tbuckley/cabot-search huggingface dataset:
Blood-tissue exchange via transport and transformation by capillary endothelial cells.
Authors: J B Bassingthwaighte, C Y Wang, I S Chan
Journal: Circulation Research (1989)

The escape of solutes from the blood during passage along capillaries in heart and skeletal muscle occurs via diffusion through clefts between endothelial cells and, for some solutes, via adsorption to or transport across the luminal plasmalemma of the endothelial cell. To quantitate the rates of permeation via these two routes of transport across capillary wall, we have developed a linear model for transendothelial transport and illustrated its suitability for the design and analysis of multiple simultaneous indicator dilution curves from an organ. Data should be obtained for at least three solutes: 1) an intravascular reference, albumin; 2) a solute transported by endothelial cells; and 3) another reference solute, of the same molecular size as solute 2, which neither binds nor traverses cell membranes. The capillary-tissue convection-permeation model is spatially distributed and accounts for axial variation in concentrations, transport through and around endothelial cells, accumulation and consumption within them, exchange with the interstitium and parenchymal cells, and heterogeneity of regional flows. The upslope of the dilution curves is highly sensitive to unidirectional rate of loss at the luminal endothelial surface. There is less sensitivity to transport across the antiluminal surface, except when endothelial retention is low. The model is useful for receptor kinetics using tracers during steady-state conditions and allows distinction between equilibrium binding and reaction rate limitations. Uptake rates at the luminal surface are readily estimated by fitting the model to the experimental dilution curves. For adenosine and fatty acids, endothelial transport accounts for 30-99% of the transcapillary extraction.
Randomized Phase II Study of Pulse Erlotinib Before or After Carboplatin and Paclitaxel in Current or Former Smokers With Advanced Non–Small-Cell Lung Cancer
Authors: Gregory J. Riely, Naiyer A. Rizvi, Mark G. Kris, Daniel T. Milton, David B. Solit, Neal Rosen, Emir Senturk, Christopher G. Azzoli, Julie R. Brahmer, Francis M. Sirotnak, Venkatraman E. Seshan, Margaret Fogle, Michelle Ginsberg, Vincent A. Miller, Charles M. Rudin
Journal: Journal of Clinical Oncology (2008)

A prior study demonstrated that addition of continuous daily erlotinib fails to improve response rate or survival in non-small-cell lung cancer (NSCLC) patients treated with carboplatin and paclitaxel. However, preclinical data support the hypothesis that intermittent administration of erlotinib before or after chemotherapy may improve efficacy. We tested this hypothesis in patients with advanced NSCLC.Eligible patients were former or current smokers with chemotherapy-naive stage IIIB or IV NSCLC. All patients received up to six cycles of carboplatin (area under the curve = 6) and paclitaxel (200 mg/m(2)), with random assignment to one of the following three erlotinib treatments: erlotinib 150 mg on days 1 and 2 with chemotherapy on day 3 (150 PRE); erlotinib 1,500 mg on days 1 and 2 with chemotherapy on day 3 (1,500 PRE); or chemotherapy on day 1 with erlotinib 1,500 mg on days 2 and 3 (1,500 POST). The primary end point was response rate.Eighty-six patients received treatment. The response rates for the 150 PRE, 1,500 PRE, and 1,500 POST arms were 18% (five of 28 patients), 34% (10 of 29 patients), and 28% (eight of 29 patients), respectively. The median overall survival times were 10, 15, and 10 months for the 150 PRE, 1,500 PRE, and 1,500 POST arms, respectively. The most common grade 3 and 4 toxicities were neutropenia (39%), fatigue (15%), and anemia (12%). Grade 3 and 4 rash and diarrhea were uncommon.Patients treated on the 1,500 PRE arm had the highest response rate and longest survival, with ranges similar to those reported for carboplatin, paclitaxel, and bevacizumab in a more restricted population. Further evaluation of this strategy in a phase III trial is proposed.
Sex and death: are they related? Findings from the Caerphilly cohort study
Authors: G. D. Smith, S. Frankel, J. Yarnell
Journal: BMJ (1997)

To examine the relation between frequency of orgasm and mortality.Cohort study with a 10 year follow up.The town of Caerphilly, South Wales, and five adjacent villages.918 men aged 45-59 at time of recruitment between 1979 and 1983.All deaths and deaths from coronary heart disease.Mortality risk was 50% lower in the group with high orgasmic frequency than in the group with low orgasmic frequency, with evidence of a dose-response relation across the groups. Age adjusted odds ratio for all cause mortality was 2.0 for the group with low frequency of orgasm (95% confidence interval 1.1 to 3.5, test for trend P = 0.02). With adjustment for risk factors this became 1.9 (1.0 to 3.4, test for trend P = 0.04). Death from coronary heart disease and from other causes showed similar associations with frequency of orgasm, although the gradient was most marked for deaths from coronary heart disease. Analysed in terms of actual frequency of orgasm, the odds ratio for total mortality associated with an increase in 100 orgasms per year was 0.64 (0.44 to 0.95).Sexual activity seems to have a protective effect on men's health.
AN UNUSUAL CASE OF SUICIDE BY SUFFOCATION
Authors: J. M. Renton
Journal: BMJ (1908)

SUICIDE BY SUFFOCATION.x B'm7 493-~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~EDC, ORA without doing anything.So that it is very desirable in such cases to decide the moment of dt atb.RomanCatholl physicians have noted the recovery, sometimes only for a sbort time, of many cases of apparent death.Dr.. A. -O'Malley, of the United States, narrates thirty cases of apparent death (query, who eaid "death" had occurred?) in four of whtch entire recovery, followed suitable skilful treatment.
IL-13 Decreases IL-17a Production In Mouse Th17 Cells Through An IL-10 Dependent Mechanism
Authors: D.C. Newcomb, M.M. Huckabee, M.G. Boswell, K. Goleniewska, S.S. Reiss, R.S. Peebles Jr.
Journal: Journal of Allergy and Clinical Immunology (2011)
Tumors induced by murine sarcoma virus contain precursor cells capable of generating tumor-specific cytolytic T lymphocytes.
Authors: J M Chapdelaine, F Plata, F Lilly
Journal: The Journal of Experimental Medicine (1979)

Leukocyte fractions extracted from the tumor mass and the lymphoid organs of C57BL/6 (B6) mice carrying murine sarcoma virus-induced tumors contained primed cytolytic T-lymphocyte (CTL) precursor cells, in addition to active cytotoxic T cells. These leukocyte fractions gave a secondary response when stimulated in vitro with syngeneic tumor cells, generating large numbers of specific CTL. The activity of these CTL (H-2b) was apparently H-2-restricted, because it was ineffective on tumor targets bearing strongly cross-reacting tumor-specific antigens but with the H-2d haplotype. Furthermore, only H-2b cells bearing the Friend, Moloney, Rauscher-associated antigen, such as Rauscher leukemia virus-induced RBL-5 cells and Friend leukemia virus-induced HFL/b cells, were lysed efficiently. B male GV cells (H-2b cells induced by Gross leukemia virus) were not affected by the same CTL. We propose the existence of a dynamic state involving the migration of primed CTL precursor cells between the lymphoid organs and the tumor mass, as well as the differentiation of these precursor cells within the tumor mass into highly specific CTL.
5-Methyltetrahydrofolate, the Active Form of Folic Acid, Restores Endothelial Function in Familial Hypercholesterolemia
Authors: Marianne C. Verhaar, Robert M. F. Wever, John J. P. Kastelein, Thea van Dam, Hein A. Koomans, Ton J. Rabelink
Journal: Circulation (1998)

Impaired nitric oxide (NO) activity is an early event in the pathogenesis of cardiovascular disease, resulting from either reduced NO formation or increased NO degradation. Administration of tetrahydrobiopterin (BH4), an essential cofactor for NO production, could restore NO activity in familial hypercholesterolemia (FH). Because folates have been suggested to stimulate endogenous BH4 regeneration, we hypothesized that administration of 5-methyltetrahydrofolate (5-MTHF, the active circulating form of folate) might improve NO formation in FH.We studied the effects of 5-MTHF on NO bioavailability in vivo in 10 patients with FH and 10 matched control subjects by venous occlusion plethysmography, using serotonin and nitroprusside as endothelium-dependent and -independent vasodilators. In vitro, we investigated the effect of 5-MTHF on NO production by recombinant endothelial NO synthase (eNOS) by use of [3H]arginine to [3H]citrulline conversion. We also studied the effects of 5-MTHF on superoxide generation by eNOS and xanthine oxidase (XO) by use of lucigenin chemiluminescence. The impaired endothelium-dependent vasodilation in FH (63% versus 90% in control subjects) could be reversed by coinfusion of 5-MTHF (117% vasodilation), whereas 5-MTHF had no significant effect on endothelium-dependent vasodilation in control subjects. 5-MTHF did not influence basal forearm vasomotion or endothelium-independent vasodilation. 5-MTHF had no direct effect on in vitro NO production by eNOS. However, we did observe a dose-dependent reduction in both eNOS- and XO-induced superoxide generation.These results show that the active form of folic acid restores in vivo endothelial function in FH. It is suggested from our in vitro experiments that this effect is due to reduced catabolism of NO.
Participation of tumor necrosis factor in the mediation of gram negative bacterial lipopolysaccharide-induced injury in rabbits.
Authors: J C Mathison, E Wolfson, R J Ulevitch
Journal: Journal of Clinical Investigation (1988)

Macrophages are induced by LPS to release a number of products that determine the host response during gram negative sepsis. To examine the role of one such substance, tumor necrosis factor (TNF), in mediating LPS-induced injury, we employed a rabbit model of endotoxic shock to (a) determine the kinetics and extent of release of TNF into plasma after injection of LPS, and (b) to evaluate the protective effect of in vivo neutralization of LPS-induced TNF by prior infusion of anti-TNF antibody. TNF was maximally induced 45-100 min after injection of 10 micrograms i.v. parent Salmonella minnesota Re595 LPS or 250 micrograms Re595 LPS-HDL complexes. Maximal induction of TNF by LPS was associated with development of hypotension, focal hepatic necrosis, intravascular fibrin deposition and lethality. Based on (a) the peak levels of TNF observed in serum, 2.5 X 10(3) U/ml, (b) the specific activity of purified rabbit macrophage-derived TNF, 1 X 10(8) U/mg, and (c) the biphasic disappearance of intravenously injected purified TNF (t1/2 = 0.5 min, 11 min) we constructed a kinetic model showing that at least 130 micrograms of TNF (1.3 X 10(7) U) was released into plasma 30-200 min postinjection of LPS. Prior infusion of anti-TNF antibody (30-45 min before LPS injection) resulted in neutralization of the LPS-induced serum TNF activity and provided significant protection from the development of hypotension, fibrin deposition, and lethality. Thus, these results provide further evidence that TNF plays a central role mediating the pathophysiologic changes that occur during gram negative endotoxic shock.
Molecular Mechanisms of Antidiuretic Effect of Oxytocin
Authors: Chunling Li, Weidong Wang, Sandra N. Summer, Timothy D. Westfall, David P. Brooks, Sandor Falk, Robert W. Schrier
Journal: Journal of the American Society of Nephrology (2007)

Oxytocin is known to have an antidiuretic effect, but the mechanisms underlying this effect are not completely understood. We infused oxytocin by osmotic minipump into vasopressin-deficient Brattleboro rats for five days and observed marked antidiuresis, increased urine osmolality, and increased solute-free water reabsorption. Administration of oxytocin also significantly increased the protein levels of aquaporin-2 (AQP2), phosphorylated AQP2 (p-AQP2), and AQP3 in the inner medulla and in the outer medulla plus cortex. Immunohistochemistry demonstrated increased AQP2 and p-AQP2 expression and trafficking to the apical plasma membrane of principal cells in the collecting duct, and increased AQP3 expression in the basolateral membrane. These oxytocin-induced effects were blocked by treatment with the vasopressin V2 receptor antagonist SR121463B, but not by treatment with the oxytocin receptor antagonist GW796679X. We conclude that vasopressin V2 receptors mediate the antidiuretic effects of oxytocin, including increased expression and apical trafficking of AQP2, p-AQP2, and increased AQP3 protein expression.
Acid, pepsin, and mucus secretion in patients with gastric and duodenal ulcer before and after colloidal bismuth subcitrate (De-Nol).
Authors: J H Baron, J Barr, J Batten, R Sidebotham, J Spencer
Journal: Gut (1986)

Basal and pentagastrin stimulated gastric secretion was measured in seven patients with duodenal, and six with gastric ulcers before and after four weeks9 treatment with colloidal bismuth subcitrate (as De-Nol), one tablet four times a day. Each duodenal and all but one of the gastric ulcers healed. After De-Nol there were no significant changes in basal, or pentagastrin stimulated volume, acid output, or primary parietal component. There were marked decreases in basal (duodenal ulcer -25%; gastric ulcer -16%) and pentagastrin stimulated total pepsin outputs, (duodenal ulcer -42%, gastric ulcer -36%). There were insignificant decreases in basal output of mucus, but postpentagastrin stimulated mucus output was significantly inhibited (p less than 0.05) in patients with duodenal (-16%) and with gastric ulcer (-27%). The drop in gastric proteolysis after De-Nol is unlikely to be because of the healing of the ulcers and is more likely to be because of the drug. The ulcer healing efficacy of De-Nol may be related to this decline in the proteolytic action of gastric juice, but is unlikely to be because of a quantitative change in mucus, or in acid secretion.
Measuring Response in Solid Tumors: Unidimensional Versus Bidimensional Measurement
Authors: K. James, E. Eisenhauer, M. Christian, M. Terenziani, D. Vena, A. Muldal, P. Therasse
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: Tumor shrinkage is a common end point used in screening new cytotoxic agents. The standard World Health Organization criterion for partial response is a 50% or more decrease in the sum of the products of two measurements (the maximum diameter of a tumor and the largest diameter perpendicular to this maximum diameter) of individual tumors. However, theoretically, the simple sum of the maximum diameters of individual tumors is more linearly related to cell kill than is the sum of the bidimensional products. It has been hypothesized that the calculation of bidimensional products is unnecessary, and a 30% decrease in the sum of maximum diameters of individual tumors (assuming spherical shape and equivalence to a 50% reduction in the sum of the bidimensional products) was proposed as a new criterion. We have applied the standard response and the new response criteria to the same data to determine whether the same number of responses in the same patients would result. METHODS: Data from 569 patients included in eight studies of a variety of cancers were reanalyzed. The two response criteria were separately applied, and the results were compared using the κ statistic. The importance of confirmatory measurements and the frequency of nonspherical tumors were also examined. In addition, for a subset of 128 patients, a unidimensional criterion for disease progression (30% increase in the sum of maximum diameters) was applied and compared with the standard definition of a 25% increase in the sum of the bidimensional products. RESULTS: Agreement between the unidimensional and bidimensional criteria was generally found to be good. The κ statistic for concordance for overall response was 0.95. CONCLUSION: We conclude that one dimensional measurement of tumor maximum diameter may be sufficient to assess change in solid tumors.
New Ethical Issues for Genetic Counseling in Common Mental Disorders
Authors: Elliot S. Gershon, Ney Alliey-Rodriguez
Journal: American Journal of Psychiatry (2013)

Objective Recent genetic findings of high-impact genetic variants in bipolar disorder, schizophrenia, and autism spectrum disorder (ASD) must lead to profound changes in genetic and family counseling. The authors present risk calculations, discuss the ethical implications of these findings, and outline the changes now required in the risk counseling process. Method The authors use data from recent mega-analyses and reviews of common and rare risk variants in bipolar disorder, schizophrenia, and ASD to calculate risks of illness based on genetic marker tests. They then consider new ethical issues in mental disorders presented by these risks, including within-family conflicts over genetic testing; effects of genetic discoveries on stigma, abortion, preimplantation procedures, and population screening for susceptibility; and genetic tests as a factor in marital choice. Results New structural mutations (de novo copy number variants [CNVs], which are chromosomal microdeletions and microduplications) are present in 4%−7% of patients with bipolar disorder, schizophrenia, or ASD and can occur almost anywhere in the genome. For a person with a de novo CNV, the absolute risk of bipolar disorder, schizophrenia, or ASD is 14%, much higher than the population risk. Rare CNVs have also been identified that are generally not new mutations but constitute very high-effect risk factors, ranging up to 82%. Conclusions A substantial minority of patients with bipolar disorder, schizophrenia, and ASD have high-impact detectable genetic events. This greatly changes psychiatric genetic counseling for these patients and families. A psychotherapeutic approach may be needed as a routine part of risk counseling, particularly for resolution of ethical issues and for within-family stigma and conflicts over genetic test results.
The plasminogen activator/plasmin system.
Authors: J D Vassalli, A P Sappino, D Belin
Journal: Journal of Clinical Investigation (1991)

proteases and inhibitors has been shown to be under the control of hormones and growth factors. Plasminogen activators (PAs) and their inhibitors (PAIs) are thought to be key participants in the balance ofproteolytic and antiproteolytic activities that regulates matrix turnover. This article summarizes the evidence that supports this contention, discusses the role ofPAspecific cell surface binding sites, and also draws attention to a number of instances in which the presence ofPAs cannot be reconciled with an exclusive function in ECM degradation.
Cholesterol Metabolism in Human Gallbladder Mucosa: Relationship to Cholesterol Gallstone Disease and Effects of Chenodeoxycholic Acid and Ursodeoxycholic Acid Treatment
Authors: Staffan Sahlin, Jon Ahlberg, Eva Reihnér, Dagny Starhlberg, Kurt Einarsson
Journal: Hepatology (1992)

The objective of this study was to investigate cholesterol metabolism in human gallbladder mucosa, especially in relation to hepatic cholesterol metabolism, gallstone disease and treatment with bile acids. Gallbladder mucosa and liver tissue samples were collected in 44 patients undergoing cholecystectomy; 30 had cholesterol gallstones and the rest were stone free. Ten of the gallstone patients were treated with chenodeoxycholic acid and eight received ursodeoxycholic acid, with a daily dose of 15 mg/kg body wt, for 3 wk before surgery. The 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, governing cholesterol synthesis, was considerably lower in the gallbladder mucosa than in liver tissue (28 +/- 6 and 120 +/- 40 pmol/min/mg protein). The acyl coenzyme A:acyltransferase activity in the gallbladder mucosa catalyzing the esterification of cholesterol was, on the other hand, several times higher than corresponding activity in the liver (92 +/- 23 and 11 +/- 2 pmol/min/mg protein). In the presence of exogenous cholesterol, the acyl coenzyme A:acyltransferase activity increased about twofold in the gallbladder mucosa. The acyl coenzyme A:acyltransferase activity of the gallbladder mucosa from untreated gallstone patients was not stimulated further by the addition of exogenous cholesterol. Otherwise, there were no significant differences in acyl coenzyme A:acyltransferase and 3-hydroxy-3-methylglutaryl coenzyme A reductase activities in the gallbladder mucosa of gallstone patients compared with gallstone-free controls. Treatment with chenodeoxycholic and ursodeoxycholic acids did not affect the 3-hydroxy-3-methylglutaryl coenzyme A reductase activity of the gallbladder mucosa but reduced the acyl coenzyme A:acyltransferase activity by 60% to 65%.(ABSTRACT TRUNCATED AT 250 WORDS)
Prospective identification, isolation, and systemic transplantation of multipotent mesenchymal stem cells in murine bone marrow
Authors: Satoru Morikawa, Yo Mabuchi, Yoshiaki Kubota, Yasuo Nagai, Kunimichi Niibe, Emi Hiratsu, Sadafumi Suzuki, Chikako Miyauchi-Hara, Narihito Nagoshi, Takehiko Sunabori, Shigeto Shimmura, Atsushi Miyawaki, Taneaki Nakagawa, Toshio Suda, Hideyuki Okano, Yumi Matsuzaki
Journal: The Journal of Experimental Medicine (2009)

Mesenchymal stem cells (MSCs) are defined as cells that undergo sustained in vitro growth and can give rise to multiple mesenchymal lineages. Because MSCs have only been isolated from tissue in culture, the equivalent cells have not been identified in vivo and little is known about their physiological roles or even their exact tissue location. In this study, we used phenotypic, morphological, and functional criteria to identify and prospectively isolate a subset of MSCs (PDGFRα+Sca-1+CD45−TER119−) from adult mouse bone marrow. Individual MSCs generated colonies at a high frequency and could differentiate into hematopoietic niche cells, osteoblasts, and adipocytes after in vivo transplantation. Naive MSCs resided in the perivascular region in a quiescent state. This study provides the useful method needed to identify MSCs as defined in vivo entities.