tbuckley/cabot-search huggingface dataset:
Nucleotide variation at the runt locus in Drosophila melanogaster and Drosophila simulans
Authors: J. A. Labate, C. H. Biermann, W. F. Eanes
Journal: Molecular Biology and Evolution (1999)

Intra- and interspecific nucleotide variation for the major developmental gene runt in Drosophila was studied in D. melanogaster and D. simulans. The 1.5-kb protein-coding region and the 0.4-kb intron of the runt gene were sequenced for 11 alleles in each species. The D. melanogaster alleles originated from east Africa. Estimated parameters of intraspecific variation in D. melanogaster (exons: theta = 0.018, pi = 0.018; intron: theta = 0.014, pi = 0.014) and D. simulans (exons: theta = 0.007, pi = 0.005; intron: theta = 0.008, pi = 0.005) were below average for other X-linked genes, while divergence between species (exons: D = 0.094; intron: D = 0.069) fell within the normal range for both silent and replacement changes. This estimate for runt, along with published values for three other genes in regions of normal recombination, show east African D. melanogaster to be roughly twice as polymorphic as D. simulans. The majority of nucleotide variation, silent and replacement, in both species was found to be selectively neutral using various statistical tests (HKA, McDonald-Kreitman, Tajima, and Fu and Li tests). Monte Carlo simulations of the coalescent process significantly rejected a Wright-Fisher model with respect to an amino acid polymorphism and the distribution of polymorphic sites among the D. simulans lines. This indicated an old lineage and may reflect ancestral population substructuring in D. simulans.
Recombinant Human Leptin in Women with Hypothalamic Amenorrhea
Authors: Corrine K. Welt, Jean L. Chan, John Bullen, Robyn Murphy, Patricia Smith, Alex M. DePaoli, Aspasia Karalis, Christos S. Mantzoros
Journal: New England Journal of Medicine (2004)

Disruptions in hypothalamic-gonadal and other endocrine axes due to energy deficits are associated with low levels of the adipocyte-secreted hormone leptin and may result in hypothalamic amenorrhea. We hypothesized that exogenous recombinant leptin replacement would improve reproductive and neuroendocrine function in women with hypothalamic amenorrhea.Eight women with hypothalamic amenorrhea due to strenuous exercise or low weight were studied for one month before receiving recombinant human leptin and then while receiving treatment for up to three months. Six control subjects with hypothalamic amenorrhea received no treatment and were studied for a mean (+/-SD) of 8.5+/-8.1 months.Luteinizing hormone (LH) pulsatility, body weight, ovarian variables, and hormone levels did not change significantly over time in the controls and during a one-month control period before recombinant leptin therapy in the treated subjects. In contrast, recombinant leptin treatment increased mean LH levels and LH pulse frequency after two weeks and increased maximal follicular diameter, the number of dominant follicles, ovarian volume, and estradiol levels over a period of three months. Three patients had an ovulatory menstrual cycle (P<0.05 for the comparison with an expected rate of spontaneous ovulation of 10 percent); two others had preovulatory follicular development and withdrawal bleeding during treatment (P<0.05). Recombinant leptin significantly increased levels of free triiodothyronine, free thyroxine, insulin-like growth factor 1, insulin-like growth factor-binding protein 3, bone alkaline phosphatase, and osteocalcin but not cortisol, corticotropin, or urinary N-telopeptide.Leptin administration for the relative leptin deficiency in women with hypothalamic amenorrhea appears to improve reproductive, thyroid, and growth hormone axes and markers of bone formation, suggesting that leptin, a peripheral signal reflecting the adequacy of energy stores, is required for normal reproductive and neuroendocrine function.
Double Antiangiogenic Protein, DAAP, Targeting VEGF-A and Angiopoietins in Tumor Angiogenesis, Metastasis, and Vascular Leakage
Authors: Young Jun Koh, Hak-Zoo Kim, Seong-Ik Hwang, Jeung Eun Lee, Nuri Oh, Keehoon Jung, Minah Kim, Kyung Eun Kim, Homin Kim, Nam-Kyu Lim, Choon-Ju Jeon, Gyun Min Lee, Byeong Hwa Jeon, Do-Hyun Nam, Hoon Ki Sung, Andras Nagy, Ook Joon Yoo, Gou Young Koh
Journal: Cancer Cell (2010)
Molecular Imaging of Angiogenesis in Early-Stage Atherosclerosis With α <sub>v</sub> β <sub>3</sub> -Integrin–Targeted Nanoparticles
Authors: Patrick M. Winter, Anne M. Morawski, Shelton D. Caruthers, Ralph W. Fuhrhop, Huiying Zhang, Todd A. Williams, John S. Allen, Elizabeth K. Lacy, J. David Robertson, Gregory M. Lanza, Samuel A. Wickline
Journal: Circulation (2003)

Angiogenesis is a critical feature of plaque development in atherosclerosis and might play a key role in both the initiation and later rupture of plaques that lead to myocardial infarction and stroke. The precursory molecular or cellular events that initiate plaque growth and that ultimately contribute to plaque instability, however, cannot be detected directly with any current diagnostic modality.Atherosclerosis was induced in New Zealand White rabbits fed 1% cholesterol for approximately 80 days. alpha(v)beta3-Integrin-targeted, paramagnetic nanoparticles were injected intravenously and provided specific detection of the neovasculature within 2 hours by routine magnetic resonance imaging (MRI) at a clinically relevant field strength (1.5 T). Increased angiogenesis was detected as a 47+/-5% enhancement in MRI signal averaged throughout the abdominal aortic wall among rabbits that received alpha(v)beta3-targeted, paramagnetic nanoparticles. Pretreatment of atherosclerotic rabbits with alpha(v)beta3-targeted, nonparamagnetic nanoparticles competitively blocked specific contrast enhancement of the alpha(v)beta3-targeted paramagnetic agent. MRI revealed a pattern of increased alpha(v)beta3-integrin distribution within the atherosclerotic wall that was spatially heterogeneous along both transverse and longitudinal planes of the abdominal aorta. Histology and immunohistochemistry confirmed marked proliferation of angiogenic vessels within the aortic adventitia, coincident with prominent, neointimal proliferation among cholesterol-fed, atherosclerotic rabbits in comparison with sparse incidence of neovasculature in the control animals.This molecular imaging approach might provide a method for defining the burden and evolution of atherosclerosis in susceptible individuals as well as responsiveness of individual patients to antiatherosclerotic therapies.
Hypothesis on the role of sub-clinical bacteria of the endometrium (bacteria endometrialis) in gynaecological and obstetric enigmas
Authors: D. Viniker
Journal: Human Reproduction Update (1999)

Unexplained infertility, recurrent abortion, dysfunctional uterine bleeding, pelvic pain, premenstrual syndrome, premature labour, placental insufficiency and pre-eclampsia are examples of common obstetric and gynaecological problems that frequently defy adequate explanation. Bacterial vaginosis, a non-inflammatory condition, is associated with premature labour, but antibiotics administered topically provide less effective prophylaxis than those administered orally. This would indicate that bacterial vaginosis might be a marker for significant genital tract bacteria, but some pathology is dependent on micro-organisms ascending out of reach of topical antibiotics. The author was led to consider the hypothesis that micro-organisms, possibly those associated with bacterial vaginosis, surreptitiously inhabit the uterine cavity (bacteria endometrialis) where they are culprits of some common gynaecological and obstetric enigmas. The objective of this review is to provide an initial theoretical examination of this hypothesis. Bacteria in the endometrium have been associated with infertility. Antiphospholipids have been linked to recurrent miscarriage and pre-eclampsia and with infections including Mycoplasma. Pre-eclampsia might be explained by an exaggerated host response to intrauterine micro-organisms or bacterial toxins. The hypothesis that one common factor, bacteria endometrialis, could provide a plausible explanation for a variety of obstetric and gynaecological mysteries is particularly intriguing. There is sufficient evidence to justify further investigation.
Cognitive Behavioral Therapy Versus Sertraline in Patients With Depression and Poorly Controlled Diabetes: The Diabetes and Depression (DAD) Study
Authors: Frank Petrak, Stephan Herpertz, Christian Albus, Norbert Hermanns, Christoph Hiemke, Wolfgang Hiller, Kai Kronfeld, Johannes Kruse, Bernd Kulzer, Christian Ruckes, Daniela Zahn, Matthias J. Müller
Journal: Diabetes Care (2015)

OBJECTIVE This study compared the long-term efficacy of a diabetes-specific cognitive behavioral group therapy (CBT) with sertraline in patients with diabetes and depression who initially responded to short-term depression treatment. RESEARCH DESIGN AND METHODS A randomized controlled single-blind trial was conducted in 70 secondary care centers across Germany comparing 12 weeks of CBT with sertraline in 251 patients with type 1 or 2 diabetes (mean HbA1c 9.3%, 78 mmol/mol) and major depression (Structured Clinical Interview for DSM-IV [SCID]). After 12 weeks, treatment responders (≥50% reduction Hamilton Depression Rating Scale [HAMD-17]) were included in the 1-year study phase where CBT patients were encouraged to use bibliotherapy and sertraline patients received continuous treatment. We analyzed differences for HbA1c (primary outcome) and reduction (HAMD-17) or remission (SCID) of depression from baseline to the 1-year follow-up using ANCOVA or logistic regression analysis. RESULTS After 12 weeks, 45.8% of patients responded to antidepressant treatment and were included in the 1-year study phase. Adjusted HbA1c mean score changes from baseline to the end of the long-term phase (−0.27, 95% CI −0.62 to 0.08) revealed no significant difference between interventions. Depression improved in both groups, with a significant advantage for sertraline (HAMD-17 change: −2.59, 95% CI 1.15–4.04, P &amp;lt; 0.05). CONCLUSIONS Depression improved under CBT and sertraline in patients with diabetes and depression, with a significant advantage for sertraline, but glycemic control remained unchanged. CBT and sertraline as single treatment are insufficient to treat secondary care diabetes patients with depression and poor glycemic control.
Preimplantation genetic diagnosis and chromosome analysis of blastomeres using comparative genomic hybridization
Authors: Leeanda Wilton
Journal: Human Reproduction Update (2004)

Numerical chromosome errors are known to be common in early human embryos and probably make a significant contribution to early pregnancy loss and implantation failure in IVF patients. Over recent years fluorescent in situ hybridization (FISH) has been used to document embryonic aneuploidies. Many IVF laboratories perform preimplantation genetic diagnosis (PGD) with FISH to select embryos that are free from some aneuploidies in an attempt to improve implantation, pregnancy and live birth rates in particular categories of IVF patients. The usefulness of FISH is limited because only a few chromosomes can be detected simultaneously in a single biopsied cell. Complete karyotyping at the single cell level can now be achieved by comparative genomic hybridization (CGH). CGH enables not only enumeration of all chromosomes but gives a more complete picture of the entire length of each chromosome and has demonstrated that chromosomal breakages and partial aneuploidies exist in embryos. CGH has provided invaluable information about the extent of mosaicism and aneuploidy of all chromosomes in early human conceptuses. CGH has been applied to clinical PGD and has resulted in the birth of healthy babies from embryos whose full karyotype was determined in the preimplantation phase.
Plasma chemokine levels correlate with the outcome of antiviral therapy in patients with hepatitis C
Authors: David Butera, Svetlana Marukian, Amy E. Iwamaye, Edgardo Hembrador, Thomas J. Chambers, Adrian M. Di Bisceglie, Edgar D. Charles, Andrew H. Talal, Ira M. Jacobson, Charles M. Rice, Lynn B. Dustin
Journal: Blood (2005)
Modulation of G-protein expression and adenylyl cyclase signaling by high glucose in vascular smooth muscle*1
Authors: S HASHIM
Journal: Cardiovascular Research (2004)

Objective: We have recently shown a decreased expression of Giα proteins and associated functions in aorta from short term (5 days) streptozotocin-induced diabetic rats. Since hyperglycemia is one of the underlying causes of diabetes-induced cardiovascular complications, it was of interest to examine if hyperglycemia may play a direct role in down regulating the expression of Giα in vascular smooth muscle cells of diabetic subjects. For this, the effect of high glucose treatment on Giα protein expression and adenylyl cyclase signaling in intact aorta and vascular smooth muscle cells (A10 cells) was investigated. Methods: The cells were grown in normal glucose (5.5 mM) medium and were subsequently exposed to high glucose (26 mM) or normal medium for various time periods (24–96 h). Aorta from control rats were exposed to normal and high glucose medium for 72 h. The levels of G-proteins were determined by immunoblotting using specific antibodies. Adenylyl cyclase activity stimulated or inhibited by agonists was determined to examine the functions of G-proteins. Results: The levels of Giα-2 and Giα-3 proteins in membranes from A10 cells and aorta exposed to high glucose for 3 or 4 days were significantly decreased as compared to control cells and control aorta, respectively, whereas the levels of Gsα protein were not altered. In addition, receptor-dependent and -independent functions of Giα proteins were attenuated in hyperglycemic cells, as demonstrated by inhibition of forskolin (FSK)-stimulated adenylyl cyclase activity by low concentration of GTPγS or by angiotensin II (Ang II), oxotremorine or C-ANP4–23 (a ring deleted analog of atrial natriuretic peptide). On the other hand, the stimulatory effects of GTPγS, glucagon, isoproterenol, FSK and sodium fluoride on adenylyl cyclase were significantly augmented in hyperglycemic cells as compared to control cells, whereas basal adenylyl cyclase activity was significantly lower in hyperglycemic cells as compared to control cells. Conclusion: These results indicate that high glucose decreased the levels and functions of Gi proteins in A10 VSMC and aorta. It may thus be suggested that decreased levels and activity of Gi proteins and adenylyl cyclase signaling induced by hyperglycemia may be one of the important mechanisms contributing to the cardiovascular complications associated with diabetes.
<i>MDM2</i> SNP309 Polymorphism as Risk Factor for Susceptibility and Poor Prognosis in Renal Cell Carcinoma
Authors: Hiroshi Hirata, Yuji Hinoda, Nobuyuki Kikuno, Ken Kawamoto, Yutaka Suehiro, Yuichiro Tanaka, Rajvir Dahiya
Journal: Clinical Cancer Research (2007)

Abstract Purpose: MDM2 is a major negative regulator of p53, and a single nucleotide polymorphism in the MDM2 promoter region SNP309 (rs2279744) has been shown to increase the affinity of the transcriptional activator Sp1, resulting in elevated MDM2 transcription and expression in some cancers. There is currently no information about the role of MDM2 polymorphism in renal cell carcinoma (RCC). We investigated polymorphisms in p53-related genes, including MDM2, and their interactions in renal cancer. Experimental Design: We genotyped three single nucleotide polymorphisms of three genes (p53 Arg72Pro, p21 Ser31Arg, and MDM2 SNP309) in 200 patients with renal cancer and 200 age- and gender-matched healthy subjects. Genotyping was confirmed by direct DNA sequencing. Samples that showed significant polymorphic variants were analyzed for MDM2 expression by immunohistochemistry. Association of polymorphic variants on survival of RCC patients was analyzed by Kaplan-Meier curves. Results: A significant increase in the GG genotype of the MDM2 SNP309 was observed in RCC patients compared with healthy controls (odds ratio, 1.80; 95% confidence interval, 1.14-2.84). To investigate the effect of the MDM2 SNP309 polymorphism on MDM2 expression, immunohistochemistry was done in genotyped RCC tissues. Positive staining for MDM2 was detected in 2 of 15 (13%) TT genotype, 4 of 15 (26%) TG genotype, and 5 of 10 (50%) GG genotype carriers. The frequency of MDM2 expression in GG genotype carriers was significantly higher than that in TT genotype carriers. Polymorphisms of p53 Arg72Pro and p21 Ser31Arg did not show significant association with RCC. In univariate and multivariate analysis, MDM2 SNP309 GG genotype was independently associated with poor prognosis. Kaplan-Meier curve analysis showed that survival of patients with GG carriers was significantly worse than that of carriers with TG + TT genotypes. Conclusions: This is the first report to show a significant association between functional polymorphisms in MDM2 and increased risk of developing renal cancer. In addition, the MDM2 polymorphism was shown to be an independent adverse prognostic factor for RCC. Patients with MDM2 309GG genotype showed worse prognosis and low survival.
AMITRIPTYLINE-PERPHENAZINE IN THE TREATMENT OF SCHIZOPHRENIA
Authors: R. E. KENNEDY, J. J. MILLER
Journal: American Journal of Psychiatry (1963)

One-hundred and thirty-seven hospitalized schizophrenic patients received amitriptyline-perphenazine for periods seldom exceeding 90 days with a remission rate of about 86%. A possible rationale for the treatment is offered.
Chronic hepatitis C and treatment outcome: correlations with apoptosis, soluble HLA class I and soluble fas ligand
Authors: F. Torre, N. Campo, P. Contini, R. Giusto, I. Comino, P. Ceppa, R. Fiocca, G. Icardi, F. Indiveri, F. Puppo, A. Picciotto
Journal: Journal of Hepatology (2001)
Post-load insulin resistance is an independent predictor of hepatic fibrosis in virus C chronic hepatitis and in non-alcoholic fatty liver disease
Authors: G Svegliati-Baroni, E Bugianesi, T Bouserhal, F Marini, F Ridolfi, F Tarsetti, F Ancarani, E Petrelli, E Peruzzi, M L. Cascio, M Rizzetto, G Marchesini, A Benedetti
Journal: Gut (2007)

Insulin resistance is a significant risk factor for hepatic fibrosis in patients with both non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC), either directly or by favouring hepatic steatosis. Several methods are available to assess insulin resistance, but their impact on this issue has never been evaluated.To determine the relative contribution of steatosis, metabolic abnormalities and insulin resistance, measured by different basal and post-load parameters, to hepatic fibrosis in CHC and in NAFLD patients.In 90 patients with CHC and 90 pair-matched patients with NAFLD, the degree of basal insulin resistance (by the homeostasis model assessment, (HOMA)) and post-load insulin sensitivity (by the oral glucose insulin sensitivity (OGIS) index) was assessed, together with the features of the metabolic syndrome according to Adult Treatment Panel III definition. Data were correlated with hepatic histopathology.The prevalence of basal insulin resistance (HOMA values >75th percentile of normal) was 23.3% in CHC patients and 57.8% in NAFLD, but it increased to 28.8 and 67.8% when measured by post-load insulin resistance (OGIS <25th percentile). In a multivariate model, after adjustment for age, gender and body mass index, OGIS was a predictor of severe fibrosis in CHC and in NAFLD patients, independently of steatosis. An OGIS value below the cut-off of the 25th percentile increased the likelihood ratio of severe fibrosis by a factor of 1.5-2 and proved to be a more sensitive and generally more specific test than HOMA-R for the identification of subjects with severe fibrosis both in NAFLD and in CHC.Post-load insulin resistance (OGIS <9.8 mg/kg/min) is associated with severe hepatic fibrosis in both NAFLD and CHC patients, and may help identify subjects at risk of progressive disease.
Letter: Medical centre for unsettled young people.
Authors: A Davies
Journal: BMJ (1974)

chlamydial infection, thus making laboratory diagnosis difficult, but will not eradicate the disease.Neomycin is not active against chlamydia, 'but is reasonably effective against bacterial infections and should be the initial antibiotic of choice until swabs can be taken and examined for chlamydia.The persistence of conjunctivitis after neomycin should lead the clinician to investigate the possibility of chlamydial infection in both the infant and its parents.-Weare, etc.,
The Hydrodynamically Relevant Endothelial Cell Glycocalyx Observed In Vivo Is Absent In Vitro
Authors: Daniel R. Potter, Edward R. Damiano
Journal: Circulation Research (2008)

In recent years, the endothelial cell surface glycocalyx has emerged as a structure of fundamental importance to a broad range of phenomena that determine cardiovascular health and disease. This new understanding of the functional significance of the glycocalyx has been made possible through recently developed experimental techniques using intravital microscopy that are capable of directly probing the glycocalyx in vivo. Using fluorescent microparticle image velocimetry in venules and endothelialized cylindrical collagen microchannels, we show that the hydrodynamically relevant endothelial cell glycocalyx surface layer observed in microvessels in vivo (0.52+/-0.28 microm thickness), which is a fundamental determinant of the hydrodynamic and mechanical environment at the endothelial cell surface, is absent from human umbilical vein (0.03+/-0.04 microm thickness) and bovine aortic (0.02+/-0.04 microm thickness) endothelial cells grown and maintained under standard cell culture conditions in vitro. An endothelial surface-bound glycosaminoglycan layer, not necessarily indicative of but having similar hydrodynamic properties to the endothelial glycocalyx observed in vivo, was detected (0.21+/-0.27 microm thickness) only after hyaluronan and chondroitin sulfate were added to the cell culture media at hyperphysiological concentrations (0.2 mg/mL perfused for 75 minutes). The implications of this glycocalyx deficiency under standard cell culture conditions in these pervasive in vitro models broadly impact a myriad of studies involving endothelial cell monolayers in which inferences are made that may depend on endothelial cell surface chemistry. In light of these findings, conclusions drawn from such studies in the areas of microvascular permeability, inflammation, mechanotransduction, and atherosclerosis must be carefully reconsidered.