tbuckley/cabot-search huggingface dataset:
Impaired Renal Sensory Responses after Unilateral Ureteral Obstruction in the Rat
Authors: Ming-Chieh Ma, Ho-Shiang Huang, Chau-Fong Chen
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Renal responses to the activation of renal sensory receptors were examined in rats after release of 24-h unilateral ureteral obstruction of the left kidney. The integrity of the renorenal reflex was examined in both 24-h unilateral ureteral obstruction-treated (UUO) and sham-operated (Sham) rats. Increased ipsilateral afferent renal nerve activity (ARNA) and reflexly decreased efferent renal nerve activity (ERNA) and increased contralateral diuresis and natriuresis produced by increasing the left intrapelvic pressure were observed in Sham rats but not in UUO rats. The lack of responsiveness of the renorenal reflex in UUO rats was associated with lower release of substance P (SP) and increased neutral endopeptidase (NEP) activity in the renal pelvis in the postobstructive kidney. Compared with Sham rats, urine and sodium excretion after acute saline loading was significantly reduced in the postobstructive kidney. The blunted excretory responses were accompanied by lower activation of ARNA and less reflex inhibition of ERNA. Renal sensory dysfunction in the postobstructive kidney was further examined by stimulation of renal mechanoreceptors and chemoreceptors. Graded increases in intrapelvic pressure or renal pelvic perfusion with hypertonic saline solution elicited, respectively, a pressure- or concentration-dependent increase in ARNA in the control kidney of Sham rats, this response being greatly attenuated in the postobstructive kidney. Western blots showed no quantitative difference in the expression of renal pelvic neurokinin 1 (NK-1) receptors between the two groups. It was concluded that renal sensory function is impaired in the postobstructive kidney of UUO rats and that this defective activation of renal sensory receptors results in an impaired renorenal reflex, which is associated with enhanced NEP activity and catabolism of SP released in the renal pelvis and is not related to the expression of NK-1 receptor protein.
Tropical respiratory medicine. 1. Pulmonary infections in the tropics: impact of HIV infection.
Authors: C L Daley
Journal: Thorax (1994)

Infection with Mycobacterium tuberculosis is so common in tropical areas that the World Health Organization (WHO) estimates more than 75% of the 8-10 million new cases of tuberculosis (TB) annually occur therein. Infection with HIV is also common in the tropics; the WHO estimated in 1992 that 9-11 million adults were infected with HIV, mostly in developing countries. This tropical overlap of HIV infection and pulmonary pathogens makes pulmonary infections a common manifestation of HIV infection, especially TB and bacterial pneumonia. Bacterial pneumonia accounts for at least 25% of medical admissions to one of East Africa's largest hospitals and recent cohort and case-control studies have shown increased rates of disease among HIV-infected individuals. Of all the pulmonary infections encountered in the tropics, however, M. tuberculosis is one of the most significant pathogens. Data from sub-Saharan Africa and Haiti have shown that 17-66% of TB cases are seropositive for HIV-1. Moreover, 50% of seropositive patients presenting with pulmonary symptoms have TB. This review, however, focuses upon non-tuberculosis pathogens affecting HIV-infected patients in tropical and developing countries. Pneumococcus, nocardiosis, and melioidosis are discussed under bacterial pneumonia and are followed by cryptococcosis, histoplasmosis, paracoccidioidomycosis, and penicillium marneffei under fungal pneumonia. Other sections explore pneumocystis pneumonia, parasitic pneumonia (strongyloidiasis), pleural effusions, and the evaluation of HIV-infected patients with pulmonary disease.
Inhibition of the Kit Ligand/c-Kit Axis Attenuates Metastasis in a Mouse Model Mimicking Local Breast Cancer Relapse after Radiotherapy
Authors: François Kuonen, Julien Laurent, Chiara Secondini, Girieca Lorusso, Jean-Christophe Stehle, Thierry Rausch, Eveline Faes-van't Hull, Grégory Bieler, Gian-Carlo Alghisi, Reto Schwendener, Snezana Andrejevic-Blant, René-Olivier Mirimanoff, Curzio Rüegg
Journal: Clinical Cancer Research (2012)

Local breast cancer relapse after breast-saving surgery and radiotherapy is associated with increased risk of distant metastasis formation. The mechanisms involved remain largely elusive. We used the well-characterized 4T1 syngeneic, orthotopic breast cancer model to identify novel mechanisms of postradiation metastasis.4T1 cells were injected in 20 Gy preirradiated mammary tissue to mimic postradiation relapses, or in nonirradiated mammary tissue, as control, of immunocompetent BALB/c mice. Molecular, biochemical, cellular, histologic analyses, adoptive cell transfer, genetic, and pharmacologic interventions were carried out.Tumors growing in preirradiated mammary tissue had reduced angiogenesis and were more hypoxic, invasive, and metastatic to lung and lymph nodes compared with control tumors. Increased metastasis involved the mobilization of CD11b(+)c-Kit(+)Ly6G(high)Ly6C(low)(Gr1(+)) myeloid cells through the HIF1-dependent expression of Kit ligand (KitL) by hypoxic tumor cells. KitL-mobilized myeloid cells homed to primary tumors and premetastatic lungs, to give rise to CD11b(+)c-Kit(-) cells. Pharmacologic inhibition of HIF1, silencing of KitL expression in tumor cells, and inhibition of c-Kit with an anti-c-Kit-blocking antibody or with a tyrosine kinase inhibitor prevented the mobilization of CD11b(+)c-Kit(+) cells and attenuated metastasis. C-Kit inhibition was also effective in reducing mobilization of CD11b(+)c-Kit(+) cells and inhibiting lung metastasis after irradiation of established tumors.Our work defines KitL/c-Kit as a previously unidentified axis critically involved in promoting metastasis of 4T1 tumors growing in preirradiated mammary tissue. Pharmacologic inhibition of this axis represents a potential therapeutic strategy to prevent metastasis in breast cancer patients with local relapses after radiotherapy.
Positionally cloned asthma susceptibility gene polymorphisms and disease risk in the British 1958 Birth Cohort
Authors: J D Blakey, I Sayers, S M Ring, D P Strachan, I P Hall
Journal: Thorax (2009)

<h3>Objective:</h3> The aim of this study was to estimate the contribution of polymorphisms in the positionally cloned asthma candidate genes <i>ADAM33, PHF11, DPP10, GPRA</i> and <i>PTGDR</i> to the risk of asthma, total and specific immunoglobulin E level, lung function and wheezing in a large, nationally representative, population. <h3>Methods:</h3> An association analysis was undertaken using genotype data for tagging and previously associated single nucleotide polymorphisms (SNPs) in regions of these genes and longitudinal phenotype data from singletons of white ethnicity in the British 1958 Birth Cohort DNA archive (n = 7703). Population-attributable risk fractions for SNPs showing association were calculated. <h3>Results:</h3> Polymorphisms producing small but statistically significant increases in asthma risk (OR 1.1 per allele) were identified in <i>DPP10</i> and <i>ADAM33</i>, with the strongest evidence being for SNPs tagging the <i>DPP10</i> gene. No individual SNP in any gene under study markedly increased risk for any of the phenotypes in the population studied. <h3>Conclusions:</h3> These data suggest that <i>DPP10</i> and <i>ADAM33</i> influence asthma risk in the UK population. However, the effects driven by any given locus are small, and genotyping of multiple polymorphisms in many genes will be needed to define a full genetic profile for disease risk.
Fluoresceinated lectins as probe for cell surface changes associated with lymphocyte transformation
Authors: James A. Strauchen
Journal: American Journal of Hematology (1982)

Abstract Lectins are plant‐derived proteins with specific affinities for simple or complex sugars and are potentially useful tools for investigation of the carbohydrate structure of the cell surface. A panel of fluoresceinated lectins was used to study the cell surface changes associated with lymphocyte transformation. The major determinants detected on peripheral blood lymphocytes were αD‐mannose,β‐D‐galactose and N‐acetyl‐glucosamine. Phytohemagglutinin transformation was associated with increased binding of lectins specific for N‐acetyl‐galactosamine. MOLT‐4, a T‐lymphoblast cell line in continuous culture, was associated with increased binding of lectins specific for N‐acetyl‐galactosamine and L‐fucose. Application of fluoresceinated lectins may be a useful tool in the classification of lymphoid cells.
Hybridoma antibodies against protective and nonprotective antigenic determinants of a structurally defined polypeptide fragment of streptococcal M protein.
Authors: D L Hasty, E H Beachey, W A Simpson, J B Dale
Journal: The Journal of Experimental Medicine (1982)

Hybridoma technology was used to produce a set of monoclonal antibodies against a purified polypeptide fragment of type 24 streptococcal M protein to delineate the protective determinants of M protein exposed on the surface of the virulent streptococci. Several hybridoma antibodies were found to be opsonic against the homologous type streptococci. At least two of these antibodies (IIC3.7 and IIC4.6) protected mice against challenge infections with the homologous, but not a heterologous, serotype of bacteria. One of the hybridoma antibodies that reacted in high dilution (1:204,800) with the isolated M protein failed to react with the M protein on the surface of type 24 streptococci, and thus did not opsonize the homologous organisms or protect mice against challenge infections. Because hybridoma antibodies are directed against a single distinct immunodeterminant, these results indicate that protective immunity may be directed at any one of several distinct antigenic determinants of M protein exposed on the surface of virulent group A streptococci.
Population pharmacokinetics and pharmacodynamics analysis of vancomycin in patients with severe lower respiratory tract gram-positive infections
Authors: Wei Yang, Bei He
Journal: European Respiratory Journal (2014)

Objectives To develop a population pharmacokinetic (PPK) model and pharmacodynamics (PD) goal of vancomycin for the severe lower respiratory tract infection(LRTI). Methods Serum vancomycin concentrations were measured by high performance liquid chromatography. The nonlinear mixed-effects model was used to analyze the PPK model. Results 267 vancomycin concentrations data from 70 subjects were collected, including 58 men, the average age was 78 years old, APACHE II score was 16.4 and CCR was 76ml/min. 48 patients used mechanical ventilation. A two-compartment model fit the data best. The final PPK model was:  CL=1.67×e 0.35   V 1 =33.04×[1-0.199×(60/Scr)] ×e 0.11   Q=7.08×2.053 AI × e 0.076   V 2 =19.29×e 0.68   (AI=1 if patients with albumin infusion; elsewise AI=0.) 42 subjects with MRSA infection were used to estimate the PD parameters. They were divided into two parts: clinical responders (n=33) and nonreponders(n=9). Logictic regression analysis revealed that C min /MIC significantly affected the clinical outcomes(P=0.014, OR=1.182), and ROC curve showed the cut-off value was 17.6, sensitivity and specificity were 87.9% and 77.8%, respectively. The 42 subjects were also divided into: bacteriology eradication (n=23) and bacteriology noneradication (n=19). C min /MIC affected the bacterial outcomes(P=0.03 3, OR=1.096), and the cut-off value was 16.5, sensitivity and specificity were 65.4% and 68.7%, respectively. Conclusions The serum creatinine and AI significant affected vancomycin PK in severe LRTI. And the cut-off value of 17.6 for C min /MIC can optimize vancomycin dose regimen to achieve clinical success.
Serum Concentrations of 1,1,1-Trichloro-2,2-bis( p -chlorophenyl)ethane (DDT) and 1,1-Dichloro-2,2-bis( p -chlorophenyl)ethylene (DDE) and Risk of Primary Liver Cancer
Authors: Katherine A. McGlynn, Christian C. Abnet, Mingdong Zhang, Xiu-Di Sun, Jin-Hu Fan, Thomas R. O'Brien, Wen-Qiang Wei, Betty A. Ortiz-Conde, Sanford M. Dawsey, Jean-Philippe Weber, Philip R. Taylor, Hormuzd Katki, Steven D. Mark, You-Lin Qiao
Journal: JNCI Journal of the National Cancer Institute (2006)

1,1,1-Trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) exposure has been demonstrated to cause liver tumors in laboratory rodents. DDT's persistent metabolite and environmental degradation product, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), has also been associated with liver tumors in laboratory animals. Whether DDT and DDE are associated with hepatocarcinogenesis in humans is not clear.We carried out a nested case-control study among the participants of the Nutritional Intervention Trials in Linxian, China. The case group included 168 individuals who developed liver cancer during the trials, and the control group included 385 individuals frequency-matched on age and sex who were alive and well at the end of the study. Serum concentrations of DDT and DDE were measured by gas chromatography-mass spectrometry. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable analysis.In multivariable-adjusted models, the risk of developing liver cancer increased with increased serum DDT concentration (OR for quintile 1 versus quintile 5 = 3.8, 95% CI = 1.7 to 8.6, P(trend) = .0024). In contrast, there was no statistically significant association between liver cancer and serum DDE concentration. The association between high serum DDT concentration and liver cancer was stronger among individuals with DDE concentrations below the median value (odds ratio for tertile 3 versus tertile 1 = 3.55, 95% CI = 1.45 to 8.74) than those with concentrations above the median (OR = 1.70, 95% CI = 0.97 to 2.98). A calculation of crude liver cancer risk found that there would be 26 liver cancers per 100 000 persons per year in the lowest quintile of DDT exposure versus 46 liver cancers per 100 000 persons per year in the highest quintile of DDT exposure.DDT may be a risk factor for liver cancer, particularly among persons with lower DDE concentrations. Risk may be particularly increased among persons exposed directly to DDT (resulting in a higher ratio of DDT to DDE) or, alternatively, risk may be associated with individual ability to metabolize DDT to DDE.
Strategies to Help a Smoker Who Is Struggling to Quit
Authors: Nancy A. Rigotti
Journal: JAMA (2012)

Tobacco use is the leading preventable cause of death worldwide. Stopping tobacco use benefits virtually every smoker. Most of the 19% of US residents who smoke want to quit and have tried to do so. Most individual quit attempts fail, but two-thirds of smokers use no treatment when trying to quit. Treating tobacco dependence is one of the most cost-effective actions in health care. With a brief intervention, physicians can prompt smokers to attempt to quit and connect them to evidence-based treatment that includes pharmacotherapy and behavioral support (ie, counseling). Physicians can link smokers to effective counseling support offered by a free national network of telephone quit lines. Smokers who use nicotine replacement therapy (NRT), bupropion, or varenicline when trying to quit double their odds of success. The most effective way to use NRT is to combine the long-acting nicotine patch with a shorter-acting product (lozenge, gum, inhaler, or nasal spray) and extend treatment beyond 12 weeks. Observational studies have not confirmed case reports of behavior changes associated with varenicline and bupropion, and these drugs' benefits outweigh potential risks. A chronic disease management model is effective for treating tobacco dependence, which deserves as high a priority in health care systems as treating other chronic diseases like diabetes and hypertension.
Polymerase chain reaction-based screening for the ceftriaxone-resistant Neisseria gonorrhoeae F89 strain
Authors: N Goire, M M Lahra, M Ohnishi, T Hogan, A E Liminios, M D Nissen, T P Sloots, D M Whiley
Journal: Eurosurveillance (2013)

Emergence and spread of Neisseria gonorrhoeae resistant to extended spectrum cephalosporins is a major problem threatening treatment of gonorrhoea and is further highlighted by the recent report of a second ceftriaxone-resistant N. gonorrhoeae strain (F89) in Europe, initially observed in France and subsequently identified in Spain. N. gonorrhoeae antimicrobial resistance (AMR) surveillance has acquired new importance and molecular tools have the potential to enhance bacterial culture-based methods. In this study, we established a polymerase chain reaction (PCR) protocol for direct detection of the F89 strain. A key component of this screening protocol was the development of a hybridisation probe-based melting curve analysis assay (mosaic501-hybPCR) to detect the presence of an A501P substitution on the N. gonorrhoeae mosaic penicillin binding protein 2 (PBP2) sequence, an important characteristic of the F89 strain. The mosaic501-hybPCR was evaluated using plasmid-derived positive controls (n=3) and characterised gonococcal (n=33) and non-gonococcal (n=58) isolates. The protocol was then applied to 159 clinical specimens from Sydney, Australia, collected during the first half of the year 2012 that were N. gonorrhoeae PCR-positive. Overall, the results indicate that the PCR-based protocol is suitable for direct detection of the N. gonorrhoeae F89 strain in non-cultured clinical samples. It therefore provides an additional tool to aid investigations into the potential spread of F89 strain throughout Europe and elsewhere.
Pathogenesis of NIDDM: A Balanced Overview
Authors: Ralph A DeFronzo, Riccardd C Bonadonna, Eleuterio Ferrannini
Journal: Diabetes Care (1992)

Non-insulin-dependent diabetes mellitus (NIDDM) results from an imbalance between insulin sensitivity and insulin secretion. Both longitudinal and cross-sectional studies have demonstrated that the earliest detectable abnormality in NIDDM is an impairment in the body's ability to respond to insulin. Because the pancreas is able to appropriately augment its secretion of insulin to offset the insulin resistance, glucose tolerance remains normal. With time, however, the β-cell fails to maintain its high rate of insulin secretion and the relative insulinopenia (i.e., relative to the degree of insulin resistance) leads to the development of impaired glucose tolerance and eventually overt diabetes mellitus. The cause of pancreatic “exhaustion” remains unknown but may be related to the effect of glucose toxicity in a genetically predisposed β-cell. Information concerning the loss of first-phase insulin secretion, altered pulsatility of insulin release, and enhanced proinsulin-insulin secretory ratio is discussed as it pertains to altered β-cell function in NIDDM. Insulin resistance in NIDDM involves both hepatic and peripheral, muscle, tissues. In the postabsorptive state hepatic glucose output is normal or increased, despite the presence of fasting hyperinsulinemia, whereas the efficiency of tissue glucose uptake is reduced. In response to both endogenously secreted or exogenously administered insulin, hepatic glucose production fails to suppress normally and muscle glucose uptake is diminished. The accelerated rate of hepatic glucose output is due entirely to augmented gluconeogenesis. In muscle many cellular defects in insulin action have been described including impaired insulin-receptor tyrosine kinase activity, diminished glucose transport, and reduced glycogen synthase and pyruvate dehydrogenase. The abnormalities account for disturbances in the two major intracellular pathways of glucose disposal, glycogen synthesis, and glucose oxidation. In the earliest stages of NIDDM, the major defect involves the inability of insulin to promote glucose uptake and storage as glycogen. Other potential mechanisms that have been put forward to explain the insulin resistance, include increased lipid oxidation, altered skeletal muscle capillary density/fiber type/blood flow, impaired insulin transport across the vascular endothelium, increased amylin, calcitonin gene-related peptide levels, and glucose toxicity.
Dietary Phylloquinone and Menaquinones Intakes and Risk of Type 2 Diabetes
Authors: Joline W.J. Beulens, Daphne L. van der A, Diederick E. Grobbee, Ivonne Sluijs, Annemieke M.W. Spijkerman, Yvonne T. van der Schouw
Journal: Diabetes Care (2010)

OBJECTIVE To investigate whether dietary phylloquinone and menaquinones intakes are related to risk of type 2 diabetes. RESEARCH DESIGN AND METHODS We used data from a prospective cohort study in 38,094 Dutch men and women, aged 20–70 years. Dietary phylloquinone and menaquinones intakes were assessed using a validated food frequency questionnaire. Diabetes case patients were ascertained mainly via self-report and verified against medical records. RESULTS During 10.3 years of follow-up, 918 incident cases of diabetes were documented. In a multivariate model adjusting for diabetes risk factors and dietary factors, phylloquinone intake tended to be associated (P = 0.08) with a reduced risk of type 2 diabetes with a hazard ratio (HR) of 0.81 (95% CI 0.66–0.99) for the highest versus the lowest quartile. For menaquinones intake, a linear, inverse association (P = 0.038) with risk of type 2 diabetes was observed with an HR of 0.93 (0.87–1.00) for each 10-μg increment in the multivariate model. CONCLUSIONS This study shows that both phylloquinone and menaquinones intakes may be associated with a reduced risk of type 2 diabetes.
In vitro killing of oral Capnocytophaga by granule fractions of human neutrophils is associated with cathepsin G activity.
Authors: K T Miyasaki, A L Bodeau
Journal: Journal of Clinical Investigation (1991)

The Capnocytophaga are inhabitants of the hypoxic human gingival crevice that are normally prevented by neutrophils from causing periodontal and systemic infection. To identify potential nonoxidative bactericidal mechanisms against Capnocytophaga within human neutrophils, gel filtration chromatography was used to fractionate neutrophil granule extracts. Seven granule fractions, designated A through G, were obtained. The Capnocytophaga were most sensitive to killing by fraction D. Fraction D exhibited substantial bactericidal activity under aerobic and anaerobic conditions. The bactericidal activity associated with ion-exchange subfractions D8-D11, which contained primarily cathepsin G as assessed by enzymatic activity, amino acid composition, and NH2-terminal sequence. Heat-inactivation, diisopropylfluorophosphate, PMSF, and N-benzyloxycarbonylglycylleucylphenylalanyl-chloromethyl ketone inhibited bactericidal activity against Capnocytophaga sputigena but not Escherichia coli. We conclude that (a) human neutrophil cathepsin G is an important antimicrobial system against the Capnocytophaga, (b) the bactericidal activity of cathepsin G against Capnocytophaga is oxygen independent, and (c) an intact enzyme active site is involved in the killing of C. sputigena but not E. coli. We suggest that human neutrophil cathepsin G is an important antimicrobial system against certain oral bacteria and that cathepsin G kills bacteria by two distinct mechanisms.
Long-term follow-up of the SBG 9401 study comparing tailored FEC-based therapy versus marrow-supported high-dose therapy
Authors: N. Wilking, E. Lidbrink, T. Wiklund, B. Erikstein, H. Lindman, P. Malmström, P. Kellokumpu-Lehtinen, N-O Bengtsson, G. Söderlund, G. Anker, E. Wist, S. Ottosson, E. Salminen, P. Ljungman, H. Holte, J. Nilsson, C. Blomqvist, J. Bergh
Journal: Annals of Oncology (2007)
Anaemia in a cardiopath: Figure 1
Authors: Gordon W Moran, Alison Brind
Journal: Gut (2012)

A 77-year-old Caucasian woman was referred for investigation of microcytic anaemia. She was known to have ischaemic heart disease and aortic valve disease. The patient complained of shortness of breath and lethargy with no other gastrointestinal specific symptoms. On examination, she had a systolic murmur in her aortic area and signs of mild heart failure with few crepitations in her chest and some lower limb oedema. Abdominal examination was normal. This woman …