tbuckley/cabot-search huggingface dataset:
Regulation of Genes for HLA Class II Antigens in Cell Lines from Patients with Severe Combined Immunodeficiency
Authors: Claude de Préval, Martin R. Hadam, Bernard Mach
Journal: New England Journal of Medicine (1988)

HLA Class ll–negative severe combined immunodeficiency (SCID) results from a congenital defect characterized by an absence of HLA Class II antigens. Patients with the disorder have no HLA-DR, DQ, or DP antigens or mRNAs in their peripheral-blood lymphocytes. The affected gene is a recessive, transacting regulatory gene that controls the expression of Class II genes. We studied the regulation of HLA Class II gene expression with the use of established Epstein–Barr virus-transformed B-cell lines and skin fibroblast lines from a group of patients with SCID. Lymphoblastoid B-cell lines from the patients contained no mRNA for HLA-DR, DQ, and DP α and β polypeptides, but did express mRNA for the HLA-associated invariant chain, which is normally coregulated with HLA Class II antigens. In the B-cell line from one patient, a very low amount of DR mRNA could be detected, indicating some heterogeneity in SCID. The lymphokine γ-interferon, a strong inducer of Class II genes in a variety of normal cells, did not restore Class II gene expression in any of the SCID B-cell lines. More important, γ-interferon was unable to induce any Class II mRNA in fibroblast lines from patients with SCID, in contrast to the efficient induction observed in normal fibroblasts. The invariant-chain gene, however, was induced in the SCID fibroblasts, confirming a unique uncoupling in the regulation of invariant and Class II genes. Thus, the genetic defect in patients with SCID affects not only the B-cell lineage but also the inducible expression of HLA Class II genes that is normally observed in Class ll–negative cells, such as fibroblasts. This unresponsiveness to γ-interferon in vitro indicates that patients with SCID will not respond to treatment with this lymphokine. Our data also increase understanding of the normal mechanisms regulating the genes for the HLA Class II cell-surface glycoproteins. (N Engl J Med 1988; 318:1295–300.)
Positron-emission tomographic localization of abnormalities of brain metabolism in patients with minimal hepatic encephalopathy
Authors: Alan H. Lockwood, Brian W. Murphy, Kerry Z. Donnelly, Thomas C. Mahl, Sean Perini
Journal: Hepatology (1993)

Many patients with compensated cirrhosis without overt hepatic encephalopathy have deficits in visual-spatial perception, a condition we call minimal hepatic encephalopathy. Five patients with alcohol-induced cirrhosis and nine control subjects underwent positron-emission tomographic imaging of the brain with 18F-fluorodeoxyglucose. Patients also underwent neuropsychological and clinical chemistry tests. The patients had mild arterial hyperammonemia (62 +/- 13 mumol/L, range = 11 to 35 mumol/L) and other abnormalities typical of patients with cirrhosis. The patients' mean percentile scores on the digit symbol and block design subtests, from the Wechsler Adult Intelligence Scale (revised), and Purdue pegboard test were 11 +/- 7, 24 +/- 7 and 7 +/- 8 (right hand). Tests of vocabulary, memory, and new learning were normal. The technique of statistical parametric mapping was used to identify regions where cerebral 18F-fluorodeoxyglucose uptake and metabolism were abnormal. We noted significant reductions in the cingulate gyrus, a center mediating attention, target analysis and response formulation and significant increases in visual associative regions subserving motion and color perception and object orientation. We suggest that minimal hepatic encephalopathy is due to a deficit in the detection and formulation of responses to visual stimuli, a function of the cingulate, which is a part of the anterior attentional system of the brain. Increases in 18F-fluorodeoxyglucose metabolism may be compensatory. These studies show that brain regions differ in their sensitivity to the agents that cause hepatic encephalopathy and that positron-emission tomography is useful in studying the pathophysiology of this disorder.
Book: Evaluating International Humanitarian Action: Reflections from Practitioners
Authors: J. Mitchell
Journal: BMJ (2002)

Eds Adrian Wood, Raymond Apthorpe, John Borton ![Graphic][1]</img>Zed Books, £14.95/$22.50, pp 233 ISBN 1 85649 976 6 Rating:![Graphic][2]</img>![Graphic][3]</img> In 1936 one of the greatest English anthropologists, Sir Edward Evans-Pritchard, began his fieldwork among the Azande people in Central Africa. He discovered a world bounded by magic and witchcraft. At the heart of this culture lay an oracle that operated by feeding poison to a chicken. The Azande would answer vital questions and events around them depending on whether the chicken died or not. Evans-Pritchard was faced with a … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
How to alienate your natural allies and attract your enemies
Authors: J. Richard Udry
Journal: Behavioral and Brain Sciences (1999)

Rose erroneously believes that the sciences of human behavior are being swept with a wave of genetic determinism. Actually, sociologists and psychologists remain predominantly hostile to any genetic influence on behavior. They will love Rose. The few behavior geneticists and sociobiologists in these disciplines are marginalized and looking for a little respect. Rose impugns their motives and ridicules their science.
Acute Inversion of the Uterus
Authors: T. Joyce
Journal: BMJ (1872)

through the row of perforations at F, into the next shelf, and so on until it escapes at Am.The size of the holes at the alternate ends of the shelves is such, that no three of them will admit sufficient air for a single respiration; therefore the air passes through all and over the whole of the superficies charged with ether.The following are some notes of cases in which ether was administered.CASE I.-(In this and the four following cases ether was given on a towel.)-Aman with a sinus in the region of the hip was brought under the influence of the ether in eight minutes.There was no strug- gling nor lividity.He was under its influence altogether a quarter of an hour, during which time he took six ounces.He was very sick directly after the operation, and continued so for a short time, but passed a good night and felt quite himself the following morning.CASE II.-A little girl aged iI, with a sinus over the lower jaw, was brought under the influence of ether in six minutes.There was no struggling nor sickness.She took about three ounces.CASE iII.-A woman aged 30, with cancer of the breast, was brought under the influence of ether in a little over four minutes.There was no struggling.The operation lasted twenty minutes, during which time she took six ounces.She was not sick till the following morning, then twice.CASE iv.-A woman aged I9, with sinuses around the ankle-joint, was brought under its influenee in three minutes.The operation lasted three minutes more, and she took three ounces.There was no strug- gling nor sickness.CASE v.-A man aged 40 was brought into the theatre for extirpa- tion of the eyeball.He struggled a good deal, but was brought under the influence of ether in four minutes.The operation lasted four minutes more, during which time he took five ounces.He was very sick.
Effect of screening sigmoidoscopy and screening colonoscopy on colorectal cancer incidence and mortality: systematic review and meta-analysis of randomised controlled trials and observational studies
Authors: H. Brenner, C. Stock, M. Hoffmeister
Journal: BMJ (2014)

<b>Objectives</b> To review, summarise, and compare the evidence for effectiveness of screening sigmoidoscopy and screening colonoscopy in the prevention of colorectal cancer occurrence and deaths. <b>Design</b> Systematic review and meta-analysis of randomised controlled trials and observational studies. <b>Data sources</b> PubMed, Embase, and Web of Science. Two investigators independently extracted characteristics and results of identified studies and performed standardised quality ratings. <b>Eligibility criteria</b> Randomised controlled trials and observational studies in English on the impact of screening sigmoidoscopy and screening colonoscopy on colorectal cancer incidence and mortality in the general population at average risk. <b>Results</b> For screening sigmoidoscopy, four randomised controlled trials and 10 observational studies were identified that consistently found a major reduction in distal but not proximal colorectal cancer incidence and mortality. Summary estimates of reduction in distal colorectal cancer incidence and mortality were 31% (95% confidence intervals 26% to 37%) and 46% (33% to 57%) in intention to screen analysis, 42% (29% to 53%) and 61% (27% to 79%) in per protocol analysis of randomised controlled trials, and 64% (50% to 74%) and 66% (38% to 81%) in observational studies. For screening colonoscopy, evidence was restricted to six observational studies, the results of which suggest tentatively an even stronger reduction in distal colorectal cancer incidence and mortality, along with a significant reduction in mortality from cancer of the proximal colon. Indirect comparisons of results of observational studies on screening sigmoidoscopy and colonoscopy suggest a 40% to 60% lower risk of incident colorectal cancer and death from colorectal cancer after screening colonoscopy even though this incremental risk reduction was statistically significant for deaths from cancer of the proximal colon only. <b>Conclusions</b> Compelling and consistent evidence from randomised controlled trials and observational studies suggests that screening sigmoidoscopy and screening colonoscopy prevent most deaths from distal colorectal cancer. Observational studies suggest that colonoscopy compared with flexible sigmoidoscopy decreases mortality from cancer of the proximal colon. This added value should be examined in further research and weighed against the higher costs, discomfort, complication rates, capacities needed, and possible differences in compliance.
Solitary crythcma migrans: a clinical, laboratory and epidemiological study of 77 Dutch patients
Authors: H. KUIPER, I. CAIRO, A. DAM, B. JONGH, T. RAMSELAAR, L. SPANJAARD, J. DANKERT
Journal: British Journal of Dermatology (1994)

Regional variations in the clinical spectrum of Lyme borreliosis have been described previously. These may be related to strain variations, or reflect selection bias. We compared the clinical and epidemiological profiles of Dutch patients presenting with solitary erythema migrans alone, with the profiles in other European studies, and studies from the U.S.A., and cultured Borrelia burgdorferi from erythema migrans to identify the genospecies. Seventy-seven consecutive patients with a final diagnosis of erythema migrans were admitted into the study. Various clinical and epidemiological data were obtained, and serum was evaluated for antibodies to Borrelia burgdorferi with an enzyme-linked immunosorbent assay. Skin biopsy specimens were taken from the border of the erythema migrans and cultured in modified Kelly's medium. The different genospecies of Borrelia burgdorferi were identified by reactivity with monoclonal antibodies H3TS, LA-26, LA-31 and D6, and by rRNA gene restriction patterns. Patients were treated with tetracycline or doxycycline, and were seen for follow-up 6 weeks after treatment. Long-term follow-up was by telephone interview. A tick bite had been noticed by 45% of the patients. The onset of erythema migrans occurred in 97% of these patients within 3 months of the tick bite. Erythema migrans was present for 1-319 days (median 2 months). No concomitant manifestations were spontaneously reported. Borrelia burgdorferi was cultured from 52 (84%) of 62 skin biopsy specimens. Fifty isolates (96%) were identified as Borrelia burgdorferi group VS461. No therapy failures occurred among patients treated with tetracycline (follow-up 1-4 years, median 27 months) or doxycycline (follow-up 6-31 months, median 19 months).(ABSTRACT TRUNCATED AT 250 WORDS)
Chronic renal failure associated with topical application of paraphenylenediamine.
Authors: J H Brown, M G McGeown, B Conway, C M Hill
Journal: BMJ (1987)

Chronic renal failure associated with topical application of paraphenylenediamine Paraphenylenediamine ("para"), a derivative of paranitroaniline, is widely used as a hair dye.It has several toxic effects, ofwhich asthma and dermatitis are common.About 4% ofapparently normal subjects are sensitive to it, and 1% are acutely sensitive.'We report two cases of vasculitis and crescentic glomerulonephritis after prolonged topical application.
Design, conduct, analysis and reporting of a multi-national placebo-controlled trial of activated protein C for persistent septic shock
Authors: Simon Finfer, V. Marco Ranieri, B. Taylor Thompson, Philip S. Barie, Jean-François Dhainaut, Ivor S. Douglas, Bengt Gårdlund, John C. Marshall, Andrew Rhodes
Journal: Intensive Care Medicine (2008)

The role of drotrecogin alfa (activated) (DAA) in severe sepsis remains controversial and clinicians are unsure whether or not to treat their patients with DAA. In response to a request from the European Medicines Agency, Eli Lilly will sponsor a new placebo-controlled trial and history suggests the results will be subject to great scrutiny. An academic steering committee will oversee the conduct of the study and will write the study manuscripts. The steering committee intends that the study will be conducted with the maximum possible transparency; this includes publication of the study protocol and a memorandum of understanding which delineates the role of the sponsor. The trial has the potential to provide clinicians with valuable data but patients will only benefit if clinicians have confidence in the conduct, analysis and reporting of the trial. This special article describes the process by which the trial was developed, major decisions regarding trial design, and plans for independent analysis, interpretation and reporting of the data.
Book: Timebomb: The Global Epidemic of Multi-Drug Resistant Tuberculosis
Authors: D. Mitchell
Journal: BMJ (2002)

Lee B Reichman with Janice Hopkins Tanne McGraw-Hill, £18.99, pp 240 ISBN 0 07 135924 9 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> Wars and famines come and go but tuberculosis is a consistent and important fixture for humanity. A third of all people are infected at some stage during their lives. For tuberculosis, the paradox is that although it is quite easy to diagnose and treat, it is an increasing global scourge and the leading cause of death from any chronic infectious disease. Why is this, when effective treatments are available? The reasons relate to geopolitical, socioeconomic and health resource factors. HIV and AIDS further aggravate the situation. In the West people thought that TB was in terminal decline until the mid-1980s when numbers in the United States started to rise. Now TB … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
On the Hemodynamic Regulation of the Secretion of Aldosterone
Authors: FREDERIC C. BARTTER, DONALD S. GANN
Journal: Circulation (1960)

Evidence is presented that the secretion of aldosterone in dogs may be considerably influeneed by hemodynamic factors. The experiments indicate that secretion of aldosterone may be decreased by expanding the "low pressure" system, and may be increased by reducing the amplitude of the pulse pressure in the carotid arteries. The decrease may be prevented by prior section of the vagi, the increase by prior denervation of the thyro-carotid arterial junctions.
Combination Therapy of Adult Acute Myelogenous Leukemia
Authors: Ian Thompson, Thomas C. Hall, William C. Moloney
Journal: New England Journal of Medicine (1965)

IN 1964 Freireich et al.1 reported on the use of combination therapy in the treatment of childhood acute leukemia, using vincristine, amethopterin, 6-mercaptopurine and prednisone simultaneously ("VAMP" program). In their experience with 18 children, most of whom were suffering from acute lymphatic leukemia, 16 had complete clinical and hematologic remissions, and the duration of remission appeared prolonged when compared to that in cases treated by other methods.1 The results of current treatment for adult acute myelogenous leukemia in our clinic and elsewhere had been so poor that in June, 1963, we began using a combination drug regimen. Among the reasons . . .
Regulation of transferrin receptor expression and ferritin content in human mononuclear phagocytes. Coordinate upregulation by iron transferrin and downregulation by interferon gamma.
Authors: T F Byrd, M A Horwitz
Journal: Journal of Clinical Investigation (1993)

We have investigated the regulation of key human iron binding proteins in mononuclear phagocytes by IFN gamma and iron transferrin. In a previous study, we demonstrated that IFN gamma downregulates the expression on human monocytes of transferrin receptors, the major source of iron for the cell. In the present study, we show that IFN gamma also downregulates the intracellular concentration of ferritin, the major iron storage protein in the cell. By radioimmunoassay, the mean ferritin content of nonactivated monocytes was 361 +/- 107 fg/monocyte (mean +/- SEM) whereas the mean ferritin content of IFN gamma-activated monocytes was 64 +/- 13 fg/monocyte, an 82% reduction with activation (P < 0.01, t test). Consistent with its downregulating effect on these iron proteins, IFN gamma treatment also results in decreased iron incorporation. IFN gamma-activated monocytes incorporated 33% less iron from 59Fe-transferrin than nonactivated monocytes (P < 0.05, t test). Gel filtration chromatography revealed that incorporated iron is located primarily in ferritin in both nonactivated and IFN gamma-activated monocytes. Ferritin in IFN gamma-activated monocytes is saturated with approximately three times as much 59Fe as ferritin in nonactivated monocytes. We have also explored the effect of iron transferrin on transferrin receptor expression and intracellular ferritin content in human monocytes. We have found that iron transferrin markedly upregulates both transferrin receptor expression and intracellular ferritin content in both nonactivated (2.3- and 1.3-fold, respectively) and IFN gamma-activated (3.4- and 2.9-fold, respectively) monocytes. This study demonstrates that transferrin receptor expression and intracellular ferritin content in human monocytes is unidirectionally and coordinately upregulated by iron transferrin and unidirectionally and coordinately downregulated by IFN gamma.
Neurological Correction of Lysosomal Storage in a Mucopolysaccharidosis IIIB Mouse Model by Adeno-associated Virus-Mediated Gene Delivery
Authors: Haiyan Fu, Richard J. Samulski, Thomas J. McCown, Yoana J. Picornell, David Fletcher, Joseph Muenzer
Journal: Molecular Therapy (2002)

Mucopolysaccharidosis (MPS) IIIB is characterized by mild somatic features and severe neurological diseases leading to premature death. No definite treatment is available for MPS IIIB patients. We constructed two recombinant adeno-associated virus (rAAV) vectors containing the human α-N-acetylglucosaminidase (NaGlu) cDNA driven by either a CMV or a neuron-specific enolase (NSE) promoter. In vitro, these rAAV vectors mediated efficient expression of recombinant NaGlu in human MPS IIIB fibroblasts and mouse MPS IIIB somatic and brain primary cell cultures. The secreted rNaGlu was taken up by both human and mouse MPS IIIB cells in culture and degraded the accumulated glycosaminoglycans (GAG). A direct microinjection (107 viral particles, 1 μl/10 minutes per injection) of vectors containing the NSE promoter resulted in long-term (6 months, the duration of the experiments) expression of rNaGlu in multiple brain structures/areas of adult MPS IIIB mice. Consistent with previous studies, the main target cells were neurons. However, while vector typically transduced an area of 400–500 μm surrounding the infusion sites, the correction of GAG storage involved neurons of a much broader area (1.5 mm) in a 6-month duration of experiments. These results provide a basis for the development of a treatment for neurological disease in MPS IIIB patients using AAV vectors.
THE QUESTION OF SPINAL BRACES IN LATERAL CURVATURE.
Authors: A. B. JUDSON
Journal: JAMA (1902)

It has been proposed that apparatus having a strong antero-posterior action for the maintenance of lordosis be used, instead of braces which make the customary pressure on the ribs, in lateral curvature of the spine. Experiments in this direction have, however, resulted in nothing notable, and the suggestion has been fruitless so far as I am aware. It may be that the inconvenience of wearing such a brace is too great in a disease which carries with it no menace to the patient's life and but little to her health and comeliness. It might be argued, but not too seriously, that lateral curvature of the spine is an attractive feature, falling in the same category as a slight cast or squint, which has been thought to add piquancy to the beauty of a pretty face. It can not be denied that the typical sigmoid curvature reproduces the technical curved line
P1-02-04: Estrogen Receptor beta Inhibits Breast Cancer EMT by Regulating the Expression of miR-200.
Authors: C Thomas, R Gayani, F Nikolos, R Hao, A Katchy, C McCollum, C Williams, M Bondesson, S Krishnamurthy, F Esteva, J-A Gustafsson
Journal: Cancer Research (2011)

Abstract Estrogen receptor beta (ERβ) mediates the effects of estrogens in a variety of human tissues and regulates cellular processes involved in initiation and progression of breast cancer such as cell proliferation and migration. Clinical studies produced contradictory data regarding the role for ERβ in prognosis of metastatic breast cancer and the molecular mechanism through which ERβ influences cell migration and invasion has not been fully elucidated. Here we show that induction of ERβ expression inhibits epithelial to mesenchymal transition (EMT) in metastatic breast cancer cells. This correlates with an ERβ-mediated induction in the expression of the epithelial marker E-cadherin and downregulation of its transcriptional repressors ZEB1 and SIP1. ERβ alters the expression of ZEB1 and SIP1 by inducing the expression of the miR-200a, miR200b and miR-429. Downregulation of these miRNAs in ERβ-expressing cells resulted in decreased cell-cell contact and decline of E-cadherin levels. In addition, ERβ was found to inhibit the invasiveness of metastatic breast cancer cells in a zebrafish xenotransplantation model. We are now examining breast cancer specimens derived from ductal carcinomas and metaplastic breast cancers to see whether ERβ levels decline in the mesenchymal regions and ERβ expression is correlated with epithelial markers. These data propose a crucial role for ERβ in the regulation of EMT and in prognosis of invasive and metastatic breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-02-04.
PHYSIOLOGY OF SYMPATHETIC NERVOUS SYSTEM IN RELATION TO CERTAIN SURGICAL PROBLEMS
Authors: ALEXANDER FORBES
Journal: JAMA (1926)

The proposal to relieve spastic paralysis by surgical interruption of the sympathetic innervation of the muscles involved rests on the theory that a special function, designated "plastic tonus," depends on the sympathetic nerve fibers, and that abolition of this plastic tonus will relieve the pathologic condition. The theory seems to have arisen, in the first place, from the anatomic observations of Boeke,<sup>1</sup>which apparently establish the innervation of certain skeletal muscle fibers by sympathetic as well as by cerebrospinal nerve fibers. Subsequent investigations by various workers leave little doubt that in some, at least, of the skeletal muscles there are striated fibers innervated by sympathetic nerve fibers; but whether these fibers exist in all muscles and whether they differ histologically from the muscle fibers innervated by medullated nerve fibers are unsettled questions. The functional significance of these fibers has been a matter of more speculation than observation. Some observers