tbuckley/cabot-search huggingface dataset:
Pervasive and Ongoing Positive Selection in the Vomeronasal-1 Receptor (V1R) Repertoire of Mouse Lemurs
Authors: Philipp Hohenbrink, Ute Radespiel, Nicholas I. Mundy
Journal: Molecular Biology and Evolution (2012)

Chemosensory genes are frequently the target of positive selection and are often present in large gene families, but little is known about heterogeneity of selection in these cases and its relation to function. Here, we use the vomeronasal-1 receptor (V1R) repertoire of mouse lemurs (Microcebus spp.) as a model system to study patterns of selection of chemosensory genes at several different levels. Mouse lemurs are small nocturnal strepsirrhine primates and have a large (~200 loci) repertoire of V1R loci that are likely important for intraspecific pheromonal communication and interspecific interactions, for example, recognition of predator cues. We investigated signals and patterns of positive selection among the 105 identified full length V1R loci in the gray mouse lemur and within 7 V1R loci amplified across multiple mouse lemur species. Phylogenetic reconstructions of published sequences revealed at least nine monophyletic clusters of V1Rs in gray mouse lemurs that have diversified since the split between lemurs and lorisoid primates. A large majority of clusters evolved under significant positive selection. Similar results were found in V1Rs of closely related greater galagos. Comparison with function of related V1R clusters in mice suggested a potential relationship between receptor function and strength of selection. Interestingly, most codons identified as being under positive selection are located in the extracellular domains of the receptors and hence likely indicate the position of residues involved in ligand binding. Positive selection was also detected within five V1R loci (=71% of analyzed loci) sequenced from 6 to 10 mouse lemur species, indicating ongoing selection within the genus, which may be related to sexual selection and, potentially, speciation processes. Variation in strength of positive selection on V1Rs showed no simple relationship to cluster size. The diversity of V1R loci in mouse lemurs reflects their adaptive evolution and is most likely related to the fundamental relevance of olfactory communication and predator recognition in these primates. Overall, adaptive evolution is the predominant mode of evolution of V1R loci at all levels, and the substantial heterogeneity in the strength of selection may be related to receptor function.
Iron deficiency in young Bradford children from different ethnic groups.
Authors: P Ehrhardt
Journal: BMJ (1986)

Haematological parameters and iron state were studied in children admitted to hospital consecutively during a six month period. A total of 147 of 598 children (24.6%) were anaemic, with haemoglobin values below the third centile of the reference range, and 131 of 400 children (32.8%) were iron deficient, with serum ferritin concentrations less than 10 micrograms/l. Both findings were more common in children from the Asian ethnic minority. The "routine" full blood count is a useful tool for the presumptive identification of iron deficiency in childhood. Iron deficiency is deleterious to the health of young children. In view of its extent and degree--not exclusively among the Asian ethnic minority--a community based preventive programme on the lines of the Stop Rickets Campaign is recommended.
Paclitaxel Coating Reduces In-Stent Intimal Hyperplasia in Human Coronary Arteries
Authors: Myeong-Ki Hong, Gary S. Mintz, Cheol Whan Lee, Jong-Min Song, Ki-Hoon Han, Duk-Hyun Kang, Jae-Kwan Song, Jae-Joong Kim, Neil J. Weissman, Neal E. Fearnot, Seong-Wook Park, Seung-Jung Park
Journal: Circulation (2003)

The aim of this study was to use serial volumetric intravascular ultrasound (IVUS) to evaluate the effect of a paclitaxel coating on in-stent intimal hyperplasia (IH).Patients were randomized to placebo (bare metal stents) or 1 of 2 doses of paclitaxel (low dose: 1.28 microg/mm2; high dose: 3.10 microg/mm2). Complete post-stent implantation and follow-up IVUS were available in 81 patients, including 25 control patients and in 28 receiving a low-dose and 28 receiving a high dose. Volumetric analysis of the stented segment and of both reference segments was performed. Baseline stent measurements and both reference measurements were similar among the groups. With increasing doses, there was a stepwise reduction in IH accumulation within the stented segment (31+/-22 mm3 in control, 18+/-15 mm3 in low dose, and 13+/-14 mm3 in high dose, P<0.001). Post hoc analysis showed less IH accumulation when low- and high-dose patients were compared with control (P=0.009 and P<0.001, respectively), but not when low-dose patients were compared with high-dose patients (P=0.2). Focal late malapposition was seen in 1 high-dose patient. With increasing doses, there was no significant change in the reference segments.Paclitaxel-coated stents are effective in reducing in-stent neointimal tissue proliferation in humans. They are not associated with edge restenosis or significant late malapposition.
Long-term viral enhancement of lung response to Saccharopolyspora rectivirgula.
Authors: Y Cormier, G M Tremblay, M Fournier, E Israël-Assayag
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

The current study was done to look at the long-term enhancing effect of a single viral infection on repeated Saccharopolyspora rectivirgula (SR) antigenic challenges in mice and at inflammatory cytokines in this enhancement. Four groups of C57BI/6 mice were studied: Group 1 received intranasal instillations of saline, 3 days per week; Group 2, intranasal instillations of saline plus one intranasal instillation of 80 hemagglutination units (HAU) of Sendai virus after 3 wk of saline; Group 3, instillations of SR, 3 days per week; and Group 4, instillations of SR, 3 days per week, plus one instillation of Sendai virus after 3 wk of SR. Bronchoalveolar lavages (BAL) were performed 15 and 30 wk after the virus inoculation in the appropriate groups. Each time, a two- to threefold increase in BAL cell counts was obtained from virus-infected animals challenged with SR compared with animals that received the SR alone. Animals infected with virus only showed values similar to those of control animals. A higher percentage of large foamy multinucleated cells were found in the BAL from the SR+Sendai group than the SR alone group (7.92 +/- 0.730% compared with 1.8 +/- 0.296%). These cells were not seen in the other groups. BAL levels of TNF-alpha and IL-1 alpha at 15 wk were much higher in SR+Sendai-treated (1,439 +/- 268 and 96 +/- 9 pg/ml, respectively) than SR alone-treated animals (361 +/- 100 and 23 +/- 4 pg/ml). BAL fluid of control animals and Sendai alone animals contained 64 +/- 24 and 65 +/- 15 pg/ml of TNF-alpha, but no IL-1 alpha was detected.(ABSTRACT TRUNCATED AT 250 WORDS)
Review of the function of a telephone helpline in the treatment of outpatients with rheumatoid arthritis
Authors: R A Hughes
Journal: Annals of the Rheumatic Diseases (2002)

Objectives: To examine the role, acceptability, and cost effectiveness of a telephone helpline organised and run by specialist nurses in a district general hospital outpatient rheumatology department. Material and methods: Patients accessed the telephone helpline by leaving a taped message on an answer phone with a 24 hour response time. Assessment included an audit of the nature and outcome of helpline calls, patient satisfaction with the helpline, and a health economic analysis of the helpline operation. A postal questionnaire was used to assess patient satisfaction; this was sent to the 87 patients who called the helpline during one month, and overall satisfaction with the helpline was assessed. The nature and outcome of all calls was analysed retrospectively using a helpline record book for February and October of one year and February of the following year. From the results of the retrospective analysis and an estimate of the number of general practitioner consultations avoided by provision of the helpline, the cost effectiveness of the helpline was calculated. Results: Of those returning questionnaires, 61/63 (97%) were satisfied with the response time, 63/63 (100%) with the courtesy, and 60/63 (95%) felt that their questions were answered directly and to their satisfaction in 62 (98%) of cases. Had the helpline not been available, 38/63 (60%) patients would have made an appointment with their GP. When these figures were extrapolated to an annual estimation, a basic cost analysis showed that the helpline produced a cost saving to the NHS, largely as a result of GP consultations avoided. Conclusion: Clinical advice and support can be provided by a rheumatology helpline set up as an adjunct to a standard outpatient service. The results of a postal questionnaire suggested more than 95% satisfaction with all aspects of the helpline service and that 99% of callers would call the helpline again. The provision of the helpline service contributes to the quality of care provided by an outpatient department and provides benefit to the NHS.
Hemodynamic Predictors of Survival in Scleroderma-related Pulmonary Arterial Hypertension
Authors: Aránzazu Campo, Stephen C. Mathai, Jérôme Le Pavec, Ari L. Zaiman, Laura K. Hummers, Danielle Boyce, Traci Housten, Hunter C. Champion, Noah Lechtzin, Fredrick M. Wigley, Reda E. Girgis, Paul M. Hassoun
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: Pulmonary arterial hypertension (PAH) related to systemic sclerosis (SSc) has a poorer prognosis compared with other forms of PAH for reasons that remain unexplained.Objectives: To identify risk factors of mortality in a well-characterized cohort of patients with PAH related to systemic sclerosis (SSc-PAH).Methods: Seventy-six consecutive patients with SSc (64 women and 12 men; mean age 61 ± 11 yr) were diagnosed with PAH by heart catheterization in a single center, starting in January 2000, and followed over time. Kaplan-Meier estimates were calculated and mortality risk factors were analyzed.Measurements and Main Results: Forty (53%) patients were in World Health Organization functional class III or IV. Mean pulmonary artery pressure was 41 ± 11 mm Hg, pulmonary vascular resistance (PVR) was 8.6 ± 5.6 Wood units, and cardiac index was 2.4 ± 0.7 L/min/m2. Median follow-up time was 36 months, with 42 deaths observed. Survival estimates were 85%, 72%, 67%, 50%, and 36% at 1, 2, 3, 4, and 5 years, respectively. Multivariate analysis identified PVR (hazard ratio [HR], 1.10; 95% confidence interval [CI], 1.03–1.18; P < 0.01), stroke volume index (HR, 0.94; 95% CI, 0.89–0.99; P = 0.02), and pulmonary arterial capacitance (HR, 0.43; 95% CI, 0.20–0.91; P = 0.03) as strong predictors of survival. An estimated glomerular filtration rate less than 60 ml/min/1.73 m2 portended a threefold risk of mortality.Conclusions: Our results suggest that specific components of right ventricular dysfunction and renal impairment contribute to increased mortality in SSc-PAH. Understanding the mechanisms of right ventricular dysfunction in response to increased afterload should lead to improved targeted therapy in these patients.
Human CTLA4 knock-in mice unravel the quantitative link between tumor immunity and autoimmunity induced by anti–CTLA-4 antibodies
Authors: Kenneth D. Lute, Kenneth F. May, Ping Lu, Huiming Zhang, Ergun Kocak, Bedrick Mosinger, Christopher Wolford, Gary Phillips, Michael A. Caligiuri, Pan Zheng, Yang Liu
Journal: Blood (2005)
Protein Profiling in Brain Tumors Using Mass Spectrometry
Authors: Sarah A. Schwartz, Robert J. Weil, Mahlon D. Johnson, Steven A. Toms, Richard M. Caprioli
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The purpose of this research was to perform a preliminary assessment of protein patterns in primary brain tumors using a direct-tissue mass spectrometric technique to profile and map biomolecules. Experimental Design: We examined 20 prospectively collected, snap-frozen normal brain and brain tumor specimens using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS), and compared peptide and protein expression in primary brain tumor and nontumor brain tissues. Results: MS can be used to identify protein expression patterns in human brain tissue and tumor specimens. The mass spectral patterns can reliably identify glial neoplasms of similar histological grade and differentiate them from tumors of different histological grades as well as from nontumor brain tissues. Initial bioinformatics cluster analysis algorithms classified tumor and nontumor tissues into similar groups comparable with their histological grade. Conclusions: We describe a novel tool for the analysis of protein expression patterns in human glial neoplasms. Initial results demonstrate that MALDI-MS technology can significantly aid in the process of unraveling and understanding the molecular complexities of gliomas. MALDI-MS accurately and reliably identified normal and neoplastic tissues, and could be used to discriminate between tumors of increasing grades.
Forkhead Box P3-Positive Regulatory T Cells As Therapeutic Target for Breast Cancer
Authors: Gianluigi Ferretti
Journal: Journal of Clinical Oncology (2007)

TO THE EDITOR: In their article, Bates et al conclude that high numbers of forkhead box P3 (FOXP3)-positive regulatory T (Treg) cells represent an important marker for the identification of breast cancer patients at risk of late relapse. Similarly, patients with stage I non–small-cell lung cancer who have a higher proportion of tumor FOXP3-positive Treg cells relative to tumor-infiltrating T-cell lymphocytes have a significantly higher risk of recurrence. In pancreatic ductal carcinoma, a high prevalence of FOXP3-positive Treg cells seems to be a marker of poor prognosis. CD25 CD4 Treg cells, which specifically express the transcription factor FOXP3, are involved in the maintenance of immunological self-tolerance and suppressive control of aberrant immune responses. In contrast, they may impede the development of effective immunity to autologous tumor cells. As recently reported, only CCR7and L-selectin (CD62L) coexpressing cells within expanded CD4 T cells with high CD25 expression levels (CD25) maintain phenotypic and functional characteristics of Treg cells. These cells originate from CD45RA naive cells within the CD4 CD25 T-cell compartment. In particular, this subpopulation homogeneously expresses FOXP3, CD62L, CCR7, cytotoxic T lymphocyte– associated antigen-4, and maintains robust suppressive activity after expansion. In contrast, cell lines derived from CD45RA memory-type CD4 CD25 T cells show only moderate suppression and do not maintain FOXP3 expression. Although the CD4 CD25 Treg compartment in adult peripheral blood comprehends naive as well as memory cells, only the naive CD45RA subpopulation gives rise to homogeneous Treg cell lines, since memory-type Treg cells (CD45RA ) could downregulate FOXP3 expression and lose their suppressive activity. For this reason, we agree with Bates et al that FOXP3-positive Treg cells represent an important therapeutic target for breast cancer.
Induction of Renoprotective Gene Expression by Cobalt Ameliorates Ischemic Injury of the Kidney in Rats
Authors: Makiko Matsumoto, Yuichi Makino, Tetsuhiro Tanaka, Hirotoshi Tanaka, Nobuhiro Ishizaka, Eisei Noiri, Toshiro Fujita, Masaomi Nangaku
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Hypoxia in the tubulointerstitium has been thought to play pivotal roles in the pathophysiology of acute renal failure and the progression of chronic kidney disease. Pre-induction of hypoxia-inducible and renoprotective gene expression may protect subsequent ischemic injury. This study evaluated the efficacy of cobalt, which inhibits HIF-1 degradation and increases the expression level of hypoxia-related genes, in an acute ischemic tubulointerstitial injury model of rats. Ischemic renal injury was induced by 45-min clamping of renal pedicles with contralateral nephrectomy. Elevation of serum creatinine and morphologic injury after the ischemic insult was observed. Administration of cobalt chloride afforded striking functional improvement (mean ± SEM creatinine in mg/dl: Co treatment group, 2.14 ± 1.21; control, 3.69 ± 1.43; P < 0.05) associated with amelioration of tubulointerstitial damage. Cobalt treatment also reduced macrophage infiltration significantly. In the kidney of rats treated with cobalt, mRNA levels of several genes that serve for tissue protection, such as HO-1, EPO, Glut-1, and VEGF, were increased before ischemic injury. Upregulation of HO-1 by cobalt was confirmed at the protein level. Subcutaneous injection of cobalt also ameliorated ischemic injury, which was associated with upregulation of renal HIF-1α protein expression. These results suggest that protection against hypoxic tubulointerstitial injury by cobalt administration is mediated by induction of renoprotective gene expression. HIF induction is one possible and attractive explanation for the observed effects. E-mail: [email protected]
Redefinition of Myocardial Infarction
Authors: Véronique L. Roger, Jill M. Killian, Susan A. Weston, Allan S. Jaffe, Jan Kors, Paula J. Santrach, Hugh Tunstall-Pedoe, Steven J. Jacobsen
Journal: Circulation (2006)

The 2000 European Society of Cardiology/American College of Cardiology definition for myocardial infarction (MI) combines ischemic symptoms, electrocardiographic changes, and troponin rather than creatine kinase levels. The use of troponins will increase the detection of MI by a magnitude to be quantified, and the clinical acceptance of the new definition is unknown.Subjects presenting to an Olmsted County facility with a troponin T value > or = 0.03 ng/mL between November 2002 and March 2005 were prospectively classified through the use of standardized MI criteria, relying on cardiac pain, Minnesota coding of the ECG, and troponin, creatine kinase, and its MB fraction measured simultaneously. Through the use of dynamic changes in troponin, 538 MIs were identified versus 327 with creatine kinase and 427 with only the MB fraction of creatine kinase. This represents a 74% (95% confidence interval [CI], 69% to 79%) increase above the number of MIs identified with creatine kinase and a 41% (95% CI, 37% to 46%) increase above the number identified with criteria including only its MB fraction. When relying on single values of troponin, increases in the number of MIs were always large but varied widely according to the threshold used for troponin. Cases meeting only troponin-based criteria were less likely to have electrocardiographic ST-segment elevation and had better survival than those identified with previous criteria. Clinician diagnoses mentioned MI in 42% (95% CI, 34% to 49%) of cases meeting only troponin-based criteria versus 74% (95% CI, 69% to 78%) for MIs meeting the previous criteria (P < 0.001).The prospective application of the new criteria in the community results in a large increase in the number of MIs and a change in case mix. The clinical acceptance of the new criteria is incomplete, and studies that rely exclusively on dismissal diagnoses to assess MI rates may underestimate the burden of disease as presently defined.
Mutations in the Cystic Fibrosis Transmembrane Regulator Gene and<b><i>In Vivo</i></b>Transepithelial Potentials
Authors: Michael Wilschanski, Annie Dupuis, Lynda Ellis, Keith Jarvi, Julian Zielenski, Elizabeth Tullis, Sheelagh Martin, Mary Corey, Lap-Chee Tsui, Peter Durie
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Aim: To examine the relationship between cystic fibrosis transmembrane regulator gene mutations (CFTR) and in vivo transepithelial potentials.Methods: We prospectively evaluated 162 men including 31 healthy subjects, 21 obligate heterozygotes, 60 with congenital bilateral absence of the vas deferens (CBAVD) and 50 with CF by extensive CFTR genotyping, sweat chloride and nasal potential difference testing.Results: Six (10%) men with CBAVD carried no CFTR mutations, 18 (30%) carried one mutation, including the 5T variant, and 36 (60%) carried mutations on both alleles, for a significantly higher rate carrying one or more mutations than healthy controls (90% versus 19%, p < 0.001). There was an overlapping spectrum of ion channel measurements among the men with CBAVD, ranging from values in the control and obligate heterozygote range at one extreme, to values in the CF range at the other. All pancreatic-sufficient patients with CF and 34 of 36 patients with CBAVD with mutations on both alleles carried at least one mild mutation. However, the distribution of mild mutations in the two groups differed greatly. Genotyping, sweat chloride and nasal potential difference (alone or in combination) excluded CF in all CBAVD men with no mutations. CF was confirmed in 56% and 67% of CBAVD men carrying 1 and 2 CFTR mutations, respectively.Conclusion: Abnormalities of CFTR transepithelial function correlate with the number and severity of CFTR gene mutations.
BMI Cut Points to Identify At-Risk Asian Americans for Type 2 Diabetes Screening
Authors: William C. Hsu, Maria Rosario G. Araneta, Alka M. Kanaya, Jane L. Chiang, Wilfred Fujimoto
Journal: Diabetes Care (2014)

According to the U.S. Census Bureau, an Asian is a person with origins from the Far East (China, Japan, Korea, and Mongolia), Southeast Asia (Cambodia, Malaysia, the Philippine Islands, Thailand, Vietnam, Indonesia, Singapore, Laos, etc.), or the Indian subcontinent (India, Pakistan, Bangladesh, Bhutan, Sri Lanka, and Nepal); each region has several ethnicities, each with a unique culture, language, and history.In 2011, 18.2 million U.S. residents self-identified as Asian American, with more than two-thirds foreign-born (1).In 2012, Asian Americans were the nation's fastestgrowing racial or ethnic group, with a growth rate over four times that of the total U.S. population.International migration has contributed .60% of the growth rate in this population (1).Among Asian Americans, the Chinese population was the largest (4.0 million), followed by Filipinos (3.4 million), Asian Indians (3.2 million), Vietnamese (1.9 million), Koreans (1.7 million), and Japanese (1.3 million).Nearly three-fourths of all Asian Americans live in 10 statesdCalifornia, New York, Texas, New Jersey, Hawaii, Illinois, Washington, Florida, Virginia, and Pennsylvania (1).By 2060, the Asian American population is projected to more than double to 34.4 million, with its share of the U.S. population climbing from 5.1 to 8.2% in the same period (2).
Normal blood pressure in patients with insulinoma despite hyperinsulinemia and insulin resistance.
Authors: P T Sawicki, T Baba, M Berger, A Starke
Journal: Journal of the American Society of Nephrology (1992)

This article examines the relationship between blood pressure and serum insulin patients with endogenous hyperinsulinemia due to insulinomas. The hypothesis that hyperinsulinemia is an independent causal factor in the development of essential hypertension in this patient population was investigated. Inappropriately high plasma concentrations of insulin and proinsulin were found in these patients; however, their blood pressure levels did not differ from those of normal control subjects. Moreover, the surgical removal of the insulinomas did not reduce their blood pressure. Therefore, these findings argue against the hypothesis that hyperinsulinemia is an independent causal factor in the development of essential hypertension in humans.