tbuckley/cabot-search huggingface dataset:
Pathogenic effects of bullous pemphigoid autoantibodies on rabbit corneal epithelium.
Authors: G J Anhalt, C F Bahn, R S Labib, J J Voorhees, A Sugar, L A Diaz
Journal: Journal of Clinical Investigation (1981)

Bullous pemphigoid (BP) is associated with circulating autoantibodies reactive with an antigen(s) of the basement membrane zone (BMZ) of skin and mucosae. The pathogenicity of these autoantibodies, although suspected, is unconfirmed. We have investigated the effects of BP autoantibodies on a closely related tissue, the corneal epithelium of the rabbit. IgG fractions from the sera of seven patients with BP were purified by (a) ammonium sulfate precipitation, (b) ion exchange chromatography, or (c) gel filtration. Control IgG was prepared by ion exchange chromatography of pooled normal human gamma globulins. 32 rabbits received corneal intrastromal injections of BP IgG fractions (50 microliter, 0.95-2.05 mg total dose) in one eye, and control IgG (50 microliter, 1.8 mg) in the contralateral cornea. 28 of 32 BP IgG injections produced corneal inflammatory lesions, 10 of which developed visible blisters. Histologically, lesions showed polymorphonuclear cells clustering along the BMZ, and subepithelial blister formation. Immunofluorescence showed in vivo bound IgG and C3 at the BMZ. The intensity of inflammation was dose dependent and correlated often with in vitro complement fixation titers of the fractions. None of 32 corneas injected with control IgG became inflamed. BP IgG fractions injected intradermally into the ear skin of rabbits failed to produce inflammation. This may be due to slow clearance of IgG in the cornea, and optimal binding by the corneal epithelium. The intracorneal injections of BP IgG reproduce the clinical, histological, and immunological features of BP. This study provides evidence that BP autoantibodies are pathogenic.
Platelet factor V New York: A defect in factor V distinct from that in factor V Quebec resulting in impaired prothrombinase generation
Authors: Harvey J. Weiss, Bruce Lages, Shilun Zheng, Catherine P.M. Hayward
Journal: American Journal of Hematology (2001)

Studies were performed on a patient with a longstanding bleeding disorder whose major defects were impaired platelet prothrombinase activity in the absence of added factor Va, and a platelet factor V value that was either decreased or at the lower limit of normal when assayed on multiple occasions. In contrast, plasma factor V values were consistently normal. Unlike Scott Syndrome, in which platelet prothrombinase activity is decreased in both the presence and absence of added factor V, her platelets appeared to utilize added factor Va normally in supporting the generation of prothrombinase activity. These findings suggest an intrinsic defect in platelet factor V as the basis of her platelet prothrombinase defect. This defect appears to be different than that described in the Quebec platelet disorder (factor V Quebec). Immunoblot analyses of washed platelet lysates demonstrated a pattern of variably sized factor V molecules that was entirely similar to that observed in normal platelets, and both the heavy and light chains of her factor V after thrombin cleavage were of the same size as that observed in normal platelets. In addition, her platelet multimerin was normal and immunoblot analysis excluded the type of generalized granular protein defect and pathological proteolysis that has been suggested to explain the factor V defect in the Quebec platelet disorder. The findings in this patient thus suggest a new type of platelet factor V defect as the basis for the impaired capacity of her activated platelets to support prothrombinase generation. The findings further support an important role for platelet factor V in hemostasis. Am. J. Hematol. 66:130–139, 2001. © 2001 Wiley-Liss, Inc.
Prevalence and Risk Factors for Insomnia in Breast Cancer Survivors Receiving Aromatase Inhibitors.
Authors: J. Mao, P. Gehrman, I. Su, D. Bruner, S. Xie, A. El Sehamy, A. DeMichele
Journal: Cancer Research (2009)

Abstract Purpose: Insomnia is increasingly recognized as a major symptom outcome in oncology; however, its prevalence and risk factors have not been previously defined in women receiving aromatase inhibitors (AI) for breast cancer.Patients and Methods: We performed a cross-sectional analysis of a cohort of postmenopausal women with stage 0-III breast cancer receiving adjuvant AI therapy at an outpatient breast oncology clinic at a large university hospital. The validated Insomnia Severity Index (ISI) was the primary outcome (Cronbach's alpha of 0.91 in this population). According to ISI, Insomnia was categorized as: no clinically significant insomnia, 0-7; sub-threshold insomnia 8-14; clinical insomnia (moderate severity), 15-12; clinical insomnia (severe), 22-28. We defined anyone who had clinical insomnia with a score of 15 or above. Multivariate logistic regression analyses were performed to assess risk factor(s).Results: 367 patients have been analyzed, with a mean age of 61.6 +/- 10 years. 83.6% were White and 12.9% Black. While 124 (34.1%) had sub-threshold insomnia, 67 (18.4%) met criteria for clinical insomnia based on ISI: 58 (15.9%) for clinically moderate insomnia and 9 (2.5%) clinically severe insomnia. Of the entire sample, 31% considered seeking treatment for insomnia over the previous month. In a multivariate logistic regression model, clinical insomnia was independently associated with current joint pain (odds ratio [OR], 4.41, 95% confidence interval [CI], 2.17-8.96, p&amp;lt;0.001) and hot flashes (OR, 3.00, 95% CI, 1.58-5.71, p=0.001). While education level (college only vs. graduate or professional degree) was also associated with increased risk for clinical insomnia (OR, 2.46, 95% CI, 1.18-5.14, p=0.016), no other demographic, clinical or treatment variable was related to clinical insomnia.Conclusions: Insomnia is a substantial problem among breast cancer survivors receiving aromatase inhibitors and is highly associated with joint pain and hot flashes. Thus, effective treatment of joint pain and hot flashes may help improve insomnia in this population. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1062.
Inherited Nephropathy: A Family Instance Associated with Gout.
Authors: David P. Nicholson
Journal: Annals of Internal Medicine (1964)

s1 October 1964Inherited Nephropathy: A Family Instance Associated with Gout.David P. Nicholson, M.D., M.R.C.P.David P. Nicholson, M.D., M.R.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-61-4-816_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThere are a number of recorded instances of families who have shown inherited or familial nephritis. Familial hyperuricemic nephropathy has been described, and in line with current thought the renal disease was ascribed to the hyperuricemia. The following family demonstrates that the renal disease may be inherited as a dominant characteristic and that clinical and laboratory indications of gout may be secondary.A 31-year-old married female, without issue, presented in June, 1961, with a history compatible with uremia and anemia. Over the next year the disease progressed to death in uremia with hyperchloraemic acidosis. Autopsy confirmed the presence of glomerulonephritis.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Dallas, Tex. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1964Volume 61, Issue 4Page: 816-817KeywordsAnemiaAutopsyClinical laboratoriesGlomerulonephritisGoutNephritisRenal diseasesResearch laboratories ePublished: 1 December 2008 Issue Published: 1 October 1964 PDF downloadLoading ...
Professorial Achievement: George W. Thorn
Authors: Francis D. Moore
Journal: New England Journal of Medicine (1972)

June 30, 1972, marks the terminus of tenure for a remarkable member of the New England community. Dr. George Widmer Thorn reaches retirement and completes 30 years as Hersey Professor of the Theory and Practice of Physic at Harvard Medical School and Physician-in-Chief at the Peter Bent Brigham Hospital. A Journal editorial based on this pivotal event might focus on general questions such as academic tenure, the balance between teaching, research, administration and patient care for a professor, the unique role of the small university hospital in the mix of medical facilities, or the decisions concerned with naming a successor. . . .
SKA-31, a novel activator of SKCa and IKCa channels, increases coronary flow in male and female rat hearts
Authors: Ramesh C. Mishra, Darrell Belke, Heike Wulff, Andrew P. Braun
Journal: Cardiovascular Research (2012)

Endothelial SKCa and IKCa channels play an important role in the regulation of vascular function and systemic blood pressure. Based on our previous findings that small molecule activators of SKCa and IKCa channels (i.e. NS309 and SKA-31) can inhibit myogenic tone in isolated resistance arteries, we hypothesized that this class of compounds may induce effective vasodilation in an intact vascular bed, such as the coronary circulation. In a Langendorff-perfused, beating rat heart preparation, acute bolus administrations of SKA-31 (0.01–5 µg) dose-dependently increased total coronary flow (25–30%) in both male and female hearts; these responses were associated with modest, secondary increases in left ventricular (LV) systolic pressure and heart rate. SKA-31 evoked responses in coronary flow, LV pressure, and heart rate were qualitatively comparable to acute responses evoked by bradykinin (1 µg) and adenosine (10 µg). In the presence of apamin and TRAM-34, selective blockers of SKCa and IKCa channels, respectively, SKA-31 and bradykinin-induced responses were largely inhibited, whereas the adenosine-induced changes were blocked by ∼40%; TRAM-34 alone produced less inhibition. Sodium nitroprusside (SNP, 0.2 μg bolus dose) evoked changes in coronary flow, LV pressure, and heart rate were similar to those induced by SKA-31, but were unaffected by apamin + TRAM-34. The NOS inhibitor L-NNA reduced bradykinin- and adenosine-evoked changes, but did not affect responses to either SKA-31 or SNP. Our study demonstrates that SKA-31 can rapidly and reversibly induce dilation of the coronary circulation in intact functioning hearts under basal flow and contractility conditions.
Downregulation of the antioxidant protein peroxiredoxin 2 contributes to angiotensin II–mediated podocyte apoptosis
Authors: Hsiang-Hao Hsu, Sigrid Hoffmann, Giovana S. Di Marco, Nicole Endlich, Jasna Peter-Katalinić, Thomas Weide, Hermann Pavenstädt
Journal: Kidney International (2011)

Podocytes have a significant role in establishing selective permeability of the glomerular filtration barrier. Sustained renin-angiotensin-aldosterone system activation is crucial to the pathogenesis of podocyte injury, but the mechanisms by which angiotensin II modulates podocyte survival due to physiological or injurious stimuli remain unclear. Here, we used proteomic analysis to find new mediators of angiotensin II-induced podocyte injury. Antioxidant protein peroxiredoxin 2 expression was decreased in cultured podocytes stimulated with angiotensin II. Peroxiredoxin 2 was found to be expressed in podocytes in vivo, and its expression was decreased in the glomeruli of rats transgenic for angiotensin II type 1 receptors in a podocyte-specific manner, or in rats infused with angiotensin II. Downregulation of peroxiredoxin 2 in podocytes resulted in increased reactive oxygen species release, protein overoxidation, and inhibition of the Akt pathway. Both treatment with angiotensin II and downregulation of peroxiredoxin 2 expression led to apoptosis of podocytes. Thus, peroxiredoxin 2 is an important modulator of angiotensin II-induced podocyte injury.
RESEARCH IN HUMAN SUBJECTS AND THE ARTIFICIAL TRAUMATIC NEUROSIS: WHERE DOES OUR RESPONSIBILITY LIE?
Authors: BERNARD BRESSLER, ALBERT J. SILVERMAN, SANFORD I. COHEN, BARRY SHMAVONIAN
Journal: American Journal of Psychiatry (1959)

In conclusion it seems that if we are to continue doing research in clinical psychiatry on human subjects, we do have a responsibility to the subjects, to somehow protect them against the possible traumatic effects of an experiment. How this might best be done should not long remain an unanswered question.
BLOOD VISCOSITY
Authors: Lovell Langstroth
Journal: The Journal of Experimental Medicine (1919)

Small amounts of potassium oxalate probably have no effect on the viscosity of the blood and changes hitherto ascribed to it can be attributed either to variation in carbon dioxide content or to sedimentation of the red blood cells. The viscosity of blood when exposed to the air increases rapidly. This change accompanies a loss of carbon dioxide and can be prevented by stoppering the container and agitating until the blood comes into carbon dioxide equilibrium with the air above it, when the viscosity remains constant. It is essential in determining the viscosity of blood that the red cells should be uniformly suspended throughout the plasma. This can be accomplished by rotating 5 to 10 cc. of blood in a separating funnel for 1 minute.
Canada's drug plan hits old, mentally ill, and those on welfare
Authors: D. Spurgeon
Journal: BMJ (1999)

Changes to Quebec's prescription drug plan, introduced in recent years to extend coverage and share costs, have benefited some previously unprotected citizens but have hurt many of the province's most vulnerable groups. That is the conclusion of a study undertaken by 16 researchers directed by Dr Robert Tamblyn of McGill University.

The researchers included doctors and pharmacists from several universities and a Montreal public health department. Their study was the first systematic examination in …
MINOR INJURIES TO THE EYE IN INDUSTRY
Authors: B. Cridland
Journal: BMJ (1929)

EYE injuries in industry have received from time a good deal of attention, has been mainly towards the major ones involvinig loss one initerest has been chiefly directed.This should be, for indlustrial eye injuries are nio the importanst cause of blindness.Thius -the report of Departmental Committee on Causes and Prevention of Blindness it is stated that 10 cent. in three of the -largest cities in the country was due accident; sixteen other causeswere mentioned, but only three of these were rlesponsible higlher percentage, and onily one of thie three (ophthalmia neonatorumn) appreciable extent.Moreover, various reasons the fiure 10 rper cent, is, I think, lower than shouLld Again, in the report of the Departmental thhee Welfare of the Blind, puiblished Professor Colis-sttates that 5 per, cent, all reported lby certifying 'surgeons-thiat is, all accidents in indtustry
CONTROL OF UTERINE HEMORRHAGE BY THE ROENTGEN RAY
Authors: J. B. Mason
Journal: JAMA (1925)

<h3>To the Editor:</h3> —The following report of a case may prove of interest in relation to the article by Dr. William S. New-comet and the discussion by Dr. John H. Girvin (The Journal, November 7): A married woman, aged 33, with three children living, was seen with Dr. J. I. Smith in 1920 because of uterine bleeding of more than a year's duration. For three or four months she had been confined to her bed and had to be carried to the office for the first roentgen-ray treatment. Examination was practically negative, revealing slight enlargement of the uterus and marked anemia. The previous history of the patient was unimportant. Treatment was given by means of the roentgen ray through two portals of entry anteriorly, with 9 inch spark gap, 5 milliamperes, 10 inch target distance, 4 mm. aluminum filter, ten minutes. This was repeated every twenty-one days for four treatments.
Book Review Malignant Liver Tumors: Current and Emerging Therapies Second edition. Edited by Pierre A. Clavien, Yuman Fong, H. Kim Lyerly, Michael A. Morse, and Alan P. Venook. 482 pp., illustrated. Sudbury, Mass., Jones and Bartlett, 2004. $174.95. 0-7637-1857-2
Authors: Adrian M. Di Bisceglie
Journal: New England Journal of Medicine (2004)
Complication of Acupuncture
Authors: Thomas E. Drake
Journal: JAMA (1974)

<h3>To the Editor.—</h3> While I was on emergency duty during my internship, an elderly Chinese man was brought in by ambulance, complaining of severe, left-sided chest pain. Although an electrocardiogram and other admitting studies gave results within normal limits, a chest roentgenogram showed a 2-cm-long needle in the left
THE CAUSATION OF THE DISEASES OF WOMEN.Read in the Section of. Obstetrics and Diseases of Women, at the Forty-fourth Annual Meeting of the American Medical Association.
Authors: CHARLES P. NOBLE
Journal: JAMA (1893)

Within recent years activity among gynecologists has taken the form of improvement in the technique of operations; and as an outgrowth of the large number of operations which have been performed, the pathology of diseases of women has likewise been improved. Comparatively little has been written concerning the causation of the diseases of women, although the subject is one of great importance, in view of its bearing upon preventive medicine. Only as the causes of disease are made known to the profession at large, is it possible to take measures for their prevention. And in gynecology, especially, prevention is far better than cure. The principal causes of the diseases of women are: 1. Imperfect development of the sexual organs. 2. Gonorrhea. 3. Septic inflammation following child-birth. 4. Lacerations due to child-birth. 5. Miscellaneous causes, including constipation, erroneous habits of life, and errors of dress. 1.—<i>Imperfect Development of the Sexual Organs</i>.—
829. Design of a Safe and Efficient Vector for Bone Marrow Chemoprotection by O6-Methyl-Guanine-DNA-MethylTransferase
Authors: Axel Schambach, Jens Bohne, Saurabh Chandra, Elke Will, Lars Mueller, Geoffrey Margison, David A. Williams, Christopher Baum
Journal: Molecular Therapy (2005)

In order to achieve efficient and safe expression of the promising chemoselection marker, O6-Methylguanine-DNA-methyltransferase (MGMT) P140K, in hematopoietic cells, we designed and compared eight vectors, three gammaretroviral (murine leukemia virus, MLV) and five lentiviral (human immunodeficiency virus, HIV-1). All vectors had monocistronic cassettes as required for clinical studies of MGMT-mediated bone marrow chemoprotection. We compared either LTR-driven or safer SIN (self-inactivating LTR) vectors. In the SIN context, we chose the human phosphoglycerokinase (hPGK), elongation factor 1a (EF1a) or SFFV U3 (MLV-derived) as an internal promoter to reveal different expression strengths. All constructs generated high titers and showed correct processing in target cells, as demonstrated by Northern, Western Blot und immunofluorescence. FACS analysis allowed sensitive detection of MGMT expression in transduced cells and revealed significant differences in MGMT levels, depending on vector design. Expression differences correlated with results of a biochemical alkyltransferase assay. The highest expression levels of MGMT P140K could be achieved using the SFFV promoter, located either in the LTR or in internal position of a SIN backbone. Gammaretroviral and lentiviral SIN vectors with comparable internal cassettes had similar titers and expression levels. An intron did not improve MGMT P140K expression. All vectors were sufficiently strong to mediate polyclonal chemoresistance, which resulted in a chimerism of >95% transduced cells in vitro, following a single exposure to BCNU. However, abundant expression of MGMT P140K, in contrast to the wild-type protein, led to a selective disadvantage of transduced cells in the absence of drug. Use of a less potent SIN vector with an internal expression cassette driven by the human PGK promoter avoided this side effect, and still allowed polyclonal chemoprotection of transduced hematopoietic cells under conditions of a low multiplicity of infection. Thus, to achieve the desired properties of efficiency and safety, less potent expression vectors for MGMT P140K represent a reasonable choice for future in vivo studies. Moreover, our preliminary data suggest that SIN vectors reduce the incidence of insertional genotoxicity in primary murine hematopoietic cells.
END RESULTS IN REMOVAL OF BLADDER NECK OBSTRUCTION
Authors: HERMAN L. KRETSCHMER
Journal: JAMA (1942)

In a perusal of the voluminous literature on the subject of the treatment of bladder neck obstruction, whether by suprapubic or perineal prostatectomy or by transurethral resection, one finds that all phases of the subject have been considered, and some of them in great detail, with the possible exception of a discussion of the end results. A good deal of argumentation is to be found in the present day literature relative to the pros and cons; that is, the arguments for and against resection in the treatment of bladder neck obstruction. But an equal amount of emphasis has not been placed on the essential aspect of the treatment, which is the relief of the obstruction. Relief of the obstruction results in cure; therefore, relief of the obstruction is the objective that must be attained, because unless the obstruction is completely relieved, no matter which method of operation is employed, one
Risk of testicular cancer after vasectomy: cohort study of over 73 000 men
Authors: H Moller, L B Knudsen, E Lynge
Journal: BMJ (1994)

<h3>Abstract</h3> <b>Objective</b>: To confirm or refute reports that vasectomy may increase the risk of cancers of the testis and prostate. <b>Design</b>: Computerised record linkage study of cohort of men with vasectomy and comparison of cancer rates with those in the whole Danish population; manual check of all records of patients with testicular and prostate cancer diagnosed within the first year of follow up. <b>Setting</b>: Denmark 1977-89. <b>Subjects</b>: Cohort of 73 917 men identified in hospital discharge and pathology registers as having had a vasectomy for any reason during 1977-89. <b>Main outcome measures</b>: Observed incidences of testicular, prostate, and other cancers up to the end of 1989. Results - The overall pattern of cancer incidence in the study cohort was similar to that expected nationally. No increased incidence in testicular cancer was observed (70 cases; standardised morbidity ratio 1.01 (95% confidence interval 0.79 to 1.28)). The incidence during the first year of follow up was also close to that expected (nine cases; standardised morbidity ratio 0.80 (0.36 to 1.51)). The incidence of prostate cancer was not increased (165 cases; standardised morbidity ratio 0.98 (0.84 to 1.14)). <b>Conclusions</b>: The incidence of testicular cancer in men with vasectomy is no higher than in other men. Vasectomy does not cause testicular cancer and does not accelerate the growth or diagnosis of pre-existing testicular neoplasms. Data concerning a20causal relation between vasectomy and prostate20cancer were inconclusive.