tbuckley/cabot-search huggingface dataset:
Identification of rab12 as a Secretory Granule Associated Small GTP-Binding Protein in Atrial Myocytes
Authors: Hiroshi Iida, Luming Wang, Kiyomasa Nishii, Akiko Ookuma, Yosaburo Shibata
Journal: Circulation Research (1996)

A subfamily of small GTP-binding proteins, rab, has been shown to be involved in regulation of vesicular traffic in eukaryotic cells. The goal of this study was to identify the rab proteins associated with atrial secretory granules. A [32P]GTP-overlay assay showed the presence of multiple small GTP-binding proteins on the atrial granules. By biochemical analysis, we have demonstrated that one of the small GTP-binding proteins associated with the atrial granules is a rab12 protein (rab12p), one of the rab proteins that are most closely related to a Sec4 protein of yeast. Association of rab12p with the atrial granules was confirmed by immunogold electron microscopy. Immunoprecipitation followed by immunoblot analysis with anti-rab12 antibody showed that in addition to atria, rab12p was expressed in multiple other organs and cell lines. These results suggest that rab12p may function in vesicular traffic in multiple diverse types of cells.
The effect of cigarette smoking on the bone marrow.
Authors: T Terashima, B Wiggs, D English, J C Hogg, S F van Eeden
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Chronic cigarette smoking produces a 20 to 25% increase in the number of peripheral blood leukocytes, and there is increasing evidence that these leukocytes are activated in the lung by the inhalation of cigarette smoke. The present study was designed to measure the effect of cigarette smoke inhalation on the rate of production and release of polymorphonuclear leukocytes (PMN) from the bone marrow into the peripheral blood. The thymidine analogue 5'-bromo-2'-deoxyuridine (BrdU) was used to pulse-label the dividing cells in the marrow of rabbits, measure their appearance in the peripheral blood, and calculate the time that PMN spend in the mitotic and postmitotic pools of the bone marrow. Comparison of animals exposed to 2 wk of cigarette smoke (n = 8) with sham-exposed controls (n = 9) showed that smoking decreased the mean transit time of PMNBrdU through the bone marrow from 97.3 +/- 3.0 h to 89.6 +/- 5.8 h (p < 0.001) by reducing the transit time of PMN in the postmitotic pool from 66.7 +/- 3.9 h to 53.7 +/- 0.7 h (p < 0.001). Both the mitotic (p < 0.05) and postmitotic (p < 0.05) pools of PMN increased in size following cigarette-smoke exposure. We conclude that chronic cigarette smoking stimulates the bone marrow, increases the size of the mitotic and postmitotic pools of PMN, and reduces the time PMN spend in the postmitotic pool in the marrow. These changes may contribute to the leukocytosis seen in cigarette smokers.
The tumor suppressor DAL-1/4.1B and protein methylation cooperate in inducing apoptosis in MCF-7 breast cancer cells
Authors: Wei Jiang, Irene F Newsham
Journal: Molecular Cancer (2006)

Abstract Background DAL-1 (Differentially Expressed in Adenocarcinoma of the Lung)/4.1B is a member of the protein 4.1 superfamily that has been shown to suppress growth in lung, breast and brain tumor cells. In the case of the caspase-3 deficient MCF-7 breast cancer cells, this growth suppression has been shown to be partially mediated by the induction of apoptosis. However the exact mechanism of action of DAL-1/4.1B is unknown. Recently, protein arginine N -methyltransferase 3 (PRMT3) was identified as a DAL-1/4.1B interacting protein. Protein arginine methyltransferases (PRMTs) posttranslationally methylate the arginine residues of proteins, a modification which has been implicated in the regulation of multiple cellular processes including nuclear-cytoplasmic transport, signal transduction, and transcription. Results To investigate the role of protein methylation in cell death induced by DAL-1/4.1B, DAL-1/4.1B-inducible MCF-7 cells were examined for apoptosis and caspase activation in the absence and presence of the protein methylation inhibitor adenosine dialdehyde (AdOX). Flow cytometry analysis revealed that apoptosis was primarily associated with the activation of caspase 8, and inhibition of this activation blocked the ability of DAL-1/4.1B to induce cell death. Conclusion These results suggest that protein methylation cooperates with DAL-1/4.1B-associated caspase 8-specific activation to induce apoptosis in breast cancer cells.
Cardiovascular Defects Associated With Abnormalities in Midline Development in the <i>Loop-tail</i> Mouse Mutant
Authors: Deborah J. Henderson, Simon J. Conway, Nicholas D. E. Greene, Dianne Gerrelli, Jennifer N. Murdoch, Robert H. Anderson, Andrew J. Copp
Journal: Circulation Research (2001)

Loop-tail (Lp) is a naturally occurring mouse mutant that develops severe neural tube defects. In this study, we describe complex cardiovascular defects in Lp homozygotes, which include double-outlet right ventricle, with obligatory perimembranous ventricular septal defects, and double-sided aortic arch, with associated abnormalities in the aortic arch arteries. Outflow tract and aortic arch defects are often related to abnormalities in the cardiac neural crest, but using molecular and anatomic markers, we show that neural crest migration is normal in Lp/Lp embryos. On the other hand, the heart fails to loop normally in Lp/Lp embryos, in association with incomplete axial rotation and reduced cervical flexion. As a consequence, the ventricular loop is shifted posteromedially relative to its position in wild-type embryos. This suggests that the observed cardiac alignment defects in the Lp mutant may be secondary to failure of neural tube closure and incomplete axial rotation. Double-sided aortic arch is a rare finding among mouse models. In humans, it is usually an isolated malformation, only rarely occurring in combination with other cardiac defects. We suggest that the double-sided arch arises as a primary defect in the Lp mutant, unrelated to the alignment defects, perhaps reflecting a role for the (as-yet-unknown) Lp gene in maintenance/regression of the aortic arch system.
The quality of quality of life
Authors: E J IRVINE
Journal: Gut (1999)

See article on page 527 

Functional bowel disorders are highly prevalent in the general population. In the US Householder Survey about 70% of respondents had at least one functional bowel disorder, 9.4% had irritable bowel syndrome (IBS) and 2.9% had functional dyspepsia.1 These disorders often have significant symptom overlap making them difficult to distinguish.2 3 In this issue (see page 527), Chassany et al describe the initial development, preliminary psychometric testing and cross-cultural assessment of a multi-item disease specific health related quality of life (HRQOL) instrument for use in multinational clinical trials of IBS or functional dyspepsia. If only an efficacious therapy could be found!

Health related quality of life assessment is becoming increasingly recognised as an important outcome and predictor for patients with chronic diseases. HRQOL is generally assessed by quantitative questionnaires completed by patients themselves which assess physical and psychosocial attitudes and function. The three kinds of HRQOL measures used in research and practice include global assessments, generic instruments and disease specific instruments.4 5The global assessment, usually a graded summary such as good, fair or poor or a 10 cm visual analog scale, may help to predict a relation between simple parameters, like disease severity and function, but is often inadequate for more sophisticated hypothesis testing. Generic instruments are multi-item problem lists that are meant to be independent of sex, age and disease and are applied to compare …
THE INFLUENCE OF DIET ON IRON ABSORPTION
Authors: Thomas D. Kinney, D. Mark Hegsted, Clement A. Finch
Journal: The Journal of Experimental Medicine (1949)

Rats placed on a corn grit diet and added iron absorbed large amounts of iron in contrast to control groups. The histological picture was that of progressive hemosiderosis of the hepatic parenchyma and of the reticuloendothelial system. On chemical analysis, the iron content of the liver was found to be greatly increased. This supports the concept that the liver represents the chief storage organ for iron so absorbed. These data indicate that a normal block for iron absorption may be overcome under certain circumstances.
Detecting recombination from gene trees
Authors: J. Maynard Smith, N. H. Smith
Journal: Molecular Biology and Evolution (1998)

In this article, a method is proposed for detecting recombination in the sequences of a gene from a set of closely related organisms. The method, the Homoplasy Test, is appropriate when the sequences are rather similar, differing by 1%-5% of nucleotides. It is effective in detecting relatively frequent recombination between a set of rather similar strains, in contrast to previous methods which detect rare or unique transfers between more distant strains. It is based on the fact that, if there is no recombination and if no repeated mutations have occurred (homoplasy), then the number of polymorphic sites, v, is equal to the number of steps, t, in a most-parsimonious tree. If the number of "apparent homoplasies" in the most-parsimonious tree, h = t-v, is greater than zero, then either homoplasies have occurred by mutation or there has been recombination. An estimate of the distribution of h expected on the null hypothesis of no recombination depends on Se, the "effective site number," defined as follows: if ps is the probability that two independent substitutions in the gene occur at the same site, then Se = 1/ps. Se can be estimated if a suitable outgroup is available. The Homoplasy Test is applied to three bacterial genes and to simulated gene trees with varying amounts of recombination. Methods of estimating the rate, as opposed to the occurrence, of recombination are discussed.
Severe bereavement stress during the prenatal and childhood periods and risk of psychosis in later life: population based cohort study
Authors: K. M. Abel, H. P. Heuvelman, L. Jorgensen, C. Magnusson, S. Wicks, E. Susser, J. Hallkvist, C. Dalman
Journal: BMJ (2014)

<b>Objective</b> To examine the risk of psychosis associated with severe bereavement stress during the antenatal and postnatal period, between conception to adolescence, and with different causes of death. <b>Design</b> Population based cohort study. <b>Setting</b> Swedish national registers including births between 1973 and 1985 and followed-up to 2006. <b>Participants</b> In a cohort of 1 045 336 Swedish births (1973-85), offspring born to mothers exposed to severe maternal bereavement stress six months before conception or during pregnancy, or exposed to loss of a close family member subsequently from birth to 13 years of age were followed until 2006. Admissions were identified by linkage to national patient registers. <b>Main outcome measures</b> Crude and adjusted odds ratios for all psychosis, non-affective psychosis, and affective psychosis. <b>Results</b> Maternal bereavement stress occurring preconception or during the prenatal period was not associated with a significant excess risk of psychosis in offspring (adjusted odds ratio, preconception 1.24, 95% confidence interval 0.96 to 1.62; first trimester 0.95, 0.58 to1.56; second trimester 0.79, 0.46 to 1.33; third trimester 1.14, 0.78 to 1.66). Risks increased modestly after exposure to the loss of a close family member from birth to adolescence for all psychoses (adjusted odds ratio 1.17, 1.04 to 1.32). The pattern of risk was generally similar for non-affective and affective psychosis. Thus estimates were higher after death in the nuclear compared with extended family but remained non-significant for prenatal exposure; the earlier the exposure to death in the nuclear family occurred in childhood (all psychoses: adjusted odds ratio, birth to 2.9 years 1.84, 1.41 to 2.41; 3-6.9 years 1.47, 1.16 to 1.85; 7-12.9 years 1.32, 1.10 to 1.58) and after suicide. Following suicide, risks were especially higher for affective psychosis (birth to 2.9 years 3.33, 2.00 to 5.56; 6.9 years 1.84, 1.04 to 3.25; 7-12.9 years 2.68, 1.84 to 3.92). Adjustment for key confounders attenuated but did not explain associations with risk. <b>Conclusions</b> Postnatal but not prenatal bereavement stress in mothers is associated with an increased risk of psychosis in offspring. Risks are especially high for affective psychosis after suicide in the nuclear family, an effect that is not explained by family psychiatric history. Future studies are needed to understand possible sources of risk and resilience so that structures can be put in place to support vulnerable children and their families.
Determinants of human adipose tissue lipoprotein lipase. Effect of diabetes and obesity on basal- and diet-induced activity.
Authors: O J Pykälistö, P H Smith, J D Brunzell
Journal: Journal of Clinical Investigation (1975)

The role of insulin in the regulation of human adipose tissue lipoprotein lipase was evaluated. Adipose tissue heparin-releasable lipoprotein lipase (thought to be related to peripheral clearance of plasma triglycerides) was low in insulin-deficient, untreated hyperglycemic diabetic subjects (P less than 0.001) and treatment of hyperglycemia returned the activity to normal. In chronic hyperinsulinism, represented by obesity, heparin-releasable activity among control subjects was correlated to percent of ideal body weight (r=0.53, P less than 0.05) and to fat cell size (r=0.61, P less than 0.02). Acetone-ether powder lipoprotein lipase activity (presumed to reflect total tissue enzyme) was also related to percent of ideal body weight (r=0.76, P less than 0.001 for controls; r=0.67, P less than 0.05 for diabetics) and to fat cell size (r=0.71, P less than 0.01 for controls; r=0.85, P less than 0.01 for diabetics. Postprandial-stimulated insulin secretion was related to diet-induced changes in lipoprotein lipase in control subjects; both were dependent upon the amount of dietary carbohydrate. In contrast, the diabetic patients with low insulin responses, failed to increase lipoprotein lipase activity with feeding. The changes in heparin-releasable (r=0.66, P less than 0.01) and acetone-ether powder (r=0.69, P less than 0.01) activity during feeding were related to the percent increase in plasma insulin. Thus, insulin appears to be important in the regulation of human adipose tissue lipoprotein lipase activity. Elevated insulin levels in obesity and increased insulin secretion after eating were associated with increased lipoprotein lipase activity. Defects in insulin secretion, both in postabsorptive and postprandial states, are associated with low adipose tissue lipoprotein lipase and may lead to hypertriglyceridemia in diabetic man.
Absence of germline mono-allelic promoter hypermethylation of the CDH1 gene in gastric cancer patients
Authors: Hidetaka Yamada, Kazuya Shinmura, Masanori Goto, Moriya Iwaizumi, Hiroyuki Konno, Hideki Kataoka, Masami Yamada, Takachika Ozawa, Toshihiro Tsuneyoshi, Fumihiko Tanioka, Haruhiko Sugimura
Journal: Molecular Cancer (2009)

Abstract Background Germline mono-allelic promoter hypermethylation of the MLH1 or MSH2 gene in families with hereditary nonpolyposis colorectal cancer has recently been reported. The purpose of this study was to evaluate if germline promoter hypermethylation of the tumor suppressor gene CDH1 ( E-cadherin ) might cause predisposition to gastric cancer. Methods We prepared two groups of samples, a group of blood samples from 22 patients with familial gastric cancer or early-onset gastric cancer selected from among 39 patients, and a group of non-cancerous gastric tissue samples from 18 patients with sporadic gastric cancer showing loss of CDH1 expression selected from among 159 patients. We then investigated the allele-specific methylation status of the CDH1 promoter by bisulfite sequencing of multiple clones. Results Although there was a difference between the methylation level of the two alleles in some samples, there was no mono-allelic promoter hypermethylation in any of the samples. Conclusion These results suggest that germline mono-allelic hypermethylation of the CDH1 promoter is not a major predisposing factor for gastric cancer.
Overexpression of Jab1 in Hepatocellular Carcinoma and Its Inhibition by Peroxisome Proliferator-Activated Receptorγ Ligands <i>In vitro</i> and <i>In vivo</i>
Authors: Ming-Chuan Hsu, Chao-Cheng Huang, Hui-Chiu Chang, Tsung-Hui Hu, Wen-Chun Hung
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Jun activation domain-binding protein 1 (Jab1) is the fifth subunit of the COP9 signalosome and exhibits oncogenic activity. We investigated Jab1 expression in hepatocellular carcinoma (HCC) tissues and cell lines and tested the effect of peroxisome proliferator-activated receptor γ (PPARγ) ligands on Jab1 expression. Experimental Design: Jab1 expression in HCC tissues and cell lines was studied by real-time reverse transcription-PCR, immunohistochemical staining, and Western blotting. Promoter activity and chromatin immunoprecipitation assays were done to address the inhibition of Jab1 promoter by PPARγ ligands. RNA interference was used to clarify PPARγ ligand-induced inhibition of Jab1. Anticancer and Jab1-suppressing activity of PPARγ ligands was tested in nude mice. Results: Jab1 was detected in the nucleus and cytoplasm of HCC tissues and 37% (37 of 99) of tissues exhibited Jab1 overexpression. Jab1 expression correlated with sex and hepatitis C virus infection, whereas it was negatively associated with hepatitis B virus infection. Additionally, Jab1 was overexpressed in HCC cell lines. PPARγ ligands troglitazone and rosiglitazone down-regulated Jab1 expression in HCC cells, and troglitazone directly suppressed Jab1 promoter activity by inhibiting Sp1- and Tcf4-mediated transcription. This suppression was mediated via both PPARγ-dependent and PPARγ-independent mechanisms. Ectopic expression of Jab1 counteracted troglitazone-induced growth inhibition. Animal studies verified that intratumor or i.p. injection of troglitazone attenuated HCC growth and reduced Jab1 expression in tumor tissues. Conclusions: Our results indicate that Jab1 is overexpressed in HCC and PPARγ ligands may suppress Jab1 to inhibit the proliferation of HCC cells.
A new gene deletion involving the α2‐, α1 ‐, and 81‐globin genes in a black family with Hb H disease
Authors: Y. J. Fei, J. C. Liu, E. L. D. Walker, T. H. J. Huisman
Journal: American Journal of Hematology (1992)

Abstract A new deletion of ∽ 8.5 kb that includes the α2‐, α1‐, and θ1‐globin genes was detected in a father and newborn son of a black family from Georgia. In the newborn baby the chromosome with the deletion occurred together with a rightward (‐α 3.7 ) deletion chromosome. The resulting Hb H disease was detected at birth by the high level of Hb Bart's; a moderate anemia with severe microcytosis and hypochromia was present at the age of 5 months. A review of cord blood testing results for a period of over 20 years, involving at least 200,000 black newborns, indicated that this baby was the first with a level of Hb Bart's in excess of 10‐15%; this underscores the rarity of α‐thalassemia‐1 in this population. © 1992 Wiley‐Liss, Inc.
CD73 is involved in lymphocyte binding to the endothelium: characterization of lymphocyte-vascular adhesion protein 2 identifies it as CD73.
Authors: L Airas, J Hellman, M Salmi, P Bono, T Puurunen, D J Smith, S Jalkanen
Journal: The Journal of Experimental Medicine (1995)

We have recently described a monoclonal antibody (mAb) 4G4 recognizing a 70-kD molecule constitutively expressed on human endothelial cells and on subpopulations of lymphocytes. We showed that this molecule, which we named lymphocyte-vascular adhesion protein 2 (L-VAP-2), mediates lymphocyte adhesion to cultured endothelial cells. Protein sequencing of tryptic peptides from immunoaffinity-purified L-VAP-2 revealed sequence identity between L-VAP-2 and CD73 (ecto-5'-nucleotidase, E.C.3.1.3.5), and COS cells transfected with a CD73 cDNA were positively stained with the mAb 4G4, which recognizes L-VAP-2. mAb 4G4 was also able to partially inhibit the ecto-5'-nucleotidase activity of peripheral blood lymphocytes. Moreover, cross-precipitation studies performed with mAb 4G4 and a CD73 workshop mAb 1E9 showed that these two antibodies recognize the same molecule. Since the tissue distribution and biochemical characteristics of the two molecules are also similar, we conclude that L-VAP-2 and CD73 are the same glycoprotein. Adhesion experiments showed significantly increased binding of freshly isolated lymphocytes to COS cells transfected with a CD73 cDNA, as compared to mock-transfected COS cells, and binding of lymphocytes to CD73-expressing COS cells was inhibited by the presence of mAb 4G4 in the adhesion assay. CD73 is a glycosyl phosphatidylinositol-linked molecule previously shown to have a cosignalling role in T lymphocyte proliferation. Our data suggest that it also has a function in mediating lymphocyte adhesion to the endothelium.
Small airways diseases: detection and insights with computed tomography
Authors: D.M. Hansell
Journal: European Respiratory Journal (2001)

Diseases affecting the small airways are difficult to detect by traditional diagnostic tests. Widespread involvement is needed before symptoms and abnormalities on pulmonary function testing or chest radiography become apparent. Obstruction of the bronchioles may be detected indirectly by computed tomography (CT) because regional under-ventilation results in reduced perfusion which in turn is shown as a mosaic attenuation pattern of the lung parenchyma. When there is inflammation of the bronchioles with accompanying exudate, the airways may become directly visible on CT, for example in cases of diffuse panbronchiolitis. Quantification of the various morphological features of small airways disease is possible from CT images and this increased precision has aided investigations of structure/function relationships. An understanding of the pathology and microscopic distribution of disease in relation to the airways allows some prediction of the likely computed tomography appearances in this wide spectrum of conditions, and thus helps to refine the differential diagnosis.
Coronary blood flow in experimental canine left ventricular hypertrophy.
Authors: D D O'Keefe, J I Hoffman, R Cheitlin, M J O'Neill, J R Allard, E Shapkin
Journal: Circulation Research (1978)

To determine whether left ventricular hypertrophy [LVH] altered total and regional coronary blood flow, we inflated a balloon around the ascending aorta of nine dogs; six acute and six sham-operated dogs were controls. After 6 weeks, all dogs were studied with an open chest under anesthesia; the balloons were deflated. There was moderate LVH as shown by increased left ventricular weight and fiber diameter. At rest there were no major differences of coronary flow or resistance per gram of muscle. With maximal coronary vasodilation due to adenosine or carbochrome, mean coronary vascular resistance was 84% higher in LVH than in normal hearts; with isoproterenol, resistance was 54% higher in LVH. These changes were similar in right and left ventricles. Minimal coronary resistance at end diastole also was higher in LVH--64% and 94% for the two sets of vasodilators, respectively. There were no significant differences in capillary or large vessel proportional volumes in LVH and control dogs, but arterial capacity could not be estimated. The raised minimal coronary resistance suggests the possibility that, with stress, coronary flow, especially to subendocardial muscle, might be inappropriate and perhaps cause ischemic damage. However, the changes noted might have been due to coronary arterial responses to raised coronary pressures rather than to hypertrophy itself.