tbuckley/cabot-search huggingface dataset:
Evidence for failure of V(D)J recombination in bone marrow pre-B cells from X-linked agammaglobulinemia.
Authors: J Schwaber
Journal: Journal of Clinical Investigation (1992)

X-linked agammaglobulinemia (XLA) results from a failure of B lymphoid development. We have previously examined pre-B cell hybrids from three patients with XLA and found them to be limited to production of a novel germ line transcript of the Ig H chain locus composed of a leader sequence (LS) spliced to the constant region of mu chain (C mu) as mRNA and polypeptide. These transcripts result from transcriptional activation of the germ line heavy chain locus from an LS exon upstream of the embryonic JH locus. Germ line LS-C mu transcripts are produced by pre-B cells from normal bone marrow and fetal liver, indicating that they are products of normal pre-B cell development, as part of the process of transcriptional activation to provide access for the recombinase. Bone marrow from three patients with XLA has been examined directly by polymerase chain reaction amplification to determine whether the exclusive production of LS-C mu by XLA pre-B cell hybrids is representative of XLA pre-B cells. I report that LS-C mu is the predominant Ig molecule produced by XLA pre-B cells, with limited production of the D mu product of DJH intermediate stage of V(D)J recombination. Mature VHDJH recombinations were not detected with a variety of primers that amplify VH sequences. I conclude that XLA is associated with a limitation in V(D)J recombination that may cause the failure of pre-B cell development.
Getting more for their dollar: a comparison of the NHS with California's Kaiser Permanente Commentary: Funding is not the only factor Commentary: Same price, better care Commentary: Competition made them do it
Authors: R. G A Feachem
Journal: BMJ (2002)

To compare the costs and performance of the NHS with those of an integrated system for financing and delivery health services (Kaiser Permanente) in California.The adjusted costs of the two systems and their performance were compared with respect to inputs, use, access to services, responsiveness, and limited quality indicators.The per capita costs of the two systems, adjusted for differences in benefits, special activities, population characteristics, and the cost environment, were similar to within 10%. Some aspects of performance differed. In particular, Kaiser members experience more comprehensive and convenient primary care services and much more rapid access to specialist services and hospital admissions. Age adjusted rates of use of acute hospital services in Kaiser were one third of those in the NHS.The widely held beliefs that the NHS is efficient and that poor performance in certain areas is largely explained by under investment are not supported by this analysis. Kaiser achieved better performance at roughly the same cost as the NHS because of integration throughout the system, efficient management of hospital use, the benefits of competition, and greater investment in information technology.
Prevalence and Incidence of Adult Pertussis in an Urban Population
Authors: Mary E. Nennig
Journal: JAMA (1996)

<h3>Objectives.</h3> —To determine the prevalence of<i>Bordetella pertussis</i>infection among adults who have prolonged cough for 2 weeks or longer and to estimate the incidence of<i>B pertussis</i>infection in adults in a defined urban population. <h3>Design.</h3> —A prospective clinical study. <h3>Setting.</h3> —Kaiser Permanente, San Francisco (Calif) Medical Center. <h3>Participants.</h3> —One hundred fifty-three referred and participating health plan members 18 years old or older with the complaint of cough persisting for 2 weeks or longer and 154 health plan members 18 years old or older with no cough for the past 3 months (controls) were enrolled. Medical records for an additional 100 patients randomly sampled from 676 patients 18 years old or older with an ambulatory diagnosis of cough (60 with prolonged cough) were also reviewed. <h3>Main Outcome Measures.</h3> —Prevalence of adult pertussis as determined by enzyme-linked immunosorbent assay IgG antibody levels to pertussis toxin in individuals with prolonged cough for 2 weeks or longer and the incidence of adult pertussis in San Francisco Kaiser health plan members. <h3>Results.</h3> —The prevalence of adult pertussis was 12.4% of the participating referrals. The incidence of adult pertussis was estimated to be 176 cases per 100 000 person-years (95% confidence interval, 97 to 255 cases). <h3>Conclusions.</h3> —Adult pertussis is a significantly greater public health threat than previously suspected. Booster doses of acellular pertussis vaccine after 7 years of age may be an effective approach to minimize transmission and infection. (<i>JAMA</i>. 1996;275:1672-1674)
Cloning and Characterization of α1H From Human Heart, a Member of the T-Type Ca <sup>2+</sup> Channel Gene Family
Authors: Leanne L. Cribbs, Jung-Ha Lee, Jie Yang, Jonathan Satin, Yi Zhang, Asif Daud, Jane Barclay, Magali P. Williamson, Margaret Fox, Michele Rees, Edward Perez-Reyes
Journal: Circulation Research (1998)

Voltage-activated Ca2+ channels exist as multigene families that share common structural features. Different Ca2+ channels are distinguished by their electrophysiology and pharmacology and can be classified as either low or high voltage-activated channels. Six alpha1 subunit genes cloned previously code for high voltage-activated Ca2+ channels; therefore, we have used a database search strategy to identify new Ca2+ channel genes, possibly including low voltage-activated (T-type) channels. A novel expressed sequence-tagged cDNA clone of alpha1G was used to screen a cDNA library, and in the present study, we report the cloning of alpha1H (or CavT.2), a low voltage-activated Ca2+ channel from human heart. Northern blots of human mRNA detected more alpha1H expression in peripheral tissues, such as kidney and heart, than in brain. We mapped the gene, CACNA1H, to human chromosome 16p13.3 and mouse chromosome 17. Expression of alpha1H in HEK-293 cells resulted in Ca2+ channel currents displaying voltage dependence, kinetics, and unitary conductance characteristic of native T-type Ca2+ channels. The alpha1H channel is sensitive to mibefradil, a nondihydropyridine Ca2+ channel blocker, with an IC50 of 1.4 micromol/L, consistent with the reported potency of mibefradil for T-type Ca2+ channels. Together with alpha1G, a rat brain T-type Ca2+ channel also cloned in our laboratory, these genes define a unique family of Ca2+ channels.
S102 The crosstalk of PDE inhibitor with BMP signalling pathway in human pulmonary arterial smooth muscle cells
Authors: J. Yang, X. Li, C. Wu, N. Morrell
Journal: Thorax (2011)

<h3>Rational</h3> Sildenafil, a potent PDE inhibitor, is an established treatment for PAH. However, the detailed mechanism of its effects on the proliferation of human pulmonary artery smooth muscle cells (hPASMCs) remains unclear. <h3>Objective</h3> Because sidenafil is effective treatments for clinical PAH, we hypothesised that these agents enhance Smad1/Id signalling through cGKI in hPASMCs. <h3>Methods and Results</h3> Sildenafil alone has no effect on Smad1 phosphorylation and Id1 gene expression in hPASMCs, However in the presence of BMP4 Sidenafil indeed enhanced BMP-induced phosphorylation of Smad1/5 and Id1 expression in a cGMP/cGKI-dependent manner in hPASMCs. The presumed mechanism is by elevation of intracellular cGKI activity which modulate smad1 phosphorylation and nuclear localisation. Knock down cGKI or use pharmalogical cGMP inhibitor abrogate the effect of Sildenafil on hPASMCs. Furthermore we confirm the rescued pSmad1 signal and elevated proliferation inhibitory effect in hPASMCs from familial pulmonary arterial hypertension patients by Sildenafil. <h3>Conclusions</h3> Sildenafil enhance BMP/Smad through cGMP/cGKI pathway to modulate hPASMCs proliferation.
Neonatologists Judge the Baby Doe Regulations
Authors: Loretta M. Kopelman, Thomas G. Irons, Arthur E. Kopelman
Journal: New England Journal of Medicine (1988)

The federal regulations now in effect governing the treatment of severely handicapped infants--the so-called Baby Doe regulations--are based on the 1984 amendments to the Child Abuse Prevention and Treatment Act; these regulations require that, except under certain specified conditions, all newborns receive maximal life-prolonging treatment. We sent questionnaires to the 1007 members of the Perinatal Pediatrics Section of the American Academy of Pediatrics to determine their views on the Baby Doe regulations and on whether the regulations had affected their practices; 494 of the members (49 percent) responded. Of the respondents, 76 percent believed that the current regulations were not necessary to protect the rights of handicapped infants; 66 percent believed that the regulations interfered with parents' right to determine what course of action was in the best interest of their children; and 60 percent believed that the regulations did not allow adequate consideration of infants' suffering. In responding to the three hypothetical cases of severely handicapped newborns, up to 32 percent of the respondents said that maximal life-prolonging treatment was not in the best interests of the infants described but that the Baby Doe regulations required such treatment. The responding neonatologists' concerns about the current Baby Doe regulations were similar to those expressed by the United States Supreme Court in rejecting an earlier set of Baby Doe regulations. This similarity suggests that the current Baby Doe regulations should be reevaluated.
SHOX2 DNA Methylation Is a Biomarker for the Diagnosis of Lung Cancer in Plasma
Authors: Christoph Kneip, Bernd Schmidt, Anke Seegebarth, Sabine Weickmann, Michael Fleischhacker, Volker Liebenberg, John K. Field, Dimo Dietrich
Journal: Journal of Thoracic Oncology (2011)
Studies of the effects of trimethoprim and sulfamethoxazole on human granulopoiesis
Authors: Barbara H. Bjornson, Angus P. McLntyre, John M. Harvey, Alfred I. Tauber
Journal: American Journal of Hematology (1986)

Abstract Trimethoprim and sulfamethoxazole (Bactrim r) is a widely used antibiotic combination effective against a broad spectrum of microbial organisms. There are reports of neutropenia developing during even brief periods of oral therapy, particularly in individuals with either folate deficiency or increased folate requirements. We have investigated the effects of these drugs on circulating granulocyte precursors (CFU‐C) from normal donors and the mechanism of inhibition on granulopoiesis using an in vitro CFU‐C assay. In 12 healthy adults, the number of circulating granulocytes and granulocyte progenitors was not significantly altered by a 5‐day course of therapy. However, in experiments that simulated the in vivo condition of folate deficiency (folate‐free cultures were prepared with cells harvested from normal donors), trimethoprim (8 μg/ml) resulted in a 47% decrease in the total number of colonies; this inhibitory effect was prevented when 100 ng of folinic acid was also added to the culture. Sulfamethoxazole (40 μg/ml) had no discernible effect on granulopoiesis. The combination of 8 μg/ml of trimethoprim and 40 μg/ml of sulfamethoxazole resulted in a 52% decrease in the number of colonies generated and this inhibition was again prevented by folinic acid. Our results suggest that the neutropenia occasionally observed in patients treated with trimethoprim‐sulfamethoxazole is due to the inhibitory effects on granulopoiesis by trimethoprim, namely its antifolate action, which is reversed by folinic acid. Based on these studies, in patients with either folate deficiency or increased folate requirements, trimethoprim‐sulfamethoxazole should be used with caution.
Spanish anaesthetist infects patients with hepatitis C
Authors: X. Bosch
Journal: BMJ (1998)

A Spanish anaesthetist is believed to have infected more than 200 patients with the hepatitis C virus.

Earlier this month the Valencian health department announced that at least 217 people have become infected with hepatitis C after undergoing surgery within the past year at two hospitals in Valencia. The health department named the primary source of the infection …
Special Issues Regarding Obesity in Minority Populations
Authors: Shiriki K. Kumanyika
Journal: Annals of Internal Medicine (1993)

Special attention must be given to obesity as it occurs in and affects ethnic minorities (that is, black Americans, Hispanic Americans, Asian and Pacific Islander Americans, American Indians and Alaska Natives, and Native Hawaiians) in the United States. In most of these groups, the prevalence of obesity is substantially higher than in whites, especially among women. Poverty and lower educational attainment, which are associated with higher than average rates of female obesity (independent of ethnicity), affect proportionately more persons in these minority populations than in white populations. Diabetes mellitus and certain other obesity-related conditions occur to a markedly greater than average extent in many minority populations. A high-risk body fat distribution (upper body or central obesity) occurs to a greater extent in some minority populations than in whites. Because of situational and cultural factors, effective obesity prevention and treatment approaches may need to be defined on an ethnicity-specific basis. Increased attention to obesity as it occurs in and affects diverse ethnic groups can help to address critical minority health issues. Such efforts can also broaden and enrich aspects of obesity research for which models based on white populations are inappropriate or limited.
Inhaled NO Protects Cerebral White Matter in Neonatal Rats with Combined Brain and Lung Injury
Authors: Hoa Pham, Gaelle Vottier, Julien Pansiot, Jérémie Dalous, Jorge Gallego, Pierre Gressens, Sy Duong-Quy, Anh-Tuan Dinh-Xuan, Jean-Christophe Mercier, Valérie Biran, Christiane Charriaut-Marlangue, Olivier Baud
Journal: American Journal of Respiratory and Critical Care Medicine (2012)
Tissue-Specific Inducible Expression of Antimicrobial Peptide Genes in Drosophila Surface Epithelia
Authors: Phoebe Tzou, Serge Ohresser, Dominique Ferrandon, Maria Capovilla, Jean-Marc Reichhart, Bruno Lemaitre, Jules A. Hoffmann, Jean-Luc Imler
Journal: Immunity (2000)
Association between breast feeding and asthma in 6 year old children: findings of a prospective birth cohort study
Authors: W H Oddy, P G Holt, P D Sly, A W Read, L I Landau, F J Stanley, G E Kendall, P R Burton
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objectives:</b> To investigate the association between the duration of exclusive breast feeding and the development of asthma related outcomes in children at age 6 years. <b>Design:</b> Prospective cohort study. <b>Setting:</b> Western Australia. <b>Subjects:</b> 2187 children ascertained through antenatal clinics at the major tertiary obstetric hospital in Perth and followed to age 6 years. <b>Main outcome measures:</b> Unconditional logistic regression to model the association between duration of exclusive breast feeding and outcomes related to asthma or atopy at 6 years of age, allowing for several important confounders: sex, gestational age, smoking in the household, and early childcare. <b>Results:</b> After adjustment for confounders, the introduction of milk other than breast milk before 4 months of age was a significant risk factor for all asthma and atopy related outcomes in children aged 6 years: asthma diagnosed by a doctor (odds ratio 1.25, 95% confidence interval 1.02 to 1.52); wheeze three or more times since 1 year of age (1.41, 1.14 to 1.76); wheeze in the past year (1.31, 1.05 to 1.64); sleep disturbance due to wheeze within the past year (1.42, 1.07 to 1.89); age when doctor diagnosed asthma (hazard ratio 1.22, 1.03 to 1.43); age at first wheeze (1.36, 1.17 to 1.59); and positive skin prick test reaction to at least one common aeroallergen (1.30, 1.04 to 1.61). <b>Conclusion:</b> A significant reduction in the risk of childhood asthma at age 6 years occurs if exclusive breast feeding is continued for at least the 4 months after birth. These findings are important for our understanding of the cause of childhood asthma and suggest that public health interventions to optimise breast feeding may help to reduce the community burden of childhood asthma and its associated traits. <h3>Key messages</h3> Asthma is the leading cause of admission to hospital in Australian children and its prevalence is increasing Whether breast feeding protects against asthma or atopy, or both, is controversial Asthma is a complex disease, and the relative risks between breast feeding and asthma or atopy are unlikely to be large; this suggests the need for investigation in a large prospective birth cohort with timely assessment of atopic outcomes and all relevant exposures Exclusive breast feeding for at least 4 months is associated with a significant reduction in the risk of asthma and atopy at age 6 years and with a significant delay in the age at onset of wheezing and asthma being diagnosed by a doctor Public health interventions to promote an increased duration of exclusive breast feeding may help to reduce the morbidity and prevalence of childhood asthma and atop
Acute myocardial infarction in Asians and whites in Birmingham.
Authors: R E Lawrence, W A Littler
Journal: BMJ (1985)

On a pense que les asiatiques immigres en Europe souffraient plus de coronaropathies que les Europeens ou que les asiatiques restant dans leur pays, ou qu'ils avaient moins acces aux services de traitement specialise. Une enquete montre qu'il n'en est rien et que les difficultes eventuelles de communication ne perturbent pas les admissions et les traitements
Anticoagulants and Myocardial Infarction
Authors: Joseph B. Wolffe
Journal: JAMA (1962)

<h3>To the Editor:—</h3> In a recent report of a 4-year Danish study of 800 patients, Drs. Tage Hilden, Michael Schwartz, Fleming Raaschou, and Kurt Iversen came to the conclusion that "anticoagulant therapy is not indicated in acute myocardial infarction." Our observations a decade ago (<i>JAMA</i><b>146</b>:1274 [July 28] 1951) were identical with those of the Danish investigators. Unfortunately, it is difficult to swim against the tide. To date, we continued our studies on more than 1,100 patients with acute myocardial infarction at the Valley Forge Heart Hospital &amp; Medical Center, Norristown, Pa., and Wolffe Hospital in Philadelphia. The best results were obtained in a group who were on placebos, purported to be anticoagulants. These patients were reexamined and reassured at similar intervals as anticoagulant-treated patients came for prothrombin determinations. This finding again focuses attention on the power of medical guidance and supposedly "drug-crutch" reliance as potent therapeutic agents. Unnecessary
Biochemical Defects in Two Types of Human Hepatic Porphyria
Authors: Leon Kaufman, Harvey S. Marver
Journal: New England Journal of Medicine (1970)

In a patient with hereditary coproporphyria, increased enzymatic synthesis of δ-aminolevulinic acid (ALA) in the liver contributed to the increased excretion of porphyrins and their precursors. A similar enzymatic abnormality has been found in acute intermittent porphyria. By contrast, in a patient with porphyria cutanea tarda, despite massive porphyrinuria, hepatic ALA synthetase was not detectably elevated. Additional experimental data indicate that heme participates in the feedback regulation of ALA synthetase. Three possible hypotheses describe the defective site of porphyrin biosynthesis in the hepatic porphyrias: a primary increase in ALA synthetase activity; partial blocks in heme biosynthesis; or diversion of heme from its role in the feedback regulation of ALA synthetase.
Pregnancy, Abortion, and Birth Rates Among US Adolescents—1980, 1985, and 1990
Authors: Alison M. Spitz
Journal: JAMA (1996)

To analyze pregnancy, abortion, and birth rates among US adolescent girls in 1980, 1985, and 1990.Retrospective analysis of trends in data on pregnancies, abortions, and births.US adolescent girls aged 13 to 19 years.Pregnancy, abortion, and birth rates (with and without adjustment for sexual experience) among teenaged girls aged 15 to 19 years and girls under 15 years.Although pregnancy rates among all teenaged girls 15 to 19 years old remained fairly stable from 1980 to 1985, they increased by 9% during the last half of the decade, totaling 95.9 pregnancies per 1000 teenaged girls 15 to 19 years old by 1990. Because rates of sexual experience increased even faster, pregnancy rates among sexually experienced teens aged 15 to 19 actually declined between 1980 and 1990 by approximately 8%. Abortion rates among these teens remained stable during the 1980s, with 35.8 and 36.0 abortions per 1000 in 1980 and 1990, respectively. As with overall pregnancy rates, abortion rates among these sexually experienced teenaged girls declined during the 1980s. Between 1980 and 1985, birth rates among teenaged girls aged 15 to 19 years declined by 4%, but they increased by 18% during the latter half of the decade, totaling 59.9 births per 1000 in 1990. Among these sexually experienced teenagers, birth rates also declined between 1980 and 1985 and then increased over the next 5 years. In 1990, pregnancies and abortions among girls younger than 15 years accounted for only 3% of all adolescent pregnancies and abortions. However, the number of births among these younger adolescents increased by 15% over the decade. In that age group, trends in pregnancy, abortion and birth rates over the decade were similar to those for older teens. However, during the late 1980s, the abortion rate declined and the pregnancy rate remained stable, resulting in a 26% increase in the birth rate.Despite efforts to reduce adolescent pregnancy in the United States, pregnancy and birth rates for that group continue to be the highest among developed countries. Considering that 95% of adolescent pregnancies are unintended, increased efforts to prevent these pregnancies are warranted.