tbuckley/cabot-search huggingface dataset:
Marfan's Syndrome Starting to Yield Secrets
Authors: Timothy F. Kirn
Journal: JAMA (1988)

A NEW ANTIBODY has led to the discovery of a previously unrecognized connective tissue protein. That discovery may help unveil some of the mystery of Marfan's syndrome, the extremely rare, but exceedingly notorious, hereditary disease, complications of which led to the untimely death of world-class volleyball star Flo Hyman two years ago and allegedly affected Abraham Lincoln, violin virtuoso Niccolo Paganini, and composer-pianist Franz Liszt.  The monoclonal antibody, developed by researchers at Oregon Health Sciences University, Portland ( J Cell Biol 1986;103:2499), binds to a protein they have named fibrillin. According to one of the investigators, it may prove to be an aid in diagnosing this confoundingly pleiotropic syndrome.  Using the monoclonal and an indirect immunofluorescence technique in cell cultures of skin from patients with Marfan's, the researchers discovered an intricate scaffolding-like array of microfibrils, often attached to elastin fibers, that seem to be composed primarily of fibrillin. It appears that
Use of Information Technology in the Examination Room—Reply
Authors: Elizabeth Toll
Journal: JAMA (2012)

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
Successful therapy with anti-HMGB1 monoclonal antibodies in two separate experimental arthritis models
Authors: H. Schierbeck, P. Lundback, K. Palmblad, L. Klevenvall, J. H. Li, S. Chavan, H. Yang, H. E. Harris, U. Andersson, L. Ottosson
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> The nuclear protein HMGB1 (high mobility group chromosomal protein 1) is secreted by activated macrophages/monocytes and promotes inflammation. Extracellular HMGB1 is present in the synovitis of rheumatoid arthritis (RA) patients and intra-articular injections of recombinant HMGB1 induce arthritis in mice. Thus, the authors hypothesise that HMGB1 represents an endogenous mediator of arthritis as well as a target molecule for successful therapeutic intervention in RA. Polyclonal anti-HMGB1 therapy or recombinant boxA protein works in experimental arthritis models. However, no monoclonal anti-HMGB1 therapy has proven efficient in arthritis models. The aim was to evaluate the antiarthritic potential of a monoclonal anti-HMGB1 antibody (2G7) in two different models of arthritis; collagen-induced arthritis (CIA) in DBA/1 mice and <i>DNase II</i><sup>−/−</sup> × <i>IFN-IR</i><sup>−/−</sup> mice which spontaneously develop chronic polyarthritis resembling RA. DNase II is specifically needed for macrophage degradation of engulfed DNA. This model is associated with abundant extracellular HMGB1 expression including serum levels of several 100 ng/ml before and during onset of disease. <h3>Materials and methods</h3> Female and male <i>DNase II</i><sup>−/−</sup> × <i>IFN-IR</i><sup>−/−</sup> mice, initially 5 weeks old, were treated in 5 weeks every second day with intraperitoneally injections with 100 μg of a mouse monoclonal anti-HMGB1 antibody 2G7 (IgG2b, non-commercial antibody, available upon request) or buffer control. Nine animals were included in each group with an equal sex distribution. Treatment of CIA in female DBA/one mice with anti-HMGB1 antibody 2G7 was initiated when the animal reached an arthritis score of ≤2. The animals were treated for 7 days with daily intraperitoneal injections of 70 μg 2G7 (12 animals) or 70 μg of irrelevant antibody (MOPC-195, mouse IgG2b, 7 animals). The outcome was evaluated by daily clinical scoring. Statistical evaluation was performed using Student9s t test calculated on area under the curve values. Serial joint sections were stained with H&amp;E to evaluate inflammatory cell infiltration or using staining with Safranin O to visualise cartilage damage and bone erosions. <h3>Results</h3> Systemic HMGB1-specific blockade significantly ameliorated the clinical course in CIA as well as in <i>DNase II</i><sup>−/−</sup> × <i>IFN-IR</i><sup>−/−</sup> mice, and a protective effect on joint destruction was observed by histological evaluation. <h3>Conclusion</h3> This study identifies beneficial effect of the HMGB1-specific mAb 2G7 in two different experimental arthritis models. The conserved structure of HMGB1 and the strong cross-reactivity between species of the investigated mAb, has thus enabled them to define a potential mAb candidate for further genetic engineering and clinical testing.
INJECTION TREATMENT OF SYPHILIS BY MEANS OF A NEW MERCURIAL FORMULA.
Authors: M. L. HEIDINGSFELD
Journal: JAMA (1902)

In 1853 Alex. Wood<sup>1</sup>of Edinburgh introduced hypodermic therapy. Mercurial injections were first administered by Charles Hunter and Barclay Hill,<sup>2</sup>two Englishmen, in 1856. Hebra<sup>3</sup>in 1864 made a vain effort to treat syphilis constitutionally by means of large injections of corrosive sublimate, and Scarenzio<sup>4</sup>one year later carried on more successful and prolonged investigations by means of calomel injections suspended in gummatous solutions. All the above mercurial investigations, on account of the severe painful reaction induced by their administration, were short-lived, and would have doubtless remained unnoted and obscure had not Lewin<sup>5</sup>aroused new and well-sustained interest in this now generally conceded important field of therapy, in 1868. Mercury and mercury alone is the sheet anchor in the treatment of the earlier stages of syphilis. It matters not through what avenue the administration takes place, lungs, intestinal tract or skin, or in what particular form—metallic,
Mepacrine decreases lung leak in rats given interleukin-1 intratracheally.
Authors: Y M Lee, B M Hybertson, L S Terada, A J Repine, H G Cho, J E Repine
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

We hypothesized that phospholipase A2 (PLA2) metabolites contribute to the acute, neutrophil-dependent, edematous lung leak that develops after administration of interleukin-1 (IL-1) intratracheally to rats and tested this premise by using mepacrine to inhibit PLA2 activity in vivo. We found that lung PLA2 activity, lung lavage phospholipid content, lung leak index, lung weight gain, and lung lavage protein concentrations were increased in rats given IL-1 intratracheally compared with sham-treated control rats. By comparison, lungs of mecaprine and IL-1-treated rats had decreased PLA2 activity, lavage phospholipid content, leak, weight gain, and lavage protein increases compared with rats given IL-1 intratracheally. Mepacrine treatment also decreased lung neutrophil accumulation, but not lung lavage cytokine-induced neutrophil chemoattractant (CINC) levels, in rats given IL-1 intratracheally. In parallel experiments, mepacrine treatment reduced the adhesion of human neutrophils to IL-1-treated human umbilical vein endothelial cells in vitro. Our results indicate that PLA2 activity participates in the lung neutrophil retention and pulmonary vascular leak that develops in rats given IL-1 intratracheally.
Plasma Volume and Its Regulatory Factors in Congestive Heart Failure After Implantation of Long-term Left Ventricular Assist Devices
Authors: Karen B. James, Patrick M. McCarthy, Safwan Jaalouk, Emmanuel L. Bravo, Adam Betkowski, James D. Thomas, Satoshi Nakatani, Fetnat M. Fouad-Tarazi
Journal: Circulation (1996)

Congestive heart failure is associated with blood volume expansion caused by stimulation of the renin-aldosterone system and arginine vasopressin. The use of left ventricular assist devices as bridges to heart transplantation has improved the survival of patients during this critical period. In studying heart failure physiology on support devices, we hypothesized that improvement of cardiac function by a left ventricular assist device is associated with normalization of volume load secondary to normalization of its regulatory substances.We studied 15 patients (13 men, 2 women: age 51 +/- 8 years) with end-stage heart failure who were cardiac transplant candidates eligible for HeartMate implantation. We measured plasma volume and plasma levels of atrial natriuretic peptide, aldosterone, renin, and arginine vasopressin sequentially before HeartMate implantation (baseline), after HeartMate implantation (weeks 4 and 8), and after transplantation. Baseline plasma volume was 123 +/- 20% of normal; it was 122 +/- 22% at week 4 and decreased to 115 +/- 14% at week 8. Atrial natriuretic peptide was 359 +/- 380 pg/mL at baseline, 245 +/- 175 pg/mL at week 4, and 151 +/- 66 pg/mL at week 8. Plasma aldosterone fell from 68 +/- 59 ng/dL at baseline to 17 +/- 16 ng/dL at week 4 (P < .05 versus baseline) and was 32 +/- 50 ng/dL at week 8. Plasma renin activity decreased from 80 +/- 88 ng/dL at baseline to 11 +/- 12 ng/dL at week 4 and was 16 +/- 38 ng/dL at week 8 (both P < .05 versus baseline). Arginine vasopressin fell from 5.0 +/- 4.8 fmol/mL at baseline to 1.1 +/- 0.7 fmol/mL at week 4 and 1.2+/-0.8 fmol/mL at week 8 (both P < .05 versus baseline).The reduction of plasma renin activity, plasma aldosterone, and arginine vasopressin occurred earlier than the reduction of plasma volume and atrial natriuretic peptide after HeartMate implantation, possibly because of decreased pulmonary congestion and improved renal perfusion. The reduction of atrial natriuretic peptide cannot be responsible for the lack of adequate decrease of plasma volume; its reduction can be taken as a marker of improved cardiac pump function and decreased atrial stretch.
SALIVARY TUMOR BLOCKING PHARYNGEAL OPENING OF LEFT EUSTACHIAN TUBE
Authors: Charles J. Adams
Journal: JAMA (1927)

I am reporting this case because the microscopic changes and the location of the tumor are most unusual. Undoubtedly this was a congenital misplacement of tissue. A woman, aged 19, single, was troubled with occasional attacks of grand mal, tubotympanic catarrah and deafness. In making a routine examination of the nose and throat, I discovered a small tumor mass in the pharyngeal opening of the left eustachian tube. While the tumor mass was freely movable, it completely blocked the tube opening, acting like a ball valve. I discovered that it was attached well up in the tube on the posterior lip by a broad base. With the aid of a nasopharyngoscope, I was easily able to remove the tumor with a snare. Microscopic examination revealed that the sections consisted chiefly of lobules of salivary gland tissue, separated by wide bands of fibrous tissue and having a narrow layer of lymphoid
Effects of Anesthetic Agents on Bile Pigment Excretion in the Rat
Authors: Glenn R. Gourley, William Mogilevsky, Richard A. Arend, Frank L. Siegel, Gerard B. Odell
Journal: Hepatology (1985)

Anesthesia–induced alterations in bilirubin conjugation were studied. Rats were fitted with bile duct and jugular vein catheters while anesthetized with diethyl ether, ketamine or pentobarbital. As anesthesia abated, bile was collected for the next 5 hr and analyzed for flow rate, total bilirubin excretion and bilirubin glucuronide composition. The high–performance liquid chromatography method used allowed direct analysis of bile without derivatization or extraction. Ether anesthesia was associated with a reversible suppression of diglucuronide formation and total bilirubin excretion, with reciprocal monoglucuronide changes. Bile flow and pigment excretion were variable with ketamine. Pentobarbital provided the most uniform excretion data, although the ratio of C–8:C–12 monoglucuronide varied with all drugs. These data are consistent with recently reported drug–induced alterations in hepatic uridine diphosphoglucuronic acid concentration and support the hypothesis that alterations in this substrate concentration are capable of influencing rates of hepatic glucuronide formation.
Prognostic Utility of Growth Differentiation Factor-15 in Patients With Chronic Heart Failure
Authors: Tibor Kempf, Stephan von Haehling, Timo Peter, Tim Allhoff, Mariantonietta Cicoira, Wolfram Doehner, Piotr Ponikowski, Gerasimos S. Filippatos, Piotr Rozentryt, Helmut Drexler, Stefan D. Anker, Kai C. Wollert
Journal: Journal of the American College of Cardiology (2007)
TCT-188 Efficacy of the Novel Ultrasonography “Vascular Elastography” Guided Endovascular Therapy
Authors: Hideyuki Takimura, Toshiya Muramatsu, Reiko Tsukahara, Yoshiaki Ito, Tsuyoshi Sakai, Hiroshi Ishimori, Keisuke Hirano, Masatsugu Nakano, Masahiro Yamawaki, Tamon Kato, Norihiro Kobayashi, Yasunari Sakamoto, Takuro Takama
Journal: Journal of the American College of Cardiology (2012)
Hyperhomocysteinemia in type 2 diabetes: relationship to macroangiopathy, nephropathy, and insulin resistance.
Authors: M Buysschaert, A S Dramais, P E Wallemacq, M P Hermans
Journal: Diabetes Care (2000)

The aim of this study was to determine the distribution of plasma total homocysteine (tHcy) concentrations in type 2 diabetic patients and to assess whether high tHcy values were related to chronic complications (particularly macroangiopathy and nephropathy) and/or the degree of insulin resistance.Fasting tHcy levels were measured in 122 type 2 diabetic patients in whom the presence of chronic complications (e.g., macroangiopathy, microalbuminuria, macroproteinuria, decreased creatinine clearance, hypertension, retinopathy, and neuropathy) was recorded alongside an assessment of insulin resistance by the homeostasis model assessment (HOMA).We found that 31% of the cohort (group 1) had raised tHcy (mean +/- 1 SD) values (20.8 +/- 5.1 micromol/l), whereas 69% (group 2) had normal values (10.2 +/- 2.0 micromol/l). The prevalence of macroangiopathy was higher in group 1 than in group 2 subjects (70 vs. 42%, P < 0.01); the prevalence of coronary artery disease was particularly higher in group 1 (46 vs. 21%, P < 0.02). The prevalence of impaired renal function, evidenced by decreased creatinine clearance, was higher in group 1 (32 vs. 10%, P < 0.005). Other clinical and biological characteristics of both groups were comparable, although group 1 had lower levels of folic acid than group 2 (5.2 +/- 2.9 vs. 7.0 +/- 3.4 ng/ml, P < 0.01). No differences were found for microalbuminuria (33 vs. 31%), retinopathy (45 vs. 42%), or neuropathy (70 vs. 59%) between groups 1 and 2, respectively The degree of insulin resistance was similar in groups 1 and 2 (46 +/- 21 and 42 +/- 20% of HOMA-insulin sensitivity) as was the assessment of beta-cell function (63 +/- 28 and 65 +/- 46%, respectively). No differences in tHcy levels were found between subjects receiving metformin and those not receiving metformin. In contrast, the plasma tHcy level was higher in diabetic patients treated with fibrates (P = 0.0016).Elevated plasma tHcy levels in type 2 diabetes is associated with a higher prevalence of macroangiopathy and nephropathy when assessed from creatinine clearance indexes and is not associated with different degrees of insulin resistance.
Newer Sedative Drugs That Can Cause States of Intoxication and Dependence of Barbiturate Type
Authors: Carl F. Essig
Journal: JAMA (1966)

This report will emphasize the states of intoxication or physical dependence, or both, which can result from abuse of certain sedative-hypnotic drugs. Chemically these drugs are not barbiturates, but the untoward effects of their excess use are like those of barbiturate abuse.<sup>1,2</sup> The term intoxication refers to the various degrees of drowsiness, impaired thinking, or motor incoordination (ataxia) that can be attributed to excess use of the drugs to be discussed. Physical dependence is defined as an altered biological state caused by repeated and chronic consumption of a drug so that its use must be continued in order to prevent emergence of a specific group of symptoms and signs known as the withdrawal syndrome. Either intoxication or physical dependence can be serious medical complications of the use of sedative drugs. The drugs to be discussed are meprobamate, glutethimide, methyprylon, ethchlorvynol, chlordiazepoxide, diazepam, and ethinamate. A more detailed review of
Multicomponent analysis of amino acid transport in human lymphocytes. Diminished L-system transport in chronic leukemic B lymphocytes.
Authors: G B Segel, W Simon, M A Lichtman
Journal: Journal of Clinical Investigation (1984)

We have examined the amino acid transport in B cell chronic lymphocytic leukemia and compared it with the amino acid transport in isolated B lymphocytes from human blood and tonsils. L-system transport was measured with 2-amino-2-carboxy-bicyclo (2,2,1)-heptane, which is a synthetic amino acid whose transport is limited to the L-system. Amino acid uptake was subjected to a multicomponent analysis that partitioned the total uptake into the saturable carrier-mediated transport system and the uptake by diffusion. The maximal velocity of L-system transport in chronic lymphocytic leukemia cells, 81 mumol/1 cell water per min, was less than 10% that of blood B lymphocytes, which was 1,029 mumol/1 cell water per min. The uptake of 2-amino-2-carboxy-bicyclo (2,2,1)-heptane by tonsillar B cells, by a B lymphocyte cell line, and by blood T-lymphocytes was also 10-fold greater than that observed in chronic lymphocytic leukemic cells. Similarly, the L-system uptake of leucine and phenylalanine, which are naturally occurring amino acids usually transported primarily by the L-system, was reduced in chronic lymphocytic leukemic B cells to 15 and 10% of normal B cells, respectively. Total leucine uptake by chronic lymphocytic leukemic cells, however, was sustained at 30% of that expected because of transport via an alternative transport system. The A- or ASC-systems, the other major amino acid transport pathways, were not defective in chronic lymphocytic leukemic cells. These data indicate that there is a specific, profound decrease in L-system carrier-mediated amino acid transport in chronic lymphocytic leukemic B cells, as judged by the system-specific synthetic amino acid, 2-amino-2-carboxy-bicyclo (2,2,1)-heptane. This defect was confirmed by studies with two naturally occurring L-system amino acids, leucine and phenylalanine. This specific abnormality of membrane transport by chronic lymphocytic leukemic B lymphocytes is not shared by other B lymphocyte types, and thus appears to be related to the neoplastic nature of the leukemic B cells rather than to their immunologic subtype.
The echocardiogram of the anterior leaflet of the mitral valve. Correlation with hemodynamic and cineroentgenographic studies in dogs.
Authors: G M Pohost, R E Dinsmore, J J Rubenstein, D D O'Keefe, R N Grantham, H E Scully, E A Beierholm, J W Frederiksen, M L Weisfeldt, W M Daggett
Journal: Circulation (1975)

The echocardiogram of the anterior leaflet of the mitral valve (ECHO) was compared to hemodynamic and cineroentgenographic data to evaluate its accuracy in timing mitral valve (MV) opening and closure, and to validate it as an indicator of MV motion. The ECHO, high speed cineroentgenography at 250 frames/sec, and/or measurement of intracardiac pressures allowed accurate timing of the events of MV motion in dogs on right heart bypass. The intersection of left ventricular and left atrial pressures in early diastole preceded the onset of rapid anterior motion of ECHO (D' point) by 17 to 33 plus or minus 7.6 msec; r equals 0.98. The onset of left ventricular systole occurred before the termination of final rapid posterior motion of the ECHO in end diastole (Co point) by 25 plus or minus 10 msec; r equals 0.96. Radiopaque clips were attached to the free edges of both leaflets of the MV. Cineroentgenographically determined plots of clip distance from the ultrasound transducer were morphologically similar to the simultaneously recorded ECHO. A delay of 23 plus or minus 3 (0 to 40) msec was observed in the ECHO peaks of diastolic anterior excursion compared to clip motion. Contrast medium advances beyond the free edges of MV leaflets mixing with left ventricular blood 43 plus or minus 3 msec after initial separation. These cineroentgenographic studies elucidate nonuniformity of leaflet motion responsible for ECHO delays. Thus, ECHO D' and Co correlate well with hemodynamic indicators of MV opening and closure. However, ECHO motion, although qualitatively similar, is unpredictably delayed compared to cineroentgenography of clips on the MV free edge. Since the ECHO correlates well with hemodynamic indices of MV opening and closure, this noninvasive technique can be used as a reference in the timing of intracardiac events and in the determination of systolic and diastolic time intervals.
UK government wants GMC to be given stronger powers
Authors: L. Beecham
Journal: BMJ (2000)

The UK government has set out radical proposals which will give the General Medical Council greater power to protect patients from dangerous doctors. The proposals are based largely on plans developed by the GMC, which has welcomed the government's consultation document.

The document proposes widening the GMC's powers so that it can impose an interim suspension on a doctor. These suspensions would apply incases in which a doctor is arrested on suspicion of committing a serious crime or …
Researchers warn of possible risks to children from new epilepsy drugs
Authors: Lynn Eaton
Journal: BMJ (2007)

New drugs for epilepsy are increasingly being given to children despite the lack of evidence for their long term safety, warn researchers at a leading UK centre for paediatric pharmacy.

Ian Wong and colleagues at the University of London's Centre for Paediatric Pharmacy reviewed the data on epilepsy drugs prescribed to under-18s between 1993 and 2005 ( British Journal of Clinical Pharmacology 2007;63:689-97). The study looked at …
Influenza-Related Mortality
Authors: David M. Morens
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 Journals 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