tbuckley/cabot-search huggingface dataset:
Glandular Fever and Chloramphenicol
Authors: P. Kane
Journal: BMJ (1951)

B 1303 has been some shortness of breath on exertion.He married in 1923 and had two children-a daughter now aged 22 and a son who died at 18 years of a stomach complaint.He has continued to have normal sexual relations with his wife about once a fortnight.He shaves each morning, but states that the beard is very soft.Family history: both parents and his only brother are dead; four sisters are alive.So far as he knew none had a dry mouth.On examination he was seen to be of medium build and average intelligence, though rather depressed in mood.His body temperature was normal.There were no telangi- ectases.The skin everywhere was a little dry, but on the legs below the knees it was greatly thickened, shiny, inelastic, and patchily pigmented.The soles of the feet were hyper- keratotic, but were softened on the instep by a fungous infection.In each leg the pulsations of the popliteal and posterior tibial arteries could be felt, but not the dorsalis pedis, perhaps because of the thickened skin.Moderate varicosity of veins was present on each side.The fingernails were normal, but the toenails showed trophic changes, and there was a small ulc* on the right shin.Body hair was scanty, especially in the axillae, and was of feminine distribution about the pubes.The genitalia were hypo- plastic.The eyes showed evidence of old blepharitis, but not of any corneal ulceration.The mucous membrane of the mouth was obviously dry, and the tongue was dry, red, and wrinkled.The nares showed the characteristic changes of atrophic rhinitis sicca with some paranasal infection.The pharynx and larynx were quite dry too, except for a little sticky mucus on the vocal cords; the voice was correspondingly rather hoarse, and the patient.statedthat when he had a cold it usually disappeared completely.The salivary and lacrimal glands were not enlarged or unduly hard.The lungs and heart were clinically normal, and the B.P. was 150/90.Optic fundi and pupils were normal, and the only changes noted in the C.N.S. had been some diminished pain and touch sense in the lower two-thirds of the legs with absent ankle-jerks.Vibration sense was present, however, in the toes.The-urine contained neither albumin nor sugar.
Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways
Authors: Geoff H. Werstuck, Steven R. Lentz, Sanjana Dayal, Gazi S. Hossain, Sudesh K. Sood, Yuan Y. Shi, Ji Zhou, Nobuyo Maeda, Skaidrite K. Krisans, M. Rene Malinow, Richard C. Austin
Journal: Journal of Clinical Investigation (2001)

Hepatic steatosis is common in patients having severe hyperhomocysteinemia due to deficiency for cystathionine β-synthase. However, the mechanism by which homocysteine promotes the development and progression of hepatic steatosis is unknown. We report here that homocysteine-induced endoplasmic reticulum (ER) stress activates both the unfolded protein response and the sterol regulatory element–binding proteins (SREBPs) in cultured human hepatocytes as well as vascular endothelial and aortic smooth muscle cells. Activation of the SREBPs is associated with increased expression of genes responsible for cholesterol/triglyceride biosynthesis and uptake and with intracellular accumulation of cholesterol. Homocysteine-induced gene expression was inhibited by overexpression of the ER chaperone, GRP78/BiP, thus demonstrating a direct role of ER stress in the activation of cholesterol/triglyceride biosynthesis. Consistent with these in vitro findings, cholesterol and triglycerides were significantly elevated in the livers, but not plasmas, of mice having diet-induced hyperhomocysteinemia. This effect was not due to impaired hepatic export of lipids because secretion of VLDL-triglyceride was increased in hyperhomocysteinemic mice. These findings suggest a mechanism by which homocysteine-induced ER stress causes dysregulation of the endogenous sterol response pathway, leading to increased hepatic biosynthesis and uptake of cholesterol and triglycerides. Furthermore, this mechanism likely explains the development and progression of hepatic steatosis and possibly atherosclerotic lesions observed in hyperhomocysteinemia.
RELATION OF A ß1-GLYCOPROTEIN OF HUMAN SERUM TO THE COMPLEMENT SYSTEM
Authors: H. J. Müller-Eberhard, U. Nilsson
Journal: The Journal of Experimental Medicine (1960)

The protein of human serum, tentatively designated ß1C-globulin, was shown to possess serological activity and to be related to the complement system. Another serum protein (ß1A-globulin) was identified as the inactivated form of ß1C-globulin. Incubation of fresh serum with various immune precipitates or with soluble γ-globulin aggregates at 37°C. resulted in the removal of ß1C-globulin. Treatment of fresh serum with zymosan at 17 and 37°C. had a similar effect. In both instances ß1C-globulin was removed from serum, apparently by conversion to ß1A-globulin. However, isolated ß1C-globulin did not react with immune precipitates or zymosan, nor did ß1C-globulin of serum previously heated at 56°C. Highly purified ß1C-globulin was tested for complement component activity by means of the usual reagents. All of the preparations examined were found to reconstitute the hemolytic activity of guinea pig R3. However, they failed to reconstitute R3 obtained from human serum. Isolated ß1A-globulin was found to be inactive in all systems. When isolated ß1C-globulin in either phosphate or in borate buffer was stored at 37°C., the activity detected by means of guinea pig R3 declined within 6 days to 20 to 30 per cent of its original value. As the activity decreased, ß1C-globulin was gradually converted to ß1A-globulin. Addition of ß1C-globulin to a limited complement system (human C') caused an increase of both initial velocity and final degree of hemolysis. Although ß1C-globulin did not cause lysis of EAC'1, 4, 2, it fully prevented the otherwise rapid decay of EAC'1, 4, 2 at 37°C., and so presumably interacted with this complex.
The green tea polyphenol, epigallocatechin-3-gallate, inhibits hepatitis C virus entry
Authors: Sandra Ciesek, Thomas von Hahn, Che C. Colpitts, Luis M. Schang, Martina Friesland, Jörg Steinmann, Michael P. Manns, Michael Ott, Heiner Wedemeyer, Philip Meuleman, Thomas Pietschmann, Eike Steinmann
Journal: Hepatology (2010)

Abstract Hepatitis C virus (HCV) is a major cause of liver cirrhosis and hepatocellular carcinoma. Current antiviral therapy fails to clear infection in a substantial proportion of cases. Drug development is focused on nonstructural proteins required for RNA replication. Individuals undergoing orthotopic liver transplantation face rapid, universal reinfection of the graft. Therefore, antiviral strategies targeting the early stages of infection are urgently needed for the prevention of HCV infection. In this study, we identified the polyphenol, epigallocatechin-3-gallate (EGCG), as an inhibitor of HCV entry. Green tea catechins, such as EGCG and its derivatives, epigallocatechin (EGC), epicatechin gallate (ECG), and epicatechin (EC), have been previously found to exert antiviral and antioncogenic properties. EGCG had no effect on HCV RNA replication, assembly, or release of progeny virions. However, it potently inhibited Cell-culture–derived HCV (HCVcc) entry into hepatoma cell lines as well as primary human hepatocytes. The effect was independent of the HCV genotype, and both infection of cells by extracellular virions and cell-to-cell spread were blocked. Pretreatment of cells with EGCG before HCV inoculation did not reduce HCV infection, whereas the application of EGCG during inoculation strongly inhibited HCV infectivity. Moreover, treatment with EGCG directly during inoculation strongly inhibited HCV infectivity. Expression levels of all known HCV (co-)receptors were unaltered by EGCG. Finally, we showed that EGCG inhibits viral attachment to the cell, thus disrupting the initial step of HCV cell entry. Conclusion: The green tea molecule, EGCG, potently inhibits HCV entry and could be part of an antiviral strategy aimed at the prevention of HCV reinfection after liver transplantation. (Hepatology 2011)
Immunohistochemical expression of matrix metalloproteinases in photodamaged skin by photodynamic therapy
Authors: M.C. Almeida Issa, J. Piñeiro-Maceira, R.E. Farias, M. Pureza, R. Raggio Luiz, M. Manela-Azulay
Journal: British Journal of Dermatology (2009)

Photodynamic therapy (PDT) has been described for photoageing treatment, but its mechanism of action is not clarified. Although PDT-induced matrix metalloproteinase (MMP) expression and collagen production have been studied in normal skin and in inflammatory disease, there is no report about the effect of PDT on the extracellular matrix in photodamaged skin.To evaluate skin remodelling induced by methyl aminolaevulinate (MAL)-PDT in photodamaged skin by histological and immunohistochemical studies.Fourteen patients were treated with two sessions of MAL-PDT. The light source was a light-emitting diode (635 nm, 37 J cm(-2)). Skin biopsies were performed in all patients before and at 3 and 6 months after treatment. Immunohistochemical studies evaluated collagen types I and III, MMP-1, MMP-3, MMP-7, MMP-9, MMP-12 and tissue inhibitor of metalloproteinases-1.Global improvement in photodamaged skin was observed. A significant increase in expression of MMP-9 in the dermis was detected at 3 months after treatment (P = 0.002). Significant increases in the expression of collagen type I at 3 months (P = 0.002) and at 6 months after treatment (P = 0.001) were also observed.Skin remodelling induced by MAL-PDT was demonstrated in photodamaged skin. Two sessions of MAL-PDT increases immunohistochemical expression of MMP-9 in the dermis at 3 months after treatment, and also of collagen type I.
Development of Somatizing Responses in Multiple Sclerosis
Authors: Marcia Pavlou, Dusan Stefoski
Journal: Psychotherapy and Psychosomatics (1983)

Chronic medical illness may produce emotional stress of a variety which encourages the development of patterns of somatization. Discussed here are patterns of somatization in multiple sclerosis. The long-term uncertainty and changing nature and severity of symptoms raises the likelihood that people will become absorbed in their bodies, will demonstrate heightened responses to minor physical change, and may come to experience psychic conflict through the language of physical symptomatology. Case examples are discussed as well as recommendations for treatment.
Direct effect of thyroid hormone on intracardiac conduction in acute and chronic hyperthyroid animals
Authors: M. E. SHAHAWY, M. A. STEFADOUROS, A. A. CARR, R. CONTI
Journal: Cardiovascular Research (1975)

Studies of intracardiac conduction utilizing His bundle electrograms demonstrate direct thyroid hormone action on the conduction system in both acute and chronic hyperthyroid animals.
Genetic Diseases in Pregnancy: Maternal Effects and Fetal Outcome
Authors: Edwin M. Gold
Journal: JAMA (1982)

ABSTRACT Health professionals involved in perinatal care find increasing difficulty keeping pace with the burgeoning of scientific, clinical, and biotechnological information related to genetic and hereditable disorders. Thus, there has been real need for a succinct, lucid, comprehensive summary of such information relevant to perinatal care.Genetic Diseases in Pregnancy fills a long-awaited need. It is a timely, well-organized, readable miniencyclopedia of genetic diseases in pregnancy. In its 13 chapters, this volume covers selected metabolic diseases; disorders of connective tissue and skeletal dysplasia; hemoglobinopathies; Rh and other blood group incompatibilities; genetic disorders of hemostasis; defects of the cardiovascular, respiratory, renal, and gastrointestinal systems; diabetes mellitus; endocrine aspects of genetic disorders in pregnancy; chromosomal abnormalities; and genetic counseling and the major psychiatric disorders. This text covers the maternal effects and fetal outcome related to the foregoing subjects. Emphasis is placed on clinical manifestations of the genetic disorders, on diagnostic screening recommendations, on
Nephrotic Syndrome Associated With Congenital Syphilis
Authors: Philip Pollner
Journal: JAMA (1966)

Congenital syphilis is a rare but definite cause of the nephrotic syndrome. The lesion has not been previously reported in patients with the acute form of the disease and only recently has been demonstrated in patients with acquired syphilis. Renal alterations demonstrated by open kidney biopsy in a patient with congenital syphilis and the nephrotic syndrome were compatible with those seen in patients with membranous glomerulonephritis and in patients with the acquired form of the disease.
The nature of the antigen-antibody complexes initiating the specific wheal-and-flare reaction in sensitized man
Authors: Bernard B. Levine, Anthony P. Redmond
Journal: Journal of Clinical Investigation (1968)

To study the nature of the antigen-antibody complexes which initiate the specific wheal-and-flare (W & F) reaction in sensitized man, a homologous series of bivalent, oligovalent, and multivalent benzylpenicilloyl (BPO) haptens were quantitatively compared for their effectiveness in eliciting W & F in BPO-sensitized human subjects.A series of seven divalent haptens were capable of eliciting W & F, but these generally were not maximally effective elicitors. Of the divalent haptens, those with separation chains of 8 or 13 A were the most effective. Of the oligovalent haptens, maximal effectiveness was attained with BPO(6)-lysine(7), and not with BPO(2)-lysine(3) or BPO(4)-lysine(4), i.e., haptens which are 6- 3- and 4-valent, respectively, from a chemical point of view. However, evidence was obtained from quantitative precipitation experiments which indicated that BPO(6)-lysine(7) functions as a trivalent hapten immunologically, i.e., capable of binding three antibody molecules per mole hapten. Large molecularsized haptens with immunological valences of 7 or 12, but in which the haptenic groups were widely separated, were comparatively ineffective elicitors of W & F. In individual subjects, threshold W & F reactions were obtained with equimolar concentrations of the differently sized divalent, oligovalent, and multivalent haptens. The results demonstrate that for maximally effective elicitation of W & F by haptens, trivalency with optimal distances of separation of haptenic groups is necessary and sufficient. These results indicate the requirement for the formation of a high energy complex of two or three membrane-fixed skin-sensitizing antibody molecules closely bridged together by the elicitor hapten as the initiator of the W & F reaction.
Vaginal Spermicides and Gonorrhea
Authors: Charles Camisa
Journal: JAMA (1983)

To the Editor.—  I was interested in the recent article by Jick et al entitled Vaginal Spermicides and Gonorrhea (1982;248:1619). While the authors have controlled for age and marital status, I still have one concern (among the several that were voiced in the editorial in the same issue by Cates et al [1982;248:1636]) that may be the most important of all—the absence of data comparing frequency of sexual intercourse and number of sexual partners among the groups of contraceptive users. It cannot be excluded from the study that these two factors influence the choice of a contraceptive by a woman. It is likely that oral contraceptives and voluntary sterilization permit casual sex more readily than spermicides. It is well known that the spontaneity of the sexual act is reduced by the insertion of a diaphragm and spermicide. Therefore, the use of the latter method may be more restricted to those
Severe Localized Epidemic of "Infantile Paralysis" in the Tropics
Authors: W. G. Kerr, N. J. Pease
Journal: BMJ (1956)

Since the last war it has become widely recognized that the low incidence of paralytic poliomyelitis in under developed countries is associated with an actual hyperendemicity of the disease in those regions. This hyperendemic state is revealed by the sporadic occurrence of cases of  infantile paralysis  and by the immune state of virtually the whole of the native population over the age of 5. The actual number of these sporadic cases is much greater than has often been realized in the past, owing to poor reporting. Quite a number of cases have also been diagnosed as sciatic palsies following the injection of quinine for  fever. This infantile pattern of infection appears to have been almost world-wide until approximately 1870 ; since then two distinct changes have been noted, beginning in the more highly developed countries. In the first phase, epidemics of the paralytic disease occurred, still confined to those under 5 and apparently unrelated to the season ; in the second phase the age incidence steadily increased, there was a marked increase in the severity of the disease, and it tended to become seasonal. The epidemic described below falls into the first phase of this change? that is, there was a sudden very high incidence of paralytic disease without any alteration in age incidence.
Abstract P3-14-11: Microarray data analysis and long term outcomes of NCIC-CTG MA.22: Neoadjuvant epirubicin and docetaxel with pegfilgrastim support for locally advanced breast cancer
Authors: M Trudeau, J-A Chapman, B Guo, M Clemons, R Dent, R Jong, H Kahn, L Shepherd, K Pritchard, J Xu, P O'Brien, A Parissenti
Journal: Cancer Research (2013)

Abstract Background: 93 patients were enrolled in sequential phase 1 and 2 trials of epirubicin (E) and docetaxel (D) given at 3 (cohort A) or 2 weekly (cohort B) intervals. We previously reported clinical (93%) and pathologic response rates (pCR 7%) as well as the association of fall in tumour RNA integrity (RIN) with response (ASCO 2010). Here we report the results of microarray analysis of tumor specimens pre-and mid-treatment to determine genes which are differentially expressed in different groups. Methods: 6 core biopsies were collected for all patients pre-, mid- and post-treatment with ED. 3 cores were used for standard pathologic assessment while 3 were used for gene expression assessment using Agilent full genome microarrays. Pre- and mid-treatment cores were used with Agilent Feature Extraction Software to assess microarrays; and baseline continuous (% positive) immunohistochemical ER, PR, HER2, and Topo2 were investigated by schedule and dose. RNAs with RIN &amp;gt; = 5.0 were subjected to microarray analysis. NIH BRB array tools were used for investigations of differential gene expressions. K-M curves were generated for the phase 2 cohorts for disease free (DFS) and event free survival (EFS), and for ER− PR− and ER or PR+ subgroups. Results: Of the 93 patients, 47 were in cohort A and 46 in cohort B. Median overall survival was 6.34 years on study. DFS at 50 months was 55% for A (phase 2) and 67% for B (phase 2), while EFS was 55% for A and 63% for B. For ER or PR+ DFS and EFS were 60% and for ER− PR− DFS and EFS were 63%. 134 arrays were available in total: 57 from A, 68 from B with 11 reference breast tumour RNAs for standardization. Patients with and without microarrays were not significantly different. Pre-treatment, we found 3 differentially expressed genes in A and 6 in B between patients who did and did not have RIN &amp;gt; = 5.0 at mid-treatment. Comparing CR to non-CR (PR, SD, PD), 40 genes were found for A and 2 genes for B. Many genes were also differentially expressed in A and B when analyzed by pathologic factors ER, PR, HER2, Topo2, schedule and dose. Mid-treatment, 4,365 genes in A and 18,770 genes in B were significantly different from pre-treatment. Conclusion: At 50 months, DFS was 55% for 3 weekly and 67% for 2 weekly schedules of ED. The genes identified in each cohort pretreatment will be investigated further for relevance to predicting sensitivity or resistance to E or D. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-14-11.
Some Responsibilities of Medical Education
Authors: C. Sidney Burwell
Journal: New England Journal of Medicine (1949)

TO DELIVER the Annual Oration of the Massachusetts Medical Society is an honorable privilege, for which I am grateful.For almost fourteen years, as dean of the Faculty of Medicine, I have had the chief responsibility for the administration of the Harvard Medical School. This experience is the reason for my choice of subject and presumably the basis of the Society's choice of an orator. The organization and progress of medical education have been my chief preoccupation for these fourteen years, and I welcome the opportunity to place on record my faith and my optimism regarding it. As I have . . .
Guidelines for Glycemic Control in Type 2 Diabetes
Authors: Leonard Pogach
Journal: Annals of Internal Medicine (1998)

Letters15 May 1998Guidelines for Glycemic Control in Type 2 DiabetesLeonard Pogach, MD and Clark T. Sawin, MDLeonard Pogach, MDVeterans Affairs New Jersey Health Care System; East Orange, NJ 07019Boston Veterans Affairs Medical Center; Boston, MA 02130Search for more papers by this author and Clark T. Sawin, MDVeterans Affairs New Jersey Health Care System; East Orange, NJ 07019Boston Veterans Affairs Medical Center; Boston, MA 02130Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-128-10-199805150-00015 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Vijan and colleagues [1] used a Markov decision model to estimate the benefit of glycemic control with respect to the end points of blindness and end-stage renal disease in persons with type 2 diabetes without preexisting microvascular complications. They found that the benefit of glycemic control decreased with increasing age at diabetes onset.The decrease in absolute risk resulting from decreased duration of diabetes permits risk stratification in determining a patient's target hemoglobin A1c level, an approach used to design the Veterans Health Administration (VHA) Guidelines for Management of Diabetes Mellitus. Developed in collaboration with members of ...References1. Vijan S, Hofer TP, Hayward RA. Estimated benefits of glycemic control in microvascular complications in type 2 diabetes. Ann Intern Med. 1997; 127:788-95. Google Scholar2. The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in the Diabetes Control and Complications Trial. Diabetes. 1995; 44:968-83. Google Scholar3. Klein R, Klein BE, Moss SE. Relation of glycemic control to diabetic microvascular complications in diabetes mellitus. Ann Intern Med. 1996; 124(1 Pt 2):90-6. Google Scholar4. Eastman RC, Javitt JC, Herman WH, Dasbach EJ, Copley-Merriman C, Maier W, et al. Model of complications of NIDDM. II. Analysis of the health benefits and cost-effectiveness of treating NIDDM with the goal of normoglycemia. Diabetes Care. 1997; 20:735-44. Google Scholar Author, Article, and Disclosure InformationAffiliations: Veterans Affairs New Jersey Health Care System; East Orange, NJ 07019Boston Veterans Affairs Medical Center; Boston, MA 02130 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByTrends in Diabetes Mellitus Indicators in Veterans with Spinal Cord Injury 15 May 1998Volume 128, Issue 10Page: 871-872KeywordsClinical trialsDiabetes mellitusHemoglobinInternetLife expectancyMarkov modelsRenal failureSimulation and modelingType 2 diabetesVeteran care Issue Published: 15 May 1998 CopyrightCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...