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Confined stimulation using dual thalamic deep brain stimulation leads rescues refractory essential tremor: report of three cases.
Deep brain stimulation (DBS) of the nucleus ventralis intermedius (VIM) provides a safe and effective therapy for medically refractory essential tremor (ET). However, as many as 9% of VIM DBS patients deteriorate after several years of good tremor control. For these patients, the high voltage needed to adequately control tremor also generates circumferential current spread causing intolerable adverse effects. We report 3 ET patients where adding a second parallel thalamic lead anterior-medially to the original and connecting the 2 adjacent leads to a dual-channel pulse generator (Medtronic Synergy, model No. 7427) successfully recaptured tremor control with fewer adverse effects. This approach allowed us to direct the stimulation field away from nearby structures responsible for the adverse effects. Such confined stimulation can be achieved by connecting 2 adjacent DBS leads to a common voltage source, providing current flow between leads. This dual lead stimulation method can be used as a reversible rescue therapy in ET patients who require unacceptably high intensity stimulation. | {
"pile_set_name": "PubMed Abstracts"
} |
Deprenyl in Parkinson's disease: mechanisms, neuroprotective effect, indications and adverse effects.
Deprenyl is a synthetic, selective inhibitor of the monoamine oxidase-B enzyme system. The mechanism of its beneficial effect in early and advanced Parkinson's disease is not settled. Increased striatal dopamine accumulation, sensitization of surviving dopamine neurons with increased dopamine production and reduced nigro-striatal toxicity may all contribute. The standard daily dose of deprenyl is 10 mg. Selectivity may be lost at higher doses. Deprenyl is especially indicated in untreated patients, improving up to 50 percent of patients with mild motor fluctuations. Major symptomatic benefit also occurs in occasional levodopa treated patients. Adverse effects are common, however. Increase dyskinesias, confusion and hallucinations, nausea and postural hypotension may necessitate drug withdrawal or the use of low dose regimens. Caution should be exercised with older patients, those with ulcer disease, which may be worsened by deprenyl, and individuals with active ischemic heart disease where the safety of this drug is not yet clear. | {
"pile_set_name": "PubMed Abstracts"
} |
Engineering Plants for Geminivirus Resistance with CRISPR/Cas9 System.
The CRISPR/Cas9 system is an efficient genome-editing platform for diverse eukaryotic species, including plants. Recent work harnessed CRISPR/Cas9 technology to engineer resistance to geminiviruses. Here, we discuss opportunities, emerging developments, and potential pitfalls for using this technology to engineer resistance against single and multiple geminivirus infections in plants. | {
"pile_set_name": "PubMed Abstracts"
} |
Sickle cell-haemoglobin E (HbSE) compound heterozygosity: a clinical and haematological study.
The paucity of clinical reports in the world literature suggests that, as a disease entity, haemoglobin SE compound heterozygosity is of negligible importance. In view of the significant community prevalence of this haemoglobinopathy in the Sultanate of Oman where it is the second most prevalent sickling disorder, a hospital study of 12 SE compound heterozygotes from six unrelated Arab families was undertaken to determine their clinico-haematological features. Our findings were compared with those reviewed in the literature. Clinical and haematological evaluation was carried out by conventional methods including chromatographic haemoglobin analysis. At least 50% of those studied were asymptomatic throughout the study period but sickling-related complications occurred in the rest and included the acute chest syndrome (1/12), severe vaso-occlusive skeletal pain (2/12), frontal bossing (1/12) possibly indicative of significant chronic haemolysis and recurrent infections of the urinary tract (1/12). Steady-state haemoglobin levels fell within the reference range while MCV and MCH values were, as expected, reduced in most cases; nevertheless, concomitant inheritance of alpha-thalassaemia trait was also likely. Red cell morphology was striking by the absence or rarity of pseudo-sickled cells in the blood films of many patients during the steady state and in crises. Bearing in mind the prevalence of 0.05% of SE compound heterozygosity in Oman, the findings in this single study of the largest number of SE patients and their relatives confirm the predominantly asymptomatic nature of this sickling disorder in individuals in the community at large. HbF levels do not appear to explain the heterogeneous nature of this haemoglobinopathy. Correlation of the variable clinical and haematological features of SE cases with their alpha-globin gene status and beta-cluster haplotypes (linked to the beta(s)- and beta(e)-genes) merits a separate investigation, which is being currently organized. | {
"pile_set_name": "PubMed Abstracts"
} |
Intraoperative digital subtraction angiography after thromboembolectomy: preliminary experience.
To evaluate the potential influence of intraoperative digital subtraction angiography (DSA) on surgical strategy after balloon thromboembolectomy for acute lower limb ischemia. Thirty-six consecutive patients with critical limb ischemia were treated with balloon catheter thromboembolectomy assessed by intraoperative digital subtraction angiography. The need for further intervention was determined by the surgeon based on the DSA information. Primary completion DSAs were made in every procedure; subsequent completion DSAs were performed after reinterventions at the discretion of the surgeon. Initial treatment in this patient group consisted of 14 embolectomies and 26 thrombectomies. From the completion DSAs of these 40 procedures, a reintervention was judged necessary in 27 (68%). Of these 27 reinterventions, 17 underwent a secondary DSA; evidence supporting a third intervention was found in 11 (64%). Overall, a total of 69 DSAs were performed in these patients. Mortality was 22% (8 patients); 38% (5) in embolectomy patients and 13% (3) in the thrombectomy cohort. Eighty-eight percent of the embolectomy survivors had an uneventful recovery, while only 25% of the thrombectomy survivors experienced an uncomplicated follow-up. In one quarter of the surviving thrombectomy patients, a surgical revascularization resulted in limb salvage; in 45%, a major amputation was the outcome. In this study, the completeness of balloon catheter thromboembolectomy was assessed by intraoperative DSA. As a result, 68% of the procedures required one or more reinterventions for residual lesions. Intraoperative DSA is a simple and quick technique that may be a promising adjunct to intraoperative balloon thromboembolectomy. | {
"pile_set_name": "PubMed Abstracts"
} |
Flavopiridol induces apoptosis of normal lymphoid cells, causes immunosuppression, and has potent antitumor activity In vivo against human leukemia and lymphoma xenografts.
Flavopiridol is a novel semisynthetic flavone derivative of the alkaloid rohitukine. Flavopiridol is known to inhibit potently the activity of multiple cyclin-dependent kinases. We have assessed its effects on normal and malignant cells in preclinical animal models of localized and disseminated human hematopoietic neoplasms. Flavopiridol, when administered as daily bolus intravenous (IV) injections, produced selective apoptosis of cells in the thymus, spleen, and lymph nodes, resulting in atrophy of these organs. With the exception of the intestinal crypts, apoptosis or tissue damage was absent in all other organs investigated (kidneys, liver, lungs, bone/bone marrow, muscle, and heart). Flavopiridol had a marked apoptotic effect documented by DNA nick-end labeling, or DNA agarose gels in xenografts of human hematopoietic tumors HL-60, SUDHL-4, and Nalm/6. After treatment with 7.5 mg/kg flavopiridol bolus IV or intraperitoneal on each of 5 consecutive days, 11 out of 12 advanced stage subcutaneous (s.c.) human HL-60 xenografts underwent complete regressions, and animals remained disease-free several months after one course of flavopiridol treatment. SUDHL-4 s.c. lymphomas treated with flavopiridol at 7.5 mg/kg bolus IV for 5 days underwent either major (two out of eight mice) or complete (four out of eight mice) regression, with two animals remaining disease-free for more than 60 days. The overall growth delay was 73.2%. The acquired immunodeficiency syndrome-associated lymphoma AS283 showed no significant response when flavopiridol was used in advanced s.c. tumors, but when treatment was initiated in early stages, there was a complete regression of the early tumors, and a significant overall growth delay (>84%). When flavopiridol was used in severe combined immunodeficient mice bearing disseminated human acute lymphoblastic leukemia Nalm/6 cells, there was 15-day prolongation in survival (P = .0089). We conclude that flavopiridol greatly influences apoptosis in both normal and malignant hematopoietic tissues. This activity was manifested in our study as a potent antileukemia or antilymphoma effect in human tumor xenografts, which was dose and schedule dependent. These findings provide compelling evidence for the use of flavopiridol in human hematologic malignancies. | {
"pile_set_name": "PubMed Abstracts"
} |
Facial attractiveness: beauty and the machine.
This work presents a novel study of the notion of facial attractiveness in a machine learning context. To this end, we collected human beauty ratings for data sets of facial images and used various techniques for learning the attractiveness of a face. The trained predictor achieves a significant correlation of 0.65 with the average human ratings. The results clearly show that facial beauty is a universal concept that a machine can learn. Analysis of the accuracy of the beauty prediction machine as a function of the size of the training data indicates that a machine producing human-like attractiveness rating could be obtained given a moderately larger data set. | {
"pile_set_name": "PubMed Abstracts"
} |
Long-term mycophenolate mofetil monotherapy in combination with calcineurin inhibitors for chronic renal dysfunction after liver transplantation.
Calcineurin inhibitors (CNIs) are the first-line immunosuppressive agents administered after liver transplantation, but they cause renal impairment. Two recent randomized trials report cellular rejection and liver graft loss when mycophenolate mofetil (MMF) monotherapy was used as a renal-sparing agent. Our experience with MMF in the same setting but with longer follow-up is described. In 45 patients with serum creatinine more than 120 micromol/L or creatinine clearance less than 50 mL/min, 2 g MMF per day was administered (median 29 months, 1-49 months) either as monotherapy (with all other immunosuppression withdrawn in 1 month) in 16 patients (group I) or in combination with low-dose CNI (trough tacrolimus </=5 ng/mL, cyclosporin A </=50 ng/mL) in 29 patients (18 patients without [group II] and 11 patients with [group III] previous refractory rejection [rejection after two episodes of treated rejection]). In group I (median interval receiving MMF, 33 months), only one patient (6%) experienced cellular rejection, and serum creatinine normalized in five of eight patients long term. In group II (median follow-up 26.5 months), none of 18 experienced rejection, and serum creatinine normalized in 6 of 10 long term. In group III (median follow-up 34 months), 5 of 11 patients (45%) experienced further rejection, one was not steroid responsive, and serum creatinine normalized in four of eight patients long term. There was no graft loss or death as a result of rejection. Our cohort with prolonged follow-up showed significant improvement in renal function with both MMF monotherapy and in combination with low-dose CNI with minimal rejection (five of six steroid responsive) and no graft loss. MMF substitution is a therapeutic strategy that deserves more extensive use in liver transplantation. | {
"pile_set_name": "PubMed Abstracts"
} |
Leopard or chameleon? The changing character of international health economics.
Over the last 25 years the discipline of health economics has developed substantially. As an applied discipline, it has adapted and changed over time in response to the changing concerns of policy-makers, planners and managers. This paper questions whether it is like a chameleon, changing its appearance in response to the external environment, or like the leopard that never changes its spots. In answering the question, the paper presents an overview of the development of health economics as it has been applied in low and middle income countries distinguishing three eras, the 1970s, 1980s, and 1990s, and argues that in each of these eras the preoccupations of health economists have been somewhat different. In each era the key contributions of health economics are identified. The paper ends by considering future research priorities, and the obligations of developed country institutions in terms of research topics and mode of work. | {
"pile_set_name": "PubMed Abstracts"
} |
[The treatment of colorectal cancers].
Results of treatment of 2900 patients with colorectal cancer in 1972-1994 yrs. period are analyzed. Diagnosis methods, kinds of operative procedures, frequency of complications occurrence are enlightened. Problematic directions of future investigations are determined. | {
"pile_set_name": "PubMed Abstracts"
} |
Isolation and Characterization of Stenotrophomonas maltophilia Isolates from a Brazilian Hospital.
Stenotrophomonas maltophilia is an emerging nosocomial pathogen responsible for several infections in immunocompromised patients. To characterize the antimicrobial resistance and virulence potential of this microorganism in a Brazilian hospital, a total of 936 samples were collected from a nosocomial environment and medical devices, and 100 isolates from clinical specimens were obtained in the same hospital. S. maltophilia was found in 3% of the samples collected, especially in bed rails from hospital rooms. The smf-1 gene was detected in 23% and 42% of the clinical and hospital environment isolates, respectively, and almost all (96.8%) isolates that harbored smf-1 were able to form biofilm. All isolates were susceptible to minocycline and chloramphenicol, and the majority of isolates were susceptible to levofloxacin. High resistance to ceftazidime was detected in both groups of isolates. Resistance to trimethoprim-sulfamethoxazole (TMP/SMX) was found in 14.8% of the isolates. All TMP/SMX-resistant isolates presented class 1 integron and sul1 gene, and 47.4% of them also harbored the sul2 gene, which was inserted into a 7.3 kb plasmid. Genetic relatedness among the isolates was evaluated by enterobacterial repetitive intergenic consensus-PCR, and eight genetic patterns were identified. One pattern comprised 54.7% of isolates and was spread among clinical and environmental (furniture and medical devices) sources. The presence of S. maltophilia in the hospital environment indicates that it can act as a reservoir of this microorganism. In addition, hospital isolates resistant to TMP/SMX showed that the genetic determinants were present in mobile elements, which can constitute great concern, as it may indicate a tendency to spread. | {
"pile_set_name": "PubMed Abstracts"
} |
Modulation of inducible nitric oxide synthase induction by prostaglandin E2 in macrophages: distinct susceptibility in murine J774 and RAW 264.7 macrophages.
Prostaglandin E2 (PGE2) is the major cyclooxygenase metabolite in macrophages with complex proinflammatory and immunoregulatory properties. In the present study, we have compared the modulatory role of PGE2/cAMP-dependent signaling on induced nitric oxide (NO) production in two murine macrophages, J774 and RAW 264.7. With no effect on NO release by itself, PGE2 co-addition with lipopolysaccharide (LPS) resulted in a concentration-dependent enhancement in NO release and inducible NO synthase induction in J774, but not in RAW 264.7, macrophages. The potentiation effect of PGE2 in J774 cells was still seen when applied within 9 h after LPS treatment. Whereas RAW 264.7 macrophages release PGE2 with greater extent than J774 macrophages in response to LPS, indomethacin and NS-398, upon abolishing LPS-induced PGE2 release, caused a more obvious inhibition of NO release from J774 than RAW 264.7 cells. Thus, we suggest a higher positive modulatory role of PGE2--either endogenous or exogenous--on NO formation in J774 cells. Supporting these findings, exogenous PGE2 triggers cAMP formation in J774 cells with higher potency and efficacy. Of interest, dBcAMP also elicits higher sensitivity in potentiating NO release in J774 cells. We conclude that the opposite effect of PGE2/cAMP signaling on macrophage NO induction depends on its signaling efficacy and might be associated with the difference in endogenous PGE2 levels. | {
"pile_set_name": "PubMed Abstracts"
} |
Incidence of dry socket, alveolar infection, and postoperative pain following the extraction of erupted teeth.
The aim of this study was to determine the incidence of dry socket, alveolar infection, and postoperative pain following the routine extraction of erupted teeth. Using a questionnaire, this prospective cross-sectional study evaluated 357 consecutive surgeries in which 473 erupted teeth were extracted by dental students under rigorous control of microbiologic contaminants during a 22-month period. The subject sample consisted of 210 (58.8%) male patients ranging in age from 11 to 79 years (mean 41 +/- 16.3). The most prevalent self-reported ethnicity was Caucasian (78.2%). The questionnaire consisted of 60 questions directed to the patient and to the dental student who performed the surgical procedure. The questionnaires were completed before and within seven days after the surgery to obtain outcomes data. Forty-five questionnaires were excluded due to lack of information, inconsistencies, or lack of contact with the patient; however, none had indications of alveolar infection or dry socket. The data were analyzed using descriptive statistics, chi-square tests (x(2)), and an odds ratio (OR) as appropriate at the critical level of significance, set at p<0.05 (x(2)) or p<0.01 (x(2), with the Monte Carlo simulation). The observed incidence was 0.6% (two cases each) for both alveolar infection and dry socket. Higher pain levels and pain persisting longer than two days were observed with more traumatic surgeries, or associated with postoperative complications. Smoking was found to be statistically associated with the development of postoperative complications. The incidence of alveolar infection, dry socket, and severe pain were very low for the routine extraction of erupted teeth. Severe pain that persists for more than two days can represent a sign of a postoperative complication such as dry socket. Dental extraction is part of the dentists' daily work and intercurrences like dry socket, infection, and pain can occur. This manuscript reports the incidence of these occurrences and search for its predisposing factors. | {
"pile_set_name": "PubMed Abstracts"
} |
Seasonality and determinants of moderate and severe COPD exacerbations in the TORCH study.
We investigated the impact of season relative to other determinants of chronic obstructive pulmonary disease (COPD) exacerbation frequency in a long-term international study of patients with forced expiratory volume in 1 s (FEV(1)) <60% predicted. COPD exacerbations were defined by worsening symptoms requiring systemic corticosteroids and/or antibiotics (moderate) or hospital admission (severe). Seasonality effect was calculated as the proportion of patients experiencing an exacerbation each month. Exacerbations in the northern and southern regions showed an almost two-fold increase in the winter months. No seasonal pattern occurred in the tropics. Overall, 38% of exacerbations were treated with antibiotics only, 19% with systemic corticosteroids only and 43% with both, while 20% required hospital admission irrespective of the season. Exacerbation frequency was associated with older age, lower body mass index, lower FEV(1) % pred and history of prior exacerbations. Females and patients with worse baseline breathlessness, assessed using the Medical Research Council (MRC) dyspnoea scale, exacerbated more often (rate ratio (RR) for male versus female 0.7, 95% CI 0.7-0.8 (p<0.001); RR for MRC dyspnoea score 3 versus 1 and 2 combined 1.1, 95% CI 1.1-1.2 (p<0.001)). The effect of season was independent of these risk factors. COPD exacerbations and hospitalisations were more frequent in winter. | {
"pile_set_name": "PubMed Abstracts"
} |
Interaction between two murein (peptidoglycan) synthases, PBP3 and PBP1B, in Escherichia coli.
The murein (peptidoglycan) sacculus is an essential polymer embedded in the bacterial envelope. The Escherichia coli class B penicillin-binding protein (PBP) 3 is a murein transpeptidase and essential for cell division. In an affinity chromatography experiment, the bifunctional transglycosylase-transpeptidase murein synthase PBP1B was retained by PBP3-sepharose when a membrane fraction of E. coli was applied. The direct protein-protein interaction between purified PBP3 and PBP1B was characterized in vitro by surface plasmon resonance. The interaction was confirmed in vivo employing two different methods: by a bacterial two-hybrid system, and by cross-linking/co-immunoprecipitation. In the bacterial two-hybrid system, a truncated PBP3 comprising the N-terminal 56 amino acids interacted with PBP1B. Both synthases could be cross-linked in vivo in wild-type cells and in cells lacking FtsW or FtsN. PBP1B localized diffusely and in foci at the septation site and also at the side wall. Statistical analysis of the immunofluorescence signals revealed that the localization of PBP1B at the septation site depended on the physical presence of PBP3, but not on the activity of PBP3. These studies have demonstrated, for the first time, a direct interaction between a class B PBP (PBP3) and a class A PBP (PBP1B) in vitro and in vivo, indicating that different murein synthases might act in concert to enlarge the murein sacculus during cell division. | {
"pile_set_name": "PubMed Abstracts"
} |
On the mechanism of the inhibition of Na(+), K(+)-ATPase activity caused by homocysteine.
In the present work, we investigated the kinetics of the inhibition of Na(+), K(+)-ATPase activity caused by homocysteine (Hcy) in rat hippocampus. We also studied the interaction between Hcy and phenylalanine (Phe) and the kinetics of alanine (Ala) reversal of the inhibition of Na(+), K(+)-ATPase caused by Hcy. The apparent K(m) and V(max) of Na(+), K(+)-ATPase for ATP as substrate were 0.55mM and 2.0nmol Pi released per min per mg of protein, respectively. K(i) value was approximately 0.1mM, and the inhibition was of the non-competitive type. The results also showed a competition between Hcy and Phe. Ala per se did not alter this enzyme, but prevented the inhibitory effect caused by Hcy, suggesting a common binding site for these substances. It is proposed that the inhibition of Na(+), K(+)-ATPase by Hcy may be one of the mechanisms related to the neuronal dysfunction observed in human homocystinuria. | {
"pile_set_name": "PubMed Abstracts"
} |
Pituitary adenoma with craniopharyngioma component.
Neoplasms consisting of pituitary adenoma and craniopharyngioma components are rare and are being increasingly recognized. Their histogenesis is not clear. Most represent collision tumors; others are difficult to assess. Here, we describe a pituitary adenoma with an intermingled craniopharyngioma component, without forming 2 distinct mass lesions or histologic delineation. Areas that suggest a transition between the 2 components were also present. It was clinically a nonfunctioning adenoma, which was also negative for pituitary hormones by immunohistochemistry. Its histogenesis and implications are discussed with a review of the literature. | {
"pile_set_name": "PubMed Abstracts"
} |
Thrombotic microangiopathy associated with tacrolimus in lung transplantation.
Thrombotic microangiopathy (TMA) is a rare complication associated with the use of calcineurin inhibitors in lung transplantation, irrespective of the underlying disease of the graft recipient. It usually occurs in incomplete forms, complicating and delaying diagnosis until damage is already irreversible. It is unrelated to time from transplantation and often presents with concomitant infection, which tends to confound diagnosis. The cases discussed here have a common causative agent and all present with concomitant infection. Treatment recommendations have changed in recent years with the introduction of plasmapheresis or, more recently, the availability of the antibody eculizumab. Notwithstanding, the most cost-effective measure is withdrawal or switching of the calcineurin inhibitor. TMA is an underdiagnosed clinical entity that should be considered in the management of transplantation patients. | {
"pile_set_name": "PubMed Abstracts"
} |
Synthesis of unsymmetrically substituted phosphane oxides (R(1)R(2)P(O)H) and phosphinous acids (R(1)R(2)POH).
This paper describes the synthesis of unsymmetrically substituted phosphinous acids and phosphane oxides featuring at least one electron-withdrawing pentafluoroethyl group. The presence of a diethylamino function as a protecting group allows a selective reaction of RClPNEt2 (R=CF3 , C6 F5 , C6 H5 ) with LiC2 F5 . On treatment with para-toluenesulfonic acid the isolated aminophosphanes R(C2 F5 )PNEt2 are readily converted into the corresponding phosphinous acids or phosphane oxides, respectively. Investigation of the tautomeric equilibrium between oxide and acid tautomer revealed (CF3 )(C2 F5 )POH as a stable phosphinous acid, whereas the pentafluorophenyl and phenyl derivatives constitute a solvent dependent equilibrium between the acid and the oxide tautomer. | {
"pile_set_name": "PubMed Abstracts"
} |
Synthesis and photophysical properties of a fluorescent cyanoquinoline probe for profiling ERBB2 kinase inhibitor response.
A fluorescent probe targeting the ERBB2 receptor tyrosine was designed, synthesized and evaluated as reporter of ERBB2 dynamics in overexpressing BT474, i.e. Her2(+), cells. Two cyanoquinazoline (CQ) probes modeled after type-I (CQ1) or active state and type-II (CQ2) or inactive state inhibitors were designed and synthesized with extended π systems that impart binding-induced, turn-on fluorescence. Solution spectroscopy revealed that CQ1 exhibited attractive photophysical properties and displayed turn-on emission in the presence of purified, soluble ERBB2 kinase domain, while CQ2 was found to be non-emissive, likely due to quenching via a photoinduced electron transfer mechanism. Live cell imaging with CQ1 revealed that this probe targeted an intracellular population of ERBB2, which increased following treatment with type-I inhibitors, gefinitib and canertinib, but showed no response to type-II inhibitors. CQ1 thus provides a novel means of imaging the dynamic response of ERBB2(+) cells to kinase inhibitors. | {
"pile_set_name": "PubMed Abstracts"
} |
Therapeutic interventions for enhancing collateral development by administration of growth factors: basic principles, early results and potential hazards.
The importance of spontaneously developing collateral vessels to supplement perfusion of tissue rendered ischemic by vascular obstruction was recognized many years ago. However, it was not until potent angiogenesis factors were identified, purified, and produced in sufficient quantities, that the field began its rapid development. In the early 1990s it was first shown that basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) proteins could actually stimulate collateral flow. However, additional studies also demonstrated that the duration of exposure of the vessels to angiogenesis factors was critical, and that the administration of proteins, with their relatively brief half-lives, may pose important practical limitations. The demonstration that gene therapy can improve collateral function presents one of the solutions to the conundrum, since gene therapy can be considered a sophisticated form of a sustained delivery system. The results of several clinical trials have been reported. All involve administration of single angiogenesis agents, and most are Phase I trials. The two studies rising to Phase II status demonstrated no treatment effect on the primary end-point. It may therefore be relevant to consider that the molecular mechanisms responsible for angiogenesis are extraordinarily complex, and an optimal angiogenesis intervention may require a 'multiple factor' strategy. It is important to note that no serious side-effects ascribable to an angiogenesis agent were recognized in these trials. However, angiogenesis agents are potent molecules with multiple activities. It is therefore possible that they might occasionally cause side-effects, some serious. Among these, based on their biologic activities, are neovascularization of non-targeted tissues, expansion and induction of instability of atherogenic plaque, and growth of tumors. In summary, there is ample experimental evidence justifying an optimistic outlook relating to our eventually being successful in enhancing collateral flow to ischemic tissue in a clinical setting. However, we are not there yet, and identification of the optimal angiogenesis strategy is still unclear. Additional experimental work, in parallel with large, carefully controlled clinical trials are needed to continue the exciting advances of the last decade, and to achieve the goal of providing patients with alternative potent therapies to improve collateral flow, and thereby to alleviate their symptoms and perhaps to prolong their lives. | {
"pile_set_name": "PubMed Abstracts"
} |
A literature overview and comparison of driving impairing condition assessment approaches by health enabling technologies.
Due to demographic change, more elderly people have the need to preserve and support mobility by car despite age-related functional limitations. Since accidents by the elderly are primarily caused by age related limitations, and not by careless or irresponsible behavior, it may be beneficial to detect driving impairing conditions. The presented review gives an overview of technologies to detect driving impairing conditions like drowsiness and stress or excessive demand. A comparison of the approaches to detect these conditions suggests that a combination of approaches is the most feasible method. However, there are still few systems that focus on the elderly. | {
"pile_set_name": "PubMed Abstracts"
} |
FTY720 for treatment of ischemia-reperfusion injury following complete renal ischemia in C57/BL6 mice.
Organ dysfunction followed by single-organ or even multiorgan failure due to ischemia-reperfusion injury (I/RI) is a common problem in liver and heart transplantation. Various approaches had been attempted to prevent this I/RI. One is the administration of FTY720, a synthetic structural analogue of sphingosine, which induces T-lymphocyte homing with consecutive lymphopenia. The purpose of this study was to evaluate the effect of intraoperative FTY720 administration following controlled bilateral kidney ischemia in comparison to steroid or placebo application. Male c57BL6/J mice (n = 115; body weight 25 to 30 g) received either FTY720 (1 mg/kg body weight) or steroids or saline solution. Ischemia was applied for 30 or 60 minutes with subsequent follow-up for 48 hours. At termination all surviving animals were sacrificed. Following 30 minutes of ischemia, FTY720, but neither steroid nor vehicle treatment showed significant protective effects on long-term survival after controlled bilateral warm kidney ischemia. Fluorescein-activated cell sorting (FACS) analysis showed a significant T-lymphocyte depletion in peripheral blood after FTY720 treatment, which was not observed after steroid or vehicle treatment. The improved long-term survival shown in this study might be due to a protective effect of FTY720 to prevent I/RI, which may be mediated by the lymphocyte depletion shown in the FACS analysis. | {
"pile_set_name": "PubMed Abstracts"
} |
Combined kidney and intestinal transplantation in patients with enteric hyperoxaluria secondary to short bowel syndrome.
Kidney transplantation is the treatment of choice for end-stage renal disease whereas indications for intestinal transplantation are currently restricted to patients with irreversible small bowel failure and severe complications of total parenteral nutrition (mostly shortage and infection of venous accesses, major electrolyte disturbances and liver failure). Enteric hyperoxaluria is secondary to certain intestinal diseases like intestinal resections, chronic inflammatory bowel disease and other malabsorption syndromes and can lead to end-stage renal disease requiring kidney transplantation. We report two patients suffering from renal failure due to enteric hyperoxaluria (secondary to extensive intestinal resection) in whom we elected to replace not only the kidney but also the intestine to prevent recurrence of hyperoxaluria in the transplanted kidney. | {
"pile_set_name": "PubMed Abstracts"
} |
Imaging brain effects of APOE4 in cognitively normal individuals across the lifespan.
The ε4 allele of the apolipoprotein E (APOE4) is associated with an increased risk of developing Alzheimer's disease (AD). Hence, several studies have compared the brain characteristics of APOE4 carriers versus non-carriers in presymptomatic stages to determine early AD biomarkers. The present review provides an overview on APOE4-related brain changes in cognitively normal individuals, focusing on the main neuroimaging biomarkers for AD, i.e. cortical beta-amyloid (Aβ) deposition, hypometabolism and atrophy. The most consistent findings are observed with Aβ deposition as most studies report significantly higher cortical Aβ load in APOE4 carriers compared with non-carriers. Fluorodeoxyglucose-positron emission tomography studies are rare and tend to show hypometabolism in brain regions typically impaired in AD. Structural magnetic resonance imaging findings are the most numerous and also the most discrepant, showing atrophy in AD-sensitive regions in some studies but contradicting results as well. Altogether, this suggests a graded effect of APOE4, with a predominant effect on Aβ over brain structure and metabolism. Multimodal studies confirm this view and also suggest that APOE4 effects on brain structure and function are mediated by both Aβ-dependent and Aβ-independent pathological processes. Neuroimaging studies on asymptomatic APOE4 carriers offer relevant information to the understanding of early pathological mechanisms of the disease, although caution is needed as to whether APOE4 effects reflect AD pathological processes, and are representative of these effects in non-carriers. | {
"pile_set_name": "PubMed Abstracts"
} |
Anecortave acetate treatment for retinal angiomatous proliferation: a pilot study.
The purpose of this study was to evaluate anecortave acetate treatment of retinal angiomatous proliferation (RAP), a neovascular form of age-related macular degeneration, with specific regard to inhibition of neovascularization and maintenance of vision. Thirty-four patients with RAP with any stage of neovascularization were randomized 1:1:1 for treatment with three different quantities (30 mg, 15 mg, 3 mg) of anecortave acetate sterile suspension for juxtascleral administration. Best-corrected visual acuity (Early Treatment Diabetic Retinopathy Study chart), intraocular pressure measurement, biomicroscopy, funduscopy, digital fluorescein, and indocyanine green angiography were recorded at baseline and at 3 months. A 6-month retreatment interval was established for this study with a follow-up of 12 months. In selected patients optical coherence tomography was performed. The outcomes were mean changes in visual acuity and lesion size at 1 year. The detachment of the neurosensory retina and retinal pigment epithelium improved in all eyes, but all neovascular lesions increased in size. Vision loss occurred in the majority of study eyes (22 out of 34 eyes, 64.7%) independent of the concentration administered. The results suggest that a posterior juxtascleral injection of anecortave acetate reduces capillary permeability in patients with RAP. However, in spite of improvement of the exudation there is a progression of neovascularization and a significant loss of vision in all these patients. Like other monotherapeutic methods used to treat this variant of neovascular age-related macular degeneration, anecortave acetate alone does not appear to benefit these patients. Future studies should investigate a combination form of therapy. | {
"pile_set_name": "PubMed Abstracts"
} |
Australian fly-in, fly-out operations: Impacts on communities, safety, workers and their families.
Australia's mineral, resource and infrastructure sectors continues to expand as operations in rural and remote locations increasingly rely on fly-in, fly-out or drive-in, drive-out workforces in order to become economically competitive. The issues in effectively managing these workforces are becoming more apparent with reported high amounts of turnover and concerns for safety and performance. The issues presented include a range of physical, mental, psychosocial, safety and community challenges. This review aims to consolidate a range of research conducted to communicate potential challenges for industry in relation to a wide variety of issues when engaging and using FIFO/DIDO workforces which includes compressed working schedule design (work schedules), working hours, fatigue, safety performance, employee wellbeing, turnover, psychosocial relationships and community concerns. A comprehensive literature review was performed using EBSCOhost, PubMed and google scholar, with a focus on FIFO or DIDO workforces engaged within the resources sector. Search terms were kept broad in order to capture all national and international research conducted and included: "fly-in, fly-out" "FIFO" "DIDO" "drive-in, drive-out" "mining". There was no date restriction included in the search. Many of the studies were focused on sleep quality, fatigue and the influence of lowered safety performance while at work, presenting an increased risk for health and safety. These issues may be exacerbated for the FIFO workforce when linked to additional research surrounding the extended periods of absence from families influencing workers personal relationships, psychological wellbeing, job satisfaction and the reported high amounts of turnover within the industry. Taken together, this presents a unique implication for the management and continued use of FIFO workforces when considering balancing safety and performance with economic viability of production and operations. The issues of long working hours, fatigue, turnover and job satisfaction are not new to the management of workers. However, FIFO workforces appear to be at an increased risk physically and mentally due to a culmination of other influences, such as extended and frequent periods of absence from friends and families which contribute to feelings of isolation and lowered psychological wellbeing. FIFO workers and their families, engage in a unique lifestyle, rarely are other workers subjected to long hours and compressed work weeks while separated or isolated from their families for extended periods of time. Recently, FIFO interest has shifted to understanding the influences on employee engagement, satisfaction, retention and safety. Considering the management of FIFO workforces from a holistic perspective incorporating all of the issues impacting on these workers may assist to ensure the challenges associated with FIFO employment are understood, addressed and communicated to workers and their families is crucial for safety and health. | {
"pile_set_name": "PubMed Abstracts"
} |
Nucleic acid detection using G-quadruplex amplification methodologies.
In the last decade, there has been an explosion in the use of G-quadruplex labels to detect various analytes, including DNA/RNA, proteins, metals and other metabolites. In this review, we focus on strategies for the detection of nucleic acids, using G-quadruplexes as detection labels or as enzyme labels that amplify detection signals. Methods to detect other analytes are briefly mentioned. We highlight various strategies, including split G-quadruplex, hemin-G-quadruplex conjugates, molecular beacon G-quadruplex or inhibited G-quadruplex probes. The tandem use of G-quadruplex labels with various DNA-modifying enzymes, such as polymerases (used for rolling circle amplification), exonucleases and endonucleases, is also discussed. Some of the detection modalities that are discussed in this review include fluorescence, colorimetric, chemiluminescence, and electrochemical methods. | {
"pile_set_name": "PubMed Abstracts"
} |
Melatonin antagonises the cyclosporine A immunosuppressive effects in rat thymuses.
Cyclosporine A (CsA) is a powerful immunosuppressant inducing marked involution of the thymus with disappearance of interdigitating cells (IDCs) and reducing the number of macrophages (Mphi). Melatonin (Mel) is a potent antioxidant agent that could be useful in attempting to reduce CsA toxicity. Moreover, Mel has been found to exert positive influence on lymphocytes, spleen and thymus. In this study, we evaluated the effects of Mel on the thymic involution induced by CsA. CsA caused profound changes in thymic cytoarchitecture, i.e. the complete disappearance of thymic medulla and reduced the number of acid phosphatase positive macrophages. There was no difference between thymic morphology of Mel-treated rats and the control animals injected only with olive oil. The simultaneous Mel-CsA administration prevented the involution of the thymic medulla and the reduction of the number of macrophages. These findings suggested that Mel probably antagonized the immunosuppressive CsA effects. | {
"pile_set_name": "PubMed Abstracts"
} |
Cytogenetics meets phylogenetics: a review of karyotype evolution in diprotodontian marsupials.
We have used a combined approach of phylogenetics and cytogenetics to describe karyotype evolution in Diprotodontia. Molecular relationships of diprotodontian marsupials have been clarified using a concatenation of 5 nuclear gene sequences from multiple exemplars of all extant genera. Our well-resolved phylogenetic tree has been used as a basis for understanding chromosome evolution both within this Order, as well as in marsupials in general. It is clear that the ancestral marsupial karyotype comprised 14 relatively large chromosomes of the form retained relatively unchanged in caenolestids, microbiotherians, peramelemorphians, vombatids, and pygmy possums. Four pericentric inversions occurred in the ancestral dasyuromorphian (chromosomes 1, 2, 4, and 6) and a different 4 in the ancestral didelphimorphian (chromosomes 1, 3, 5 and 6). Within Diprotodontia, although the ancestral marsupial karyotype has been retained in some families such as the extant wombats and pygmy possums, there have been major karytoypic repatternings early in the evolution of others. Chromosome rearrangements in diprotodontia include centric fissions and fusions, translocations, and centromere shifts. Karyotypic changes are discussed in the context of current hypotheses concerning centromeres, chromosomal fragile sites, and mobile elements in marsupials and the probable repeated involvement of these elements in karyotypic restructuring. | {
"pile_set_name": "PubMed Abstracts"
} |
Use of benzodiazepines in primary-care geriatric patients.
From a sample of 257 elderly patients, 93 subjects who had received benzodiazepine (mainly diazepam) prescriptions for one or more years were interviewed about their subjective perception of the drug's effects and their attitudes regarding its use. The subjects were predominantly women: mean age was 72 years. All subjects had begun use of benzodiazepine more than two years earlier, although some had since stopped using the drug; more than a third had used it for more than six years. About half of the subjects said they took no more of the drug than had been initially prescribed, and three quarters reported they took the medications only when a need was felt. The principal indication for use of benzodiazepines was described as tension. Those who were still taking the drug at the time of interview were more likely to live alone and to say that they had the same problems as when they began its use. None of the subjects who had discontinued use of the drugs had been aware of withdrawal symptoms, and there was no evidence that any subject had become addicted, although several expressed a fear of this. It appears that in this age group, prolonged use of benzodiazepine at low doses, with the patients regulating the quantity, is safe and may be helpful. Most subjects, even if not helped, always kept some of the drug at home in case they might need it. | {
"pile_set_name": "PubMed Abstracts"
} |
A versatile micro-mechanical tester for actin stress fibers isolated from cells.
Conventional atomic force microscopy is one of the major techniques to evaluate mechanical properties of cells and subcellular components. The use of a cantilever probe for sample manipulation within the vertical plane often makes absolute positioning of the probe, subject to thermal drift, difficult. In addition, the vertical test is unable to observe changes in the sample structure responsible for mechanical behavior detected by the probe. In the present study, an alternative mechanical tester was developed that incorporated a pair of micro-needles to manipulate a sample in a project plane, allowing acquisition of the accurate probe position and entire sample image. Using a vision-based feedback control, a micro-needle driven by a piezo actuator is moved to give user-defined displacements or forces to sample. To show its usefulness and versatility, three types of viscoelastic measurements on actin stress fibers isolated from smooth muscle cells were demonstrated: strain rate-controlled tensile tests, relaxation tests and creep tests. Fluorescence imaging of the stress fibers using Qdots over the course of the measurements, obtained through multiple image detectors, was also carried out. The technique described here is useful for examining the quantitative relationship between mechanical behavior and related structural changes of biomaterials. | {
"pile_set_name": "PubMed Abstracts"
} |
A review of canine pseudocyesis.
The purpose of this article is to review the most relevant features of the physiology, clinical signs, diagnosis, treatment and prevention of canine pseudocyesis (PSC). This is a physiological syndrome, characterized by clinical signs such as: nesting, weight gain, mammary enlargement, lactation and maternal behaviour, which appears in non-pregnant bitches at the end of metaoestrus. PSC is a frequent finding in domestic dogs. Although it is generally admitted that prolactin (PRL) plays a central role in the appearance of PSC, its precise aetiophysiology is not completely understood yet. A number of clinical studies suggest that at some point of metaoestrus circulating PRL levels rise in overtly pseudopregnant bitches. Individual differences in sensitivity to PRL as well as the existence of molecular variants of canine PRL with different bioactivity versus immunoreactivity ratios may help clarify the aetiopathology of PSC. Diagnosis of PSC is based on the presence of typical clinical signs in metaoestrous non-pregnant bitches. Considering that PSC is a self limiting physiological state, mild cases usually need no treatment. Discouraging maternal behaviour and sometimes fitting Elizabethan collars to prevent licking of the mammary glands may suffice in these cases. Sex steroids (oestrogens, progestins and androgens) have been traditionally used to treat PSC but the side-effects usually outweigh the benefits of these medications. Inhibition of PRL release by ergot derivatives [bromocriptine (10-100 microg/kg per day for 10-14 days], cabergoline (5 microg/kg per day during 5-10 days), metergoline (0.2 mg/kg per day during 8-10 days) has proved to be effective for the treatment of canine PSC. Although some of these ergot derivatives present some untoward side-effects, they are transient and can usually be managed. Predisposed bitches not intended for breeding should be spayed as ovariectomy is the only permanent preventive measure. | {
"pile_set_name": "PubMed Abstracts"
} |
Attentional focus on subjective interoceptive experience in patients with fibromyalgia.
The hypervigilance model of pain perception states that patients with fibromyalgia (FM) have an enhanced sensitivity to aversive and non-aversive stimuli. Few studies have focused on enhanced interoceptive sensitivity in FM. Therefore, the aim of the present study was to investigate spontaneous sensations (SPS) in FM. SPS are those tingling, tickly and other kind of sensations usually perceived on the skin during periods of rest and without any external trigger. Therefore, we have investigated SPS by requiring participants to focus attention on each hand. Eighteen patients with a diagnosis of FM and 18 matched healthy participants had to direct their gaze toward the hand tested for a period of 10s. Subsequently, they had to map and report the intensity, the number and the qualitative properties of sensations arising spontaneously. Finally, participants had to fill out questionnaires assessing cognitive and affective status that may influence the interoceptive sensations feedback. Patients with FM perceived SPS as significantly more intense than controls did. Additionally, SPS were perceived by the FM group as occupying an overall larger area on the hand than those reported by controls. Importantly, entering scores of pain and catastrophism as covariates produced a relative effect on the feeling of SPS. The outcome of this study supports the generalized hypervigilance model, suggesting that patients with FM have a perceptual style of amplification of non-aversive interoceptive stimulation, modulated by pain and catastrophizing. This is discussed in relationship to interoceptive awareness. | {
"pile_set_name": "PubMed Abstracts"
} |
High-dose ara-C with autologous peripheral blood progenitor cell support induces a marked progenitor cell mobilization: an indication for patients at risk for low mobilization.
A high-dose (HD) chemotherapy scheme was designed for the collection of large numbers of peripheral blood progenitor cells (PBPC) in lymphoma patients who were candidates for myeloablative therapy with autograft. The scheme included the sequential administration of HD cyclophosphamide (CY) (7 g/m(2)) and HD ara-C (2 g/m(2) twice a day for 6 consecutive days), followed by final consolidation with PBPC autograft. PBPC harvests were scheduled following both HD CY and HD ara-C. To minimize hematologic toxicity, small aliquots of PBPC (<or=3 x 10(6) CD34(+) cells/kg) collected following HD CY were reinfused following HD ara-C. The treatment was delivered to 112 patients (median age: 43 years) with lymphoid malignancies (107 non-Hodgkin's lymphoma, four Hodgkin's lymphoma, one amyloidosis); 75 patients were at disease onset, whereas 37 had relapsed or were refractory after first-line conventional therapy. PBPC mobilization was assessed in terms of peak values of circulating CD34(+) cells/microl, as well as total CD34(+) cells/kg collected. In a few patients CFU-GM/kg were also evaluated. At the time of maximal mobilization following HD CY, 93 'high-mobilizer' patients had >20 circulating CD34(+) cells/microl, whereas the remaining 19 'low-mobilizer' patients did not reach this cut-off value. In spite of poor mobilization after HD CY, 16 out of 19 low mobilizers provided good harvests following HD ara-C; overall, median collected CD34(+) cells x 10(6)/kg were 1.4 (0-3.1) and 10.2 (0-37) after HD CY and HD ara-C, respectively (P = 0.00007). Similar patterns were observed when PBPC were evaluated by CFU-GM/kg. Complete and durable hemopoietic reconstitution followed autograft with post HD ara-C PBPC. Within the high-mobilizer group, 88 patients received HD ara-C and 79 (90%) still showed high mobilization; overall, median collected CD34(+)cells x 10(6)/kg were 17.8 (range 3-94) and 19 (range 0-107) after HD CY and HD ara-C respectively (P = NS). Thus, the scheme allowed sufficient PBPC collections for autografting in low mobilizer patients; in addition, the scheme could be considered whenever extensive chemotherapy debulking is needed prior to PBPC collection. | {
"pile_set_name": "PubMed Abstracts"
} |
Ovarian steroidogenic responses to gonadotropin-releasing hormone agonist testing with nafarelin in hirsute women with adrenal responses to adrenocorticotropin suggestive of 3 beta-hydroxy-delta 5-steroid dehydrogenase deficiency.
Nonclassical 3 beta-hydroxy-delta 5-steroid dehydrogenase (3 beta-HSD) deficiency type of congenital adrenal hyperplasia has been hypothesized to occur in as many as 10-40% of hirsute women, based on the adrenal steroidogenic responses to ACTH. However, diagnostic criteria for this "late-onset" 3 beta-HSD deficiency are not clearly established. Among 40 successive hyperandrogenic women undergoing evaluation of adrenal steroidogenic responses to ACTH, 8 had responses suggestive of 3 beta-HSD deficiency. Since 3 beta-HSD is present in both the ovary and adrenal, we attempted to document the defect in the ovary by stimulating their ovarian function with a gonadotropin-releasing hormone agonist test using nafarelin (6-D-[2-naphthyl]alanine-gonadotropin-releasing hormone). The eight hirsute women had steroid responses to ACTH suggestive of 3 beta-HSD deficiency, namely, the values of the delta 5-steroids, 17-hydroxypregnenolone and dehydroepiandrosterone, 30 and 60 min after ACTH in each hirsute woman were greater than 2 SD above the normal mean. Seven of the eight hirsute women had at least one elevated delta 5/delta 4-steroid ratio; however, only three of the hirsute women had two abnormal ratios. Furthermore, the response of the delta 4-steroid androstenedione and the ratio of androstenedione to cortisol after ACTH were significantly increased in the hirsute women, findings not consistent with 3 beta-HSD deficiency. After nafarelin, five and six hirsute patients had elevated values of the delta 4-steroids androstenedione and 17-hydroxyprogesterone, respectively. No patient had an elevated delta 5/delta 4-steroid ratio after nafarelin. Thus, ovarian steroidogenic responses to nafarelin did not support the diagnosis of 3 beta-HSD deficiency. Rather, they are consistent in most cases with polycystic ovary syndrome due to dysregulation of 17-hydroxylase and 17,20-lyase activities. We propose that increased activity of the enzyme P450c17 alpha in the adrenal cortex is responsible for most of what is often termed late-onset 3 beta-HSD deficiency. | {
"pile_set_name": "PubMed Abstracts"
} |
Probabilistic risk model of norovirus transmission during handling and preparation of fresh produce in school foodservice operations.
Human noroviruses (NoV) are recognized worldwide as important pathogens and the primary cause of foodborne disease outbreaks from contaminated food in the U.S. They are often transmitted by infected food handlers manipulating foods during preparation, such as fresh fruits and vegetables. This paper provides a study to model the transfer of NoV between food handlers and vegetables during salad preparation in school food services based on direct observation data. Three transfer pathways were modeled by considering different initial contamination sources (environment, handlers and contaminated produce). The probability of infection by NoV was also estimated based on the NoV levels at consumption obtained from each simulated transfer pathway. A scenario analysis ranging a wide concentration from 102 to 107 NoV infective particles was performed to represent different levels of NoV in the initial contamination sources. In addition, a sensitivity analysis was applied to identify the most important model inputs and determine the safest handling practices to be implemented in school food service operations. The pathway describing transfer from contaminated surfaces or handlers to foods indicated that initial levels of ≤104 NoV particles/fomite resulted in <0.5% cases per serving of NoV infection. When initial levels were higher, % cases of NoV infection was estimated to be ca. 3%. This rise in % cases of infection was linked to higher doses (5% serving with ≥15 NoV particles/serving) and prevalence levels at consumption (>0.2). In the pathway modeling cross contamination from contaminated vegetables to non-contaminated vegetables, all scenarios could lead to infected individuals, although number of cases of infection were lower (<1.3%), despite concentration levels were higher. On the contrary, for this pathway, prevalence was 2-fold lower than that observed in the pathways describing transfer from contaminated surfaces and hands. Based on the sensitivity analysis, NoV transfers to fresh produce may be minimized by improving hand washing, and therefore effective training programs need to be carried out specifically addressing hand washing. Moreover, the produce's washing step showed to be an effective control measure, depending on the desinfectant efficacy, by reducing % cases of NoV infection from 6 to 1%. The model in this study might be used, in the future, to evaluate the impact on the risk associated with NoV transmission of specific and effective training programs, aimed at food chain operators. | {
"pile_set_name": "PubMed Abstracts"
} |
Control of the autophagy maturation step by the MAPK ERK and p38: lessons from environmental carcinogens.
Macroautophagy (hereafter referred to as autophagy) is the major degradative pathway of long-lived proteins and organelles that fulfils key functions in cell survival, tissue remodeling and tumor suppression. Consistently, alterations in autophagy have been involved in a growing list of pathologies including toxic injury, infections, neurodegeneration, myopathies and cancers. Although critical, the molecular mechanisms that control autophagy remain largely unknown. We have recently exploited the disruption of autophagy by environmental carcinogens as a powerful model to uncover the underlying signaling pathways. Our work published in Cancer Research revealed that the sustained activation of the MAPK ERK pathway by the carcinogen Lindane or the MEK1(+) oncogene alters autophagy selectively at the maturation step resulting in the accumulation of large defective autolysosomes. Consistent with our findings, a similar defect is observed with other common xenobiotics such as dichlorodiphenyltrichloroethane and biphenol A that specifically activate ERK. Conversely, Pentachlorophenol that activates both ERK and p38, fails to induce autophagic vacuolation. In addition, evidence is provided that abrogation of p38 by SB203580 is sufficient to interfere with the normal autophagic maturation step. Altogether, these findings underscore the critical role played by MAPK ERK and p38 in the tight control of the autophagy process at the maturation step. | {
"pile_set_name": "PubMed Abstracts"
} |
Oxidative stress developed during the reperfusion of ischemic myocardium induces apoptosis.
Apoptosis or programmed cell death is a genetically controlled response for cells to commit suicide and, is associated with DNA fragmentation or laddering. The common inducers of apoptosis include oxygen free radicals/oxidative stress and Ca2+ which are also implicated in the pathogenesis of myocardial ischemic reperfusion injury. To examine whether ischemic reperfusion injury is mediated by apoptotic cell death, isolated perfused rat hearts were subjected to 15, 30 or 60 min of ischemia as well as 15 min of ischemia followed by 30, 60 or 120 min of reperfusion. At the end of each experiment, hearts were processed for the evaluation of apoptosis, DNA laddering. Apoptosis was studied by visualizing the apoptotic cardiomyocytes by direct fluorescence detection of digoxigenin-labeled genomic DNA using APOPTAG in situ apoptosis detection kit. DNA laddering was evaluated by subjecting the DNA obtained from the hearts to 1.8% agarose gel electrophoresis and photographed under UV illumination. The results of our study revealed apoptotic cells only in the 60 and 120 min reperfused hearts as demonstrated by the intense fluorescence of the immunostained digoxigenin-labeled genomic DNA when observed under fluorescence microscopy. None of the ischemic hearts showed any evidence of apoptosis. These results corroborated with the findings of DNA fragmentation which showed increased ladders of DNA bands in the same reperfused hearts representing integer multiples of the intenucleosomal DNA length (about 180 bp). The presence of apoptotic cells and DNA fragmentation in the myocardium were abolished by preperfusing the hearts in the presence of ebselen, which also removed the oxidative stress developed in the heart. Taken together, these results clearly demonstrate that oxidative stress developed in the ischemic reperfused myocardium induces apoptosis. | {
"pile_set_name": "PubMed Abstracts"
} |
Repeatability and sources of variability in multi-center assessment of segmental foot kinematics in normal adults.
Multi-site application of biomechanical models can be a powerful tool as quantitative methods are employed to improve clinical care and to assess larger populations for research purposes. However, the use of such models depends on adequate validation to assure reliability in inter-site measures. We assessed repeatability and sources of variability associated with the assessment of segmental foot kinematics using the Milwaukee Foot Model during multiple testing sessions at two sites. Six healthy ambulators were instrumented and tested during comfortable ambulation; data were analyzed with variance components analysis using a mixed effects linear model. Results indicated that the largest source of variability was inter-subject; measurement error associated with Site and Session fell below 3.5 degrees in over 80% of position measurements and below 2.5 degrees in over 80% of ROM measurements. These findings support the continued use of the segmental foot model at multiple sites for clinical and research purposes. | {
"pile_set_name": "PubMed Abstracts"
} |
Stereoselective reduction of 1-o-isopropyloxygenipin enhances its neuroprotective activity in neuronal cells from apoptosis induced by sodium nitroprusside.
Genipin is a Chinese herbal medicine with both neuroprotective and neuritogenic activity. Because of its unstable nature, efforts have been to develop more stable genipin derivatives with improved biological activities. Among the new compounds reported in the literature, (1R)-isopropyloxygenipin (IPRG001) is a more stable but less active compound compared with the parent, genipin. Here, two new IPRG001 derivatives generated by stereoselective reduction of the C6 =C7 double bond were synthesized. The 1R and 1S isomers of (4aS,7S,7aS)-methyl-7-(hydroxymethyl)-1-isopropoxy-1,4a,5,6,7,7a-hexahydrocyclopenta[c]pyran-4-carboxylate (CHR20 and CHR21) were shown to be very stable both in high-glucose cell culture medium and in mice serum at 37 °C. Evaluation using an MTT assay and Hoechst staining showed that CHR20 and CHR21 promote the survival of rat adrenal pheochromocytoma (PC12) and retinal neuronal (RGC-5) cells from injury induced by sodium nitroprusside (SNP). The neuroprotective effects of CHR20 and CHR21 were greater than both isomers of IPRG001, the parent compounds. These results indicate that reduction of 1-O-isopropyloxygenipin enhances its neuroprotective activity without affecting its stability. | {
"pile_set_name": "PubMed Abstracts"
} |
Stimulus enhancement in greylag geese: socially mediated learning of an operant task.
We recently observed the spreading of a novel tradition in a flock of semiferal greylag geese, Anser anser: an increasing number of individuals began to bite and chew the stems of butterbur, Petasites hybridus. Because this behaviour spread particularly fast within families, social learning seemed to be involved. We therefore designed an experiment with hand-reared goslings, which were socially imprinted on humans, to investigate whether and how the observation of an experienced tutor affects the acquisition of a novel skill. Goslings had to open the gliding lid of a box to get at a food reward. To each of seven hand-reared observers a human tutor demonstrated where and how to open the lid, whereas seven controls remained untutored. All observers learned to perform the task but only one of the controls succeeded. The observers explored more often at the position shown by the tutor than elsewhere and seemingly learned by trial and error. In contrast, control birds explored primarily at positions that did not allow them to open the box. These results indicate that in greylag goslings the observation of an experienced model facilitates the learning of an operant task. We conclude that stimulus enhancement followed by operant conditioning were the mechanisms involved, which may have accounted for the fast spread of the stem-chewing tradition between family members. Copyright 2000 The Association for the Study of Animal Behaviour. | {
"pile_set_name": "PubMed Abstracts"
} |
Salivary Candida, caries and Candida in toothbrushes.
Candida species are common inhabitants of the normal oral microbiota. A few studies founded a relationship between high levels of Candida albicans in the oral cavity and high DMF scores. Toothbrushes can also be reservoirs of microorganisms, the proliferation of these microorganism on a toothbrush could be a major factor for its distribution in the oral cavity. To examine the associations between salivary Candida and DMF, and between salivary Candida and Candida in the toothbrush. 46 healthy school children, who attended a University pediatric dental clinic, were tested for Candida in their saliva and in their toothbrush. Their DMF was recorded. 38 children were Candida-positive (79.2%), out of whom 5 demonstrated a positive growth of Candida in the toothbrushes. No correlation was found between Candida in the saliva and in the toothbrush. The number of Candida-positive girls was significantly higher than the number in boys. No significant relationship between caries experience and the presence of Candida was found No correlation was found between Candida in the saliva and in the toothbrush. The origin of the Candida in the toothbrush is not totally clear. | {
"pile_set_name": "PubMed Abstracts"
} |
Convention on the Battle Against Desertification, 8 August 1988.
Tunisia ratified the Convention on the Battle Against Desertification on 27 October 1988. See Journal Officiel de la Republique Tunisienne, No. 74, 1 November 1988, p. 1507. | {
"pile_set_name": "PubMed Abstracts"
} |
Body proportions in Hyaenidae.
Indexes of skeletal measurements are used to compare body proportions in Hyaenidae, Canidae and Felidae. Hyaena and Crocuta are characterized by a long neck and long forelimbs. The humerus is relatively short and the radius and metacarpal bones are long. In the the os femoris is long and the tibia short. The proportions are adapted to carry large and heavy prey and provide maximum static stability. Proteles cristatus which mainly feeds on termites and insects has the long neck and forelimb in common with the other Hyaenidae, but its hindlimbs are longer and the length of the limbsegments reveals more canid proportions. | {
"pile_set_name": "PubMed Abstracts"
} |
[Tuberculosis of the respiratory system--clinical picture].
Analysis of the clinical development of tuberculosis in 100 patients admitted in 1995 to the Clinic of Pneumology and Thoracic Surgery of the 3rd Medical Faculty Charles University is focused on the pitfalls of correct diagnosis and treatment. The development of the disease is influenced by a number of risk factors and serious associated diseases. Proper verification of TB is emphasized: in addition to laboratory methods also the surgical approach with histological confirmation holds its place. Antituberculotic treatment according to recommended regimens calls in indicated cases of drug intolerance for pharmacokinetic examination. Tuberculosis is a disease which requires a multidisciplinary approach. | {
"pile_set_name": "PubMed Abstracts"
} |
Evaluation of parameters critical to observing proteins inside living Escherichia coli by in-cell NMR spectroscopy.
Our recently developed in-cell NMR procedure now enables one to observe protein conformations inside living cells. Optimization of the technique demonstrates that distinguishing the signals produced by a single protein species depends critically on protein overexpression levels and the correlation time in the cytoplasm. Less relevant is the selective incorporation of (15)N. Poorly expressed proteins, insoluble proteins, and proteins that cannot tumble freely due to associations within the cell cannot yet be observed. We show in-cell NMR spectra of bacterial NmerA and human calmodulin and discuss limitations of the technique as well as prospects for future applications. | {
"pile_set_name": "PubMed Abstracts"
} |
Attenuation and Morphologic Characteristics Distinguishing a Ground-Glass Nodule Measuring 5-10 mm in Diameter as Invasive Lung Adenocarcinoma on Thin-Slice CT.
OBJECTIVE. The purpose of this study is to comprehensively investigate the role of multiple features seen on thin-section CT (TSCT) in the differential diagnosis of ground-glass nodules (GGNs) measuring 5-10 mm in diameter as invasive adenocarcinoma (IAC). MATERIALS AND METHODS. The TSCT features of 313 surgically diagnosed GGNs from 288 patients were retrospectively reviewed. A logistic regression model was applied, and the AUC values for the model and the size and attenuation of the lesions were compared using ROC curve analysis. RESULTS. A total of 247 lung adenocarcinomas in situ (AISs) and minimally invasive adenocarcinomas (MIAs) (hereafter referred to as the AIS-MIA group) and 66 invasive adenocarcinomas (IACs) were identified. Compared with the AIS-MIA group, the IAC groups were significantly larger in size and had higher attenuation values, a higher frequency of mixed GGNs (all p < 0.001), bubblelike appearance, spiculation, pleural indentation, different locations, and a lower frequency of clear tumor-lung interface (all p < 0.05). The logistic model included size and attenuation (both p < 0.001; odds ratio [OR], 1.872 and 1.009, respectively) as well as tumor-lung interface (p = 0.001; OR, 0.242), bubblelike appearance (p < 0.05; OR, 2.205), and type of nodule. The AUC value for the logistic model was 0.847 (sensitivity, 80.3%; specificity, 81.0%) and was significantly higher than that for size or attenuation (both p < 0.01). CONCLUSION. Radiologic features could help in the differential diagnosis of a GGN that was 5-10 mm in diameter as IAC versus AIS or MIA. GGNs larger than 8.12 mm and with attenuation greater than -449.52 HU were more likely to be IAC. | {
"pile_set_name": "PubMed Abstracts"
} |
Corynebacterium kutscheri invasiveness of the gastrointestinal tract in young mice.
Corynebacterium kutscheri invasiveness of the tissues of the gastrointestinal tract in mice was investigated by the fluorescent antibody technique. The invasion was clearly recognized in 3-week-old mice infected intragastrically along with gastric mucin and a subcutaneous dose of cortisone; 10(7) organisms caused a notable invasion of the gastric and duodenal tissues. Furthermore, marked bacterial invasion of the large intestine appeared in mice challenged perorally with 7 x 10(7) organisms. | {
"pile_set_name": "PubMed Abstracts"
} |
Modulation of Na-H exchange activity by angiotensin II in opossum kidney cells.
Angiotensin II (ANG II) was shown to modulate transport in the renal proximal tubule through both inhibition of adenylate cyclase and protein kinase C (PKC) activation. We evaluated the effects of ANG II on adenosine 3',5'-cyclic monophosphate (cAMP) content and Na-H exchange activity (amiloride-sensitive Na influx) in two strains of opossum kidney (OK) cells originating from different sources, OK-VD and OK-RR cells. In OK-VD cells, ANG II inhibited basal and parathyroid hormone (PTH)-induced cAMP generation in a pertussis toxin-sensitive manner and reversed PTH inhibition of Na-H exchange. These effects of ANG II were prevented by PD 123319, a selective nonpeptide antagonist of AT2 receptors. In contrast, DuP 753, which antagonizes selectively AT1 receptors, had no effect. In OK-RR cells, ANG II had no effect on cAMP content and decreased Na-H exchange activity. The effect of ANG II persisted in the presence of PTH but was abolished by PKC downregulation and by DuP 753, but not by PD 123319. In conclusion, two types of ANG II receptors, coupled to distinct signaling pathways, were expressed independently in OK cells originating from two different sources and mediated opposite effects of ANG II on Na-H exchange activity. Those models provide a powerful tool for studying the intracellular steps involved in the tubular effects of ANG II and to evaluate the effect of pharmacological inhibitors of ANG II binding to its receptors. | {
"pile_set_name": "PubMed Abstracts"
} |
Tracers for paralysis agitans in epidemiological research. V. Prevalence of the disease in Swedish counties.
The prevalence of parkinsonism varies severalfold between different countries in the world. This could be due to an accumulation of risk factors in certain areas. In the present paper we have analyzed the regional distribution of parkinsonism in Sweden in order to see if such areas could be found within one country. The study was based on sales of levodopa in the different counties of Sweden, and the results were standardized for age and quality of health services as indicated by the local infant mortality rates. The mean prevalence of the different Swedish counties was estimated to be in the middle range of known prevalences. There was a 60% variation within Sweden between the different counties, but the regional distribution did not show a systematic pattern. Further analysis of the causes for this variation showed that differences in case ascertainment and in drug policy could well account for the observed regional differences in parkinsonism prevalence. | {
"pile_set_name": "PubMed Abstracts"
} |
Do natriuretic peptides modify arterial baroreflexes in sheep?
While atrial and B-type natriuretic peptides (ANP and BNP) have been shown to enhance reflex responses attributed to cardiac vagal afferents, their effects on arterial baroreceptor reflex function remain controversial. The actions of C-type natriuretic peptide (CNP) in this regard are unknown. To clarify their actions on arterial baroreflexes, we tested whether i.v. infusions of ANP, BNP or CNP at 10 pmol kg(-1) min(-1) modified the steady-state mean arterial blood pressure-heart rate (MAP-HR) relationship in conscious sheep. At this dose, all three natriuretic peptides are known to enhance the cardiac chemoreflex response to phenylbiguanide (Bezold-Jarisch reflex). Sigmoid MAP-HR relationships were constructed from the steady-state responses to alternating injections of vasopressor (phenylephrine, 1-15 microg kg(-1)) and vasodepressor agents (nitroprusside, 1-15 microg kg(-1)) in the absence and presence of infused ANP, BNP or CNP (tested in random order at least 1 week apart). No parameter of the steady-state baroreflex relationship was significantly altered by infusion of any of the three natriuretic peptides. We conclude that in conscious sheep, normal arterial baroreceptor-HR reflex function prevails in the presence of moderate doses of ANP, BNP or CNP. | {
"pile_set_name": "PubMed Abstracts"
} |
Nitroglycerin application during cesarean delivery: plasma levels, fetal/maternal ratio of nitroglycerin, and effects in newborns.
We sought to investigate maternal and fetal nitroglycerin metabolization and to assess the clinical condition of neonates after intravenous nitroglycerin application during cesarean delivery. At the time of the uterine puncture incision, either 0. 25 mg or 0.5 mg nitroglycerin or a physiologic sodium chloride solution was administered as an intravenous bolus. Plasma concentrations of nitroglycerin and its metabolites were measured in maternal venous blood and in umbilical blood samples taken immediately after cord clamping. Arterial blood pressure, pulse rates, and Apgar scores were recorded for the neonates 1, 5, and 10 minutes after birth. Sixty-two patients were included in the pharmacokinetic study. Median maternal plasma levels 1 and 5 minutes after injection of 0.5 mg nitroglycerin were 80 and 3.2 ng/mL, respectively; median maternal plasma levels 1 and 5 minutes after injection of 0.25 mg nitroglycerin were 38 and 1.2 ng/mL, respectively. In the umbilical vein 1 minute after application of 0. 5 mg or 0.25 mg nitroglycerin, the plasma levels were 0.41 and 0.09 ng/mL, respectively, and in the umbilical artery they were 0.03 and 0.008 ng/mL, respectively. Circulatory parameters and Apgar scores in the neonates did not differ significantly from those found in the placebo group. The level of nitroglycerin in umbilical plasma was two to three orders of magnitude lower than that found in maternal plasma and clearly in a subtherapeutic range. There was no indication that prenatal application of nitroglycerin to facilitate obstetric management is hazardous for neonates. | {
"pile_set_name": "PubMed Abstracts"
} |
Primary structure of myohemerythrin from the annelid Nereis diversicolor.
The metal-free form of Nereis diversicolor myohemerythrin was purified from whole animal extracts by trichloroacetic acid precipitation and ion exchange chromatography. The amino acid sequence of myohemerythrin has been determined. The protein is composed of 120 residues, possesses an unblocked N-terminus and is devoid of cysteine residues. It bears 62% sequence identity with Themiste zostericola myohemerythrin, the only other member of this subfamily sequenced to date. Within the family of hemerythrins, homology is particularly high in the segments involved in the binding of the two iron atoms and in the beta-turn-rich N-terminal segment. | {
"pile_set_name": "PubMed Abstracts"
} |
Layer-by-layer epitaxy in limited mobility nonequilibrium models of surface growth.
We study, using noise-reduction techniques, layer-by-layer epitaxial growth in limited mobility solid-on-solid nonequilibrium surface growth models, which have been introduced in the context of kinetic surface roughening in ideal molecular beam epitaxy. Multiple hit noise reduction and long surface diffusion length lead to qualitatively similar layer-by-layer epitaxy in (1+1)- and (2+1)-dimensional limited mobility growth simulations. We discuss the dynamic scaling characteristics connecting the transient layer-by-layer growth regime with the asymptotic kinetically rough growth regime. | {
"pile_set_name": "PubMed Abstracts"
} |
A carnivore species (Canis familiaris) expresses circadian melatonin rhythm in the peripheral blood and melatonin receptors in the brain.
Dogs kept under controlled photoperiodic conditions of 12 h light and 12 h dark expressed a clear diurnal melatonin rhythm in the peripheral blood, with a swift peak restricted to the late part of the scotophase. The highest density of high-affinity, G-protein-linked 2-[125I]iodomelatonin binding sites was found in the pars tuberalis of the pituitary gland. Binding sites were found also in the pars distalis, and light microscopy/high-resolution autoradiography showed that binding was located exclusively over the chromophobe and basophilic cells forming the adenopituitary zona tuberalis, well developed in this species, and extending into the gland as a continuation of pars tuberalis. Cords of basophilic cells located in the pars distalis proper also expressed high receptor density. The eosinophils in the adenohypophysis and the neural lobe were devoid of binding. Heavily labeled were the external laminar and the mitral cell layers of the olfactory bulbs, but no binding was detected in the filae nervi olfactorii or tractus olfactorius. The hypothalamic suprachiasmatic nuclei were discernible clearly. Quantitative autoradiography inhibition experiments revealed that the apparent melatonin inhibitory constant (IC50) in all those areas was around 0.1 nmol/l, which is a physiologically appropriate value considering the peripheral blood melatonin levels. Co-incubation with guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) led to a consequential decrease in the binding density. The specific binding observed in other areas (hippocampus, frontal, parietal, occipital cortex and cerebellum) was rather weak, diffuse and could not be attributed to a particular layer; the apparent IC50 for melatonin was about 1 mumol/l, and co-incubation with GTP gamma S did not modify the binding density. Collectively, these data show that the dog possess all the prerequisites for an efficient network adapted to photoperiodic time measurements. A circadian melatonin signal in the peripheral blood and an apparently functional readout receptor system located in key positions within the brain are both present in this species. | {
"pile_set_name": "PubMed Abstracts"
} |
The clinical importance of "bamboo joint-like appearance" on upper gastrointestinal endoscopy for the diagnosis of Crohn's disease.
Upper gastrointestinal (GI) lesions are frequently reported in Crohn's disease, in which the entire GI tract is affected. In these cases, erosive fissures regularly transversing folds that are longitudinally aligned along the lesser curvature of the gastric body and cardia are described as having a "bamboo joint-like appearance". We designed a blinded experiment in which upper GI imaging without a final diagnosis was checked by three observers to determine the usefulness of the bamboo joint-like appearance in the diagnosis of Crohn's disease. For the three observers, sensitivities of appearance were 30.5%, 56.9%, and 51.4%, while specificities were 99.6%, 98.5%, and 99.3%. Thus, the bamboo joint-like appearance was not useful for the identification of Crohn's disease patients. Nevertheless, patients exhibiting the bamboo joint-like appearance in upper GI imaging should undergo further examination due to the high probability of Crohn's disease. | {
"pile_set_name": "PubMed Abstracts"
} |
Contributions of electron microscopy and single-particle techniques to the determination of the ryanodine receptor three-dimensional structure.
The ryanodine receptor is the main intracellular calcium release channel from the sarcoplasmic reticulum in striated muscle. It is the largest ion channel known, composed of four identical major subunits of 565 kDa and four smaller 12-kDa subunits, identified as FK-506 binding protein. The successful isolation of the ryanodine receptor together with the development of cryoelectron microscopy and single-particle image processing techniques have enabled major progress to be made in the determination of the receptor's structure over the past decade. Three-dimensional reconstruction shows the receptor to be composed of two main parts, a large square shaped cytoplasmic assembly and a smaller transmembrane assembly. The cytoplasmic assembly has an unusual architecture in which about 10 domain-like structures are interconnected in a loosely packed manner. Subsequent studies have started to reveal conformational changes associated with channel gating and the localization of binding sites for some proteins with which the receptor interacts (calmodulin, and FK-506 binding protein). It is becoming clear that long-range induced conformational changes must be involved in the mechanisms of modulation of the receptor's gating properties. | {
"pile_set_name": "PubMed Abstracts"
} |
Additions and corrections to the systematics of mayfly species assigned to the genus <i>Callibaetis</i> Eaton 1881 (Ephemeroptera: Baetidae) from South America.
Due to historical taxonomic impediments, species of Callibaetis Eaton are difficult to identify. Recent studies have attempted to resolve this problem, although many species still lack complete descriptions; nymphs of several species remain undetermined; and type specimens are lost or poorly known. Given these hindrances, the aim of this study is to review some of the type specimens of Callibaetis from South America. This review provides a series of taxonomic additions and corrections supported by improved morphological evaluations, illustrations and photographs of Callibaetis camposi Navás, C. (Abaetetuba) capixaba Cruz, Salles & Hamada, C. gregarius Navás, C. (C.) guttatus Navás, C. jaffueli Navás, C. (C.) jocosus Navás, C. nigrivenosus Banks, C. (A.) pollens Needham & Murphy, C. (C.) radiatus Navás, C. (A.) sellacki (Weyenbergh), C. stictogaster Navás, C. (C.) viviparus Needham & Murphy, C. (C.) willineri Navás, and C. (C.) zonalis Navás. From among these species, C. stictogaster and C. jaffueli are revalidated; C. nigrivenosus and C. gregarius are designated as nomina dubia; C. (C.) fluminensis Cruz, Salles & Hamada is proposed as a junior subjective synonym of C. (C.) zonalis; and C. gloriosus Navás is proposed as a junior subjective synonym of C. (A.) sellacki (Weyenbergh). Lectotypes are designated for C. camposi, C. jaffueli, C. (C.) radiatus and C. stictogaster. | {
"pile_set_name": "PubMed Abstracts"
} |
Analysis of alpha- and beta-tubulin genes of Bombyx mori using an EST database.
Tubulin is one of the most widespread classes of multiprotein families and is well known to construct microtubules with two different subunits, alpha- and beta-tubulin. In the course of genome analysis of Bombyx mori, we have constructed an EST database by large-scale sequencing of clones that were randomly selected from cDNA libraries of various tissues and organs belonging to different developmental stages. Using this EST database, we have identified four types of beta-tubulin gene and three types of alpha-tubulin gene. Based on the analysis of deduced amino acid sequences, we have determined the phylogenetic relationships of tubulins between Bombyx and Drosophila melanogaster as well as two other moth species, suggesting that each tubulin is classified into at least three distinct subfamilies: a ubiquitously expressed one, a developmentally regulated one and a testis specific one. | {
"pile_set_name": "PubMed Abstracts"
} |
Selecting a measure of health related quality of life.
Quality of life is becoming recognized increasingly as an important outcome measure which needs to be considered by social workers. However, there does not appear to be a clear consensus about the definition of quality of life. In addition, social workers are likely to experience difficulties choosing and applying an appropriate instrument with which to measure quality of life because of the many available instruments purporting to assess quality of life. This paper discusses the definition of health-related quality of life and explains the main measurement properties of an instrument that must be appraised when considering whether or not an instrument is appropriate. The paper will assist social workers to make an informed choice about measures of health-related quality of life. | {
"pile_set_name": "PubMed Abstracts"
} |
Clinical and pathological features of a neonate with autosomal recessive polycystic kidney disease caused by a nonsense PKHD1 mutation.
Autosomal recessive polycystic kidney disease (ARPKD) is one of the most common hereditary nephropathies in childhood. We report a neonate with ARPKD presenting with oligohydramnios, enlargement and increased echogenicity of both kidneys shown by antenatal sonograms after a 29-week gestation and died within the first few hours of life. The neonate was investigated pathologically post-mortem. PCR-DNA direct sequencing was performed to detect the exons of the PKHD1 gene for mutation analysis. Autopsy findings of the kidney and liver confirmed the diagnostic hypothesis. PKHD1 mutation analysis revealed that there was a homozygous nonsense mutation c.9319C>T (p.R3107X), which was found to be pathogenic, in exon 58 in the neonate. The recurrence of PKHD1 mutation c.9319C>T (p.R3107X) in the ARPKD population might be a good evidence that it is disease associated. Given the limitations of antenatal ultrasound, PKHD1 mutation analysis is helpful for accurate genetic counseling and early prenatal diagnosis. | {
"pile_set_name": "PubMed Abstracts"
} |
Infertility among African American women with systemic lupus erythematosus compared to healthy women: A pilot study.
Some treatments for systemic lupus erythematosus (SLE) can cause infertility, but the effect of SLE itself on fertility, particularly in African American women, is less clear. We examined infertility experiences in African American women with SLE compared to healthy women. We enrolled women ages 22-40, living in the Atlanta metropolitan area, who were diagnosed with SLE after age 17. Women ever treated with cyclophosphamide or who had a hysterectomy were excluded. African American women ages 22-40 from the same area recruited from a marketing list were used for comparison. Women were interviewed about their reproductive histories and goals. Periods of infertility were identified as times when they had regular, unprotected sex for ≥12 months without conceiving after age 20. We separately considered any period of infertility and periods of infertility when attempting pregnancy. We used Cox proportional hazards regression to examine the association between SLE and time to infertility. Models were adjusted for age, nulliparity and smoking. An age-matched analysis was also used to examine periods of infertility occurring after SLE diagnosis. Our sample included 75 women with SLE and 154 women without SLE. SLE was associated with any infertility (adjusted hazard ratio [aHR]: 2.08; 95% CI: 1.38, 3.15), but less so with infertility when attempting pregnancy (aHR: 1.30; 95% CI: 0.62, 2.71). The matched analysis generated similar point estimates. Women with SLE may be more likely to experience episodes of infertility, but this may not translate to an inability to meet reproductive goals. This article is protected by copyright. All rights reserved. | {
"pile_set_name": "PubMed Abstracts"
} |
Active disturbance rejection control: methodology and theoretical analysis.
The methodology of ADRC and the progress of its theoretical analysis are reviewed in the paper. Several breakthroughs for control of nonlinear uncertain systems, made possible by ADRC, are discussed. The key in employing ADRC, which is to accurately determine the "total disturbance" that affects the output of the system, is illuminated. The latest results in theoretical analysis of the ADRC-based control systems are introduced. | {
"pile_set_name": "PubMed Abstracts"
} |
Multiple resource supplements synergistically enhance predatory mite populations.
Many plants offer food rewards such as extrafloral nectar and food bodies, which have been shown to attract and retain entomophagous arthropods. In addition to food rewards, plants may possess structures that serve as shelter and/or oviposition sites for beneficial arthropods, so-called domatia. Acarodomatia are commonly used by beneficial mites for oviposition and protection from intraguild predators and adverse climatic conditions (drought). While in nature these food and shelter traits often occur in combination, they have been largely studied in isolation and we know little about how these traits interact, i.e., whether they act independently, antagonistically or synergistically. In the present study, we used citrus seedlings to test the impact of provisioning fibers (as a proxy for acarodomatia), as well as two different categories of food rewards (pollen and sugars) on oviposition and population development of phytoseiid mites. The highest oviposition and abundance of predatory mites was obtained in the treatment where the three resources were offered in combination. The combined impact of the three resources when provided jointly was up to five times higher than the summed impacts of each resource provided individually, thus providing evidence for a three-way synergy between the fibers, pollen and sugars. From an ecological point of view, our results demonstrate that combining multiple indirect defensive traits can strongly enhance the impact on the mutualistic arthropods. Differences in resource provisioning strategies in plant-phytoseiid and plant-ant mutualisms are being discussed. The presented results are of particular importance for our understanding of the functioning of defensive plant-arthropod mutualisms, as well as for the use of predatory mites in conservation- or inundative biological control. | {
"pile_set_name": "PubMed Abstracts"
} |
Ab Initio Simulations of Water Dynamics in Aqueous TMAO Solutions: Temperature and Concentration Effects.
We use ab initio molecular dynamics simulation to study the effect of hydrophobic groups on the dynamics of water molecules in aqueous solutions of trimethylamine N-oxide (TMAO). We show that hydrophobic groups induce a moderate (<2-fold) slowdown of water reorientation and hydrogen-bond dynamics in dilute solutions, but that this slowdown rapidly increases with solute concentration. In addition, the slowdown factor is found to vary very little with temperature, thus suggesting an entropic origin. All of these results are in quantitative agreement with prior classical molecular dynamics simulations and with the previously suggested excluded-volume model. The hydrophilic TMAO headgroup is found to affect water dynamics more strongly than the hydrophobic moiety, and the magnitude of this slowdown is very sensitive to the strength of the water-solute hydrogen-bond. | {
"pile_set_name": "PubMed Abstracts"
} |
A laboratory exercise using a physical model for demonstrating countercurrent heat exchange.
A physical model was used in a laboratory exercise to teach students about countercurrent exchange mechanisms. Countercurrent exchange is the transport of heat or chemicals between fluids moving in opposite directions separated by a permeable barrier (such as blood within adjacent blood vessels flowing in opposite directions). Greater exchange of heat or chemicals between the fluids occurs when the flows are in opposite directions (countercurrent) than in the same direction (concurrent). When a vessel loops back on itself, countercurrent exchange can occur between the two arms of the loop, minimizing loss or uptake at the bend of the loop. Comprehension of the physical principles underlying countercurrent exchange helps students to understand how kidneys work and how modifications of a circulatory system can influence the movement of heat or chemicals to promote or minimize exchange and reinforces the concept that heat and chemicals move down their temperature or concentration gradients, respectively. One example of a well-documented countercurrent exchanger is the close arrangement of veins and arteries inside bird legs; therefore, the setup was arranged to mimic blood vessels inside a bird leg, using water flowing inside tubing as a physical proxy for blood flow within blood vessels. | {
"pile_set_name": "PubMed Abstracts"
} |
[Study on the effects of taxol on Hep-2 cell lines in larynx carcinoma].
To investigate the sensitivity of Hep-2 cell lines in larynx squamous cell carcinoma to the taxol in vitro and to provide experimental basis for clinical therapy. Techniques of cell culture and randomized blank-contrast design were used. The degree and dose-dependency of taxol which induced growth inhibition in Hep-2 cell lines were observed and the alteration of cell cycle was analysed by flow cytomethy. All cells died at the concentration of taxol 1 x 10(-8) M; growth inhibition was observed clearly at the concentration of 5 x 10(-9) M and 2.5 x 10(-9) M. Flow cytometric data showed a G0/G1 arrest and apoptosis (28.96%) in two cell lines after exposure to taxol for 48 h at low and medium concentrations. There is a high sensitivity of Hep-2 cell to taxol in vitro. The cells show G0/G1 arrest and apoptosis. This results may provide reliable guidance for treating largnx carcinoma. | {
"pile_set_name": "PubMed Abstracts"
} |
Antipsychotic drugs and the risk of hyperglycemia in older adults without diabetes: a population-based observational study.
To determine whether current antipsychotic use among older persons without diabetes is associated with a higher risk of hospital visits for hyperglycemia, as previous studies in this population have yielded conflicting results. A nested case-control study within a population-based cohort of persons aged 66 years or older without diabetes, who initiated antipsychotic therapy between April 1, 2002, and March 31, 2006. Cohort members were identified using health databases from Ontario, Canada, and were followed from treatment start until March 31, 2007. Cases were patients with a hospital visit (emergency department visit or hospital admission) for hyperglycemia. We matched each case with up to 10 controls. We compared the risk of hyperglycemia among current antipsychotic users to that of remote users (discontinued > 180 days). The cohort consisted of 44,121 subjects, mean age of 78.3 years, followed for a mean of 2.2 years. Compared to remote antipsychotic use, current treatment with any antipsychotic was associated with a significantly increased risk of hospital visits for hyperglycemia (adjusted odds ratio [aOR]: 1.52; 95% confidence interval [CI]: 1.07-2.17). The risk was elevated for both atypical (aOR: 1.44; 95% CI: 1.01-2.07) and typical (aOR: 2.86; 95% CI: 1.46-5.59) antipsychotic agents. Current use of either atypical or typical antipsychotic agents was associated with a significantly increased risk of hospital visits for hyperglycemia among older persons without diabetes. These findings highlight the need for close glucose monitoring during antipsychotic therapy in older populations. | {
"pile_set_name": "PubMed Abstracts"
} |
[The Results of the Method Percutaneous Intracoronary Intervention in Patients of Both Male and Female].
To assess gender differences among patients subjected to percutaneous coronary intervention (PCI) according to data of the "Register of performed operations of percutaneous transluminal coronary angioplasty (PTCA)". The Register was conducted from 1996 to 2012 years and comprised 4890 patients (4121 men and 769 women). Women compared to men were older (58.2+/-8.6 vs 53.4+/-8.3 years; <0.001), had higher body mass index (31.4+/-5.3 vs 29.0+/-4.4 kg/m2; <0.001), level of total cholesterol (5.6+/-1.5 vs 5.3+/-1.3 mmol/l%; <0.001), systolic (141.1+/-22.2 vs 135.1+/-20.8 mmHg, <0.001) and diastolic blood pressure (86.5+/-11.8 vs 85.4+/-12.0 mmHg; =0.014). Compared to male cohort females more often had diabetes mellitus (22.5% vs 10.0%; <0.001), arterial hypertension (92.1 vs 75.6%; <0.001), family history of ischemic heart disease (IHD) (31.3 vs 23.4%; <0.001). Moreover, severe functional classes of effort angina (class III-IV 62.8 vs 50.0%; <0.001) and heart failure (NYHA class III-IV 28.1 vs 13.4%; <0.001) were more often detected in women. In men more frequent were smoking (45.4 vs 9.9%; <0.001), alcohol consumption (26.6 vs 9.0%; <0.001) and history of myocardial infarction (51.8 vs 40.2%; <0.001). Linear heart dimensions were larger in men. Men had more severe left ventricular (LV) asynergy (15.9+/-15.1 vs 13.7+/-14.7%; <0.001) and lower LV ejection fraction (54.5+/-8.7 vs 55.4+/-8.6 %; =0.03). As compared with men, portion of women subjected to primary PTCA was higher (14.3 vs 9.2%; <0.001), likewise coronary stenting was more often performed in women (93.6 vs 88.5%; <0.001). Optimal angiographic results were more frequently achieved in women (97.9 vs 96.4%; =0.04). Incidence of post-punctional hematoma was higher in female cohort (15.0 vs 4.6%; <0.001). There were no significant differences between men and women in post-operative mortality and rate of major adverse noncardiac events after primary and planned PTCA. Despite the detected clinical, functional, and echocardiographic gender differences both for men and women PCI was safe and highly efficient method of IHD treatment. | {
"pile_set_name": "PubMed Abstracts"
} |
Non-invasive in vivo spectrophotometric monitoring of brain cytochrome aa3 revisited.
Cytochrome aa3 (cyt aa3) is the main catalyst of cellular oxygen consumption. The properties of cyt aa3 will define the tissue oxygen requirements and provide an insight into energy supply and demand. Currently dual-wavelength (605-590 or 605-620 nm) reflectance spectrophotometry is used to monitor cyt aa3 redox state in vivo. We have experimentally demonstrated that the compensation for blood contamination in the surveyed tissue by these wavelength pairs is less than optimal. An alternative approach, similar to spectrophotometric analysis of multicomponent systems used in vitro, is presented in the triple wavelength equation as follows: delta cyt aa3 = 1.000 (delta A605) - 0.662 (delta A586.1) + 0.316 (delta A580) Based on a series of experiments performed in cuvette in vitro, isolated perfused rat head in situ, and living rat head in vivo, we have demonstrated that the cyt aa3 equation fully compensates for changes in cerebral blood volume and saturation. This non-invasive method of in vivo monitoring of cyt aa3 can provide the means to reliably and accurately determine tissue oxygen delivery under physiological conditions. | {
"pile_set_name": "PubMed Abstracts"
} |
Crystal structure of E. coli ZinT with one zinc-binding mode and complexed with citrate.
The ZnuABC ATP-binding cassette transporter found in gram-negative bacteria has been implicated in ensuring adequate zinc import into Zn(II)-poor environments. ZinT is an essential component of ZnuABC and contributes to metal transport by transferring metals to ZnuA, which delivers them to ZnuB in periplasmic zinc recruitment. Although several structures of E. coli ZinT have been reported, its zinc-binding sites and oligomeric state have not been clearly identified. Here, we report the crystal structure of E. coli ZinT at 1.76 Å resolution. This structure contains one zinc ion in its calycin-like domain, and this ion is coordinated by three highly conserved histidine residues (His167, His176 and His178). Moreover, three oxygen atoms (O1, O6 and O7) from the citrate molecule interact with zinc, giving the zinc ion stable octahedral coordination. Our EcZinT structure shows the fewest zinc ions bound of all reported EcZinT structures. Crystallographic packing and size exclusion chromatography suggest that EcZinT prefers to form monomers in solution. Our results provide insights into the molecular function of ZinT. | {
"pile_set_name": "PubMed Abstracts"
} |
Comparison of antibacterial-coated and non-coated suture material in intraoral surgery by isolation of adherent bacteria.
In general surgery the incidence of postoperative wound infections is reported to be lower using triclosan-coated sutures. In intraoral surgery, sutures are faced with different bacterial species and the question arises whether the antibacterial-coated suture material has the same positive effects. Triclosan-coated and uncoated suture materials were applied in 17 patients undergoing wisdom tooth extraction. Postoperatively, sutures were removed and adherent bacteria were isolated, colony-forming units (cfu) were counted, and species identified. Oral bacteria were found in high numbers (cfu>10(7)) on both Vicryl and the triclosan-coated Vicryl Plus. The total number of bacteria isolated from Vicryl Plus was 37% higher than for Vicryl, mainly due to increased numbers of anaerobes. The number of bacterial strains identified was higher for Vicryl ( n=203) than for Vicryl Plus (n=198), but the number of pathogens was higher on Vicryl Plus (n=100) than on Vicryl (n=97). Fewer Gram-positive strains were found on Vicryl Plus (n=95) than on Vicryl (n=107) and, conversely, more Gram-negative strains on Vicryl Plus (103vs.96). In terms of the total number of oral bacteria, and especially oral pathogens, that adhered to suture material, no reduction was demonstrated for Vicryl Plus. The use of triclosan-coated suture material offers no advantage in intraoral surgery. | {
"pile_set_name": "PubMed Abstracts"
} |
Immunologic responses in experimental cytomegalovirus labyrinthitis.
To better understand the pathogenesis of cytomegalovirus labyrinthitis, a guinea pig model was created. Following inoculation at several sites (cardiac, perilymph, and endolymphatic sac) in both seronegative and seropositive animals, the immunologic, histologic, and electrophysiologic responses were measured. Seronegative animals uniformly showed progressive hearing loss with marked inflammation and degeneration of neural elements. In animals inoculated into the endolymphatic sac, an associated endolymphatic hydrops developed in addition to deafness. Seropositivity protected the hearing, but endolymphatic sac inoculations resulted in mild hydrops due to local inflammation that was devoid of evidence of viral replication. The question of whether hearing loss was attributable to local inflammatory responses rather than the cytopathic effects of the virus was then examined. To test this hypothesis, animals were immunosuppressed with cyclophosphamide prior to intracochlear inoculation of cytomegalovirus. The immunosuppressed animals showed significantly better hearing than the controls, and this correlated directly with the degree of cellular infiltration of the scala tympani. These studies confirm the importance of host immune responses in the pathogenesis of hearing loss due to cytomegalovirus. | {
"pile_set_name": "PubMed Abstracts"
} |
Sixty years of blood transfusion: a memoir.
Paul Schmidt was born in 1925 into the Greatest Generation. Events during military service decided him on the study of medicine. Early research training in red cell preservation that continued during his medical studies opened a 20-year career at the National Institutes of Health (NIH). Beginning in 1954 at the Blood Bank of the NIH Clinical Center, he had exposure to the pioneers who had translated transfusion's wartime beginnings into civilian applications. Work inside the unique NIH clinical research atmosphere together with many of his students provided a fertile field for the growth of what has become transfusion medicine. Topics described range from early studies on platelets and on hepatitis to the background in Washington health politics leading to the National Blood Policy. National and global organizational activity and a second career in community blood service added to his 65 years of experience. The story as transfusion history is presented as a template for future progress. | {
"pile_set_name": "PubMed Abstracts"
} |
Right coronary artery motion analysis: a novel method to measure right ventricular systolic function by selective coronary angiography.
Right ventricular systolic dysfunction is prognostic in various cardiovascular diseases. Right ventricular systolic function is not commonly assessed in the catheterization laboratory. Therefore, we developed a novel, reproducible method to measure right ventricular systolic function during selective coronary angiography. We analyzed the angiographic systolic translational motion and maximum speed of the right coronary artery (RCA) in 97 consecutive patients and compared it to the tricuspid annular plane systolic excursion (TAPSE) as measured by echocardiography. All measurements were performed by two independent operators on two occasions. Inter-observer variability and intra-observer variability were excellent for RCA motion distance and for RCA maximum speed. There was a significant correlation of the RCA motion distance and RCA maximum speed with the TAPSE measured by echocardiography (Pearson's correlation for RCA distance: r = 0.59, p < 0.001, r2 = 0.35; for RCA speed: r = 0.40, p < 0.001, r2 = 0.16). The area under the receiver operating curve for the RCA motion distance was 0.88 (95% CI 0.80-0.96) for discrimination of normal and abnormal right ventricular systolic function. A cut-off value less than 22.3 mm systolic RCA motion had a specificity of 93.3% and a sensitivity of 75.6% for identifying an abnormal right ventricular systolic function. Analysis of the RCA motion is a reproducible and reliable method to measure right ventricular systolic function during selective coronary angiography. It is a simple and useful tool to assess right ventricular function in the catheterization laboratory and may serve for risk assessment for right ventricular failure. CLINICAL TRIAL REGISTRATION: Data for this study was collected retrospectively from Swiss Transcatheter Aortic Valve Implantation Registry (NCT01368250). https://clinicaltrials.gov/show/NCT01368250 . | {
"pile_set_name": "PubMed Abstracts"
} |
Beyond Koopmans' theorem: electron binding energies in disordered materials.
The topical review focuses on calculating ionization energies (IE), or electronic polarons in quasi-particle terminology, in large disordered systems, e.g. for a solute dissolved in a molecular solvent. The simplest estimate of the ionization energy is provided by one-electron energies in the Hartree-Fock theory, but the calculated quantities are not accurate. Density functional theory as many-body theory provides a principal opportunity for calculating one-electron energies including correlation and relaxation effects, i.e. the true energies of electronic polarons. We argue that such a principal possibility materializes within the concept of optimally tuned range-separated hybrid functionals (OT-RSH). We describe various schemes for optimal tuning. Importantly, the OT-RSH scheme is investigated for systems capped with dielectric continuum, providing a consistent picture on the QM/dielectric boundary. Finally, some limitations and open issues of the OT-RSH approach are addressed. | {
"pile_set_name": "PubMed Abstracts"
} |
Role of magnesium cations in the yeast orotate phosphoribosyltransferase catalyzed reaction. Mechanism of the inhibition by Cu++ and Ni++ ions.
The magnesium chelate of the N(3)H tautomer of orotate, L3Mg, is the true substrate in the biosynthesis of orotidine 5'-monophosphate (OMP) catalyzed by yeast orotate phosphoribosyltransferase (OPRTase, E.C. 2.4.210) with a Michaelis constant KmL3Mg equal to 12(2) muM. It is postulated that Mg++ cations activate the transport of orotate to the active site by neutralizing the orotate charges; the ligand N(3)H is then exchanged between the incoming cation and the cation bound to the enzyme, thus ensuring the stabilization of the appropriate isomeric structure of orotate. This scheme, together with kinetic and thermodynamic data on orotate complexation by Mg++ and Ca++, accounts for the role of Ca++ cations that neither activate nor inhibit OMP synthesis. Cu++ and Ni++ inhibiting properties arise from the formation of inert complexes of orotate. Ni++ complexes have a poor affinity for the protein, whereas Cu++ complexes have a Michaelis constant similar to that of the L3Mg active species. The inertness of these complexes is tentatively understood in terms of low phosphoribosyl transfer rates as postulated from the kinetic study of the protonation of the complexes in water. | {
"pile_set_name": "PubMed Abstracts"
} |
A novel and selective photoisomerization of allylic benzoates.
[reaction: see text]. Ultraviolet irradiation of a series of polyunsaturated allylic benzoates results in highly selective E/Z interconversion of the allylic double bond. | {
"pile_set_name": "PubMed Abstracts"
} |
Siderochelin, a new ferrous-ion chelating agent produced by Nocardia.
A new ferrous-ion chelating agent, siderochelin, was isolated from fermentation broths of Nocardia sp. SC 11,340. Siderochelin was produced by conventional submerged culture and purified by solvent extraction and recrystallization. The antibiotic was crystallized from acetonitrile as a mixture of diastereoisomers. The molecular formula of siderochelin was determined as C11H13N3O3 on the basis of elemental analysis and mass spectrometry, and the structure was elucidated by X-ray crystallography. The compound shows a broad spectrum of antimicrobial activity, being active against bacteria, fungi and protozoa. | {
"pile_set_name": "PubMed Abstracts"
} |
Effects of acute or prolonged exposure to leptin on hepatic glucose oxidation.
To observe the short-term and long-term effects of leptin on hepatic glucose oxidation and glucokinase gene expression. Rat hepatic cell line BRL was incubated with leptin of different doses (range from 10 ng/ml-200 ng/ml) for 1 h or 24 h. Glucose oxidation was determined by liquid scintillation counting. Glucokinase gene expression (corrected by beta-actin) was determined by reverse transcription semi-quantitative polymerase chain reaction. Treatment with leptin 10 ng/ml for 1 h had no significant effects on glucose oxidation in hepatic cells. However, at the doses ranging from 50 ng/ml to 200 ng/ml, leptin significantly inhibited glucose oxidation. These effects disappeared when the hepatic cells were exposed to leptin for 24 h. Glucokinase mRNA expression was reduced significantly after both 1 h and 24 h exposure to leptin (100 ng/ml) as compared to that of the control group. A low dose of leptin has no significant effect on glucose oxidation in hepatic cells. A relatively high dose of leptin has an acute inhibitory effect on the glucose oxidation in hepatic cells. This effect may likely involve the inhibition of glucokinase gene expression. The inhibitory effect on glucose oxidation is transient and disappears with prolonged exposure time. | {
"pile_set_name": "PubMed Abstracts"
} |
Adult respiratory distress syndrome associated with adult epiglottitis.
Adult respiratory distress syndrome (ARDS) is an increased permeability pulmonary edema syndrome known to be associated with a variety of direct and indirect pulmonary insults. ARDS occurred in a 37-year-old woman during an episode of epiglottitis. The patient was treated with endotracheal intubation and mechanical ventilation and recovered, to be discharged from the hospital 1 week after presentation. There are only two cases of ARDS reported in this setting, and in each case, pulmonary edema followed cardiac arrest and the patients had a fatal outcome. | {
"pile_set_name": "PubMed Abstracts"
} |
Selective photoaffinity labeling of acetylcholine receptor using a cholinergic analogue.
A bisazido derivative was synthesized from bis(3-aminopyridinium)-1,10-decane diiodide and it was shown that it was bound (KD congruent to 2.2 muM) specifically to purified acetylcholine receptor and fulfilled the requirements for a photoaffinity label. Like the parent compound the derivative could transform membrane-bound receptor from a low ligand affinity conformation(s) to a high ligand affinity form (s), a transition which is thought to resemble desensitization processes observed in vivo. Photolysis of 3H-labeled bisazido reagent was carried out in the presence of the receptor. After dodecyl sulfate-polyacrylamide gel electrophoresis of labeled purified receptor two of the four subunits (mol wt 40 000 and 60 000) contained 90% of the bound radioactivity while for membrane-bound receptor the subunits of mol wt 40 000 and 50 000 were labeled. The results favor the assumption that the specific ligand binding sites are located on mol wt 40 000 subunits and labeling of the other subunits reflects (a) their proximity to the ligand-binding site and (b) alterations in subunit topography between membrane-bound and solubilized states. | {
"pile_set_name": "PubMed Abstracts"
} |
Apolipoprotein B100 danger-associated signal 1 (ApoBDS-1) triggers platelet activation and boosts platelet-leukocyte proinflammatory responses.
Low-density lipoproteins (LDL), occurring in vivo in both their native and oxidative form, modulate platelet function and thereby contribute to atherothrombosis. We recently identified and demonstrated that 'ApoB100 danger-associated signal 1' (ApoBDS-1), a native peptide derived from Apolipoprotein B-100 (ApoB100) of LDL, induces inflammatory responses in innate immune cells. Platelets are critically involved in the development as well as in the lethal consequences of atherothrombotic diseases, but whether ApoBDS-1 has also an impact on platelet function is unknown. In this study we examined the effect of ApoBDS-1 on human platelet function and platelet-leukocyte interactions in vitro. Stimulation with ApoBDS-1 induced platelet activation, degranulation, adhesion and release of proinflammatory cytokines. ApoBDS-1-stimulated platelets triggered innate immune responses by augmenting leukocyte activation, adhesion and transmigration to/through activated HUVEC monolayers, under flow conditions. These platelet-activating effects were sequence-specific, and stimulation of platelets with ApoBDS-1 activated intracellular signalling pathways, including Ca2+, PI3K/Akt, PLC, and p38- and ERK-MAPK. Moreover, our data indicates that ApoBDS-1-induced platelet activation is partially dependent of positive feedback from ADP on P2Y1 and P2Y12, and TxA2. In conclusion, we demonstrate that ApoBDS-1 is an effective platelet agonist, boosting platelet-leukocyte's proinflammatory responses, and potentially contributing to the multifaceted inflammatory-promoting effects of LDL in the pathogenesis of atherothrombosis. | {
"pile_set_name": "PubMed Abstracts"
} |
Detection of respiratory enzyme activity in Giardia cysts and Cryptosporidium oocysts using redox dyes and immunofluorescence techniques.
The fluorescent redox dye 5-cyano-2,3-ditolyl tetrazolium chloride (CTC), combined with fluorescein-labeled antibodies, was tested for the simultaneous detection of the respiratory electron transport system (ETS) activity and enumeration of Giardia cysts and Cryptosporidium oocysts by spectral microfluorometry and epifluorescence microscopy. The reduction of CTC and p-iodonitrotetrazolium violet (INT), a non-fluorescent redox dye, was compared with propidium iodide (PI) and fluorescein diacetate (FDA) for the measurements of Giardia cyst viability over time. According to the PI and FDA staining techniques, nearly 60% of the cysts tested viable at the beginning of the observations; after 21 days their viability decreased to 5%. The redox dyes indicated that approximately 4-10% of the cysts were metabolically active 48 h after they were shed, followed by a decline in enzyme activity to near undetectable levels after 4 days. Spectral analysis on individual cysts indicated that the fluorescence emission of the reduced CTC and the fluorescein-labeled antibodies is distinctive for each compound and suitable for their simultaneous determination by microphotometry, flow cytometry and epifluorescence microscopy. The fluorescence signal remained without alteration when the cysts were transferred onto microscope slides coated with an optical embedding medium and stored at -20 degrees C. The fluorescence intensity of the reduced CTC, when properly standardized, can provide quantitative measurements of ETS activity of the cysts. This is the first report of a method to determine enzyme redox activity on intact cysts applicable to water, laboratory and animal samples. | {
"pile_set_name": "PubMed Abstracts"
} |
[Levels of lactate dehydrogenase isoenzymes in the serum of Hansen's disease patients].
The LDH isoenzymes levels in fresh serum of seven patients affected by different forms of hanseniasis from Argentina, were measured by acrylamide electrophoresis. In all cases the LDH-4 fraction was found elevated; on the contrary, LDH-2 was reduced. The LDH-5 fraction was detected in only three serums, all of them significantly increased when compared with controls. | {
"pile_set_name": "PubMed Abstracts"
} |
Dermal patch anesthesia: pain-free puncture of blood access in hemodialysis patients.
Clinical application of dermal patch anesthesia to relieve pain at venous cannulation of blood-access was studied in hemodialysis patients. Aqueous gel of 10% lidocaine base with 3% glycyrrhetinic acid monohemiphthalate disodium (GA MHPh 2Na) was applied for 60 minutes to the skin of the patients. Degree of pain was expressed as a pain score. Analgesic effect of the lidocaine gel was evaluated in 16 patients in a placebo-controlled, double-blind, cross-over design by comparing the gel with lidocaine with a placebo gel without lidocaine. The mean pin-prick pain score (1.0 +/- 0.5) in the lidocaine gel patch (n = 16) was significantly lower than that (2.3 +/- 0.3) in the placebo gel patch (P < 0.01). In 8.8% of the patients, blood pressure was elevated after venous cannulation, but this tendency was modified by dermal patch anesthesia with the lidocaine gel. Plasma concentration of lidocaine was under the detection limit of assay (< 0.05 micrograms/mL) after dermal patch anesthesia in six subsequent dialysis treatments. | {
"pile_set_name": "PubMed Abstracts"
} |
Direct recognition of LPS by human but not murine CD8+ T cells via TLR4 complex.
LPS comprises a major PAMP and is a key target of the immune system during bacterial infection. While LPS can be recognised by innate immune cells via the TLR4 complex, it is unknown whether T lymphocytes, especially CD8(+) T cells are also capable of doing so. We report here that naive human CD8(+) T cells, after activation by TCR stimulation, express surface TLR4 and CD14. These activated CD8(+) T cells can then secrete high concentrations of IFN-gamma, granzyme and perforin in response to LPS. These effects can be specifically inhibited using siRNA for TLR4. Furthermore, LPS can synergize with IL-12 to polarize the CD8(+) T cells into cytotoxic T-cell 1 (Tc1) that produce IFN-gamma but not IL-4, with or without TCR activation. Moreover, CD8(+)CD45RO(+) memory T cells constitutively expressed TLR4 and markedly enhanced IFN-gamma production when stimulated with LPS. In contrast, activated murine CD8(+) T cells lack TLR4 and CD14 expression and fail to respond to LPS for proliferation and cytokine production. Thus, human but not murine CD8(+) T cells are able to directly recognise bacterial LPS via LPS receptor complex and TLR4 provides a novel signal for the activation of effector and memory human CD8(+) T cells. | {
"pile_set_name": "PubMed Abstracts"
} |
The effects of 10 days of spaceflight on the shuttle Endeavor on predominantly fast-twitch muscles in the rat.
The primary purpose of this investigation was to determine the effects of microgravity on muscle fibers of the predominantly fast-twitch muscles in the rat. Cross sectional area and myosin heavy chain (MHC) composition were assessed in order to establish the acute effects of microgravity associated with spaceflight. The extensor digitorum longus (EDL) and gastrocnemius muscles were removed from 12 male Fisher 344 rats which had undergone 10 days of spaceflight aboard the space shuttle Endeavor and from 12 age- and weight-matched control animals. Both groups of animals received similar amounts of food and water and were synchronized for photoperiods, environmental temperature, and humidity. Significant (P < 0.05) reductions in muscle fiber size were observed in the gastrocnemius (fiber types I, IIA, IIDB, and IIB) and EDL (fiber type IIB) muscles after spaceflight. Significant MHC isoform transformations also resulted during this brief period of microgravity exposure with a significant decrease in MHC IId isoform in the EDL muscle. A significant decrease was also observed in the MHC IId isoform in the superficial (white) component of the gastrocnemius muscle after spaceflight, although no alterations in MHC profile were demonstrated in the deep (red) component of this muscle. These findings highlight the rapid plasticity of skeletal muscle during short-term spaceflight. If such pronounced adaptations to spaceflight also occur in humans, then astronauts are likely to suffer severe decrements in skeletal muscle performance with long-term space flight and upon return to earth after both short- and long-term missions. Thus, countermeasures aimed at slowing or even preventing muscle fiber atrophy are warranted. | {
"pile_set_name": "PubMed Abstracts"
} |
A comparison of glypican-3 with alpha-fetoprotein as a serum marker for hepatocellular carcinoma: a meta-analysis.
Glypican-3(GPC3) has been reported as one of the most promising serum markers for hepatocellular carcinoma (HCC), while several studies have conflicting results for the diagnostic accuracy between GPC3 and alpha-fetoprotein (AFP). Studies that explored the diagnostic value of GPC3 and AFP in HCC were searched in MEDLINE, EMBASE, PUBMED, the Cochrane Library and Chinese biomedical literature database (CBM). Sensitivity, specificity and other measures about the accuracy of serum GPC3 and AFP in the diagnosis of HCC were pooled using random effects models. Summary receiver operating characteristic curve (sROC) analysis was used to summarize the overall test performance. Ten studies were included in our meta-analysis. The pooled sensitivity for AFP and GPC3 is 51.9% (95% confidence interval (CI) 0.47-0.56) and 59.2% (95% CI 0.55-0.63), respectively, while the pooled specificity for AFP and GPC3 is 94% (95% CI 92.1-95.6%) and 84.8% (95% CI 82-87.3%), respectively. The pooled diagnostic odds ratio (DOR) for AFP and GPC3 were 23.4 (95% CI 10.3-53.2) and 17.99 (95% CI 5.4-60.4), respectively. Area under sROC for both AFP and GPC3 is 0.81 (95% CI 0.77-0.84). GPC3 is comparable to AFP as a serum marker for the diagnosis of HCC, combination of AFP and GPC3 can elevate the sensitivity of diagnosis. | {
"pile_set_name": "PubMed Abstracts"
} |
Interventional neuroradiology--anesthetic management.
Interventional Neuroradiology is a rather young department, that asks for an appropriate anesthesia management. This article highlights mainly the practical approach, with special directions for a thorough premedication, monitoring and patient positioning and extra attention to heparinisation and allergic reactions. Different anesthetic techniques are dealt with, namely conscious sedation and general anesthesia, as well as directives concerning potential complications. | {
"pile_set_name": "PubMed Abstracts"
} |
[The essentials of workplace analysis for examining occupational disability claims].
The insurance branch that covers the risk of occupational disability ranks among the most important private entities for offering security as far as the limitation or loss of one's ability to work is concerned. The financial risk of the insurer, the existential concerns and expectations of the claimant, as well as the legal framework and the need for a careful interdisciplinary evaluation, necessitate a professional review and assessment of the facts conducted with a sense of both responsibility and sensitivity. Carefully deliberated and sustainable decisions benefit both insurers and the insured. In order to achieve this, an opinion is required in many--and especially the more complex--cases from an external medical expert, which in turn can only be plausible and conclusive when based on a comprehensive review of the claimant's working environment and its particular (and often unique) requirements. This article is intended to increase the reader's understanding of the coherencies of workplace analysis and medical assessments, as required by insurance law and legislation. In addition, the article delivers valuable clues and guidance, both for medical experts and claims managers at insurance companies. Primarily, the claimant's occupation, as conceived in the terms and conditions of the insurance companies, is explained. The reader is then introduced to the various criteria to be considered when a claimant has several jobs at the same time, is self-employed, could be transferred to another job, is simply unable to commute to the workplace, or is prevented from working due to legal restrictions related to an illness. The article goes on to address the crucial aspect of how the degree of disability is to be measured under different circumstances, namely using the quantitative and the qualitative approach. As a reliable method for obtaining the essential data regarding the claimant's specific working conditions, which are required by both the medical expert and the insurance company's claims manager, the reader is provided with an insider's insights into on-site workplace analysis. The value of this pragmatic and proven method is subsequently demonstrated when the article addresses the often decisive part of the medical expert's assessment. In its conclusion the article points out the importance of workplace analysis to the entire process of evaluating occupational disability claims and the effort and monies to be saved by attaching value to thorough workplace analysis at an early stage. | {
"pile_set_name": "PubMed Abstracts"
} |
Efficacy of Dentaq® Oral and ENT Health Probiotic Complex on Clinical Parameters of Gingivitis in Patients Undergoing Fixed Orthodontic Treatment: A Pilot Study.
Probiotics act as a unique approach to maintaining oral health by supplementing the endogenous oral bacteria with additional naturally occurring beneficial microbes to provide defense against pathogens harmful to teeth and gingiva. The aim of this pilot study was to clinically evaluate the effects of probiotics on plaque accumulation and gingival inflammation in subjects with fixed orthodontics. The pilot study was comprised of 15 healthy patients, aged 11 to 18 years, undergoing fixed orthodontic treatment. Patients used an all-natural, dissolving lozenge containing six proprietary probiotic strains (Dentaq® Oral and ENT Health Probiotic Complex)for 28 days. Gingival Index (GI) according to Löe-Silness and Plaque Index (PI) according to Quigley-Hein for all teeth were measured at baseline (Day Zero) and at the end of the probiotic regimen (Day 28). The mean baseline GI and PI scores within each patient decreased by 28.4% and 35.8%, respectively, by Day 28. Patients reported decreased tooth and gingival pain, decreased oral bleeding, and increased motivation to maintain proper oral hygiene over the course of the study. This pilot study provided preliminary support for the use of Dentaq Oral and ENT Health Probiotic Complex as a safe and effective natural health product for the reduction of plaque accumulation and gingival inflammation. The results demonstrate its potential therapeutic value and open the door for larger scale placebo-controlled clinical studies to verify these findings. | {
"pile_set_name": "PubMed Abstracts"
} |
Population views on access to community nursing services in Finland.
The aim of this study was to evaluate potential access to personal community nursing services and the desirability of these services from the point of view of different population groups. Potential access to personal community nursing services was defined as having one or more particular nurses to contact when needing help and advice in health matters. The desirability of these services was defined as the respondents' estimation of how useful they considered it to be for them to have access to personal community nursing services. A computer-assisted telephone interview for the population living in the catchment areas of 10 health centres in Finland was conducted. A random sample of the total population aged 16-79 years was drawn from the population register. Logistic regression revealed that gender, type of community and employment status had best explanatory power in having potential access to personal nursing services and in considering these services desirable. However, many of those who considered personal nursing services very desirable, indicated that they did not have potential access to such services. Most of these persons were elderly and had a chronic disease or disability. Developing access to personal community nursing services particularly for these population. groups appears to be needed. | {
"pile_set_name": "PubMed Abstracts"
} |
[Immune system and diseases that vary with circumstance and physical condition].
Empirically we all know that our immune system varies depending on environmental factors and physical conditions. However, such recognition has remained at an empirical level for a long time without the accumulation of scientific data. The major reason is that the substance and its receptor that connect physical conditions with the immune system have previously been obscure. Adrenergic and cholinergic receptors on leukocytes may be important in understanding that relationship. Furthermore, we have to consider the mutually antagonistic functions of granulocytes and lymphocytes in the body. All stimuli from environmental factors change our physical conditions and subsequent changes in the autonomic nervous system influence our immune system through adrenergic receptors on granulocytes and cholinergic receptors on lymphocytes. Overactivation of granulocytes induces purulent diseases or tissue destruction, whereas overactivation of lymphocytes induces allergic diseases. | {
"pile_set_name": "PubMed Abstracts"
} |
Low pH hydrothermal synthesis and properties of lanthanide-organic frameworks with (4(10),6(5))(4(9),6(6)) topology constructed from Ln-Hbptc building blocks.
Two novel lanthanide-organic frameworks (LnOFs) with (4(10),6(5))(4(9),6(6)) topology, [Ln(Hbptc)(H(2)O)](n) (Ln = Eu(1), Gd(2); H(4)bptc = 3,3',4,4'-biphenyltetracarboxylic acid) were synthesized via the hydrothermal in situ reaction between lanthanide salts and 3,3',4,4'-biphenyltetracarboxylic dianhydride (bpta) under low pH conditions. In complexes 1 and 2, homohelix bundles with opposite chirality are assembled alternately and result in pillar-like 3D extended networks incorporated with coordinated water molecules, which show high thermal stability. The luminescence properties are illustrated by the Eu(III) complex (1) and its Gd-doped compound, which are intensive red emitters. The magnetic properties of complexes 1 and 2 are also investigated. | {
"pile_set_name": "PubMed Abstracts"
} |
[Studies of genetic polymorphisms of ADH2 and ALDH2 among the Han population in Luoyang China].
In order to investigate genetic polymorphisms of ADH2 and ALDH2 among the Han population in Luoyang City,portions of exon 3 of ADH2 and exon 12 of ALDH gene were amplified by using polymerase chain reaction. The amplified products were electrophoresed on 10% undenatured vertical polyacrylamide gels and stained with argentine. Frequencies of ADH2*1 and ADH2*2 alleles are 42.86% and 57.14%. Frequencies of three genotypes of ADH2 are 22.86%,40.00% and 37.14%,respectively. Frequencies of ALDH2*1 and ALDH2*2 alleles are 85.24% and 14.76%. Genotype frequencies of ALDH2 loci are 71.43%,27.62% and 0.95%,respectively. Genetic polymorphisms of ADH2 and ALDH2 among the Han population in Luoyang City are different from those among Taiwanese and Shanghainese. Frequency of ALDH2*1/*1 in Luoyang people is higher than those in Shanghai and Taiwan. Therefore,there is a higher resistance to alcohol drinking in the Han population in Luoyang. | {
"pile_set_name": "PubMed Abstracts"
} |
Macrophage roles in the clearance of apoptotic cells and control of inflammation in the prostate gland after castration.
Androgen deprivation results in massive apoptosis in the prostate gland. Macrophages are actively engaged in phagocytosing epithelial cell corpses. However, it is unknown whether microtubule-associated protein 1 light chain 3 alpha (LC3)-associated phagocytosis (LAP) is involved and contribute to prevent inflammation. Flow cytometry, RT-PCR and immunohistochemistry were used to characterize the macrophage subpopulation residing in the epithelial layer of the rat ventral prostate (VP) after castration. Stereology was employed to determine variations in the number of ED1 and ED2. Mice were treated with either chloroquine or L-asparagine to block autophagy. M1 (iNOS-positive) and M2 macrophages (MRC1+ and ARG1+) were not found in the epithelium at day 5 after castration. The percentage of CD68+ (ED1) and CD163+ (ED2) phenotypes increased after castration but only CD68+ cells were present in the epithelium. RT-PCR showed increased content of the autophagy markers Bcl1 and LC3 after castration. In addition, immunohistochemistry showed the presence of LC3+ and ATG5+ cells in the epithelium. Double immunohistochemistry showed these cells to be CD68+ /LC3+ , compatible with the LAP phenotype. LC3+ cells accumulate significantly after castration. Chloroquine and L-asparagine administration caused inflammation of the glands at day 5 after castration. CD68+ macrophages phagocytose apoptotic cell corpses and activate the LAP pathway, thereby contributing to the preservation of a non-inflammed microenvironment. Marked inflammation was detected when autophagy blockers were administered to castrated animals. | {
"pile_set_name": "PubMed Abstracts"
} |
Low testosterone level is an independent determinant of endothelial dysfunction in men.
We investigated whether a low plasma testosterone level is related to endothelial dysfunction in men with coronary risk factors. One hundred and eighty-seven consecutive male outpatients (mean age+/-SD: 47+/-15 years) who underwent measurement of flow-mediated vasodilation (FMD) of the brachial artery using ultrasonography were enrolled. The relationship between plasma hormones and FMD was analyzed. Total and free testosterone and dehydroepiandrosterone-sulfate (DHEA-S) were significantly correlated with %FMD (r=0.261, 0.354 and 0.295, respectively; p<0.001), while estradiol and cortisol were not. %FMD in the highest quartile of free testosterone was 1.7-fold higher than that in the lowest quartile. Multiple regression analysis revealed that total and free testosterone were related to %FMD independent of age, body mass index, hypertension, hyperlipidemia, diabetes mellitus and smoking (beta=0.198 and 0.247, respectively; p<0.01), and were independent of age, body mass index, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose, smoking and nitroglycerin-induced dilation (beta=0.196 and 0.227, respectively; p<0.01). DHEA-S was not significantly related to %FMD in multivariate analysis. In conclusion, a low plasma testosterone level was associated with endothelial dysfunction in men independent of other risk factors, suggesting a protective effect of endogenous testosterone on the endothelium. | {
"pile_set_name": "PubMed Abstracts"
} |
Validation of the Brazilian version of Guy's neurological disability scale.
The Guy's neurological disability scale (GNDS) has recently been introduced as a new measure of disability in multiple sclerosis. It is patient-oriented, multidimensional, and not biased towards any particular disability. The purpose of the present study was to validate the Brazilian version of the GNDS. The adaptation of the scale was based on the translation/back-translation methodology. Sixty-two patients with clinically definite multiple sclerosis (CDMS) according to Poser's criteria were recruited for this study. GNDS was administered individually to each subject. The EDSS and the ambulation index (AI) scores were assigned by a neurologist. The intraclass correlation coefficient and the Cronbach's alpha values of the Brazilian version of GNDS (0.94 and 0.83, respectively) were comparable to the original one (0.98 and 0.79, respectively). Furthermore, the factor analysis of the Brazilian version of GNDS suggested, as the original article, a four-factor solution which accounted for 68.8% of the total variance. The Brazilian version of GNDS was found to be clinically relevant as it correlated significantly with the EDSS and AI. In conclusion, the Brazilian version of GNDS can be considered an important tool to evaluate the disability in MS patients, with clinical usefulness and psychometrics soundness. | {
"pile_set_name": "PubMed Abstracts"
} |
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