tbuckley/cabot-search huggingface dataset:
Targeted disruption of TGF-β1/Smad3 signaling protects against renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction
Authors: Misako Sato, Yasuteru Muragaki, Shizuya Saika, Anita B. Roberts, Akira Ooshima
Journal: Journal of Clinical Investigation (2003)

Tubulointerstitial fibrosis is the final common result of a variety of progressive injuries leading to chronic renal failure. Transforming growth factor-β (TGF-β) is reportedly upregulated in response to injurious stimuli such as unilateral ureteral obstruction (UUO), causing renal fibrosis associated with epithelial-mesenchymal transition (EMT) of the renal tubules and synthesis of extracellular matrix. We now show that mice lacking Smad3 (Smad3ex8/ex8), a key signaling intermediate downstream of the TGF-β receptors, are protected against tubulointerstitial fibrosis following UUO as evidenced by blocking of EMT and abrogation of monocyte influx and collagen accumulation. Culture of primary renal tubular epithelial cells from wild-type or Smad3-null mice confirms that the Smad3 pathway is essential for TGF-β1–induced EMT and autoinduction of TGF-β1. Moreover, mechanical stretch of the cultured epithelial cells, mimicking renal tubular distention due to accumulation of urine after UUO, induces EMT following Smad3-mediated upregulation of TGF-β1. Exogenous bone marrow monocytes accelerate EMT of the cultured epithelial cells and renal tubules in the obstructed kidney after UUO dependent on Smad3 signaling. Together the data demonstrate that the Smad3 pathway is central to the pathogenesis of interstitial fibrosis and suggest that inhibitors of this pathway may have clinical application in the treatment of obstructive nephropathy.
Defective B-Lymphocyte Function in Homosexual Men in Relation to the Acquired Immunodeficiency Syndrome
Authors: SAVlTA G. Pahwa, Maria Theresa J. Quilop, Michael Lange, Rajendra N. Pahwa, Michael H. Grieco
Journal: Annals of Internal Medicine (1984)

Patients with the acquired immunodeficiency syndrome manifest a wide spectrum of immunologic abnormalities. Polyclonal and antigen-specific differentiation of B lymphocytes into immunoglobulin- and antibody-secreting cells was studied in-vitro in three groups of homosexual volunteers: asymptomatic men; men who were symptomatic but lacked clinical criteria for the acquired immunodeficiency syndrome; and those having the syndrome. Although mean responses of all three groups were significantly lower than those of healthy heterosexual male controls, those of the asymptomatic group were least affected. Abnormalities in the symptomatic group were equal to or greater than those of patients with the syndrome, but responses of the latter group were the least augmentable by in-vitro manipulations. Severe impairment of B-cell function appeared to favor clinical deterioration. Antibody replenishment might be of value as adjunctive therapy in persons with the acquired immunodeficiency syndrome or as prophylaxis in certain at-risk persons.
Mural Thrombosis and Arterial Embolism in Mitral Stenosis
Authors: ROBERT A. JORDAN, CHARLES H. SCHEIFLEY, JESSE E. EDWARDS
Journal: Circulation (1951)

A clinicopathologic study of 51 cases of mitral stenosis with intracardiac mural thrombi is presented with particular reference to the locations of these thrombi and their relationship to the associated thromboembolic phenomena. In 27 cases the thrombi were present only in the left side of the heart, in 15 cases they were in both sides of the heart, and in 9 cases they were present only in the right atrium. Of 42 cases in which thrombi were located in the left side of the heart, in 20 the thrombi were limited to the left auricular appendage. In the remaining 22 cases in this group the thrombi in the left side of the heart were situated on the main atrial wall, in the auricular appendage and on the main atrial wall together, or in the left ventricle. Systemic arterial emboli occurred frequently regardless of the particular site in the left side of the heart at which the thrombus formed. Of 24 cases in which thrombi were situated in the right side of the heart, in 20 the thrombi were restricted to the right auricular appendage.
Cooperation of Human Tumor-Reactive CD4+ and CD8+ T Cells after Redirection of Their Specificity by a High-Affinity p53A2.1-Specific TCR
Authors: Jürgen Kuball, Frank W. Schmitz, Ralf-Holger Voss, Edite Antunes Ferreira, Renate Engel, Philippe Guillaume, Susanne Strand, Pedro Romero, Christoph Huber, Linda A. Sherman, Matthias Theobald
Journal: Immunity (2005)
Immunosuppression in Steroid-Resistant Nephropathy.
Authors: E. J. Bardana
Journal: Annals of Internal Medicine (1969)

s1 May 1969Immunosuppression in Steroid-Resistant Nephropathy.E. J. Bardana Jr., M.D., G. A. Porter, M.D., G. A. Jacobsen, B.S., R. T. Gourley, M.D., B. Pirofsky, M.D.E. J. Bardana Jr., M.D.Search for more papers by this author, G. A. Porter, M.D.Search for more papers by this author, G. A. Jacobsen, B.S.Search for more papers by this author, R. T. Gourley, M.D.Search for more papers by this author, B. Pirofsky, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-70-5-1093_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptNineteen patients with steroid-resistant lupus 1 nephritis and nephrotic syndrome secondary to membranous glomerulonephritis and proliferative glomerulonephritis were treated with sustained low-dose azathioprine (2.0 mg/kg body weight/day) and prednisone (5 to 15 mg/day) for up to 14 months. Serial determinations were measured to assess: [1] functional response; [2] criteria for patient selection; and [3] relationship of renal functional improvement with changes in the immune apparatus. Renal function was measured by creatinine clearance, albumin-to-globulin ratio, quantitation and selectivity of urinary protein, cholesterol, and renal biopsy. Cellular immunity was studied by skin tests with mumps,Candida, or 2,4-dinitrochlorobenzene antigens. Humoral antibody response... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Portland, Oregon PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1969Volume 70, Issue 5Page: 1093-1093KeywordsCandidaCholesterolCreatinineGlomerulonephritisImmune responseImmunityMumpsNephritisProteinsSkin tests Issue Published: 1 May 1969 PDF DownloadLoading ...
Provision of ERCP Services and Training in the United Kingdom
Authors: M. C. Allison, D. N. Ramanaden, M. G. Fouweather, D. K. Knight Davis, D. G. Colin-Jones
Journal: Endoscopy (2000)

A rising demand for hands-on training in endoscopic retrograde cholangiopancreatography (ERCP) has coincided with a need for increased scrutiny of outcomes (clinical governance) and the development of less invasive methods of pancreaticobiliary imaging. We surveyed the current provision of ERCP facilities and training throughout the United Kingdom.Questionnaires were sent to senior endoscopists in 252 acute hospitals and to 500 trainees in gastroenterology.Completed forms were returned from 180 hospitals (a 71% response rate) and from 233 trainees (a 47% response rate). A median of 210 ERCPs per year are carried out at each centre (range 40-1000), under the supervision of 345 senior endoscopists. ERCP training had been started by 163 trainees (70%), of whom 42 (26%) had been given one or fewer procedures to start per week. Trainees rated their training as excellent (25%), good (28%), adequate (24%) or inadequate (22%); 193 (83%) perceived that they needed training in ERCP to ensure that future career opportunities were not denied to them.Some centres have insufficient capacity for training in ERCP. Some form of preselection for both trainers and trainees may be required to ensure that quality is maintained. Gastroenterology training programmes should move away from encouraging all trainees to learn ERCP, and should promote the acquisition of alternative skills.
Maternal leucocyte zinc deficiency at start of third trimester as a predictor of fetal growth retardation.
Authors: J L Wells, D K James, R Luxton, C A Pennock
Journal: BMJ (1987)

Leucocyte zinc concentrations were measured in 70 mothers at the beginning of the third trimester of pregnancy and compared with the weight centiles of their subsequently delivered babies. The median maternal leucocyte zinc concentrations rose progressively with weight centile. Thus the median leucocyte zinc concentration of the mothers delivering babies weighing below the 10th centile was 112 nmol/10(9) leucocytes and that of the mothers with babies weighing above the 90th centile was 229.5 nmol/10(9) leucocytes. A maternal leucocyte zinc concentration less than 120 nmol/10(9) leucocytes strongly predicted a baby weighing below the 10th centile (positive predictive value = 71.9%, negative predictive value = 91.5%, sensitivity = 64.3%, specificity = 81.8%). These findings suggest that maternal zinc concentration might have a role in antenatal screening, but larger studies are required.
Upper airway surgery should not be first line treatment for obstructive sleep apnoea in adults
Authors: Adam G Elshaug, John R Moss, Janet E Hiller, Guy J Maddern
Journal: BMJ (2008)

#### Key points

The prevalence of obstructive sleep apnoea in high income countries is estimated to be 20% for mild disease and 6-7% for moderate or severe disease. The condition is associated with multiple morbidities, motor vehicle crashes, and reduced health related quality of life.1 Clinical guidelines recommend continuous positive airway pressure (CPAP) with weight and alcohol management (if indicated) as first line treatment for symptomatic, moderate to severe obstructive sleep apnoea.2 3 Upper airway surgery (such as uvulopalatopharyngoplasty) may also be done, but evidence does not support its use.4 However, use of surgical procedures is widespread and increasing in Australia and elsewhere (such as the Nordic countries).5 6 We propose that upper airway surgery should not be first line treatment for obstructive …
Damage-associated molecular pattern activated Toll-like receptor 4 signalling modulates blood pressure in l-NAME-induced hypertension
Authors: Daniel Sollinger, Ruth Eißler, Steffen Lorenz, Susanne Strand, Stefan Chmielewski, Cristiane Aoqui, Christoph Schmaderer, Hans Bluyssen, Josef Zicha, Oliver Witzke, Elias Scherer, Jens Lutz, Uwe Heemann, Marcus Baumann
Journal: Cardiovascular Research (2013)

Recent publications have shed new light on the role of the adaptive and innate immune system in the pathogenesis of hypertension. However, there are limited data whether receptors of the innate immune system may influence blood pressure. Toll-like receptor 4 (TLR4), a pattern recognition receptor, is a key component of the innate immune system, which is activated by exogenous and endogenous ligands. Hypertension is associated with end-organ damage and thus might lead to the release of damage-associated molecular patterns (DAMPs), which are endogenous activators of TLR4 receptors. The present study aimed to elucidate whether TLR4 signalling is able to modulate vascular contractility in an experimental model of hypertension thus contributing to blood pressure regulation. NG-nitro-l-arginine methyl ester (l-NAME)-induced hypertension was blunted in TLR4−/− when compared with wild-type mice. Treatment with l-NAME was associated with a release of DAMPs, leading to reactive oxygen species production of smooth muscle cells in a TLR4-dependent manner. As oxidative stress leads to an impaired function of the NO-sGC-cyclic GMP (cGMP) pathway, we were able to demonstrate that TLR4−/− was protected from sGC inactivation. Consequently, arterial contractility was reduced in TLR4−/−. Cell damage-associated TLR4 signalling might act as a direct mediator of vascular contractility providing a molecular link between inflammation and hypertension.
Mannitol and Amphotericin B
Authors: Temple W. Williams
Journal: JAMA (1976)

<h3>To the Editor.—</h3> We wish to comment on the recent report by Rosch et al (235:1995, 1976) that suggests a protective effect of mannitol when used in conjunction with the nephrotoxic antifungal agent amphotericin B. Although the single case report suggests a role for mannitol, it nevertheless remains anecdotal. The hazard of extending this type of information to clinical practice must be emphasized. Although a report<sup>1</sup>from this institution likewise suggested a beneficial effect of mannitol in recipients of amphotericin B, a controlled study that we are currently concluding indicates no protective role. An identical conclusion was reached by Bullock et al.<sup>2</sup>These investigators found no differences in the degree of renal impairment between groups of patients receiving amphotericin alone, and amphotericin plus mannitol. We therefore urge that purported beneficial results of therapy be subjected to controlled trial before acceptance by the medical community.
NHS: a time to choose.
Authors: T. Smith
Journal: BMJ (1989)

NHS: a time to choose Either health insurance or higher taxes Twelve months ago in a new year message the BMJ described the NHS as in terminal decline, warning that urgent action was needed to prevent its disintegration.'The government responded to widespread public disquiet by announcing its own internal inquiry (which has yet to report).It has also given a substantial pay rise to nurses -but managed to antagonise many of them by imposing bureaucratic rigidity on their regrading programme.And this autumn the government gave the public the impression that it was restoring the finances of the NHS by a massive extra payment of £1 8 billion.2These actions have allayed much of the public anxiety, but they have done nothing to tackle the underlying problems.There is no sign of any political will to face the central issue - that no nation with a low tax philosophy can fund its health services adequately from taxation.We live in an era of managed information, but the public cannot for ever go on believing that the problems of the NHS can be solved by efficiency savings, ingenious accounting schemes, and tougher controls on doctors.Any objective outside observer would have to conclude that the future of the NHS is just as uncertain as it was this time last year.A health expert arriving in Britain for the first time and looking at the hospital and community services would find: * One quarter of health authorities in England planning reductions in services so that they can stay within cash limited budgets.That means more bed closures, cuts in staff numbers, and recruitment freezes' * Waiting lists as long as ever, with 678 800 waiting for inpatient treatment in England at 31 March 1988.Of that total a quarter had been waiting for over one year4 * Hospitals in a sorry state of disrepair; around £2000m needs to be spent on essential maintenance and construction to restore existing buildings to an adequate standard,s though the latest payment from the Chancellor included an extra £89m.But even if repaired Britain would still have the oldest hospitals in western Europe * Academic medicine contracting, having been forced to reduce its numbers of clinical staff from 2165 in 1979 to 1728 in 1985-around 20% in five years6 * Finally, staff morale low and unlikely to improve.Nurses' and midwives' discontents are regularly seen on television and in the press; but hospital doctors, too, are depressed.Surgeons are told to restrict their elective surgery; physicians are told not to admit patients for investigation; junior staff say LONDON, SATURDAY
Measurement of pain in juvenile chronic polyarthritis.
Authors: P J Scott, B M Ansell, E C Huskisson
Journal: Annals of the Rheumatic Diseases (1977)

Pain can be measured using a visual analogue scale in children with juvenile chronic polyarthritis. In a study of 100 children failures were uncommon after the age of 5. Pain severity was strikingly lower than in a group of adults with rheumatoid arthritis and correlated poorly with other measures of disease severity and activity. Because of the low scores, measurement of pain is likely to be less useful in children for assessing the effects of treatment than it is adults.
Prognosis of biliary atresia in the era of liver transplantation: French national study from 1986 to 1996
Authors: Christophe Chardot, Matthieu Carton, Nathalie Spire-Bendelac, Christophe Le Pommelet, Jean-Louis Golmard, Bertran Auvert
Journal: Hepatology (1999)

Since the sequential treatment of Kasai operation with or without liver transplantation became available, the overall prognosis of biliary atresia remains unclear. This study examined the prognostic factors from diagnosis. All patients with biliary atresia living in France and born in the years 1986 to 1996 were reviewed. Actuarial survival rates were calculated for survival with native liver, survival after liver transplantation, and overall survival. Potential prognostic factors were analyzed using the logrank test and the Cox model. A total of 472 patients were identified. Ten-year overall survival was 68%. Independent prognostic factors for overall survival were (S = 10-year rates) performance of Kasai operation (performed: S = 69%; not performed: S = 50%), age at Kasai operation (</=45 days: S = 80%; >45 days: S = 66%), anatomical pattern of extrahepatic bile ducts, polysplenia syndrome, experience of the center (</=2 new biliary atresia [BA] patients/year [24 centers]: S = 54%; 3 to 5 [2 centers]: S = 60%; >/=20 [1 center]: S = 78%). Survival with native liver depended on the same independent prognostic factors. In conclusion (1) Kasai operation remains the first line treatment of BA, and (2) early performance of Kasai operation and treatment in an experienced center reduces the need for liver transplantation in infancy and childhood and provides children with the best chance of survival.
TRANSMISSION OF MONONUCLEOSIS
Authors: ROBERT J. HOAGLAND
Journal: Annals of Internal Medicine (1966)

Letters and Comments1 March 1966TRANSMISSION OF MONONUCLEOSISROBERT J. HOAGLANDROBERT J. HOAGLANDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-64-3-720 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor: The December 1965 issue of the ANNALS OF INTERNAL MEDICINE contains an article "A Syndrome Resembling Infectious Mononucleosis After Splenectomy for Idiopathic Thrombocytopenic Purpura." The authors reported that 3 of 34 patients who had splenectomy for the above disorder (in the decade 1955 to 1965) became ill 21 to 24 days after splenectomy. They stated: "There would seem to be little doubt that the cases reported herein represent true instances of infectious mononucleosis"; I concur in their belief.The purpose of this communication is to point out that in 1955, in an article stating the methods of...References1. HOAGLAND RJ: The transmission of infectious mononucleosis. Amer. J. Med. Sci. 229: 262, 1955. CrossrefMedlineGoogle Scholar2. DE VOSKUIPERS JF: Een geval van mononucleosis infectiosa overgebract door bloedtransfusie. Nederl. T. Genesk. 95: 3036, 1951. MedlineGoogle Scholar3. HOAGLAND RJ: The incubation period of infectious mononucleosis. Amer. J. Public Health 54: 1699, 1964. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByOccurrence of Epstein-Barr Virus Illness in Children Diagnosed with Group A Streptococcal PharyngitisInfectious mononucleosis 1 March 1966Volume 64, Issue 3Page: 720-720KeywordsIdiopathic thrombocytopenic purpuraSplenectomy Issue Published: 1 March 1966 PDF DownloadLoading ...
Enkephalins and Endorphins: A Major Discovery?
Authors: Robert M. S. Bell
Journal: JAMA (1976)

Enkephalins and endorphins are naturally occurring polypeptides recently found in various parts of the brain. They have been shown to mimic the activity of morphine in isolated smooth-muscle preparations, opiate-receptor binding assays, and analgesic tests. There is currently considerable interest and speculation regarding the physiological role of these substances. Could they be the key to the long sought-after mechanisms of analgesia, tolerance, and drug dependence? Will they explain the analgesia seen with acupuncture and electrical stimulation of the brain? Is their inappropriate secretion or release associated with disease states? What eventual therapeutic opportunities will they provide?  Workers in the field are so excited by their discoveries that one is reminded of the enthusiasm generated by the finding of the prostaglandins. Such enthusiasm was well demonstrated at the recent International Narcotics Research Conference (Marischal College, Aberdeen, Scotland, July 1976), where more than 35 papers dealing with these endogenous opiate-like substances were
Case of Murine Typhus in London
Authors: T. B. Dunn
Journal: BMJ (1948)

MEDBRuRNL 9 two minutes, whilst the third collapsed after about six minutes and then appeared unconscious, cold, and with a barely perceptible and irregular radial pulse.No convulsions were observed in any of the patients.The survivor was given 1 ml. of nikethamide subcutaneously, and artificial respiration was applied.She recovered consciousness and was detained for observation.Post-mortem examinations were performed upon the two fatal cases, but nothing of note was discovered except a remark- able and quite unusual degree of flaccidity of the heart, the musculature appearing otherwise normal.In both cases the lungs were extremely congested.At this time the true nature of the accident was not realized and the livers were sent to the Government analyst, who subsequently reported the presence of bismuth therein.Because of this report, the survivor was treated with " ametox " and intravenous salines, but signs of bismuth poisonring rapidly appeared and a blue line was visible on the gums on the third day.Diminution of urinary output occurred almost at once, and complete anuria resulted on the fifth day.Intra- venous sodium sulphate solution caused excretion to recom- mence and increase daily until 16 oz.(450 ml.) was passed on the tenth day, when death occurred.All urine passed after admission contained albumin, red blood corpuscles, and casts.The blood-urea estimations showed a rapid rise to a maximurmi Uof 240 mg. per 100 ml. on the seventh day, falling to 208 mg.on the day of death.Post-mortem examination disclosed marked blue gingivitis.The abdomen contained about a litre of clear pale amber fluid.The liver was enlarged, soft, and covered with recent fibrinous adhesions which anchored it to the surrounding viscera.The kidneys were both very pale and swollen, with fine punctate "aemorrhages on the surface.The lower colon and rectum were inflamed, with small haemorrhagic spots.No other finding of note was discovered.Microscopy of the kidneys revealed 'almost complete destruction of the tubular epithelium, with many granular and fatty casts.The liver showed little histological change, but both kidneys and liver contained quan- tities of extremely finely divided fat throughout the tissue.The relative quantities of bismuth given and demonstrated by the analyst were as follows Mg.Sobi'a per Mg.Bi per kg.Body Weight kg.Liver Case 1 (immediate death) .1340 Case 2 ( ,, ,, ).10 30Case 3 (delayed death) .