tbuckley/cabot-search huggingface dataset:
PKCδ regulates hepatic insulin sensitivity and hepatosteatosis in mice and humans
Authors: Olivier Bezy, Thien T. Tran, Jussi Pihlajamäki, Ryo Suzuki, Brice Emanuelli, Jonathan Winnay, Marcelo A. Mori, Joel Haas, Sudha B. Biddinger, Michael Leitges, Allison B. Goldfine, Mary Elizabeth Patti, George L. King, C. Ronald Kahn
Journal: Journal of Clinical Investigation (2011)

C57BL/6J and 129S6/Sv (B6 and 129) mice differ dramatically in their susceptibility to developing diabetes in response to diet- or genetically induced insulin resistance. A major locus contributing to this difference has been mapped to a region on mouse chromosome 14 that contains the gene encoding PKCδ. Here, we found that PKCδ expression in liver was 2-fold higher in B6 versus 129 mice from birth and was further increased in B6 but not 129 mice in response to a high-fat diet. PRKCD gene expression was also elevated in obese humans and was positively correlated with fasting glucose and circulating triglycerides. Mice with global or liver-specific inactivation of the Prkcd gene displayed increased hepatic insulin signaling and reduced expression of gluconeogenic and lipogenic enzymes. This resulted in increased insulin-induced suppression of hepatic gluconeogenesis, improved glucose tolerance, and reduced hepatosteatosis with aging. Conversely, mice with liver-specific overexpression of PKCδ developed hepatic insulin resistance characterized by decreased insulin signaling, enhanced lipogenic gene expression, and hepatosteatosis. Therefore, changes in the expression and regulation of PKCδ between strains of mice and in obese humans play an important role in the genetic risk of hepatic insulin resistance, glucose intolerance, and hepatosteatosis; and thus PKCδ may be a potential target in the treatment of metabolic syndrome.
A historic issue of the Annals: three papers examine paracetamol in osteoarthritis
Authors: R Neame
Journal: Annals of the Rheumatic Diseases (2004)

The CONSORT statement for the full reporting of clinical trials should be consistently applied

Although current European League Against Rheumatism (EULAR)1 and American College of Rheumatology (ACR)2 guidelines both support paracetamol (acetaminophen) as the first line oral analgesic for patients with knee osteoarthritis (OA), until now there has been a paucity of clinical trial data to confirm the efficacy of paracetamol in large joint OA. This issue of the Annals is unique in containing one meta-analysis and two large placebo controlled studies that examine evidence for the efficacy of paracetamol in OA. Never in the 127 years of paracetamol’s existence have so much trial data on OA been reported.

Because of the marked placebo effect in pain trials3 comparison with a placebo is clearly important to determine the true efficacy of any analgesic. Therefore it is surprising that despite the widespread use and support of paracetamol in OA until now there have been only four placebo controlled trials of this drug in OA. The first two studies reported in 19834 and in 19955 both demonstrated the superiority of paracetamol over placebo for pain relief in large joint OA using parallel group designs. However, the first study contained only 25 patients with knee OA followed up for just 6 weeks.4 The second study was larger (60 patients) but was of just 1 week’s duration and contained a mixed population with knee or hip OA.5 A third parallel group study was reported in 2003.6 This compared paracetamol, diclofenac, and placebo over a 12 week period in 82 patients with knee OA but was the first negative study for paracetamol, showing no difference between paracetamol and placebo using Western Ontario McMaster Osteoarthritis Index (WOMAC) assessments. Most recently, Pincus et al carried out a crossover study …
Postoperative gas gangrene.
Authors: R Maudsley, G P Arden
Journal: BMJ (1969)

BRItIH 301 low figures were found in all three cases of P.N.H. in which this test was performed.Ham's test and the sugar-lysis test were also strongly positive.A low figure of AChE (less than 0 550 pH units/hour) was also found in several cases of myeloproliferative disorder, including polycythaemia vera, myelo- sclerosis, di Guglielmo's disease, thrombo- cythaemia, and myeloid reticulosis.In some of these cases there was also slightly increased lysis in the sucrose-veronal buffer.Though there was not complete correlation between a low AChE and increased sugar lysis, the high proportion of abnormal results in the diseases under discussion supports Dameshek's5 speculation that they are con- nected.-Iam, etc.,
Anemia-induced Changes in Cardiac Output in Dogs Treated with Dichloroisoproterenol
Authors: CHARLES W. GOWDEY
Journal: Circulation Research (1962)

The cardiac output of anesthetized dogs was markedly elevated by the production of severe acute anemia by exchanging dextran for blood. Dichloroisoproterenol, in a dose which completely blocked the positive chronotropic effect of epinephrine and several reflexes, usually had minimal effects on the cardiac output. The cardiac responses to acute anemia were not different in the DCI-treated and the control groups. It is concluded that the effect of acute anemia on cardiac output is probably not mediated by the action of adrenergic substances on the heart.
Ubiquitination of molluscum body and its implications for pathophysiology
Authors: K. Yoneda, T. Demitsu, A. Kon, C. Sadahira, T. Moriue, J. Katsuura, Y. Matsuoka, I. Takai, M. Noda, N. Inagaki, Y. Kubota
Journal: British Journal of Dermatology (2006)

Conflicts of interest: none declared. Sir, Ubiquitin (Ub) is a 8·6‐kDa protein composed of 76 amino acid residues and is widely expressed in various types of cells.1 Proteolytic degradation by the ubiquitin–proteasome system (UPS) is essential for normal cell cycle progression, cellular differentiation and stress responses. Proteins conjugated to Ub are marked for progressive degradation by the 26S proteasome. Recently, this pathway has been shown to be involved in the pathogenesis of various diseases including Parkinson's disease, polyglutamine disease, prion disease and Alexander's disease.2 Molluscum contagiosum virus (MCV) is a human poxvirus, which has a linear double‐stranded DNA genome of 185 000–195 000 bp.3 MCV contains two open reading frames. MC159 and MC160 encode proteins with death effector domains.4 MC159 and MC160 share substantial homology to the death effector domain present in the adaptor molecule Fas‐associated death domain protein (FADD) and the initiating death protease caspase 8.5–8 FADD and caspase 8 participate in generating the death signal from both tumour necrosis factor receptor (TNFR)‐1 and the CD95 receptor. The flow of death signals from TNFR‐1 occurs through the adaptor molecule TNFR‐associated death domain protein (TRADD) to FADD to caspase 8, whereas for CD95 the receptor directly communicates with FADD and then caspase 8. MC159 inhibited both TNFR‐1‐ and CD95‐induced apoptosis as well as killing cells mediated by overexpression of the downstream adaptors TRADD and FADD. It seems that MCV has a strategy to attenuate host immune killing mechanisms.
Vaccination and Immunosuppressive Therapy
Authors: D. C. Martin, W. E. Goodwin
Journal: JAMA (1967)

<h3>To the Editor:—</h3> We read with interest "Vaccination of a Patient Receiving Immunosuppressive Therapy for Lymphosarcoma" by Rosenbaum, Cohen, and Glatstein (<b>198</b>: 737, 1966). Their report of a generalized vaccinia in a patient with lymphosarcoma and hypogammaglobulinemia sounds a warning to physicians caring for patients receiving immunosuppressives. One of our renal transplant recipients (case 8)<sup>1</sup>received a smallpox vaccination at a student health clinic at another university. At the time of vaccination, approximately two years after renal transplantation, the patient was receiving 100 mg azathioprine and 20 mg prednisone daily. Her serum creatinine level averaged 2 mg/100 ml, with an endogenous creatinine clearance of 35 ml/min. The patient observed a marked delay in the onset of the local reaction at the site of vaccination, and the first evidence of an inflammatory reaction occurred approximately 14 days after vaccination. The entire inflammatory process took place at a very slow pace.
Activation of hageman factor by collagen
Authors: G. D. Wilner, H. L. Nossel, E. C. LeRoy
Journal: Journal of Clinical Investigation (1968)

Purified acid-soluble and insoluble human collagen accelerated the clotting of plateletpoor plasma in silicone-treated tubes. The clot-promoting effect did not appear to be due to thromboplastic activity since the collagen preparations did not activate factor X in the presence of factor VII and calcium. Instead, collagen appeared to accelerate clotting by activating Hageman factor (factor XII) on the basis of the following findings: collagen increased the clot-promoting activity of partially purified Hageman factor but exerted no further effect in the presence of kaolin, a known activator of Hageman factor; clot-promoting eluates were obtained from collagen exposed to normal, hemophilic, or PTC-deficient plasma but not from collagen exposed to Hageman or PTA-deficient plasma. The collagen molecule itself appeared to be required for the clot-promoting activity since digestion with collagenase or thermal denaturation at pH 2.5 (about 35 degrees C) resulted in very marked reduction in clot-promoting activity. Since thermal denaturation is associated with transformation of collagen structure from triple helical to random coil form, it is suggested that the native form of collagen is essential for the ability to activate Hageman factor. Blockage of the free amino groups by treatment with nitrous acid or dinitrofluorobenzene only slightly reduced the clot-promoting activity of collagen. In contrast, since addition of cationic proteins to collagen markedly reduced pro-coagulant activity it is suggested that negatively charged sites on the collagen molecule are critical for Hageman factor activation. This suggestion is supported by the finding that pepsin treatment of collagen, which removes the predominantly negatively charged telopeptides, results in significant decrease in coagulant activity. Esterification of collagen, which neutralizes 80-90% of the free carboxyl groups, reduced coagulant activity by over 90% and it is suggested that the free carboxyl groups of glutamic and aspartic acids provide the negatively charged sites critical for Hageman factor activation.
Development and characterization of biodegradable nanospheres as delivery systems of anti-ischemic adenosine derivatives
Authors: Alessandro Dalpiaz, Eliana Leo, Federica Vitali, Barbara Pavan, Angelo Scatturin, Fabrizio Bortolotti, Stefano Manfredini, Elisa Durini, Flavio Forni, Barbara Brina, Maria Angela Vandelli
Journal: Biomaterials (2004)
Seroepidemiology of Human T-Lymphotropic Virus Type III Among Homosexual Men with the Acquired Immunodeficiency Syndrome or Generalized Lymphadenopathy and Among Asymptomatic Controls in Boston
Authors: JEROME E. GROOPMAN
Journal: Annals of Internal Medicine (1985)

We studied a cohort of 45 homosexual men with the acquired immunodeficiency syndrome, 78 with persistent unexplained generalized lymphadenopathy, and 160 asymptomatic homosexual controls for serologic evidence of infection with human T-lymphotropic virus type III (HTLV-III). Study participants were recruited from a community-based health center and a university hospital practice. Ninety-eight percent of men with the syndrome and greater than 90% of men with generalized lymphadenopathy had antibody to HTLV-III, while 21% of the controls were positive (p 〈 0.001). Six patients with generalized lymphadenopathy developed the acquired immunodeficiency syndrome over 2 years; all were seropositive for HTLV-III. Thirty-six asymptomatic controls had had sexual contact with a man with the syndrome; receptive anal intercourse in this group was associated with seropositivity for HTLV-III. These data suggest that persistent generalized lymphadenopathy and the acquired immunodeficiency syndrome are part of a clinical spectrum of HTLV-III infection and that most high-risk homosexual men in some regions of the United States have not yet been infected with this virus.
Multiple Sounds in Paroxysmal Ventricular Tachycardia
Authors: W. Proctor Harvey, Michael A. Corrado
Journal: New England Journal of Medicine (1957)

THE diagnosis of paroxysmal ventricular tachycardia may be more quickly made at the bedside by the hearing of multiple sounds. These are usually of low frequency and are best heard if one listens specifically for them at the apex. Figure 1 shows the phonocardiogram of a patient taken during episodes of ventricular tachycardia, at which time these extra sounds were easily detected at the bedside. Immediately after reversion they were not present.The auscultatory features of ventricular tachycardia,1 , 2 well emphasized in the past, are as follows: a change in intensity of the first heart sound; slightly irregular ventricular rate; and failure of . . .
Teaching Clinical Skills
Authors: JAMES B. REULER
Journal: Annals of Internal Medicine (1977)

Comments and Correction1 February 1977Teaching Clinical SkillsJAMES B. REULER, M.D., DONALD E. GIRARD, M.D., DAVID A. NARDONE, M.D.JAMES B. REULER, M.D.Search for more papers by this author, DONALD E. GIRARD, M.D.Search for more papers by this author, DAVID A. NARDONE, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-86-2-246_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: We read with interest the recent article by Benbassat and Schiffmann (1) detailing an introductory course in clinical medicine for medical students. Another article, recently published by Wiener and Nathanson (2), is also of interest to everyone involved in medical education and housestaff training. In it, they describe a program started in 1970 at the Long Island Jewish-Hillside Medical Center whereby history taking and physical examination methods are monitored on an on-going basis. Through a program of...References1. BENBASSATSCHIFFMANN JA: An approach to teaching the introduction to clinical medicine. Ann Intern Med 84:477-481, 1976 LinkGoogle Scholar2. WEINERNATHANSON SM: Physical examination: frequently observed errors. JAMA 236:852-855, 1976 CrossrefMedlineGoogle Scholar3. SEEGALWERTHEIM DA: On the failure to supervise students' performance of complete physical examinations. JAMA 180:476-477, 1962 Google Scholar4. ENGEL G: The deficiencies of the case presentation as a method of clinical teaching: another approach. N Engl J Med 284:20-24, 1971 CrossrefMedlineGoogle Scholar5. ENGEL G: Are medical schools neglecting clinical skills? (editorial) JAMA 236:861-863, 1976 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Department of Medicine Ambulatory Care Veterans Administration Hospital Portland, OR 97201 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1977Volume 86, Issue 2Page: 246-247KeywordsMedical education Issue Published: 1 February 1977 PDF DownloadLoading ...
On the Utility and Distinctness of the Concept of Behavioral Equipoise
Authors: J. S. Swindell Blumenthal-Barby
Journal: The American Journal of Bioethics (2011)

In their paper, “Behavioral Equipoise: A Way to Resolve Ethical Stalemates in Clinical Research,” Peter Ubel and Robert Silbergleit (2011) argue that the traditional concept of clinical equipoise i...
Multiple gonococcal pilin antigenic variants are produced during experimental human infections.
Authors: H S Seifert, C J Wright, A E Jerse, M S Cohen, J G Cannon
Journal: Journal of Clinical Investigation (1994)

Gonococcal pilin variation is thought to allow immune evasion and change the adherence properties of the pilus. We have examined the process of pilin antigenic variation in human volunteers inoculated with strain FA1090. Our data show that pilin variation occurred throughout the process of infection, that at each time sampled after inoculation multiple pilin variants were present, and that later pilin variants appear to be recombinants between previously expressed genes and the silent storage pilin copies. Thus, during infection a large repertoire of proteins are available to the population to help avoid immune responses, to provide pili with varying functions, and to transmit to a new host.
A CASE OF CONGENITAL MALFORMATION OF THE HEART.
Authors: A. H. SCOFIELD
Journal: JAMA (1898)

Mrs. B., was confined May 5, 1898, at 3 A.M. Ineffectual pains had persisted at intervals since 2 A.M., May 2, with partial escape of amniotic fluid at that time. It was not, however, till the evening of the 4th that the uterine contractions became regular and vigorous. The case was a brow presentation. The head was considerably deformed by pressure and a couple of minutes elapsed before respiration was established. The child's cries were weak and hoarse. It was remarked that the action of the heart was unusually vigorous. After an hour the child was left in apparently good condition. At 5 A.M. the writer was summoned with the report that after a feeble attempt at nursing the child had died in the mother's arms while she was sleeping. An autopsy made a few hours later showed the lungs only partially distended. The heart was normal in appearance, filled
Paradoxical Embolism — Thrombus in Transit through a Patent Foramen Ovale
Authors: T N Srivastava, M F Payment
Journal: New England Journal of Medicine (1997)

Figure 1. An obese 46-year-old man came to the emergency room with the acute onset of numbness and a cold feeling in both hands; he had had shortness of breath and chest pain for the preceding 48 hours. Physical examination showed that he had no radial pulses. After arteriography that revealed emboli involving the right brachial and left axillary arteries, the patient underwent bilateral brachial embolectomy, and normal circulation was restored. Because paradoxical embolism was strongly suspected, two-dimensional transesophageal echocardiography was performed with an omniplane transducer. Panel A shows an image of the heart in the oblique plane (50 degrees), . . .
Research on the Condemned
Authors: Zachary Slomovitz
Journal: JAMA (1964)

ABSTRACT To the Editor:— I read with interest the communication, Coronary Artery Disease and Arteriosclerosis: A Possible Method for Predicting Their Presence (JAMA187:67 [Jan 4] 1964) and must object to doing research on human beings who are about to be executed.The role of physician as scientist is distinctly second to the role of physician as humanitarian. At his best the physician has always led the way in the civilizing process. He demeans himself and his profession when he lends comfort directly or indirectly to an act or procedure, such as capital punishment, that lessens the dignity and worth of individual human life.So long as responsible people, particularly in our profession, continue to remain silent on matters such as these, or, worse still, to condone them when deriving some secondary gain, the struggle for the civilizing process will be made more difficult.
Anaphylaxis and toxic epidermal necrolysis or Stevens–Johnson syndrome after nonmucosal topical drug application: fact or fiction?
Authors: B. Sachs, W. Fischer‐Barth, S. Erdmann, H. F. Merk, J. Seebeck
Journal: Allergy (2007)

Drug-induced anaphylaxis and toxic epidermal necrolysis (TEN) or Stevens-Johnson syndrome (SJS) represent severe immediate and delayed-type adverse drug reactions (ADRs), respectively. Occurrence of such reactions after topical drug application has only rarely been reported. Hence, we compiled a large number of such cases which we systematically analyzed.All such cases contained in the ADR database of the competent pharmacovigilance authority in Germany and cases reported in literature were identified, evaluated and analyzed with regard to potential risk factors. Since the application of drugs to mucous membranes facilitates their entry to the systemic circulation only cases occurring after non-mucosal topical drug application were considered.After evaluation 28 anaphylaxis database cases and 48 anaphylaxis literature cases remained for analysis. Application to skin wounds or to skin with impaired barrier function was identified as a risk factor in 10/28 (36%) of the database cases and in 42/48 (88%) of the literature cases. In 9/28 database cases (32%), anaphylaxis was induced by drugs used for their hyperemizing effect and, in 8/28 cases (29%) by antibiotics or antiseptics. In the literature cases, anaphylaxis was induced by antibiotics or antiseptics in 35/48 cases (73%). Only one SJS database case and one TEN literature case remained after case evaluation.Anaphylaxis does occur after non-mucosal topical drug administration. Application of drugs to skin wounds or to skin with impaired barrier function may pose a risk factor for its occurrence. TEN or SJS following non-mucosal topical drug application seems to be extremely rare.
Chronic diarrhoea in a teenager
Authors: S. Saxena, S. G Mitton, R. Pollok
Journal: BMJ (2008)

A 14 year old boy has a three year history of loose stools with intermittent abdominal pain. He is the smallest boy in his class.

### What is the risk of underlying disease?

Chronic diarrhoea is defined as >3 loose or liquid stools a day, lasting more than three weeks. This may indicate an underlying non-infectious diagnosis, such as coeliac or inflammatory bowel disease, particularly if accompanied by delayed development or growth retardation. A key consideration is whether the boy’s gastrointestinal symptoms and growth are pathological, and if so, whether they are related. Since issues around puberty and diarrhoea may be embarrassing for him, it may be better to conduct the consultation without his mother present.

### History

Ask about consistency and frequency of diarrhoea. Paleness and foul smell with residual fat droplets in the toilet water suggests fat malabsorption. Blood in the stool may occur with infection or inflammatory bowel disease. Mucus and pus are more likely with inflammatory bowel disease. A history of foreign travel in developing countries may indicate bacterial or …
Congenital Deficiency of Fibrin-Stabilizing Factor
Authors: Agathe Barry, Jean-Marie Delâge, P. Q. Quebec
Journal: New England Journal of Medicine (1965)

SINCE the discovery by Laki and Lorand1 of a plasma factor responsible for rendering a fibrin clot insoluble in 5-M urea and in 1 per cent monochloracetic acid in the presence of ionized calcium, the importance of Laki-Lorand factor,2 also called fibrinase3 or fibrin-stabilizing factor (F.S.F.),4 has been recognized in the physiology of blood coagulation. The first researchers in this field concentrated on the identification,2 purification,5 , 6 measure of activity7 and mechanism of action of this factor,8 but at that time, its clinical implications were still unknown.Since 1960, when Duckert et al.9 first observed a familial hemorrhagic disorder by congenital . . .
HELICAL BLOOD FLOW IN PULMONARY ARTERY VISUALIZED WITH PHASE-RESOLVED 3D CINE PHASE CONTRAST MRI (4D-FLOW)
Authors: Kenichiro Suwa, Takeji Saito, Makoto Sano, Mamoru Nobuhara, Masao Saotome, Tsuyoshi Urushida, Hideki Katoh, Hiroshi Satoh, Yasuo Takehara, Marcus Alley, Harumi Sakahara, Hideharu Hayashi
Journal: Journal of the American College of Cardiology (2013)