tbuckley/cabot-search huggingface dataset:
Effects of hematocrit on renal hemodynamics and sodium excretion in hydropenic and volume-expanded dogs
Authors: Robert W. Schrier, Laurence E. Earley
Journal: Journal of Clinical Investigation (1970)

The effects of hematocrit on renal hemodynamics and sodium excretion were studied in anesthetized dogs during both hydropenia and volume expansion. The hematocrit was decreased by isovolemic exchange with the animal's own previously harvested plasma and increased by isovolemic exchange with fresh, washed red blood cells. Renal perfusion pressure was maintained constant throughout the experiments by the adjustment of a suprarenal aortic clamp. During hydropenia, a decrease in hematocrit was associated with an increase in sodium and potassium excretion and solutefree water reabsorption. These changes were accompained by an increase in renal plasma flow and renal blood flow and a decrease in renal vascular resistance. Glomerular filtration rate was unchanged and filtration fraction was significantly decreased as hematocrit was lowered. Increasing hematocrit during hydropenia had the opposite effects on electrolyte excretion, solute-free water reabsorption, and renal hemodynamics. In another group of animals, hematocrit was lowered during volume expansion with either saline or plasma, then returned to the control level by isovolemic exchange with washed red blood cells. This increase in hematocrit during volume expansion had a similar effect on electrolyte excretion, solute-free water reabsorption, and renal hemodynamics as during hydropenia. These results therefore suggest that acute changes in hematocrit may significantly affect sodium excretion and renal hemodynamics during both hydropenia and volume expansion. The changes in solute-free water reabsorption and potassium excretion suggest that the alterations in hematocrit may affect primarily the reabsorption of sodium in the proximal tubule. The concommitant effects of hematocrit on renal vascular resistance and filtration fraction may mediate this change in sodium reabsorption by altering hydrostatic and oncotic pressures in the peritubular circulation.
Prevalence of and Factors Associated with Suboptimal Care before Initiation of Dialysis in the United States
Authors: GREGORIO T. OBRADOR, ROBIN RUTHAZER, PRADEEP ARORA, ANNAMARIA T. KAUSZ, BRIAN J. G. PEREIRA
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Despite improvements in dialysis care, the mortality of patients with end-stage renal disease (ESRD) in the United States remains high. Factors that thus far have received scant attention, but could significantly affect morbidity and mortality in dialysis patients, are the timing and quality of care before the initiation of dialysis (pre-ESRD). Data from the new version of the Health Care Financing Administration (HCFA) 2728 Form were used to examine the prevalence of and factors associated with hypoalbuminemia, severe anemia, and erythropoietin (EPO) use among 155,076 incident chronic dialysis patients in the United States between April 1, 1995 and June 30, 1997. At initiation of dialysis, the median serum albumin and hematocrit were 3.3 g/dl and 28%, respectively. Sixty percent of patients had a serum albumin below the lower limit of normal and 51% had a hematocrit &lt;28%. Overall, only 23% had received EPO pre-ESRD. Among patients with hematocrit &lt;28%, only 20% were receiving EPO, compared to 27% among patients with hematocrit ≥28%. In a multivariate analysis that adjusted for diabetes, functional status, and demographic, socioeconomic, and geographic factors, the odds ratios for hypoalbuminemia, hematocrit &lt;28%, and lack of EPO use were higher for African-Americans, patients with non-private insurance or no insurance, and patients who were started on hemodialysis. There were also significant differences in odds ratios for these outcomes between different geographic regions in the United States. The high prevalence of pre-ESRD hypoalbuminemia, hematocrit &lt;28%, and lack of EPO use suggests that the quality of pre-ESRD care in the United States is suboptimal. Improvement in pre-ESRD care could potentially improve outcomes among ESRD patients.
Soluble thrombomodulin concentration is raised in scleroderma associated pulmonary hypertension
Authors: Richard J Stratton, Lucie Pompon, John G Coghlan, Jeremy D Pearson, Carol M Black
Journal: Annals of the Rheumatic Diseases (2000)

<h3>OBJECTIVE</h3> To investigate the expression of thrombomodulin in scleroderma associated pulmonary hypertension. <h3>METHODS</h3> Soluble thrombomodulin (sTM), was measured in plasma samples from 34 scleroderma patients shown to have pulmonary hypertension at echocardiogram, and comparison drawn against samples from 38 scleroderma control patients, and 20 healthy controls. Serial measurements of sTM were performed in the 34 patients with scleroderma associated pulmonary hypertension to investigate possible changes in sTM concentration with progression of the condition. <h3>RESULTS</h3> Mean sTM was raised in scleroderma associated pulmonary hypertension when compared with scleroderma controls (mean sTM 65.4 ng/ml<i>v</i> 43.3 ng/ml, p&lt;0.05), and when compared with healthy controls (mean sTM 38.1 ng/ml, p&lt;0.05). There was no significant difference between mean sTM in scleroderma controls and healthy controls. Mean sTM concentration did not change with progression of pulmonary hypertension. <h3>CONCLUSION</h3> Plasma sTM is raised in scleroderma associated pulmonary hypertension. The pathogenesis of scleroderma associated pulmonary hypertension may be distinct from the pathogenesis of other forms of pulmonary vascular disease.
Addition of ascorbic acid to the extracellular environment activates lipoplexes of a ferrocenyl lipid and promotes cell transfection
Authors: Burcu S. Aytar, John P.E. Muller, Sharon Golan, Shinichi Hata, Hiro Takahashi, Yukishige Kondo, Yeshayahu Talmon, Nicholas L. Abbott, David M. Lynn
Journal: Journal of Controlled Release (2011)
Eliminating Inpatient Sliding-Scale Insulin: A Reeducation Project With Medical House Staff
Authors: David Baldwin, Griselda Villanueva, Robert McNutt
Journal: Diabetes Care (2005)

We thank Peterson, Charney, and Rennert (1) for their interest in our study (2). We share and applaud their interest in improving the level of house staff education for inpatient diabetes management. When we began our program 3 years ago, all inpatients received sliding-scale regular insulin and perpetual hyperglycemia was the rule. We felt that most of our 1st year residents did not know how to manage inpatient hyperglycemia, thus the …
Controversies in the Treatment of Local and Locally Advanced Gastric and Esophageal Cancers
Authors: Deirdre J. Cohen, Lawrence Leichman
Journal: Journal of Clinical Oncology (2015)

Despite overall progress in the therapy of local and locally advanced esophageal, gastroesophageal junction, and gastric adenocarcinomas, death as a result of these tumors remains a common outcome. Most randomized phase III trials on which level-one evidence has been built have included the heterogeneous histologies and locations associated with these tumors. However, the different etiologies, molecular biology, and recurrence patterns associated with gastroesophageal malignancies suggest the need to split rather than lump. Biologic and response differences exist between squamous and adenocarcinomas, as well as diffuse and intestinal histologies. This may be a cause behind conflicting outcomes in similar trials. The accepted standard of chemoradiotherapy for locally advanced esophageal and gastroesophageal junction cancers is based on a few positive trials, with the best chemotherapy and total dose of radiation remaining controversial. In the West, the staging evaluations of locally advanced gastric cancer are not uniform. Yet, these evaluations will inform the results of preoperative and perioperative treatments. Although postoperative chemoradiotherapy for gastric cancer has been an accepted treatment option for the last decade, more recent studies have called into question the need for radiotherapy. In perioperative strategies, it has yet to be determined whether histologic or molecular changes in the operative specimen should inform postoperative treatment. An appropriate place for targeted therapy needs to be found in preoperative and postoperative treatment regimens. Finally, because so much is lost when trials are forced to close for lack of accrual, it is imperative to build multidisciplinary consensus before they are launched.
TETRABENACINE TREATMENT IN PERSISTING DYSKINESIA CAUSED BY PSYCHOPHARMACA
Authors: ERIK BRANDRUP
Journal: American Journal of Psychiatry (1961)

In 3 patients suffering from schizophrenia and one patient with arteriosclerotic dementia persisting dyskinetic movements caused by psychopharmaca disappeared almost or completely after treatment with tetrabenacine (Nitoman®). The schizophrenics received a daily dose of 75 mg., whereas it was necessary to give the patient with dementia 150-300 mg. per day in order to obtain a satisfactory effect. This patient responded by developing a certain degree of drowsiness, while no side effects were observed in the other cases.
Repression of phosphoinositide-dependent protein kinase 1 expression by ciglitazone via Egr-1 represents a new approach for inhibition of lung cancer cell growth
Authors: SWei Hann, Qing Tang, Fang Zheng, Shunyu Zhao, Jianping Chen, ZhiYu Wang
Journal: Molecular Cancer (2014)

Peroxisome proliferator-activated receptors gamma (PPARγ) ligands have been shown to inhibit the growth of non-small cell lung cancer (NSCLC) cells. However, the mechanisms underlying this effect remain incompletely elucidated. Cell proliferation and apoptosis were measured by cell viability, MTT and caspase3/7 activity assays. Phosphorylation/protein expression and gene silence/overexpression of AMPKα, phosphoinositide-dependent protein kinase 1 (PDK1), Egr-1 and PPARγ were performed by Western blot and siRNA/transfection assays. Dual-Luciferase Reporter Kit was used to measure the PPAR response elements (PPRE) reporter and PDK1 promoter activities, and ChIP assay was used to detect the Egr-1 protein binding to the DNA site in the PDK1 gene promoter. We found that ciglitazone, one synthetic PPARγ ligand, inhibited growth and induced apoptosis of NSCLC cells through decreased expression of PDK1, which was not blocked by GW9662 (a specific PPARγ antagonist). Overexpression of PDK1 overcame the effect of ciglitazone on cell growth and caspase 3/7 activity. Ciglitazone increased the phosphorylation of AMPKα and c-Jun N-terminal kinase (JNK), and the inhibitor of AMPK (compound C), but not JNK (SP600125), reversed the effect of ciglitazone on PDK1 protein expression. Ciglitazone reduced PDK1 gene promoter activity, which was not observed in cells exposed to compound C, but not silenced of PPARγ siRNA. Combination of ciglitazone and metformin further reduced PDK1 expression and promoter activity. Furthermore, we showed that ciglitazone induced the protein expression of Egr-1, which was not observed in cells silencing of AMPKα. Moreover, silencing of Egr-1 abrogated the effect of ciglitazone on PDK1 promoter activity and cell growth. On the contrary, overexpression of Egr-1 enhanced the effect of ciglitazone on PDK1 gene promoter activity. ChIP assays demonstrated that ciglitazone induced Egr-1 protein bind to the specific DNA site in the PDK1 gene promoter. Collectively, our results demonstrate that ciglitazone inhibits PDK1 expression through AMPKα-mediated induction of Egr-1 and Egr-1 binding to the specific DNA site in the PDK1 gene promoter, which is independent of PPARγ. Activation of AMPKα by metformin enhances the effect of ciglitazone. In turn, this leads to inhibition of NSCLC cell proliferation.
Compliance to Self-Monitoring of Blood Glucose: A Marked-Item Technique Compared with Self-Report
Authors: Rena R Wing, Leonard H Epstein, Mary Patricia Nowalk, Nancyxs Scott, Randi Koeske
Journal: Diabetes Care (1985)

This study compared subjects' self-reported rates of compliance to self-monitoring of blood glucose (SMBG) with an objective measure based on a “marked-item” technique. We followed 25 obese patients with type II diabetes who were participating in a behavorial weight control program and monitoring their blood glucose with Chemstrips bG (Bio-Dynamics, Inc., Indianapolis, Indiana). Subjects' self-report significantly overestimated actual compliance as assessed by the marked-item technique. Moreover, the self-report measure failed to identify 35–45% of the noncompliant patients. Compliance decreased steadily over the course of the 37-wk program. Accuracy of SMBG was less problematic than compliance; 85% of patients were able to read Chemstrips bG within 20% of actual blood sugar, and the average blood sugar reading obtained from 2 mo of SMBG correlated highly (r = 0.78, P &amp;lt; 0.01) with HbA1. Our data suggest that objective measures such as the marked-item technique described in this article should be used to assess compliance to SMBG and behavioral strategies to improve compliance should be developed.
The Impact of Heat Waves and Cold Spells on Mortality Rates in the Dutch Population
Authors: Maud M. T. E. Huynen, Pim Martens, Dieneke Schram, Matty P. Weijenberg, Anton E. Kunst
Journal: Environmental Health Perspectives (2001)

We conducted the study described in this paper to investigate the impact of ambient temperature on mortality in the Netherlands during 1979-1997, the impact of heat waves and cold spells on mortality in particular, and the possibility of any heat wave- or cold spell-induced forward displacement of mortality. We found a V-like relationship between mortality and temperature, with an optimum temperature value (e.g., average temperature with lowest mortality rate) of 16.5 degrees C for total mortality, cardiovascular mortality, respiratory mortality, and mortality among those [Greater and equal to] 65 year of age. For mortality due to malignant neoplasms and mortality in the youngest age group, the optimum temperatures were 15.5 degrees C and 14.5 degrees C, respectively. For temperatures above the optimum, mortality increased by 0.47, 1.86, 12.82, and 2.72% for malignant neoplasms, cardiovascular disease, respiratory diseases, and total mortality, respectively, for each degree Celsius increase above the optimum in the preceding month. For temperatures below the optimum, mortality increased 0.22, 1.69, 5.15, and 1.37%, respectively, for each degree Celsius decrease below the optimum in the preceding month. Mortality increased significantly during all of the heat waves studied, and the elderly were most effected by extreme heat. The heat waves led to increases in mortality due to all of the selected causes, especially respiratory mortality. Average total excess mortality during the heat waves studied was 12.1%, or 39.8 deaths/day. The average excess mortality during the cold spells was 12.8% or 46.6 deaths/day, which was mostly attributable to the increase in cardiovascular mortality and mortality among the elderly. The results concerning the forward displacement of deaths due to heat waves were not conclusive. We found no cold-induced forward displacement of deaths.
Maximum Likelihood Implementation of an Isolation-with-Migration Model with Three Species for Testing Speciation with Gene Flow
Authors: T. Zhu, Z. Yang
Journal: Molecular Biology and Evolution (2012)

We implement an isolation with migration model for three species, with migration occurring between two closely related species while an out-group species is used to provide further information concerning gene trees and model parameters. The model is implemented in the likelihood framework for analyzing multilocus genomic sequence alignments, with one sequence sampled from each of the three species. The prior distribution of gene tree topology and branch lengths at every locus is calculated using a Markov chain characterization of the genealogical process of coalescent and migration, which integrates over the histories of migration events analytically. The likelihood function is calculated by integrating over branch lengths in the gene trees (coalescent times) numerically. We analyze the model to study the gene tree-species tree mismatch probability and the time to the most recent common ancestor at a locus. The model is used to construct a likelihood ratio test (LRT) of speciation with gene flow. We conduct computer simulations to evaluate the LRT and found that the test is in general conservative, with the false positive rate well below the significance level. For the test to have substantial power, hundreds of loci are needed. Application of the test to a human–chimpanzee–gorilla genomic data set suggests gene flow around the time of speciation of the human and the chimpanzee.
Impact of urbanization on detection rates of eating disorders
Authors: H W Hoek, A I Bartelds, J J Bosveld, Y van der Graaf, V E Limpens, M Maiwald, C J Spaaij
Journal: American Journal of Psychiatry (1995)

The purpose of this study was to examine the incidence of anorexia nervosa and bulimia nervosa among patients in primary care and to evaluate the impact of urbanization, age and sex differences, and changes over time.During 1985-1989, 58 general practitioners, trained in diagnosing eating disorders, registered all of their patients who had diagnoses of anorexia nervosa and/or bulimia nervosa according to strict criteria. The study population (N = 151,781) was 1% of the population of the Netherlands; the distribution of sexes, ages, geographical locations, and degrees of urbanization in the study group was representative of the Dutch population. Main outcome measures were rates of newly detected cases and age-adjusted rate ratios.The crude annual incidence rate of detected cases in primary care per 100,000 person-years was 8.1 for anorexia nervosa and 11.5 for bulimia nervosa. The incidence of bulimia nervosa was lowest in rural areas, intermediate in urbanized areas, and highest in large cities (6.6, 19.9, and 37.9, respectively, per 100,000 females per year); no rural-urban differences for anorexia nervosa were found. Pronounced sex and age differences in incidence rates were observed. Over the 5-year period, there was no time trend in the incidence of anorexia nervosa, but the incidence of bulimia nervosa tended to increase.The incidence rates of eating disorders--as defined by detection rates in primary care--are higher than previously reported. Urbanization seems to be a risk factor for bulimia nervosa but not for anorexia nervosa.
Reduced Isotype Switching in Splenic B Cells from Mice Deficient in Mismatch Repair Enzymes
Authors: Carol E. Schrader, Winfried Edelmann, Raju Kucherlapati, Janet Stavnezer
Journal: The Journal of Experimental Medicine (1999)

Mice deficient in various mismatch repair (MMR) enzymes were examined to determine whether this repair pathway is involved in antibody class switch recombination. Splenic B cells from mice deficient in Msh2, Mlh1, Pms2, or Mlh1 and Pms2 were stimulated in culture with lipopolysaccharide (LPS) to induce immunoglobulin (Ig)G2b and IgG3, LPS and interleukin (IL)-4 to induce IgG1, or LPS, anti–δ-dextran, IL-4, IL-5, and transforming growth factor (TGF)-β1 to induce IgA. After 4 d in culture, cells were surface stained for IgM and non-IgM isotypes and analyzed by FACS®. B cells from MMR-deficient mice show a 35–75% reduction in isotype switching, depending on the isotype and on the particular MMR enzyme missing. IgG2b is the most affected, reduced by 75% in Mlh1-deficient animals. The switching defect is not due to a lack of maturation of the B cells, as purified IgM+IgD+ B cells show the same reduction. MMR deficiency had no effect on cell proliferation, viability, or apoptosis, as detected by [3H]thymidine incorporation and by propidium iodide staining. The reduction in isotype switching was demonstrated to be at the level of DNA recombination by digestion-circularization polymerase chain reaction (DC-PCR). A model of the potential role for MMR enzymes in class switch recombination is presented.
Podocyte Expression of Hypoxia-Inducible Factor (HIF)–1 and HIF–2 during Glomerular Development
Authors: Paul B. Freeburg, Barry Robert, Patricia L. St. John, Dale R. Abrahamson
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. The heterodimeric transcription factors, hypoxia-inducible factor (HIF)–1 and HIF-2, are essential for the maintenance of cellular oxygen homeostasis. In response to hypoxia, stabilized HIF-1α and HIF-2α proteins bind HIF-1β and initiate expression of genes that alleviate hypoxic stress, including those promoting neovascularization. Both HIF-1 and HIF-2 stimulate transcription of vascular endothelial growth factor (VEGF), a crucial regulator of vascular development. Because VEGF is highly expressed by metanephric podocytes and collecting ducts, developing mouse kidney was examined for the presence and distribution of HIF-1α, HIF-2α, and HIF-1β. The expression of HIF-1α and HIF-2α mRNAs in newborn mouse kidney was confirmed by RT-PCR and Northern blot analysis. By in situ hybridization, HIF-1α and HIF-2α mRNAs were highly expressed in the nephrogenic zone of newborn kidney cortex and in the medulla. Particularly intense hybridization was found in podocytes of developing glomeruli and in medullary collecting ducts. Both HIF-1 and HIF-2 heterodimers were identified in newborn kidney lysates by immunoprecipitation with HIF-1α, HIF-2α, and HIF-1β antibodies and Western blots. Immunofluorescence analysis of the hypoxia marker, pimonidazole, showed that collecting ducts and many developing tubules undergo severe hypoxia in developing kidney. Immunohistochemistry of newborn kidney demonstrated widespread expression of HIF-1β protein in nuclei of glomeruli and all tubular segments, whereas HIF-2α protein expression was more restricted and localized chiefly to podocytes of developing glomeruli and developing tubules. HIF-1α and HIF-2α protein and VEGF mRNA were all strongly induced in embryonic kidneys maintained in hypoxic organ cultures. Collectively, these data suggest that HIF stabilization, by hypoxia and/or by other means, may be critical for VEGF production and kidney vascular development. E-mail: [email protected]
IMMUNE RESPONSE TO CHEMICALLY MODIFIED FLAGELLIN
Authors: C. R. Parish
Journal: The Journal of Experimental Medicine (1971)

Flagellin (mol. wt. 40,000) from S. adelaide organisms was acetoacetylated to varying extents with diketene (acetoacetic anhydride). Chemical studies demonstrated that the amino groups of flagellin were more readily acetoacetylated than the hydroxyl groups. Several antigenic tests revealed that as flagellin was acetoacetylated to increasing extents there was a steady decline in the affinity of the molecule for anti-flagellin antibodies. Loss in antigenic activity following acetoacetylation was not related to the number of acetoacetyl groups attached but was determined by the type of residue substituted. Reactive lysine residues were much less important anti-genically than easily substituted hydroxyl groups. Acetoacetylation very readily destroyed the antibody-forming capacity of flagellin in rats. This fall in immunogenicity was related to the antigenic activity of the preparations. In fact, only a 40% reduction in the antigenic activity of flagellin produced a 90-95% reduction in primary antibody formation. The more heavily acetoacetylated flagellins produced no detectable antibody and, in fact, rendered adult rats tolerant (in terms of antibody formation) to a subsequent challenge of flagellin. Tolerance was induced by acetoacetylated flagellins which had drastically reduced affinities for anti-flagellin antibodies. These results were interpreted as indicating that the affinity of antigen for receptors on cells appears to be of crucial importance in determining whether antibody formation or immunological tolerance (antibody suppression) occurs.