tbuckley/cabot-search huggingface dataset:
Gender identity in testicular feminisation Phenotypically, anatomically, legally, and socially female
Authors: J A O Ahlquist, None Anonymous
Journal: BMJ (1994)

EDITOR, - The personal view on testicular feminisation expresses poignantly the difficulties facing someone who has to come to terms with the condition.1 The author was clearly distressed to learn that she was “chromosomally male, a pseudohermaphrodite,” and highlights the essence of the problem in asking “What makes a person female?” Doctors make a fundamental mistake in cases of testicular feminisation if they concentrate on the chromosomal definition of sex - a definition that is unhelpful to the patient.

There are many definitions of a person's gender: genotypic (chromosomal pattern); gonadal (testis or ovary); phenotypic (including body habitus and genital anatomy); hormonal (oestrogen or androgen effects in the target tissues); legal (birth certificate, passport, etc); and, most importantly, social, which includes how we see ourselves, how others see us, the approach to sexual relationships, and everyday matters such as which changing room to use and which schools we may go to. Discordance among these definitions of gender may lead to problems in sexual identity. But patients with testicular feminisation have a high degree of concordance in their sexual …
Higher dynamic medial knee load predicts greater cartilage loss over 12 months in medial knee osteoarthritis
Authors: Kim L Bennell, Kelly-Ann Bowles, Yuanyuan Wang, Flavia Cicuttini, Miranda Davies-Tuck, Rana S Hinman
Journal: Annals of the Rheumatic Diseases (2011)

Objective Mechanical factors, in particular increased medial knee joint load, are believed to be important in the structural progression of knee osteoarthritis. This study evaluated the relationship of medial knee load during walking to indices of structural disease progression, measured on MRI, in people with medial knee osteoarthritis. Methods A longitudinal cohort design utilising a subset of participants (n=144, 72%) enrolled in a randomised controlled trial of lateral wedge insoles was employed. Medial knee load parameters including the peak knee adduction moment (KAM) and the KAM impulse were measured at baseline using three-dimensional gait analysis during walking. MRI at baseline and at 12 months was used to assess structural indices. Multiple regression with adjustment for covariates assessed the relationship between medial knee load parameters and the annual change in medial tibial cartilage volume. Binary logistic regression was used for the dichotomous variables of progression of medial tibiofemoral cartilage defects and bone marrow lesions (BML). Results A higher KAM impulse, but not peak KAM, at baseline was independently associated with greater loss of medial tibial cartilage volume over 12 months (β=29.9, 95% CI 6.3 to 53.5, p=0.01). No significant relationships were seen between medial knee load parameters and the progression of medial tibiofemoral cartilage defects or BML. Conclusion This study suggests knee loading, in particular the KAM impulse, may be a risk factor for loss of medial tibial cartilage volume. As knee load is modifiable, load-modifying treatments may potentially slow disease progression.
Epidemiology and Prevention of Periodontal Disease in Individuals With Diabetes
Authors: Patricia P Katz, M Robert Wirthlin, Susan M Szpunar, Joseph V Selby, Stephen J Sepe, Jonathan A Showstack
Journal: Diabetes Care (1991)

This article reviews the epidemiological evidence of the relationship between diabetes and periodontal disease, possible physiological mechanisms for the association, and effects of interventions on the occurrence and severity of periodontal disease among individuals with diabetes.A comprehensive qualitative review of published literature in the area was performed.Much of the research in this area was found to contain methodological problems, such as failing to specify the type of diabetes, small sample sizes, and inadequate control of covariates such as age or duration of diabetes.Trends indicate that periodontal disease is more prevalent and more severe among individuals with diabetes. This trend may be modified by factors such as oral hygiene, duration of diabetes, age, and degree of metabolic control of diabetes. Generally, poor oral hygiene, a long history of diabetes, greater age, and poor metabolic control are associated with more severe periodontal disease. The association of diabetes and periodontal disease may be due to numerous physiological phenomena found in diabetes, such as impaired resistance, vascular changes, altered oral microflora, and abnormal collagen metabolism. With some modifications, the same prevention and treatment procedures for periodontal disease recommended for the general population are appropriate for those with diabetes. People with diabetes who appear to be particularly susceptible to periodontal disease include those who do not maintain good oral hygiene or good metabolic control of their diabetes, those with diabetes of long duration or with other complications of diabetes, and teenagers and pregnant women.
Investigational Immunotherapeutics for B-Cell Malignancies
Authors: Alfonso Quintás-Cardama, William Wierda, Susan O'Brien
Journal: Journal of Clinical Oncology (2010)

The use of rituximab-based chemoimmunotherapy regimens has remarkably improved the response rates, long-term outcomes, and quality of life of patients with B-cell malignancies. However, a substantial number of patients exhibit either primary or acquired resistance to rituximab, which suggests that novel immunotherapeutics with distinct mechanisms of action are necessary. A series of monoclonal antibodies with specificity against different surface antigens expressed on malignant B cells (eg, CD22, CD23, CD40, CD70) and novel immunotherapeutics (eg, bispecific monoclonal antibodies, small-modular immunopharmaceuticals, T-cell engagers) are currently in clinical or final preclinical stages of development. Although these agents offer reason for optimism, considerable challenges lie ahead in establishing their real clinical value, as well as in integrating them into current therapeutic algorithms for patients with B-cell malignancies. This review describes some of the most promising investigational immunotherapeutics for the treatment of B-cell malignancies.
Outbreak of Guillain-Barre syndrome associated with water pollution.
Authors: N A Sliman
Journal: BMJ (1978)

Sixteen cases of Guillain-Barré syndrome occurred in the third week of a diarrhoea epidemic caused by water pollution in EL-Sult, Jordan. Of 30 000 people exposed to polluted water, 5000 developed diarrhoea, 74 typhoid, and 30 infectious hepatitis. Thirteen of the 16 patients with Guillain-Barré syndrome had been mildly affected by diarrhoea 8-24 days before the onset of peripheral neuropathy. Paralysis progressed rapidly, reaching a peak in one to five days, and recovery began three to seven days after the start of the most severe symptoms. All but four patients had recovered completely after one year. Rapid progress of paralysis and a delayed interval between maximum weakness and start of recovery were both associated with poor prognosis.
Chow's defense of null-hypothesis testing: Too traditional?
Authors: Robert W. Frick
Journal: Behavioral and Brain Sciences (1998)

I disagree with several of Chow's traditional descriptions and justifications of null hypothesis testing: (1) accepting the null hypothesis whenever p &gt; .05; (2) random sampling from a population; (3) the frequentist interpretation of probability; (4) having the null hypothesis generate both a probability distribution and a complement of the desired conclusion; (5) assuming that researchers must fix their sample size before performing their study.
Targeted therapy for hepatic cancer: Good in theory, problematic in practice
Authors: Teresa L. Wright
Journal: Hepatology (1989)

We present evidence that normal hepatocytes can be specifically protected from galactosamine toxicity in vitro by targeting an antagonist to these cells via receptor-mediated endocytosis. The strategy is based upon the following principles: 1) galactosamine is a highly selective hepatotoxin that causes a dose-dependent depletion of uridine intermediates; 2) galactosamine toxicity can be antagonized by supplemental administration of uridine; 3) normal hepatocytes possess unique cell-surface receptors that can internalize galactose terminal (asialo-) glycoproteins with subsequent degradation of the glycoprotein ligand. Based on these facts, we hypothesized that chemical coupling of a galactosamine antagonist to an asialoglycoprotein could result in cell-specific delivery and protection of normal hepatocytes by targeting the antagonist via asialoglycoprotein receptors. Using a model system consisting of freshly isolated rat hepatocytes (receptor(+)) and Morris 7777 rat hepatoma (receptor (−)) cells, sensitivity to galactosamine in vitro was determined and found to be similar for both types of cells. A targetable antagonist was synthesized by coupling uridine monophosphate to asialoorosomucoid in a molar ratio of 5 to 1. Exposure of Morris 7777 cells to the targetable antagonist in the presence of a toxic concentration of galactosamine did not protect these cells as evidenced by a steady decline in the number of viable cells in a fashion identical to cells treated with galactosamine alone. However, normal hepatocytes that received the conjugate in the presence of galactosamine were protected as their viable cell number remained the same as control (untreated) cells. Competition by an excess of asialoglycoprotein inhibited the protective effect of the conjugate, supporting the concept that the asialoglycoprotein component of the conjugate was responsible for the specific delivery of the antagonist to the target cells.
Mammary Stem Cell-Like Gene Expression and Relation to Cancer.
Authors: C. Williams, L. Helguero, K. Edvardsson, L. Haldosén, J. Gustafsson
Journal: Cancer Research (2009)

Abstract Mammary stem cells are bipotential and suggested to be the origin of breast cancer development, but are elusive and vaguely characterized.Breast tumors can be divided into subgroups, each one requiring specific treatment. To determine a possible association between mammary stem cells and breast cancer, we have previously made a detailed characterization of the transcriptome in murine mammary epithelial stem-like cell line (HC11) and made a thorough investigation of global gene-expression changes during stepwise differentiation using dual-color comparative microarray technique.Subsequently, we performed a cross-species comparison to reveal conserved gene expression between stem cells and subtype-specific and prognosis gene signatures, and correlated gene expression to in vivo mammary gland development. Our analysis provided a unique map of the transcriptomic changes and a number of novel mammary stem cell markers. Interestingly, our comparisons show that specific subtypes of breast cancers with poor prognosis and metastasizing capabilities show resemblance to stem-like gene expression. We are now investigating several marker candidates and regulations of miRNAs during differentiation. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1162.
Abstract 4614: Identification of two salinomycin binding targets in neuroblastoma
Authors: Shuang Zhou, Fengfei Wang, Shi-Hua Xiang, Eric T. Wong, Wallace W. Muhonen, Ekokobe Fonkem, Tze-chen Hsieh, David W. Li, Ruiwen Zhang, John B. Shabb, Joseph M. Wu, Min Wu, Erxi Wu
Journal: Cancer Research (2014)

Abstract Salinomycin, a widely used anti-coccidial agent isolated from a Streptomyces albus strain, was recently identified from a library of 16,000 natural and commercial chemical compounds based on its highly selective inhibitory effect on breast cancer stem cells (CSCs), with more than 100-fold greater potency than paclitaxel. Salinomycin also exhibits cytotoxic effects on other types of cancer cells and CSCs and overcomes drug resistance. However, the exact mechanism of salinomycin, especially its direct binding target(s), and its effects on neuroblastoma (NB) are yet not known. NB is one of the most common solid tumors in children and infants, and a leading cause of mortality in children. Despite advances in diagnosis and treatment, currently, 35% of patients with NB remain incurable. In addition, the majority survivors of NB suffer from long-term side effects of current therapies and are at risk for disease relapse or getting a second, different cancer. More effective therapies are pressingly needed. Since the existence of CSCs in human NB cell lines and NB tumors from patients has been well documented, and has been closely associated with chemoresistance or tumor relapse, therapeutic targeting of NB CSCs may be a critical novel approach to conquer the challenges in NB therapy. Aiming to improve NB therapy, we examined the efficacy and mechanism of salinomycin in human NB cells. Our study showed that salinomycin markedly inhibits NB cell proliferation and tumorsphere formation. Treatment of salinomycin induced G2 cell cycle arrest with an up-regulation of Cyclin A and a down-regulation of p21 protein levels. We further identified TIF1β and NCL as novel direct binding proteins of salinomycin by using comprehensive methods, including chemical proteomics and functional genomics. Furthermore, by analyzing tumor samples from a cohort of 88 NB patients, we found that the elevated level of these proteins is associated with poor prognosis for NB patients. Thus, our results indicate salinomycin is a potential new therapeutic agent and TIF1β and NCL as new therapeutic targets/biomakers for NB therapy. Citation Format: Shuang Zhou, Fengfei Wang, Shi-Hua Xiang, Eric T. Wong, Wallace W. Muhonen, Ekokobe Fonkem, Tze-chen Hsieh, David W. Li, Ruiwen Zhang, John B. Shabb, Joseph M. Wu, Min Wu, Erxi Wu. Identification of two salinomycin binding targets in neuroblastoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4614. doi:10.1158/1538-7445.AM2014-4614
Course of radiographic damage over 10 years in a cohort with early rheumatoid arthritis
Authors: E Lindqvist
Journal: Annals of the Rheumatic Diseases (2003)

<b>Objective:</b> To investigate development of radiographic damage in hands and feet of patients with early rheumatoid arthritis (RA) monitored prospectively for 10 years, and to search for prognostic factors. <b>Patients and methods:</b> 181 patients with early RA (mean disease duration one year) were assessed annually with radiographs of hands and feet during years 0–5 and at year 10. Radiographs were evaluated according to Larsen (range 0–200). Predictive factors for progressive disease for years 0–5 and 5–10 were evaluated by logistic regression analyses. <b>Results:</b> 82/168 (49%) patients had erosions at inclusion and almost all became erosive with time (90% after two years and 96% after 10 years). Radiographic progression was most rapid during the first two years and 75% of all damage occurred during the first five years. The median Larsen score increased from 6 at inclusion to 41 after five years and 54 after 10 years. Only 5.3% of all evaluated joints became maximally eroded, the second metacarpophalangeal joint being the most commonly affected. Mean ESR during the first three months and rheumatoid factor status were significant predictors for radiographic progressive disease, it was not possible to predict non-progressive disease. <b>Conclusions:</b> Joint damage in hands and feet developed early and progression was most rapid during the first years of disease. The different rates of progression at different stages should be considered in the design of trials of drugs aimed at retarding joint damage. Disease activity at study start influenced the degree of joint damage during the entire 10 years.
Clinical and experimental studies on electromechanical dissociation.
Authors: J L Vincent, L Thijs, M H Weil, S Michaels, R A Silverberg
Journal: Circulation (1981)

Electromechanical dissociation (EMD) is the most frequent cause of unsuccessful cardiac resuscitation in critically ill patients. In a clinical study of cardiac arrest, including 54 episodes in 50 fully monitored patients, 14 episodes of ventricular fibrillation were observed and seven were reversed. In the remaining 40 instances, 36 cases of EMD were initially observed. Four patients had asystole. None of the patients with EMD or asystole were successfully resuscitated. For objective study of EMD and its treatment, we developed an experimental model in which ventricular fibrillation was induced in mechanically ventilated dogs. EMD was predictably observed when, after an interval of 120 seconds, ventricular fibrillation was reversed with an external countershock. Neither metabolic acidosis nor metabolic alkalosis modified the incidence of EMD. A few dogs were pretreated with glucose-insulin-potassium or pharmacologic doses of methylprednisolone, but this did not clearly reduce the incidence of EMD. However, the onset of EMD was delayed when the body temperature of the animal was spontaneously reduced.
Terminology for Granulomatous Disorders
Authors: DAVID NICHOLSON
Journal: Annals of Internal Medicine (1979)

Letters and Corrections1 January 1979Terminology for Granulomatous DisordersDAVID NICHOLSON, M.D.DAVID NICHOLSON, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-90-1-129 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The editorial by Dr. Fauci in the December 1977 issue, "Granulomatous Vasculitides: Distinct but Related" (Ann Intern Med 87:782-783, 1977), reflects on an issue other than that addressed at the time, and this is the question of terminology.Granulomatous vasculitis may be a sound description for a group of disorders variously encumbered by such terms as "granulomatosis," "lymphatoid," and necrotising "sarcoid" angiitis. It may be time for some clarification in this area of confusing terminology to avoid further proliferation of vague and portmanteau terms.A library search of a number of standard pathology books revealed a fairly...References1. WALTERISRAEL JM: General Pathology, 4th ed. New York, Longman, Inc., 1974, p. 126 Google Scholar2. EPSTEINSKAHENKRASNOBROD WJH: The organized epitheloid cell granuloma: differentiation of allergic (zirconium) from colloidal (silica) types. Am J Pathol 43:391-397, 1963 MedlineGoogle Scholar3. LIEBOW A: Pulmonary angiitis and granulomatosis. Am Rev Respir Dis 108:1-18, 1973 MedlineGoogle Scholar4. ISRAELPATCHEFSKYSALDANA HAM: Wegener's granulomatosis, lymphomatoid granulomatosis, and benign lymphocyte angiitis and granulomatosis of lung. Recognition and treatment. Ann Intern Med 87:691-699, 1977 LinkGoogle Scholar5. KATZENSTEINLIEBOWFRIEDMAN AAP: Bronchocentric granulomatosis, mucoid impaction and hypersensitivity reaction to fungi. Am Rev Respir Dis 111:497-537, 1975 MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Veterans Administration Medical Center Little Rock, AR 72114 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 January 1979Volume 90, Issue 1Page: 129-129KeywordsLibrariesVasculitis Issue Published: 1 January 1979 PDF downloadLoading ...
The effects of anti-prostaglandin agents on epidermal proliferation induced by dermal inflammation
Authors: A. J. FRANCIS, R. MARKS
Journal: British Journal of Dermatology (1977)

Experimentally induced dermal inflammatory lesions cause epidermal hyperplasia and increased thymidine autoradiographic indices in the overlying epidermis. In the experiments described here anti-prostaglandin agents (indomethacin, aspirin, prednisolone and polyphloretin phosphate) were given to guinea-pigs with experimentally induced dermal granulomata in an effort to learn more about the dennal control of epidermal proliferation. Indomethacin caused a significant reduaion in the epidermal hyperplasia and labelling index in the epidermis overlying carageenan granulomata. Similar but less marked reductions in epidermal proliferation were seen with the other agents used. Some reduction, which proved not to be statistically significant, was also seen in the epidermal proliferation due to kaolin granulomata. Slight reduction in epidermal hyperplasia, but no effect on thymidine incorporation, was seen in proliferation induced by tape stripping.
Collection and Analysis of Exhaled Breath Condensate in Humans
Authors: GÖKHAN M. MUTLU, KEVIN W. GAREY, RICHARD A. ROBBINS, LARRY H. DANZIGER, ISRAEL RUBINSTEIN
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Traditional methods of sampling secretions from the lower respiratory tract include sputum collection, sputum induction, and bronchoscopy with bronchoalveolar lavage (BAL). By far, bronchoscopy with BAL has become the preferred method for sampling the lining fluid of the lower respiratory tract. The invasive nature of bronchoscopy has led to a constant search for less intrusive methods that are easier to implement in ambulant individuals, particularly children. Recently there has been an increasing interest in using exhaled breath as a simple, noninvasive means to sample the lower respiratory tract in humans. The lining fluid of the lower respiratory tract contains various nonvolatile and over 200 volatile substances (1, 2). Although initial attempts were aimed at identifying volatile substances, particularly nitric oxide (NO), studies are now being conducted to detect nonvolatile macromolecules present in exhaled breath, including proteins, lipids, oxidants, and nucleotides. Analysis of these nonvolatile substances requires cooling of the expired breath, which results in condensation. These macromolecules represent biomarkers of various pathological processes in the lungs. In this review, we present the current body of knowledge on exhaled breath condensate as published in peer-reviewed journals in the English language. We focus on the use of this modality in determining host inflammatory response to injury in the lung as well as possible future applications, particularly its potential use as a single, noninvasive sampling method for point-of-care real-time analysis.
Divergent functions for airway epithelial matrix metalloproteinase 7 and retinoic acid in experimental asthma
Authors: Sangeeta Goswami, Pornpimon Angkasekwinai, Ming Shan, Kendra J Greenlee, Wade T Barranco, Sumanth Polikepahad, Alexander Seryshev, Li-zhen Song, David Redding, Bhupinder Singh, Sanjiv Sur, Prescott Woodruff, Chen Dong, David B Corry, Farrah Kheradmand
Journal: Nature Immunology (2009)