tbuckley/cabot-search huggingface dataset:
Abstract B15: Genetic variation in DNA repair pathway genes and melanoma risk
Authors: Mingfeng Zhang, Abrar Qureshi, Qun Guo, Jiali Han
Journal: Clinical Cancer Research (2010)

Abstract Reduced DNA repair capacity has been proposed as a predisposing factor for melanoma. We comprehensively evaluated 1465 genetic variants across 60 DNA repair-related pathway genes in relation to melanoma risk in a nested case-control study of 218 melanoma cases and 218 matched controls within the Nurses’ Health Study (NHS). We then genotyped the two variants with the smallest P value in two replication sets: 184 melanoma cases and 184 matched controls in the Health Professionals Follow-Up Study (HPFS); and 183 melanoma cases and 183 matched controls in the NHS. The SNP rs3219125 in the PARP1 gene was significantly associated with melanoma risk in the discovery set (odds ratio (OR) 3.14; 95% confidence interval (CI) 1.70-5.80) and in the HPFS replication set (OR, 1.92; 95%CI, 1.05-3.54), but not in the NHS replication set (OR, 1.07; 95%CI, 0.58-1.97), while in the joint analysis, the OR was 1.89 (95%CI, 1.34-2.68) for this polymorphism. Given that DNA repair protects against UV-induced melanoma, the sun-exposed body sites are more prone to insufficiency in DNA repair capacity. Thus, we further conducted subgroup analysis of this SNP by body sites and found that the increased risk of this variation was more pronounced among patients with lesions in head/neck (OR, 3.19; 95% CI, 1.77-5.73 for head/neck, and OR, 1.54; 95% CI, 1.03-2.30 for other sites, P value for heterogeneity test = 0.036), which further suggested the involvement of this locus in the etiology of melanoma via its influence on DNA repair capacity. In addition, there were significantly fewer head/neck melanoma cases in the NHS replication set (20.4% in the discovery set, 28.1 % in the HPFS replication set, and 9.5% in the NHS replication set, P &amp;lt; 0.001), which may explain the failure of the replication in the NHS replication set. In conclusion, our findings implicate the PARP1 variant in the etiology of melanoma cancer, especially for sites with high sun exposure. Further work is needed to replicate these results and clarify the mechanism by functional studies. Citation Information: Clin Cancer Res 2010;16(14 Suppl):B15.
Psychoneurosis and Obesity— The Hen and Egg Dilemma
Authors: Samuel Vaisrub
Journal: JAMA (1974)

Despite decades of concern—one might even say preoccupation—with obesity, its treatment remains an exercise in frustration. More than 90% of dieters regain lost weight after a variable temporary weight loss. What's more disquieting is the possibility that this weight loss may be attained at the expense of mental and emotional stability. Such a possibility is indicated by Glucksman et al<sup>1</sup>in their studies of six obese patients observed in a metabolic ward for an eight-month period of dieting. The caloric intake during the first six weeks was aimed at maintaining admission weight. During the following 15 weeks—the period of weight loss—only 600 calories were given daily. The caloric regimen during the last six weeks was adjusted to preserve the lowest weight achieved at the end of the weight loss. The behavior of these patients was evaluated with rating interviews and psychological tests during the period of weight loss and the
Interrelationship of Drugs Influencing Arterial Pressure in Man
Authors: WALTER REDISCH, FRANCISCO F. TANGCO, ARTHUR J. LEWIS, MARIA AURORA ANTONIO, KURT DECRINIS, J. MURRAY STEELE, Dorothy Andrews, Stephen Menkes
Journal: Circulation (1958)

Comparison of hemodynamic changes (cardiac output, renal plasma flow, and extremity blood flow) observed during reserpine-induced hypotension with those occurring during pentolinium-induced hypotension suggests better adaptation following reserpine. This difference is believed to be related to the gradation of onset of hypotension. It was found that reserpine-induced hypotension is potentiated by norepinephrine, and pentolinium-induced hypotension by serotonin. Pretreatment with the hypotensive agent increased the pressor response to norepinephrine and serotonin respectively, if the pressor substance was administered before the onset of hypotension.
Abnormal Balance in the Angiopoietin-Tie2 System in Human Brain Arteriovenous Malformations
Authors: Tomoki Hashimoto, Tiffany Lam, Nancy J. Boudreau, Andrew W. Bollen, Michael T. Lawton, William L. Young
Journal: Circulation Research (2001)

Brain arteriovenous malformations (BAVMs) are congenital vascular lesions that often present as cerebral hemorrhage in young adults. The variable nature of the clinical course, especially with respect to spontaneous hemorrhage, recurrence, growth, and regression, suggests that BAVMs are lesions with active angiogenesis and vascular remodeling. We examined mRNA and protein expression of angiopoietin 1 (Ang1) and Ang2 by semiquantitative reverse transcriptase–polymerase chain reaction, in situ hybridization, and Western blot in BAVMs and control brains obtained from temporal lobectomy for medically intractable seizures. Although Ang1 mRNA levels were similar in BAVMs and controls, Ang1 protein levels were 30% lower in BAVMs than in controls. Ang2 mRNA levels were 40% higher and Ang2 protein levels were 8-fold higher in BAVMs than in controls. In situ hybridization showed that the Ang2 mRNA was localized to the perivascular area in BAVMs. This abnormal balance in the Ang-Tie2 system may, in part, explain the aberrant vascular phenotype in BAVMs.
Individual Level Injection History: A Lack of Association with HIV Incidence in Rural Zimbabwe
Authors: Ben A Lopman, Geoff P Garnett, Peter R Mason, Simon Gregson
Journal: PLoS Medicine (2005)

Background It has recently been argued that unsafe medical injections are a major transmission route of HIV infection in the generalised epidemics of sub-Saharan Africa. Methods and Findings We have analysed the pattern of injections in relation to HIV incidence in a population cohort in Manicaland in a rural area of Zimbabwe. In Poisson regression models, injections were not found to be associated with HIV in males (rate ratio = 0.33; 95% confidence interval: 0.07 to 1.46) or females (rate ratio = 1.04; 95% confidence interval: 0.59 to 1.85). Conclusion It is important that unsafe medical injections can be confidently excluded as a major source of HIV infection. In rural Zimbabwe the evidence is that they can.
A Retreat from SI Units
Authors: Edward W. Campion
Journal: New England Journal of Medicine (1992)

For the past five years, the Journal has required that authors express all measurements in Système International (SI) units, although conventional units could also be given. This policy was adopted at a time when many medical journals in the United States were making SI units their standard. The rationale for the use of SI units has been stated clearly,1 2 3 and it is hard to disagree with. Measurements are scientifically more informative when expressed on a molar basis than when expressed on the conventional basis of weight. Medicine and biologic science are international concerns, so the use of the same system . . .
Abstract IA23: Functional and structural studies of HP1 heterochromatin
Authors: Daniele Canzio, Moafu Liang, Nariman Naber, Adam Larson, Diana Marina, Jennifer Garcia, Hiten Madhani, Roger Cooke, Peter Schuck, Yifan Cheng, Geeta J. Narlikar
Journal: Cancer Research (2013)

Abstract During normal development the spread of heterochromatin provides a mechanism to heritably silence large regions of the genome. This allows selective transcription of a subset of genes required for determining and maintaining cell identity. Defects in heterochromatin assembly are associated with various cancers including breast cancer metastasis and acute myeloid leukemias. The most conserved form of heterochromatin is characterized by methylation of lysine 9 on histone H3 (H3K9me3). Key to both the assembly and the spreading process is the heterochromatin protein 1 (HP1), which binds the H3K9me3 mark via its chromodomain (CD). This interaction forms a versatile platform for recruitment of diverse chromatin modifying proteins. However, the molecular basis of how the HP1-H3K9me3 chromatin complex achieves these diverse interactions is poorly understood. Our work on the major S. pombe HP1 protein, Swi6, suggests that Swi6 switches between an auto-inhibited state and a spreading competent state upon binding methylated chromatin. Cryo-EM allows visualization of the spreading competent state of Swi6 on a methylated nucleosome. Our data suggest testable hypothesis for how specific post-translation modifications on HP1 can regulate its association with methylated chromatin and its interaction with different heterochromatin proteins. Citation Format: Daniele Canzio, Moafu Liang, Nariman Naber, Adam Larson, Diana Marina, Jennifer Garcia, Hiten Madhani, Roger Cooke, Peter Schuck, Yifan Cheng, Geeta J. Narlikar. Functional and structural studies of HP1 heterochromatin. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr IA23.
Disorders of the shoulder joint.
Authors: A. C. Boyle
Journal: BMJ (1969)

Though the shoulder joint is often considered to be synonymous with the glenohumeral joint, movement also takes place at the acromioclavicular and sternoclavicular joints, and a gliding movement of the scapula over the thoracic cage may contribute to shoulder movement.The head of the humerus is held in the glenoid fossa by the musculotendinous rotator cuff, which is composed of the insertions of the supraspinatus, infraspinatus, subscapularis, and teres minor muscles, all of which blend with the joint capsule.The tendon of the long head of the biceps brachii muscle arises from the supraglenoid tubercle, and encased in its synovial sheath passes through the glenohumeral joint deep to the capsule and the rotator cuff and so to the bicipital groove on the anterior surface of the humerus.The subdeltoid (or subacromial) bursa lies superficial to the rotator cuff tendons, separating them from the arch formed by the acromion, coracoid process, the coraco-acromial ligament, and the deltoid muscle. Clinical ExaminationInspection.-This may reveal muscle wasting (Fig. 1), effu- sion within the joint (usually presenting anteriorly), or redness of the overlying skin.
Abstract 1793: 5-Fluorouracil chemotherapy acts synergistically with adoptive dendritic cell immunotherapy to induce durable anti-tumor responses <i>in vivo</i>
Authors: Patrick Williams, Manaf Bouchentouf, Moutih Rafei, Raphaelle Romieu-Mourez, Shala Yuan, Kathy A. Forner, Elena Birman, Jacques Galipeau
Journal: Cancer Research (2011)

Abstract Introduction: 5-Fluorouracil induces a form of cell death that facilitates the presentation of antigens by dendritic cells and depletes myeloid suppressor cells in vivo. The resulting immune modulation plays a substantial role in prolonging survival of mice with cancer. Our lab has previously demonstrated that a fusion of granulocyte-colony macrophage-stimulating-factor (GM-CSF) and Interleukin (IL) – 21, hereafter GIFT-21, could differentiate monocytes into a novel dendritic cell population (GIFT-21 DC). Characterization of these cells revealed a unique phenotype, with the expression of markers normally associated with both conventional and plasmacytoid dendritic cells. They are effective at cross-presenting antigens and secrete substantial amounts of CCL2, IL-6, TNF-α and IFN-α. When injected into tumor-bearing mice, they migrate to and sample from tumors in vivo, allowing them to educate CD8 T cells to recognize tumor antigens, which then significantly impeded the growth of B16 and D2F2 Neu tumors in mice. Hypothesis: We propose that 5-Fluorouracil mediated immune modulation can be combined with adoptively transferred autologous GIFT-21 DCs to treat established cancer, and lead to a synergistic anticancer immune response. Methods and Results: Twelve days following a subcutaneous tumor implantation, mice with established B16 tumors (average volume of 40mm3) were treated daily with 1.5 mg 5-Fluorouracil for 2 days and then injected on the third day with 1.5×106 syngeneic GIFT-21 DCs intraperitoneally. The treatment was repeated one week later. While 5-FU treatment alone or dendritc cell therapy alone had no significant impact on the growth of pre-established melanoma, the combination of 5-Fluorouracil with GIFT-21 DC-based immunotherapy reduced the rate of tumor growth by 75% over 5-FU and 85% over untreated mice, while eventually leading to the regression of the pre-established B16 tumors. Conclusion: These findings demonstrate how chemotherapy can be combined with immunotherapy to target cancers for which tumors antigens are unknown or ill-defined. While chemotherapy suppresses some elements of the immune system in the short term, we speculate that modulating the endogenous immunological processes secondary to chemotherapy shows promising synergy with adoptive cell therapy and is a promising avenue of future research in cancer immunotherapy. 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 1793. doi:10.1158/1538-7445.AM2011-1793
Sustained Attention Deficit and Schizotypal Personality Features in Nonpsychotic Relatives of Schizophrenic Patients
Authors: Wei J. Chen, Shi K. Liu, Ching-Jui Chang, Ying-Ju Lien, Yu-Hui Chang, Hai-Gwo Hwu
Journal: American Journal of Psychiatry (1998)

Objective: The authors investigated whether nonpsychotic relatives of schizophrenic probands have an elevated risk of deficits in sustained attention as measured by the Continuous Performance Test (CPT), whether such deficits are associated with specific factors of schizotypy, and whether poor CPT performance by probands predicts poor performance by their relatives. In addition, the heritability of CPT performance in the families of schizophrenic probands was estimated.Method: The study subjects were 60 schizophrenic probands, 148 of their first-degree relatives, 20 normal comparison probands, and 42 of the comparison probands' first-degree relatives. Subjects completed undegraded and 25% degraded sessions of the CPT and were interviewed with use of the Chinese version of the Diagnostic Interview for Genetic Studies. Subjects' CPT sensitivity indexes, d′, were standardized against those of a community sample of 345 subjects, with adjustment for age, sex, and level of education.Results: On average, the d′ values of the relatives of schizophrenic probands were lower than those of the relatives of comparison probands but higher than those of schizophrenic probands. Lower sensitivity indexes among the relatives of schizophrenic patients were associated with the interpersonal dysfunction and disorganization factors of schizotypy but not the cognitive/perceptual factor. When schizophrenic probands were divided into two subgroups by a cutoff of –3.0 for adjusted z score on the CPT, the d′ values of relatives of probands with CPT deficits were lower than those of relatives of probands without deficits. The estimated heritability of performance on the CPT ranged from 0.48 to 0.62.Conclusions: Sustained attention deficit may be a genetic vulnerability marker for schizophrenia, and it may be more useful in linkage analysis than traditional phenotype definitions of schizophrenia. Am J Psychiatry 1998; 155: 1214-1220
THE ACTION OF THE INTEACELLULAE POISON OF THE COLON BACILLUS.
Authors: VICTOR C. VAUGHAN
Journal: JAMA (1905)

It is now generally conceded that the pathogenic bacteria bring about those changes in the body cells which form the basis of what we call disease by virtue of certain poisons which they produce. These poisons are supposed to be specific for each kind of bacteria and to them the name of toxin has been given. Certain bacteria possess a toxin which is not an integral part of the cell itself, and hence is not essential to its existence. As examples of such organisms may be mentioned the bacillus of tetanus and that of diphtheria. With these bacteria the toxin is found free in the culture medium and there are differences in opinion concerning its origin, some regarding it as a cleavage product formed by the action of the bacillus either directly or through a chemical ferment on the constituents of the culture medium, while others think that the soluble toxin represents a group of the bacterial cell which easily drops off. On the other hand, the filtrates of cultures from such bacteria as the typhoid and the colon bacillus are non-toxic, or, at the most, possessed of but feeble toxicity.
Cardiac Changes in Rheumatoid Arthritis
Authors: N. Egelius, O. Gohle, E. Jonsson, F. Wahlgren
Journal: Annals of the Rheumatic Diseases (1955)

The present investigation represents a continua- tion of inquiries by Jonsson, Berglund, Gohle, Ejrup, and Friedman (1952) first reported in 1949 at the Seventh International Congress of Rheumatology, New York.Previous Investigations Pathological Studies.-In a series of 25 autopsies of cases of rheumatoid arthritis, Baggenstoss and Rosenberg (1941) found "lesions of the type produced by rheumatic fever" in fourteen, though there was a history of rheumatic fever in only two; they concluded that "chronic infectious arthritis" and rheumatic fever might be in some way related.Fingerman and Andrus (1943) reported positive findings in nineteen of 61 cases, only two of which had a history of rheumatic fever.Reports have also been made by Bayles (1943), Bennett (1943), Young and Schwedel (1944), Rosenberg and others (1944), Clark and Bauer (1948), Graef and others (1949), Snorrason (1950), Bywaters (1950), and Sokoloff (1953).The percentages of rheumatic cardiac changes recorded by these authors varies a great deal, but 117 (27 per cent.) of the total of 439 cases assembled from these reports, revealed signs of rheumatic cardiac disease, and 133 (30 per cent.)signs of pericardial changes.Table I shows the nature of cardiac lesions in 288 of the cases reported in the literature, but in some reports the data were too incom- plete for classification.Clinical Studies.-In the majority of clinical investi- gations cardiac lesions were found much less frequently than in the pathological studies.However, Kahlmeter (1934) found electrocardiographic changes in up to 27 per cent. of cases of "secondary chronic polyarthritis", and in up to 12 per cent. of cases of "primary chronic poly-arthritis"; in a control series, pathological electrocardiograms were obtained in only 2-6 per cent.Dawson and Tyson (1936) found cardiac changes of a rheumatic nature in 7 per cent. of 100 cases.Monroe (1939) noted rheumatic valvular defects in 4 per cent. of 267 patients.Feiring (1945) reported pathological cardiac findings in 29 per cent. of 27 cases, but these included two with a history of rheumatic fever and another two in which that diagnosis seemed probable.Rogen (1947) reported positive cardiac findings in only 3 per cent. of 33 cases.Jonsson and others (1952) examined (by radiography, electrocardiography, hypoxaemia test, auscultation, and phonocardiography) 37 cases of rheumatoid arthritis and 37 controls; positive cardiac findings amounted to eleven cases (30 per cent.) in the rheumatoid group, and three (8 1 per cent.) in the control group.Gil (1949) recorded endomyocardiac lesions in 5-5 per cent. of 360 cases; apart from a greater frequency of aortic defects, the symptoms were of the same type as those seen in rheumatic fever, and 3-3 per cent.showed BLE I
Autoimmunity in juvenile diabetics and their families.
Authors: J I Mann, B Winearls, M Thorogood, G F Bottazzo, J D Baum
Journal: BMJ (1978)

Pancreatic islet cell, thyroid, and gastric antibodies were studied in 116 young insulin-dependent diabetics and 257 relatives. Seventy-four per cent of the diabetics studied within three months of diagnosis had islet-cell antibodies but only 20% of those studied three years or more after diagnosis. Persistence of these antibodies was associated with a high prevalence of thyrogastric autoimmunity, which suggests that some cases have an aetiology similar to that of "polyendocrine" autoimmune disease. Retinopathy or nephropathy, or both, was present in 10 diabetics, who were all members of "autoimmune" families, in which one or more members had organ-specific antibodies. Nine of the 10 healthy relatives with islet-cell antibodies and all families with more than one diabetic were also in this autoimmune group. These data suggest that an autoimmune factor may contribute to juvenile diabetes and that such autoimmune diabetes has a tendency to run in families and may be more likely to cause complications.
By Trust Betrayed: Patients
Authors: George J. Annas
Journal: JAMA (1990)

Paralyzed by poliomyelitis in 1952 when he was 19, Hugh Gallagher has been observing the reactions of physicians and his fellow citizens to the disabled for almost 40 years. His previous books include one on Franklin D. Roosevelt, who he concluded was "a great President, but no role model for disabled people." <i>By Trust Betrayed</i>, which he describes as a message from "the land of the crippled," is devoted to going beyond surfaces to discover how the disabled are perceived and how perceptions determine the way society treats disabled people. Most of the book is devoted to medical killing by the physicians in the Third Reich. There is little new here, and this story has been better told by, among others, Robert Jay Lifton (<i>The Nazi Doctors</i>) and Robert Proctor (<i>Racial Hygiene</i>). Nonetheless, viewing the Third Reich from the perspective of the handicapped is provocative and devastating. The book also