tbuckley/cabot-search huggingface dataset:
The Hair Follicle as an Estrogen Target and Source
Authors: Ulrich Ohnemus, Murat Uenalan, José Inzunza, Jan-Åke Gustafsson, Ralf Paus
Journal: Endocrine Reviews (2006)

For many decades, androgens have dominated endocrine research in hair growth control. Androgen metabolism and the androgen receptor currently are the key targets for systemic, pharmacological hair growth control in clinical medicine. However, it has long been known that estrogens also profoundly alter hair follicle growth and cycling by binding to locally expressed high-affinity estrogen receptors (ERs). Besides altering the transcription of genes with estrogen-responsive elements, 17β-estradiol (E2) also modifies androgen metabolism within distinct subunits of the pilosebaceous unit (i.e., hair follicle and sebaceous gland). The latter displays prominent aromatase activity, the key enzyme for androgen conversion to E2, and is both an estrogen source and target.
TRAVEL NOTES FROM SOUTH AMERICA.
Authors: NICHOLAS SENN
Journal: JAMA (1907)

<h3>I. BRAZIL AND BAHIA.</h3><h3>INTRODUCTION—THE TWIN CONTINENTS OF AMERICA.</h3> As an American and one who has seen much of the world, it has always seemed strange to me that the people of the twin continents of America know so little about each other. It is safe to make the statement that the average North American is more familiar with all the countries of Europe, Egypt, India and the Holy Land, than he is with his next-door neighbors, the sister republics of South America. North and South America are still parts of the same continent and will remain so until the connecting link is severed by the construction of the Panama Canal, when each twin will become a separate continent. In glancing over the early history of the New World it becomes clear why the two continents have failed in cultivating closer relationships in commercial and educational affairs, and remain comparative
Techniques for assessment of teratogenic effects: developmental enzyme patterns
Authors: F. D. Andrew
Journal: Environmental Health Perspectives (1976)

Most studies designed for assessing teratogenic effects focus on only three of four types of final manifestations of abnormal development; namely intrauterine death, malformations, and growth retardation. Developmental toxicity evaluations generally do not include functional deficits. Current techniques are inadequate for assessing functional capability during perinatal development, and there is a need for improved measures. Thus, measurement of developmental enzyme patterns is proposed as an approach that directly evaluates acquisition of metabolic competence of fundamental organ systems. During ontogenesis most organs acquire their full complement of enzyme activities in a programmed sequence which corresponds to attainment of complete functional capability. The usual alterations in enzyme activity that characterize these patterns occur at one of three time periods, namely, late fetal, early neonatal, or late suckling. Qualitative or quantitative changes in these patterns at any time by one or more key enzymes of a tissue could be indicative of developmental toxicity. Factors are outlined relating to consideration of developmental enzyme profiles as indices of maturation capable of reflecting the action of toxic agents. This presentation: (1) reviews the current state of the art for evaluating effects on development, (2) considers the applicability of enzyme patterns for biochemical assessment of development, (3) characterizes the target tissues and those metabolic pathways and/or specific enzymes most sensitive and adaptable to practical toxicity evaluations, and (4) describes the steps being taken to validate this system. The ultimate objective of this approach is to determine whether alterations in developmental enzyme profiles will provide a technique with improved capability for assessing developmental toxicity.
Evidence for a single genetic locus in Clouston's hidrotic ectodermal dysplasia
Authors: H P Stevens, S E Choon, H C Hennies, D P Kelsell
Journal: British Journal of Dermatology (1999)

Sir, Clouston's hidrotic ectodermal dysplasia is a rare autosomal dominant ectodermal dysplasia first reported by Nicolle and Hallipré.1 A large French‐Canadian family was subsequently described by Clouston.2 The disease in this family has been linked to the chromosomal region 13q11–q12.1 by Kibar et al.3 Following the demonstration of linkage to 13q11–q12.1 in a number of other families4, 5 linkage analyses were performed on a large pedigree of Chinese–Malay descent with Clouston's hidrotic ectodermal dysplasia (HED).6 Fourteen affected members in three generations of the Chinese–Malay family were examined. The palmoplantar specific keratoderma was inherited as an autosomal dominant with complete penetrance but variable expressivity. A diffuse warty palmoplantar keratoderma developed over the entire sole and the hypothenar eminence of the hands. The skin changes extended to involve the periungual regions of the nails. The nail changes were variable and ranged from discoloured, thickened and dystrophic nails to hypoplasia with a classical cone‐shaped or triangular nail. The distal ends of the fingers were thickened and the digits appeared 'clubbed'. The hair loss was variable and appeared progressive. Some developed a severe alopecia in infancy while in others it occurred later. The eyebrows, eyelashes, pubic and axillary hair were almost invariably involved and were either very sparse or lost completely. Sweating, teeth, breast development and oral mucosa all appeared normal.
Behavior of various cholesterol crystals in bile from patients with gallstones
Authors: P Portincasa, K J van Erpecum, A Jansen, W Renooij, M Gadellaa, G P van Berge-Henegouwen
Journal: Hepatology (1996)

Besides classical plate-like cholesterol monohydrate crystals, a variety of crystal shapes have recently been described in model biles but their relevance for human gallstone formation is unknown. We therefore studied crystallization behavior in gallbladder bile from cholesterol stone patients (54 untreated, 13 ursodeoxycholate-treated) and 6 pigment stone patients. Bile preparation by ultrafiltration or ultracentrifugation left biliary lipid composition unchanged but plates and their aggregates, and arcs and needles crystallized more extensively while spirals and tubules crystallized less extensively in ultra-centrifuged bile than in ultrafiltered bile. Plates, aggregates, and arcs/needles were seen in 90%, 36%, and 18% of the cases respectively of fresh unfiltered biles of untreated cholesterol stone patients, while spirals and tubules were always absent. In ultrafiltered biles arcs/needles, plates and aggregates progressively developed as persistent forms. Spirals and tubules occurred transiently and were associated with increased deoxycholic acid (+41%, P = .039) and with more extensive cholesterol crystallization. Rate/extent of crystallization of all crystal forms was higher ( P &lt; .0001) for multiple than solitary cholesterol stone patients. Ursodeoxycholate-treated patients had atypical platelike cholesterol crystals in fresh unfiltered biles that decreased in size at prolonged observation and in 2 cases even dissolved after 15 and 20 days. No crystals ever developed in ultra-filtered bile of ursodeoxycholic acid (UDCA)-treated patients during 21 days. Pigment stone patients seldom developed crystals. Thus, plates, aggregates and arcs/needles are persistent forms with high crystallization rate in multiple cholesterol stone patients. Tubules and spirals are transient forms that are associated with more extensive crystallization. Patients treated with ursodeoxycholate often have atypical crystals in their fresh bile.
Kinesin Family Member 6 Variant Trp719Arg Does Not Associate With Angiographically Defined Coronary Artery Disease in the Ottawa Heart Genomics Study
Authors: Alexandre F.R. Stewart, Sonny Dandona, Li Chen, Olivia Assogba, Melanie Belanger, Gwen Ewart, Rosemary LaRose, Heather Doelle, Kathryn Williams, George A. Wells, Ruth McPherson, Robert Roberts
Journal: Journal of the American College of Cardiology (2009)
Clever-1/Stabilin-1 Controls Cancer Growth and Metastasis
Authors: Marika Karikoski, Fumiko Marttila-Ichihara, Kati Elima, Pia Rantakari, Maija Hollmén, Tiina Kelkka, Heidi Gerke, Ville Huovinen, Heikki Irjala, Rikard Holmdahl, Marko Salmi, Sirpa Jalkanen
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Immunosuppressive leukocytes and vasculature are important host cell components regulating tumor progression. Clever-1/Stabilin-1, a multifunctional scavenger and adhesion receptor, is constitutively present on a subset of type II macrophages and lymphatic endothelium, but its functional role in cancer is unknown. Experimental Design: Here, we generated full Clever-1 knockout mice and cell-specific ones lacking Clever-1 either on macrophages or endothelium. We also used anti-Clever-1 antibody therapy to treat B16 melanoma and EL-4 lymphoma. Results: Clever-1–deficient mice had smaller primary and metastatic tumors than wild-type (WT) controls. Growth of primary tumors, but not of metastases, was attenuated also in mice lacking Clever-1 selectively in macrophages or in vascular endothelium. Anti-Clever-1 antibody treatment inhibited tumor progression in WT mice. Both genetically and therapeutically induced absence of functional Clever-1 led to diminished numbers of immunosuppressive leukocyte types in tumors. Functionally Clever-1 mediated binding of immunosuppressive leukocytes to the intratumoral blood vessels aberrantly expressing Clever-1, and tumor cell traffic via the lymphatics. The antibody therapy did not aggravate autoimmunity. Conclusion: This work identifies Clever-1 in type II macrophages and in tumor vasculature as a new immunosuppressive molecule in cancer. Our finding that Clever-1 supports binding of tumor-infiltrating lymphocytes to tumor vasculature increases our understanding of leukocyte immigration to tumors. The ability of anti-Clever-1 antibody treatment to attenuate tumor progression in WT mice in vivo is therapeutically relevant. Thus, Clever-1 may be an emerging new target for modulating immune evasion and lymphatic spread in cancer. Clin Cancer Res; 20(24); 6452–64. ©2014 AACR.
Verbal Toys in the "Otic"
Authors: James Ransom
Journal: JAMA (1964)

<h3>To the Editor:—</h3> Your word man (<i>JAMA</i><b>186</b>:138 [Oct 12] 1963), unable to find "tuberculotic" in the vocabulary of medicine in spite of what he refers to as the "fact" that "where there is an '-osis' there must be an '-otic,' " is too easily bemused. Among countless examples, the following nonexistent words spring readily to mind: endometriotic, adenomyotic, thyrotoxicotic, osteoporotic, avitaminotic, hemochromatotic, dermatotic, erythrocytotic furunculotic, dermatophytotic, pediculotic, berylliotic, halitotic, rickettsiotic, and bartonellotic. One might think that my favorite among the missing words would be "pneumonultramicroscopicosilicovolcanoconiotic," but it isn't; it's "reticuloendotheliotic." Can Dr. Gode think of any "-otic" words for which there is no "-osis"? Only two offhand: "polyostotic," "leprotic." Plus, of course, the rather obvious "idiotic."
Scottish health board could face criminal charges over missing critical incident reports
Authors: B. Christie
Journal: BMJ (2012)

Claims that a Scottish health board tried to cover up information about critical incident reviews involving the deaths of 20 patients have been strongly denied by NHS Ayrshire and Arran.

A file on the cases has been passed to Strathclyde police, which has confirmed it is assessing the information to determine if any criminal charges should be brought.

The move follows a complaint raised by a charge nurse, Rab Wilson, who became concerned that reports on serious adverse events were not being made routinely available to staff. …
In Vivo Transduction by Intravenous Injection of a Lentiviral Vector Expressing Human ADA into Neonatal ADA Gene Knockout Mice: A Novel Form of Enzyme Replacement Therapy for ADA Deficiency
Authors: Denise A. Carbonaro, Xiangyang Jin, Denise Petersen, Xingchao Wang, Fred Dorey, Ki Soo Kil, Melissa Aldrich, Michael R. Blackburn, Rodney E. Kellems, Donald B. Kohn
Journal: Molecular Therapy (2006)

Using a mouse model of adenosine deaminase-deficient severe combined immune deficiency syndrome (ADA-deficient SCID), we have developed a noninvasive method of gene transfer for the sustained systemic expression of human ADA as enzyme replacement therapy. The method of delivery is a human immunodeficiency virus 1-based lentiviral vector given systemically by intravenous injection on day 1 to 2 of life. In this article we characterize the biodistribution of the integrated vector, the expression levels of ADA enzyme activity in various tissues, as well as the efficacy of systemic ADA expression to correct the ADA-deficient phenotype in this mouse model. The long-term expression of enzymatically active ADA achieved by this method, primarily from transduction of liver and lung, restored immunologic function and significantly extended survival. These studies illustrate the potential for sustained in vivo production of enzymatically active ADA, as an alternative to therapy by frequent injection of exogenous ADA protein.
Parvovirus B19 and acute joint swelling in rheumatoid arthritis patients.
Authors: J R Kerr, W P Ferguson, S A Mcmillan, I N Bruce, A L Bell
Journal: Annals of the Rheumatic Diseases (1996)

advantageous against development of neoplasia?Although a good deal is known about the late occurrence of malignancy in the connective tissue disorders and other vasculitides, including the autoimmune diseases, for example, rheumatoid arthritis, progressive systemic sclerosis, Sjogren syndrome, systemic lupus erythematosus, and so on,'
A trial of parent held child health records in the armed forces.
Authors: S A Miller
Journal: BMJ (1990)

BrMedJ 1990;300:1046 The strategy of issuing parents with the main record of their children's development was considered likely to benefit families in the armed forces because it would provide those who have to move home regularly with an up to date record of immunisation procedures and developmental checks. The scheme was therefore introduced in the British army and Royal Air Force garrisons in West Germany for a trial period. From October 1987 health visitors issued child health records to the parents of newborn babies, and the reliability of parents as custodians of these documents was tested by conducting a follow up study.
GSK breached marketing code
Authors: Owen Dyer
Journal: BMJ (2006)

Pharmaceutical giant Glaxo-SmithKline (GSK) has been ruled in breach of industry marketing rules after the company was found to have used a patients' support website to promote an unlicensed drug for the controversial condition known as restless legs syndrome (also known as Ekbom's syndrome).

In advertisements placed in doctors' magazines between September 2004 and November 2005, the company sought to raise awareness of the condition. The advertisements directed people with the syndrome to a support group website, the Ekbom Support Group. That website described GlaxoSmithKline's drug ropinirole as an effective treatment for the condition.

Ropinirole, originally used to treat Parkinson's disease, is now being marketed as a treatment for restless legs syndrome …
HIV-associated Hodgkin lymphoma during the first months on combination antiretroviral therapy
Authors: Emilie Lanoy, Philip S. Rosenberg, Fabien Fily, Anne-Sophie Lascaux, Valerie Martinez, Maria Partisani, Isabelle Poizot-Martin, Elisabeth Rouveix, Eric A. Engels, Dominique Costagliola, James J. Goedert
Journal: Blood (2011)
Timing of Subsequent New Tumors in Patients Who Present With Basal Cell Carcinoma or Cutaneous Squamous Cell Carcinoma
Authors: Mackenzie R. Wehner, Eleni Linos, Rupa Parvataneni, Sarah E. Stuart, W. John Boscardin, Mary-Margaret Chren
Journal: JAMA Dermatology (2015)

Patients with basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (SCC) (often termed nonmelanoma skin cancer or keratinocyte carcinoma [KC]) often develop new KCs, but information is limited on the frequency and timing of these subsequent tumors. This information is crucial to guide follow-up care.To determine the timing of subsequent new KCs in patients who present with KC.We enrolled a consecutive cohort of 1426 patients diagnosed as having biopsy-proven KC from January 1, 1999, through December 31, 2000, in a university dermatology practice and its affiliated Department of Veterans Affairs dermatology service. After exclusion of patients with basal cell nevus syndrome and immunocompromise, 1284 patients (90.0%) were followed up prospectively for a mean of 5.7 (range, 0-12.3) years.We assessed the risks for subsequent KCs over time using single-failure and multiple-failure models. We separately assessed outcomes after first lifetime KCs and after nonfirst lifetime KCs. We also performed secondary analyses of the risk for a subsequent BCC after a prior BCC diagnosis and the risk for a subsequent SCC after a prior SCC diagnosis.The risk for a subsequent KC was substantially lower after the first lifetime KC diagnosis: 14.5% (95% CI, 11.9%-17.7%) at 1 year, 31.1% (95% CI, 27.3%-35.3%) at 3 years, and 40.7% (95% CI, 36.5%-45.2%) at 5 years, than after a nonfirst KC: 43.9% (95% CI, 42.0%-45.9%) at 1 year, 71.1% (95% CI, 69.1%-73.0%) at 3 years, and 82.0% (95% CI, 80.2%-83.7%) at 5 years. Secondary analyses of the risks for a subsequent BCC after a prior BCC diagnosis and of a subsequent SCC after a prior SCC diagnosis yielded results consistent with the analyses for the pooled KC sample.Although all patients with KC are assumed to be at high risk for subsequent tumors, a subset may not develop another KC after their first tumor. Whether these findings are related to biological or behavioral differences or to differences in health care services should be investigated further to inform and improve care. Ongoing routine screening for subsequent KC may not be indicated for all patients with KC. Skin cancer screening can be improved with a better understanding of the course and frequency of subsequent KC diagnoses.
Medical Marijuana: A Trial of Science and Politics
Authors: Rebecca Voelker
Journal: JAMA (1994)

IN THE WORLD of community-based clinical trials, one of the goals is evaluating commonly used treatments, regardless of whether they're prescribed by physicians. Among those with HIV infection in San Francisco's Community Consortium, one such therapy is marijuana. For the past 2 years, Donald Abrams, MD, the consortium's chairman, has been trying to devise a trial to compare the efficacy of inhaled marijuana with dronabinol (Marinol, Roxane Laboratories Inc, Columbus, Ohio) as an appetite stimulant for patients with HIV wasting syndrome. Designing such a study to yield meaningful data is a trial in itself. Ushering it through a regulatory maze because it uses a schedule I controlled substance adds to the complexities. "It's difficult," says Abrams, also a professor of clinical medicine at the University of California-San Francisco. "If the science survives the politics, we'll be ready. But there are a lot of politics around this field. I want to
Allergy or tolerance in children sensitized to peanut: Prevalence and differentiation using component-resolved diagnostics
Authors: Nicolaos Nicolaou, Maryam Poorafshar, Clare Murray, Angela Simpson, Henric Winell, Gina Kerry, Annika Härlin, Ashley Woodcock, Staffan Ahlstedt, Adnan Custovic
Journal: Journal of Allergy and Clinical Immunology (2010)
Identification of osteopontin as a novel marker for early hepatocellular carcinoma
Authors: Sufen Shang, Amelie Plymoth, Shaokui Ge, Ziding Feng, Hugo R. Rosen, Suleeporn Sangrajrang, Pierre Hainaut, Jorge A. Marrero, Laura Beretta
Journal: Hepatology (2011)

Abstract The aim of this study was to identify a biomarker that could improve alpha-fetoprotein (AFP) performance in hepatocellular carcinoma (HCC) surveillance among patients with cirrhosis. We performed proteomic profiling of plasma from patients with cirrhosis or HCC and validated selected candidate HCC biomarkers in two geographically distinct cohorts to include HCC of different etiologies. Mass spectrometry profiling of highly fractionated plasma from 18 cirrhosis and 17 HCC patients identified osteopontin (OPN) as significantly up-regulated in HCC cases, compared to cirrhosis controls. OPN levels were subsequently measured in 312 plasma samples collected from 131 HCC patients, 76 cirrhosis patients, 52 chronic hepatitis C (CHC) and B (CHB) patients, and 53 healthy controls in two independent cohorts. OPN plasma levels were significantly elevated in HCC patients, compared to cirrhosis, CHC, CHB, or healthy controls, in both cohorts. OPN alone or in combination with AFP had significantly better area under the receiver operating characteristic curve, compared to AFP, in comparing cirrhosis and HCC in both cohorts. OPN overall performance remained higher than AFP in comparing cirrhosis and the following HCC groups: HCV-related HCC, HBV-associated HCC, and early HCC. OPN also had a good sensitivity in AFP-negative HCC. In a pilot prospective study including 22 patients who developed HCC during follow-up, OPN was already elevated 1 year before diagnosis. Conclusion : OPN was more sensitive than AFP for the diagnosis of HCC in all studied HCC groups. In addition, OPN performance remained intact in samples collected 1 year before diagnosis. (Hepatology 2012)
Protooncogene bcl-2 gene transfer abrogates Fas/APO-1 antibody-mediated apoptosis of human malignant glioma cells and confers resistance to chemotherapeutic drugs and therapeutic irradiation.
Authors: M Weller, U Malipiero, A Aguzzi, J C Reed, A Fontana
Journal: Journal of Clinical Investigation (1995)

The majority of human malignant glioma cells express Fas/APO-1 and are susceptible to Fas/APO-1 antibody-mediated apoptosis in vitro. The sensitivity of Fas/APO-1-positive glioma cell lines to Fas/APO-1 antibody-mediated killing correlates inversely with the constitutive expression of the antiapoptotic protooncogene bcl-2. Here we report that BCL-2 protein expression of human glial tumors in vivo correlates with malignant transformation in that BCL-2 immunoreactive glioma cells were more abundant in WHO grade III/IV gliomas than in grade I/II gliomas. Fas/APO-1 antibody-sensitive human glioma cell lines stably transfected with a murine bcl-2 cDNA acquired resistance to Fas/APO-1 antibody-mediated apoptosis. Forced expression of bcl-2 also attenuated TNF alpha-mediated cytotoxicity of glioma cell lines in the presence of actinomycin D and cycloheximide and conferred partial protection from irradiation and the cancer chemotherapy drugs, cisplatin and BCNU. Preexposure of the glioma cell lines to the cytokines, IFN gamma and TNF alpha, which sensitize for Fas/APO-1-dependent killing, partially overcame bcl-2-mediated rescue from apoptosis, suggesting that multimodality immunotherapy involving cytokines and Fas/APO-1 targeting might eventually provide a promising approach to the treatment of human malignant gliomas.