tbuckley/cabot-search huggingface dataset:
The Art of Betting: Which of a Bleeder's Female Relatives Is a Carrier?
Authors: OSCAR D. RATNOFF
Journal: Annals of Internal Medicine (1978)

Editorials1 August 1978The Art of Betting: Which of a Bleeder's Female Relatives Is a Carrier?OSCAR D. RATNOFF, M.D., PAUL K. JONES, PH.D.OSCAR D. RATNOFF, M.D.Search for more papers by this author, PAUL K. JONES, PH.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-89-2-281 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptClassic hemophilia is a rare disease and Christmas disease, rarer still. These two disorders are essentially limited to males, in whom the bleeding propensity is roughly proportional to the degree of deficiency of antihemophilic factor (AHF, factor VIII) or Christmas factor (factor IX), as measured in assays of clotting function. The female relatives of these bleeders are ordinarily asymptomatic, but some may transmit the bleeding tendency to their sons.For many reasons, classic hemophilia and Christmas disease have evoked a disproportionate interest among physicians; one such reason may be a fascination with the peculiar pattern of inheritance, a pattern that...References1. SHANBERGEGORE JI: Studies on the immunologic and physiologic activities of antihemophilic factor (AHF) (abstract). J Lab Clin Med 50:954, 1957 Google Scholar2. ZIMMERMANRATNOFFPOWELL TOA: Immunologic differentiation of classic hemophilia (factor VIII deficiency) and von Willebrand's disease. J Clin Invest 50:244-254, 1971 CrossrefMedlineGoogle Scholar3. BENNETTHUEHNS EE: Immunological differentiation of three types of haemophilia and identification of some female carriers. Lancet 2:956-958, 1970 CrossrefMedlineGoogle Scholar4. RATNOFFJONES OP: The laboratory diagnosis of the carrier state for classic hemophilia. Ann Intern Med 86:521-528, 1977 LinkGoogle Scholar5. Methods for the detection of haemophilia carriers: a memorandum. Bull WHO 55:675-702, 1977 MedlineGoogle Scholar6. RATNOFF O: Implications of the identification of carriers of chronic disease (editorial). J Chronic Dis 30:543-545, 1977 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByPrenatal diagnosis of haemophilia A and Christmas diseaseIdentifying Carriers of Mild Haemophilia 1 August 1978Volume 89, Issue 2Page: 281-282KeywordsHemophilia AHemophilia BHemorrhage Issue Published: 1 August 1978 PDF DownloadLoading ...
Searching for reliable research evidence need not be difficult
Authors: T. A Sheldon, J. Glanville
Journal: BMJ (1999)

EDITOR—Samanta and Beardsley summarise their search for and use of research evidence to inform their treatment of a patient with low back pain due to sciatica that did not respond to conservative treatment.1 They are to be applauded for their explicit and conscientious use of research, but we are surprised by their method of searching for relevant systematic reviews and trials.

Instead of …
The tumor-associated antigen EBAG9 negatively regulates the cytolytic capacity of mouse CD8+ T cells
Authors: Constantin Rüder, Uta E. Höpken, Jana Wolf, Hans-Willi Mittrücker, Boris Engels, Bettina Erdmann, Susanne Wollenzin, Wolfgang Uckert, Bernd Dörken, Armin Rehm
Journal: Journal of Clinical Investigation (2009)

CTLs eliminate virus-infected and tumorigenic cells through exocytosis of cytotoxic agents from lytic granules. While insights into the intracellular mechanisms facilitating lytic granule release have been obtained through analysis of loss-of-function mutations in humans and mice, there is a paucity of information on negative regulators of secretory lysosome release at the molecular level. By generating and analyzing estrogen receptor–binding fragment-associated antigen 9–KO (Ebag9 KO) mice, we show here that loss of EBAG9 confers CTLs with enhanced cytolytic capacity in vitro and in vivo. Although loss of EBAG9 did not affect lymphocyte development, it led to an increase in CTL secretion of granzyme A, a marker of lytic granules. This resulted in increased cytotoxicity in vitro and an enhanced cytolytic primary and memory T cell response in vivo. We further found that EBAG9 interacts with the adaptor molecule γ2-adaptin, suggesting EBAG9 is involved in endosomal-lysosomal biogenesis and membrane fusion. Indeed, granzyme B was sorted to secretory lysosomes more efficiently in EBAG9-deficient CTLs than it was in WT CTLs, a finding consistent with the observed enhanced kinetics of cathepsin D proteolytic processing. While EBAG9 deficiency did not disrupt the formation of the immunological synapse, lytic granules in Ebag9–/– CTLs were smaller than in WT CTLs. These data suggest that EBAG9 is a tunable inhibitor of CTL-mediated adaptive immune response functions.
New concepts on erythema annulare centrifugum: a clinical reaction pattern that does not represent a specific clinicopathological entity
Authors: M. Ziemer, K. Eisendle, B. Zelger
Journal: British Journal of Dermatology (2008)

Erythema annulare centrifugum (EAC) is considered an inflammatory skin disease with unknown aetiology. In most textbooks it is assigned to the incoherent conglomeration of figurate or gyrate erythemas.To re-evaluate a large cohort of patients with EAC and to assess the evidence for infection with Borrelia.We retrospectively investigated 90 cases with the diagnosis of EAC. Haematoxylin and eosin sections were re-examined and diagnoses were specified; these were then confirmed by clinicopathological correlation. Infection with Borrelia was assessed by focus-floating microscopy and by a Borrelia-specific polymerase chain reaction (PCR).Besides a miscellaneous group of annular disorders at times confused with EAC such as urticaria, leucocytoclastic vasculitis and psoriasis (20 of 90; 22%), EAC appeared to serve as a collective term for three main clinicopathological reaction patterns: (i) (tumid) lupus erythematosus (29 of 90; 32%), (ii) spongiotic dermatitides (25 of 90; 28%) and (iii) pseudolymphoma (16 of 90; 18%). In 13 of 16 (81%) cases with a pseudolymphomatous reaction pattern spirochaetes stained positive but were negative in other reaction patterns of EAC as well as in negative controls. These findings were confirmed by a Borrelia-specific PCR which was positive in two of three (67%) of these pseudolymphomatous EAC cases but was negative in all other variants of EAC (none of five) as well as 20 controls.We conclude that 'EAC' is a clinical reaction pattern that does not represent a specific clinicopathological entity and should lead to consideration of mainly lupus erythematosus, dermatitis and, in some cases, cutaneous Lyme disease.
Esomeprazole With Aspirin Versus Clopidogrel for Prevention of Recurrent Gastrointestinal Ulcer Complications
Authors: Kam–Chuen Lai, Kent–Man Chu, Wai–Mo Hui, Benjamin Chun–Yu Wong, Wai–Ka Hung, Ching–Kong Loo, Wayne Hsing–Ching Hu, Annie On–On Chan, Ka–Fai Kwok, Tang–Tat Fung, John Wong, Shiu–Kum Lam
Journal: Clinical Gastroenterology and Hepatology (2006)
On Methods and Materials
Authors: David A. Sacks
Journal: Diabetes Care (2002)

Parretti et al. (1) were very meticulous in assuring that their subjects had similar demographics and were glucose tolerant, healthy, and of similar gestational age. Of note is their finding of a mean fasting glucose value of 56.2 mg/dl and mean 24-h glucose values of 74.7 mg/dl. These results are substantially lower than those found by previous investigators who reported fasting plasma glucose concentrations between 78 and 80 mg/dl (2–4) and 24-h mean glucose …
A direct clinical role for intravascular ultrasound: Utility in the assessment and treatment of coarctation of the aorta
Authors: Brenda Sanzobrino, Linda Gillam, Raymond McKay, Leon Chameides, Daniel Diana, Harris Leopold, Steven Schwartz, Sarah Katz, Tsui-Lieh Hsu, Natesa Pandian
Journal: Journal of the American College of Cardiology (1991)
Angiolymphoid hyperplasia with eosinophilia affecting the penis
Authors: P. Dewan, N.D. Francis, J.T. Lear, C.B. Bunker
Journal: British Journal of Dermatology (2008)

Journal Article Angiolymphoid hyperplasia with eosinophilia affecting the penis Get access P. Dewan, P. Dewan Department of Dermatology, Chelsea and Westminster Hospital, Imperial College School of Medicine, London SW10 9NH, U.K. E‐mail: priyadewan111@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar N.D. Francis, N.D. Francis Department of Histopathology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.T. Lear, J.T. Lear Department of Dermatology, Manchester Royal Infirmary, Manchester, U.K. Search for other works by this author on: Oxford Academic Google Scholar C.B. Bunker C.B. Bunker Department of Dermatology, Chelsea and Westminster Hospital, Imperial College School of Medicine, London SW10 9NH, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 159, Issue 3, 1 September 2008, Pages 755–757, https://doi.org/10.1111/j.1365-2133.2008.08733.x Published: 01 September 2008
Enhancer-dependent and -independent steps in the rearrangement of a human T cell receptor delta transgene.
Authors: P Lauzurica, M S Krangel
Journal: The Journal of Experimental Medicine (1994)

The rearrangement and expression of T cell receptor (TCR) gene segments occurs in a highly ordered fashion during thymic ontogeny of T lymphocytes. To study the regulation of gene rearrangement within the TCR alpha/delta locus, we generated transgenic mice that carry a germline human TCR delta minilocus that includes V delta 1, V delta 2, D delta 3, J delta 1, J delta 3, and C delta segments, and either contains or lacks the TCR delta enhancer. We found that the enhancer-positive construct rearranges stepwise, first V to D, and then V-D to J. Construct V-D rearrangement mimics a unique property of the endogenous TCR delta locus. V-D-J rearrangement is T cell specific, but is equivalent in alpha/beta and gamma/delta T lymphocytes. Thus, either there is no commitment to the alpha/beta and gamma/delta T cell lineages before TCR delta gene rearrangement, or if precommitment occurs, it does not operate directly on TCR delta gene cis-acting regulatory elements to control TCR delta gene rearrangement. Enhancer-negative mice display normal V to D rearrangement, but not V-D to J rearrangement. Thus, the V-D to J step is controlled by the enhancer, but the V to D step is controlled by separate elements. The enhancer apparently controls access to J delta 1 but not D delta 3, suggesting that a boundary between two independently regulated domains of the minilocus lies between these elements. Within the endogenous TCR alpha/delta locus, this boundary may represent the 5' end of a chromatin regulatory domain that is opened by the TCR delta enhancer during T cell development. The position of this boundary may explain the unique propensity of the TCR delta locus to undergo early V to D rearrangement. Our results indicate that the TCR delta enhancer performs a crucial targeting function to regulate TCR delta gene rearrangement during T cell development.
Pregravid Liver Enzyme Levels and Risk of Gestational Diabetes Mellitus During a Subsequent Pregnancy
Authors: Sneha B. Sridhar, Fei Xu, Jeanne Darbinian, Charles P. Quesenberry, Assiamira Ferrara, Monique M. Hedderson
Journal: Diabetes Care (2014)

Liver enzymes are independent predictors of type 2 diabetes. Although liver fat content correlates with features of insulin resistance, a risk factor for developing gestational diabetes mellitus (GDM), the relationship between liver enzymes and GDM is unclear. The objective of this study was to assess whether pregravid liver enzyme levels are associated with subsequent risk of GDM.A nested case-control study was conducted among women who participated in the Kaiser Permanente Northern California multiphasic health checkup (1984-1996) and had a subsequent pregnancy (1984-2009). Case patients were 256 women who developed GDM. Two control subjects were selected for each case patient and matched for year of blood draw, age at examination, age at pregnancy, and number of intervening pregnancies.Being in the highest quartile versus the lowest quartile of γ-glutamyl transferase (GGT) levels was associated with a twofold increased risk of subsequent GDM (odds ratio 1.97 [95% CI 1.14-3.42]), after adjusting for race/ethnicity, prepregnancy BMI, family history of diabetes, and alcohol use. This result was attenuated after adjusting for homeostasis model assessment of insulin resistance (HOMA-IR), fasting status, and rate of gestational weight gain. There was significant interaction between GGT and HOMA-IR; the association with GGT was found among women in the highest tertile of HOMA-IR. Aspartate aminotransferase and alanine aminotransferase were not associated with increased GDM risk.Pregravid GGT level, but not alanine aminotransferase or aspartate aminotransferase level, predicted the subsequent risk of GDM. Markers of liver fat accumulation, such as GGT level, are present years before pregnancy and may help to identify women at increased risk for subsequent GDM.
Randomised, double blind, placebo controlled trial of inosine pranobex in rheumatoid arthritis.
Authors: M Brzeski, R Madhok, J A Hunter, H A Capell
Journal: Annals of the Rheumatic Diseases (1990)

In a randomised, placebo controlled, double blind study inosine pranobex was assessed as a possible second line drug in rheumatoid arthritis. Twenty four patients received inosine pranobex (3 g/day) and 26 patients received placebo for up to 24 weeks. Morning stiffness, articular index, grip strength, pain score, erythrocyte sedimentation rate, C reactive protein, IgG, IgM, and serum urate were assessed at weeks 0, 12, and 24. Baseline characteristics were similar except for a significantly higher C reactive protein in the placebo group. No significant improvement occurred in any variable: (a) when comparing week 0 with week 12 or week 24 for either group, (b) comparing active drug with placebo at week 12 or 24, or (c) taking all 50 patients as one group. Withdrawal from the study for lack of response or side effects was similar in both groups. Serum urate increased transiently but significantly with inosine pranobex (a recognised side effect). It is concluded that inosine pranobex has no second line activity in rheumatoid arthritis. Further, 50 patients effectively given placebo showed no spontaneous improvement in their disease activity.
ASSESSMENT OF NONCULPRIT VULNERABLE PLAQUE WITH CORONARY COMPUTED TOMOGRAPHY ANGIOGRAPHY IN COMPARISON TO INTRAVASCULAR ULTRASOUND
Authors: Kunihiko Makino, Takuro Takagi, Tetsuo Lee, Yuta Tajiri, Yukiko Kusunose, Yoshinari Enomoto, Yoshinori Nagashima, Kenji Yamazaki, Tadashi Araki, Masato Nakamura, Kaoru Sugi
Journal: Journal of the American College of Cardiology (2014)
Famotidine Therapy for Active Duodenal Ulcers
Authors: James C. Reynolds
Journal: Annals of Internal Medicine (1989)

Objective: To identify factors that influence the rate of healing of duodenal ulcers. Design: A stepwise multivariable statistical analysis of patients with duodenal ulcer in a multicenter, prospective, open-label study. Healing was assessed by endoscopy at 4 or 8 weeks. Antacid use and symptoms were recorded in a daily diary. Subjects: Of 135 patients, ages 19 to 86, 50% had a previous duodenal ulcer, 46.7% smoked, and 34.8% had melena or hematemesis. Interventions: Famotidine, 40 mg orally, at bedtime for 4 or 8 weeks depending on endoscopic evaluation of ulcer healing. Limited antacid use was permitted. Setting: Office practices, hospital practices, and university-based medical centers. Measurements and Main Results: Multivariable analysis identified five independent predictors present at the time of diagnosis that influenced ulcer healing. The odds of not healing for each risk factor after simultaneous adjustment of the other risk factors were as follows: alcohol use, 6.5 (CI, 2.0 to 20.7, P < 0.002); ulcer size > 10 mm, 4.2 (CI, 1.5 to 11.6, P < 0.005), bleeding symptoms, 3.5 (CI, 1.2 to 10.2, P < 0.03); and a previous duodenal ulcer, 3.1 (CI, 1.05 to 9.0, P < 0.04). The use of salicylates or nonsteroidal anti-inflammatory drugs before treatment was associated with an improved odds of healing (adjusted odds ratio, 0.2; CI, 0.1 to 0.9, P < 0.04). The percentage of patients achieving complete ulcer healing after 4 weeks of famotidine decreased inversely with the number of risk factors present, ulcer size, and the quantity of daily alcohol use (P < 0.001). Fewer than half of those patients who still had severe pain at day 7 achieved healing at 4 weeks (P < 0.001). In contrast, smoking and 23 other factors had no statistically discernible effect on ulcer healing with famotidine. Conclusions: Five variables present at the time of diagnosis independently influenced the rate of ulcer healing at 4 weeks: alcohol use, ulcer size, bleeding symptoms, a previous duodenal ulcer, and previous use of salicylates or nonsteroidal anti-inflammatory drugs.
NHS continuing care for people with learning disabilities
Authors: D. Chakraborti
Journal: BMJ (1993)

post-term delivery.'A review of 55 636 deliveries at the National Maternity Hospital, Dublin, reported an incidence of seizures of 5-4 per 1000 in those delivered after 42 weeks, compared with 0 9 per 1000 in those delivered before 42 weeks.3Cardozo states that it is important to involve the mother in decision making.Again, in her own trial 10% of the mothers refused randomisation to conservative management.2In an analysis of women's attitude towards elective delivery Roberts and Young concluded that most pregnant women are unwilling to accept conservative management of prolonged pregnancy and become more reluctant to do so by 41 weeks' gestation.4In 1990 the rate of induction among the 16 units in North West Thames region varied between 1O% and 25%.Obviously, views differ greatly, but many obstetricians will, with some justification, counsel patients with regard to elective delivery 10 to 12 days after the due date and many women will accept.
Pelvic Stress Fracture in Female Runners
Authors: DAVID A. THORNE, FREDERICK L. DATZ
Journal: Clinical Nuclear Medicine (1986)

Stress fractures are a common injury in long-distance runners, and typically involve the lower extremities. Although relatively rare, pubic ramus stress fractures also occur, primarily in female runners. Bone imaging visualized a pubic stress fracture and a tibial stress fracture in a female long-distance runner with groin pain. Pubic stress fractures should be considered in female runners who present with groin pain. Radionuclide bone imaging is useful in diagnosing these lesions.
Abstract LB-263: Novel tumor suppressors and mutationally affected signaling pathways in small-cell lung cancer identified by whole exome sequencing
Authors: Martin Peifer, Roman K. Thomas
Journal: Cancer Research (2011)

Abstract Small-cell lung cancer (SCLC) is an aggressive lung cancer subtype characterized by early metastasis and a peculiar neuroendocrine phenotype. Unfortunately, SCLC is difficult to sample because these patients are not routinely undergoing surgery. In order to shed light on the biology of this tumor type and to discover novel therapeutic targets, we have conducted whole-exome sequencing of 24 SCLC tumors as well as high-density gene copy number analyses of 64 SCLC specimens. On average we observe a high mutation rate of 7.9±1.0 protein changing mutations per million basepairs and an unusually high C:G&amp;gt;A:T transversion rate that has been associated with excessive smoking. In addition to frequent mutations in TP53 (80%) and RB1(63%), we identified mutations in LRP1B (13/24 samples), a gene that is known to be frequently mutated in lung adenocarcinoma. To our surprise, we found a significant enrichment of neuronal genes (FDR q-value: &amp;lt; 10e-10) suggesting that the neuroendocrine differentiation of SCLC might be primarily driven by mutational events. Other frequently mutated genes encode proteins involved in cell-cell and cell-matrix interactions. This observation might explain the aggressiveness and metastatic capability of SCLC. A systematic analysis of copy number losses and loss of heterozygosity revealed a distinct pattern for novel candidate tumor suppressor genes when integrated with somatic mutations. Performing the pathway analysis on each individual sample clearly showed that SCLC tumors segregate by mutational landscape. Furthermore, the analysis of autopsy-derived tumor specimens revealed that surgically resected tumors are not dissimilar to late-stage SCLC. In summary, we have defined the mutational and genomic landscape of SCLC that may help explaining some of the phenotypic and clinical properties of this fatal tumor type. Our data provides a rich source for future functional analyses of putative tumor suppressor genes and oncogenes as well as for potential novel drug targets. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-263. doi:10.1158/1538-7445.AM2011-LB-263
331. Small Fragment Homologous Replacement (SFHR) Modification of Genomic HPRT Occurs in the Presence of Wild-Type p53 in Lymphoblastoid Cells
Authors: Babak Bedayat, Alireza Abdolmohammadi, Rosalie Maurisse, Jennifer Shwarz, Judi Cheung, David De Semir, Patric K O'Neill, Janice A. Nicklas, Dieter C. Gruenert
Journal: Molecular Therapy (2006)

Gene therapy has opened the door to new therapeutic interventions for the treatment of genetic diseases. In addition to the standard cDNA-based approaches, alternative gene targeting strategies have been developed. In this study, one of these gene targeting strategies, small fragment homologous replacement (SFHR), has been used to correct a point mutation in exon 3 of the hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene. This point mutation inactivates HPRT gene and allows the cells to grow in 6-thioguanine (6TG) containing medium, but not in hypoxanthine/ aminopterin/thymidine (HAT) containing medium. The HPRT mutant lymphoblastoid cell line, LT1-1B1 (p53+), was transfected with a 579-bp small DNA fragment (SDF) comprising the mutant exon (exon 3) using the AMAXA Nucleofection/Electroporation system. Several different SDF doses were evaluated. Since the cells contained wild-type p53, it was also possible to determine if p53 inhibited SFHR-mediated modification. Corrected cells were selected in HAT containing medium and further analyzed by PCR and by direct sequencing. Quantitative analysis showed an SFHR correction frequency between 0.1 to 2% in three separate experiments.