tbuckley/cabot-search huggingface dataset:
A search for doxycycline-dependent mutations that increase Drosophila melanogaster life span identifies the VhaSFD, Sugar baby, filamin, fwd and Cctlgenes
Authors: Gary N Landis, Deepak Bhole, John Tower
Journal: Genome biology (2003)

A P-type transposable element called PdL has been engineered with a doxycycline-inducible promoter directed out through the 3' end of the element. Insertion of PdL near the 5' end of a gene often yields doxycycline-dependent overexpression of that gene and a mutant phenotype. This functional genomics strategy allows for efficient screening of large numbers of genes for overexpression phenotypes.PdL was mobilized to around 10,000 new locations in the Drosophila melanogaster genome and used to search for genes that would extend life span when overexpressed. Six lines were identified in which there was a 5-17% increase in life span in the presence of doxyxcycline. The mutations were molecularly characterized and in each case a gene was found to be overexpressed using northern blots. Two genes did not have previously known phenotypes and are implicated in membrane transport: VhaSFD encodes a regulatory subunit of the vacuolar ATPase proton pump (H+-ATPase), whereas Sugar baby (Sug) is related to a maltose permease from Bacillus. Three PdL mutations identified previously characterized genes: filamin encodes the homolog of an actin-polymerizing protein that interacts with presenilins. four wheel drive (fwd) encodes a phosphatidylinositol-4-kinase (PI 4-kinase) and CTP:phosphocholine cytidylyltransferase-l (Cctl) encodes the rate-limiting enzyme in phosphatidylcholine synthesis. Finally, an apparently novel gene (Red herring, Rdh) was found in the first intron of the encore gene.Screening for conditional mutations that increase Drosophila life span has identified genes implicated in membrane transport, phospholipid metabolism and signaling, and actin cytoskeleton organization.
A specific antibody response to HCV E2 elicited in mice by intramuscular inoculation of plasmid DNA containing coding sequences for E2
Authors: V Tedeschi, T Akatsuka, J W Shih, M Battegay, S M Feinstone
Journal: Hepatology (1997)

ABSTRACT As the chimpanzee, the only reliable animal model for hepatitis C virus (HCV) infection, is impractical for early stage testing of HCV vaccine candidates, we have evaluated the immune response in mice to an experimental plasmid based HCV vaccine. We used this system because DNA vaccines can be rapidly constructed without the necessity of large scale protein production and purification. In this preliminary study we tested the immune response in mice to HCV envelope glycoprotein, E2, induced by a eukaryotic expression plasmid. Protein expression was monitored by immunofluorescence in transfected tissue culture cells. Each mouse was inoculated intramuscular with 100 microg plasmid DNA and some mice were boosted after 5 weeks. Among 12 BALB/C mice inoculated, 10 developed antibody to E2 by the second week. The antibody levels increased steadily before reaching a plateau in mice receiving the booster, but in the nonboosted mice the antibody declined over time. The serum from one mouse was tested against a series of overlapping peptides covering most of E2. This serum contained antibodies recognizing two distinct epitopes beginning at amino acid 57 and amino acid 113 but no antibody was directed against peptides representing the hypervariable region of E2, antibody to which is thought to be important in HCV neutralization. We have shown that the use of plasmid based vaccines can induce a specific immune response in mice against HCV antigens. This system should be useful as the first step in vaccine development.
Genetic Determinants and Epidemiology of Cystic Fibrosis–Related Diabetes
Authors: Amanda I. Adler, Brian S.F. Shine, Parinya Chamnan, Charles S. Haworth, Diana Bilton
Journal: Diabetes Care (2008)

Longer survival of patients with cystic fibrosis has increased the occurrence of cystic fibrosis-related diabetes (CFRD). In this study we documented the incidence of CFRD and evaluated the association between mutations responsible for cystic fibrosis and incident CFRD, while identifying potential risk factors.This was a population-based longitudinal study of 50 cystic fibrosis speciality clinics in the U.K. Subjects included 8,029 individuals aged 0-64 years enrolled in the U.K. Cystic Fibrosis Registry during 1996-2005. Of these, 5,196 with data and without diabetes were included in analyses of incidence, and 3,275 with complete data were included in analyses of risk factors. Diabetes was defined by physician diagnosis, oral glucose tolerance testing, or treatment with hypoglycemic drugs.A total of 526 individuals developed CFRD over 15,010 person-years. The annual incidence was 3.5%. The incidence was higher in female patients and in patients with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene in classes I and II. In a multivariate model of 377 cases of 3,275 patients, CFTR class (relative risk 1.70 [95% CI 1.16-2.49], class I or II versus others), increasing age, female sex, worse pulmonary function, liver dysfunction, pancreatic insufficiency, and corticosteroid use were independently associated with incident diabetes.The incidence of CFRD is high in Britain. CFTR class I and II mutations increase the risk of diabetes independent of other risk factors including pancreatic exocrine dysfunction.
Circadian rhythm in serum parathyroid hormone concentration in human subjects: correlation with serum calcium, phosphate, albumin, and growth hormone levels
Authors: William Jubiz, Janet M. Canterbury, Eric Reiss, Frank H. Tyler
Journal: Journal of Clinical Investigation (1972)

A circadian variation in serum calcium, albumin and PTH concentration in normal subjects has been demonstrated. The levels of the three blood constituents were remarkably constant during the day, but striking night and early morning changes occurred. Serum calcium levels were highest at 8:00 p.m. and reached a nadir between 2:00 and 4:00 a.m. Serum albumin levels were parallel to those of serum calcium. PTH levels began to rise after 8:00 p.m., reached the highest levels between 2:00 and 4:00 a.m., and fell to baseline values by 8:00 a.m. The nocturnal fall in serum calcium levels appears to be secondary to dilution of serum proteins by increasing blood volume. The nocturnal rise in PTH levels appears to be independent of serum calcium levels within the normal range but it can be abolished by induced hypercalcemia. Serum phosphate levels were lowest between 8:00 a.m. and 10:00 a.m. and highest between 2:00 a.m. and 4:00 a.m. The data presented suggest that circadian changes in serum phosphate levels are not mediated in toto by parathyroid hormone but they are exaggerated when the secretion of this hormone is inhibited. They are independent of growth hormone levels and activity but they are greatly modified during a prolonged fast.
Alkaline Reflux Gastritis and Esophagitis
Authors: B J Nath, A L Warshaw
Journal: Annual Review of Medicine (1984)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
THE RENAL LESION ASSOCIATED WITH HEMOGLOBINEMIA
Authors: John R. Jaenike
Journal: The Journal of Experimental Medicine (1966)

A method is presented for the production of a reproducible and reversible renal lesion in the rat by the intravenous injection of a relatively small amount of homologous hemoglobin (40 mg/100 g body weight). Production of the lesion is dependent on prior water deprivation and its severity is related to the degree of dehydration. Ether anesthesia, at the time of hemoglobin injection, predisposes to a severe and reproducible functional defect in the dehydrated rat. In contrast, injection of hemoglobin during pentobarbital anesthesia results in a significant lesion only sporadically. The functional evolution of the lesion has been characterized by inulin clearance measurements. Functional impairment occurs abruptly, within 1 hr after hemoglobin injection, and persists unchanged over the ensuing several hours. Some increase in inulin clearance rate is usually observed at 24 hr after injection, but severe functional impairment persists. Between 24 and 72 hr, a considerable increase in inulin clearance rate occurs, so that only moderate restriction of excretory function is present at the latter time. A further moderate increase in inulin clearance rate is apparent at 7 days after hemoglobin injection, but some reduction in function. persisted in all rats studied at this time. Hemoglobinuria is slight or inapparent in animals manifesting the most marked depression of excretory function, indicating that a severe renal lesion may exist in the absence of visible urinary pigment. Hemoglobinemia is evanescent at the dosage used in this study. These observations suggest that clinical acute renal failure secondary to hemoglobinemia may readily go unrecognized and that this may be a more frequent association than is now appreciated.
Impacts of biological invasions: what's what and the way forward
Authors: Daniel Simberloff, Jean-Louis Martin, Piero Genovesi, Virginie Maris, David A. Wardle, James Aronson, Franck Courchamp, Bella Galil, Emili García-Berthou, Michel Pascal, Petr Pyšek, Ronaldo Sousa, Eric Tabacchi, Montserrat Vilà
Journal: Trends in Ecology & Evolution (2012)
Reliable change assessment with practice effects in sport concussion research: a comment on Hinton-Bayre
Authors: G H Maassen, E R Bossema, N Brand
Journal: British Journal of Sports Medicine (2006)

In his comments on our previous article, Hinton-Bayre advocates the use of the regression based approach in most cases of determining reliable change. This article comments on Hinton-Bayre’s argument, discusses cases where the regression method might not be the preferred method, and presents adjustments that make the method more generally preferable.
Generalized Resistance to Thymic Deletion in the NOD Mouse
Authors: Adrian Liston, Sylvie Lesage, Daniel H.D. Gray, Lorraine A. O'Reilly, Andreas Strasser, Aude M. Fahrer, Richard L. Boyd, Judith Wilson, Alan G. Baxter, Elena M. Gallo, Gerald R. Crabtree, Kaiman Peng, Susan R. Wilson, Christopher C. Goodnow
Journal: Immunity (2004)
Outcomes of hospitalization in pregnant women with CNS neoplasms: a population-based study
Authors: A. R. Terry, F. G. Barker, L. Leffert, B. T. Bateman, I. Souter, S. R. Plotkin
Journal: Neuro-Oncology (2012)

Managing a CNS neoplasm during pregnancy presents complex challenges, and population-based studies are lacking. We designed a retrospective cohort study using the Nationwide Inpatient Sample (NIS) to investigate pregnancy outcomes in women with CNS neoplasms. We constructed a logistic regression model for maternal mortality, preterm labor, intrauterine growth restriction (IUGR), and Caesarean delivery, controlling for age, comorbidities, and demographic characteristics. We identified 379 malignant brain tumors, 437 benign brain tumors, and 44 spine tumors among 19 million pregnancy-related admissions from 1988 through 2009. Malignant brain tumors were associated with maternal mortality (odds ratio [OR], 143), preterm labor (OR, 3.4), and IUGR (OR, 2.9). Benign brain tumors were associated with preterm labor (OR, 2.3). A diagnosis of hyperemesis gravidarum was more common in malignant (OR, 2.2) and benign (OR, 2.8) brain tumors. Compared with the general population, Caesarean delivery was more frequent for malignant (OR, 6.4) and benign (OR, 2.8) brain tumors and spine tumors (OR, 3.9). Admission without delivery was more common for malignant (OR, 8.6) and benign (OR, 4.3) brain tumors and spine tumors (OR, 3.8; P < .05 for all outcomes). Thirty-three percent of all hospitalizations involved neurosurgical procedures, but pregnancy complications were not significantly more likely to occur in surgical patients. In conclusion, malignant brain tumors were associated with adverse pregnancy outcomes, and CNS neoplasms were associated with higher rates of Caesarean delivery. Additional research is needed to improve understanding of obstetric risk in these patients and to assist with treatment, counseling, and monitoring during delivery.
Controversies in the Management of Clinical Stage I Testis Cancer
Authors: Ronald de Wit, Karim Fizazi
Journal: Journal of Clinical Oncology (2006)

During the last two decades, definitive primary treatments and surveillance with definitive treatment deferred until relapse have demonstrated 98% to 99% cure rates in patients with stage I testis cancer, and these options have obtained firm positions in standard management. The development of optimal management strategies in various countries were at least partly guided by available surgical expertise in retroperitoneal lymph node dissection in the United States, and easy access to reference hospitals in densely populated countries in Western Europe that facilitated close surveillance programs; hence, treatment preferences differ on the two sides of the Atlantic. The success of both approaches is highly dependent on the skills of the practitioner, particularly of surgery and of scrutinized surveillance. As a result, local expertise and familiarity with a chosen modality has strengthened over the years, and investigators have been reluctant to embark on randomized trials designed to compare one modality with another. Such expertise with one particular technique, with the other approach being less familiar territory, has created controversy, because both physicians and patients seek evidence-based data coming from randomized clinical trials on which to make management decisions. Moreover, the reduced risk of relapse resulting from the use of radiotherapy or carboplatin in stage I seminoma and of cisplatin-based chemotherapy in stage I nonseminoma must be balanced against the potential long-term adverse effects in this population of patients with a normal life expectancy. The purpose of this review is to present the currently available data and discuss the merits and the disadvantages of the various approaches, yielding to the possible conclusion that all options appear to be equal in terms of efficacy, but that modality-associated adverse effects differ.
Performance vigilance task and sleepiness in patients with sleep-disordered breathing
Authors: E. Sforza, J. Haba-Rubio, F. De Bilbao, T. Rochat, V. Ibanez
Journal: European Respiratory Journal (2004)

Altered vigilance performance has been documented in patients with sleep-related breathing disorders (SRBDs). Sleep fragmentation, sleepiness, respiratory disturbances and nocturnal hypoxaemia have been suggested as the pathogenesis of these deficits, yet it remains difficult to find a good correlation between performance deficits and the above factors. In the present study, which performance measure better characterised SRBD patients and the main factors implicated in these disturbances were examined. The study group consisted of 152 patients and 45 controls, all examined using a performance vigilance task and subjective sleepiness assessment. Speed and accuracy in the psychomotor vigilance task (PVT) were measured in patients and controls. Objective daytime sleepiness was assessed in the patient group using the maintenance of wakefulness test. In comparison with controls, PVT accuracy rather than speed seems to be affected in SRBD patients, with lapses and false responses significantly greater in patients with more severe objective sleepiness and higher apnoea/hypopnoea index. Although slowing and increased variability in reaction time were associated with shorter sleep latency in the maintenance of wakefulness test, subjective sleepiness, sleep fragmentation, nocturnal hypoxaemia and apnoea/hypopnoea index influenced mainly PVT accuracy. It is concluded that vigilance impairment, sleep fragmentation and severity of disease may partially and differentially contribute to the diurnal performance consequences found in sleep-related breathing disorders. Since the psychomotor vigilance task worsening is more marked in accuracy that in speed, measurement of lapses and false responses would better characterise the degree of diurnal impairment in these patients.
Neutrophil Serine Proteases Promote IL-1β Generation and Injury in Necrotizing Crescentic Glomerulonephritis
Authors: Adrian Schreiber, Christine T.N. Pham, Ying Hu, Wolfgang Schneider, Friedrich C. Luft, Ralph Kettritz
Journal: Journal of the American Society of Nephrology (2012)

The pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated necrotizing crescentic GN (NCGN) is incompletely understood. Dipeptidyl peptidase I (DPPI) is a cysteine protease required for the activation of neutrophil serine proteases (NSPs) cathepsin G, neutrophil elastase, and proteinase 3, which are enzymes that modulate inflammation. We used a mouse model of anti-myeloperoxidase (MPO) antibody-induced NCGN to determine whether active NSPs contribute to its pathogenesis. MPO-deficient animals immunized with murine MPO, irradiated, and transplanted with wild-type bone marrow developed NCGN. In contrast, transplantation with bone marrow that lacked DPPI or lacked both neutrophil elastase and proteinase 3 protected mice from NCGN induced by anti-MPO antibody. The kidneys of mice reconstituted with DPPI-deficient bone marrow generated significantly less IL-1β than did those of mice reconstituted with wild-type bone marrow; similarly, in vitro, DPPI-deficient monocytes produced significantly less IL-1β in response to anti-MPO antibody than did wild-type monocytes. This reduction in IL-1β was NSP dependent; exogenous addition of PR3 restored IL-β production in DPPI-deficient monocytes. Last, the IL-1 receptor antagonist anakinra protected animals against anti-MPO antibody-induced NCGN (16.7%±6.0% versus 2.4%±1.7% crescents), suggesting that IL-1β is a critical inflammatory mediator in this model. These data suggest that the development of anti-MPO antibody-induced NCGN requires NSP-dependent IL-1β generation and that these processes may provide therapeutic targets for ANCA-mediated diseases in humans.
CTGF Mediates TGF-β–Induced Fibronectin Matrix Deposition by Upregulating Active α5β1 Integrin in Human Mesangial Cells
Authors: Benjamin S. Weston, Nadia Abdel Wahab, Roger M. Mason
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Excessive deposition of fibronectin in the glomerular mesangium in diabetic nephropathy (DN) is partly due to the induction of transforming growth factor-β (TGF-β) by high glucose. TGF-β induces its downstream mediator connective tissue growth factor (CTGF), which stimulates fibronectin matrix synthesis, a process that requires the presence of α5β1 integrin. Although TGF-β has been shown to upregulate α5β1 integrin expression in human mesangial cells (HMC), little is known about the effect of CTGF on levels of this receptor. This study tested whether CTGF modulates α5β1 expression by HMC in culture and whether changes induced by TGF-β are mediated through the induction of CTGF. FACS analysis showed that both TGF-β and CTGF significantly increased cell-surface α5β1 levels compared with basal conditions. RT-PCR indicated that the changes were at the level of transcription. Treatment of cells with TGF-β and antisense CTGF oligonucleotides significantly reduced the TGF-β–induced increases in α5β1 levels. CTGF and TGF-β also significantly increased levels of ligand-occupied cell-surface β1 integrins and cell adhesion to fibronectin, the main α5β1 substrate. Antisense CTGF significantly reduced the number of adherent cells from TGF-β–stimulated cultures. Finally, α5β1 blocking antibodies inhibited HMC fibronectin matrix deposition, confirming the importance of this receptor for this process. Taken together, these data provide evidence that CTGF controls α5β1 expression by HMC in vitro. Alterations in α5β1 levels induced by TGF-β are mediated at least in part through the induction of CTGF, and specific targeting of either α5β1 or CTGF could be useful in controlling excessive fibronectin matrix production in DN. E-mail [email protected]
Progressive Multifocal Leukoencephalopathy in Patients on Immunomodulatory Therapies
Authors: Eugene O. Major
Journal: Annual Review of Medicine (2009)

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the white matter of the human brain caused by lytic infection of oligodendrocytes with the human polyomavirus JCV. Although the majority of PML cases occur in severely immune-suppressed individuals, with HIV-1 infection as the predominant factor, PML has been increasingly diagnosed in patients treated with biological therapies such as monoclonal antibodies that modulate immune system functions. Monoclonal antibodies that target the cell adhesion molecules VLA-4 (natalizumab; Tysabri for multiple sclerosis and Crohn's disease) or LFA-1 (efalizumab; Raptiva for severe forms of plaque psoriasis) to prevent extravasation of inflammatory T cells into tissues, or target the cell surface marker CD20 (rituximab; Rituxan for hematologic malignancies and rheumatoid arthritis) to deplete peripheral circulating B cells, have all been associated with PML. The link between the effects of these therapies on the immune system and the occurrence of PML has prompted investigations on JCV sites of latency in the bone marrow, the migration of bone marrow derived cells into the circulation, and intracellular virus entry into the brain.
Value of smear and PCR in bronchoalveolar lavage fluid in culture positive pulmonary tuberculosis
Authors: C. Tueller, P. N. Chhajed, C. Buitrago-Tellez, R. Frei, M. Frey, M. Tamm
Journal: European Respiratory Journal (2005)

At present, further investigations are needed in patients with suspected pulmonary tuberculosis (TB) and either negative sputum smear or without sputum. The aim of the present study was to analyse the yield of bronchoalveolar lavage fluid (BALF) smear and PCR in patients with confirmed pulmonary TB. Patients with a positive culture for Mycobacterium tuberculosis complex in sputum or BALF were analysed over 5 yrs. In total, 90 out of 230 (39%) patients with culture-positive pulmonary TB had a positive sputum smear, and 120 patients underwent bronchoscopy. BALF smear was positive in 56 (47%), BALF PCR in 93 (78%) patients, and BALF smear and/or PCR was positive in 83%. In total, 71 patients who underwent bronchoscopy and had complete clinical records were further analysed. BALF (smear or Mycobacterium tuberculosis complex-PCR) allowed a rapid diagnosis in 10 (59%) out of 17 patients who had a negative sputum smear, and 49 (91%) out of 54 patients without sputum production. Of these 71 patients, 12 (17%) were only culture positive. Rapid diagnosis of pulmonary TB by smear and/or PCR was made in 190 out of 210 patients (90%) in sputum or BALF. In conclusion, combined use of bronchoalveolar lavage fluid smear and Mycobacterium tuberculosis complex-PCR has a good diagnostic yield in patients with sputum smear-negative tuberculosis or without sputum production.