Jewish Hospital

About: Jewish Hospital is a healthcare organization based out in Cincinnati, Ohio, United States. It is known for research contribution in the topics: Antigen & Population. The organization has 3881 authors who have published 3414 publications receiving 123044 citations.

The influence of acetylsalicylic acid on the binding of acetrizoate to human albumin

Abstract: Several years ago, investigations were initiated to study the binding properties of various urographic contrast media to plasma proteins. One particular contrast medium, 3-acetamido-2,4,6-triiodobenzoate (acetrizoate) , was especially interesting, because this anion exhibited an enhanced binding affinity for a protein in the serum from some patients with rheumatoid arthritis.lI2 Similar to many anions, acetrizoate (FIGURE 1 ) bouild loosely to albumin when equilibrium dialysis was performed at a free acetrizoate concentration of 2 X 1 0 4 M; at this concentration, the amount of acetrizoate bound by all human sera or purified human serum albumin (HSA) was directly proportional to the concentration of HSA. However, when similar binding studies were performed at a free acetrizoate concentration of 1.0 X 10-7 M, sera from rheumatoid arthritis patients bound significantly more acetrizoate than normal serum; furthermore, such enhanced acetrizoate binding could not be accounted for on the basis of the HSA concentration in the individual serum samples. Subsequent studies demonstrated that the enhanced acetrizoate binding was due to what was thought to be an abnormal albumin in some patients with rheumatoid a r th r i t i~ .~ The presence of the abnormal albumin could not be correlated with the clinical history, various laboratory tests, such as the erythrocyte sedimentation rate and rheumatoid factor, clinical progress, steroid therapy, or blood salicylate levels. The latter observation indicated that salicylate probably had not altered HSA but did not exclude the possibility that acetylsalicylate (aspirin) might be involved. Indeed, this was shown to be the case when enhanced acetrizoate binding developed in the sera of seven volunteers after the ingestion of 2.4 g aspiridday for 21-56 days.4 In addition, in vitro exposure of HSA to aspirin enhanced acetrizoate binding, whereas

Thalidomide causes sinus bradycardia in ALS.

Abstract: Neuroinflammation contributes to motor neuron degeneration in ALS. Thalidomide (THL) shows potent anti-inflammatory properties and increased the lifespan in ALS transgenic mice. Thalidomide was therefore suggested as atherapeutic intervention for the treatment of ALS.We conducted a pilot, randomized clinical trial of THL in patients with ALS to assess safety, feasibility, and preliminary estimates of treatment efficacy. Patients were randomized to THL in combination with riluzole (n = 18) or riluzole alone (n = 19). THL was initiated at 100 mg per day for 6 weeks. Thereafter, the dose was increased every week by 50 mg until reaching the dose of 400 mg per day and planned to continue for another 12 weeks. Within 12 weeks of THL treatment, nine THL patients (50%) developed bradycardia defined as a heart rate below 60 beats per minute (bpm) and ranged from 46 to 59 bpm. Mean heart rate dropped by 17 bpm with THL treatment. Severe symptomatic bradycardia of 30 bpm occurred in one patient. A further patient died from sudden unexpected death. The study was terminated prematurely for safety concerns. The secondary outcome variables showed similar results for both groups. Bradycardia was the most common adverse event of THL treatment in ALS. THL-related bradycardia does not appear to be ALS-specific. It is conceivable, however, that the unexpected frequency and severity of THL-induced bradycardia may be related to subclinical involvement of the autonomic nervous system in ALS. The cardiac toxicity discourages further clinical trials and compassionate use of THL in ALS. ClinicalTrials.gov Identifier: NCT00231140.

Calcification in a marine coccolithophorid

Abstract: The use of microorganisms to explore general problems of biochemistry and physiology has become an accepted approach. While bacteria, yeasts, and fungi primarily serve as test objects, the successful domestication of protozoa has made these primitive animals available for investigative purposes. Most of the protozoa now in use are f&h water varieties. Through the efforts of Prova801i1 and of Droop2 protista of marine origin are now available to the interested student. The problems posed by maintaining such microorganisms in cultures free from all other living forms are complicated by their need for an oceanic environment. The variations in crop yields, physiological activities, and morphological manifestations resulting from artificial cultivation must be recognized and separated from findings which are the consequence of experimental manipula t ion~.~ In other words, while the size of the test animal has decreased, the complexities of living protoplasm have not. The advantages offered by microbial forms of life to the investigator lie in their short generation times, the enormity of the populations which can be kept without mortgaging everything to feed them, and especially their lack of specializatioii a t the cellular level; that is, the individual cell performs all the functions of the entire organism. When to this last property is added the ability to extrude microscopic structures of high mineral content, one can appreciate why such strange bedfellows as microbiologists, orthopedic surgeons, and anatomists can fhd a common ground for a collaborative effort,. It is perhaps appropriate at this juncture to devote a few moments to

The factor V Leiden mutation, high factor VIII, and high plasminogen activator inhibitor activity: Etiologies for sporadic miscarriage

Abstract: We hypothesized that the thrombophilic G1691A factor V Leiden gene mutation was a common significant cause of sporadic first trimester miscarriage. We compared thrombophilia and hypofibrinolysis in 92 women (85 white, 5 black, 2 other) with 1 or more pregnancies and 1 miscarriage (143 live births, 92 miscarriages) (cases) and in 380 female controls (355 white, 21 black, 4 other) with 1 or more pregnancies and 0 miscarriages (964 live births). We used polymerase chain reaction techniques to characterize thrombophilic gene mutations (G1691A V Leiden [FV], G20210A prothrombin, C677T/A1298C MTHFR) and hypofibrinolytic gene mutations (plasminogen activator inhibitor [PAI-1] activity 4G4G). We carried out serologic measures of thrombophilia (homocysteine, anticardiolipin antibodies [ACLA] immunoglobulin G and immunoglobulin M, lupus anticoagulant, factor VIII, factor XI, protein C, total and free protein S, antithrombin III) and hypofibrinolysis (plasminogen activator inhibitor activity [PAI-Fx], lipoprotein[a]). Of the 380 controls, 6 (1.6%) had FV heterozygosity vs 12 heterozygous and 2 homozygous FV cases (15.2% [14/92]; P 150%) in 15 (31%) of 48 cases vs 19 (18%) of 103 controls (P = .079). By logistic regression, with age and factor VIII (categorical [≤150%, >150%]) as explanatory variables and group (cases, controls) as the dependent variable, after adjusting for age, high factor VIII was a significant predictor for miscarriage (odds ratio, 3.28; 95% confidence interval, 1.34-8.04; P = .01). There were no other group differences (P > .05) in measures of thrombophilia and hypofibrinolysis. After unexplained sporadic first trimester miscarriage, we suggest that measurements be done of the FV mutation, PAI-Fx, and factor VIII, etiologies for sporadic miscarriage.