tbuckley/cabot-search huggingface dataset:
Epitope focusing in the primary cytotoxic T cell response to Epstein-Barr virus and its relationship to T cell memory.
Authors: N M Steven, A M Leese, N E Annels, S P Lee, A B Rickinson
Journal: The Journal of Experimental Medicine (1996)

The relationship between primary and memory cytotoxic T lymphocyte (CTL) responses, and the factors influencing entry into memory, are poorly understood. Here we address this in the context of Epstein-Barr virus (EBV), a persistent human herpesvirus in which memory CTL responses in long-term virus carriers are highly focused on epitopes preferentially drawn from just three of the eight available virus latent proteins, EBNAs 3A, 3B, and 3C. To determine whether this unusual level of focusing is a consequence of long-term virus challenge, we carried out a detailed analysis of EBV antigen/epitope specificities in the primary virus-induced CTL response in 10 infectious mononucleosis (IM) patients of different HLA types. Primary effectors, studied in ex vivo assays and by limiting dilution cloning in vitro, were again highly skewed toward a small number of viral epitopes, almost all derived from the EBNA3 proteins, with CTL to the immunodominant epitope accounting for at least 1% of the circulating CD8+ IM T cell pool. This is the first unequivocal demonstration of an EBV-specific CD8+ CTL response in IM. Prospective studies on individual patients showed that, whereas all of the EBV reactivities found in CTL memory had been detectable earlier during primary infection, the memory population was not simply a scaled down version of the primary response. In particular (a) differences in the relative frequencies of CTL to immunodominant versus subdominant epitopes appeared to be much less marked in memory than in primary populations, and (b) we found at least one clear example in which a significant virus-specific reactivity within the primary response was never detectable in memory.
NERVOUS AND MENTAL DISTURBANCES OF THE MALE CLIMACTERIC
Authors: ARCHIBALD CHURCH
Journal: JAMA (1910)

It may be acknowledged at once that the term "male climacteric" is a bit sensational, in view of the fact that it is not specifically recognized by any physiologist. For instance, the "American Text-Book of Physiology" denies that the male presents either a monthly molimen or a climacteric comparable to that in the female. If we confine our attention on the subject of menstruation entirely to the monthly flow, and see in this rhythmic manifestation nothing but an ovarian activity, we need go no further in the discussion of the question of a male climacteric. But it is a well-established anatomic fact that the early months of embryonic life show no sexual differentiation, and that all of the constituents that subsequently under variation develop into the sexual apparatus of male and female, are indifferently present in either sex, not only up to a certain period of intra-uterine life but in
Generation of EBV-specific cytotoxic T cells that are resistant to calcineurin inhibitors for the treatment of posttransplantation lymphoproliferative disease
Authors: Jennifer Brewin, Christoph Mancao, Karin Straathof, Helen Karlsson, Sujith Samarasinghe, Persis J. Amrolia, Martin Pule
Journal: Blood (2009)
Evidence of Detrimental Effects of Environmental Contaminants on Growth and Reproductive Physiology of White Sturgeon in Impounded Areas of the Columbia River
Authors: Grant W. Feist, Molly A.H. Webb, Deke T. Gundersen, Eugene P. Foster, Carl B. Schreck, Alec G. Maule, Martin S. Fitzpatrick
Journal: Environmental Health Perspectives (2005)

This study sought to determine whether wild white sturgeon from the Columbia River (Oregon) were exhibiting signs of reproductive endocrine disruption. Fish were sampled in the free-flowing portion of the river (where the population is experiencing reproductive success) and from three reservoirs behind hydroelectric dams (where fish have reduced reproductive success). All of the 18 pesticides and almost all of the 28 polychlorinated biphenyls (PCBs) that were analyzed in livers and gonads were detected in at least some of the tissue samples. Metabolites of p,p -dichlorodiphenyltrichloroethane (DDT) [p,p -dichlorodiphenyldichloroethylene (DDE) and p,p -1,1-dichloro-2,2-bis(4-chlorophenyl)ethane (DDD)]were consistently found at relatively high levels in fish. Some males and immature females showed elevated plasma vitellogenin; however, concentrations were not correlated with any of the pesticides or PCBs analyzed. Negative correlations were found between a number of physiologic parameters and tissue burdens of toxicants. Plasma triglycerides and condition factor were negatively correlated with total DDT (DDD + DDE + DDT), total pesticides (all pesticides detected - total DDT), and PCBs. In males, plasma androgens and gonad size were negatively correlated with total DDT, total pesticides, and PCBs. Fish residing in the reservoir behind the oldest dam had the highest contaminant loads and incidence of gonadal abnormalities, and the lowest triglycerides, condition factor, gonad size, and plasma androgens. These data suggest that endocrine-disrupting chemicals may be accumulating behind dams over time. Overall, results of this study indicate that exposure to environmental contaminants may be affecting both growth and reproductive physiology of sturgeon in some areas of the Columbia River.
Alpha and beta chains of SB and DR antigens are structurally distinct
Authors: CK Hurley, S Shaw, L Nadler, S Schlossman, JD Capra
Journal: The Journal of Experimental Medicine (1982)

Limited amino-terminal amino acid sequences of the HLA-controlled SB and DR antigens from the cell line PREISS (DR4/4, SB3/4) show differences in both the alpha and beta chain sequences of the two molecules. SB antigens, like DR antigens, appear to be homologues of the murine I-E antigens.
Chlamydia screening can have high take-up rates if right methodology is used
Authors: J. Macleod, G. D. Smith
Journal: BMJ (1999)

EDITOR—A report by the expert advisory group to the chief medical officer suggested that a screening programme in the United Kingdom for Chlamydia trachomatis should be based around the opportunistic testing of women attending primary care and the tracing of their contacts.1 Duncan and Hart discuss some of the possible negative consequences of this decision.2 There are some further reasons why the Department of Health's stated strategy is a bad idea.

Chlamydia screening has …
Efficacy and Safety of a Novel Dual Modulator of Adenosine Triphosphate-Citrate Lyase and Adenosine Monophosphate-Activated Protein Kinase in Patients With Hypercholesterolemia
Authors: Christie M. Ballantyne, Michael H. Davidson, Diane E. MacDougall, Harold E. Bays, Lorenzo A. DiCarlo, Noah L. Rosenberg, Janice Margulies, Roger S. Newton
Journal: Journal of the American College of Cardiology (2013)
Preclinical Therapeutic Efficacy of a Novel Pharmacologic Inducer of Apoptosis in Malignant Peripheral Nerve Sheath Tumors
Authors: Vincent Chau, S. Kyun Lim, Wei Mo, Chiachi Liu, Amish J. Patel, Renée M. McKay, Shuguang Wei, Bruce A. Posner, Jef K. De Brabander, Noelle S. Williams, Luis F. Parada, Lu Q. Le
Journal: Cancer Research (2013)

Abstract Neurofibromatosis type I (NF1) is an autosomal disorder that affects neural crest-derived tissues, leading to a wide spectrum of clinical presentations. Patients commonly present with plexiform neurofibromas, benign but debilitating growths that can transform into malignant peripheral nerve sheath tumors (MPNST), a main cause of mortality. Currently, surgery is the primary course of treatment for MPNST, but with the limitation that these tumors are highly invasive. Radiotherapy is another treatment option, but is undesirable because it can induce additional mutations. Patients with MPNST may also receive doxorubicin as therapy, but this DNA-intercalating agent has relatively low tumor specificity and limited efficacy. In this study, we exploited a robust genetically engineered mouse model of MPNST that recapitulates human NF1-associated MPNST to identify a novel small chemical compound that inhibits tumor cell growth. Compound 21 (Cpd21) inhibits growth of all available in vitro models of MPNST and human MPNST cell lines, while remaining nontoxic to normally dividing Schwann cells or mouse embryonic fibroblasts. We show that this compound delays the cell cycle and leads to cellular apoptosis. Moreover, Cpd21 can reduce MPNST burden in a mouse allograft model, underscoring the compound's potential as a novel chemotherapeutic agent. Cancer Res; 74(2); 586–97. ©2013 AACR.
Adjuvant Chemotherapy With Cyclophosphamide, Doxorubicin, and Cisplatin in Patients With Completely Resected Stage I Non-Small-Cell Lung Cancer
Authors: R. Feld, L. Rubinstein, P. A. Thomas, None The Lung Cancer Study Group
Journal: JNCI Journal of the National Cancer Institute (1993)

Background : Most studies of adjuvant chemotherapy, radiotherapy, or immunotherapy in non-small-cell lung cancer patients with complete surgical resection of disease have shown negative results. However, two studies of stage II and III disease by our Lung Cancer Study Group suggested an advantage to adjuvant therapy with cyclophosphamide, doxorubicin, and cisplatin (CAP). Purpose : Since neither of those studies had an untreated control, the Lung Cancer Study Group undertook a trial that included a control group and also offered the potential benefit of adjuvant therapy with CAP to patients with T1, N1 or T2, N0 (stage I) non-small-cell lung cancer. Methods : After complete resection, eligible patients with stage I disease were classified by known prognostic factors and randomly assigned to receive or not to receive four courses of CAP at 3-week intervals beginning on day 30 after surgery. The CAP regimen consisted of 400 mg/m 2 cyclophosphamide, 40 mg/m 2 doxorubicin, and 60 mg/m 2 cisplatin. Stratification by prognostic factors was as follows: histology (squamous versus nonsquamous), white blood cell count before surgery (≥9100/mm 3 versus <9100/mm 3 ), and Karnofsky performance status before surgery (≤90% versus 100%). Results : Of the 269 patients entered in the study, 101 had recurrence and 127 have died. Mean time since randomization is 6.4 years; mean follow-up is 3.8 years. There were no differences in time to recurrence or overall survival (not stratified by histology) between the two groups, even when analyses were adjusted for prognostic variables. There was one treatment-related death on the CAP arm due to infection during neutropenia. Only 53% of the eligible patients received all four courses of CAP, and only 57% of such patients received all four cycles on time. In 74% of the patients, the site of initial recurrence was distant. Conclusions : The most likely explanations for the lack of efficacy of CAP are poor compliance to the protocol and relative inactivity of the regimen, compared with the activity of drug combinations used in more recent studies. On the basis of this trial, adjuvant therapy with CAP should not be recommended for patients with resected stage I lung cancer. Implications : Further trials to test adjuvant therapy are indicated, but investigators should use better antiemetics to improve patient compliance as well as more active chemotherapy regimens. [J Natl Cancer Inst 85: 299–306, 1993]
Medical Education Gets Wired: Interactive Media Laboratory Targets Patients and Physicians
Authors: Joan Stephenson
Journal: JAMA (1996)

AS DIRECTOR of the Interactive Media Laboratory (IML) at Dartmouth Medical School, Hanover, NH, Joseph V. Henderson, Jr, MD, has at his disposal a technophile's paradise of computers, video and sound equipment, and other multimedia paraphernalia—all tools for crafting the award-winning interactive educational programs aimed at health care professionals, medical and nursing students, and patients for which he and the IML have become known. But as Henderson knows, what really creates powerful learning experiences is not the technology itself but its capacity to engage viewers emotionally and give them a sense of having had a life experience. It accomplishes this, he says, by conveying information through interactive exercises—such as getting feedback on good and bad decisions in managing the care of a simulated patient—and combining them with cinematic elements, in which the stories and circumstances of real and fictional patients provide an emotional overlay that can make learning more engaging
Differential risk of death in older residents in nursing homes prescribed specific antipsychotic drugs: population based cohort study
Authors: K. F. Huybrechts, T. Gerhard, S. Crystal, M. Olfson, J. Avorn, R. Levin, J. A. Lucas, S. Schneeweiss
Journal: BMJ (2012)

To assess risks of mortality associated with use of individual antipsychotic drugs in elderly residents in nursing homes.Population based cohort study with linked data from Medicaid, Medicare, the Minimum Data Set, the National Death Index, and a national assessment of nursing home quality.Nursing homes in the United States.75,445 new users of antipsychotic drugs (haloperidol, aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone). All participants were aged ≥ 65, were eligible for Medicaid, and lived in a nursing home in 2001-5.Cox proportional hazards models were used to compare 180 day risks of all cause and cause specific mortality by individual drug, with propensity score adjustment to control for potential confounders.Compared with risperidone, users of haloperidol had an increased risk of mortality (hazard ratio 2.07, 95% confidence interval 1.89 to 2.26) and users of quetiapine a decreased risk (0.81, 0.75 to 0.88). The effects were strongest shortly after the start of treatment, remained after adjustment for dose, and were seen for all causes of death examined. No clinically meaningful differences were observed for the other drugs. There was no evidence that the effect measure modification in those with dementia or behavioural disturbances. There was a dose-response relation for all drugs except quetiapine.Though these findings cannot prove causality, and we cannot rule out the possibility of residual confounding, they provide more evidence of the risk of using these drugs in older patients, reinforcing the concept that they should not be used in the absence of clear need. The data suggest that the risk of mortality with these drugs is generally increased with higher doses and seems to be highest for haloperidol and least for quetiapine.
Cervical Cytology and Reimbursement Issues-Reply
Authors: D. K. Ohrt
Journal: JAMA (1990)

<h3>In Reply.—</h3> Dr Keffer appropriately emphasizes a number of reimbursement issues relevant to quality. I agree and have clearly stated that adequate financing of diagnostic cytology is necessary. The clinician or the clinician's agent must negotiate quality back into the price. Dr Neely is correct in stating that the American College of Obstetrics and Gynecology technical bulletin does not delineate a "treat and repeat approach" to a specific category of atypical Papanicolaou smears. A close reading of this document leaves much to the imagination. It clearly makes a recommendation for colposcopic evaluation of preinvasive cervical neoplasia, but nothing is spelled out regarding follow-up for the mild abnormalities, including inflammatory and regenerative processes and metaplasia. Such lesions are currently subject to discretion in clinical management. By inference and experience, I have interpreted the American College of Obstetrics and Gynecology's recommendation to mean that watchful waiting is the preferred course for most
Increased levels of type I and III collagen and hyaluronan in scleroderma skin
Authors: K. SOSNDERGAARD, L. HEICKENDORFF, L. RISTELI, J. RISTELLI, H. ZACHARIAE, K. STENGAARD-PEDERSHN, B. DELEURAN
Journal: British Journal of Dermatology (1997)

The aminoterminal propeptide of type III procollagen (PIIINP) and the carboxyterminal propeptide of type I procollagen (PICP) and hyaluronan (HA) were measured in plasma and suction blister fluid from 13 systemic sclerosis patients and 11 healthy volunteers. Suction blisters and skin biopsies were from the transition zone between normal skin and scleroderma, and uninvolved abdominal skin of patients. The median value of suction blister PIIINP from the transition zone was 38% higher than suction blister PIIINP from uninvolved skin. PIIINP was localized to the dermis by immunohistochemical techniques. PICP and HA levels in blisters from the transition zone were 87% and 53%, respectively, above the levels measured in uninvolved skin. Furthermore, PICP and HA blister levels from the transition zone were 67% and 63%, respectively, higher than the levels measured in healthy volunteers. In plasma from scleroderma patients levels of PIIINP and HA were 38% and 127% higher, respectively, than in plasma of healthy volunteers. The plasma PICP level was not significantly higher in scleroderma patients. Finally, PICP, PIIINP and HA levels were several times higher in suction blister fluid than in plasma. The data indicate that a fibrogenetic process takes place in the transition zone of scleroderma. The method may be used to monitor the progression of scleroderma skin lesions in vivo.
Abstract PR1: NKX2-1/TITF1/TTF-1-induced ROR1 is required to sustain EGFR survival signaling in lung adenocarcinoma
Authors: Tomoya Yamaguchi, Kiyoshi Yanagisawa, Ryoji Sugiyama, Yasuyuki Hosono, Yukako Shimada, Chinatsu Arima, Seiichi Kato, Shuta Tomida, Motoshi Suzuki, Hirotaka Osada, Takashi Takahashi
Journal: Clinical Cancer Research (2012)

Abstract Emerging evidence, though currently sparse, suggests that “lineage-specific transcription factors” with developmental roles in normal progenitor cells of particular lineages may also confer dependency for survival to certain types of cancer cells. Accumulated evidence indicates that NKX2-1, a lineage-specific transcription factor also known as TITF1 and TTF-1, which is expressed in a major fraction of lung adenocarcinomas, plays essential roles in peripheral lung development. We previously identified NKX2-1 as a lineage-survival oncogene in lung adenocarcinoma, while other investigators reached similar conclusions through genome-wide searches for focal genomic aberrations. Previous findings including ours thus clearly indicate the requirement of sustained NKX2-1 expression for lung adenocarcinoma survival, while it remains elusive how NKX2-1 mediates survival signals. In the present study, we show that NKX2-1 induces the expression of the receptor tyrosine kinase-like orphan receptor 1 (ROR1), which in turn sustains a favorable balance between prosurvival PI3K-AKT and proapoptotic p38 signaling, in part through ROR1 kinase-dependent c-Src activation. Interestingly, ROR1 was also identified as a receptor tyrosine kinase with a “sustainer role” for the interaction of EGFR-ERBB3 and ERBB3 phosphorylation in a ROR1 kinase-independent manner, consequentially leading to PI3K activation. It was also of note that ROR1 knockdown effectively inhibited lung adenocarcinoma cell lines irrespective of their EGFR status, including those with resistance to the EGFR tyrosine kinase inhibitor gefitinib. Secondary EGFR mutation, MET amplification, and HGF overexpression may arise in lung adenocarcinomas in patients undergoing EGFR-TKI treatment, leading to treatment resistance. The existence of such diverse mechanisms makes it difficult to predict which should be targeted to prevent expansion of resistant clones. From a clinical point of view, it is thus of particular interest that ROR1 inhibition appears to be effective for treatment of gefitinib-resistant lung adenocarcinomas with various resistance mechanisms. Taken together, the present findings identify ROR1 as an “Achilles' heel” in lung adenocarcinomas. Future development of novel therapeutic means including ROR1-specific antibodies and small molecules that inhibit both or either of the two distinct prosurvival signal-sustaining functions is greatly anticipated for attempts to reduce the intolerable death toll from currently “hard-to-cure” lung adenocarcinomas. This proffered talk is also presented as Poster A28.
Current Therapy of Diabetes Mellitus
Authors: John B. Buse
Journal: Annals of Internal Medicine (1998)

Medical Writings15 February 1998Current Therapy of Diabetes MellitusJohn B. Buse, MD, PhDJohn B. Buse, MD, PhDUniversity of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North CarolinaSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-128-4-199802150-00054 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Defronzo RA. 273 pages. St. Louis: Mosby-Year Book; 1997. $64.95. ISBN 081512757X. Order phone 800-426-4545.Field of medicine: Endocrinology, general medicine, and primary care.Format: Hardcover book.Audience: Primary care providers, endocrinologists, other medical specialists, allied health professionals, and trainees in any specialty.Purpose: To provide a simple and pragmatic approach to the treatment of diabetes and its complications.Content: The book is a well-organized series of 43 chapters, each approximately six pages long, that cover type 1 diabetes, type 2 diabetes, complications of diabetes, and special problems. Each chapter starts from a brief discussion of pathophysiology to concisely review ... Author, Article, and Disclosure InformationAffiliations: University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 February 1998Volume 128, Issue 4Page: 331-332KeywordsAllied health care professionalsDiabetes mellitusDisabilitiesEndocrinologyHealth care providersQuality of lifeType 1 diabetesType 2 diabetes ePublished: 15 August 2000 Issue Published: 15 February 1998 Copyright & PermissionsCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Points: Benzodiazepines on trial
Authors: R T Owen
Journal: BMJ (1984)

and Dr R Wise (21 April, p 1179) emphasised the toll exacted by pneumococcal infections but did not make it clear that pneu- mococcal bacteraemia generally occurs in people with pre-existing disease.In a study of 103 cases of pneumococcal bacteraemia at East Birmingham Hospital pre-existing disease was found in 820' of the 79 patients aged over 20 and in 38 of the 41 aged between 40 and 70.1 Most of the underlying diseases involved the respiratory system, major metabolic processes, or the immune system.In the latter group the most common disorder was hyposplenism.
A meta-analysis of genome-wide association studies for serum total IgE in diverse study populations
Authors: Albert M. Levin, Rasika A. Mathias, Lili Huang, Lindsey A. Roth, Denise Daley, Rachel A. Myers, Blanca E. Himes, Isabelle Romieu, Mao Yang, Celeste Eng, Julie E. Park, Karla Zoratti, Christopher R. Gignoux, Dara G. Torgerson, Joshua M. Galanter, Scott Huntsman, Elizabeth A. Nguyen, Allan B. Becker, Moira Chan-Yeung, Anita L. Kozyrskyj, Pui-Yan Kwok, Frank D. Gilliland, W. James Gauderman, Eugene R. Bleecker, Benjamin A. Raby, Deborah A. Meyers, Stephanie J. London, Fernando D. Martinez, Scott T. Weiss, Esteban G. Burchard, Dan L. Nicolae, Carole Ober, Kathleen C. Barnes, L. Keoki Williams
Journal: Journal of Allergy and Clinical Immunology (2012)