tbuckley/cabot-search huggingface dataset:
Genetic Variants of the Protein Kinase C-β 1 Gene and Development of End-Stage Renal Disease in Patients With Type 2 Diabetes
Authors: Ronald C. W. Ma
Journal: JAMA (2010)

Protein kinase C-beta (PKC-beta) is a cell-signaling intermediate implicated in development of diabetic complications.To examine the risk association of PKC-beta 1 gene (PRKCB1) polymorphisms and end-stage renal disease (ESRD) in an 8-year prospective cohort of Chinese patients with type 2 diabetes.We genotyped 18 common tag single-nucleotide polymorphisms (SNPs) that span the PRKCB1 gene (r(2) = 0.80) in 1172 Chinese patients (recruited 1995-1998) without renal disease at baseline. A validation cohort included an additional 1049 patients with early-onset diabetes who were free of renal disease at baseline and were recruited after 1998.Associations of PRKCB1 polymorphisms under additive, dominant, and recessive genetic models with new onset of ESRD (defined as estimated glomerular filtration rate <15 mL/min/1.73 m(2) or dialysis or renal-related death) were assessed by Cox proportional hazard regression, adjusted for all conventional risk factors including use of medications.After a mean (SD) of 7.9 (1.9) years, 90 patients (7.7%) progressed to ESRD. Four common SNPs were associated with ESRD (P < .05). The closely linked T allele at rs3760106 and G allele rs2575390 (r(2) = 0.98) showed the strongest association with ESRD (hazard ratio [HR], 2.25; 95% confidence interval [CI], 1.31-3.87; P = .003, and HR, 2.26; 95% CI, 1.31-3.88; P = .003, respectively). Four common variants predicted ESRD in separate models. The HR for ESRD increased with increasing number of risk alleles (P < .001) in the joint effect analysis. The adjusted risk for ESRD was 6.04 (95% CI, 2.00-18.31) for patients with 4 risk alleles compared with patients with 0 or 1 risk allele. Incidence was 4.4 per 1000 person-years (95% CI, 0.5-8.2) among individuals with 0 or 1 risk allele compared with 20.0 per 1000 person-years (95% CI, 8.8-31.1) in those carrying 4 risk alleles (6.9% of the cohort). These results were validated in a separate prospective cohort of young-onset diabetic patients. Of 1049 patients in the validation cohort, 151 (14.3%) developed chronic kidney disease (CKD) during follow-up, and there were significant associations between both the T allele of rs3760106 and the G allele of rs2575390 and development of CKD (HR, 1.68; 95% CI, 1.10-2.57; P = .02, and HR, 1.62; 95% CI, 1.07-2.47; P = .02, respectively).Genetic variants in the PRKCB1 gene were independently associated with development of ESRD in Chinese patients with type 2 diabetes.
CORRESPONDENCE: Soft-Laser Therapy for Iatrogenic Mucositis in Cancer Patients Receiving High-Dose Fluorouracil: A Preliminary Report
Authors: N. POURREAU-SCHNEIDER, M. SOUDRY, J. C. FRANQUIN, H. ZATTARA, P. M. MARTIN, G. CLAIS, N. MOISE, M. SCHNEIDER, C. PIERRE, F. DEMARD
Journal: JNCI Journal of the National Cancer Institute (1992)
Chemotherapy permits resection of metastatic colorectal cancer: experience from Intergroup N9741
Authors: T. Delaunoit, S.R. Alberts, D.J. Sargent, E. Green, R.M. Goldberg, J. Krook, C. Fuchs, R.K. Ramanathan, S.K. Williamson, R.F. Morton, B.P. Findlay
Journal: Annals of Oncology (2005)
In vivo observation of subendocardial microvessels of the beating porcine heart using a needle-probe videomicroscope with a CCD camera.
Authors: T Yada, O Hiramatsu, A Kimura, M Goto, Y Ogasawara, K Tsujioka, S Yamamori, K Ohno, H Hosaka, F Kajiya
Journal: Circulation Research (1993)

We developed a portable needle-probe videomicroscope with a charge-coupled device (CCD) camera to visualize the subendocardial microcirculation. In 12 open-chest anesthetized pigs, the sheathed needle probe with a doughnut-shaped balloon and a microtube for flushing away the intervening blood was introduced into the left ventricle through an incision in the left atrial appendage via the mitral valve. Images of the subendocardial microcirculation of the beating heart magnified by 200 or 400 on a 15-in. monitor were obtained. The phasic diameter change in subendocardial arterioles during cardiac cycle was from 114 +/- 46 microns (mean +/- SD) in end diastole to 84 +/- 26 microns in end systole (p &lt; 0.001, n = 13, ratio of change = 24%) and that in venules from 134 +/- 60 microns to 109 +/- 45 microns (p &lt; 0.001, n = 15, ratio of change = 17%). In contrast, the diameter of subepicardial arterioles was almost unchanged (2% decrease, n = 5, p &lt; 0.01), and the venular diameter increased by 19% (n = 8, p &lt; 0.001) from end diastole to end systole. Partial kinking and/or pinching of vessels was observed in some segments of subendocardial arterioles and venules. The percentage of systolic decrease in the diameter from diastole in the larger (&gt; 100 microns) subendocardial arterioles and venules was greater than smaller (50-100 microns) vessels (both p &lt; 0.05). In conclusion, using a newly developed microscope system, we were able to observe the subendocardial vessels in diastole and systole.(ABSTRACT TRUNCATED AT 250 WORDS)
Penetration of intra-arterially administered vincristine in experimental brain tumor
Authors: Frances M Boyle, Susan L Eller, Stuart A Grossman
Journal: Neuro-Oncology (2004)

Vincristine is an integral part of the “PCV” regimen that is commonly administered to treat primary brain tumors. The efficacy of vincristine as a single agent in these tumors has been poorly studied. This study was designed to determine whether vincristine enters normal rat brain or an intracranially or subcutaneously implanted glioma and to assess the presence of the efflux pump P-glycoprotein (P-gp) on tumor and vascular endothelial cells. The 9L rat gliosarcoma was implanted intracranially and subcutaneously in three Fischer 344 rats. On day 7, [3H]vincristine (50 μCi, 4.8 μg) was injected into the carotid artery, and the animals were euthanized 10 or 20 min later. Quantitative autoradiography revealed that vincristine levels in the liver were 6- to 11-fold greater than in the i.c. tumor, and 15- to 37-fold greater than in normal brain, the reverse of the expected pattern with intra-arterial delivery. Vincristine levels in the s.c. tumor were 2-fold higher than levels in the i.c. tumor. P-gp was detected with JSB1 antibody in vascular endothelium of both normal brain and the i.c. tumor, but not in the tumor cells in either location, or in endothelial cells in the s.c. tumor. These results demonstrate that vincristine has negligible penetration of normal rat brain or i.c. 9L glioma despite intra-arterial delivery and the presence of blood-brain barrier dysfunction as demonstrated by Evan's blue. Furthermore, this study suggests that P-gp-mediated efflux from endothelium may explain these findings. The lack of penetration of vincristine into brain tumor and the paucity of single-agent activity studies suggest that vincristine should not be used in the treatment of primary brain tumors.
The Effect of Chronic Sodium Loading and Sodium Restriction on Plasma Prostaglandin A, E and F Concentrations in Normal Humans
Authors: Randall M. Zusman, David Spector, Burton V. Caldwell, Leon Speroff, George Schneider, Patrick J. Mulrow
Journal: Journal of Clinical Investigation (1973)

It has been suggested that prostaglandins may be involved in the control of sodium homeostasis. Prostaglandin A and prostaglandin E have been shown to increase renal blood flow and urinary sodium excretion and prostaglandin A has been shown to stimulate aldosterone release. The purpose of this study was to determine the effect of chronic sodium loading and sodium restriction on plasma prostaglandin A, E, and F concentrations. SEVEN NORMAL HUMAN VOLUNTEERS WERE PLACED ON THREE SODIUM INTAKE DIETS: (a) ad lib. sodium intake, (b) high sodium intake, and (c) low sodium intake. Plasma prostaglandin A, E, and F concentrations were measured by radioimmunoassay. Mean prostaglandin A levels on the ad lib. diet were 1.60 ng/ml. Prostaglandin A levels decreased 49% to 0.82 ng/ml on the high sodium intake and increased 34% to 2.14 ng/ml on the low sodium intake. Prostaglandin A levels increased 161% on the low sodium diet in comparison with levels on the high sodium diet. Plasma prostaglandin E and F concentrations did not change significantly during variation in sodium intake. These results show that dietary sodium content markedly effects plasma prostaglandin A levels and that prostaglandins may play a role in the physiologic mechanism of sodium homeostasis.
Systematic review of topical capsaicin for the treatment of chronic pain
Authors: Lorna Mason, R Andrew Moore, Sheena Derry, Jayne E Edwards, Henry J McQuay
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To determine the efficacy and safety of topically applied capsaicin for chronic pain from neuropathic or musculoskeletal disorders. <b>Data sources</b> Cochrane Library, Medline, Embase, PubMed, an in-house database, and contact with manufacturers of topical capsaicin. <b>Study selection</b> Randomised controlled trials comparing topically applied capsaicin with placebo or another treatment in adults with chronic pain. <b>Data extraction</b> Primary outcome was dichotomous information for the number of patients with about a 50% reduction in pain. Outcomes were extracted at four weeks for musculoskeletal conditions and eight weeks for neuropathic conditions. Secondary outcomes were adverse events and withdrawals due to adverse events. <b>Data synthesis</b> Six double blind placebo controlled trials (656 patients) were pooled for analysis of neuropathic conditions. The relative benefit from topical capsaicin 0.075% compared with placebo was 1.4 (95% confidence interval 1.2 to 1.7) and the number needed to treat was 5.7 (4.0 to 10.0). Three double blind placebo controlled trials (368 patients) were pooled for analysis of musculoskeletal conditions. The relative benefit from topical capsaicin 0.025% or plaster compared with placebo was 1.5 (1.1 to 2.0) and the number needed to treat was 8.1 (4.6 to 34). Around one third of patients experienced local adverse events with capsaicin, which would not have been the case with placebo. <b>Conclusions</b> Although topically applied capsaicin has moderate to poor efficacy in the treatment of chronic musculoskeletal or neuropathic pain, it may be useful as an adjunct or sole therapy for a small number of patients who are unresponsive to, or intolerant of, other treatments.
Membrane-bound serine protease matriptase-2 (Tmprss6) is an essential regulator of iron homeostasis
Authors: Alicia R. Folgueras, Fernando Martín de Lara, Alberto M. Pendás, Cecilia Garabaya, Francisco Rodríguez, Aurora Astudillo, Teresa Bernal, Rubén Cabanillas, Carlos López-Otín, Gloria Velasco
Journal: Blood (2008)
Abstract P2-01-19: Long-term follow-up of the node-negative breast cancer patients before treatment evaluated with sentinel node biopsy alone following neoadjuvant chemotherapy
Authors: Hiroko Nogi, Ken Uchida, Makiko Kamio, Kumiko Kato, Yasuo Toriumi, Hiroshi Takeyama
Journal: Cancer Research (2015)

Abstract BACKGROUND Sentinel node biopsy (SNB) for the node negative breast cancer is standard treatment as an accurate assessment of axillary lymph node status. The use of neoadjuvant chemotherapy (NAC) has increased during the past several years. At present, the use of SNB following NAC is controversial. Proponents of SNB after NAC prefer a single surgical procedure with potential for fewer axillary dissections. OBJECTIVE Our objective was to examine SNB evaluation alone following NAC in patients with clinically node-negative breast cancer before treatment and to evaluate the axillary lymph node recurrence for patients undergoing NAC versus patients undergoing surgery first. METHODS A total of 1176 patients with clinically node negative breast cancer underwent SNB from 2007 to 2013. Clinicopathologic and survival data were reviewed and comparisons made between patients receiving NAC and those undergoing surgery first. Lymphatic mapping was performed with both radioactive colloid and blue dye. Patients with negative SN for metastasis were followed without axillary lymph node dissection (ALND). Patients with metastases to a SN underwent ALND. RESULTS Of the patients, 180 (15.3%) underwent SNB following NAC and 996 (84.7%) underwent surgery first. SN identification rates were 98.3% in the NAC group and 98.9% in the surgery first group. 152 (84.4%) patients in the NAC group and 877 patients (88.1%) had negative SNs. At median follow-up of 49.2 months, 1 patient (0.007%) in the NAC group and 3 patients (0.003%) in surgery first group had axillary lymph node recurrences. There were not any significant differences between the NAC group and the surgery first group. CONCLUSION The SNB following NAC in patients with node-negative breast cancer has a low axillary recurrence rate and could be acceptable. Citation Format: Hiroko Nogi, Ken Uchida, Makiko Kamio, Kumiko Kato, Yasuo Toriumi, Hiroshi Takeyama. Long-term follow-up of the node-negative breast cancer patients before treatment evaluated with sentinel node biopsy alone following neoadjuvant chemotherapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-19.
Chronic Hepatitis C in Patients With Persistently Normal Alanine Transaminase Levels
Authors: Mitchell L. Shiffman, Moisés Diago, Albert Tran, Paul Pockros, Robert Reindollar, Daniele Prati, Maribel Rodríguez–Torres, Pilar Lardelli, Steven Blotner, Stefan Zeuzem
Journal: Clinical Gastroenterology and Hepatology (2006)

Many patients with chronic hepatitis C virus (HCV) have persistently normal serum alanine transaminase (ALT) levels. We compared characteristics of chronic hepatitis C patients with patients with normal and elevated ALT levels using data from 3 randomized phase III trials of peginterferon alfa-2a (40 kDa).The characteristics of 480 patients with normal ALT values (on >or=3 occasions without any increases in ALT level over a 6- to 18-month period) and 1993 patients with elevated ALT levels were compared. Sixty-eight of the 480 patients with normal ALT levels were randomized to no treatment and monitored for 72 weeks.More patients with normal ALT levels than patients with elevated ALT levels were women (59% vs 32%; P<.01). The serum HCV RNA titer was significantly lower in patients with normal ALT levels (P<.01 vs in patients with elevated ALT levels). Patients with normal ALT levels had significantly lower inflammation and fibrosis scores on liver biopsy examination than patients with elevated ALT levels, but almost two-thirds had portal fibrosis and 10% had bridging fibrosis. No correlation between baseline ALT activity, HCV RNA level, and liver histology was observed in patients with normal ALT levels. During the 72-week follow-up period, ALT activity elevated above the upper limit of normal in 53% of the untreated patients with normal levels of ALT. None became HCV RNA undetectable.Chronic hepatitis C patients with normal ALT levels should be evaluated in a similar manner as patients with elevated ALT levels because they are at risk for developing significant liver disease. The decision to treat with peginterferon alfa and ribavirin should be based on multiple factors, rather than on ALT levels alone.
Wave Propagation in the Pulmonary Circulation
Authors: FRED WIENER, EUGENE MORKIN, RICHARD SKALAK, ALFRED P. FISHMAN
Journal: Circulation Research (1966)

A mathematical model of the entire pulmonary circulation of the dog, based on branching elastic tubes, is shown to yield a useful description of the propagation of pulmonary vascular pressure and flow waves. The pressure and flow pulses throughout the model are computed from the pressures measured at the arterial and venous ends of the system. Computed flow pulses at each end of the system agree with experimental findings. Contour changes in the pressure and flow pulses are shown to be primarily due to dispersion and amplitude changes associated with reflected waves. Wave reflections are distributed throughout the model, and no specific site can be designated as the major source for reflections. Blood pressure and flow computed from the model remain pulsatile in the microcirculation; pressure pulses are attenuated but flow pulses pass essentially unchanged through the microcirculation. The computed results support the conclusion previously drawn from experimental evidence that pressure and flow pulses in the pulmonary veins originate primarily in the right ventricle and are propagated through the pulmonary capillary bed. A retrograde pulse, resulting from pressure fluctuations in the left atrium, is also present in both arteries and veins, but has only a secondary effect on the contours of pulmonary vascular pressures and flows.
Monocyte chemoattractant protein 1 (MCP-1) released from Helicobacter pylori stimulated gastric epithelial cells induces cyclooxygenase 2 expression and activation in T cells
Authors: S Futagami
Journal: Gut (2003)

and aims: To clarify the interaction between gastric epithelial and mucosal T cells, we examined the role of cytokines released from epithelial cells in response to Helicobacter pylori water extract protein (HPWEP) in regulating T cell cyclooxygenase 2 (COX-2) expression and activation.Media from MKN-28 cells incubated with HPWEP for 48 hours were added to Jurkat T cells and human peripheral T cells. C-C and CXC chemokine concentrations in MKN-28 cell media, and COX-2 expression, interferon gamma (IFN-gamma), and interleukin (IL)-4 secretions in T cells were determined by western blot analysis and ELISA methods. Distributions of COX-2 positive T cells and monocyte chemoattractant protein 1 (MCP-1) in tissue specimens with H pylori associated gastritis were determined as single or double labelling by immunohistochemistry.MCP-1, IL-7, IL-8, and RANTES were detected in media from MKN-28 cells incubated with HPWEP. Media as a whole, and MCP-1 alone, stimulated COX-2 expression and peripheral T cell proliferation. Anti-MCP-1 antibody inhibited media stimulated COX-2 mRNA expression in Jurkat T cells. Media stimulated IFN-gamma but not IL-4 secretion from peripheral T cells, while MCP-1 stimulated IL-4 but not IFN-gamma secretion. Both stimulated cytokine release, and peripheral T cell proliferation was partially inhibited by NS-398, a specific COX-2 inhibitor. In mucosa with gastritis, COX-2 was expressed in T cells and MCP-1 was localised mainly in epithelial and mononuclear cells. MCP-1 levels and the intensity of COX-2 expression in tissue samples were closely related.Cytokines such as MCP-1, released from gastric epithelial cells in response to HPWEP, seem to modulate T cell immune responses, at least in part via COX-2 expression.
TRANSFER OF ALLERGIC ENCEPHALOMYELITIS IN RATS BY MEANS OF LYMPH NODE CELLS
Authors: Philip Y. Paterson
Journal: The Journal of Experimental Medicine (1960)

Transfer of allergic encephalomyelitis has been accomplished by injection of lymph node cells, obtained from donor rats sensitized to spinal cord, into recipient rats pretreated neonatally with normal rat spleen cells. Transfer of the disease may be achieved most frequently when the recipients are pretreated with spleen cells of the prospective lymph node cell donors. These transfers are attributed to the use of recipients which have acquired immunological tolerance to donor lymph node cells, as a result of the spleen cell pretreatment, and in which, therefore, the donor cells can survive and function longer after transfer.
Antiidiotypic immunity in interstitial nephritis. II. Rats developing anti-tubular basement membrane disease fail to make an antiidiotypic regulatory response: the modulatory role of an RT7.1+, OX8- suppressor T cell mechanism.
Authors: E G Neilson, E McCafferty, S M Phillips, M D Clayman, C J Kelly
Journal: The Journal of Experimental Medicine (1984)

Antiidiotypic immunity can successfully inhibit the development of antitubular basement membrane (alpha TBM) disease that produces interstitial nephritis. Rats normally immunized to produce disease, however, do not develop this regulatory and protective antiidiotypic effect. The failure to see such a regulatory response is functionally related to the influence of a nonspecific, RT7.1+, OX8-suppressor T cell that appears shortly after immunization. While this suppressor cell system can partially reduce the intensity of disease, it also limits the host's ability to specifically regulate the alpha TBM immune response and, hypothetically, leaves the disease process in an operationally active mode.
Standardized Reporting Criteria for Studies Evaluating Suspected Acute Heart Failure Syndromes in the Emergency Department
Authors: Alan B. Storrow, Christopher J. Lindsell, Sean P. Collins, Deborah B. Diercks, Gerasimos S. Filippatos, Brian C. Hiestand, Judd E. Hollander, J. Douglas Kirk, Phillip D. Levy, Chadwick D. Miller, Allen J. Naftilan, Richard M. Nowak, Peter S. Pang, W. Frank Peacock, Mihai Gheorghiade, John G.F. Cleland
Journal: Journal of the American College of Cardiology (2012)
Follicular development and oocyte maturation in hypogonadotrophic women employing recombinant follicle-stimulating hormone: the role of oestradiol
Authors: B. Fauser
Journal: Human Reproduction Update (1997)

Both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are required for follicle development and oestrogen production. Moreover, under normal conditions a close association between dominant follicle size and serum and intrafollicular oestradiol levels is observed. With the recent availability of human recombinant FSH (recFSH), it was possible for the first time to study effects of FSH alone, in the complete absence of endogenous or exogenous LH, on ovarian function. Recent studies applying recFSH in hypogonadotrophic women have shown convincingly that normal growth of follicles up to the preovulatory stage occurs despite extremely low oestradiol levels, in keeping with previous observations using exogenous gonadotrophins in women incapable of synthesizing oestradiol due to steroid enzyme abnormalities. Insufficient data are presently available in humans to conclude whether or not oocyte quality is compromised under these circumstances. It should, however, be realized that sufficient oestradiol levels are required for fertilization in vivo. Therefore LH, or human chorionic gonadotrophin (HCG), should be added to stimulation protocols in hypogonadotrophic individuals. These observations may also be relevant for monitoring of ovarian response during recFSH therapy, especially when combined with gonadotrophin-releasing hormone agonists for ovarian hyperstimulation for in-vitro fertilization. Keywords: follicular development/hypogonadotrophic women/oestradiol/recombinant FSH
HLA DR antigens and gold toxicity.
Authors: J T Gran, G Husby, E Thorsby
Journal: Annals of the Rheumatic Diseases (1983)

One hundred and thirty-two patients with rheumatoid arthritis treated with gold have been studied for possible associations between HLA DR antigens and different adverse reactions occurring during such therapy. Patients possessing HLA DR3 had a significantly greater frequency of side effects than patients lacking this antigen. It was particularly noticed that DR3 positive patients on gold treatment had an 11 times higher risk of getting proteinuria than those without DR3. The lowest frequency of side effects was seen in DR7 positives. No significant differences between the DR antigen groups with respect to skin eruptions, liver reactions, or leucopenia were evident.