tbuckley/cabot-search huggingface dataset:
Epidermolysis bullosa simplex in Japanese and Korean patients: genetic studies in 19 cases
Authors: K. Yasukawa, D. Sawamura, M. Goto, H. Nakamura, S-Y. Jung, S-C. Kim, H. Shimizu
Journal: British Journal of Dermatology (2006)

Epidermolysis bullosa simplex (EBS) comprises a group of hereditary bullous diseases characterized by intraepidermal blistering caused by mutations in either keratin gene, KRT5 or KRT14. Significant correlation between the position of mutations within these proteins and the clinical severity of EBS has been noted. A recent report showed EBS cases in Israel had unique genetic features compared with European or U.S.A. associated families, which suggests that the ethnic and geographical features of EBS patients may be different.To assess the possibility that EBS may present with certain specific features in Japanese and Koreans and to identify additional EBS mutations for genotype/phenotype correlation.EBS was clinically diagnosed and confirmed by transmission electron microscopic examination of a skin biopsy. Mutation analysis of KRT5 and KRT14 was performed by direct sequencing in 17 Japanese and two Korean EBS patients.We have identified six novel KRT5 missense mutations (V143D, D158V, V186M, Q191P, R352S, G517D). R352S is the first mutation in the 2A domain. Most of these novel mutations changed amino acids that were evolutionarily conserved. Eight including all five mutations in EBS-Dowling-Meara patients have been previously reported. We were unable to detect mutations in five sporadic EBS-Koebner patients. The proportion of mutations in KRT5 (11 of 14; 78%) is higher than that for KRT14 mutations (3 of 14; 21%) in these Japanese and Korean EBS patients.Japanese and Korean patients with EBS showed very similar phenotype and genotype correlations with patients from Western countries. Whether the higher proportion of KRT5 mutations is a definite characteristic of Japanese and Korean patients with EBS or not, requires further research into mutations in Japanese and Korean people.
Neonatal Weight Loss and Aldosterone Excretion
Authors: Saad K. Al-Agba
Journal: JAMA (1969)

<h3>To the Editor:—</h3> Aldosterone excretion in urine has been measured in few infants and newborns. The aim of this study was to determine serially normal aldosterone excretion during the newborn period and to see whether there was a relationship between the initial neonatal weight loss and aldosterone excretion. Four normal premature male infants were studied because of the relative ease of collecting 24-hour urine samples in males. Their birth weights ranged between 1,814 to 2,267 gm (4 to 5 lb) and their gestational ages were between 33 and 35 weeks. Three 24-hour urine samples were collected from each: (1) during the first 24 hours; (2) during the 24 hours when they had reached the lowest weight; and (3) during the 24 hours when the regained their birth weight. These infants were fed 5% dextrose in water at 4, 8, and 12 hours of age, and then were fed a milk
Diagnosis of Uterine Abnormalities With Radionuclide Imaging
Authors: ASEEM BHATNAGAR, RAVI SHANKAR, ANUPAM MONDAL, MAHINDER K. CHOPRA, MAJ L. SATIJA, RAJAN V. NARAYANAN
Journal: Clinical Nuclear Medicine (1995)

A pelvic hypervascular blush often creates a diagnostic dilemma during radionuclide abdominal imaging studies in females. This blush is shown to be due to uterine vascularity that is more prominent in the secretory and menstrual phases of the menstrual cycle. Significant uterine vascularity in the earlier phases is inappropriate and may be pathologic. Three such cases are presented in which increased uterine vascularity on radionuclide imaging during the proliferative phase either lead to a diagnosis or supported a clinical finding.
PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene
Authors: Nazneen Rahman, Sheila Seal, Deborah Thompson, Patrick Kelly, Anthony Renwick, Anna Elliott, Sarah Reid, Katarina Spanova, Rita Barfoot, Tasnim Chagtai, Hiran Jayatilake, Lesley McGuffog, Sandra Hanks, D Gareth Evans, Diana Eccles, Douglas F Easton, Michael R Stratton
Journal: Nature Genetics (2006)
Response of Non-insulin-dependent Diabetic Patients to an Intensive Program of Diet and Exercise
Authors: R James Barnard, Leza Lattimore, Robert G Holly, Samuel Cherny, Nathan Pritikin
Journal: Diabetes Care (1982)

To assess the effectiveness of the Pritikin program of diet and exercise for treating patients with non-insulin-dependent diabetes mellitus (NIDDM), data were obtained from 60 patients who completed the 26-day residential program. Of the 23 patients who were taking oral hypoglycemic agents upon entry, all but 2 were off medication by the end of the program. Of the 17 patients who were taking insulin, all but 4 were off medication at discharge. Two of the four had their insulin reduced by 50% while the remaining two had no major change in their insulin dosage. Fasting blood glucose was reduced from 194.9 +/- 10.1 to 144.6 +/- 7.1 mg/dl. Serum cholesterol was reduced from 225.4 +/- 5.7 to 181.7 +/- 4.9 mg/dl while triglycerides were reduced from 283.7 +/- 28.8 to 186.2 +/- 11.6 mg/dl. The group as a whole lost an average of 4.3 kg/body wt and achieved 40.5% of their desired weight loss. Maximum work capacity increased from 5.6 +/- 0.3 to 7.9 +/- 0.4 METs, while daily walking increased from 11.7 +/- 2.4 to 102.8 +/- 4.8 min/day. The decrease in fasting glucose was not correlated with weight loss (r = 0.24), increase in walking time (r = 0.00), or increase in MET capacity (r = 0.05). We conclude that the total program is an effective means for treating NIDDM patients. We also feel that the high-complex-carbohydrate, high-fiber, low-fat diet is of primary importance.
A mycobacterial 65-kD heat shock protein induces antigen-specific suppression of adjuvant arthritis, but is not itself arthritogenic.
Authors: M E Billingham, S Carney, R Butler, M J Colston
Journal: The Journal of Experimental Medicine (1990)

A recombinant (r)65-kD protein from Mycobacterium leprae, at levels far in excess of those present in whole mycobacteria, was unable to induce arthritis. Even when combined with a synthetic adjuvant, CP20961, to mimic the peptidoglycan adjuvant component of the mycobacterial cell wall, the r65-kD protein failed to induce arthritis. Pretreatment with as little as 1 microgram r65-kD protein protected rats against arthritis induced by M. tuberculosis, but this r65-kD protein was markedly less able to protect against arthritis induced by the synthetic adjuvant, CP20961, or type II collagen. The r65-kD protein appears, therefore, to produce an antigen-specific protection against arthritis induced by bacterial cell walls containing the 65-kD protein. Such protection can be overcome, however, by arthritogenic T lymphocytes, suggesting that protection occurs by preventing clonal proliferation of autoreactive T lymphocytes that are induced by the adjuvant properties of mycobacterial cell walls. How the r65-kD protein abrogates this particular adjuvant activity, and the nature of the arthritogenic self antigen(s), remain to be elucidated.
Genotypic toxicity: implications for individuals and populations.
Authors: M H Depledge
Journal: Environmental Health Perspectives (1994)

The goals of genetic ecotoxicology are discussed and redefined. New directions in which genotoxicity "effect" studies might be pursued are outlined. Recognition of the genotoxic disease syndrome in lower animals suggests that more attention should be given to exploring the relationships between DNA damage (adduct formation, gene mutations, etc.) and its manifestation at the level of individuals. Within a given population, not all individuals are equally susceptible to pollutant toxicity (including genotoxicity). It is proposed therefore, that more attention be paid to identifying the factors underlying interindividual variability in susceptibility. Examples are provided of specific cases in which differences in susceptibility to pollutants have been directly related to genotypic predisposition. This approach is also advocated for investigating the individual and population level consequences of genotoxic damage. The possibility of using phenotypic traits to recognise subsets of individuals within populations possessing similar genotypes is discussed.
Committee condemns Indian government for failing to withdraw 33 drugs that lack evidence
Authors: S. Bhaumik
Journal: BMJ (2013)

A parliamentary committee on health has severely criticised India’s government for its “evasive” response to recommendations it made in May last year on tightening the regulation of drugs.

It accused the government of “dillydallying and procrastination” in failing to enforce proper procedures for approving drugs, for not following global bans on harmful drugs, and for failing to withdraw 33 drugs that were approved without clinical trials.

The Parliamentary Standing Committee on Health And Family Welfare presented its 66th report into the operation …
TREATMENT OF ACUTE DINITROPHENOL POISONING
Authors: M. L. Tainter
Journal: JAMA (1935)

Because of the widespread use of alpha-dinitrophenol in treating obesity and the repeated emphasis on its toxicity when taken in overdosage, a new toxicologic problem seems to be developing. This arises chiefly from the selection of dinitrophenol as the lethal drug by would-be suicides, but partly also as accidental poisoning resulting from use of proprietary or secret products containing the drug. In order to attain a position in the list of popular suicidal agents, a drug apparently must combine certain properties not necessarily related to its therapeutic usage. That is, its action must be dramatic enough to be associated in the lay mind with powerful effects and certainly fatal outcome. The drug must be commonly available, so that it can be taken without undue delay when the decision for suicidal attempt is made. It is also well known that the popularity of a drug for this purpose
Ruptured Spleen Simulating Pneumonia
Authors: Alan R. Gerstein
Journal: JAMA (1967)

To the Editor:—  In the absence of recent trauma, ruptured spleen may be temporarily unsuspected. This report describes a patient in whom atypical signs resulted in a month of hospitalization before surgery.  Report of a Case:—  This 42-year-old man was admitted because of productive cough, chills, sweats, headache, epigastric pain, and pleuritic left shoulder pain of one day's duration. He was a smoker and had a chronic cough. He admitted moderate alcoholic intake without intoxication in the last five months. Despite repeated questioning, he denied trauma since an auto accident five years earlier. The blood pressure was 128/70 mm Hg, the pulse 96 beats per minute, and the temperature 100.4 F. Abnormal physical findings were limited to flatness and decreased breath sounds at the left base and slight direct midepigastric tenderness. The spleen was not palpable at any time. Results of laboratory studies included a white blood cell count
Cytokine and Ig‐production by CG‐containing sequences with phosphorodiester backbone and dumbbell‐shape
Authors: M. Schmidt, K. Anton, C. Nordhaus, C. Junghans, B. Wittig, M. Worm
Journal: Allergy (2005)

Background: Immunostimulatory oligodeoxynucleotides (CpG‐ODN) usually contain phosphorothioate (PS) backbones for nucleotide protection, which may result in some nonspecific side‐effects like prolongation of coagulation time. Objective: The aim of the present study was to investigate the immunomodulatory potential of DNA molecules without PS backbones. Thus, we designed phosphorodiester (PO) molecules with a dumbbell‐like covalently‐closed structure (dSLIM‐30L1). Methods: We analyzed their effects on peripheral blood mononuclear cells (PBMC) from spontaneous high and low immunoglobulin (Ig)E producer (allergic and nonallergic donors) in comparison with linear CpG‐ODN (lin‐30L1) with PS backbones, using enzyme‐linked immunosorbent assay and flow cytometry. Results: We observed a decrease of spontaneous IgE levels in PBMC from high IgE producer of approximately 27% with both dSLIM‐30L1 and lin‐30L1. In addition, both molecules enhanced the production of IgA, IgM and IgG1/IgG2, but with a slightly different pattern. Both molecules stimulated the secretion of the T H 1‐like cytokines interleukin (IL)‐2, interferon‐ γ and IL‐12p40 and the pro‐inflammatory cytokine IL‐6. The immunomodulatory potential of dSLIM‐30L1 and lin‐30L1 was also effective in PBMC from nonallergic donors, as was confirmed for IL‐2, IL‐12p40, IgG1/IgG2 and IgM. Conclusion: Our data show an inhibition of IgE production but also enhancement of the inflammatory cytokine response in PBMC from allergic and nonallergic donors by covalently‐closed PO‐based dSLIM‐30L1 with a pattern similar to that of linear PS‐based lin‐30L1, while avoiding PS‐modifications and thus PS‐mediated side‐effects. Whether such molecules are useful for the treatment of allergic diseases will need further clarification by appropriate in vivo studies.
Flecainide-induced arrhythmia in canine ventricular epicardium. Phase 2 reentry?
Authors: S C Krishnan, C Antzelevitch
Journal: Circulation (1993)

BACKGROUND We recently reported that sodium channel block can produce opposite effects on action potential duration (APD) and refractoriness in epicardial versus endocardial tissues of the canine ventricle. In addition, strong sodium channel current inhibition was found to cause loss of the action potential dome in epicardium but not endocardium, thus inducing a marked dispersion of repolarization and refractoriness between epicardium and endocardium as well as among neighboring epicardial sites. The marked heterogeneity that evolves under these conditions provides a substrate for the development of arrhythmias. Flecainide was found to induce extrasystolic activity more readily than other sodium blockers. The present study contrasts the electrophysiological actions of flecainide in canine ventricular epicardium and endocardium and examines the characteristics of flecainide-induced arrhythmias in epicardial sheets of canine ventricle. METHODS AND RESULTS Standard microelectrode techniques were used. Flecainide (10-20 microM) produced either prolongation or marked abbreviation of APD in epicardium but only minor changes in the APD of endocardium. Marked abbreviation of APD in epicardium was due to loss of the action potential dome (plateau phase). Arrhythmias displaying characteristics of reentry could be readily induced in flecainide-treated preparations either by increasing the stimulation rate or by introduction of extrastimuli. Flecainide-induced slowing of conduction, more accentuated at the faster stimulation rates, appeared to act synergistically with the drug-induced dispersion of repolarization to generate reentry in these relatively small sheets of epicardium. 4-Aminopyridine, a transient outward current (Ito) blocker, reversed the flecainide-induced marked abbreviation of APD in epicardium and abolished reentrant activity in all cases. Flecainide failed to induce reentry in preparations pretreated with 4-aminopyridine. CONCLUSIONS Our data suggest that the presence of a prominent Ito in epicardium contributes the development of marked electrical heterogeneity in the ventricle after exposure to flecainide. Flecainide-induced dispersion of repolarization, especially when accompanied by prominent conduction delays, results in extrasystolic activity via a mechanism that we have termed "phase 2 reentry." Our results also suggest a role for Ito blockers in the treatment of reentrant arrhythmias.
The biology of Nociceptin/Orphanin FQ (N/OFQ) related to obesity, stress, anxiety, mood, and drug dependence
Authors: Jeffrey M. Witkin, Michael A. Statnick, Linda M. Rorick-Kehn, John E. Pintar, Michael Ansonoff, Yanyun Chen, R. Craig Tucker, Roberto Ciccocioppo
Journal: Pharmacology & Therapeutics (2013)
SAT0182 Relationship Between HLA-A Or -B LOCI and Behcet’S Disease in Japan. B51 is Related to Pathogenesis and A26 is Related to Ocular Lesions
Authors: T. Kobashigawa, Y. Nanke, M. Kawamoto, T. Yago, H. Yamanaka, S. Kotake
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Behçet's disease (BD) was reported to be associated with 6 human leukocyte antigen (HLA) loci. (1-7) In our 1st report on the relationships between BD and the HLA-A or B locus, we demonstrated that HLA-B27 and B51 were associated with the onset of BD, and HLA-A26 was associated with ocular lesions of BD; however, analyses of the HLA locus lacked integrity. (9) <h3>Objectives</h3> To investigate the relationships between the development or symptoms of BD and HLA-A/B loci. <h3>Methods</h3> Three hundred and nine out-patients with BD visited our hospital from January 2009 to December 2011. Out of the 179 out-patients diagnosed with definite or probable BD by Japanese and international criteria, and who had visited since September 2006, after our 1st HLA survey for our BD out-patients, we enrolled 69 patients with BD: 18 males, 51 females; mean age (SD, median, 25th and 75th percentile), 41.0 (13.3, 41, 31, and 53) years old, enough to survey the associations of HLA loci in our BD out-patients and the pathogenesis of BD. Each doctor of the patients obtained informed consent, and HLA loci were analyzed with PCR-rSSO methods. The HLA data from the HLA laboratory (8) were used as data for the healthy control group. We statistically analyzed the relationships between BD lesions and each HLA-A/B locus. <h3>Results</h3> The characteristics of BD out-patients were as follows: 21(30.4%) ocular lesion; 67 (97.1%) oral aphthous ulcers, 54 (78.3%) genital lesions, 65 (94.2%) skin lesions, 38 (55.1%) cases of arthritis, 17 (24.6%) intestinal lesions, 5 (7.3%) CNS, 3 (4.4%) vascular lesions, 2 (11.1%) cases of epidydimitis out of 18 males, and 1 (1.5%) positive pathergy test. Moreover, 17.4% were the complete type and 82.6% were the incompletetype, in Japanese BD criteria. The HLA-B51 (p=0.0395, OR: 1.66, 95% CI: 1.03-2.68) was strongly associated with development of BD based on our case-control study. The locus HLA-A26 (p=0.015, OR: 4.09, 95% CI: 1.35-12.38) was significantly correlated with ocular lesions of BD after analyzing the relationships between 24 loci and the 10 lesions of BD in our patients. <h3>Conclusions</h3> An HLA locus, B51, was related to the development of BD. A significant correlation between HLA loci and BD lesions was detected between the HLA-A26 locus and ocular lesions. <h3>References</h3> Akpolat T et al., Eur J Med, 1992. Itoh Y et al., Tissue Antigens, 2006. Mizuki N et al., Tissue Antigens, 1997. Kaya TI et al., Clin Exp ermatol, 2002. Gul A et al., Genes and Immunity, 2002. Ohno S et al., Lancet, 1973. Paul M et al., Tissue Antigens, 2001. The HLA laboratory, http://www.hla.or.jp. Kobashigawa et al. EULAR2008 (abstract). <h3>Disclosure of Interest</h3> None Declared
The SUPPORT Project and Improving Care for Seriously III Patients
Authors: Greg A. Sachs
Journal: JAMA (1996)

<h3>To the Editor.</h3> —The similarity between the SUPPORT<sup>1</sup>intervention and the way many hospitals responded to the Patient Self-determination Act (PSDA) is striking.<sup>2</sup>Many hospitals' PSDA policies use clerks, nurses, social workers, and other nonphysician staff to promote advance directive use, often without significant impact. Physicians remain disengaged from these PSDA efforts. The advance directive effort appears to be tolerated by physicians almost because they expect it to have little impact on their usual practice. Likewise, the SUPPORT intervention used computer models, written materials for the medical record, and nurse specialists. Despite the participating physicians' willingness to be part of SUPPORT, I wonder if they simply tolerated the intervention because it did not interfere too much with existing practice, rather than being committed to improving the designated outcomes. It would be interesting to have had a measure that reflected the extent to which participating physicians embraced the notion
THE TREATMENT OF LUPUS ERYTHEMATOSUS BY REPEATED REFRIGERATION WITH ETHYL CHLORID.
Authors: M. B. HARTZELL
Journal: JAMA (1904)

A distinguished teacher of dermatology was in the habit of saying to his class, when presenting a case of erythematous lupus: "Gentlemen, I show you an example of a disease which, although not incapable of recovery, is the most refractory to treatment of all cutaneous affections." And I am sure that all who have had any experience, even a limited one, in the treatment of this obstinate malady will agree with that teacher. The long list of remedies to be found in every text-book of diseases of the skin said to be more or less useful (usually less than more) in this disease is additional evidence, if any were needed, of its refractoriness to treatment, for the curability of any disease is usually in inverse proportion to the number of remedies proposed for its cure. So many forms of treatment, both internal and external, have had their praises loudly
Smoking and Esophageal Pain
Authors: MICHAEL MCCUNE
Journal: Annals of Internal Medicine (1976)

Comments1 March 1976Smoking and Esophageal PainMICHAEL MCCUNE, M.D., GLEN LEHMAN, M.D.MICHAEL MCCUNE, M.D.Search for more papers by this author, GLEN LEHMAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-84-3-342_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In a recent paper (Ann Intern Med 83:1-7, 1975) Friedman, Siegelaub, and Dales conclude that smoking is associated with an increased prevalence of chest pain, but the mechanism(s) for this remains undefined. Although pulmonary, cardiac, and musculoskeletal origins of pain are discussed, the authors make no mention of possible esophageal origin of the chest pain. Positive responses to pain "after a big meal," "awakened from sleep," and "lasting over 10 minutes" are all suggestive of reflux esophagitis. In their 200-part questionnaire, were patients questioned for heartburn, sour brash, dysphagia, or antacid relief of pain?Dennish and Castell...References1. DENNISH G and CASTELL D: Inhibitory effect of smoking on the lower esophageal sphincter. N Engl J Med 284:1136-1137, 1971 CrossrefMedlineGoogle Scholar2. COHEN S and HARRIS L: Does hiatus hernia affect competence of the gastroesophageal sphincter? N Engl J Med 284:1053-1056, 1971 CrossrefMedlineGoogle Scholar3. STANCIU C and BENNETT J: Smoking and gastro-oesophageal reflux. Br Med J 3:793-795, 1972 CrossrefMedlineGoogle Scholar4. ROBERTS , HENDERSON R, and WINGLE E: Esophageal disease as a cause of severe retrosternal chest pain. Chest 67:523-526, 1975 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: MICHAEL MCCUNE, M.D.; GLEN LEHMAN, M.D.Affiliations: Division of Gastroenterology Indiana University Medical Center Indianapolis, Indiana 46202 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 March 1976Volume 84, Issue 3Page: 342-343KeywordsDysphagiaIschemiaQuestionnairesSleep ePublished: 1 December 2008 Issue Published: 1 March 1976 PDF downloadLoading ...