tbuckley/cabot-search huggingface dataset:
Gomez?Lopez?Hernandez syndrome: another consideration in focal congenital alopecia
Authors: D.J. Purvis, A. Ramirez, N. Roberts, J.I. Harper
Journal: British Journal of Dermatology (2007)

Conflicts of interest: none declared. Sir, Gomez–Lopez–Hernandez syndrome (GLHS), also known as cerebellotrigeminal‐dermal dysplasia (OMIM 601 853), is a rare neurocutaneous disorder. Features include cerebellar malformation, trigeminal anaesthesia, focal scalp alopecia and craniosynostosis. We report a case of GLHS, initially referred as possible temporal triangular alopecia (TTA). The patient is the second son of healthy unrelated parents. Antenatal scans detected hydrocephalus, and delivery was by emergency caesarean section at term for fetal distress. Bitemporal alopecia was present from birth. During the first year of life he had hypotonia and plagiocephaly. Chromosomes, metabolic screening and head ultrasound scan were normal. His gross motor milestones were delayed and he received developmental physiotherapy. He had strabismus requiring patching and recurrent middle ear effusions requiring grommets, but his hearing was normal. Between the ages of 2 and 7 years the patient had several generalized febrile convulsions each lasting less than 2 min. He stopped physiotherapy at 4·5 years as he was functioning normally for his age, although with poor balance. He attended mainstream school where he was academically above average, and participated in rugby and cricket. At 9 years he sustained a mild head injury with subsequent double vision and headaches, which gradually resolved.
Rituximab induces remission in refractory HCV associated cryoglobulinaemic vasculitis
Authors: P Lamprecht
Journal: Annals of the Rheumatic Diseases (2003)

To report the successful induction of remission with the monoclonal anti-CD20 antibody rituximab in a patient with hepatitis C virus (HCV) associated cryoglobulinaemic vasculitis and a non-Hodgkin's lymphoma (NHL) resistant to previously advocated conventional treatments.The patient was a 45 year old woman with HCV associated cryoglobulinaemic vasculitis, with purpura, arthralgia, constitutional symptoms, and a polyneuropathy. A malignant NHL was found as underlying lymphoproliferative disease. At this stage the disease was refractory to interferon alpha2b and ribavirin and to subsequent immunosuppressive treatment with cyclophosphamide. Six rituximab infusions targeting the CD20 antigen on cells of the B cell lineage induced remission of the vasculitis. Bone marrow biopsy disclosed absence of the NHL. Remission has subsequently been maintained and HCV eliminated with the new pegylated interferon alpha2b and ribavirin for nearly one year.Transition of the underlying "benign" lymphoproliferative disease to a malignant lymphoma may result in difficult to treat HCV associated cryoglobulinaemic vasculitis. Rituximab offers a new possibility for inducing remission in refractory HCV associated cryoglobulinaemic vasculitis and the lymphoproliferative disorder. After remission, HCV may subsequently be eliminated with pegylated interferon alpha2b and ribavirin.
Psychological aspects of training for leisure
Authors: W. Ramsay
Journal: British Journal of Sports Medicine (1973)

In the course of this paper I intend to examine the psychological aspects of training for leisure under two main headings, Learning and Motivation.These two are not, of course, mutually independent.Complex learning, at least, is heavily dependent on the motivation of the student; and conversely, some psychologists would main- tain that without learning, the variety of human motives would not be nearly so great as it is.
IMPACT OF T-CELL DEPLETION ON OUTCOME OF ALLOGENEIC BONE-MARROW TRANSPLANTATION FOR STANDARD-RISK LEUKAEMIAS
Authors: D. Maraninchi, D. Blaise, B. Rio, V. Leblond, F. Dreyfus, E. Gluckman, D. Guyotat, J.L. Pico, M. Michallet, N. Ifrah, A. Bordigoni
Journal: The Lancet (1987)
Protein Kinase G Transmits the Cardioprotective Signal From Cytosol to Mitochondria
Authors: Alexandre D.T. Costa, Keith D. Garlid, Ian C. West, Thomas M. Lincoln, James M. Downey, Michael V. Cohen, Stuart D. Critz
Journal: Circulation Research (2005)

Ischemic and pharmacological preconditioning can be triggered by an intracellular signaling pathway in which G i -coupled surface receptors activate a cascade including phosphatidylinositol 3-kinase, endothelial nitric oxide synthase, guanylyl cyclase, and protein kinase G (PKG). Activated PKG opens mitochondrial K ATP channels (mitoK ATP ) which increase production of reactive oxygen species. Steps between PKG and mitoK ATP opening are unknown. We describe effects of adding purified PKG and cGMP on K + transport in isolated mitochondria. Light scattering and respiration measurements indicate PKG induces opening of mitoK ATP similar to K ATP channel openers like diazoxide and cromakalim in heart, liver, and brain mitochondria. This effect was blocked by mitoK ATP inhibitors 5-hydroxydecanoate, tetraphenylphosphonium, and glibenclamide, PKG-selective inhibitor KT5823, and protein kinase C (PKC) inhibitors chelerythrine, Ro318220, and PKC-ε peptide antagonist εV 1-2 . MitoK ATP are opened by the PKC activator 12-phorbol 13-myristate acetate. We conclude PKG is the terminal cytosolic component of the trigger pathway; it transmits the cardioprotective signal from cytosol to inner mitochondrial membrane by a pathway that includes PKC-ε.
Early alterations of lung parenchyma in acromegaly
Authors: Alida Benfante, Alessandro Ciresi, Maria Bellia, Fabio Cannizzaro, Vincenzo Bellia, Carla Giordano, Nicola Scichilone
Journal: European Respiratory Journal (2014)

Background : Acromegaly is an insidious disorder caused by a pituitary growth hormone (GH)-secreting adenoma resulting in high circulating levels of GH and insulin-like growth factor (IGF)-I. Although not common, the lung involvement can severely impact on quality of life, eventually affecting mortality.  Methods : We enrolled 10 consecutive patients (M/F: 5/5) affected by acromegaly. Ten healthy age-matched subjects served as controls. All patients underwent clinical, lung functional, biological and radiological assessments.  Results : We did not find statistically significant differences in lung function between acromegalic and healthy subjects (p≥ 0.05 for all analyses). However, the KCO% predicted was significantly lower in the acromegalic group than in healthy subjects (p=0.04). In addition, none of the lung function parameters correlated with duration of the disease, nor with inflammatory markers of the airways (FENO and CANO). The total lung volume measured by HRCT was 3540±1555 ml in acromegalics and the mean lung density was -711±73 HU. Lung function variables did not correlate with imaging parameters. However, TLCO% predicted significantly correlated with the lung density evaluated by HRCT (r= 0.70, p=0.03) None of the lung functional, radiological and biological findings correlated with GH or IGF-1 levels and no correlation was found with duration of disease.  Conclusions : Lung function evaluation allowed to detect early alterations of lung parenchyma, as assessed by diffusing capacity for CO and HRCT-associated structural alterations of the lung. These findings suggest to routinely evaluate lung function for a proper management of acromegaly.
Syntaxin-1A inhibition of P-1075, cromakalim, and diazoxide actions on mouse cardiac ATP-sensitive potassium channel
Authors: Betty Ng, Youhou Kang, Huanli Xie, Hui Sun, Herbert Y Gaisano
Journal: Cardiovascular Research (2008)

Syntaxin (Syn)-1A binds sulfonylurea receptor (SUR) nucleotide binding folds of cardiac myocyte (SUR2A) and islet beta-cells (SUR1) to inhibit ATP-sensitive potassium (K(ATP)) channels. We further reported that Syn-1A reduced the potency and efficacy of beta-cell-specific K(ATP) channel openers (KCOs). Here, we examined whether Syn-1A would influence non-specific (diazoxide) and SUR2-specific KCOs [N-cyano-N'-(1,1-dimethylpropyl)-N''-3-pyridylguanidine (P-1075) and cromakalim] on cardiac myocyte K(ATP) channels activation.Confocal microscopy and Western blotting verified the presence of both Syn-1A and -1B expressions on rodent cardiac ventricular myocytes. Inside-out patch-clamp electrophysiology was utilized to examine the effects of these syntaxins on K(ATP) macroscopic currents activated by various KCOs from a stable cell line expressing the potassium inward rectifier 6.2 (Kir6.2)/SUR2A and from C57BL/6 male mouse ventricular myocytes. Syn-1A inhibited the current amplitude activated by P-1075, cromakalim and diazoxide via its H3 but not Habc domain. Syn-1B exhibited similar inhibitory effects on P-1075 activation of K(ATP) currents. In examining for direct effects of Syn-1A on the KCO binding to cardiac SUR2 receptors, we found that Syn-1A did not directly affect [(3)H]-P-1075 binding to rat cardiac membrane SUR2A at maximum binding capacity, but was able to mildly reduce the affinity of cold P-1075 and cromakalim to displace [(3)H]-P-1075 binding.In conclusion, Syn-1A (and Syn-1B) could inhibit K(ATP) currents activated by SUR2A-acting KCOs. Potential fluctuations in the levels of these syntaxins in the myocardium may affect the therapeutic effectiveness of cardiac KCOs.
Blockade of HIV-1 Infection of New World Monkey Cells Occurs Primarily at the Stage of Virus Entry
Authors: Jason A. LaBonte, Gregory J. Babcock, Trushar Patel, Joseph Sodroski
Journal: The Journal of Experimental Medicine (2002)

HIV-1 naturally infects chimpanzees and humans, but does not infect Old World monkeys because of replication blocks that occur after virus entry into the cell. To understand the species-specific restrictions operating on HIV-1 infection, the ability of HIV-1 to infect the cells of New World monkeys was examined. Primary cells derived from common marmosets and squirrel monkeys support every phase of HIV-1 replication with the exception of virus entry. Efficient HIV-1 entry typically requires binding of the viral envelope glycoproteins and host cell receptors, CD4 and either CCR5 or CXCR4 chemokine receptors. HIV-1 did not detectably bind or utilize squirrel monkey CD4 for entry, and marmoset CD4 was also very inefficient compared with human CD4. A marmoset CD4 variant, in which residues 48 and 59 were altered to the amino acids found in human CD4, supported HIV-1 entry efficiently. The CXCR4 molecules of both marmosets and squirrel monkeys supported HIV-1 infection, but the CCR5 proteins of both species were only marginally functional. These results demonstrate that the CD4 and CCR5 proteins of New World monkeys represent the major restriction against HIV-1 replication in these primates. Directed adaptation of the HIV-1 envelope glycoproteins to common marmoset receptors might allow the development of New World monkey models of HIV-1 infection.
Antiperspirant Use and the Risk of Breast Cancer
Authors: Dana K Mirick, Scott Davis, David B Thomas
Journal: JNCI Journal of the National Cancer Institute (2002)

The rumor that antiperspirant use causes breast cancer continues to circulate the Internet. Although unfounded, there have been no published epidemiologic studies to support or refute this claim. This population-based case- control study investigated a possible relationship between use of products applied for underarm perspiration and the risk for breast cancer in women aged 20-74 years. Case patients (n = 813) were diagnosed between November 1992 and March 1995; control subjects (n = 793) were identified by random digit dialing and were frequency-matched by 5-year age groups. Product use information was obtained during an in-person interview. Odds ratios (ORs) and 95% confidence intervals were estimated by the use of conditional logistic regression. P values were determined with the Wald chi(2) test. All statistical tests were two-sided. The risk for breast cancer did not increase with any of the following activities: 1) antiperspirant (OR = 0.9; P =.23) or deodorant (OR = 1.2; P =.19) use; 2) product use among subjects who shaved with a blade razor; or 3) application of products within 1 hour of shaving (for antiperspirant, OR = 0.9 and P =.40; for deodorant, OR = 1.2 and P =.16). These findings do not support the hypothesis that antiperspirant use increases the risk for breast cancer.
Determinants of mild clinical symptoms in cystic fibrosis patients. Residual chloride secretion measured in rectal biopsies in relation to the genotype.
Authors: H J Veeze, D J Halley, J Bijman, J C de Jongste, H R de Jonge, M Sinaasappel
Journal: Journal of Clinical Investigation (1994)

Previous Ussing chamber measurements of secretagogue-provoked changes in short circuit current in rectal suction biopsies of cystic fibrosis (CF) patients showed that in a minority of patients chloride secretion in response to cholinergic agonists is reduced but not completely absent. To assess a possible relationship between this phenomenon and both the genotype and the phenotype, we performed Ussing chamber experiments on rectal suction biopsies of 51 CF patients. The CF mutation was identified in 89 out of 102 CF alleles. No apparent chloride secretion was found in 30 CF patients (group I). Low residual chloride secretion was found in 11 CF patients (group II), while a relatively high residual secretion appeared in 10 CF patients (group III). Pancreatic function was preserved more frequently in CF patients displaying residual secretion: 0% in group I, 27% in group II, and 60% in group III (P < 0.001). The age at diagnosis (mean +/- SEM) in group III (18.4 +/- 6.6) was significantly different from group I (1.2 +/- 0.4, P < 0.01) and group II (3.5 +/- 1.4, P = 0.05). Residual chloride secretion was found in some of the 28 dF508 homozygous patients (three in group II, and one in group III), disclosing that other factors than the CF gene defect itself affect the transepithelial chloride transport. The age at diagnosis correlates significantly with the magnitude of the secretory response, even within the dF508 homozygous patients (r = 0.4, P < 0.05). We conclude that residual chloride secretion in CF is the pathophysiological basis of preserved pancreatic function and delayed presentation of the disease, which is not exclusively determined by the CF genotype.
Immunogenic DNA-related factors. Nucleosomes spontaneously released from normal murine lymphoid cells stimulate proliferation and immunoglobulin synthesis of normal mouse lymphocytes.
Authors: D A Bell, B Morrison, P VandenBygaart
Journal: Journal of Clinical Investigation (1990)

The cell-free supernatants of normal spleen and thymus lymphocytes in short-term culture release low molecular weight (LMW) DNA protein molecules that have an immunoproliferative effect (polyclonal B cell activation) in vitro. We have determined that the protein-LMW DNA complexes responsible for these effects are nucleosomal constituents of chromatin, since the mitogenically active fractions of these cell-free supernatants contain the constituents of core histones (H3, H2A, H2B, H4) together with LMW DNA (140-180 bp), and since the immunoproliferative effects of these cell-free supernatants could be mimicked by various other nucleoprotein preparations (including calf thymus and chicken erythrocyte nucleosomes). The spontaneous cellular release of cleaved chromatin constituents in vitro can be attributed to a form of programmed cell death termed apoptosis, since the cultured spleen cells exhibited (a) morphologic evidence consistent with this process by electron microscopy, and (b) evidence of intracellular cleavage of chromatin which, like apoptosis, could be blocked with ZnSO4. This resulted in inhibition of the extracellular release of nucleosomal constituents as well as the immunoproliferative effects of the cell-free supernatants. The immunoproliferative effect of nucleosomes released from cells during apoptosis could be responsible for previously observed spontaneous in vitro anti-DNA and anti-histone antibody responses of murine spleen cells, and in vivo in normal lymphoid tissues, resulting in renewed cellular proliferation after cell death. In pathological states, this could result in abnormal polyclonal B cell proliferation and autoantibody formation.
Combination of Antidepressant Medications From Treatment Initiation for Major Depressive Disorder: A Double-Blind Randomized Study
Authors: Pierre Blier, Herbert E Ward, Philippe Tremblay, Louise Laberge, Chantal Hébert, Richard Bergeron
Journal: American Journal of Psychiatry (2009)

Various classes of antidepressant medications generally induce remission of major depressive disorder in only about one-third of patients. In a previous study using mirtazapine or paroxetine alone or in combination from treatment initiation, the rate of patients who remitted within a 6-week period was twice that of patients using either drug alone. In this double-blind study, the authors sought to produce evidence for the superiority of different combinations of antidepressant drugs from treatment initiation.Patients (N=105) meeting DSM-IV criteria for major depressive disorder were randomly assigned to receive, from treatment initiation, either fluoxetine monotherapy (20 mg/day) or mirtazapine (30 mg/day) in combination with fluoxetine (20 mg/day), venlafaxine (225 mg/day titrated in 14 days), or bupropion (150 mg/day) for 6 weeks. The primary outcome measure was the Hamilton Depression Rating Scale (HAM-D) score.The overall dropout rate was 15%, without notable differences among the four groups. Compared with fluoxetine monotherapy, all three combination groups had significantly greater improvements on the HAM-D. Remission rates (defined as a HAM-D score of 7 or less) were 25% for fluoxetine, 52% for mirtazapine plus fluoxetine, 58% for mirtazapine plus venlafaxine, and 46% for mirtazapine plus bupropion. Among patients who had a marked response, double-blind discontinuation of one agent produced a relapse in about 40% of cases.The combination treatments were as well tolerated as fluoxetine monotherapy and more clinically effective. The study results, which add to a growing body of evidence, suggest that use of antidepressant combinations from treatment initiation may double the likelihood of remission compared with use of a single medication.
TNF-α is crucial for the development of autoimmune arthritis in IL-1 receptor antagonist–deficient mice
Authors: Reiko Horai, Akiko Nakajima, Katsuyoshi Habiro, Motoko Kotani, Susumu Nakae, Taizo Matsuki, Aya Nambu, Shinobu Saijo, Hayato Kotaki, Katsuko Sudo, Akihiko Okahara, Hidetoshi Tanioka, Toshimi Ikuse, Naoto Ishii, Pamela L. Schwartzberg, Ryo Abe, Yoichiro Iwakura
Journal: Journal of Clinical Investigation (2004)

IL-1 receptor antagonist–deficient (IL-1Ra–/–) mice spontaneously develop autoimmune arthritis. We demonstrate here that T cells are required for the induction of arthritis; T cell–deficient IL-1Ra–/– mice did not develop arthritis, and transfer of IL-1Ra–/– T cells induced arthritis in nu/nu mice. Development of arthritis was also markedly suppressed by TNF-α deficiency. We found that TNF-α induced OX40 expression on T cells and blocking the interaction between either CD40 and its ligand or OX40 and its ligand suppressed development of arthritis. These findings suggest that IL-1 receptor antagonist deficiency in T cells disrupts homeostasis of the immune system and that TNF-α plays an important role in activating T cells through induction of OX40.
Altered Nuclear Receptor Corepressor Expression Attenuates Vitamin D Receptor Signaling in Breast Cancer Cells
Authors: Claire M. Banwell, Donia P. MacCartney, Michelle Guy, Alice E. Miles, Milan R. Uskokovic, Janine Mansi, Paul M. Stewart, Laura P. O'Neill, Bryan M. Turner, Kay W. Colston, Moray J. Campbell
Journal: Clinical Cancer Research (2006)

Abstract Purpose: We hypothesized that deregulated corepressor actions, with associated histone deacetylation activity, epigenetically suppressed vitamin D receptor (VDR) responsiveness and drives resistance towards 1α,25-dihydroxyvitamin D3. Experimental Design: Profiling, transcriptional, and proliferation assays were undertaken in 1α,25(OH)2D3-sensitive MCF-12A nonmalignant breast epithelial cells, a panel of breast cancer cell lines, and a cohort of primary breast cancer tumors (n = 21). Results: Elevated NCoR1 mRNA levels correlated with suppressed regulation of VDR target genes and the ability of cells to undergo arrest in G1 of the cell cycle. A similar increased ratio of corepressor mRNA to VDR occurred in matched primary tumor and normal cells, noticeably in estrogen receptor α–negative (n = 7) tumors. 1α,25(OH)2D3 resistance in cancer cell lines was targeted by cotreatments with either 1α,25(OH)2D3 or a metabolically stable analogue (RO-26-2198) in combination with either trichostatin A (TSA; histone deacetylation inhibitor) or 5-aza-2′-deoxycytidine (DNA methyltransferase inhibitor). Combinations of vitamin D3 compounds with TSA restored VDR antiproliferative signaling (target gene regulation, cell cycle arrest, and antiproliferative effects in liquid culture) to levels which were indistinguishable from MCF-12A cells. Conclusions: Increased NCoR1 mRNA is a novel molecular lesion in breast cancer cells, which acts to suppress responsiveness of VDR target genes, resulting in 1α,25(OH)2D3 resistance and seems to be particularly associated with estrogen receptor negativity. This lesion provides a novel molecular diagnostic and can be targeted by combinations of vitamin D3 compounds and low doses of TSA.
Correlates of Mycobacterium tuberculosis infection in a prison population
Authors: S. Carbonara, S. Babudieri, B. Longo, G. Starnini, R. Monarca, B. Brunetti, M. Andreoni, G. Pastore, V. De Marco, G. Rezza
Journal: European Respiratory Journal (2005)

Prisons represent a crucial setting for tuberculosis control. Currently, there is scarce information concerning Mycobacterium tuberculosis (MT) infection in European prisons, and no data are available for Italy. This study aims to describe the prevalence and correlates of MT infection in an Italian prison population. In this multicentre cross-sectional study, 1,247 inmates from nine prisons were recruited and asked to undergo questioning regarding socio-economic and demographic variables, tuberculin skin testing (TST), chest radiographs and testing for HIV, hepatitis B and hepatitis C virus infection. TST was positive in 17.9% of the 448 evaluable subjects. With multivariate logistic regression (performed among male inmates), MT infection was correlated with age (adjusted odds ratio (OR) 4.12 for inmates aged 31–40 yrs; 3.78 for those aged &gt;40 yrs), being foreign-born (OR = 4.9), education ≤5 yrs (OR = 1.88) and length of detention (increased risk per yr: 11%). As with elsewhere in the world, the prison system in Italy features a population with an increased rate of Mycobacterium tuberculosis infection and at-risk rate for Mycobacterium tuberculosis transmission. Improved tuberculosis surveillance and control measures are deemed necessary in correctional facilities nationwide, especially for subjects with the above risk factors and those who are HIV infected, in whom the tuberculin skin testing can be misleading. The screening of entrants is particularly important to avoid undiagnosed smear-positive tuberculosis cases.