tbuckley/cabot-search huggingface dataset:
An Enzyme Defect in Metabolic Gout
Authors: BRYAN T. EMMERSON
Journal: Annals of Internal Medicine (1968)

Editorial Notes1 March 1968An Enzyme Defect in Metabolic GoutBRYAN T. EMMERSON, M.D., F.R.A.C.P.BRYAN T. EMMERSON, M.D., F.R.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-68-3-707 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptGout is now recognized as a syndrome with numerous causes rather than as a distinct disease entity. With the recognition of more and more conditions associated with hyperuricemia and gout, the simple classification into primary or idiopathic gout and gout secondary to hemopoietic overactivity has lost its usefulness. A number of patients with hyperuricemia unassociated with any other disease are known to produce excessive quantities of urate—the overproducers—while other clinically similar patients without appreciable renal disease have been shown to excrete less urate than normal—the underexcretors. A further group seems to demonstrate features of both of these defects.Research over...References1. CASKEY CT, ASHTON DM, and WYNGAARDEN JB: The enzymology of feedback inhibition of glutamine phosphoribosylpyrophosphate amidotransferase by purine ribonucleotides. J. Biol. Chem. 239: 2570, 1964. CrossrefMedlineGoogle Scholar2. LESCH M and NYHAN WL: A familial disorder of uric acid metabolism and central nervous system function. Amer. J. Med. 36: 561, 1964. CrossrefMedlineGoogle Scholar3. SORENSEN LB and BENKE PJ: Biochemical evidence for a distinct type of primary gout. Nature (London) 213: 1122, 1967. CrossrefMedlineGoogle Scholar4. DAVIDSON JD and WINTER TS: Purine nucleotide pyrophosphorylases in 6-mercaptopurine-sensitive and -resistant human leukemias. Cancer Res. 24: 261, 1964. MedlineGoogle Scholar5. SEEGMILLER JE, ROSENBLOOM FM, and KELLEY WN: Enzyme defect associated with a sex-linked human neurological disorder and excessive purine synthesis. Science 155: 1682, 1967. CrossrefMedlineGoogle Scholar6. KELLEY WN, ROSENBLOOM FM, HENDERSON JF, and SEEGMILLER JE: A specific enzyme defect in gout associated with overproduction of uric acid. Proc. Nat. Acad. Sci. USA 57: 1735, 1967. CrossrefMedlineGoogle Scholar7. WYNGAARDEN JB, SEEGMILLER JE, LASTER L, and BLAIR AE: Utilization of hypoxanthine, adenine and 4-amino -5- imidazolecarboxamide for uric acid synthesis in man. Metabolism 8: 455, 1959. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: BRYAN T. EMMERSON, M.D., F.R.A.C.P. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPurine metabolism and human disease 1 March 1968Volume 68, Issue 3 Page: 707-708 Keywords Enzymes Gout Metabolic disorders Renal diseases Uric acid ePublished: 1 December 2008 Issue Published: 1 March 1968 PDF downloadLoading ...
P131 Myocardial Injury and Dysfunction during COPD Exacerbations
Authors: ARC Patel, BS Kowlessar, GC Donaldson, AJ Mackay, R Singh, JA Wedzicha, JR Hurst
Journal: Thorax (2013)

<h3>Introduction</h3> Cardiac biomarkers of myocardial injury and dysfunction are commonly raised in patients hospitalised with COPD exacerbations and are independent predictors of mortality. The relevance of this to the majority of community-treated events has not previously been studied. <h3>Methods</h3> We prospectively measured serum troponin T and N-terminal brain pro-natriuretic peptide (NT-proBNP) in 55 patients from the London COPD Cohort in the stable state, at exacerbation onset and thereafter at days 3 (n = 44), 7 (n = 39), 14 (n = 38), and 35 (n = 25) during recovery. Exacerbation assessments were undertaken within one week of symptom onset, prior to therapy, and defined by two consecutive days of new or increased respiratory symptoms on prospectively-completed daily patient diary cards requiring at least one major (dyspnoea, sputum purulence, sputum volume) and another major or minor symptom (coryza, wheeze, sore throat and cough). <h3>Results</h3> Cardiac biomarkers rose from the stable state to exacerbation (mean ( ± SD) troponin T 0.012 ( ± 0.011) vs 0.017 ( ± 0.016) µg/L, p &lt; 0.001; NT-proBNP 23.1 ( ± 39.2) vs 36.0 ( ± 56.5) pg/ml, p &lt; 0.001). These increases were significantly higher in those with known IHD (n = 12) compared to those without IHD (n = 43) (mean ( ± SD) increase in troponin T 0.011 ( ± 0.009) vs 0.003 ( ± 0.006) µg/L, p = 0.003; NT-proBNP 38.1 ( ± 37.7) vs 5.9 ( ± 12.3) pg/ml, p &lt; 0.001). Cardiac biomarkers did not fall during the initial five-week exacerbation recovery period (troponin T -0.0003µg/L/day (95% CI -0.0008 to 0.0004), p = 0.431; NT-proBNP -0.096 pg/ml/day (95% CI -0.631 to 0.438), p = 0.723). They remained more elevated in those with IHD (n = 12) than in those without IHD (n = 43) during the five week recovery period (troponin T AUC 0.368 ± 0.311 µg/L/35days vs 0.088 ± 0.174 µg/L/35days, p &lt; 0.001; NT-proBNP AUC 1590 ± 2620 pg/ml/35days vs 279 ± 725 pg/ml/35days, p = 0.005). Longer exacerbations were associated with greater myocardial injury at exacerbation (higher serum troponin T) and the magnitude of change from the stable state (rho = 0.323, p = 0.027; rho = 0.390, p = 0.007 respectively). <h3>Conclusions</h3> Myocardial injury and dysfunction is common and clinically significant during COPD exacerbations in those with underlying IHD and relates to exacerbation length. Alternative approaches to mitigate cardiovascular complications, in stable COPD and at exacerbation, require further study.
HIV-1 reprograms the migration of macrophages
Authors: Christel Vérollet, Shanti Souriant, Emilie Bonnaud, Paul Jolicoeur, Brigitte Raynaud-Messina, Cassandre Kinnaer, Isabelle Fourquaux, Andrea Imle, Serge Benichou, Oliver T. Fackler, Renaud Poincloux, Isabelle Maridonneau-Parini
Journal: Blood (2014)
XeCl laser-induced fluorescence of atherosclerotic arteries. Spectral similarities between lipid-rich lesions and peroxidized lipoproteins.
Authors: A A Oraevsky, S L Jacques, G H Pettit, R A Sauerbrey, F K Tittel, J H Nguy, P D Henry
Journal: Circulation Research (1993)

Autofluorescence spectroscopy of arterial surfaces provides information about the distribution and composition of atherosclerotic plaques. The aim of the study was to determine whether accumulation of peroxidized lipoproteins in arterial walls, a process postulated to play a role in initiating atherosclerotic changes, can be demonstrated by fluorescence spectroscopy. XeCl excimer laser (308 nm)-induced fluorescence of human aortas containing early lipid-rich noncollagenous lesions exhibited marked red shifts and broadening of the fluorescence spectra compared with spectra from nonatherosclerotic aortas. Similar profiles were observed in spectra obtained from oxidatively modified low density lipoprotein but not native low density lipoprotein. In hypercholesterolemic rabbits with early foam cell lesions, spectral shifts resembled those of oxidized beta-very low density lipoprotein, the major lipoprotein accumulating in arteries of rabbits fed cholesterol. XeCl laser-fluorescence spectroscopy of arterial surfaces may be useful for the identification of arteries accumulating modified lipoproteins (oxidized low density lipoprotein), a chemical change indicative of atherosclerosis in its early and probably reversible stages.
Growing, Evolving HIV/AIDS Pandemic Is Producing Social and Economic Fallout
Authors: Joan Stephenson
Journal: JAMA (2003)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Intracellular β-blockade: overexpression of Gαi2 depresses the β-adrenergic response in intact myocardium
Authors: Paul M.L Janssen, Wolfgang Schillinger, J.Kevin Donahue, Oliver Zeitz, Shahriyar Emami, Stephan E Lehnart, Joachim Weil, Thomas Eschenhagen, Gerd Hasenfuss, Juergen Prestle
Journal: Cardiovascular Research (2002)

Increased levels of inhibitory G proteins have been observed in heart failure, but their physiological relevance in mediating the reduced beta-adrenergic response is largely unknown.To evaluate the functional consequences of Galpha(i2) overexpression, we studied myocardial contraction in intact isometric contracting cardiac rabbit trabeculae and isolated myocytes after adenovirus-mediated gene transfer of Galpha(i2).Neither Galpha(i2) nor lacZ (control) overexpression altered baseline contractile force. After 72 h of continuous contractions, developed force (F(dev)) increased after addition of 1 microM isoproterenol by 28.5+/-9.7 mN/mm(2) in the control group, which was unchanged from the initial response at t=0 h (23.7+/-3.8 mN/mm(2)). In sharp contrast, in preparations transfected with AdGalpha(i2), the response to isoproterenol was significantly attenuated (5.9+/-2.0 vs. 27.6+/-4.2 mN/mm(2), t=72 vs. 0 h, respectively, P<0.01). In a primary culture of transfected isolated myocytes from a nearly identical baseline, isoproterenol increased cell shortening by 3.1+/-0.6% in the lacZ transfected myocytes, but only by 1.3+/-0.5% in Galpha(i2) transfected myocytes (t=72 h, P<0.01). In Galpha(i2) transfected myocytes, pertussis toxin restored beta-adrenergic responsiveness, indicating specificity of attenuation by the transgene.Overexpression of Galpha(i2) attenuates the positive inotropic effects of beta-adrenergic stimulation in myocardium. In addition, the method we developed allows investigation of a causal link between altered protein expression and subsequent alterations in contractile function in a physiological relevant in vitro manner.
Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma
Authors: Gustav Mattiasson, Mehrdad Shamloo, Gunilla Gido, Kavitha Mathi, Gregor Tomasevic, Saili Yi, Craig H. Warden, Roger F. Castilho, Thorsten Melcher, Mirella Gonzalez-Zulueta, Karoly Nikolich, Tadeusz Wieloch
Journal: Nature Medicine (2003)
Hit Parade for Adoptive Cell Transfer Therapy: The Best T Cells for Superior Clinical Responses
Authors: Daniel E. Speiser
Journal: Cancer Discovery (2013)

Adoptive cell transfer (ACT) of T cells has great clinical potential, but the numerous variables of this therapy make choices difficult. A new study takes advantage of a novel technology for characterizing the T-cell responses of patients. If applied systematically, this approach may identify biomedical correlates of protection, thereby supporting treatment optimization.
Case of Immune Aplastic Haemolytic Anaemia with Thrombocytopenia
Authors: M. H. Lees, O. D. Fisher, J. M. Shanks
Journal: BMJ (1960)

reticulosarcoma have succumbed despite regression of the tumours.In the patient affected with Ewing's tumour asaline gave a transient effect, and growth of the tumour has recurred even during the administration of the drug.Asaline was well tolerated by the patients.No depressing effect on haemopoiesis was noted.The Results of Treatment No. of Effect on Tumour Kind of Tumour Patients Yes No Metastases of seminoma of testis 4 3 Reticulosarcoma ..2 2 -Ewing bone tumour .. 2 Myelomatosis ..
Growth factor expression in aorta of normotensive and hypertensive rats.
Authors: R Sarzani, P Brecher, A V Chobanian
Journal: Journal of Clinical Investigation (1989)

Hypertension causes biochemical and morphological changes in the vessel wall by unknown mechanisms. Locally produced substances may have a role in mediating these vascular changes. We have studied the expression of platelet-derived growth factor (PDGF) B chain and PDGF A chain, insulin-like growth factor (IGF)-I and IGF-II, endothelial cell growth factor (ECGF), basic fibroblast growth factor (bFGF), and transforming growth factor-beta (TGF-beta) in aortic tissue from normotensive rats and rats made hypertensive by deoxycorticosterone (DOC)/salt treatment. Using Northern blotting, we found that genes for each of these growth factors were transcriptionally active in the aorta of both normotensive and hypertensive rats. TGF-beta aortic mRNA levels increased up to threefold as a result of DOC/salt hypertension. In contrast, no major changes in the expression of either PDGF chain, IGF-I or II, ECGF, or bFGF were detectable. The results indicate that at least seven genes coding for growth factors that were shown previously to influence growth and function of vascular cells in vitro, are expressed in rat aorta in vivo. These findings support the hypothesis that synthesis and release of growth factors in the arterial wall are involved in autocrine and/or paracrine regulatory mechanisms. In addition, the increased expression of TGF-beta in vivo may have a role in mediating the aortic changes induced by hypertension.
Physiologically Significant Specializations of the Cell Surface
Authors: DON W. FAWCETT
Journal: Circulation (1962)

This paper presents a brief review of the ultrastructure of some of the structural elaborations of the plasma membrane that may be regarded as adaptations for specific cell functions. Among the relatively stable specializations of the free surface, it considers the striated border of the intestinal mucosa, the brush border in the nephron, and filamentous coatings on the membranes of certain cells of the gastric mucosa. It then turns to those transient configurations of cell surfaces involved in the dynamic processes of pinocytosis, phagocytosis, and liberation of secretory products and considers the turnover of membranes associated with these phenomena. Discussion of specializations of the contact surfaces includes the desmosomes and terminal bars and the present status of intercellular cement and interfacial canals. A section on specializations of the cell base considers the basement membrane and basal infoldings of the plasma membrane in cells engaged in active transport. And finally, there is a description of the terminal web and the marginal band of nucleated erythrocytes—specializations of the superficial cytoplasm concerned with maintenance of cell shape.
STUDIES OF THE PRINCIPLE IN LIVER EFFECTIVE IN PERNICIOUS ANEMIA. IV. THE THERAPEUTIC ACTIVITY OF ITS MULTIPLE FACTORS 12
Authors: Bernard M. Jacobson, Y. Subbarow
Journal: Journal of Clinical Investigation (1937)

Early in the course of an investigation of the principle in liver effective in pernicious anemia certain observations suggested the possibility that the therapeutic activity of liver extract might de- pend upon the presence of several chemically distinct substances.The evidence for this view was the fact that continued purification of therapeuti- cally active liver extract, in the absence of sig- nificant losses and of destructive procedures, resulted in partial or complete extinction of therapeutic activity.On the other hand, the ad- mixture with such highly purified materials of other fractions derived from liver extract re- sulted in the recovery of therapeutic activity.These latter fractions we have termed accessory factors, for they appeared to augment the activity of the primary factor (or factors), while in the absence of the primary factor they were thera- peutically inert.This communication describes in detail the observations mentioned above, part of which have already been presented in a preliminary report (1). METHODS AND MATERIALSThe patients studied were suffering from classical Addisonian pernicious anemia in relapse.Complications such as severe combined system disease and hemorrhage were absent.No infec- tions occurred during the periods of observations, except for cystitis in three patients (Cases 7, 9, and 12, Table I).During the prolonged periods 1 Presented in part at the meeting of the American Society for Clinical Investigation, Atlantic City, May 6, 1935.
Foot Small Muscle Atrophy Is Present Before the Detection of Clinical Neuropathy
Authors: Robert L. Greenman, Lalita Khaodhiar, Christina Lima, Thanh Dinh, John M. Giurini, Aristidis Veves
Journal: Diabetes Care (2005)

OBJECTIVE—To characterize structural changes and the metabolic profile of foot muscles and correlate them with diabetic neuropathy measurements using phosphorus-31 (31P) rapid acquisition with relaxation enhancement (RARE) magnetic resonance imaging (MRI). RESEARCH DESIGN AND METHODS—We studied 12 control subjects, 9 nonneuropathic diabetic patients, and 12 neuropathic diabetic patients using 31P RARE and proton (1H) MRI at 3 Tesla. The ratio of the total cross-sectional area of the foot to that of the muscle tissue was calculated from transaxial 1H and 31P images. The average 31P concentration across the metatarsal head region was measured from the 31P images. RESULTS—The muscle area−to−total area ratio differed among all three groups (means ± SD): 0.55 ± 0.04 vs. 0.44 ± 0.05 vs. 0.06 ± 0.06 for control, nonneuropathic, and neuropathic subjects, respectively (P &amp;lt; 0.0001). The average 31P concentration also differed among all groups: 27.7 ± 3.8 vs. 21.7 ± 4.8 vs. 7.9 ± 8.8 mmol/l for control, nonneuropathic, and neuropathic subjects (P &amp;lt; 0.0001). The muscle area−to−total area ratio strongly correlated with clinical measurements: Neuropathy Disability Score, r = −0.83, P &amp;lt; 0.0001; vibration perception threshold, r = −0.79, P &amp;lt; 0.0001; and Semmes-Weinstein monofilaments, r = −0.87, P &amp;lt; 0.0001. CONCLUSIONS—Small muscle atrophy is present in diabetes before clinical peripheral neuropathy can be detected using standard clinical techniques. The 31P RARE MRI method evaluates the severity of muscle atrophy, even in the early stages when neuropathy is absent. This technique may prove to be a useful diagnostic tool in identifying early-stage diabetic foot problems.
Hormonal Relationships During the Menstrual Cycle
Authors: S. S. C. Yen
Journal: JAMA (1970)

Physiologic fluctuation of follicle-stimulating hormone (FSH), luteinizing hormone (LH), human-growth hormone (HGH), and progesterone concentrations in serum samples of women with ovulatory menstrual cycles were determined by radioimmunoassay and protein-binding assay. During the follicular phase of the cycle, the tonic secretion of FSH showed an initial rise followed by a progressive fall toward the midcycle. In contrast, LH secretion showed a steady increase. A clear elevation of progesterone concentration was observed 48 hours after the onset of a simultaneous surge of LH and FSH at midcycle. Progesterone levels rose rapidly reaching maximal concentration (mean 12.2 mμg/ml) five days after LH surge and remained elevated for five to six days. Thereafter, progesterone levels fell rapidly to an undetectable level on the day after onset of menstruation. This was accompanied by a significant elevation of the FSH and LH levels from their low concentration observed during the late luteal phase. Human-growth hormone levels observed while the patient was in a fasting, ambulant state showed a progressive rise reaching a peak just prior to LH surge and there was a random fluctuation during luteal phase of the cycle.
Utility of Bone Scintigraphy to Determine the Appropriate Vertebral Augmentation Levels
Authors: Eric Jordan, Dong Choe, Todd Miller, Murthy Chamarthy, Allan Brook, Leonard M. Freeman
Journal: Clinical Nuclear Medicine (2010)

Vertebral augmentation procedures have been used as an effective treatment for back pain due to vertebral compression fracture from different causes, including metastatic disease and osteoporosis. However, diagnosis and localization of the causative vertebral level(s) may be difficult using any single imaging modality. In this retrospective study, we assessed the ability of preprocedural bone scans to determine the appropriate level(s) of subsequent vertebroplasty.The study consisted of a retrospective chart review of 44 patients who underwent bone scintigraphs and vertebroplasties at Montefiore Medical Center from 2002 to 2008. Online medical records and reports were used to determine the level of vertebroplasty and the preprocedure bone scan levels. The data was reviewed by a panel consisting of a neuroradiologist and nuclear medicine physician for agreement.Our retrospective study assessed the utility of bone scans as a diagnostic tool to identify candidate vertebral levels for vertebroplasty and determined that bone scans were positive in 78.3% of all fractures that subsequently underwent vertebral augmentation procedures. Although no significant difference was seen in the positivity of bone scans to subsequent vertebroplasty levels between benign or metastatic compression fractures (79% vs. 76%), a difference was observed when single level vertebroplasty patients were compared with multiple-level vertebroplasty patients (87% vs. 69%). Our results support the use of whole body bone scintigraphy as a diagnostic tool prior to vertebroplasty, especially in cases where a single vertebral level is involved or MRI might be contraindicated.
Expression of osteopontin in gentamicin-induced acute tubular necrosis and its recovery process
Authors: Yuansheng Xie, Shinichi Nishi, Seitaro Iguchi, Naofumi Imai, Minoru Sakatsume, Akihiko Saito, Mika Ikegame, Noriaki Iino, Hisaki Shimada, Mitsuhiro Ueno, Hiroyuki Kawashima, Masaaki Arakawa, Fumitake Gejyo
Journal: Kidney International (2001)
CASE OF LITHOTOMY PRESENTING UNUSUAL DIFFICULTIES, AND ONE OF STAPHYLORAPHY
Authors: A. Prichard
Journal: BMJ (1855)

JOURNA 11 o.itted, as it does not ; and the solution of the chlo- ride of lime to be continued. 9. Scrotal and perineal ulcers healed, whilst that on the pubes is enlarged.Hair to be removed, and the sore treated with a solution of the sulphate of copper (gr.x ad Vj); gr.viij of the iodide of potassium ter die, and gr.v of the blue pill every night.Dec. 15th.Mfuch better in every respect.Ulcer on the pubes rapidly cicatrising.Dec. 26th.Going on well.Ulcer on the pubes nearly healed.Dec. 29th.
Private doctors must improve their treatment of tuberculosis, says WHO
Authors: P. Brown
Journal: BMJ (2002)

Global targets for the control of tuberculosis will not be met unless the public sector can engage the growing army of private doctors who now treat patients with tuberculosis and improve these doctors' management of the disease.

This is one key conclusion of a working group at the World Health Organization (WHO). The group is calling for increased resources and urgent action to build partnerships between private and public sectors in countries where the tuberculosis burden is high, including India, Indonesia, and the Philippines.

“It is time to move from research to action,” said Dr Mukund Uplekar, coordinator of the WHO working group and a former private physician from Mumbai, India. There are already successful examples of partnerships, he says–for example, in Hyderabad, Delhi, and …