tbuckley/cabot-search huggingface dataset:
More answers about cGMP-gated channels pose more questions
Authors: Theodore G. Wensel, Joseph K. Angleson
Journal: Behavioral and Brain Sciences (1995)

Abstract Our understanding of the molecular properties and cellular role of cGMP-gated channels in outer segments of vertebrate photo-receptors has come from over a decade of studies which have continuously altered and refined ideas about these channels. Further examination of this current view may lead to future surprises and further refine the understanding of cGMP-gated channels.
Genetic Modifiers of Systemic Lupus Erythematosus in FcγRIIB−/− Mice
Authors: Silvia Bolland, Young-Sun Yim, Katalin Tus, Edward K. Wakeland, Jeffrey V. Ravetch
Journal: The Journal of Experimental Medicine (2002)

FcγRIIB is a potent lupus susceptibility gene as demonstrated by the observation that mice deficient in this molecule develop spontaneous antinuclear antibodies (ANA) and fatal glomerulonephritis when on the C57BL/6 background. To determine the mechanisms underlying the epistasis displayed by this gene we have constructed hybrids between FcγRIIB−/− and the systemic lupus erythematosus (SLE) modifiers yaa and lpr and the susceptibility locus Sle1. Sle1 and B6.RIIB−/− are both physically and functionally coupled; compound heterozygotes of Sle1 and B6.RIIB−/− develop significant disease, while single heterozygotes display no evidence of autoimmunity or disease, indicating that these genes lie on the same genetic pathway resulting in the loss of tolerance to nuclear antigens. However, the generation of ANA in itself is insufficient to account for the severity of autoimmune disease in this model, as demonstrated by analysis of yaa and lpr hybrids. Thus, B6.RIIB−/−/lpr mice are protected from disease progression, despite equivalent titers of ANA. In contrast, B6.RIIB−/−/yaa mice have significantly enhanced disease despite reduced ANA titers. Yaa modifies the specificity and thus the pathogenicity of the B6. RIIB−/− ANA, by converting them to antinucleolar antibodies. In addition to these known modifier pathways, we have discovered two novel, recessive loci contributed by the C57BL/6 genome that are required for the ANA phenotype, further indicating the epistatic properties of this SLE model.
High Frequency of BRCA1 185delAG Mutation in Ovarian Cancer in Israel
Authors: B Modan, E Gak, R B Sade-Bruchim, G Hirsh-Yechezkel, L Theodor, F Lubin, G Ben-Baruch, U Beller, A Fishman, R Dgani, J Menczer, M Papa, E Friedman
Journal: JAMA (1996)

<h3>Objective.</h3> —To determine the role of<i>BRCA1</i>185delAG mutation in ovarian carcinogenesis. <h3>Design.</h3> —Genetic testing of a subset of cases from an ongoing study of ovarian cancer and of controls. <h3>Setting.</h3> —A community-based case-control incidence study. <h3>Subjects.</h3> —Seventy-nine patients with ovarian cancer, 62 hospitalized women without cancer (controls), and 120 healthy women participating in a fragile X screening program (also controls), examined for the presence of germline<i>BRCA1</i>185delAG mutation. <h3>Main Outcome Measures.</h3> —Polymerase chain reaction-amplified<i>BRCA1</i>exon 2 fragments generated from patients' and controls' blood samples, analyzed by heteroduplex gel shift assay and direct sequence analyses. <h3>Results.</h3> —The 185delAG mutation was detected in 38.9% (7/18) of ovarian cancer patients with familial history, and 13.1% (8/61) of family history-negative ovarian cancer cases. Only 1 carrier was detected among the 120 healthy controls, and none in the hospital controls. A significant difference in mutation carrier rates between family history-negative cases and control groups of 120 and 62 subjects was identified (Fisher exact test,<i>P</i>=.001 and<i>P</i>=.003, respectively). The median age (±SE) at disease diagnosis was lower among both familial and family history-negative mutation carriers, as compared with mutation-negative, family history-negative cases—50 (±1.4) vs 60.5 (±3.5) years old, respectively (hazard ratio, 1.68; 95% confidence interval, 0.94-3.01). <h3>Conclusions.</h3> —Our data are preliminary but suggest that<i>BRCA1</i>185delAG germline mutation is frequent in Israeli ovarian cancer patients, irrespective of family history, and may confer an early-onset phenotype of ovarian cancer.
Diagnostic value of lung clearance of 99mTc DTPA compared with other non-invasive investigations in Pneumocystis carinii pneumonia in AIDS.
Authors: M J O'Doherty, C J Page, T O Nunan, N T Bateman
Journal: Thorax (1992)

Diagnostic value of lung clearance of SSmTc DTPA compared with other non- invasive investigations in Pneumocystis carinii pneumonia in AIDS We read with interest the paper by Dr D S Robinson and others (October 1991;46:722- 6), which reported the finding of a biphasic or biexponential DTPA clearance curve and its use in the management of patients with HIV infection and pneumocystis pneumonia.We have found the test sensitive and useful.'2There are, however, some issues raised by the method used that are worth exploring.The most crucial point is the lack of separation of the patients with pneumocystis pneumonia and those that are smokers without pneumo- cystis pneumonia.This observation makes the suggestion that an analysis of the first seven minutes of data acquisition is suffi-
Mild Measles and Secondary Vaccine Failure During a Sustained Outbreak in a Highly Vaccinated Population
Authors: M B Edmonson, D G Addiss, J T McPherson, J L Berg, S R Circo, J P Davis
Journal: JAMA (1990)

A prolonged school-based outbreak of measles provided an opportunity to study "vaccine-modified" mild measles and secondary vaccine failure. Thirty-six (97%) of 37 unvaccinated patients had rash illnesses that met the Centers for Disease Control clinical case definition of measles, but 29 (15%) of 198 vaccinated patients did not, primarily because of low-grade or absent fever. Of 122 patients with seroconfirmed measles, 10 patients (all previously vaccinated) had no detectable measles-specific IgM and significantly milder illness than either vaccinated or unvaccinated patients with IgM-positive serum. Of 108 vaccinated patients with seroconfirmed measles, 17 patients (16%) had IgM-negative serology or rash illnesses that failed to meet the clinical case definition; their mean age (13 years), age at the time of vaccination, and time since vaccination did not differ from those of other vaccinated patients. The occurrence of secondary vaccine failure and vaccine-modified measles does not appear to be a major impediment to measles control in the United States but may lead to underreporting of measles cases and result in overestimation of vaccine efficacy in highly vaccinated populations.
Dysbindin-1 is reduced in intrinsic, glutamatergic terminals of the hippocampal formation in schizophrenia
Authors: Konrad Talbot, Wess L. Eidem, Caroline L. Tinsley, Matthew A. Benson, Edward W. Thompson, Rachel J. Smith, Chang-Gyu Hahn, Steven J. Siegel, John Q. Trojanowski, Raquel E. Gur, Derek J. Blake, Steven E. Arnold
Journal: Journal of Clinical Investigation (2004)

Eleven studies now report significant associations between schizophrenia and certain haplotypes of single-nucleotide polymorphisms in the gene encoding dysbindin-1 at 6p22.3. Dysbindin-1 is best known as dystrobrevin-binding protein 1 (DTNBP1) and may thus be associated with the dystrophin glycoprotein complex found at certain postsynaptic sites in the brain. Contrary to expectations, however, we found that when compared to matched, nonpsychiatric controls, 73–93% of cases in two schizophrenia populations displayed presynaptic dysbindin-1 reductions averaging 18–42% (P = 0.027–0.0001) at hippocampal formation sites lacking neuronal dystrobrevin (i.e., β-dystrobrevin). The reductions, which were not observed in the anterior cingulate of the same schizophrenia cases, occurred specifically in terminal fields of intrinsic, glutamatergic afferents of the subiculum, the hippocampus proper, and especially the inner molecular layer of the dentate gyrus (DGiml). An inversely correlated increase in vesicular glutamate transporter-1 (VGluT-1) occurred in DGiml of the same schizophrenia cases. Those changes occurred without evidence of axon terminal loss or neuroleptic effects on dysbindin-1 or VGluT-1. Our findings indicate that presynaptic dysbindin-1 reductions independent of the dystrophin glycoprotein complex are frequent in schizophrenia and are related to glutamatergic alterations in intrinsic hippocampal formation connections. Such changes may contribute to the cognitive deficits common in schizophrenia.
Effect of Low-Intensity Physical Activity and Moderate- to High-Intensity Physical Exercise During Adjuvant Chemotherapy on Physical Fitness, Fatigue, and Chemotherapy Completion Rates: Results of the PACES Randomized Clinical Trial
Authors: Hanna van Waart, Martijn M. Stuiver, Wim H. van Harten, Edwin Geleijn, Jacobien M. Kieffer, Laurien M. Buffart, Marianne de Maaker-Berkhof, Epie Boven, Jolanda Schrama, Maud M. Geenen, Jetske M. Meerum Terwogt, Aart van Bochove, Vera Lustig, Simone M. van den Heiligenberg, Carolien H. Smorenburg, Jeannette A.J.H. Hellendoorn-van Vreeswijk, Gabe S. Sonke, Neil K. Aaronson
Journal: Journal of Clinical Oncology (2015)

We evaluated the effectiveness of a low-intensity, home-based physical activity program (Onco-Move) and a moderate- to high-intensity, combined supervised resistance and aerobic exercise program (OnTrack) versus usual care (UC) in maintaining or enhancing physical fitness, minimizing fatigue, enhancing health-related quality of life, and optimizing chemotherapy completion rates in patients undergoing adjuvant chemotherapy for breast cancer.We randomly assigned patients who were scheduled to undergo adjuvant chemotherapy (N = 230) to Onco-Move, OnTrack, or UC. Performance-based and self-reported outcomes were assessed before random assignment, at the end of chemotherapy, and at the 6-month follow-up. We used generalized estimating equations to compare the groups over time.Onco-Move and OnTrack resulted in less decline in cardiorespiratory fitness (P < .001), better physical functioning (P ≤ .001), less nausea and vomiting (P = .029 and .031, respectively) and less pain (P = .003 and .011, respectively) compared with UC. OnTrack also resulted in better outcomes for muscle strength (P = .002) and physical fatigue (P < .001). At the 6-month follow-up, most outcomes returned to baseline levels for all three groups. A smaller percentage of participants in OnTrack required chemotherapy dose adjustments than those in the UC or Onco-Move groups (P = .002). Both intervention groups returned earlier (P = .012), as well as for more hours per week (P = .014), to work than the control group.A supervised, moderate- to high-intensity, combined resistance and aerobic exercise program is most effective for patients with breast cancer undergoing adjuvant chemotherapy. A home-based, low-intensity physical activity program represents a viable alternative for women who are unable or unwilling to follow the higher intensity program.
Catecholamine Metabolism in Hypertensive Rats
Authors: WILLIAM J. LOUIS, KENNETH R. KRAUSS, IRWIN J. KOPIN, ALBERT SJOERDSMA
Journal: Circulation Research (1970)

The possible role of catecholamines in two forms of experimental hypertension in rats was investigated further. Inbred, spontaneously hypertensive (SH) Wistar rats had unchanged endogenous levels of norepinephrine (NE) in the three tissues studied, and a significantly ( P &lt;0.05) decreased rate of NE synthesis ( 14 C-tyrosine technique) in heart and brainstem but not in gut, in comparison to normotensive Wistar rats. Also, the levels of free fatty acids (FFA) and major urinary catecholamine metabolites in plasma revealed no evidence of increased catecholamine turnover or release. Sprague-Dawley rats rendered hypertensive by treatment with desoxycorticosterone acetate and 1% salt had decreased cardiac NE concentration and increased cardiac NE turnover ( 3 H-NE technique) and cardiomegaly, confirming the work of others. However, urinary normetanephrine and plasma FFA did not differ from those in normal rats. These and other results fail to support but do not completely exclude a primary role for catecholamines in either type of hypertension.
Gene targeting. The precise manipulation of the mammalian genome.
Authors: J Robbins
Journal: Circulation Research (1993)

Genetics is a powerful tool for studying the function of different gene products as well as the physiological consequences of a normal or aberrant polypeptide. Until recently, the most powerful genetic applications have been restricted to relatively simple organisms whose genomes are more easily manipulated. For a number of years, in lower organisms, it has been possible to create defined genetic changes that are targeted to a specific locus or even to a defined codon or transcriptional regulatory sequence. With the development of gene targeting using embryonic stem cells derived from the preimplantation blastocyst of a mouse, it has become possible to extend these experiments to a mammalian system. Via homologous recombination, one can ablate, or "knock out," a defined genetic locus or mutate a particular set of nucleotides that encodes a peptide domain of interest. These techniques, when applied to genes that underlie normal cardiovascular function, promise to define the exact role(s) different proteins play during the development, growth, and maintenance of the heart. The ability to generate defined animal models of human disease in which the primary genetic defect is known should lead to fundamental advances in the study of the normal and failing heart.
Malignant lymphoma with dual B and T cell markers. Analysis of the neoplastic cells with monoclonal antibodies directed against T cell subsets.
Authors: A C Aisenberg, K J Bloch, B M Wilkes
Journal: The Journal of Experimental Medicine (1981)

In the course of analyzing human lymphoma tissue with conventional surface marker techniques and with monoclonal antibodies directed against T cell subsets, five tumors were encountered with dual B and T cell determinants. All bore on their surface membrane IgM of kappa light chain type, complement receptors, and the Ia-like antigen. In each of the five cases, the neoplastic lymphocytes reacted with a monoclonal antibody that detects the sheep erythrocyte receptor (OKT11); all but one reacted with a monoclonal antibody for peripheral T cells (OKT3); and all but one reacted with a monoclonal antibody specific for either the inducer-helper (OKT4) or the cytotoxic-suppressor (OKT8) T cell subsets. In addition, lymphocytes from two of the five cases formed spontaneous rosettes with sheep erythrocytes (E-rosettes). These tumors with dual B and T surface characteristics were confined to human malignant lymphomas that originate from B lymphocytes of the follicle center.
Some myths are slow to die
Authors: Rafael Salin-Pascual, Dmitry Gerashchenko, Priyattam J. Shiromani
Journal: Behavioral and Brain Sciences (2000)

Solms and the other authors in this series of BBS target articles accept the findings that the executive control of the REM/NREM cycle is still localized within a narrow region of the pontine brainstem. However, recent findings challenge this notion. We will review the recent data and suggest instead that the hypothalamus is the primary regulator of states of consciousness. If the hypothalamus indeed controls all the fun stuff, such as sex, eating, drinking, sleeping, and so on, then one can more easily accept Solms's argument that dreams are also generated from the forebrain. [Solms]
Bilateral increases in histamine after unilateral nasal allergen challenge.
Authors: M Wagenmann, F M Baroody, C C Cheng, A Kagey-Sobotka, L M Lichtenstein, R M Naclerio
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Studying the inflammatory response that follows the early response to nasal challenge with antigen provides a better understanding of allergic rhinitis than just studying the immediate (early) response. Nine allergic volunteers were challenged unilaterally with antigen-containing discs, and bilateral changes in physiologic responses as well as in the concentration of histamine in nasal secretions were measured for 11 h. We found significant immediate increases in symptoms, sneezes, ipsilateral nasal airway resistance, and ipsilateral histamine in the early phase response. Two-thirds of the allergen-challenged volunteers showed increases in physiologic parameters or histamine in the hours after allergen challenge. The pooled data of all subjects exhibited significant increases in bilateral nasal airway resistance and in ipsilateral and contralateral histamine, hours after unilateral provocation. These responses differed significantly from control subjects. In another group of 11 volunteers challenged ipsilaterally with antigen, the number of basophils increased both on the side of challenge and on the contralateral side. The magnitude of the increase on the ipsilateral side correlated with the increase on the contralateral side (r(s) = 0.72). The basophils are the most likely source of the contralateral increase in histamine as they are on the ipsilateral side. Although the mechanisms underlying this contralateral increase in basophils and histamine are not known, we speculate that delayed, neurogenic responses play a contributory role.
Norwegian scabies and lymphatic leukaemia
Authors: J. C. P. Logan, P. W. Grant, K. Keczkes
Journal: British Journal of Dermatology (1967)

Journal Article Norwegian scabies and lymphatic leukaemia Get access J. C. P. Logan, J. C. P. Logan Stobhill General Hospital, Glasgow, N.I Search for other works by this author on: Oxford Academic Google Scholar P. W. Grant, P. W. Grant Stobhill General Hospital, Glasgow, N.I Search for other works by this author on: Oxford Academic Google Scholar K. Keczkes K. Keczkes Stobhill General Hospital, Glasgow, N.I Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 79, Issue 5, 1 May 1967, Pages 303–305, https://doi.org/10.1111/j.1365-2133.1967.tb11497.x Published: 01 May 1967
Air pollution during pregnancy and lung function in newborns: a birth cohort study
Authors: P. Latzin, M. Röösli, A. Huss, C. E. Kuehni, U. Frey
Journal: European Respiratory Journal (2008)

Post-natal exposure to air pollution is associated with diminished lung growth during school age. The current authors aimed to determine whether pre-natal exposure to air pollution is associated with lung function changes in the newborn. In a prospective birth cohort of 241 healthy term-born neonates, tidal breathing, lung volume, ventilation inhomogeneity and exhaled nitric oxide (eNO) were measured during unsedated sleep at age 5 weeks. Maternal exposure to particles with a 50% cut-off aerodynamic diameter of 10 μm (PM 10 ), nitrogen dioxide (NO 2 ) and ozone (O 3 ), and distance to major roads were estimated during pregnancy. The association between these exposures and lung function was assessed using linear regression. Minute ventilation was higher in infants with higher pre-natal PM 10 exposure (24.9 mL·min −1 per μg·m −3 PM 10 ). The eNO was increased in infants with higher pre-natal NO 2 exposure (0.98 ppb per μg·m −3 NO 2 ). Post-natal exposure to air pollution did not modify these findings. No association was found for pre-natal exposure to O 3 and lung function parameters. The present results suggest that pre-natal exposure to air pollution might be associated with higher respiratory need and airway inflammation in newborns. Such alterations during early lung development may be important regarding long-term respiratory morbidity.
Down-Regulation of <i>LATS1</i> and <i>LATS2</i> mRNA Expression by Promoter Hypermethylation and Its Association with Biologically Aggressive Phenotype in Human Breast Cancers
Authors: Yuri Takahashi, Yasuo Miyoshi, Chie Takahata, Natsumi Irahara, Tetsuya Taguchi, Yasuhiro Tamaki, Shinzaburo Noguchi
Journal: Clinical Cancer Research (2005)

Abstract Purpose: LATS1 and LATS2 are tumor suppressor genes implicated in the regulation of cell cycle. Methylation status of the promoter regions of these genes as well as its correlation with their mRNA levels were studied in human breast cancers. Correlation of LATS1 and LATS2 mRNA levels with clinicopathologic characteristics of breast tumors were also studied. Experimental Design: Methylation status of promoter regions of LATS1 and LATS2 was studied by a methylation-specific PCR and mRNA expression levels of LATS1 and LATS2 were determined by a real-time PCR assay in 30 breast cancers. In addition, correlation of LATS1 and LATS2 mRNA levels with clinicopathologic characteristics was studied in 117 breast cancers. Results: Methylation-specific PCR showed that of 30 tumors, LATS1 promoter region was hypermethylated in 17 tumors (56.7%) and LATS2 promoter region was hypermethylated in 15 (50.0%) tumors. LATS1 mRNA levels in breast tumors with hypermethylation (2.15 ± 0.37, mean ± SE) were significantly (P &amp;lt; 0.01) lower than those without hypermethylation (6.09 ± 1.38), and LATS2 mRNA levels in breast tumors with hypermethylation (1.42 ± 0.66) were also significantly (P &amp;lt; 0.01) lower than those without hypermethylation (3.10 ± 1.00). The decreased expression of LATS1 or LATS2 mRNA was significantly associated with a large tumor size, high lymph node metastasis, and estrogen receptor and progesterone receptor negativity. Furthermore, the decreased expression of LATS1 mRNA, but not LATS2 mRNA, was significantly (P &amp;lt; 0.05) associated with a poor prognosis. Conclusions: Hypermethylation of the promoter regions of LATS1 and LATS2 likely plays an important role in the down-regulation of their mRNA levels in breast cancers, and breast cancers with a decreased expression of LATS1 or LATS2 mRNA levels have a biologically aggressive phenotype.
A cardiotoxic factor in serum and blast cell extract of patients with acute myeloid leukaemia
Authors: M A MIR
Journal: Cardiovascular Research (1981)

A low molecular weight fraction separated from leukaemic serum and blast cell extract decreased the amplitude of left ventricular contraction and decreased the oxygen uptake in the isolated rabbit heart. The primitive white cells either manufacture or transport the cardiodepressant factor, which is present in the serum and blast cell extract of patients with acute myeloid leukaemia. This factor is heat stable at 80° C for 30 min.
Lack of an exaggerated inflammatory response on virus infection in cystic fibrosis
Authors: E. Kieninger, M. Vareille, B.S. Kopf, F. Blank, M.P. Alves, F.M. Gisler, P. Latzin, C. Casaulta, T. Geiser, S.L. Johnston, M.R. Edwards, N. Regamey
Journal: European Respiratory Journal (2011)

Respiratory virus infections play an important role in cystic fibrosis (CF) exacerbations, but underlying pathophysiological mechanisms are poorly understood. We aimed to assess whether an exaggerated inflammatory response of the airway epithelium on virus infection could explain the increased susceptibility of CF patients towards respiratory viruses. We used primary bronchial and nasal epithelial cells obtained from 24 healthy control subjects and 18 CF patients. IL-6, IL-8/CXCL8, IP-10/CXCL10, MCP-1/CCL2, RANTES/CCL5 and GRO-α/CXCL1 levels in supernatants and mRNA expression in cell lysates were measured before and after infection with rhinoviruses (RV-16 and RV-1B) and RSV. Cytotoxicity was assessed by lactate dehydrogenate assay and flow cytometry. All viruses induced strong cytokine release in both control and CF cells. The inflammatory response on virus infection was heterogeneous and depended on cell type and virus used, but was not increased in CF compared with control cells. On the contrary, there was a marked trend towards lower cytokine production associated with increased cell death in CF cells. An exaggerated inflammatory response to virus infection in bronchial epithelial cells does not explain the increased respiratory morbidity after virus infection in CF patients.