tbuckley/cabot-search huggingface dataset:
Allocation concealment versus blinding in randomised controlled trials
Authors: P. Sedgwick
Journal: BMJ (2013)

Researchers investigated the effectiveness of the provision of whole food to enhance the completion of treatment for tuberculosis. A parallel group randomised controlled trial study design was used. The intervention was a nutritious culturally appropriate daily meal (weeks 1-8) and food package (weeks 9-32). Control treatment was nutritional advice alone at enrolment. Both intervention and control groups received standard care throughout the study period. The primary outcome was completion of treatment (clearance of acid fast bacilli from the sputum after treatment or the completion of eight months of treatment, or both).1

Participants were 270 adults (aged over 18 years) with previously untreated and newly diagnosed pulmonary tuberculosis, recruited from primary care clinics in Dili, Timor-Leste. Participants were randomised to treatment group after they had started standard tuberculosis treatment. The randomisation sequence was computer generated. Allocation concealment was ensured by the use of sequentially numbered, opaque, sealed envelopes. An independent observer, blinded to the allocated treatment, assessed the primary outcome.

There was no significant difference between treatment groups in the proportion of participants who achieved the primary outcome (intervention 76% …
Lack of Dosage Compensation Accompanies the Arrested Stage of Sex Chromosome Evolution in Ostriches
Authors: Sofia Adolfsson, Hans Ellegren
Journal: Molecular Biology and Evolution (2013)

Sex chromosome evolution is usually seen as a process that, once initiated, will inevitably progress toward an advanced stage of degeneration of the nonrecombining chromosome. However, despite evidence that avian sex chromosome evolution was initiated >100 Ma, ratite birds have been trapped in an arrested stage of sex chromosome divergence. We performed RNA sequencing of several tissues from male and female ostriches and assembled the transcriptome de novo. A total of 315 Z-linked genes fell into two categories: those that have equal expression level in the two sexes (for which Z-W recombination still occurs) and those that have a 2-fold excess of male expression (for which Z-W recombination has ceased). We suggest that failure to evolve dosage compensation has constrained sex chromosome divergence in this basal avian lineage. Our results indicate that dosage compensation is a prerequisite for, not only a consequence of, sex chromosome evolution.
Pleiotropism of Adiponectin
Authors: Guido Krenning, Jan-Renier A.J. Moonen, Martin C. Harmsen
Journal: Circulation Research (2009)

C ardiovascular complications are a major culprit in the pathogenesis of obesity and diabetes.The increased prevalence of cardiovascular complications in diabetes is attributed to the disturbed balance between increased endothelial injury and hampered endothelial repair processes. 1etinopathy, a blinding disease, is a major morbidity in diabetic patients.Diabetic retinopathy is initiated by hyperglycemia-induced endothelial cell injury, retinal vessel loss, and the adaptation of an inflammatory phenotype by the endothelium.Secretion of proangiogenic factors and proinflammatory cytokines from the ischemic retina lead to an exacerbated compensatory neovascularization, resulting in abnormal retinal neovascularization. 2 Hence, the primary treatment of retinopathy aims to preserve vision through the inhibition of excessive vascularization and reduction of vascular damage.Interestingly, endothelial dysfunction, hampered endothelial repair, and pathological neovascularization during retinopathy reflect similar molecular alterations partially related to a state of mild chronic inflammation, ie, overproduction of inflammatory cytokines and reactive oxygen species, increased leukocyte extravasations, and vascular leakage.
The fate of self-reactive B cells depends primarily on the degree of antigen receptor engagement and availability of T cell help.
Authors: D A Fulcher, A B Lyons, S L Korn, M C Cook, C Koleda, C Parish, B Fazekas de St Groth, A Basten
Journal: The Journal of Experimental Medicine (1996)

Self-reactive B cells from tolerant double-transgenic (Dbl-Tg) mice coexpressing hen egg lysozyme (HEL) and rearranged anti-HEL immunoglobulin genes have a relatively short life span when compared to normal B cells, irrespective of whether they are exposed to antigen in multivalent membrane-bound form (mHEL-Dbl-Tg mice) or soluble form (sHEL-Dbl-Tg mice). The factors responsible for determining the fate of these B cells after encounter with self-antigen were investigated using a cell-tracking technique in which anti-HEL Ig-Tg spleen cells were labeled with the intracellular dye 5-carboxyfluorescein diacetate-succinimidyl ester (CFSE) and injected either into non-Tg recipients or a variety of HEL-Tg hosts. In non-Tg recipients, HEL-binding B cells persisted in the circulation and could be detected in the follicles of the spleen for at least 5 d. On transfer into either mHEL-Tg or sHEL-Tg hosts, they underwent activation and then rapidly disappeared from the blood and spleen over the next 3 d, consistent with the short life span reported previously. Immunohistology of spleens from sHEL-Tg recipients indicated that the transferred B cells had migrated to the outer margins of the periarteriolar lymphoid sheath (PALS), where they were detectable for 24 h before being lost. The positioning of B cells in the outer PALS depended on a critical threshold of Ig receptor binding corresponding to a serum HEL concentration between 0.5 and 15 ng/ml, but was not restricted to endogenously expressed HEL in that the same migratory pattern was observed after transfer into non-Tg recipients given exogenous (foreign) HEL. Moreover, bone marrow-derived immature Ig-Tg B cells homed to the outer PALS of sHEL-Tg mice and then disappeared at the same rate as mature B cells, indicating that the stage of maturation did not influence the fate of self-reactive B cells in a tolerant environment. On the other hand, HEL-binding B cells transferred into sHEL-Dbl-Tg recipients persisted over the 3-d period of study, apparently due to insufficient availability of antigen, as indicated by the fact that the degree of Ig receptor downregulation on the transferred B cells was much less than in sHEL-Tg recipients. If T cell help was provided to Ig-Tg B cells at the time of transfer into sHEL-Tg recipients in the form of preactivated CD4+ T cells specific for major histocompatibility complex-peptide complexes on the B cell surface, HEL-binding B cells migrated through the outer PALS of the spleen to the follicle, where they formed germinal centers, or to adjacent red pulp, where they formed proliferative foci and secreted significant amounts of anti-HEL antibody. Taken together, these results indicated that the outcome of the interaction between self-antigen and B cells is largely determined by a combination of the degree of receptor engagement and availability of T cell help.
Induction of antibodies to the PreS region of surface antigens of woodchuck hepatitis virus (WHV) in chronic carrier woodchucks by immunizations with WHV surface antigens
Authors: Mengji Lu, Ruediger Klaes, Stephan Menne, Wolfram Gerlich, Benno Stahl, Hans-Peter Dienes, Uta Drebber, Michael Roggendorf
Journal: Journal of Hepatology (2003)
Human neocortical excitability is decreased during anoxia via sodium channel modulation.
Authors: T R Cummins, C Jiang, G G Haddad
Journal: Journal of Clinical Investigation (1993)

When the central nervous system in humans is deprived of oxygen, the effects are potentially disastrous. Electroencephalographic activity is lost and higher brain function ceases rapidly. Despite the importance of these effects, the mechanisms underlying the loss of cortical activity are poorly understood. Using intracellular recordings of human neocortical neurons in tissue slices, we show that, whereas anoxia produces a relatively small depolarization and modest alterations in passive properties, it causes a major decrease in excitability. Whole-cell voltage-clamp studies of acutely isolated human neocortical pyramidal neurons demonstrate that anoxia and metabolic inhibition produce a large negative shift in the steady-state inactivation [h infinity (V)] curve for the voltage-dependent sodium current (INa). Inclusion of ATP in the patch pipette decreased the shift of the h infinity (V) curve by two-thirds. Because increased inactivation of INa decreases cellular metabolic demand, we postulate that this promotes neuronal survival during periods of oxygen deprivation. These data show a novel mechanism by which anoxia links metabolism to membrane ionic conductances in human cortical neurons.
Science, medicine, and the future: Prospecting for gold in the human genome
Authors: J. Savill
Journal: BMJ (1997)

Doctors struggling with the daily problems of clinical medicine usually have little time for molecular and cell biology. But genetic research is producing an explosion of knowledge which doctors will need to understand in order to join in the ethical and financial debates that will inevitably follow the new treatments discovered. There may, indeed, be therapeutic gold hidden in our genes, but the price for it could be more than we can afford. This is the first of three articles introducing a series which aims to convey the excitement and potential power of biomedical science by speculating how current research will impinge on clinical management of common conditions.
Association of Cerebral Deficits With Clinical Symptoms in Antipsychotic-Naive First-Episode Schizophrenia: An Optimized Voxel-Based Morphometry and Resting State Functional Connectivity Study
Authors: Su Lui, Wei Deng, Xiaoqi Huang, Lijun Jiang, Xiaohong Ma, Huafu Chen, Tijiang Zhang, Xiuli Li, Dongming Li, Ling Zou, Hehan Tang, Xiaohong Joe Zhou, Andrea Mechelli, David A. Collier, John A. Sweeney, Tao Li, Qiyong Gong
Journal: American Journal of Psychiatry (2008)

The purpose of the present study was to characterize the association between clinical symptoms and anatomical and functional cerebral deficits in a relatively large sample of antipsychotic-naive first-episode schizophrenia patients using optimized voxel-based morphometry and resting state functional connectivity analysis.Participants were 68 antipsychotic-naive first-episode schizophrenia patients and 68 matched healthy comparison subjects. Both patients and healthy comparison subjects were scanned using a volumetric three-dimensional spoiled gradient recall sequence and a gradient-echo echo-planar imaging sequence. Psychopathology of first-episode schizophrenia patients was evaluated using the Positive and Negative Syndrome Scale (PANSS). Optimized voxel-based morphometry was used to characterize gray matter deficits in schizophrenia patients. The clinical significance of regional volume reduction was investigated by examining its association with symptoms in patients with first-episode schizophrenia and with alterations in resting state functional connectivity when brain regions with gray matter volume reduction were used as seed areas.Significantly decreased gray matter volume was observed in schizophrenia patients in the right superior temporal gyrus (Brodmann's area 41), right middle temporal gyrus (Brodmann's area 21), and right anterior cingulate gyrus (Brodmann's area 32). Decreased gray matter volume in these brain regions was related to greater disturbance as shown on PANSS scores for positive symptoms, general psychopathology symptoms, thought disturbance, activation, paranoia, and impulsive aggression as well as total PANSS scores. A positive correlation was observed between PANSS scores for thought disturbance and temporo-putamen connectivity, and negative correlations were found between temporo-precuneus connectivity and total PANSS scores as well as scores for negative symptoms and anergia.The findings revealed volume loss in the right superior temporal gyrus, right middle temporal gyrus, and right anterior cingulate gyrus among antipsychotic-naive first-episode schizophrenia patients. In addition, the functional networks involving the right superior temporal gyrus and middle temporal gyrus were associated with clinical symptom severity. No abnormalities were observed in resting state connectivity with regions of identified gray matter deficits.
A trans-acting major histocompatibility complex-linked gene whose alleles determine gain and loss changes in the antigenic structure of a classical class I molecule.
Authors: A M Livingstone, S J Powis, A G Diamond, G W Butcher, J C Howard
Journal: The Journal of Experimental Medicine (1989)

The RT1.A locus of the rat MHC encodes the H chain of the single classical class I molecule of this species. One of the alleles of this polymorphic locus, RT1.Aa, is present in several laboratory inbred, congenic, and MHC recombinant rat strains. Studies of the RT1.Aa class I molecule from a number of these strains as a target for CTL show that its antigenicity, both as an alloantigen and a restricting element, is subject to gain and loss alterations by the action of a gene mapping in the MHC to the right of RT1.A. This locus is apparently present in two allelic forms (one possibly a null allele) corresponding to the presence or absence of a dominant transacting modifier, and has been named class I modification, or cim. The antigenic change brought about by cim is scarcely detectable serologically but highly immunogenic for CTL. Biochemical investigations show that cim affects the post-translational modification of RT1.Aa.
Acute hypercapnic respiratory failure in patients with chronic obstructive lung disease: risk factors and use of guidelines for management.
Authors: A A Jeffrey, P M Warren, D C Flenley
Journal: Thorax (1992)

BACKGROUND: On the basis of a retrospective survey by this unit it was suggested that patients with acute ventilatory failure should be given sufficient controlled oxygen treatment to raise the arterial oxygen tension (PaO2) to above 6.6 kPa, with the addition of a respiratory stimulant if the hydrogen ion concentration ([H+]) rose above 55 nmol/l and assisted ventilation if the patient remained acidotic despite these measures. This study was designed to verify the prognostic factors that determine survival in acute ventilatory failure and determine the outcome when our guidelines were implemented. METHODS: One hundred and thirty nine episodes of acute hypercapnic (type II) respiratory failure were studied prospectively in 95 patients admitted with acute exacerbations of chronic obstructive lung disease. Patients had to have a PaO2 below 6.6 kPa and an arterial carbon dioxide tension (PaCO2) above 6.6 kPa while breathing air. RESULTS: The mortality associated with episodes of acute ventilatory failure was 12%. Patients who died tended to be older and were significantly more acidotic, hypotensive, and uraemic on admission than those who survived, but they had similar degrees of hypoxaemia and hypercapnia. Death occurred in 10 of the 39 episodes in which arterial [H+] rose to 55 nmol/l or above, compared with seven of the 100 episodes in which it remained below 55 nmol/l. The respiratory stimulant doxapram was used in 37 episodes and was associated with a reduction in [H+] below 55 nmol/l within 24 hours in 23 episodes. Assisted ventilation was used in only four episodes. CONCLUSION: Arterial [H+] is an important prognostic factor for survival. Most patients treated according to the guidelines outlined above can be managed successfully without assisted ventilation.
Hyperglycemia Has a Greater Impact on Left Ventricle Function in South Asians Than in Europeans
Authors: Chloe M. Park, Therese Tillin, Katherine March, Arjun K. Ghosh, Siana Jones, Andrew Wright, John Heasman, Darrel Francis, Naveed Sattar, Jamil Mayet, Nish Chaturvedi, Alun D. Hughes
Journal: Diabetes Care (2013)

OBJECTIVE Diabetes is associated with left ventricular (LV) diastolic and systolic dysfunction. South Asians may be at particular risk of developing LV dysfunction owing to a high prevalence of diabetes. We investigated the role of diabetes and hyperglycemia in LV dysfunction in a community-based cohort of older South Asians and white Europeans. RESEARCH DESIGN AND METHODS Conventional and Doppler echocardiography was performed in 999 participants (542 Europeans and 457 South Asians aged 58-86 years) in a population-based study. Anthropometry, fasting bloods, coronary artery calcification scoring, blood pressure, and renal function were measured. RESULTS Diabetes and hyperglycemia across the spectrum of HbA1c had a greater adverse effect on LV function in South Asians than Europeans (N-terminal-probrain natriuretic peptide β ± SE 0.09 ± 0.04, P = 0.01, vs. -0.04 ± 0.05, P = 0.4, P for HbA1c/ethnicity interaction 0.02), diastolic function (E/e' 0.69 ± 0.12, P < 0.0001, vs. 0.09 ± 0.2, P = 0.6, P for interaction 0.005), and systolic function (s' -0.11 ± 0.06, P = 0.04, vs. 0.14 ± 0.09, P = 0.1, P for interaction 0.2). Multivariable adjustment for hypertension, microvascular disease, LV mass, coronary disease, and dyslipidemia only partially accounted for the ethnic differences. Adverse LV function in diabetic South Asians could not be accounted for by poorer glycemic control or longer diabetes duration. CONCLUSIONS Diabetes and hyperglycemia have a greater adverse effect on LV function in South Asians than Europeans, incompletely explained by adverse risk factors. South Asians may require earlier and more aggressive treatment of their cardiometabolic risk factors to reduce risks of LV dysfunction.
Arthritis Critically Dependent on Innate Immune System Players
Authors: Hong Ji, Koichiro Ohmura, Umar Mahmood, David M Lee, Frans M.A Hofhuis, Susan A Boackle, Kazue Takahashi, V.Michael Holers, Mark Walport, Craig Gerard, Alan Ezekowitz, Michael C Carroll, Michael Brenner, Ralph Weissleder, J.Sjef Verbeek, Veronique Duchatelle, Claude Degott, Christophe Benoist, Diane Mathis
Journal: Immunity (2002)
Treatment of Waldenström’s Macroglobulinemia With Rituximab
Authors: Meletios A. Dimopoulos, Constantinos Zervas, Athanassios Zomas, Christos Kiamouris, Nora A. Viniou, Vassiliki Grigoraki, Christos Karkantaris, Chrisanthi Mitsouli, Dimitra Gika, John Christakis, Nikolaos Anagnostopoulos
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Waldenström’s macroglobulinemia (WM) is a low-grade lymphoplasmacytic lymphoma in which CD20 is usually expressed on tumor cells. There is evidence that patients with WM may benefit from treatment with the anti-CD20 monoclonal antibody rituximab. We performed a prospective phase II study to clearly define the activity of rituximab in patients with this disease. PATIENTS AND METHODS: Twenty-seven patients with WM were treated with rituximab 375 mg/m 2 intravenously (IV) for 4 weeks. Three months after completion of rituximab, patients without evidence of progressive disease received repeat 4-week courses of this agent. All patients were symptomatic, their median age was 72 years, and 15 patients were previously untreated. RESULTS: Twelve patients (44%; 95% confidence interval, 25.5% to 64.7%) achieved a partial response after treatment with rituximab. Median time to response was 3.3 months (range, 2.2 to 7.1 months). Responses occurred in six (40%) of 15 previously untreated patients and in six (50%) of 12 pretreated patients. Patients with a serum immunoglobulin M less than 40 g/L had a significantly higher response rate. The median time to progression for all patients was 16 months, and with a median follow-up of 15.7 months, nine of 12 responding patients remain free of progression. Treatment with rituximab was well tolerated, with approximately one fourth of patients experiencing some mild form of infusion-related toxicity, usually fever and chills. CONCLUSION: Our prospective data indicate that rituximab is well tolerated and active in patients with WM. Previously untreated and pretreated patients seem to benefit equally. Repeat 4-week courses of rituximab may prolong the duration of response of the disease, but this observation requires confirmation in prospective, randomized trials. Furthermore, studies that will combine rituximab with chemotherapy may be relevant.
The role of toll like receptors on tuberculosis infection
Authors: Oguz Oben Biyikli, Aysegul Baysak, Gulfem Terek Ece, Adnan Tolga Oz, Mustafa Hikmet Ozhan, Afig Berdeli
Journal: European Respiratory Journal (2013)

Aim:  One third of the world population is infected with  Mycobacterium tuberculosis . It is still one of the most important reasons of morbidity and mortality and threatens the global health. A new horizon has been opened with the investigation of toll like receptors (TLR) in the in the immunopthogenesis of the disease. TLRs can recognize some of the ligands with lipoprotein structure in the bacilli and with the help of this mechanism a signal pathway is activated and cytokine production begins and natural immunity takes place. TLR-2 and TLR-4 are defined in tuberculosis. The aim of our study was to investiagate the relationship between TLR polymorphism and infection progress.   Materials and Methods:  TLR-2 and TLR-4 polymorphisms and allel distribution were compred to 100 healthy control subjects.   Results:  19 of the 29 patients with tuberculosis had TLR-2 polymorphism. Twelve of the healthy subjects had polymorphism (p   Conclusion:  TLR agonist development, immunity, easier and faster polymorphism detection and prophilaxy are developing fields of investgation and further studies with greater number of patients are required for future studies which need to be supported with immunological parameters.
An investigation of rheumatoid arthritis loci in patients with early-onset psoriasis validates association of the<i>REL</i>gene
Authors: F.R. Ali, A. Barton, R.L.I. Smith, J. Bowes, E. Flynn, M. Mangino, V. Bataille, J.P. Foerster, J. Worthington, C.E.M. Griffiths, R.B. Warren
Journal: British Journal of Dermatology (2012)

Phenotypically diverse autoimmune conditions share common genetic susceptibility loci and underlying molecular pathways.By systematically searching for single nucleotide polymorphisms (SNPs) associated with another autoimmune disease, rheumatoid arthritis (RA), we aimed to elucidate novel genetic markers of psoriasis.We investigated 18 SNPs, previously confirmed as being associated with RA, in a U.K. cohort of 623 patients with early-onset psoriasis (presenting before age 40 years), comparing them with 2662 control subjects.Our findings confirm the association of early-onset psoriasis with REL (rs13031237, P=0·0027). The minor allele of REL had opposing effects upon susceptibility to disease in patients with psoriasis and RA.Similar exploration of additional autoimmune loci and fine mapping of such regions may provide further insight into the genetics and molecular pathophysiology of psoriasis.