tbuckley/cabot-search huggingface dataset:
Observational study of vaccine efficacy 14 years after trial of hepatitis B vaccination in Gambian children
Authors: H. Whittle
Journal: BMJ (2002)

To determine the duration of protection from hepatitis B vaccine given in infancy and early childhood.Cross sectional serological study of hepatitis B virus infection in children of various ages 14 years after the start of a trial of vaccination regimens.Two villages in the Gambia.Children and adolescents given hepatitis B vaccine in infancy or early childhood: 232 were aged 1-5 years, 225 aged 5-9 years, 220 aged 10-14 years, and 175 aged 15-19 years.Vaccine efficacy against infection and against chronic infection in the different age groups.Vaccine efficacy against chronic carriage of hepatitis B virus was 94% (95% confidence interval 89% to 97%), which did not vary significantly between the age groups. Efficacy against infection was 80% (76% to 84%). This was significantly lower in the oldest age group (65%, 56 to 73). Of the uninfected participants in this age group, 36% had no detectable hepatitis B virus surface antibody. Time since vaccination and a low peak antibody response were the most powerful risk factors for breakthrough infection (P<0.001 in each case). Low peak antibody response was also a risk factor for chronic carriage (odds ratio 95, 19 to 466).Children vaccinated in infancy are at increased risk of hepatitis B virus infection in the late teens. The risk of chronic carriage after sexual exposure needs further assessment to determine if booster vaccines are necessary.
Review, reevaluation, and new results in quantitative structure-activity studies of anticonvulsants
Authors: Dimitra Hadjipavlou-Litina
Journal: Medicinal Research Reviews (1998)

This paper reviews and reevaluates all of the published QSAR treatments of anticonvulsants and extends them to a new relationship. This reveals that in almost all cases, the Clog P relationship plays a significant part in the QSAR relationship whether the data stems from receptor to whole animal studies. In some cases the steric factors (B5, B1, and L) are important and, in one case, the log VW relationship is of marginal importance. Electronic effects, except for the Hammett's constant σ, are comparatively unimportant. This suggests that the receptors involved possess a special stereochemical and electronic feature: The aromatic ring and the nitrogen moieties (e.g., an amide group) are the primary binding groups. The study shows that log P, as calculated by the Clog P program, is suitable for this form of QSAR study. Log Po of 2 was found to be ideal for passive penetration of these agents into the CNS. © 1998 John Wiley & Sons, Inc., Med Res Rev, 18, No. 2, 91–119, 1998.
Nancy Rushton Brueton
Authors: R. B. M. B. H. Austin
Journal: BMJ (2014)

Nancy Rushton was born in 1919 in Wood Green, north London, and lived there until 1930, when her father, Oswald Rushton Baldwin, became headmaster of St George’s Grammar School in Bristol. The family moved to Bristol, where Nancy spent most of her life. She went to Redland High School, where she became head girl. She then went to Bristol University to study medicine, qualifying MB ChB in 1942, and gaining a distinction in Surgery.

Two weeks later, she married Neville Brueton, who …
Adult T‐cell leukemia/lymphoma with two distinct clones in the peripheral blood and lymph node
Authors: Keisuke Shibata, Yoshinori Shimamoto, Kenji Suga, Masayuki Watanabe, Masako Kikuchi, Masaya Yamaguchi
Journal: American Journal of Hematology (1995)

Abstract A case of adult T‐cell leukemia/lymphoma (ATL) with two different clones in the peripheral blood and lymph nodes is reported here. When cellular DNA from the lymph node was digested with EcoRI , one band larger than 9 Kb was detected. Digestion of the cellular DNA with PstI resulted in one clear band in addition to three internal fragments. In contrast, when cellular DNA from malignant peripheral blood lymphocytes (PBL) was digested with the same endonucleases, distinct bands at positions different from those observed in the lymph node were detected, indicating two separate malignant clones in the patient. Monoclonality of the tumor cells was shown by T‐cell receptor‐β (TCR‐β) gene rearrangement in both PBL and lymph node. Furthermore, there was a difference in the surface phenotype between tumor cells taken from peripheral blood (CD4+, CD8–) and lymph node (CD4+, CD8+). These findings suggest the presence of two different ATL clones in PBL and lymph node in a single patient simultaneously, which is distinguishable by the integration pattern of human T‐cell leukemia virus type I (HTLV‐I) proviral DNA.
Genetic Control of the Quantitative Activity of a Serum Enzyme in Man
Authors: Howard J. Wetstone
Journal: JAMA (1965)

THE GENETIC CONTROL of the quantitative activity of a serum enzyme was first suggested by Augustinsson and Olsson with serum arylesterase (aryl ester hydrolase [International Union of Biochemistry 3.1.1.2] ) 1 in Swedish Landrace swine. 2 However, the authors are unaware of a report of hereditary control of the quantitative activity of a serum enzyme in man although several examples of qualitative differences exist. 3 These qualitative differences of the gene may result, of course, in gross changes in the quantitative activity of an enzyme as it acts upon a substrate. However, they do not express themselves as continuous quantitative changes in phenotype over a normal range of enzyme activity.  Such qualitative differences of serum cholinesterase (acylcholine acyl-hydrolase [IUB 3.1.1.8] ) 4 in man involve the atypical serum cholinesterase first described by Kalow, 3 the C 5 extra component which is most likely nonallelic with respect to the atypical gene 5 a
Dysbiotic gut microbiota causes transmissible Crohn's disease-like ileitis independent of failure in antimicrobial defence
Authors: Monika Schaubeck, Thomas Clavel, Jelena Calasan, Ilias Lagkouvardos, Sven Bastiaan Haange, Nico Jehmlich, Marijana Basic, Aline Dupont, Mathias Hornef, Martin von Bergen, André Bleich, Dirk Haller
Journal: Gut (2015)

Dysbiosis of the intestinal microbiota is associated with Crohn's disease (CD). Functional evidence for a causal role of bacteria in the development of chronic small intestinal inflammation is lacking. Similar to human pathology, TNF(deltaARE) mice develop a tumour necrosis factor (TNF)-driven CD-like transmural inflammation with predominant ileal involvement.Heterozygous TNF(deltaARE) mice and wildtype (WT) littermates were housed under conventional (CONV), specific pathogen-free (SPF) and germ-free (GF) conditions. Microbial communities were analysed by high-throughput 16S ribosomal RNA gene sequencing. Metaproteomes were measured using LC-MS. Temporal and spatial resolution of disease development was followed after antibiotic treatment and transfer of microbial communities into GF mice. Granulocyte infiltration and Paneth cell function was assessed by immunofluorescence and gene expression analysis.GF-TNF(deltaARE) mice were free of inflammation in the gut and antibiotic treatment of CONV-TNF(deltaARE) mice attenuated ileitis but not colitis, demonstrating that disease severity and location are microbiota-dependent. SPF-TNF(deltaARE) mice developed distinct ileitis-phenotypes associated with gradual loss of antimicrobial defence. 16S analysis and metaproteomics revealed specific compositional and functional alterations of bacterial communities in inflamed mice. Transplantation of disease-associated but not healthy microbiota transmitted CD-like ileitis to GF-TNF(deltaARE) recipients and triggered loss of lysozyme and cryptdin-2 expression. Monoassociation of GF-TNF(deltaARE) mice with the human CD-related Escherichia coli LF82 did not induce ileitis.We provide clear experimental evidence for the causal role of gut bacterial dysbiosis in the development of chronic ileal inflammation with subsequent failure of Paneth cell function.
Mitral Valve Repair Versus Revascularization Alone in the Treatment of Ischemic Mitral Regurgitation
Authors: Duk-Hyun Kang, Mi-Jeong Kim, Soo-Jin Kang, Jong-Min Song, Hyun Song, Myeong-Ki Hong, Kee-Joon Choi, Jae-Kwan Song, Jae-Won Lee
Journal: Circulation (2006)

Background— For patients with ischemic mitral regurgitation (MR), it is not clear whether adjunctive mitral valve (MV) repair at the time of coronary artery bypass graft surgery (CABG) is beneficial. We sought to test the hypothesis that MV repair with CABG is superior to CABG alone in improving MR without increasing operative or long-term mortality. Methods and Results— A total of 107 consecutive patients with moderate or severe ischemic MR, as determined by preoperative echocardiography, underwent CABG with concomitant MV repair (repair group, n=50) or CABG only (CABG group, n=57). Degree of MR was graded as none, mild, moderate, or severe by the proximal isovelocity surface area method. The groups were similar with respect to age, gender, baseline New York Heart Association class, ejection fraction, and number of bypass grafts. The repair group had a higher percentage of patients with atrial fibrillation or severe MR than the CABG group. The operative mortality was significantly higher for the repair group (12%) than the CABG group (2%), whereas the 5-year actuarial survival rate of the 2 groups was similar (88%±5% versus 87%±6%). On multivariate logistic regression analysis, older age, higher New York Heart Association class, and atrial fibrillation were independent predictors of operative mortality ( P &lt;0.05). Among patients with severe MR, ischemic MR was improved in all patients of the repair group and in 67% of patients in the CABG group ( P &lt;0.001), whereas improvement rates in patients with moderate MR were similar in the 2 groups (75% versus 67%, P=NS). Conclusions— Although MV repair appears to be more effective at reducing ischemic functional MR, CABG alone may be a preferable treatment option for patients with moderate MR and high operative risk factors such as old age or atrial fibrillation.
Intraperitoneal povidone-iodine
Authors: P. D. Goldenheim
Journal: JAMA (1989)

<h3>In Reply.—</h3> I thank Dr Goldenheim for reemphasizing an important point from my initial comments, namely, the difficulty in comparing results of numerous studies that have a multitude of variables. While there has been "favorable experience" with povidone-iodine solution in prevention of intra-abdominal infection, other studies have failed to show any advantage over saline or antibiotic solutions. Furthermore, my comments addressed the use of povidone-iodine solution only as it relates to intra-abdominal infection; Dr Goldenheim's comments regarding its efficacy in other settings are irrelevant. I share the concerns of Dr Goldenheim regarding extrapolation of in vitro data to the clinical situation. Nonetheless, the ideal way to evaluate a clinical problem is to minimize the number of variables. This is best accomplished in the in vitro setting, and information obtained in this manner usually is vital to our understanding of clinical problems. The final paragraph of my initial reply merely states
Expression of cytosolic retinoid-binding protein genes in human skin biopsies and cultured keratinocytes and fibroblasts
Authors: H. TÖRMÄ, W. LÖNTZ, WEI LIU, O. ROLLMAN, A. VAHLQUIST
Journal: British Journal of Dermatology (2006)

Using reverse transcription coupled to polymerase chain reaction we have studied the mRNA expression of serum retinol-binding protein and cytosolic receptors for retinol and retinoic acid in skin biopsies, and in cultured epidermal keratinocytes and dermal fibroblasts. Transcripts for cellular retinol-binding protein (CRBP) I and cellular retinoic-acid-binding protein (CRABP) I were found in normal skin, keratinocytes, and fibroblasts. CRABP II transcripts were detected in skin and keratinocytes. A decreased mRNA expression of CRABP I and an increased mRNA expression of CRABP II were found in lesional psoriatic skin compared with uninvolved skin. mRNA transcripts for serum retinol-binding protein (s-RBP) were detected in all tissues and cells. The biological importance of s-RBP expression in keratinocytes and fibroblasts is not known, but hypothetically this protein may be involved in the intracellular shuttling of retinol and retinoic acid, or in the retransportation of cellular retinoids into the extracellular space.
Abstract 246: Calmodulin binding to death receptor-5 regulates pancreatic cancer apoptosis
Authors: Kaiyu Yuan, Tong Zhou, Jay McDonald, Yabing Chen
Journal: Cancer Research (2012)

Abstract Targeting the extrinsic apoptosis pathway initiated by death receptors has been shown to be a promising therapy for pancreatic cancer. TRA-8, a humanized activating antibody for the death receptor 5 (DR5), is a potent therapeutic reagent for pancreatic cancer. However, several pancreatic cell lines are resistant to TRA-8-induced cell death. We have previously demonstrated that calmodulin (CaM) is recruited into the death-inducing signaling complex (DISC) by Fas death receptor activation, and that antagonists of CaM regulate DISC formation. Therefore, we determined the function of CaM in DR5-induced apoptosis of pancreatic cancer cells. We found that trifluoperazine (TFP), a CaM antagonist, enhanced TRA-8-induced cell death of pancreatic cells, PANC-1 and S2VP10, by 55% and 45% respectively. Consistent with the increased apoptosis, TFP increased TRA-8-induced activation of caspase 8 and caspase 3 in these cells. To determine the underlying molecular mechanisms, we analyzed the DR5-induced DISC. Interaction of CaM and DR5 was demonstrated by co-immunoprecipitation by using DR5 antibody. Activation of DR-5 by TRA-8 increased recruitment of CaM into the DISC which was inhibited by treatment with TFP. In addition, TFP decreased recruitment of the adaptor protein, FADD, and recruitment of other DISC proteins that regulate cell survival, including Src and FLICE-like inhibitory protein (FLIP), an inhibitor of caspase-8. These results suggest an important role for CaM in DR5-induced DISC formation in pancreatic cancer cells, regulating DR5-mediated survival and apoptotic signaling. In summary, we have demonstrated that CaM antagonism sensitizes pancreatic cancer cell to TRA 8-induced cell death, and that CaM binding to DR5 regulates DR5-induced DISC formation. Defining the function of CaM in regulating DR5-induced signaling pathways may lead to novel therapeutic strategies for pancreatic cancer therapy including possible combination therapy with TRA-8 and calmodulin antagonists. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 246. doi:1538-7445.AM2012-246
Ecology of Staphylococcal Disease
Authors: Ruth B. Kundsin
Journal: JAMA (1963)

An epidemiological and bacteriological survey was made of a detached community of young married graduate students with a high proportion of young children to determine the prevalence of presumed staphylococcal disease. Of these families, 94% cooperated. The number of infections reported was higher (31%) for families with children less than 2 years of age as opposed to families (10%) with no children or older children. Larger families had a higher prevalence of infections. Cultures of 388 persons revealed a 57% carrier rate of Staphylococcus aureus, higher than rates reported for other populations. Hospitals are implicated as the origin of the S aureus in this community. Staphylococci are introduced into the home by a colonized newborn and subsequently maintained by carriers in the family—particularly the mother. Housekeeping and laundry practices perpetuate and redistribute the bacteria. HOSPITALS HAVE BEEN ACCUSED of accumulating reservoirs of<i>Staphylococcus aureus</i>, then colonizing patients and releasing
THE PRESENT STATUS OF THE TRANSMISSIBILITY OF BOVINE TUBERCULOSISAS ILLUSTRATED BY INFANTS AND YOUNG CHILDREN.
Authors: HENRY LARNED KEITH SHAW
Journal: JAMA (1907)

Koch, in his historic address before the British Congress for Tuberculosis in 1901, called the attention of the medical profession throughout the world to the question of the intercommunicability of bovine and humane tuberculosis. That there was a distinct difference in the morphology of the tubercle bacillus of bovine and of human origin had been convincingly shown by Theobald Smith of Boston in 1898. Koch went further and denied the transmissibility from man to cow and<i>vice versa</i>. He was the first to state authoritatively that tuberculous cattle are not a source of infection to human beings. Behring takes the opposite view and claims that all tuberculosis is of bovine origin, the bacilli entering the system during childhood and in most cases remaining latent for years. Such diverse opinions, held by eminent and scientific authorities, have aroused the widest interest and bred countless controversies. No attempt will be made in
Nitric Oxide Deficiency in Fenfluramine- and Dexfenfluramine-induced Pulmonary Hypertension
Authors: STEPHEN L. ARCHER, KHIER DJABALLAH, MARC HUMBERT, E. KENNETH WEIR, MURIEL FARTOUKH, JOSETTE DALL'AVA-SANTUCCI, JEAN-CHRISTOPHE MERCIER, GERALD SIMONNEAU, A. TUAN DINH-XUAN
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Dexfenfluramine and fenfluramine greatly increase the risk of developing pulmonary hypertension (PHT). The mechanism of anorexigen-associated PHT (AA-PHT) and the reason PHT occurs in a minority of people exposed are unknown. Anorexigens are weak pulmonary vasoconstrictors, but they become potent when synthesis of the endogenous vasodilator nitric oxide (NO) is suppressed. We hypothesized NO deficiency predisposes affected individuals to develop AA-PHT. A prospective, case-control, study was performed on consecutive patients with AA-PHT (n = 9). Two sex-matched control groups were selected: patients with primary PHT (P-PHT, n = 8) and normal volunteers (n = 12). Lung NO production (VNO) and systemic plasma oxidation products of NO (NOx) were measured at rest and during exercise. AA-PHT developed 17 ± 6 mo after a short course of anorexigen (6 ± 2 mo) and was irreversible. VNO was lower in AA-PHT than in P-PHT and correlated inversely with PVR (p < 0.05). The apparent VNO deficiency may have resulted from increased oxidative inactivation of NO in patients with AA-PHT, as their NOx levels were elevated (p < 0.05) in inverse proportion to VNO (r2 = 0.55; p < 0.02). In susceptible persons, anorexigens can cause an irreversible syndrome of PHT, hypoxemia, and systemic vascular complications after brief exposures. These patients have a relative NO deficiency years after discontinuing the anorexigen, perhaps explaining their original susceptibility.
Surveillance of extensively drug-resistant tuberculosis in Europe, 2003-2007
Authors: I Devaux, D Manissero, K Fernandez de la Hoz, K Kremer, D van Soolingen, None on behalf of the EuroTB network
Journal: Eurosurveillance (2010)

This paper describes the results of second-line drug (SLD) susceptibility tests among multidrug-resistant tuberculosis (MDR TB) cases reported in 20 European countries aiming to identify extensively drug-resistant tuberculosis (XDR TB) cases. A project on molecular surveillance of MDR TB cases was conducted by EuroTB and the National Institute for Public Health and the Environment (RIVM) from 2005 to 2007. Information on drug susceptibility testing (DST) was provided to this project and case-based data on MDR TB cases were reported on a quarterly basis by 20 countries of the World Health Organization s European Region, including 15 European Union Member States. Data included SLD susceptibility test results, enabling a retrospective description of XDR TB cases notified between 2003 and 2007 .In 18 countries DST was performed for two or more of the SLD included in the XDR TB definition. The proportion of MDR TB isolates tested for SLD varied widely between countries (range 20 to 100 percent). In the 18 countries, 149 (10%) XDR TB cases were reported among MDR TB cases with available DST results for SLD. Sixteen additional MDR TB cases were reported by the MDR TB surveillance system when compared with the number of routinely reported MDR TB cases to EuroTB in ten countries with representative data reported during three consecutive years (2003-2005). To counter the threat of XDR TB in Europe, a standardised approach to XDR TB surveillance and DST for SLD is needed, as well as increased laboratory capacity across European countries.
Psoriasis: a defect in the regulation of epidermal proteases, as shown by serial biopsies after cantharidin application
Authors: L. DUBERTRET, B. BERTAUX, M. FOSSE, R. TOURAINE
Journal: British Journal of Dermatology (1984)

The possible role of epidermal serine proteases in the genesis of psoriatic lesions was investigated by sequential biopsies of the epidermal damage induced by topical cantharidin. In the skin of normal subjects, epidermal damage was followed by the transient appearance of proteolytic activity in the upper epidermis accompanied by temporary hyperacanthosis and perivascular inflammatory cells in the superficial dermis. In the uninvolved skin of five patients with psoriasis this proteolysis persisted longer, for more than 7 days. Thereafter, in three of the patients, the proteolysis abated, and this was followed by disappearance of the hyperacanthosis and the dermal infiltrate; in the other two psoriatics the proteolysis and hyperacanthosis increased, and a typical Koebner phenomenon ensued. Migration of neutrophils into the epidermis occurred as a later event. Thus the abnormal persistence of proteolytic activity in the upper epidermis after cantharidin application distinguishes the normal from the psoriatic skin injury response and might initiate the psoriatic lesion.
Idiopathic Hemochromotosis and Alpha-1-Antitrypsin Deficiency: Coexistence in a Family with Progressive Liver Disease in the Proband
Authors: Suri Anand, Robert R. Schade, Carlos Bendetti, Robert Kelly, Bruce S. Rabin, John Krause, Thomas E. Starzl, Shunzaburo Iwatsuki, David H. Van Thiel
Journal: Hepatology (1983)

A patient with coexistent hemochromatosis and alpha-1-antitrypsin deficiency which led to cirrhosis and death despite adequate therapy for hemochromatosis is reported. Evaluation of the family revealed first degree relatives with iron overload and others with alpha-1-antitrypsin deficiency but none with both conditions. The role of family studies in the early recognition and possible prevention of overt clinical disease in individuals with either of these two genetic diseases is discussed.