficult to diagnose. However, its diagnosis is critical to initiate an appropriate course of treatment. We present a patient in whom lung carcinoma metastasis to the trapezium was definitively diagnosed upon surgical management of symptoms that were consistent with thumb carpometacarpal arthritis.
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10.1016/j.jhsa.2012.03.006
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pubmed_647_12476
|
BACKGROUND
Cholinesterase inhibitors are used to treat mild to moderate Alzheimer's disease. Their role in patients with concurrent cerebrovascular disease has been less well studied, and the influence of vascular risk factors on response to treatment is uncertain. We investigated the effect of hypertension and white matter lesions (WML) on response.
METHODS
A retrospective sample of 160 consecutive out-patients who had blood pressure measured and the presence or absence of WML recorded at baseline and who completed six months treatment with a cholinesterase inhibitor was studied. Subjects scored either zero or one on the Modified Hachinski Ischaemic Scale. Subjects were assessed using the Mini-Mental State Examination (MMSE), the Digit Symbol Substitution test (DSST) and both the Instrumental Activities of Daily Living (IADL) and Social Behaviour (SB) sub-scales of the Nurses Observation Scale for Geriatric Patients (NOSGER).
RESULTS
43.9% of the total study population were classified as good responders using our criteria. Neither the presence of hypertension nor the presence of WML alone influenced outcome. However, there was a statistically significant interaction between blood pressure and WML on outcome variables on multiple analysis of variance (MANOVA) (F(4, 139) = 5.60, p < 0.0005). Subjects with both hypertension and WML deteriorate to a significantly greater extent in IADL and SB scores than any other group (p < 0.05 in each case). This effect could not be explained by age or by smoking status.
CONCLUSION
Our results support the hypothesis that there is an interaction between hypertension and WML that adversely influences functional change during cholinesterase inhibitor treatment. Our results are a contrast to suggestions that subjects with vascular disease show a better response to cholinesterase inhibitors. We recommend careful exploration of factors that may influence outcome.
|
10.1002/gps.1331
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pubmed_76_24092
|
While much of the current literature concurs that neuropsychological decline does not occur among gay men in the early stages of HIV infection, there is no comparable body of evidence with regard to seropositive intravenous drug users (IVDU). In this study, 45 seropositive (CDC groups 2, 3, and 4a) IVDU in recovery and 55 seronegative IVDU in recovery were given a complete battery of neuropsychological tests measuring attention, language, visual-motor, memory, and conceptual skills. The groups were not significantly different in age, incidence of childhood and adult head injury, types of drugs used, length of use of cocaine, crack, amphetamines and hallucinogens, overdose history, and length of time in recovery. In addition, groups were statistically corrected for education level and length of heroin use. Results indicate that the seropositive participants scored significantly lower on measures of divided attention, visual short-term memory, graphomotor speed and accuracy, auditory language shortterm memory and abstract concept formation. Further analyses revealed that 18% of participants with Persistent Generalized Lymphadenopathy (CDC group III) and 27% of those with constitutional disease (CDC group IVa) were neuropsychologically impaired, as their performance was two standard deviations or more below the normative mean on two or more measures. These results are similar to the reported performance of gay men with full-blown AIDS in a number of studies. It is hypothesized that because of premorbid neurological insult, the toxic effects of drug abuse on brain tissue, and the immunosuppressive effects of the drugs, subcortical brain cells of IVDU are more vulnerable to the invasion of HIV, and neurological deterioration may occur at earlier stages of HIV Spectrum Disease in IVDU than in gay men.
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10.3109/00207459209000544
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pubmed_400_19266
|
BACKGROUND AND OBJECTIVE
Exacerbation of chronic obstructive pulmonary disease (COPD) is one of the most frequent causes of hospital admission. We examined the results and feasibility of two programs conducted by a hospital respiratory unit aimed to reduce both the length of hospital stay and the number of hospital admissions for COPD acute exacerbation.
PATIENTS AND METHOD
a) Assisted hospital discharge program: Patients admitted for acute exacerbation who met our criteria for early discharge were sent home with the support of a respiratory nurse. Home visits were carried out and direct phone contact with the nurse and physician was provided during a limited period of 6 weeks. Outcome variables studied were length of hospital admission and need for hospital reentry. b) Exacerbation prevention program: A group of patients with severe COPD and at least 3 hospital admissions for exacerbation during the previous year were included. These patients underwent an educational program and were given unlimited direct phone access to the respiratory nurse and physician. When necessary, home visits were carried out. The main outcome variable of this program was the number of hospital admissions.
RESULTS
a) Assisted hospital discharge program: A total of 97 patients were included. The mean length of hospital stay was 5.4 1.7 days, which was significantly shorter than the previous average length of stay in our respiratory unit for a diagnosis of COPD exacerbation (8.52 days). The rate of hospital reentry was 17% (within the first 3 months). b) Exacerbation prevention program: 23 patients were enrolled. In this group, the number of hospital admissions decreased significantly from 5.0 1.8 to 1.7 2.4 per year (p = 0.001). Visits to the emergency department were also decreased, from 1.2 1.6 to 0.4 1.6 per patient (p = 0.05). Finally, the length of hospital stay decreased from 38 17 to 16 20 days (p = 0.0001).
CONCLUSIONS
A combined use of hospital resources and home care programs which are specifically addressed to severe COPD patients can reduce the need for hospital admission.
|
10.1016/s0025-7753(03)73720-8
|
pubmed_150_8709
|
OBJECTIVES/HYPOTHESIS
Plasma Epstein-Barr virus (EBV) DNA concentrations predict prognosis in patients with nasopharyngeal carcinoma (NPC). Recent evidence also indicates that intratumor heterogeneity on F-18 fluorodeoxyglucose positron emission tomography (18 F-FDG PET) scans is predictive of treatment outcomes in different solid malignancies. Here, we sought to investigate the prognostic value of heterogeneity parameters in patients with primary NPC.
STUDY DESIGN
Retrospective cohort study.
METHODS
We examined 101 patients with primary NPC who underwent pretreatment 18 F-FDG PET/computed tomography. Circulating levels of EBV DNA were measured in all participants. The following PET heterogeneity parameters were collected: histogram-based heterogeneity parameters, second-order texture features (uniformity, contrast, entropy, homogeneity, dissimilarity, inverse difference moment), and higher-order (coarseness, contrast, busyness, complexity, strength) texture features.
RESULTS
The median follow-up time was 5.14 years. Total lesion glycolysis (TLG), tumor heterogeneity measured by histogram-based parameter skewness, and the majority of second-order or higher-order texture features were significantly associated with overall survival (OS) and/or recurrence-free survival (RFS). In multivariate analysis, age (P =.005), EBV DNA load (P = .0002), and uniformity (P = .001) independently predicted OS. Only skewness retained the independent prognostic significance for RFS. Tumor stage, standardized uptake value, or TLG did not show an independent association with survival endpoints. The combination of uniformity, EBV DNA load, and age resulted in a more reliable prognostic stratification (P < .001).
CONCLUSIONS
Tumor heterogeneity is superior to traditional PET parameters for predicting outcomes in primary NPC. The combination of uniformity with EBV DNA load can improve prognostic stratification in this clinical entity.
LEVEL OF EVIDENCE
4 Laryngoscope, 127:E22-E28, 2017.
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10.1002/lary.26172
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pubmed_887_15105
|
After 21 days of twice daily i.p. injections of bupropion (10 mg/kg), B.W.306U (10 mg/kg) or saline, 5 rat brain regions were removed for [3H]flunitrazepam binding assay. Scatchard analysis of the binding data revealed no change in the Bmax in any brain regions in drug-treated rats compared to controls. There was, however, a significant change in the Kd value in the limbic forebrain of B.W.306U-treated rats.
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10.1016/0006-8993(86)91624-0
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pubmed_642_19365
|
Hesperidin, the major flavonoid in citrus species, possesses various biological functions and pharmacological activities, however, its insolubility in water limits its bioavailability and medical or food application. When 8 g/L octenyl succinic anhydride modified sweet potato starch (OSA-SPS) with degree of substitution 0.0051 was applied to solubilize hesperidin under the conditions of stirring the mixture for 6 h at 2400 r/min, 50 °C and unadjusted pH, the solubilization efficiency of hesperidin was 6.52 folds higher than that without OSAS addition. It was noteworthy that the solubilization of hesperidin was obviously different from that of hesperetin (hydrolysate of hesperidin) either in starch origin of OSAS or in the influence of external factors. The interaction between OSA-SPS and hesperidin had been certified by means of FT-IR, XRD, DSC, 1H/2D NMR. These results would give a fundamental reference for probing specific mechanism between hesperidin and OSAS in the further research.
|
10.1016/j.foodchem.2019.01.138
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pubmed_752_5688
|
We propose to construct electron correlation methods that are scalable in both molecule size and aggregated parallel computational power, in the sense that the total elapsed time of a calculation becomes nearly independent of the molecular size when the number of processors grows linearly with the molecular size. This is shown to be possible by exploiting a combination of local approximations and parallel algorithms. The concept is demonstrated with a linear scaling pair natural orbital local second-order Møller-Plesset perturbation theory (PNO-LMP2) method. In this method, both the wave function manifold and the integrals are transformed incrementally from projected atomic orbitals (PAOs) first to orbital-specific virtuals (OSVs) and finally to pair natural orbitals (PNOs), which allow for minimum domain sizes and fine-grained accuracy control using very few parameters. A parallel algorithm design is discussed, which is efficient for both small and large molecules, and numbers of processors, although true inverse-linear scaling with compute power is not yet reached in all cases. Initial applications to reactions involving large molecules reveal surprisingly large effects of dispersion energy contributions as well as large intramolecular basis set superposition errors in canonical MP2 calculations. In order to account for the dispersion effects, the usual selection of PNOs on the basis of natural occupation numbers turns out to be insufficient, and a new energy-based criterion is proposed. If explicitly correlated (F12) terms are included, fast convergence to the MP2 complete basis set (CBS) limit is achieved. For the studied reactions, the PNO-LMP2-F12 results deviate from the canonical MP2/CBS and MP2-F12 values by <1 kJ mol(-1), using triple-ζ (VTZ-F12) basis sets.
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10.1021/ct500725e
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pubmed_70_6275
|
Icosahedral clusters in Ti and Ni are studied with first-principles density functional calculations. We find significant distortion on the Ti icosahedron caused by the strong interaction between surface atoms on the icosahedron but not between the center atom and surface atoms, whereas no such distortion is observed on Ni clusters. In addition, distortion becomes more severe when atoms are added to the Ti(13) cluster resulting in short bonds. Such distorted icosahedra having short bonds are essential in explaining the structure factor of Ti liquid obtained in experiment.
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10.1063/1.2800026
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pubmed_225_2795
|
Some [beta-(Aroylamino)ethyl]piperazines and -piperidines and [2-[(Arylamino)carbonyl]ethyl]piperazines, -piperidines, -pyrazinopyridoindoles, and -pyrazinoisoquinolines have been synthesized and their H1-antagonistic activity studied in isolated guinea pig ileum. Quantitative structure-activity relationship analysis indicates that the hydrophobicity of the side chain of these compounds plays a major role in their activity while steric and electronic factors are of secondary importance. All these compounds act on a common receptor and appear to interact similarly with the receptor.
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10.1021/jm00173a011
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pubmed_1029_9628
|
The purpose of this study was to determine whether axillofemoral bypass was justified as an alternative revascularization procedure to direct reconstruction and to specifically define the indications for this extraanatomical bypass. Forty-one patients operated on between 1978 and 1985 were evaluated. The average age was 69 years. Indications were based upon limb salvage for aortoiliac occlusive disease in the following situations: infected aortobifemoral bypass graft (8 patients) and high risk with co-existing medical problems (33 patients). Patients were classified according to Goldman's Multifactorial Index of Cardiac Risk and Cooperman's Cardiovascular Risk Index. Twenty-four patients had axillobifemoral bypass and 17 had unilateral axillofemoral procedures. In 66 femoral anastomoses there were 13 extended profundaplasties, 25 profunda arterioplasties, 11 profunda patch angioplasties and 16 anastomoses to the common femoral artery. Postoperative mortality was 4.8% (2 patients). Cumulative survival at 60 months was 43% +/- 11% and primary patency rate of the axillofemoral bypass was 69 +/- 9.8%. We conclude that axillo-femoral bypass is indicated in the presence of infection, in patients who fall into Goldman's Class III-IV or in patients with risk greater than 10% as calculated by Cooperman's equation.
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10.1016/S0890-5096(07)60008-9
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pubmed_298_9003
|
Patients with neurofibromatosis type 1 (nf1) are at increased risk for both benign and malignant tumours, and distinguishing the malignant potential of an individual tumour is a common clinical problem in these patients. Here, we review two cases of uncommon malignancies (Hodgkin lymphoma and mediastinal germ-cell tumour) in patients with nf1. Although (18)F-fluorodeoxyglucose positron-emission tomography (fdg-pet) has been used to differentiate benign neurofibromas from malignant peripheral nerve sheath tumours, fdg-pet characteristics for more rare tumours have been poorly described in children with nf1. Here, we report the role of pet imaging in clinical decision-making in each case. In nf1, fdg-pet might be useful in the clinical management of unusual tumour presentations and might help to provide information about the malignant potential of uncommon tumours.
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10.3747/co.21.1803
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pubmed_924_24042
|
AIMS
To appraise the literature on long-term neuropsychological and functional outcomes in stroke survivors and identify the gaps, challenges and future research in this area.
BACKGROUND
Stroke care resources are scarce, and the number of stroke survivors is likely to increase with the ageing of the population. Thus, evaluating the cost, frequency and prognostic factors of long-terms stroke functional and neuropsychological outcomes is of paramount importance for evidence-based clinical decision making, including the rationale, planning, provision and allocation of health services, and the development of effective interventions. Summary of review Stroke has an enormous physical, emotional and economic impact on the patients, families and society. However, accurate data on frequency, relationship and predictors of various long-term functional (body functioning, activity and participation) outcomes and costs of stroke are scarce, and no accurate and comprehensive data exist on long-term neuropsychological outcomes and their relationships with other functional outcomes poststroke.
CONCLUSIONS
There is a lack of accurate data on the frequency, relationship and predictors of various long-term functional outcomes and costs of stroke. There is a pressing need for good-quality population-based studies for evaluating the frequency and prognostic factors of long-term functional and neuropsychological outcomes of stroke in various populations.
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10.1111/j.1747-4949.2008.00177.x
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pubmed_704_7982
|
This study aimed to identify prostaglandin synthases (PGS) that mediate bisphenol A (BPA)-induced prostatic hyperplasia and explore their underlying mechanisms. In an in vivo study, male adult Sprague-Dawley rats were treated with different concentrations of BPA (10, 30, 90, or 270 μg/kg, i.g., daily), or with vehicle for 4 weeks. Results revealed that low-dose BPA induced prostatic hyperplasia with increased PCNA/TUNEL ratio. It significantly upregulated the expression of cyclooxygenase-2 (COX-2) and NF-κB in the dorsolateral prostate (P < 0.05) and the expression of lipocalin-type prostaglandin D synthase (L-PGDS) in ventral prostate (P < 0.05). The level of estradiol (E2)/testosterone (T) and expression of androgen receptor (AR) and estrogen receptor α (ERα) were also altered. In vitro studies showed that low-dose BPA (0.1-10 nM) promoted the proliferation of human prostate fibroblasts and epithelial cells, and significantly upregulated the expression of COX-2 and L-PGDS in the cells. The two types of cell proliferation induced by BPA were inhibited by COX-2 inhibitor (NS398) and L-PGDS inhibitor (AT56), with increased apoptosis level. These findings suggested that COX-2 and L-PGDS could mediate low-dose BPA-induced prostatic hyperplasia through pathways involved in cell proliferation and apoptosis, which might be related to the functions of ERα and AR. The role of COX-2/NF-κB pathway in dorsolateral prostate requires further research.
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10.1038/s41598-020-69809-y
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pubmed_1100_13438
|
In the period from April 1965 to August 1988 the kidneys of 65 patients were removed in the pretransplantation period in the Department of Kidney Transplantation of the All-Union Research Center of Surgery, AMS USSR. The operation was undertaken for the hypertonic form of chronic glomerulonephritis in 36 and for pyelonephritis and polycystic disease of the kidneys in 34 patients. The effect of anemia and hypoproteinemia on postoperative lethality was analysed. A direct correlative dependence between the postoperative lethality and the above-listed factors was detected. The results of the study provide evidence of the importance of the effect of the character of the preoperative preparation on the results of nephrectomy in the early postoperative period.
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pubmed_1100_13438
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pubmed_926_12055
|
OBJECTIVES
Over the past 30 years, surface imaging has made tremendous progress. Surgical management has also been subject of numerous technical and strategic developments. For a better understanding of the curative strategies of face aging, the authors have put into perspective the three-dimensional data acquired up to date.
METHOD
A review of the literature focused on the three-dimensional study of facial aging was carried out.
RESULTS
Thanks to the precision of new surface acquisition systems and larger patient cohorts, our understanding of surfaces and volumes is now much more accurate. 3D, particularly highlights the major impact of aging on the perioral area, which was up to now neglected compared to other facial areas.
CONCLUSION
A technical discussion is needed to identify the best techniques to correct the defects and provide a natural result for those anatomical areas that are heavily impacted by aging but not corrected in the final.
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10.1016/j.anplas.2017.09.001
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pubmed_879_2361
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Thallium(Tl), an extremely toxic metal, is posing great hazards to water safety through anthropogenic activities (e.g., Pb-Zn smelter) and natural weathering in riverine systems. However, the relative contribution from each source remains obscure. This study investigated enrichment pattern of Tl and its isotopic compositions in sediment profiles from a recipient river, which was continuously collecting various Tl-bearing wastes discharged from a large Pb-Zn smelter in South China. Results show that high Tl content and ultra-fine particles (~ μm) of Tl-bearing mineral assemblages, probably derived from Pb-Zn smelting wastes, were ubiquitously observed in both of the depth profiles. In addition, the sediments generally yielded intermediate ε205Tl values of -3.76 to 1.01, which resembled those found in smelting wastes. A ternary mixing model was for the first time proposed for quantifying relative Tl contributions from each possible source. The calculation suggests that the smelter wastes are the major contributors, contributing approximately 80% of Tl contamination. All these results indicate that Tl isotope can be used as powerful proxies for quantitatively identifying potential different contributors in the environment. This is of critical importance to further implementation of pollution control and remediation strategy for the riverine systems in the near future.
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10.1016/j.jhazmat.2021.127594
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pubmed_537_23457
|
The effect of snail-conditioned water (SCW) from Biomphalaria alexandrina, a pigmented and an albino strain of B. glabrata, and Lymnaea stagnalis on the host-finding behavior of miracidia of two Brazilian and one Egyptian strain of Schistosoma mansoni was studied. Miracidia of the Egyptian strain significantly preferred their suitable host B. alexandrina versus the other snail species with their behavior patterns of host location and their responses after contact with the host. However, miracidia of both Brazilian strains did not differentiate between SCW from three of the snail species; only the pigmented B. glabrata elicited weaker responses. The releasing cues of SCW for miracidial host-finding phases are macromolecular glycoconjugates. An analysis of SCW by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), blotting, and subsequent carbohydrate detection showed that the band patterns of glycoconjugates differed significantly among the four snail strains. Therefore, differing chemical characteristics of the signaling glycoconjugates could be the basis for the observed host specificity in miracidial host-finding.
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10.1007/s004360050059
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pubmed_1127_10005
|
By using podophyllotoxin as a phytoinsecticidal lead compound, 15 novel aromatic esters of 4'-demethyl-4-deoxypodophyllotoxin were semisynthesized and preliminarily tested for their insecticidal activity against the pre-third-instar larvae of Mythimna separata Walker in vivo for the first time. Among all of the tested compounds, especially two compounds, 4m and 4o, containing a pyridinyl group, for which final corrected mortality rates against M. separata at 1 mg/mL were 62.9 and 59.2%, respectively, showed the most promising and pronounced insecticidal activity as compared with toosendanin, a commercial insecticide derived from Melia azedarach . The quantitative structure-activity relationships (QSAR) of compounds 4a-4o showed that the relative number of benzene rings and final heat of formation were very important descriptors to their insecticidal activity.
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10.1021/jf9020812
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pubmed_512_3231
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The tetrahydroisoquinoline trabectedin is a marine compound with approved activity against human soft-tissue sarcoma. It exerts antiproliferative activity mainly by specific binding to the DNA and inducing DNA double-strand breaks (DSB). As homologous recombination repair (HRR)-deficient tumors are more susceptible to trabectedin, hyperthermia-mediated on-demand induction of HRR deficiency represents a novel and promising strategy to boost trabectedin treatment. For the first time, we demonstrate enhancement of trabectedin effectiveness in human sarcoma cell lines by heat and characterize cellular events and molecular mechanisms related to heat-induced effects. Hyperthermic temperatures (41.8 or 43°C) enhanced significantly trabectedin-related clonogenic cell death and G2/M cell cycle arrest followed by cell type-dependent induction of apoptosis or senescence. Heat combination increased accumulation of γH2AX foci as key marker of DSBs. Expression of BRCA2 protein, an integral protein of the HRR machinery, was significantly decreased by heat. Consequently, recruitment of downstream RAD51 to γH2AX-positive repair foci was almost abolished indicating relevant impairment of HRR by heat. Accordingly, enhancement of trabectedin effectiveness was significantly augmented in BRCA2-proficient cells by hyperthermia and alleviated in BRCA2 knockout or siRNA-transfected BRCA2 knockdown cells. In peripheral blood mononuclear cells isolated from sarcoma patients, increased numbers of nuclear γH2AX foci were detected after systemic treatment with trabectedin and hyperthermia of the tumor region. The findings establish BRCA2 degradation by heat as a key factor for a novel treatment strategy that allows targeted chemosensitization to trabectedin and other DNA damaging antitumor drugs by on-demand induction of HRR deficiency.
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10.1002/ijc.30070
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pubmed_556_26126
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Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumors in the gastrointestinal tract. Surgical resection is the only curative treatment, while imatinib is the first-line therapy for recurrent, metastatic, and unresectable GIST. However, more than half of GIST patients suffer from secondary resistance to imatinib within 2 years after treatment initiation. Therefore, early diagnosis, drug resistance and recurrence surveillance are critical for GIST patients. Liquid biopsy is a new method which utilizes the detection of tumor biomarkers in peripheral blood for early diagnosis and therapeutic efficacy assessment. In recent years, liquid biopsy has achieved significant research progress in several kinds of malignancy. This review aims at presenting an overview on research advance of liquid biopsy in GIST and may provide a new method for early diagnosis and therapeutic efficacy assessment of GIST.
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10.3760/cma.j.cn.441530-20200604-00339
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pubmed_839_11804
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Cyanide (CN) is considered to be a terrorist chemical weapon due to its ready availability in multi-kilogram quantities and multi-modal means of intoxication. The body uses the sulfur transferase enzyme rhodanese to detoxify cyanide via conversion of cyanide to thiocyanate. This paper explores the potential energy surfaces for the conversion of cyanide anion and hydrogen cyanide to thiocyanate anion and thiocyanic acid, respectively. The potential energy surface for the conversion of cyanide anion to thiocyanate shows that the formation of thiocyanate (SCN) is vastly preferred to formation of its isomer SNC. However, the potential energy surface for the conversion of hydrogen cyanide to thiocyanic acid reveals that the formation of HSCN and HNCS would be relatively equal. The failure for analytical methods to detect HNCS is rationalized by the observation that deprotonation of either HNCS or HSCN leads to the same thiocyanate anion.
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10.1016/j.jmgm.2009.06.005
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pubmed_681_3588
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OBJECTIVE
To prevent and manage frequent complications after endovascular repair of infrarenal abdominal aortic aneurysm (AAA).
METHODS
The data of 71 cases of infrarenal abdominal aortic aneurysm (AAA) treated by endovascular repair were analysed retrospectively. The reasons, managements, results and prognosis of frequent complications were investigated.
RESULTS
Seventy-one cases of infrarenal AAA were treated by endovascular repair with 100% success rate. There was no surgical conversion to open aneurysm repair. There were 8 cases of primary endoleak, 1 case of nervous complication and acute thrombosis. An average follow-up period was 26 +/- 5 months. Three persistent endoleaks and 4 secondary endoleaks were found during the follow-up period. The endoleak rate was 9.8% (7/71) within 1 month postoperatively and mortality rate was 1.3% (1/71). Total mortality rate was 4.2% (3/71). Two patients died from acute myocardial infarction and one from acute heart failure.
CONCLUSIONS
Endovascular treatment of abdominal aortic aneurysm is technically feasible and can effectively exclude aortic aneurysms from the circulation. Endoleak is a chief complication after endovascular repair of infrarenal AAA.Additional procedures and follow up are very important. Endoleak with enlarged aneurysm should be treated actively.
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pubmed_681_3588
|
pubmed_649_7261
|
In this article, we discuss our review of 284 shoulder injuries that were seen and treated arthroscopically during a five-year period. All of the injuries were related to the athletes' particular sport. We describe the biomechanical basis for these injuries and review the data gathered on the forces involved in the act of throwing.
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10.1093/ptj/66.12.1901
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pubmed_609_22382
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Fractures of the coracoid and acromial processes and avulsion fractures of the scapula are uncommon with the vast majority being managed quite successfully nonoperatively. On occasion, however, these injuries may be significantly displaced and of functional importance, thus making surgical management a consideration. Diagnosis is radiographic. Due to the complex anatomy in the area, CT scanning is often necessary to detect and accurately define these injuries. The various fracture patterns that occur as well as mechanisms of injury are described. Surgical indications are detailed as are the various fixation techniques that may be employed or required. The postoperative rehabilitation program is as important as the surgical procedure.
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pubmed_609_22382
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pubmed_674_6093
|
OBJECTIVE
The aim of this study was to clarify the characteristics of paroxysmal nonepileptic events (PNEs) suspected as being epileptic seizures by families of children with epilepsy.
METHODS
The video-EEG (vEEG) recordings of habitual paroxysmal events in children with epilepsy at Nagoya University Hospital between October 2006 and January 2016 were reviewed. Based on the doctor's suspicion before the vEEG, the PNEs were divided into two groups that included PNEs suspected as epileptic seizures and PNEs suspected as PNEs. PNEs in the former group were classified based on the suspected seizure type.
RESULTS
Of 886 habitual paroxysmal events, vEEG confirmed that 83 events (68 children) were PNEs. The median age of the 68 children was 3.2 years. Concurrent epilepsies included focal epilepsies (n=33), infantile spasms (n=16), and other types (n=19). The most common types of PNEs were sleep myoclonus (n=11), followed by stereotypies (n=9), awake myoclonus (n=8), paroxysmal ocular deviations (PODs, n=8), and tonic posturing (n=8). Even after direct observation or video viewing, the doctors suspected epileptic seizures in all three of the PODs and two of the tonic posturing children. Before the vEEG, however, the accurate visual information led to the speculation that the four psychogenic and two sleep myoclonus events were all PNEs. Myoclonus, stereotypies, and head drops were often misdiagnosed as epileptic spasms, while PODs and tonic posturing were often misdiagnosed as focal seizures with motor components. Additionally, staring and motion arrest during a drowsy state were often misdiagnosed as focal dyscognitive seizures. Seven of eight patients with PODs had epileptic spasms that were concurrent with epileptic seizures. A diffuse cerebral lesion or reduced visual acuity was seen in seven patients with PODs.
CONCLUSION
We re-emphasize that vEEG is essential for accurate diagnosis and provides evidence for listing POD in the differential diagnosis of oculomotor paroxysmal events.
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10.1016/j.eplepsyres.2017.02.009
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pubmed_989_16138
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Ischemia/reperfusion (I/R) is one of the major causes of acute kidney injury (AKI) and associated with increased mortality and progression to chronic kidney injury (CKI). Molecular mechanisms underlying I/R injury involve the production and excessive accumulation of reactive oxygen species (ROS). Peroxiredoxin (Prx) V, a cysteine-dependent peroxidase, is located in the cytosol, mitochondria, and peroxisome and has an intensive ROS scavenging activity. Therefore, we focused on the role of Prx V during I/R-induced AKI using Prx V knockout (KO) mice. Ablation of Prx V augmented tubular damage, apoptosis, and declined renal function. Prx V deletion also showed higher susceptibility to I/R injury with increased markers for oxidative stress, ER stress, and inflammation in the kidney. Overall, these results demonstrate that Prx V protects the kidneys against I/R-induced injury.
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10.3390/antiox9080769
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pubmed_1076_7192
|
Mesoporous SiO2-P2O5 films were synthesized from the vapor phase onto a silicon substrate. First, a precursor solution of cetyltrimethylammonium bromide (C16TAB), H3PO4, ethanol, and water was deposited on a silicon substrate by a spin-coating method. Then, the C16TAB-H3PO4 composite film was treated with tetraethoxysilane (TEOS) vapor at 90-180 degrees C for 2.5 h. The H3PO4-C16TAB composite formed a hexagonal structure on the silicon substrate before vapor treatment. The TEOS molecules penetrated into the film without a phase transition. The periodic mesostructure of the SiO2-P2O5 films was retained after calcination. The calcined films showed a high proton conductivity of about 0.55 S/cm at room temperature. The molar ratio of P/Si in the SiO2-P2O5 film was as high as 0.43, a level that was not attained by a premixing sol-gel method. The high phosphate group content and the ordered periodic mesostructure contributed to the high proton conductivity.
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10.1021/la070081d
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pubmed_56_10271
|
Cord blood stem cells are an attractive starting source for the production of red blood cells in vitro for therapy because of additional expansion potential compared with adult peripheral blood progenitors and cord blood banks usually being more representative of national populations than blood donors. Consequently, it is important to establish how similar cord RBCs are to adult cells. In this study, we used multiplex tandem mass tag labeling combined with nano-LC-MS/MS to compare the proteome of adult and cord RBCs and reticulocytes. 2838 unique proteins were identified, providing the most comprehensive compendium of RBC proteins to date. Using stringent criteria, 1674 proteins were quantified, and only a small number differed in amount between adult and cord RBC. We focused on proteins critical for RBC function. Of these, only the expected differences in globin subunits, along with higher levels of carbonic anhydrase 1 and 2 and aquaporin-1 in adult RBCs would be expected to have a phenotypic effect since they are associated with the differences in gaseous exchange between adults and neonates. Since the RBC and reticulocyte samples used were autologous, we catalogue the change in proteome following reticulocyte maturation. The majority of proteins (>60% of the 1671 quantified) reduced in abundance between 2- and 100-fold following maturation. However, ∼5% were at a higher level in RBCs, localized almost exclusively to cell membranes, in keeping with the known clearance of intracellular recycling pools during reticulocyte maturation. Overall, these data suggest that, with respect to the proteome, there is no barrier to the use of cord progenitors for the in vitro generation of RBCs for transfusion to adults other than the expression of fetal, not adult, hemoglobin.
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10.1074/mcp.M115.057315
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pubmed_346_12490
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Flavoxate is a smooth muscle relaxant widely used to treat urgency and urge incontinence. It has been used in an unblinded, uncontrolled clinical trial in 14 urology departments in universities and major hospitals in the People's Republic of China involving 361 patients with urgency/incontinence of various types. Patients were given 200 mg three times daily, orally, for 2 weeks, although 33 patients received a daily dosage of 1200 mg. Frequency, urgency, dysuria, nocturia and incontinence were assessed and scored clinically prior to and after treatment. Three departments also included urodynamic investigations, e.g. monitoring of the end-residual volume. Results from 336 evaluable patients indicate that 228 (67%) were completely cured of urgency/incontinence symptoms, 66 (20%) were improved and 42 (13%) patients were unchanged. Flavoxate was also effective in 77.4% of patients refractory to previous anti-cholinergic treatment. Treatment did not increase the end-residual volume and adverse events occurred only in four (1.3%) patients, two (0.6%) of which discontinued the therapy. The 1200 mg dose produced a complete cure in 82% of patients and improvement in the remaining 18%, with no side-effects. In conclusion, flavoxate is an effective and well tolerated treatment for urgency/incontinence of various causes.
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pubmed_346_12490
|
pubmed_701_9536
|
The effects of general anaesthesia and surgical trauma on neutrophil function were studied in 60 female ASA 1 and 2 patients undergoing anaesthesia for gynaecological surgery. Patients were divided into three groups depending on the degree of trauma and duration of surgery. Group 1 (n = 15) were patients for dilatation and curettage (minor surgical trauma) and were given 2% halothane. Group 2 (n = 30) had laparoscopic surgery (moderate surgical trauma) and received either 0.5% halothane or 1% enflurane. Group 3 (n = 15) were those having hysterectomy (major surgical trauma) and received 0.5% halothane for a longer duration. Venous samples were taken 30 min before anaesthesia (control value), 10 min after induction of anaesthesia, 10 min after the start of surgery, 30 min after the end of anaesthesia and 24 h later. Phagocytic index, nitroblue tetrazolium reduction test, total leucocyte count, and differential leucocyte counts were performed on each sample. Data were analysed by paired t-test to compare findings in the same patient and by unpaired t-test for differences between groups. Anaesthesia with halothane 0.5% to 2% caused a dose-related depressant effect on leucocyte function which reversed. Enflurane 1% on the other hand caused significantly greater depression of leucocyte function compared with 0.5% halothane which persisted during the recovery period and recovered on the first postoperative day. Total leucocyte counts also showed a fivefold increase in the major surgery groups.
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10.1111/j.1365-2044.1995.tb06137.x
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pubmed_285_17423
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The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAMTS2, 3 and 14), the cartilage oligomeric matrix protein-cleaving enzymes (ADAMTS7 and 12), the von-Willebrand Factor proteinase (ADAMTS13) and a group of orphan enzymes (ADAMTS6, 10, 16, 17, 18 and 19). Control of the structure and function of the extracellular matrix (ECM) is a central theme of the biology of the ADAMTS, as exemplified by the actions of the procollagen-N-propeptidases in collagen fibril assembly and of the aggrecanases in the cleavage or modification of ECM proteoglycans. Defects in certain family members give rise to inherited genetic disorders, while the aberrant expression or function of others is associated with arthritis, cancer and cardiovascular disease. In particular, ADAMTS4 and 5 have emerged as therapeutic targets in arthritis. Multiple ADAMTSs from different sub-groupings exert either positive or negative effects on tumorigenesis and metastasis, with both metalloproteinase-dependent and -independent actions known to occur. The basic ADAMTS structure comprises a metalloproteinase catalytic domain and a carboxy-terminal ancillary domain, the latter determining substrate specificity and the localization of the protease and its interaction partners; ancillary domains probably also have independent biological functions. Focusing primarily on the aggrecanases and proteoglycanases, this review provides a perspective on the evolution of the ADAMTS family, their links with developmental and disease mechanisms, and key questions for the future.
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10.1186/s13059-015-0676-3
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pubmed_385_16920
|
cellular level is not completely understood, but both aging and loading-induced stresses have been shown to undermine cell functions related to the maintenance and restoration of the cartilage matrix. Based on precedents set by studies of other age-related degenerative diseases, we have focused our laboratory work on senescence as the cause of age-dependent decline in chondrocytes and on the impact of excessive mechanical stresses in promoting senescence. We hypothesized that senescent chondrocytes accumulate with age in articular cartilage and we propose that excessive mechanical stress plays a role in this process by promoting oxidative damage in chondrocytes that ultimately causes them to senesce. To test this hypothesis, we measured cell senescence markers (beta-galactosidase expression, mitotic activity, and telomere length) in human articular cartilage chondrocytes, and determined the effects of chronic exposure to oxidative stress on chondrocyte growth and senescence. In addition, we measured the effects of abnormally high levels of mechanical shear stress on the release of oxidants in cartilage explants. We found that senescent chondrocytes accumulated with age in articular cartilage. In vitro studies showed that chronic oxidative stress caused by repeated exposure to peroxide, or by growth under superphysiologic oxygen tension caused chondrocyte populations to senesce prematurely, before extensive telomere erosion occurred. Mechanical shear stress applied to cartilage explants considerably increased the production of oxidants. These observations support the hypothesis that senescence accounts for age-related decline in chondrocyte function and indicate that mechanically induced oxidative damage plays a role in this process. This suggests that new efforts to prevent the development and progression of osteoarthritis should include strategies that slow the progression of chondrocyte senescence or replace senescent cells.
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10.1097/01.blo.0000143818.74887.b1
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pubmed_318_8100
|
Intracoronary injection of tolazoline in dogs produces transient coronary vasodilatation with marked reduction in the arteriovenous oxygen difference and little change in myocardial oxygen consumption. At lower doses coronary effects are produced almost exclusively but as the dose increases, systemic cardiovascular changes occur also. No fatalities occurred even with large doses of tolazoline into the coronary arteries of these healthy dogs. Since intraarterial tolazoline is used to improve visualization of vascular beds in other portions of the body, its possible use for coronary arteriography is discussed.
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pubmed_318_8100
|
pubmed_687_9540
|
OBJECTIVE
To analyze the range of values of the contact pressure between the membranous vocal folds with Reinke's edema and to compare it to those observed in the absence of such a lesion.
METHODS
Two human larynges were separately tested on the experimental bench, one of them with a bilateral loose swelling of the vocal folds. Once in a glottal prephonatory configuration, airflow was increased until achievement of self-sustained oscillations while recording aerodynamic, acoustic, electroglottographic data, and contact pressure between the folds.
RESULTS
We observed well-documented variations in acoustical parameters, as the decrease of the fundamental frequency and the increase of the phonation threshold pressure. The results of the study also point to a significant increase in the amplitude of the contact pressure in presence of the Reinke's edema, and a lower degree of harmonicity of the produced sounds.
CONCLUSION
This is the first report of ex vivo study of a larynx with Reinke's edema. It highlights the increase in the contact pressure during phonation, which possibly contributes to sustain the lesion once it appeared.
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10.1016/j.jvoice.2020.02.020
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pubmed_986_6521
|
It was shown that mitotic activity of the gastric mucosa epithelium in Citelius erythrogenus Br. is characterized by pronounced seasonal changes. The highest mitotic index was recorded 3-4 days after the arousal from hibernation, while the lowest one during summer time (May-June). The mitoses are blocked during winter torpor. The circadian peak of the mitotic activity in summer was recorded at 10 p.m. The mitotic cells were discovered not only in the generative zone but also at all the levels of the fundal and pyloric glands. Radioautography with 3H-thymidine administration in vivo is not fit for studying the synthesis of DNA in sousliks.
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pubmed_986_6521
|
pubmed_628_11212
|
There is evidence that malnutrition is an important cause of morbidity and mortality in lung cancer patients and may have an impact on the clinical course of disease. The simplest way to assess nutritional status at the patient's bedside remains recourse to anthropometric measurements. This study was carried out in order to assess the clinical and prognostic significance of triceps skinfold thickness (TST), arm circumference (AC), and wrist circumference (WC) in lung cancer. The patient population was a consecutive series of 388 patients seen for a newly diagnosed primary non-small-cell lung cancer during the last 4 years. A set of 22 anthropometric, clinical, physical, laboratory, radiological, and pathological variables was prospectively recorded for all patients. Patients were carefully followed up, and their subsequent clinical course was recorded. The median values of TST, WC and AC were 8 mm (range 2-25 mm), 18 cm (range 10-27 cm), and 25 cm (range 15-35 cm), respectively. In 107 patients (27.6% of the total) TST values were below the reference value, and 37 of these patients also had a pathologically low small circumference. In all, AC was below the normality range in 60 of the 388 subjects (15.5%). Among the three variables, the strongest relationships were those between AC and WC (r(s)=0.541), and between TST and AC (r(s)=0.521). Univariate analyses of survival showed that TST was strongly predictive of a better prognosis (P<0.001), while WC was unrelated to outcome (P=0.101). Patients with higher values of AC had significantly longer survival than patients with lower values (P<0.018). The multivariate model, in contrast, did not confirm the prognostic capability of any of the anthropometric measures. These data indicate that the anthropometric measures may be significant predictors of survival, although not independently of the other prognostic factors.
|
10.1007/s005200100268
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pubmed_1003_18375
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We developed a clinically applicable approach for noninvasive monitoring of reporter-therapeutic linked gene expression in the whole heart of large animals using PET imaging and further validated the efficacy and cardiac adverse effects of reporter-therapeutic linked gene transfer in a rabbit cervical heterotopic functional heart transplant model. Cationic liposome complexed with a vector containing a herpes simplex virus type 1 mutant thymidine kinase (HSV1-sr39tk) as the reporter gene and a recombinant human immunosuppressive cytokine, interleukin-10 (hIL-10), as the therapeutic gene was ex vivo intracoronarily delivered into cardiac allografts before implantation. Long-term HSV1-sr39tk and hIL-10 transgene and protein overexpression associated with myocardial PET reporter probe 9-(4-[18F]fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG) accumulation was observed in the allografts. The expression of the HSV1-sr39tk gene was significantly correlated with the hIL-10 gene expression and the total myocardial [18F]FHBG accumulation quantified as a percentage of intravenously injected [18F]FHBG dose. A homogeneous distribution of [18F]FHBG accumulation was seen in the whole heart similar to the distribution of [18F]fluorodeoxyglucose, a PET glucose metabolism probe. The immunosuppressive therapeutic efficacy remained the same in allografts treated with reporter-therapeutic linked gene and therapeutic gene only. No cardiac adverse effect was found. Our results demonstrate for the first time that PET reporter-therapeutic linked gene imaging is applicable for noninvasively monitoring ex vivo intracoronarily delivered therapeutic transgene expression in the whole heart.
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10.1016/j.ymthe.2005.03.004
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pubmed_28_26051
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BACKGROUND
A growing body of evidence suggests that Hsp70, which is overexpressed in human breast tumors, plays a role in tumorigenesis and tumor progression in breast cancer as well as in its aggressive phenotypes. Hsp70 constitutes a potential therapeutic target in the treatment of this disease.
METHODS
We developed a new series of rhodacyanine-based Hsp70 inhibitors, represented by compounds 1 and 6, in which the cationic pyridin-1-ium or thiazol-3-ium ring of existing Hsp70 inhibitors (e.g., JG-40 and JG-98) was replaced by a corresponding benzo- fused N-heterocycle.
RESULTS
Several lines of evidence suggest that these benzo-fused derivatives may exert their antitumor activities, in part, by targeting Hsp70. These putative inhibitors displayed differential antiproliferative efficacy against breast cancer cells (IC50 as low as 0.25 μM) versus nontumorigenic MCF-10A breast epithelial cells (IC50 ≥ 5 μM). This was correlated with the corresponding Hsp70 expression levels. Using a protein refolding assay, we confirmed that these agents effectively inhibited the chaperone activity of Hsp70. Moreover, these inhibitors effectively suppressed the expression of well-known oncogenic client proteins of Hsp70's, including FoxM1, HuR, and Akt, which paralleled their antiproliferative efficacy. Supporting the established role of Hsp70 in regulating protein refolding, these derivatives induced autophagy, as manifested by the conversion of LC3B-I to LC3B-II. Notably, these putative Hsp70 inhibitors did not cause a compensatory elevation in Hsp90 expression, contrasting with the previously reported effects of Hsp90 inhibitors on Hsp70 upregulation.
CONCLUSION
Together with the finding that compounds 1 and 6 showed improved microsomal stability, these results suggest the translational potential of these putative Hsp70 inhibitors to foster new strategies for cancer therapy. However, whether these benzo-fused rhodacyanines act on kinases or other targets remains unclear. It is currently under investigation.
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10.2174/0929867328666210203204254
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pubmed_719_21206
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Holographic phase-only projection technique utilizing spatial light modulators (SLM) as an active element may be intended to work in environments in which the temperature changes with time, such as outdoors or automotive applications. In order to achieve maximum possible resolution, the thermally induced aberrations of the SLM must be corrected in real time. We present the results of non-invasive determination of the SLM aberrations in holographic image projection, caused mostly by thermal strains of SLM, with the use of one fixed camera detector and iterative phase retrieval. We show real-time wavefront correction leading to experimentally proven, diffraction-limited image quality in a wide range of SLM temperatures.
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10.1364/OE.27.010193
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pubmed_670_3488
|
Computer modeling was applied for the first time to investigate previously reported complementarity of progesterone and cavities formed between base pairs in partially unwound double stranded DNA. Computer graphics enabled a more objective assessment of complementarity; energy calculations provided a rigorous method to evaluate degree of fit. Graphics confirmed that the complementarity was virtually "lock and key", i.e. close contacts were formed between van der Waals surfaces in the progesterone/DNA complexes and hydrogen bonds were formed between the two carbonyl groups on opposite ends of the steroid and phosphate groups on adjacent strands of DNA. Molecular mechanics calculations revealed that insertion of the steroid resulted in a relatively stable complex i.e. both van der Waals and electrostatic energies were lowered due to favorable steric interactions and stereospecific hydrogen bonds, respectively. Three published X-ray crystal structures of progesterone exhibited similar complementarity. Ent-progesterone which does not occur naturally possessed very poor complementarity. These findings confirm that the structure of progesterone is directly reflected in the stereochemistry of DNA. While no mechanistic explanation for these results is proffered, we hypothesize that such complementarity must have played a decisive role in the evolution of steroid hormone structure and function.
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10.1016/0960-0760(91)90054-9
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pubmed_161_12441
|
Previous electrocardiographic models of myocardial ischemic injury have assumed that transmembrane potential changes are uniform throughout a region of ischemia such that injury currents arise exclusively at the boundary between normal and ischemic myocardium. In such models, the distribution and amplitude of ST segment deflections are considered to arise from a polarized surface interfacing normal and ischemic myocardium. This concept in modeling ischemic injury was derived from the application of principles of electric field theory which had been successfully applied previously to ventricular activation in which QRS potentials are considered to arise from polarized surfaces representing the relatively narrow interfaces between depolarized and nondepolarized myocardium. The present paper outlines the limitations of modeling ischemic injury as a polarized surface in terms of the failure of the predictions of such a model to be supported by the experimentally observed: 1) distribution and relative amplitude of epicardial ST segment elevation overlying a region of ischemia; 2) directional changes in epicardial ST segment elevation that occur with changes in the size of an ischemic region; and 3) nonuniform distribution of transmembrane potential changes which occur within a region of ischemia. A new electrocardiographic model of ischemic injury is formulated which accounts for the nonuniform distribution of transmembrane potential changes which occur throughout a region of ischemia. The model accurately describes experimental observations regarding ST segment deflections which had remained inconsistent with previous models.
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10.1016/s0022-0736(83)80001-6
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pubmed_655_18800
|
CD28 and CTLA-4 are related receptors that differentially regulate T cell activation. Despite the fact that they bind the same ligands, CD28 is a classical costimulator enhancing proliferation whereas CTLA-4 appears to perform negative regulatory functions. In this study, we have utilized the natural ligand for CD28 and CTLA-4 (CD80) to determine under what circumstances positive and negative effects are operative. We show here that the stimulation of purified human T cells with phorbol ester and ionomycin is inhibited in the presence of Chinese hamster ovary (CHO) cells expressing CD80. This inhibition is reversed by blocking with both anti-CD80 or Fab fragments of anti-CTLA-4 but also requires CD28 engagement. Furthermore, we show that the inhibitory function of CD80 requires elevated intracellular calcium since inhibition was observed only in the presence of ionomycin. In the absence of intracellular calcium elevation, CTLA-4 was not expressed at the cell surface, and CD80 acted positively as a costimulator of T cells, via CD28. These results demonstrate that the natural ligand CD80 can either costimulate or inhibit T cell responses depending on the conditions of T cell stimulation.
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pubmed_655_18800
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pubmed_372_21475
|
BACKGROUND
The incidence rate of colorectal cancer (CRC) is increasing among patients below 50 years of age. The reason for this is unclear, but could have to do with the fact that indicative variables, such as tumour location, gender preference and genetic preponderance have not been followed up in a consistent mann er. The current study was primarily conducted to improve the hereditary CRC screening programme by assessing the demographic and clinicopathological characteristics of early-onset CRC compared to late-onset CRC in northeast Iran.
METHODS
This retrospective study, carried out over a three-year follow-up period (2014-2017), included 562 consecutive CRCs diagnosed in three Mashhad city hospital laboratories in north-eastern Iran. We applied comparative analysis of pathological and hereditary features together with information on the presence of mismatch repair (MMR) gene deficiency with respect to recovery versus mortality. Patients with mutations resulting in absence of the MMR gene MLH1 protein product and normal BRAF status were considered to be at high risk of Lynch syndrome (LS). Analyses using R studio software were performed on early-onset CRC (n = 222) and late-onset CRC (n = 340), corresponding to patients ≤50 years of age and patients > 50 years.
RESULTS
From an age-of-onset point of view, the distribution between the genders differed with females showing a higher proportion of early-onset CRC than men (56% vs. 44%), while the late-onset CRC disparity was less pronounced (48% vs. 52%). The mean age of all participants was 55.6 ± 14.8 years, with 40.3 ± 7.3 years for early-onset CRC and 65.1 ± 9.3 years for late-onset CRC. With respect to anatomical tumour location (distal, rectal and proximal), the frequencies were 61, 28 and 11%, respectively, but the variation did not reach statistical significance. However, there was a dramatic difference with regard to the history of CRC in second-degree relatives between two age categories, with much higher numbers of family-related CRCs in the early-onset group. Expression of the MLH1 and PMS2 genes were significantly different between recovered and deceased, while this finding was not observed with regard to the MSH6 and the MSH2 genes. Mortality was significantly higher in those at high risk of LS.
CONCLUSION
The variation of demographic, pathological and genetic characteristics between early-onset and late-onset CRC emphasizes the need for a well-defined algorithm to identify high-risk patients.
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10.1186/s12885-021-09132-5
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pubmed_827_2258
|
BACKGROUND
The CAPRIE study showed the superiority of clopidogrel over acetylsalicylic acid (ASA) for reducing the combined risk of major atherothrombotic events in patients with recent myocardial infarction (MI), recent ischaemic stroke (IS) or established peripheral arterial disease. The benefit of clopidogrel over ASA is amplified in high-risk patients. Proof of concept for the benefit of clopidogrel in addition to ASA in patients with coronary manifestations of atherothrombosis was provided by the CURE trial.
METHODS
MATCH is a randomized, double-blind, placebo-controlled trial that compares clopidogrel and ASA versus clopidogrel alone in high-risk patients with recently symptomatic cerebrovascular disease. Eligible patients have experienced a transient ischaemic attack (TIA) or IS within the last 3 months and have evidence of at least 1 additional risk factor within the last 3 years (prior IS, MI, stable or unstable angina pectoris, diabetes or symptomatic peripheral arterial disease). Patients were randomized to receive ASA 75 mg once daily or placebo, with both groups receiving clopidogrel 75 mg once daily as part of standard therapy. The primary end point is the composite of IS, MI, vascular death and rehospitalization for an acute ischaemic event. The duration of treatment and follow-up is 18 months for each patient.
RESULTS
Enrollment was completed in April 2002, with 7,599 patients randomized to receive the study medication. The mean age at randomization was 66 years, and the qualifying event was IS in 78.9% of patients and TIA in 21.1%. The baseline features of the study cohort indicate a population that is at a high risk for atherothrombotic recurrence.
CONCLUSION
MATCH is a major ongoing trial that will provide important data on the benefit of clopidogrel and ASA compared with clopidogrel alone for reduction of vascular ischaemic events in patients with recent TIA or IS who are at high risk of atherothrombotic event recurrence.
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10.1159/000076962
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pubmed_584_2415
|
The ciliary neurotrophic factor alpha-receptor (CNTFRalpha) is required for motoneuron survival during development, but the relevant ligand(s) has not been determined. One candidate is the heterodimer formed by cardiotrophin-like cytokine (CLC) and cytokine-like factor 1 (CLF). CLC/CLF binds to CNTFRalpha and enhances the survival of developing motoneurons in vitro; whether this novel trophic factor plays a role in neural development in vivo has not been tested. We examined motor and sensory neurons in embryonic chicks treated with CLC and in mice with a targeted deletion of the clf gene. Treatment with CLC increased the number of lumbar spinal cord motoneurons that survived the cell death period in chicks. However, this effect was regionally specific, because brachial and thoracic motoneurons were unaffected. Similarly, newborn clf-/- mice exhibited a significant reduction in lumbar motoneurons, with no change in the brachial or thoracic cord. Clf deletion also affected brainstem motor nuclei in a regionally specific manner; the number of motoneurons in the facial but not hypoglossal nucleus was significantly reduced. Sensory neurons of the dorsal root ganglia were not affected by either CLC treatment or clf gene deletion. Finally, mRNA for both clc and clf was found in skeletal muscle fibers of embryonic mice during the motoneuron cell death period. These findings support the view that CLC/CLF is a target-derived factor required for the survival of specific pools of motoneurons. The in vivo actions of CLC and CLF can account for many of the effects of CNTFRalpha on developing motoneurons.
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pubmed_584_2415
|
pubmed_804_22625
|
Metabolite diffusion in tissues produces gradients and heterogeneous microenvironments that are not captured in standard 2D cell culture models. Here we describe restricted exchange environment chambers (REECs) in which diffusive gradients are formed and manipulated on length scales approximating those found in vivo. In REECs, cells are grown in 2D in an asymmetric chamber (<50 μL) formed between a coverglass and a glass bottom cell culture dish separated by a thin (~100 μm) gasket. Diffusive metabolite exchange between the chamber and bulk media occurs through one or more openings micromachined into the coverglass. Cell-generated concentration gradients form radially in REECs with a single round opening (~200 μm diameter). At steady state only cells within several hundred micrometers of the opening experience metabolite concentrations that permit survival which is analogous to diffusive exchange near a capillary in tissue. The chamber dimensions, the openings' shape, size, and number, and the cellular density and metabolic activity define the gradient structure. For example, two parallel slots above confluent cells produce the 1D equivalent of a spheroid. Using REECs, we found that fibroblasts align along the axis of diffusion while MDCK cells do not. MDCK cells do, however, exhibit significant morphological variations along the diffusive gradient.
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10.2144/btn-2017-0110
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pubmed_989_6151
|
BACKGROUND
Unintended pregnancies may be mistimed or unwanted. It represents 40% of all pregnancies, and it had multiple risky health outcomes. It is essential to understand the factors affecting unintended pregnancies and their consequences to develop strategies that help prevent them. The present study is conducted to identify the prevalence, determinants, and outcomes of unintended pregnancies in Sohag district, Egypt.
METHODS
A cross-sectional study was conducted in Sohag district, 2016. Five hundred fifty-four ever married women aged 18-49 years whose last pregnancy was in the 3 years preceding the data collection date were randomly selected from rural and urban localities. Data were collected through home visits using a validated questionnaire. In this study, Sohag city represents the urban place, while Tunis and El-Sheikh Makram villages represent the rural places.
RESULTS
Nearly one third (30.7%) of the study sample had an unintended pregnancy within the last 3 years from the time of interview. Regression analysis showed that young women < 30 (OR = 2.24, 95% CI 1.12-4.48, p = 0.02), young husbands ≤ 30 (OR = 5.44, 95% CI 1.14-26.11, p = 0.03), women working for cash (OR = 6.16, 95% CI 3.15-13.92, p < 0.0001), monthly income ≤ 1200 LE (OR = 34, 95% CI 6.41-187.52, p < 0.0001), and spacing < 24 months (OR = 8.79, 95% CI 4.33-17.80, p < 0.0001) were risk factors for mistimed pregnancy. On the other hand, women working for cash (OR = 11.43, 95% CI 3.22-40.62, p < 0.0001), living children ≥ 5 (OR = 11.45, 95% CI 2.84-46.07, p = 0.001), and the woman's perception of her family size as higher than the ideal (OR = 394.8, 95% CI 97.36-1601.17, p < 0.0001) were risk factors for unwanted pregnancy. Mistimed and unwanted pregnancies were significantly associated with late start of antenatal care (ANC), low birth weight (LBW), and no breastfeeding. In addition, unwanted pregnancies were associated with more pregnancy complications.
CONCLUSIONS AND RECOMMENDATIONS
Unintended pregnancy represents a public health problem in Sohag. Therefore, improving services in rural areas and improving the economic level and effective use of family planning methods could reduce the risks associated with the unintended pregnancy.
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10.1186/s42506-019-0014-9
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pubmed_503_11896
|
Analysis of non-Hodgkin lymphoma (NHL) involvement of bone marrow trephine biopsy specimens by morphologic features and immunohistochemistry is often difficult, and the criteria for involvement are ill defined. We compared the morphologic and immunohistochemical analysis of B-cell NHL involvement with immunoglobulin heavy chain gene (IgH) rearrangement analysis by polymerase chain reaction (PCR) amplification of the complementarity determining region 3 (CDR3) in bone marrow biopsy specimens from patients with mantle cell lymphoma (n = 53) or hairy cell leukemia (n = 71). By combing morphologic features and phenotype, 54 specimens were considered positive, 62 negative, and 8 inconclusive. PCR analysis showed clonal IgH rearrangements in 46 positive and 6 inconclusive specimens. No clonal IgH rearrangements were present in 61 negative specimens. The 1 false-positive and most false-negative PCR results were likely due to sampling error or DNA degradation of the fixed tissues. In most cases, bone marrow involvement by NHL can be identified by histologic and immunohistochemical examination. Furthermore, clonality of the B-cell population can be detected by amplification of the IgH CDR3 on DNA extracted from bone marrow trephine biopsy sections, which can be helpful in cases diagnosed as inconclusive.
|
10.1093/ajcp/111.2.179
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pubmed_71_6430
|
Prasinophytes, a group of eukaryotic phytoplankton, has a global distribution and is infected by large double-stranded DNA viruses (prasinoviruses) in the family Phycodnaviridae. This study examines the genetic repertoire, phylogeny, and environmental distribution of phycodnaviruses infecting Micromonas pusilla, other prasinophytes and chlorophytes. Based on comparisons among the genomes of viruses infecting M. pusilla and other phycodnaviruses, as well as the genome from a host isolate of M. pusilla, viruses infecting M. pusilla (MpVs) share a limited set of core genes, but vary strongly in their flexible pan-genome that includes numerous metabolic genes, such as those associated with amino acid synthesis and sugar manipulation. Surprisingly, few of these presumably host-derived genes are shared with M. pusilla, but rather have their closest non-viral homologue in bacteria and other eukaryotes, indicating horizontal gene transfer. A comparative analysis of full-length DNA polymerase (DNApol) genes from prasinoviruses with their overall gene content, demonstrated that the phylogeny of DNApol gene fragments reflects the gene content of the viruses; hence, environmental DNApol gene sequences from prasinoviruses can be used to infer their overall genetic repertoire. Thus, the distribution of virus ecotypes across environmental samples based on DNApol sequences implies substantial underlying differences in gene content that reflect local environmental conditions. Moreover, the high diversity observed in the genetic repertoire of prasinoviruses has been driven by horizontal gene transfer throughout their evolutionary history, resulting in a broad suite of functional capabilities and a high diversity of prasinovirus ecotypes.
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10.3390/v9050116
|
pubmed_754_9886
|
Common features in two patients with chronic suppurative lesions of the maxillofacial region from vegetable foreign bodies were : foreign body origin of the accident ; chronic nature of the suppuration (7 and 23 months respectively) ; multiple operations by different surgical teams ; radiotransparency of the foreign bodies. Positive signs on CT scanning can confirm the diagnosis, but cannot exclude it when normal images are obtained. The number and localization of wood fragments may limit the value of the scan, and fistulography and xeroradiography may then provide confirmation of the diagnosis. Operative treatment may be difficult due to fragmentation of the wood into multiple pieces, a possible source of recurrence of infection.
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pubmed_754_9886
|
pubmed_948_5405
|
The objective of this investigation was to test the effects of glycine, a cytoprotectant in normothermic in vitro models of renal ischemia, in a model of hypothermic renal preservation injury. This study also probes possible physiological mechanisms of glycine protection during renal hypothermic ischemia-reperfusion injury. Canine kidneys were subjected to 48 h of hypothermic ischemia (4 degrees C) after intravascular flush with cold conventional Collins solution (G. H. Collins, M. B. Bravo-Shugarman, and P. I. Terasaki, Lancet 2: 1219-1223, 1969) and were subsequently revascularized for 1 h. After 1 h of reperfusion, glomerular filtration rate, urine production, and electrolyte excretion were dramatically higher when the Collins flush contained 5 mM glycine, compared with the 0 mM glycine controls. Renal tissue adenine nucleotides and glutathione levels progressively declined with graded cold ischemia times, and glycine had no effect on these levels. However, renal tissue ATP levels (but not glutathione) were significantly higher when kidneys were flushed with glycine, stored for 48 h, and reoxygenated in vitro for 1 h at 37 degrees C, compared with kidneys flushed without glycine. Analysis of CoA esters from ischemic renal tissue indicated altered production of only butyryl CoA after 48 and 72 h of cold ischemia, but no differences were detected in glycine or control kidneys. In conclusion, this study reports dramatic functional preservation with glycine in kidneys subjected to hypothermic ischemia and in vivo reperfusion. The mechanisms of these effects appear not to be attributable to the maintenance of cellular adenine nucleotide or glutathione levels nor to the scavenging of accumulated amphipathic acyl CoA esters.
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10.1152/ajprenal.1991.261.5.F841
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pubmed_1014_15727
|
BACKGROUND
Leptin, which has been identified as an antiobesity hormone, regulates body weight by controlling food intake and energy expenditure via the hypothalamic-pituitary-gonadal axis. It appears that leptin may be an important factor in obesity management. Orlistat, a pancreatic lipase inhibitor, could reduce fat absorption and promote weight loss due to leptin metabolism.
OBJECTIVE
The purpose of this study was to investigate the effects of orlistat therapy on serum leptin levels.
METHODS
Obese women (body mass index [BMI], 30 kg/m(2)) aged 18 to 50 years were randomly assigned to receive 12 weeks of oral treatment with diet-orlistat (120 mg TID) (DO group) or diet-placebo (DP group). During the treatment period, patients were asked to eat a balanced diet of -1200 to 1600 kcal/d. Body composition was determined by bioelectrical impedance. Serum leptin levels were measured using radioimmunoassay at baseline and at study end.
RESULTS
A total of 24 patients entered the study; 14 patients (mean [SE] BMI, 37.7 [1.1] kg/m(2)) received orlistat and 10 patients (mean [SE] BMI, 39.4 [1.3] kg/m(2)) received placebo. Compared with baseline, mean percentages of loss of body weight and fat mass after 12 weeks of treatment were significant in the DO group (9.1% and 14.8%, respectively; both P = 0.001) and in the DP group (9.5% and 17.6%; both P = 0.005). The between-group differences were not statistically significant. Mean (SE) serum leptin levels also decreased significantly after treatment in the DO group (16.2 [1.2] vs 9.0 [1.0] ng/mL; P = 0.001) and in the DP group (19.3 [2.1] vs 9.7 [1.4] ng/mL; P = 0.005). The between-group difference was not statistically significant.
CONCLUSIONS
In this study of obese women, orlistat treatment was associated with a similar decrease in body weight, fat mass, and serum leptin levels as placebo over a 12-week period. In this regard, short-term orlistat therapy may not provide an additional effect on serum leptin levels, and reduction in leptin levels were closely related to the decrease in fat mass.
|
10.1016/S0011-393X(04)90025-2
|
pubmed_1033_16777
|
The GP.Mur (Miltenberger class III) phenotype was found to occur in about 6.3 percent of Hong Kong (HK) Chinese blood donors. The incidence of antibodies directed against antigenic determinants of GP.Mur cells (anti-Mi) among patients was 0.34 percent, similar to that in Taiwan Chinese. A case of hydrops fetalis probably attributable to maternal anti-Mi was encountered in an HK Chinese woman during her sixth pregnancy. The anti-Mi was potent (titer 512, score 99). It fixed complement and was a mixture of IgG1 and IgG3. Two biological assays, the monocyte monolayer assay and the chemiluminescence test, were strongly positive. The father was found to be heterozygous for the GP.Mur gene.
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pubmed_1033_16777
|
pubmed_1129_169
|
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. It has been previously reported that CSN5 depletion is an effective method in human HCC. In the current study, we aimed to uncover gene signatures and key pathways during HCC. Gene expression profiles of GSE26485 were downloaded from GEO database. Totally, 101 differentially expressed genes (DEGs) were up-regulated and 146 ones were down-regulated. Biological processes (BP) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) analysis showed that the DEGs were mainly enriched in regulation of cell growth, oxidation-reduction process, mitotic cytokinesis, negative regulation of macroautophagy, endosome organization, lysosome, biosynthesis of antibiotics, small cell lung cancer and glutathione metabolism and so on (P < 0.05). Protein-protein interaction (PPI) network, Kaplan-Meier, log-rank method, western blot, immunohistochemistry and encyclopedia of DNA elements (ENCODE) analysis showed that CSN5 depletion took effects through down-regulation of SMAD5-related pathways which include EXO1, CENPA and NCAPG, resulting in the inactivation of H3K4me3 and H3K36me3. Those genes represent the promising targets for therapeutic intervention in HCC patients.
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10.1016/j.cellsig.2018.06.002
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pubmed_953_25221
|
BACKGROUND
GB virus C (GBV-C) is a flavivirus that was characterized in 1995. The prevalence of GBV-C RNA in HIV-infected subjects has not been previously studied in Iran and was therefore determined.
METHODS
We have investigated serum samples of 80 patients from Imam Khomeini Hospital, Tehran, Iran, whose HIV infection was confirmed in our laboratory by Western-blotting. We used nested-PCR to detect GBV-C/HGV RNA in their sera.
RESULTS
GBV-C/HGV RNA was detected in 15 (18.8%) of 80 patients. There was no significant difference in GBV-C/HGV RNA prevalence between males and females, in different age groups and HIV viral loads groups.
CONCLUSION
The prevalence of GBV-C RNA was high in HIV-infected patients. There was no association between GBV-C RNA prevalence and specific gender, age, and HIV viral loads groups.
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pubmed_953_25221
|
pubmed_156_1338
|
Blood monocyte phagocytic functions were evaluated by chemotaxis, phagocytosis, and superoxide anion production in nine patients with common variable immunodeficiency (CVI), eight patients with X-linked agammaglobulinemia (XLA), and in 17 normal subjects. Further laboratory diagnosis included the determination of the Bruton's tyrosine kinase (Btk) protein expression in monocytes using flow cytometry. The analysis of monocyte phagocytic function demonstrated that CR3-, CR1-, and Fc-mediated phagocytosis (p = 0.0001) were significantly decreased in CVI and XLA patients, and chemotaxis of monocytes (p = 0.0082) was reduced in XLA patients. Superoxide anion production, however, did not differ between the CVI, XLA, and the control groups. The cytoplasmic expression of Btk protein in monocytes was normal in CVI patients and decreased or not detected in XLA patients. It is proposed that impaired chemotaxis and phagocytosis by monocytes may be a characteristic of the innate immune system in CVI and XLA patients, providing a new direction for the physiopathology of these immunodeficiencies.
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pubmed_156_1338
|
pubmed_492_5773
|
The slow-closing phase of the mastication cycle plays a major role in the mastication of foods. However, the neuronal mechanism underlying the slow-closing phase remains unknown. The isometric contraction of jaw-closing muscles is developed through the recruitment of jaw-closing motoneurons during the slow-closing phase. It is well established that motor units are recruited depending on the order of sizes or input resistances (IRs) of motoneurons, which is known as the size principle. Two-pore-domain acid-sensitive K(+) (TASK1/3) channels are recently found to be the molecular correlates of the IR, and also found to be expressed in the masseter motoneurons. Here, we addressed the question whether spindle Ia inputs onto masseter motoneurons can induce the orderly recruitment of motoneurons in slice preparations of the rat brain using voltage-sensitive dye imaging and whole-cell patch-clamp methods. Voltage-sensitive dye imaging revealed the recruitment of many motoneurons in the whole nucleus of masseter in response to repetitive stimulation of the presumed spindle Ia inputs. Dual whole-cell recordings obtained from two adjacent motoneurons revealed the IR-ordered recruitment of motoneurons in response to repetitive stimulation of the presumed spindle Ia inputs. Thus, Ia inputs are likely to play a crucial role in the orderly recruitment of motoneurons of the trigeminal motor nucleus, which would be progressed during the slow-closing phase of the mastication cycle. Possible involvements of TASK channels in the orderly recruitment are discussed.
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10.1016/B978-0-444-53613-6.00011-3
|
pubmed_170_22792
|
Turner syndrome is associated with spatial and numerical cognitive impairments. We hypothesized that these nonverbal cognitive impairments result from limits in spatial and temporal processing, particularly as it affects attention. To examine spatiotemporal attention in girls with Turner syndrome versus typically developing controls, we used a multiple object tracking task during functional magnetic resonance (fMRI) imaging. Participants actively tracked a target among six distracters or passively viewed the animations. Neural activation in girls with Turner syndrome during object tracking overlapped with but was dissimilar to the canonical frontoparietal network evident in typically developing controls and included greater limbic activity. Task performance and atypical functional activation indicate anomalous development of cortical and subcortical temporal and spatial processing circuits in girls with Turner syndrome.
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10.1352/1944-7558-115.2.140
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pubmed_285_8650
|
Pooled data from 16 radiology centers were retrospectively analyzed to seek patients with pathologically proven testicular lymphoma and grayscale and color Doppler images available for review. Forty-three cases were found: 36 (84%) primary and 7 (16%) secondary testicular lymphoma. With unilateral primary lymphoma, involvement was unifocal (n = 10), multifocal (n = 11), or diffuse (n = 11). Synchronous bilateral involvement occurred in 6 patients. Color Doppler sonography showed normal testicular vessels within the tumor in 31 of 43 lymphomas (72%). Testicular lymphoma infiltrates through the tubules, preserving the normal vascular architecture of the testis. Depiction of normal testicular vessels crossing the lesion is a useful adjunctive diagnostic criterion.
|
10.7863/ultra.34.6.1139
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pubmed_133_12212
|
Septal cholinergic neurons may affect hippocampal memory encoding and retrieval by differentially targeting parvalbumin (PARV)-containing basket cells and neuropeptide Y (NPY) interneurons. Thus, the cellular associations of cholinergic efferents, identified by the low-affinity, p75 neurotrophin receptor (p75(NTR)), with interneurons containing either PARV or NPY in the hilus of the rat dentate gyrus were examined in single sections using dual labeling immunoelectron microscopy. Most profiles immunoreactive (IR) for PARV and NPY were perikaryal and dendritic and found within the infragranular and central hilar regions, respectively, whereas most profiles with p75(NTR)-labeling were unmyelinated axons and axon terminals. Although PARV-labeled profiles were more numerous, p75(NTR)-labeled axons and terminals contacted few PARV-IR profiles compared to NPY-labeled profiles (2% of 561 for PARV vs 12% of 433 for NPY). Moreover, structures targeted by p75(NTR)-IR axon terminals varied depending on the presence of PARV or NPY immunoreactivity. p75(NTR)-IR terminals primarily contacted PARV-IR dendrites (87%) compared to somata (13%); however, they contacted more NPY-IR somata (57%) than dendrites (43%). p75(NTR)-labeled terminals formed exclusively symmetric (inhibitory-type) synapses with PARV-IR somata and dendrites; however, they formed mostly symmetric but also asymmetric (excitatory-type) synapses with NPY-IR somata and dendrites. These results suggest that septal cholinergic efferents in the dentate gyrus: (1) preferentially innervate NPY-containing interneurons compared to PARV-containing basket cells; and (2) may provide a more powerful (i.e., somatic contacts), yet functionally diverse (i.e., asymmetric and symmetric synapses), modulation of NPY-containing interneurons. Moreover, they provide evidence that neurochemical subsets of hippocampal interneurons can be distinguished by afferent input.
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pubmed_133_12212
|
pubmed_1065_3313
|
BACKGROUND AND PURPOSE
The developing fetal skull base has previously been studied via dissection and low-resolution CT. Most of the central skull base develops from endochondral ossification through an intermediary chondrocranium. We traced the development of the normal fetal skull base by using plain radiography, MR imaging, and CT.
METHODS
Twenty-nine formalin-fixed fetal specimens ranging from 9 to 24 weeks' gestational age were examined with mammographic plain radiography, CT, and MR imaging. Skull base development and ossification were assessed.
RESULTS
The postsphenoid cartilages enclose the pituitary and fuse to form the basisphenoid, from which the sella turcica and the posterior body of the sphenoid bone originate. The presphenoid cartilages will form the anterior body of the sphenoid bone. Portions of the presphenoid cartilage give rise to the mesethmoid cartilage, which forms the central portion of the anterior skull base. Ossification begins in the occipital bone (12 weeks) and progresses anteriorly. The postsphenoid (14 weeks) and then the presphenoid portion (17 weeks) of the sphenoid bone ossify. Ossification is seen laterally (16 weeks) in the orbitosphenoid, which contributes to the lesser wing of the sphenoid, and the alisphenoid (15 weeks), which forms the greater wing.
CONCLUSION
MR imaging can show early progressive ossification of the cartilaginous skull base and its relation to intracranial structures. The study of fetal developmental anatomy may lead to a better understanding of abnormalities of the skull base.
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pubmed_1065_3313
|
pubmed_733_19744
|
BACKGROUND
Patients with T3 and/or N1 prostate carcinoma have poor cure rates. The authors sought to improve the relapse free, cancer specific survival of these patients by adding chemohormonal therapy to radiation.
METHODS
Twenty-five men with clinical Stage III positive seminal vesicles or positive nodes received six courses of vinblastine, doxorubicin, and mitomycin with simultaneous radiation and permanent androgen deprivation. Prostate specific antigen (PSA) testing was the sole criterion for relapse. Median followup was 10.5 years.
RESULTS
Treatment was well tolerated. Patients received 91-95% of each drug and all planned radiation. At 10 years the cumulative relapse free rate determined by continuously undetectable PSA levels was 73%, and the cumulative cancer specific survival was 81%. Of node-positive patients, 82% were relapse-free at 10 years.
CONCLUSIONS
The addition of chemotherapy to hormonal and radiation therapy is feasible and is accepted by most men when they are openly informed of their prognosis with conventional therapy. Results in the current small series appear excellent and may be superior to radiation plus hormones alone. Larger randomized studies are warranted.
|
10.1002/cncr.10527
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pubmed_576_19260
|
Little is known about the role of the tonsils in HTLV-I infection. We performed molecular pathologic studies of tonsils in individuals positive or negative for anti-HTLV-I antibodies (HTLV-I-Ab) to clarify histologic characteristics of tonsils in HTLV-I infection. We collected tonsils and peripheral blood samples from patients who underwent tonsillectomy in a prospective manner. HTLV-I-Ab in serum was examined and presence of HTLV-I provirus was detected by polymerase chain reaction (PCR) in extracted DNA of both peripheral blood and tonsils. Histopathologic and immunohistochemical evaluations of tonsils were performed. HTLV-I seropositivity and PCR detection of HTLV-I provirus matched perfectly. Tonsil samples from seropositive individuals showed atrophy of the mantle zone and high numbers of T cells in the marginal zone compared with findings in HTLV-I-negative samples. HTLV-I provirus could be detected only from extracted DNA of extrafollicular areas. PCR in situ hybridization also showed positive signals in some mononuclear cells located in the marginal zone. There was a significant correlation between HTLV-I proviral load in tonsils and in peripheral blood. These results suggest the presence of characteristic histologic changes and deviated localization of HTLV-I-infected cells in the tonsils of individuals positive for HTLV-I.
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10.1097/00126334-199910010-00014
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pubmed_521_3459
|
The feasibility of replacing natural service in the suckler herd with artificial breeding (artificial insemination or embryo transfer), following synchronisation of oestrus in breeding animals, was investigated. In 1991 a herd of 143 spring-calving beef cows, matched for date and ease of calving, sex of calf, parity, body condition score and liveweight, were assigned to one of five controlled breeding programmes: natural service (group 1); single oestrus synchronisation using a norgestomet implant and fixed time insemination followed by natural service (group 2); double synchronisation with two consecutive norgestomet implants each with fixed-time insemination followed by natural service (group 3); synchronised as for group 2, but subjected to a movement stress two days after insemination (group 4); and cows synchronised by intravaginal progesterone/prostaglandin regimen with non-surgically transferred in vitro fertilised embryos followed by natural service (group 5). The percentage pregnancy rates to the first and second heats and overall were, respectively: group I, 55.5, 66.7 and 92.6; group 2, 44.4, 71.4 and 89.9; group 3, 52.0, 78.0 and 96.0; group 4, 55.0, 58.3 and 81.5, and group 5, 40.0, 68.2 and 85.7 per cent. In groups 2, 3, 4 and 5 the costs per pregnancy for artificial insemination or embryo transfer were 40.50 pounds, 56.62 pounds, 32.40 pounds and 149.98 pounds, respectively, and the calf weaning weights for groups 1, 2, 3, 4 and 5, adjusted for date of calving, were 250 kg, 255 kg, 252 kg, 261 kg and 259 kg, respectively.
|
10.1136/vr.135.1.9
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pubmed_993_4414
|
The effect of "low dose" heparin therapy on fibrinogen survival in patients with cirrhosis was studied in six patients. Survival of I-125 radiolabeled fibrinogen was measured using both autologous and homologous material. Average fibrinogen half-life before heparin therapy was 52 hours and after 3000 units of intravenous heparin every 6 hours was 101.8 hours. Median survival before heparin therapy was 56 hours and after therapy was 91 hours. In every instance fibrinogen survival was improved by heparin administration. These data indicate that "low dose" heparin improves fibrinogen survival in cirrhosis and suggest that disseminated intravascular coagulation is a primary process in the defibrination syndrome associated with cirrhosis.
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10.7326/0003-4819-83-1-79
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pubmed_573_10634
|
Polycalcium is a mixture of Polycan and calcium lactate-gluconate 1:9 (w/w) with demonstrated antiosteoporosis activity in vitro and in vivo studies. These studies were a 4-week open-label, single-center trial to evaluate the efficacy of oral Polycalcium on bone metabolism and safety. In total, 30 healthy women (range 40-60 years) were administered 400 mg of Polycalcium for 4 weeks. The primary efficacy parameter was urinary deoxypyridinoline (DPYR) levels, and serum osteocalcin (OSC), bone-specific alkaline phosphatase (BALP), urinary cross-linked C-telopeptide of type-1 collagen (CTx), urinary cross-linked N-telopeptide of type-1 collagen (NTx), calcium (Ca), and phosphorus (P) levels, which were evaluated for comparison before and after administration of Polycalcium. After 4 weeks of Polycalcium administration, 27 subjects completed the test plan. Three subjects withdrew their consent to participate. The values of blood OSC, BALP, serum Ca, and serum P from baseline to 4 weeks of treatment were changed by -28.44%, 14.37%, 6.11%, and 1.42%, respectively. Biomarkers of bone resorption: urinary DPYR, serum CTx, serum NTx, urinary Ca, and urinary P, at baseline after 4 weeks of treatment were changed by -13.40%, 6.67%, -5.13%, -22.43%, and -3.04%, respectively. Additionally, when considering the subjects' adverse effects and the results of the blood and urine tests over the 4-week trial period, the dose of 400 mg Polycalcium showed efficacy for improving bone metabolism and was well tolerated and safe. Polycalcium was apparently safe and efficacious.
|
10.1089/jmf.2012.2537
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pubmed_628_5361
|
In a pilot study of combination therapy with ribavirin and IFN alpha conducted in anti-HBe-positive individuals with chronic hepatitis B, 21% of patients achieved a sustained ALT normalization and clearance of hepatitis B virus (HBV) DNA as measured by PCR. The present work has assessed whether these sustained responses are lasting long-term. In addition, IFN gamma levels were tested serially in serum as a measure of the immune system activation during treatment. By extending the post-treatment follow-up period 2 years the occurrence of delayed HBV DNA relapses was observed. A low serum level of IFN gamma was detected during and after treatment. IFN gamma demonstrated a multiphasic time-course: the amount of IFN gamma increased in parallel with reductions in HBV DNA but also with ALT flare-ups. In conclusion, the extended follow-up study of anti-HBe-positive patients after combined treatment with ribavirin and IFN alpha has shown that sustained responses are lasting in 17% patients but also that a late onset HBV DNA relapse may occur.
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10.1016/s0166-3542(01)00179-6
|
pubmed_888_7839
|
OBJECTIVE
To study the barrier function, absorption, permeability and peristalsis of intestine in sepsis in rats.
METHODS
A Wistar rat model of sepsis was reproduced by ischemia/reperfusion (I/R) of the intestine combined with endotoxin challenge. Animal were randomly divided into normal, I/R 1 hours (I/R 1), I/R 2 hours (I/R 2), I/R 4 hours (I/R 4) and I/RL groups. The following parameters were measured in the experiments: (1) diamin oxidase activity (DAO), D-lactate and D-xylose levels in blood using spectrophotometry; (2) transit function of small intestine; (3) pathological examination of small intestine by light microscope.
RESULTS
The results showed that plasma DAO activity was increased in I/R 1, I/R 4 and I/RL (all P<0.05), and small intestinal tissue DAO was decreased in I/R 2 and I/RL (both P<0.05). Negative correlations were found between plasma and intestinal DAO (r=-0.909, P<0.001). Plasma D-lactate was elevated significantly in I/R 1, I/R 2, and I/RL (all P<0.05). D-xylose content was increased at I/R1 and I/RL groups (both P<0.05), and it was significantly higher than controls at 3 hours. Similarly, a positive correlation was found between plasma DAO activity and plasma D-lactate level (r=0.559, P<0.05).
CONCLUSION
The intestinal barrier function, absorption function, permeability, and transit are impaired after gut ischemia/reperfusion combined with endotoxin challenge.
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pubmed_888_7839
|
pubmed_89_5869
|
The maxillary anterior region is considered to be the esthetic zone of human dentition. Missing teeth in this area leads to severely compromised esthetics and function. Endosseous implants are a viable treatment option in this scenario, but the placement of endosteal implants requires adequate bone volume for successful osseointegration. When the morphology of the bone does not allow proper implant placement, there are various bone augmentation procedures which aid in reconstruction of the residual alveolar ridge for ideal implant placement. The mandibular parasymphysis can act as an excellent source of autogenous bone for the augmentation of alveolar ridge deficiencies. This article describes successful augmentation of the maxillary alveolar ridge using block bone autografts harvested from the mandibular symphysis along with platelet-rich fibrin. At 6 months after surgery, implant was inserted, and after a healing period of 5 months, permanent restoration was placed.
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10.4103/ccd.ccd_154_20
|
pubmed_740_13145
|
Ascaridoids are among the commonest groups of zooparasitic nematodes (roundworms) and occur in the alimentary canal of all major vertebrate groups, including humans. They have an extremely high diversity and are of major socio-economic importance. However, their evolutionary history remains poorly known. Herein, we performed a comprehensive phylogenetic analysis of the Ascaridoidea. Our results divided the Ascaridoidea into six monophyletic major clades, i.e., the Heterocheilidae, Acanthocheilidae, Anisakidae, Ascarididae, Toxocaridae, and Raphidascarididae, among which the Heterocheilidae, rather than the Acanthocheilidae, represents the sister clade to the remaining ascaridoids. The phylogeny was calibrated using an approach that involves time priors from fossils of the co-evolving hosts, and dates the common ancestor of the Ascaridoidea back to the Early Carboniferous (approximately 360.47-325.27 Ma). The divergence dates and ancestral host types indicated by our study suggest that members of the Ascaridoidea first parasitized terrestrial tetrapods, and subsequently, extended their host range to elasmobranchs and teleosts. We also propose that the fundamental terrestrial-aquatic switches of these nematodes were affected by changes in sea-level during the Triassic to the Early Cretaceous.
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10.1093/sysbio/syy018
|
pubmed_303_2056
|
Authors describe a new method of treatment for bone and soft tissue infections using polymethyl methacrylate balls containing Gentamycin. Advantages of this method can be summarized in 3 points: 1. From the patients point of view saving the rinsing-sucking drainage, early mobilisation etc. 2. From nursing point of view a significant facilitation of the patient's care. 3. From the hospital management's point of view: improved hygienic conditions by eliminating the possible infections related to a rinsing-sucking wet system. Cutting down hospital expences both by abbreviation of the time of hospitalization and saving on expensive antibiotics.
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pubmed_303_2056
|
pubmed_940_8355
|
It is well established that phosphorylation and dephosphorylation are key cellular events which regulate important metabolic activities such as gene expression, cell cycle progression, and apoptosis. The polyether fatty acid, okadaic acid has been shown previously to activate apoptosis in a variety of cell lines. Although this marine sponge toxin is known to inhibit protein phosphatase (PP)-2A and PP-1, it is not certain in most cases whether inhibition of PP-1 or PP-2A is necessary to activate apoptosis. Furthermore, it is not clear how inhibition of these phosphatases leads to apoptosis. Here we present evidence that inhibition of PP-2A by okadaic acid does not activate apoptosis in the lens system. However, when PP-1 is inhibited by okadaic acid, rabbit lens epithelial cells undergo rapid apoptosis. Associated with this process is the several-fold up-regulation of the tumor suppressor gene p53 and the pro-apoptotic gene bax at both mRNA and protein levels. Analyses of the temporal pattern of expression of the two genes reveal that the up-regulation is maximized in a few hours after treatment with okadaic acid, when the majority of the treated cells become committed to apoptosis. A brief treatment of the cells with a protein synthesis inhibitor can abolish okadaic acid-induced up-regulation of both P53 and Bax proteins. Concomitant with this inhibition, okadaic acid-induced apoptosis is also temporarily blocked. These results suggest that okadaic acid-induced expression of p53, bax, and other genes are necessary for the activation of the apoptotic programs in lens systems.
|
10.1046/j.1432-1327.1998.2570351.x
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pubmed_545_17283
|
Craniofacial development requires extremely fine-tuned developmental coordination of multiple specialized tissues. It has been evidenced that a folate deficiency (vitamin B9), or its synthetic form, folic acid (FA), in maternal diet could trigger multiple craniofacial malformations as oral clefts, tongue, or mandible abnormalities. In this study, a folic acid-deficient (FAD) diet was administered to eight-week-old C57/BL/6J female mouse for 2-16 weeks. The head symmetry, palate and nasal region were studied in 24 control and 260 experimental fetuses. Our results showed a significant reduction in the mean number of fetuses per litter according to maternal weeks on FAD diet (p < 0.01). Fetuses were affected by cleft palate (3.8%) as well as other severe congenital abnormalities, for the first time related to maternal FAD diet, as head asymmetries (4.6%), high arched palate (3.5%), nasal septum malformed (7.3%), nasopharynx duct shape (15%), and cilia and epithelium abnormalities (11.2% and 5.8%). Dysmorphologies of the nasal region were the most frequent, appearing at just four weeks following a maternal FAD diet. This is the first time that nasal region development is experimentally related to this vitamin deficiency. In conclusion, our report offers novel discoveries about the importance of maternal folate intake on midface craniofacial development of the embryos. Moreover, the longer the deficit lasts, the more serious the consequent effects appear to be.
|
10.3390/nu13010251
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pubmed_130_24785
|
Allelopathy is an important process in plant communities. The effects of allelopathy on seed germination and seedling development have been extensively investigated. However, the influences of extract soaking time and concentration on the foregoing parameters are poorly understood. Here, we conducted a seed germination assay to determine the allelopathic effects of the donor herbs Achnatherum splendens (Trin.) Nevski, Artemisia frigida Willd., and Stellera chamaejasme L., from a degraded grassland ecosystem in northern China, on lettuce (Lactuca sativa L.) seed germination and early seedling growth. Extract soaking times (12 h or 24 h) did not exhibit significantly different effects on lettuce seed germination or seedling development. However, all aqueous herb extracts inhibited lettuce seed germination and root length (RI < 0) and promoted lettuce shoot length, stem length, leaf length, and leaf width (RI > 0) at both low (0.005 g mL-1) and high (0.05 g mL-1) concentrations. Moreover, A. splendens extracts increased seedling biomass (RI > 0) and synthetical allelopathic effect (SE > 0) at both concentrations. In contrast, both A. frigida and S. chamaejasme extracts had hormesis effects, which stimulate at low concentrations (RI > 0) but inhibit at high concentrations (RI < 0) on seedling biomass and synthetical allelopathic effect (SE). The results suggest that allelopathic potential may be an important mechanism driving the dominance of A. frigida and S. chamaejasme in degraded grasslands. Reseeding allelopathy-promoting species such as A. splendens may be beneficial to grassland restoration. The present study also demonstrated that seedling biomass, root and shoot length, and seed germination rate are the optimal bioindicators in allelopathy assays and could be more representative when they are combined with the results of multivariate analyses.
|
10.3390/plants11040486
|
pubmed_953_25041
|
Dysfunction in energy metabolism-including in pathways localized to the mitochondria-has been implicated in the pathogenesis of a wide array of disorders, ranging from cancer to neurodegenerative diseases to type II diabetes. The inherent complexities of energy and mitochondrial metabolism present a significant obstacle in the effort to understand the role that these molecular processes play in the development of disease. To help unravel these complexities, systems biology methods have been applied to develop an array of computational metabolic models, ranging from mitochondria-specific processes to genome-scale cellular networks. These constraint-based (CB) models can efficiently simulate aspects of normal and aberrant metabolism in various genetic and environmental conditions. Development of these models leverages-and also provides a powerful means to integrate and interpret-information from a wide range of sources including genomics, proteomics, metabolomics, and enzyme kinetics. Here, we review a variety of mechanistic modeling studies that explore metabolic functions, deficiency disorders, and aberrant biochemical pathways in mitochondria and related regions in the cell.
|
10.3389/fphys.2012.00404
|
pubmed_702_18661
|
Unfortunately, interim analyses of the long-awaited ERSPC and PLCO trial data have generated conflicting conclusions. Here, two European authors speculate as to the reasons underlying this contradiction, while highlighting clinically relevant points that are supported by both studies. Particular attention is paid to the potential consequences of overdiagnosis and overtreatment.
|
10.1038/nrurol.2009.92
|
pubmed_952_4430
|
A young man was followed-up over three years who had severe obsessive-compulsive rituals and ruminations, interpersonal deficits, complicating depression and a history of childhood autism. Intensive behavioural treatment was given in an operant framework, with exposure in vivo, modelling, response prevention and social skills training. Compulsive rituals improved markedly and lastingly, but ruminations and social defects persisted. When intercurrent depression occurred dothiepin facilitated behavioural treatment. Adjustment remained fragile. Minimum maintenance treatment in the community could not be adequately arranged, so that gains made in hospital were partly lost at follow-up, despite continuing improvement in rituals.
|
10.1192/bjp.130.6.592
|
pubmed_223_2659
|
Recently, the microbiome has been gaining traction as a major player regulating various functions that correlate with many pathological conditions, including cancer. The central gut microbiota population has the capability to regulate normal inflammatory, immune, and metabolic functions, and disturbance in the balance of the normal microbiota population can subsequently induce pathological responses that closely relate with the mechanistic development and progression of cancer in various forms and sites. As a disease with major socioeconomic burden partly due to its current therapeutic options, modulating the imbalanced gut microbiota represents a novel option not only as an adjuvant therapy to relieve cancer treatment-related symptoms but also to influence cancer progression itself. In this review, we will discuss how the microbiome, specifically the gut microbiota, could affect cancer pathogenesis and what the effect of gut microbiota-targeting treatment options have on the many aspects of cancer pathologies based on the knowledge of recent years.
|
10.1177/1534735420920721
|
pubmed_240_21611
|
Magnetite nanoparticles (MNPs) coated with poly(acrylic acid-co-maleic acid) polyelectrolyte (PAM) have been prepared with the aim of improving colloidal stability of core-shell nanoparticles for biomedical applications and enhancing the durability of the coating shells. FTIR-ATR measurements reveal two types of interaction of PAM with MNPs: hydrogen bonding and inner-sphere metal-carboxylate complex formation. The mechanism of the latter is ligand exchange between uncharged -OH groups of the surface and -COO(-) anionic moieties of the polyelectrolyte as revealed by adsorption and electrokinetic experiments. The aqueous dispersion of PAM@MNP particles (magnetic fluids - MFs) tolerates physiological salt concentration at composition corresponding to the plateau of the high-affinity adsorption isotherm. The plateau is reached at small amount of added PAM and at low concentration of nonadsorbed PAM, making PAM highly efficient for coating MNPs. The adsorbed PAM layer is not desorbed during dilution. The performance of the PAM shell is superior to that of poly(acrylic acid) (PAA), often used in biocompatible MFs. This is explained by the different adsorption mechanisms; metal-carboxylate cannot form in the case of PAA. Molecular-level understanding of the protective shell formation on MNPs presented here improves fundamentally the colloidal techniques used in core-shell nanoparticle production for nanotechnology applications.
|
10.1021/la302660p
|
pubmed_0_5842
|
We introduce perhaps the simplest models of graph evolution with choice that demonstrate discontinuous percolation transitions and can be analyzed via mathematical evolution equations. These models are local, in the sense that at each step of the process one edge is selected from a small set of potential edges sharing common vertices and added to the graph. We show that the evolution can be accurately described by a system of differential equations and that such models exhibit the discontinuous emergence of the giant component. Yet they also obey scaling behaviors characteristic of continuous transitions, with scaling exponents that differ from the classic Erdos-Rényi model.
|
10.1103/PhysRevLett.104.195702
|
pubmed_202_13977
|
Three aged (10-year-old) German Shepherd Dog litter mates, separately reared, were affected with familial and adult onset peripheral neuropathy. They developed clinical signs, unsteady gait of their hind legs with progressive muscular weakness at almost the same time. The main lesions were systemic neurogenic muscular atrophy, segmental demyelination and Wallerian degeneration of the peripheral nerve fibres. Histochemically, collateral ramification and multiple terminal arborization were observed in terminal axons of motor neurones in the muscles. These changes were attributed to a dying-back process.
|
10.1016/0021-9975(92)90033-q
|
pubmed_307_706
|
The asymmetric unit of the title compound, C(23)H(23)N(5)OS, contains two independent mol-ecules. In one mol-ecule, the thia-zole and pyrimidine rings are almost co-planar, making a dihedral angle of 2.48 (8)°. In the other mol-ecule, the corresponding dihedral angle is 12.82 (8)°. The crystal structure is stabilized by weak inter-molecular N-H⋯N and C-H⋯O inter-actions that extend along the b axis.
|
10.1107/S1600536810053559
|
pubmed_789_10557
|
INTRODUCTION
Superior mesenteric venous thrombosis as a result of acute cytomegalovirus infection is rare, with only a few cases reported in the literature.
CASE PRESENTATION
We present the case of a 40-year-old Caucasian man who was admitted to our hospital with a 5-day history of fever. His serological test and pp65 antigen detection of cytomegalovirus were positive, suggesting acute infection. On the sixth day after his admission, the patient complained of acute, progressive abdominal pain. Abdominal computed tomography revealed acute superior mesenteric venous thrombosis. An emergency laparotomy showed diffuse edema and ischemic lesions of the small bowel and its associated mesentery with a 50-cm-long segmental infarction of the proximal jejunum. An extensive enterectomy of about 100 cm of jejunum that included the necrotic segment was performed, followed by an end-to-end anastomosis. Anti-coagulation therapy was administered pre-operatively in the form of small-fractionated heparin and continued postoperatively. The patient had an uneventful recovery and was discharged on the 11th postoperative day.
CONCLUSION
Acute cytomegalovirus infection can contribute to the occurrence of mesenteric venous thrombosis in immunocompetent patients. It is important for physicians and internists to be aware of the possible thrombotic complications of cytomegalovirus infection. A high level of clinical suspicion is essential to successfully treat a potentially lethal condition such as superior mesenteric venous thrombosis.
|
10.1186/1752-1947-6-118
|
pubmed_906_6615
|
Molecular genetics studies often infer the occurrence of gene conversion events based on simple sequence similarity observations that do not include any statistical analyses. I show that the statistical significance of two previously proposed gene conversion events can easily be tested and point out that a variety of methods are available to perform gene conversion analyses.
|
10.1007/s00239-001-0026-9
|
pubmed_550_20715
|
In this study, we employed a panel of cell lines to determine whether p53-dependent cell death in neuroblastoma (NB) cells is caused by apoptotic cellular function, and we further studied the molecular mechanism of apoptosis induced via the p53-dependent pathway. We obtained evidence that a type of p53-dependent stress, doxorubicin (Doxo) administration, causes accumulation of p53 in the nucleus of NB cells and phosphorylation of several serine residues in both Doxo-sensitive and -resistant cell lines. Upregulation of p53-downstream molecules in cells and upregulation of Noxa in the mitochondrial fraction were observed only in Doxo-sensitive NB cells. Significance of Noxa in the Doxo-induced NB cell death was confirmed by Noxa-knockdown experiments. Mitochondrial dysfunction, including cytochrome-c release and membrane potential disregulation, occurred and resulted in the activation of the intrinsic caspase pathway. However, in the Doxo-resistant cells, the accumulation in the nucleus and phosphorylation of p53 did not induce p53-downstream p21(Cip1/Waf1) expression and the Noxa upregulation, resulting in the retention of the mitochondrial homeostasis. Taken together, these findings indicate that the p53 pathway seems to play a crucial role in NB cell death by Noxa regulation in mitochondria, and inhibition of the induction of p53-downstream effectors may regulate drug resistance of NB cells.
|
10.1038/sj.onc.1210672
|
pubmed_497_4326
|
Cloning by the transplantation of somatic nuclei into unfertilized eggs requires a dramatic remodeling of chromosomal architecture. Many proteins are specifically lost from nuclei, and others are taken up from the egg cytoplasm. Recreating this exchange in vitro, we identified the chromatin-remodeling nucleosomal adenosine triphosphatase (ATPase) ISWI as a key molecule in this process. ISWI actively erases the TATA binding protein from association with the nuclear matrix. Defining the biochemistry of global nuclear remodeling may facilitate the efficiency of cloning and other dedifferentiation events that establish new stem cell lineages.
|
10.1126/science.289.5488.2360
|
pubmed_873_15233
|
Southwest Siberia encompasses the forest-steppe and sub-taiga climatic zones and has historically been utilized for agriculture. Coinciding with predicted changes in climate for the region is the pressure of agricultural development; however, a characterization of the soil water and carbon dynamics is lacking. We assessed current soil water properties and soil organic carbon turnover in forests and grasslands for two sites that span the forest steppe and sub-taiga bioclimatic zones. Soil evaporation was 0.62 ± 0.17 mm d-1 (mean ± standard error) in grasslands and 0.45 ± 0.08 mm d-1 in the forests of the forest-steppe site. Evaporation at the sub-taiga site was 1.80 ± 1.70 mm d-1 in grasslands and 0.96 ± 0.05 mm d-1 in forest plots. Evaporation was significantly greater at the sub-taiga site than the forest-steppe site. The density of fine roots explained the soil water isotopic patterns between vegetation types and sites. We found soil organic matter turnover to be three times faster in the sub-taiga site than in the forest-steppe site. Our results show that while climate factors, in particular snow levels, between the two sites are drivers for water and carbon cycles, site level hydrology, soil characteristics, and vegetation directly interact to influence the water and carbon dynamics.
|
10.1038/s41598-018-28977-8
|
pubmed_878_10553
|
Leiomyosarcomas of vascular origin are rare. They originate from the smooth muscles of tunica media of major blood vessels. The majority of such tumours arising in the extremities affect the femoral vascular bundle. There is limited knowledge and experience of the clinical presentation, pathological reports and results of treatment of this type of tumour. A case of primary leiomyosarcoma of femoral vein is being reported from a subtropical region of India that developed over the right thigh of a 35-year-old male farmer and was clinically diagnosed as benign soft tissue tumour. The diagnosis was confirmed by histopathology and immunohistochemistry.
|
10.4066/AMJ.2013.1874
|
pubmed_211_16399
|
Although hypothermia-related deaths are prevalent during the winter in states that have moderately cold (e.g., Illinois, New York, and Pennsylvania) to severely cold (e.g., Alaska and North Dakota) winters and in states with mountainous or desert terrain (e.g., Arizona, Montana, and New Mexico), hypothermia-related deaths also occur in states with milder climates (e.g., Georgia, Mississippi, and South Carolina), where weather systems can cause rapid changes in temperature. This report summarizes three hypothermia-related deaths in Fulton County, Georgia, representing persons in the highest risk groups for hypothermia; and summarizes hypothermia-related deaths in Georgia during January 1996-December 1997 and in the United States during 1979-1995.
|
pubmed_211_16399
|
pubmed_411_2761
|
This paper summarizes a personal perspective on key learnings from projects the author was involved in over the last 20 years. For example, the discovery of macitentan, the most successful molecule to date from this personal collection, marketed by J&J for the treatment of pulmonary arterial hypertension (PAH). [1] Then the discovery of ACT-462206, a dual orexin receptor antagonist for the treatment of insomnia disorder with a serendipitously short story from the screening hit to the drug [2] followed by the identification of daridorexant, another dual orexin receptor antagonist. Daridorexant successfully passed first pivotal phase 3 clinical trial in April 2020 for the treatment of insomnia disorder [3] ("Good things come to those who wait"). Finally, ACT-451840, an antimalarial drug with a novel mechanism of action, identified in the perfect collaboration between academia and industry. The compound is in phase 2 clinical development. [4] In addition, the importance of the screening compound collection is briefly discussed, as a key asset for drug discovery. The measures Idorsia implemented to obtain valuable hits from high-throughput screening (HTS) campaigns are elaborated. [5] Drug discovery is a multi-disciplinary business with unlimited exciting challenges asking for excessive optimism when tackling them in a playful manner.
|
10.2533/chimia.2020.549
|
pubmed_665_8929
|
A dissipative process in systems subjected to a boundary perturbation is analyzed on the basis of quantum mechanics. We show that the response of the system to the perturbation can be expressed in terms of the first-passage time defined appropriately by quantum mechanics. In other words, the first-passage-time distribution plays the role of the response function in the linear response theory. We apply this formalism to the one-dimensional Anderson model in which a current is introduced at one end of the system and the other is connected to an absorbing wall. We find that the frequency-dependent oscillations of the susceptibility reflect the narrowness of the first-passage-time distribution in disordered systems.
|
10.1103/PhysRevE.73.026128
|
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