tbuckley/cabot-search huggingface dataset:
Expression of platelet-derived growth factor receptors in normal and diseased human kidney. An immunohistochemistry and in situ hybridization study.
Authors: L Gesualdo, S Di Paolo, S Milani, M Pinzani, C Grappone, E Ranieri, G Pannarale, F P Schena
Journal: Journal of Clinical Investigation (1994)

We studied the expression of PDGF-alpha and -beta receptors in 10 normal and 40 pathologic human kidneys (five minimal change disease, five membranous nephropathy, 25 IgA nephropathy, five lupus nephritis), by both immunohistochemistry and in situ hybridization techniques. In normal-appearing kidneys, both PDGF-alpha and -beta receptors were expressed at the glomerular and interstitial level, the latter receptor more intensely than the former. The distribution and degree of expression of both receptors in nonproliferative glomerulonephritides were comparable with those found in normal-appearing kidneys. PDGF-beta receptor gene and protein expression were upregulated in proliferative nephritides both at the glomerular and the interstitial level and strictly correlated with the grade of histologic lesions. Finally, PDGF beta receptor expression was observed at a low level in normal-appearing renal vessels, and strikingly increased in injured arteries. Diseased kidneys displayed only a slight increase of PDGF-alpha receptor expression, chiefly at the interstitial level. Noteworthy, a few cases of lupus nephritis showed a moderate increase of PDGF-alpha receptor also at the glomerular level. These data establish PDGF-beta receptor activation as a candidate for driving glomerular and interstitial proliferation and, probably, expansion of extracellular matrix in proliferative glomerulonephritis, while the role of PDGF-alpha receptor activation at the renal level remains to be elucidated.
Heat Shock Transcription Factor 1 Protects Cardiomyocytes From Ischemia/Reperfusion Injury
Authors: Yunzeng Zou, Weidong Zhu, Masaya Sakamoto, Yingjie Qin, Hiroshi Akazawa, Haruhiro Toko, Miho Mizukami, Norihiko Takeda, Tohru Minamino, Hiroyuki Takano, Toshio Nagai, Akira Nakai, Issei Komuro
Journal: Circulation (2003)

Because cardiomyocyte death causes heart failure, it is important to find the molecules that protect cardiomyocytes from death. The death trap is a useful method to identify cell-protective genes.In this study, we isolated the heat shock transcription factor 1 (HSF1) as a protective molecule by the death trap method. Cell death induced by hydrogen peroxide was prevented by overexpression of HSF1 in COS7 cells. Thermal preconditioning at 42 degrees C for 60 minutes activated HSF1, which played a critical role in survival of cardiomyocytes from oxidative stress. In the heart of transgenic mice overexpressing a constitutively active form of HSF1, ischemia followed by reperfusion-induced ST-segment elevation in ECG was recovered faster, infarct size was smaller, and cardiomyocyte death was less than wild-type mice. Protein kinase B/Akt was more strongly activated, whereas Jun N-terminal kinase and caspase 3 were less activated in transgenic hearts than wild-type ones.These results suggest that HSF1 protects cardiomyocytes from death at least in part through activation of Akt and inactivation of Jun N-terminal kinase and caspase 3.
Immunobiology and Therapeutic Manipulation of Heterotransplanted Nb Rat Prostate Adenocarcinoma Into Congenitally Athymic (Nude) Mice. I. Hormone Dependency and Histopathology&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Joseph R. Drago, M. Eric Gershwin, Robert E. Maurer, Richard M. Ikeda, David D. Eckels
Journal: JNCI Journal of the National Cancer Institute (1979)

Journal Article Immunobiology and Therapeutic Manipulation of Heterotransplanted Nb Rat Prostate Adenocarcinoma Into Congenitally Athymic (Nude) Mice. I. Hormone Dependency and Histopathology Get access Joseph R. Drago, M.D., Joseph R. Drago, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar M. Eric Gershwin, M.D., M. Eric Gershwin, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert E. Maurer, M.D., Robert E. Maurer, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard M. Ikeda, M.D., Richard M. Ikeda, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar David D. Eckels, M.D. David D. Eckels, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 62, Issue 4, April 1979, Pages 1057–1066, https://doi.org/10.1093/jnci/62.4.1057 Published: 01 April 1979 Article history Received: 07 July 1978 Accepted: 10 July 1978 Published: 01 April 1979
Altered major histocompatibility complex restriction in the NK1.1+Ly-6Chi autoreactive CD4+ T cell subset from class II-deficient mice.
Authors: I Kariv, R R Hardy, K Hayakawa
Journal: The Journal of Experimental Medicine (1994)

We previously demonstrated selective enrichment of major histocompatibility complex (MHC) class II-specific autoreactive T cells in a subset of mouse CD4+ thymocytes. Here we show that a significant fraction of these autoreactive cells in the normal adult thymus expresses NK1.1 and high levels of Ly-6C and also exhibits flexibility in MHC restriction. In normal mice, this NK1.1+Ly-6Chi subfraction accounts for 10-50% of the CD4+ autoreactive subset and is enriched for MHC class II-restricted autoreactive cells as determined by mixed leukocyte reaction frequency analysis, similar to NK1.1-Ly-6C-CD4+ autoreactive cells. In contrast, in the thymus of class II-deficient littermate mice, NK1.1+Ly-6Chi cells account for most of the mature heat stable antigen (HSA)-CD4+ fraction and exhibit MHC-restricted non-class II autoreactivity. Thus, NK1.1+Ly-6ChiCD4+ T cells show flexibility in MHC class restriction, but their autoreactivity remains MHC dependent.
A CONTRIBUTION TO THE PHYSIOLOGICAL DIFFERENTIATION OF PNEUMOCOCCUS AND STREPTOCOCCUS, AND TO METHODS OF STAINING CAPSULES
Authors: Philip Hanson Hiss
Journal: The Journal of Experimental Medicine (1905)

By morphological examination and with current cultural methods a clear differentiation cannot always be made between pneumococci and streptococci. The chief differential character usually depended upon is the capsule of the pneumococcus. Well-marked capsules, however, may occur on organisms which have with reason been classified as streptococci. On the other hand, capsules may not he demonstrable on pneumococci by the usual methods, especially when growing on artificial culture media. The usual cultural characters and reactions are at best not diagnostic, and are subject to variations which may render them useless as evidence of specific difference. The experiments recorded in this paper, however, afford some evidence that there are well-marked differences between the metabolic activities of pneumococci and streptococci, which may prove useful in the differentiation of these organisms. These differences in metabolism become apparent when the pneumococci and streptococci are cultivated in an alkaline serum medium, or in a serum medium to which the carbohydrate, inulin, has been added. Pneumococci slowly produce acid in the alkaline serum.
Abstract 19008: Is Cold Pressor Cardiac Magnetic Resonance Imaging Testing Useful for Detection of Coronary Endothelial Dysfunction?
Authors: Sherwin Dela Cruz, Janet Wei, Chrisandra Shufelt, Puja Mehta, Andre Rogatko, Xiao Zhang, Louise E Thomson, John Petersen, R. David Anderson, Carl J Pepine, Daniel S Berman, C. Noel Bairey Merz
Journal: Circulation (2014)

Background: Coronary endothelial dysfunction is typically assessed by invasive coronary reactivity testing (CRT) to measure coronary blood flow ([[Unable to Display Character: &amp;#8710;]]CBF) and diameter responses to acetylcholine (Ach). We evaluated if cold pressor testing (CPT) during noninvasive cardiac magnetic resonance imaging (CMRI) measurement of myocardial perfusion reserve index (MPRI) reflects invasive measurements with Ach and CPT in subjects suspected of having endothelial dysfunction. Methods: CRT was performed in 137 symptomatic women using incremental infusions of Ach in the left coronary artery for 3 minutes and with CPT using ice pack on their hand and forearm for 2 minutes. Quantitative coronary angiography was performed 5 mm distal to the Doppler wire positioned in the proximal left anterior descending artery. In 132 women, [[Unable to Display Character: &amp;#8710;]]CBF was calculated from average peak velocity and vessel cross sectional area. Invasive CPT could not be completed on 4 women. All women underwent CPT CMRI (1.5 T) to measure MPRI as a ratio of stress and rest upslopes of the whole myocardium. Five definitions of normal invasive CPT and Ach diameter response (dilation &gt; 0, 5, 10, 15 or 20%) were compared to two abnormal definitions (≤ 0 or - 5%) of endothelial function. Normal [[Unable to Display Character: &amp;#8710;]]CBF was defined as ≤ 50%. We used Wilcoxon Two-Sample statistical test to compare MPRI in each group. Results: CPT MPRI was significantly different in those with normal versus abnormal invasive Ach when Ach diameter response was defined as ≥ 20% or &lt; - 5 % (p=0.04), though not with other thresholds (Table). Conclusion: Noninvasive CPT CMRI may not be useful for detection of endothelial dysfunction in symptomatic women as no significant difference in MPRI was found in those with normal and abnormal invasive CRT. However, there may be a role for CPT MPRI in detecting endothelial dysfunction at higher thresholds of normal diameter response. Additional investigation will evaluate CPT CMRI and cardiovascular outcomes.
The Efficacy of the Novel Dual PI3-Kinase/mTOR Inhibitor NVP-BEZ235 Compared with Rapamycin in Renal Cell Carcinoma
Authors: Daniel C. Cho, Matthew B. Cohen, David J. Panka, Michael Collins, Musie Ghebremichael, Michael B. Atkins, Sabina Signoretti, James W. Mier
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Inhibitors of TORC1 have been shown to be active in patients with metastatic renal cell carcinoma (RCC). As the phosphatidylinositol 3-kinase (PI3K) pathway activates numerous other kinases, transcription factors, and proteins associated with cell growth and survival besides mammalian target of rapamycin (mTOR), disruption of this pathway upstream of mTOR may be more effective than inhibition of TORC1 alone. Experimental Design: To investigate this possibility, the dual PI3K/mTOR inhibitor NVP-BEZ235 was compared with rapamycin in RCC cell lines and xenografts generated from 786-O and A498 cells. Results: Treatment of RCC cell lines with NVP-BEZ235 in vitro resulted in the nuclear translocation of p27, greater reduction in tumor cell proliferation, and more complete suppression of Akt, Mnk-1, eIF4E, and 4EBP-1 phosphorylation and cyclin D1 and hypoxia-inducible factor 2α (HIF2α) expression than that achieved with rapamycin. The reduction of HIF2α levels correlated with reduced HIF activity as determined by luciferase assay. NVP-BEZ235 induced growth arrest in both the 786-O and A498 xenografts that was associated with inhibition of Akt and S6 phosphorylation as well as the induction of apoptosis and reduction in markers of tumor cell proliferation. In contrast, rapamycin induced only minimal growth retardation. Conclusion: Dual inhibition of PI3K/mTOR with NVP-BEZ235 induced growth arrest in RCC cell lines both in vitro and in vivo more effectively than inhibition of TORC1 alone. These results provide the rationale for the clinical assessment of agents such as NVP-BEZ235 in patients with advanced RCC. Clin Cancer Res; 16(14); 3628–38. ©2010 AACR.
Effect of Single-Agent Rituximab Given at the Standard Schedule or As Prolonged Treatment in Patients With Mantle Cell Lymphoma: A Study of the Swiss Group for Clinical Cancer Research (SAKK)
Authors: Michele Ghielmini, Shu-Fang Hsu Schmitz, Sergio Cogliatti, Francesco Bertoni, Ursula Waltzer, Martin F. Fey, Daniel C. Betticher, Hubert Schefer, Gabriella Pichert, Rolf Stahel, Nicolas Ketterer, Mario Bargetzi, Thomas Cerny
Journal: Journal of Clinical Oncology (2004)

To evaluate the effect of single-agent rituximab given at the standard or a prolonged schedule in patients with newly diagnosed, or refractory or relapsed mantle cell lymphoma (MCL).After induction treatment with the standard schedule (375 mg/m2 weekly x 4), patients who were responding or who had stable disease at week 12 from the start of treatment were randomly assigned to no further treatment (arm A) or prolonged rituximab administration (375 mg/m2) every 8 weeks for four times (arm B).The trial enrolled 104 patients. After induction, clinical response was 27% with 2% complete responses. Among patients with detectable t(11;14)-positive cells in blood and bone marrow at baseline, four of 20, and one of 14, respectively, became polymerase chain-reaction-negative after induction. Anemia was the only adverse predictor of response in the multivariate analysis. After a median follow-up of 29 months, response rate and duration of response were not significantly different between the two schedules in 61 randomly assigned patients. Median event-free survival (EFS) was 6 months in arm A versus 12 months in arm B; the difference was not significant (P = .1). Prolonged treatment seemed to improve EFS in the subgroup of pretreated patients (5 months in arm A v 11 months in arm B; P = .04). Thirteen percent of patients in arm A and 9% in arm B presented with grade 3 to 4 hematologic toxicity.Single-agent rituximab is active in MCL, but the addition of four single doses at 8-week intervals does not seem to significantly improve response rate, duration of response, or EFS after treatment with the standard schedule.
α-Dicarbonyls Increase in the Postprandial Period and Reflect the Degree of Hyperglycemia
Authors: Paul J. Beisswenger, Scott K. Howell, Rita M. O’Dell, Mary E. Wood, Allison D. Touchette, Benjamin S. Szwergold
Journal: Diabetes Care (2001)

OBJECTIVE—Chronic hyperglycemia is known to increase tissue glycation and diabetic complications, but controversy exists regarding the independent role of increased postprandial glucose excursions. To address this question, we have studied the effect of postprandial glycemic excursions (PPGEs) on levels of methylglyoxal (MG) and 3-deoxyglucosone (3-DG), two highly reactive precursors of advanced glycation end products (AGEs). RESEARCH DESIGN AND METHODS—We performed 4-month crossover studies on 21 subjects with type 1 diabetes and compared the effect of premeal insulin lispro or regular insulin on PPGEs and MG/3-DG excursions. PPGE was determined after standard test meal (STMs) and by frequent postprandial glucose monitoring. HbA1c and postprandial MG and d-lactate were measured by HPLC, whereas 3-DG was determined by gas chromatography/mass spectroscopy. RESULTS—Treatment with insulin lispro resulted in a highly significant reduction in PPGEs relative to the regular insulin–treated group (P = 0.0005). However, HbA1c levels were similar in the two groups, and no relationship was observed between HbA1c and PPGE (P = 0.93). Significant postprandial increases in MG, 3-DG, and d-lactate occurred after the STM. Excursions of MG and 3-DG were highly correlated with levels of PPGE (R = 0.55, P = 0.0002 and R = 0.61, P = 0.0004; respectively), whereas a significant inverse relationship was seen between PPGE and d-lactate excursions (R = 0.40, P = 0.01). Conversely, no correlation was observed between HbA1c and postprandial MG, 3-DG, or d-lactate levels. CONCLUSIONS—Increased production of MG and 3-DG occur with greater PPGE, whereas HbA1c does not reflect these differences. Reduced PPGE also leads to increased production of d-lactate, indicating a role for increased detoxification in reducing MG levels. The higher postprandial levels of MG and 3-DG observed with greater PPGE may provide a partial explanation for the adverse effects of glycemic lability and support the value of agents that reduce glucose excursions.
Modulation Of Human Basophil Degranulation By Geranylgeranyl Compounds
Authors: Yuko Nakase, Masao Yamaguchi, Naoya Sugimoto, Maho Suzukawa, Hiroyuki Tamiya, Yasuhiro Kojima, Hisanao Yoshihara, Michio Kuramochi, Hidenori Arai, Hiroyuki Nagase, Ken Ohta
Journal: Journal of Allergy and Clinical Immunology (2014)
Estrogen Causes Dynamic Alterations in Endothelial Estrogen Receptor Expression
Authors: Christopher E. Ihionkhan, Ken L. Chambliss, Linda L. Gibson, Lisa D. Hahner, Michael E. Mendelsohn, Philip W. Shaul
Journal: Circulation Research (2002)

Estrogen receptor (ER)alpha mediates many of the effects of estrogen on the vascular endothelium. The purpose of the present study was to determine whether estrogen modifies endothelial ERalpha expression. In experiments in cultured ovine endothelial cells, physiological concentrations of 17beta-estradiol (E2, 10(-10) to 10(-8) mol/L) caused an increase in ERalpha protein abundance that was evident after 6 hours of hormone exposure. Shorter (2-hour) E2 treatment caused ERalpha downregulation. In contrast to the upregulation in ERalpha after long-term E2, the expression of the other ER isoform, ERbeta, was downregulated. Both nonselective ER antagonism with ICI 182,780 and the inhibition of gene transcription with actinomycin D blocked the increase in ERalpha with E2. In studies using the human ERalpha gene promoter P-1 coupled to luciferase, an increase in ERalpha gene transcription was evident in endothelial cells within 4 hours of E2 exposure. The transcriptional activation was fully blocked by ICI 182,780, whereas the specific ERbeta antagonist RR-tetrahydrochrysene yielded partial blockade. Overexpression of ERalpha or ERbeta caused comparable 10- and 8-fold increases, respectively, in ERalpha promoter activation by E2. Thus, long-term exposure to E2 upregulates ERalpha expression in endothelial cells through the actions of either ERalpha or ERbeta on ERalpha gene transcription; in contrast, E2 causes ERbeta downregulation in the endothelium. We postulate that E2-induced changes in ERalpha and ERbeta expression modify the effects of the hormone on vascular endothelium.
Supplemental putrescine reverses ethanol-associated inhibition of liver regeneration
Authors: Anna Mae Diehl, Suzan Abdo, Nesbitt Brown
Journal: Hepatology (1990)

Biosynthesis of the polyamines, putrescine, spermidine and spermine, is required for DNA synthesis and liver regeneration after partial hepatectomy. Chronic ethanol consumption impairs polyamine synthesis during the prereplicative phase after partial hepatectomy. To determine whether this delay in polyamine synthesis contributes to ethanol's inhibition of liver regeneration, the ability of supplemental putrescine to improve regeneration in ethanol-fed rats was tested. Chronically ethanol-fed rats and isocalorically maintained controls underwent partial hepatectomy and were injected intraperitoneally with saline or putrescine (0.03 or 0.30 mmol/kg) at 0, 4, 8 and 12 hr after partial hepatectomy. Rats were killed at 24, 48 or 72 hr, 1 hr after exposure to [ 3 H]thymidine, so that DNA synthesis could be estimated. DNA synthesis was significantly inhibited in ethanol-fed rats treated with saline compared with saline-treated pair-fed controls. Supplemental putrescine did not affect DNA synthesis in pair-fed rats. In contrast, putrescine significantly improved [ 3 H]thymidine incorporation 24 to 72 hr after partial hepatectomy in ethanol-fed rats. Intraperitoneal injection of putrescine (1.2 mmol/kg) at the time of partial hepatectomy increased hepatic polyamine concentrations for the first 6 hr after partial hepatectomy despite significantly inhibiting the activity of ornithine decarboxylase, the rate-limiting enzyme for polyamine synthesis, in both groups. Hepatic polyamine levels after putrescine injection were greater in ethanol-fed rats than in similarly treated controls. These data suggest that putrescine treatment triggers events that normalize DNA synthesis in ethanol-fed rats. These results confirm the hypothesis that ethanol's antiregenerative mechanism intimately involves inhibition of putrescine synthesis. (HEPATOLOGY 1990;12:633-637).
Reduced efficacy of selection in regions of the Drosophila genome that lack crossing over.
Authors: Penelope R Haddrill, Daniel L Halligan, Dimitris Tomaras, Brian Charlesworth
Journal: Genome biology (2007)

The recombinational environment is predicted to influence patterns of protein sequence evolution through the effects of Hill-Robertson interference among linked sites subject to selection. In freely recombining regions of the genome, selection should more effectively incorporate new beneficial mutations, and eliminate deleterious ones, than in regions with low rates of genetic recombination. We examined the effects of recombinational environment on patterns of evolution using a genome-wide comparison of Drosophila melanogaster and D. yakuba. In regions of the genome with no crossing over, we find elevated divergence at nonsynonymous sites and in long introns, a virtual absence of codon usage bias, and an increase in gene length. However, we find little evidence for differences in patterns of evolution between regions with high, intermediate, and low crossover frequencies. In addition, genes on the fourth chromosome exhibit more extreme deviations from regions with crossing over than do other, no crossover genes outside the fourth chromosome. All of the patterns observed are consistent with a severe reduction in the efficacy of selection in the absence of crossing over, resulting in the accumulation of deleterious mutations in these regions. Our results also suggest that even a very low frequency of crossing over may be enough to maintain the efficacy of selection.
Integrating Human and Rodent Data to Identify the Genetic Factors Involved in Chronic Kidney Disease
Authors: Michael R. Garrett, Marcus G. Pezzolesi, Ron Korstanje
Journal: Journal of the American Society of Nephrology (2010)

The increasing numbers of patients with chronic kidney disease combined with no satisfying interventions for preventing or curing the disease emphasize the need to better understand the genes involved in the initiation and progression of complex renal diseases, their interactions with other host genes, and the environment. Linkage and association studies in human, rat, and mouse have been successful in identifying genetic loci for various disease-related phenotypes but have thus far not been very successful identifying underlying genes. The purpose of this review is to summarize the progress in human, rat, and mouse genetic studies to show the concordance between the loci among the different species. The collective utilization of human and nonhuman mammalian datasets and resources can lead to a more rapid narrowing of disease loci and the subsequent identification of candidate genes. In addition, genes identified through these methods can be further characterized and investigated for interactions using animal models, which is not possible in humans.
ON THE SEROLOGICAL SPECIFICITY OF PEPTIDES
Authors: K. Landsteiner, J. van der Scheer
Journal: The Journal of Experimental Medicine (1932)

With the idea that studies on the serological properties of peptides may ultimately aid in the understanding of the precipitin reactions of proteins, antigens have been prepared containing aminobenzoylated dipeptides, namely glycyl-glycine, glycyl-d, l-leucine, d, l-leucyl-glycine and d, l-leucyl-d, l-leucine. These four antigens were found to be different serologically, their specificity depending on the structure of the terminal amino acid carrying the free carboxyl group, and to a less degree also on the second amino acid. The results were obtained by means of precipitin and inhibition tests. Analogies to observations on enzyme specificity are discussed.