tbuckley/cabot-search huggingface dataset:
A method for determining segmental resistances in the microcirculation from pressure-flow measurements.
Authors: S H Nellis, B W Zweifach
Journal: Circulation Research (1977)

On the basis of an electrical analog, open circuit impedance functions were used to analyze the microcirculation. No specific structure need be assumed except a two-port, two-terminal network in which the major artery and vein supplying the tissue represent the input port and the two ends of the microvessel under study are the output port. The open circuit measurements were made by occluding microvessels in the exteriorized omentum of anesthetized rabbits. The pressure upstream and downstream to the occlusion defines the source pressure of a Thévenin's equivalent circuit. The equivalent resistance value was calculated by plotting the flow through a given microvessel against the pressure developed during a gradual occlusion. The changes in pressure vs. the changes in flow during a progressive occlusion were found to be linearly related. The Thévenin's equivalent resistance was maximum downstream to an occluded artery and upstream to the occluded vein. Within the capillary network, source pressures consistently were within a narrow range. Topically applied norepinephrine resulted in marked changes in source resistance and no changes in source pressures. Threshold doses of norepinephrine given intravenously resulted in changes in source pressures, but minimal changes in source resistance, even though a substantial change in vascular resistance was indicated when calculated on the basis of arterial pressure minus micropressure divided by microvessel flow. The present method defines the functional characteristics of the distributing vessels in terms of two pressures and two equivalent resistances and is relatively easy to perform. The technique can be used to determine the vascular components involved in the response to particular stimuli.
Cytotoxic T lymphocytes against disease-associated determinant(s) in ankylosing spondylitis.
Authors: A F Geczy, L E McGuigan, J S Sullivan, J P Edmonds
Journal: The Journal of Experimental Medicine (1986)

Cytotoxic T lymphocytes, induced by stimulating the PBMC of an HLA-B27+ normal individual (B27+, AS-) with the PBMC of an HLA-identical sibling suffering from ankylosing spondylitis (AS) (B27+, AS+), specifically lyse B27+, AS+ PBMC but not PBMC from HLA-27+ or B27-, AS- normal controls, or from HLA-B27- AS patients (B27-,AS+). CTL of similar specificity can also be raised by immunizing in vitro B27+,AS- cells with autologous cells modified by cross-reactive bacterial antigens. These results suggest that CTL can recognize certain bacterial antigens in association with HLA-B27 and that this interaction may lead to an inflammatory episode during the initial stages of the disease.
In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion
Authors: Andreea Ianus, George G. Holz, Neil D. Theise, Mehboob A. Hussain
Journal: Journal of Clinical Investigation (2003)

Bone marrow harbors cells that have the capacity to differentiate into cells of nonhematopoietic tissues of neuronal, endothelial, epithelial, and muscular phenotype. Here we demonstrate that bone marrow–derived cells populate pancreatic islets of Langerhans. Bone marrow cells from male mice that express, using a CRE-LoxP system, an enhanced green fluorescent protein (EGFP) if the insulin gene is actively transcribed were transplanted into lethally irradiated recipient female mice. Four to six weeks after transplantation, recipient mice revealed Y chromosome and EGFP double-positive cells in their pancreatic islets. Neither bone marrow cells nor circulating peripheral blood nucleated cells of donor or recipient mice had any detectable EGFP. EGFP-positive cells purified from islets express insulin, glucose transporter 2 (GLUT2), and transcription factors typically found in pancreatic β cells. Furthermore, in vitro these bone marrow–derived cells exhibit — as do pancreatic β cells — glucose-dependent and incretin-enhanced insulin secretion. These results indicate that bone marrow harbors cells that have the capacity to differentiate into functionally competent pancreatic endocrine β cells and that represent a source for cell-based treatment of diabetes mellitus. The results generated with the CRE-LoxP system also suggest that in vivo cell fusion is an unlikely explanation for the “transdifferentiation” of bone marrow–derived cells into differentiated cell phenotypes.
Genetic Polymorphisms in Genes Encoding Antioxidant Enzymes Are Associated With Diabetic Retinopathy in Type 1 Diabetes
Authors: Tinka Hovnik, Vita Dolžan, Nataša Uršič Bratina, Katarina Trebušak Podkrajšek, Tadej Battelino
Journal: Diabetes Care (2009)

OBJECTIVE Oxidative stress plays an important role in the development of microangiopathic complications in type 1 diabetes. We investigated polymorphic markers in genes encoding enzymes regulating production of reactive oxygen species in association with diabetic retinopathy or diabetic nephropathy. RESEARCH DESIGN AND METHODS A total of 124 patients with type 1 diabetes were investigated in this case-control study. All subjects were matched for sex, age, and duration of diabetes. Genotyping was conducted using real-time PCR for p.Val16Ala polymorphism in the MnSOD gene and c.C−262T in the promoter region of the CAT gene. Multiplex PCR method was used for determination of GSTM1 and GSTT1 polymorphic deletions. Fluorescence-labeled PCR amplicons and fragment analysis was used for assessing the number of pentanucleotide (CCTTT)n repeats in inducible nitric oxide synthase. RESULTS A positive association of MnSOD genotype Val/Val (odds ratio [OR] 2.49, 95% CI 1.00–6.16, P = 0.045) and GSTM1–1 genotype (2.63, 1.07–6.47, P = 0.031) with diabetic retinopathy but not with diabetic nephropathy was demonstrated. Additionally, the combination of the two genotypes conveyed an even higher risk (4.24, 1.37–13.40, P = 0.009). No other investigated genetic polymorphisms were associated with either diabetic retinopathy or diabetic nephropathy. CONCLUSIONS Selected polymorphisms in genes encoding MnSOD and GSTM1 could be added to a panel of genetic markers for identification of individuals with type 1 diabetes at an increased risk for developing diabetic retinopathy.
Mitochondrial Genome of the Colorless Green Alga Polytomella capuana: A Linear Molecule with an Unprecedented GC Content
Authors: D. R. Smith, R. W. Lee
Journal: Molecular Biology and Evolution (2008)

One common observation concerning mitochondrial genomes is that they have a low guanine and cytosine content (GC content); of the complete mitochondrial genome sequences currently available at the National Center for Biotechnology Information (NCBI) (July 2007), the GC content ranges from 13.3% to 53.2% and has an average value of 38%. Here, we present the GC-rich mitochondrial genome (57% GC) of the colorless green alga Polytomella capuana. The disproportion of GC among the different regions of the P. capuana mitochondrial DNA (mtDNA) suggests that a neutral process is responsible for the GC bias. We propose that a biased gene conversion mechanism resulted in the GC-rich state of the P. capuana mtDNA. In addition, our analysis indicates that the P. capuana mitochondrial genome is a single 13-kb linear molecule with telomeres, which have a closed (hairpin-loop) conformation: a novel terminal structure among described linear green-algal mtDNAs. Furthermore, using a series of GC-rich inverted repeats found within the P. capuana mitochondrial genome, we describe recombination-based scenarios of how intact linear mtDNA conformations can be converted into the fragmented forms found in other Polytomella taxa.
Increased renal vascular reactivity to angiotensin II but not to nerve stimulation or exogenous norepinephrine in renal hypertensive rats.
Authors: M G Collis, P M Vanhoutte
Journal: Circulation Research (1978)

We isolated and perfused both the "clipped" and "contralateral" kidneys from Goldblatt renal hypertensive and sham-operated control rats, 1--104 days postoperatively. Responses to renal nerve stimulation were depressed in clipped kidneys from hypertensive rats (1 day postoperative), and these kidneys were supersensitive to exogenous norepinephrine (1--31 day) when compared with the contralateral organ of the same animal. Similar alterations were found between clipped and contralateral kidneys from sham-operated control rats. There was no difference in responses to renal nerve stimulation of norepinephrine between clipped kidneys from hypertensive and control rats, but clipped kidneys from hypertensive rats were supersensitive to angiotensin II (17 and 31 days). Comparison of contralateral kidneys from hypertensive and control rats revealed no change in norepinephrine sensitivity or in responses to renal nerve stimulation, but there was a reduction in the slope of the dose-response curve to norepinephrine and of the maximal effect of the catecholamine (104 days) and a pronounced supersensitivity to angiotensin II (17--104 days) in the hypertensive rats. These results indicate that (1) renal nerve function and norepinephrine sensitivity of the isolated renal vasculature are unchanged in renal hypertension, but clipping partially denervates the kidney causing depressed nerve function and unilateral norepinephrine supersensitivity, unrelated to hypertension; (2) the prolonged high pressure load on the contralateral kidney may impair the function of the vascular smooth muscle; and (3) bilateral supersensitivity to angiotensin II is associated with hypertension but is not solely a consequence of the high pressure.
Effect of antibiotic treatment on inflammatory markers and lung function in cystic fibrosis patients with Pseudomonas cepacia.
Authors: D Peckham, S Crouch, H Humphreys, B Lobo, A Tse, A J Knox
Journal: Thorax (1994)

BACKGROUND--The acquisition of Pseudomonas cepacia in patients with cystic fibrosis is associated with increasing deterioration in lung function and more frequent hospital admissions. Pseudomonas cepacia is usually resistant to several antibiotics in vitro, but the response of patients colonised with the organism has not been extensively studied in vivo. METHODS--A three month prospective study was performed to investigate the response of 14 Ps cepacia positive patients and 10 Ps cepacia negative patients to a two week course of intravenous antibiotics. All those who were Ps cepacia negative and six of the 14 Ps cepacia positive patients had Ps aeruginosa in their sputum which was sensitive to the prescribed therapy. The inflammatory markers C-reactive protein, white blood cell count, serum lactoferrin, neutrophil elastase/alpha 1-antitrypsin complex, and tumour necrosis factor alpha were measured at the start and end of each antibiotic course. RESULTS--The median (range) % improvement in baseline FEV1 and FVC following treatment in the group as a whole was 15.2% (-23.5% to 156.3%) and 23.9% (-36.8% to 232.7%) respectively. There was no statistical difference in improvement in lung function, body weight, or inflammatory markers between individuals who were Ps cepacia positive and those who were Ps cepacia negative. CONCLUSIONS--Patients who are Ps cepacia positive appear to respond as well to intravenous antibiotics as those who are Ps cepacia negative, despite having lower lung function and a bacterium in their sputum which is resistant in vitro to the antibiotics used.
Effect of isradipine on the formation and regression of fatty streaks in cholesterol fed rabbits
Authors: R Kunjara-Na-Ayudhya, A B R Thomson, C T Kappagoda
Journal: Cardiovascular Research (1994)

Objective: The aim was to determine whether the antiatherogenic effect of the calcium channel blocker isradipine on fatty streak formation was dependent upon a temporal relationship between cholesterol feeding and administration of the drug. Methods: The study was done in New Zealand White rabbits fed a diet supplemented with cholesterol (2.5% w/w) for three weeks. Such a regimen results in loss of endothelium dependent relaxation and accumulation of cholesterol in the aorta four weeks later. The calcium antagonist isradipine was given in a dose of 0.25 mg·kg−1·d−1 at specified periods during the study to seven subgroups of animals: (1) standard diet + 2.5% cholesterol for three weeks; (2) standard diet + 2.5% cholesterol for three weeks followed by standard diet for four weeks; (3) standard diet + 2.5% cholesterol for three weeks followed by standard diet for 12 weeks; (4) standard diet + 2.5% cholesterol + isradipine for three weeks followed by standard diet alone for four weeks; (5) standard diet + 2.5% cholesterol for three weeks followed by standard diet for four weeks with isradipine given throughout the seven weeks; (6) standard diet + 2.5% cholesterol for three weeks followed by standard diet for four weeks with isradipine given during the final four weeks only; (7) standard diet+ 2.5% cholesterol for three weeks followed by standard diet for 12 weeks with isradipine given during the final eight weeks. Aortic tissue was removed for measurement of cholesterol content, endothelium dependent relaxation to acetylcholine and the calcium ionophore A23187, and relaxant responses to sodium nitrite. Serum was collected for measurement of cholesterol and triglyceride concentration. Results: When isradipine was given either during cholesterol feeding and continued for four weeks following it (subgroup 5) or during the four weeks following cholesterol feeding (subgroup 6), loss of endothelium dependent relaxation and the accumulation of cholesterol in the aorta was prevented. However, administration of isradipine during the period of cholesterol feeding alone (subgroup 4) was without effect. Also, administration of isradipine after lesions of fatty acid streak type were established appeared to have a favourable effect on removal of cholesterol from the aorta. Conclusions: Isradipine protects against the development of fatty streaks in rabbits fed a diet supplemented with 2.5% cholesterol. Administration of this drug after fatty streaks are formed also promotes their resolution. Cardiovascular Research 1994;28:1089-1095
Early health effects of the emerging tobacco epidemic in China. A 16-year prospective study
Authors: Z. M. Chen
Journal: JAMA (1997)

In recent decades, there has been a rapid and substantial increase in tobacco consumption in China, particularly by men, but little is known from local epidemiologic studies about the pattern of smoking-related deaths.To assess the current health effects of cigarette smoking in Shanghai, China.Prospective observational study of mortality in relation to cigarette smoking.Eleven factories in urban Shanghai.A total of 9351 adults (6494 men and 2857 women) aged 35 to 64 years at baseline survey during the 1970s.All-cause and cause-specific mortality.During an average follow-up of 16 years, 881 men and 207 women died. Among men, 61% had described themselves as current cigarette smokers at baseline, and their overall mortality was significantly greater than that of nonsmokers (relative risk [RR], 1.4; 95% confidence interval [CI], 1.2-1.7; P<.001). The excess was almost twice as great (RR, 1.8; 95% CI, 1.5-2.2 [corrected]; P<.001) among the men who had begun smoking before the age of 25 years and was significantly associated with the number of cigarettes smoked (P<.001 for trend) after adjustment for other major risk factors. The chief sources of the excess were lung cancer (RR, 3.8; 95% CI, 2.1-6.8; P<.001), esophageal cancer (RR, 3.6; 95% CI, 1.2-10.5; P=.02), liver cancer (RR, 2.0; 95% CI, 1.1-3.7; P=.03), coronary heart disease (RR, 1.8; 95% CI, 1.0-3.2; P=.04), and chronic obstructive pulmonary disease (RR, 2.5; 95% CI, 1.4-4.4; P<.01). Among the men in this Chinese population, about 20% (95% CI, 12%-29%) of all deaths during the study period could be attributed to cigarette smoking. Of these deaths, one third involved lung cancer, one third involved other cancers, and one third involved other diseases. Only 7% of women described themselves as current cigarette smokers at baseline, but among them there was also a statistically significant excess of overall mortality (RR, 1.7; 95% CI, 1.2-2.5; P<.01).Cigarette smoking is already a major cause of death in China, and among middle-aged Shanghai men, about 20% of all deaths during the 1980s were due to smoking. The excess was greatest among men who began smoking before the age of 25 years, about 47% of whom would, at 1987 mortality rates, die between the ages of 35 and 69 years (compared with only 29% of nonsmokers). These estimates reflect the consequences of past smoking patterns. The future health effects of current smoking patterns are likely to be greater because of the recent large increase in cigarette consumption, particularly at younger ages, in China.
How do non-invasive fibrosis scoring systems compare with transient elastography in the diagnosis of fibrosis in patients with non alcoholic fatty liver disease
Authors: I. Barnova, B. Lopez, R. Przemioslo
Journal: Gut (2011)

<h3>Introduction</h3> Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver disease in the western world with a subgroup of patients developing fibrosis (NASH). The gold standard for the assessment of liver fibrosis is liver biopsy, which is invasive, subject to sampling error, interobserver and intraobserver variability and impractical for screening. Several non-invasive fibrosis scoring systems have been proposed to identify advanced fibrosis in patients with NAFLD. Transient elastography (TE) has a high negative predictive value for advanced fibrosis and has been suggested for non-invasive screening. Accurate evaluation of liver fibrosis in patients with NAFLD is important to identify patients who may develop complications. The aim of this study was to compare the performance of four non-invasive fibrosis scoring systems (BFS) with TE. <h3>Methods</h3> Patients attending the hepatology clinic with a positive diagnosis of NAFLD were identified. Data from TE assessment was compared with BFS scores using four scores ALT/AST, BARD, FIB-4 and NAFLD score. The TE cut off stiffness score for no fibrosis was &lt;6 kPa 6–14 kPa for mild-moderate fibrosis (MMF) and &gt;14 kPa for cirrhosis. The authors defined no fibrosis if all BFS were negative and severe fibrosis, if at least 3 out of 4 BFS systems were positive for fibrosis. 1 or 2 positive BFS was considered as suggestive of MMF. <h3>Results</h3> 61 patients underwent TE. Poor quality readings (IQR of &lt;2 or &gt;25% of median) were excluded (n=19) and 42 patients were included in the study. The average age was 50 years, average BMI of 32.3 and 19 patients had diagnosis of DM. Two patients had TE scores of over 14 kPa consistent with cirrhosis and these patients had BFS markers (3 out of 4 positive) consistent with advanced fibrosis (100%). 32 patients had MMF range readings on TE and only 9 patients would have been classified with MMF using BFS markers (28.1%), Of the remaining 23 patients, 19 patients would have been classified as no fibrosis (59.4%) and 4 patients would have been classified as advanced fibrosis using BFS markers (12.5%). 8 patients had TE scores consistent with no fibrosis and only 5 patients would have been classified as such using BFS markers (62.5%), 2 patients would have been classified as advanced fibrosis (25%) and 1 patient would have been classified as MMF (12.5%). <h3>Conclusion</h3> A number of patients in this cohort would have been classified very differently depending on whether TE or BFS was used. The National Liver strategy is recommending that patients with suspected liver disease in primary care undergo a liver screen which should include a marker or measure(s) of liver fibrosis. This study suggests that approaches using BFS or TE are not interchangeable.
RHOA and PRKCZ control different aspects of cell motility in pancreatic cancer metastatic clones
Authors: Marco Della Peruta, Cinzia Giagulli, Carlo Laudanna, Aldo Scarpa, Claudio Sorio
Journal: Molecular Cancer (2010)

Abstract Background Our understanding of the mechanism regulating pancreatic cancer metastatic phenotype is limited. We analyzed the role of RHOA and PRKCZ in the motility attitude of two subclones of the pancreatic adenocarcinoma cell line SUIT-2 (S2), with different in vivo metastatic potential in nude mice: S2-m with a low metastatic potential and highly metastatic S2-CP9 using RHOA and PRKCZ cell-permeable inhibitory peptides. Methods Adhesion assays, cell permeable peptides, RHOA activity assay, western blotting Results When used in combination cell-permeable inhibitory peptides partially inhibited cell adhesion by about 50% in clone S2-CP9. In clone S2-m, the effect was limited to 15% inhibition. In a wound healing assay, S2-CP9 was sensitive only to treatment with the combination of both RHOA and PRKCZ inhibitory peptides. Conversely, S2-m was unable to migrate toward both ends of the wound in basal conditions. Migration of cells through a membrane with 8 μm pores was completely abolished in both clones by individual treatment with RHOA and PRKCZ inhibitory peptides. Conclusion Herein, we demonstrate a critical role for RHOA and PRKCZ in the regulation of different aspects of cell motility of pancreatic adenocarcinoma and demonstrate the need to inhibit both pathways to obtain a functionally relevant effect in most assays. These results indicate that RHOA and PRKCZ, and their downstream effectors, can represent important pharmacological targets that could potentially control the highly metastatic attitude of PDAC.
Dissociable Reward and Timing Signals in Human Midbrain and Ventral Striatum
Authors: Miriam C. Klein-Flügge, Laurence T. Hunt, Dominik R. Bach, Raymond J. Dolan, Timothy E.J. Behrens
Journal: Neuron (2011)

Reward prediction error (RPE) signals are central to current models of reward-learning. Temporal difference (TD) learning models posit that these signals should be modulated by predictions, not only of magnitude but also timing of reward. Here we show that BOLD activity in the VTA conforms to such TD predictions: responses to unexpected rewards are modulated by a temporal hazard function and activity between a predictive stimulus and reward is depressed in proportion to predicted reward. By contrast, BOLD activity in ventral striatum (VS) does not reflect a TD RPE, but instead encodes a signal on the variable relevant for behavior, here timing but not magnitude of reward. The results have important implications for dopaminergic models of cortico-striatal learning and suggest a modification of the conventional view that VS BOLD necessarily reflects inputs from dopaminergic VTA neurons signaling an RPE.