Mark H. Zweig

A sensitive and specific fluorescence assay for tissue serotonin

Abstract A sensitive and specific method for the estimation of serotonin in biological materials is described. In this method, serotonin is reacted with ninhydrin to form a product whose fluorescence is eight times more intense than the native fluorescence of serotonin in strong acid solution. With this method it is possible to measure serotonin in organs in which endogenous serotonin had not been previously detected and to study the subcellular distribution of this amine in the rat pineal and adrenal glands.

Interaction of some colchicine analogs, vinblastine and podophyllotoxin with rat brain microtubule protein

Abstract The interaction of seventeen colchicine analogs, vinblastine and podophyllotoxin with rat brain microtubule protein has been sudied by measuring their ability to displace 3H-colchicine. The following analogs competitively displaced 3H-colchicine from rat brain microtubule protein: cholchiceinamide, N-desacetylthiocolchicine, demecolcine, N-acetyliodocolchinol, trimethylcolchicinie acid (TMCA) methyl ether, N-acetylcolchinol, and TMCA ethyl ether. Isocolchicine, isocolchiceinamide, iso-TMCA methyl ether, colchiceine, TMCA, N-benzoyl TMCA, colchicosamide, colchicoside, colchinol and colchinoic acid did not inhibit the binding of 3H-colchicine to rat brain microtubule protein. A good correlation was found between the ability of a given analog to displace 3H-colchicine from rat brain microtubule protein and its antimitotic or antigout properties. Podophyllotoxin and vinblastine, both potent antimitotic agents, inhibited 3H-colchicine binding competitively and non-competitively respectively.

Thyroid dysfunction associated with immunotherapy for patients with cancer.

The authors performed a prospective study to evaluate thyroid dysfunction in 130 patients with cancer who were receiving interleukin‐2 (IL‐2)‐based immunotherapy. Primary hypothyroidism was the most common abnormality, occurring in 12% of patients before, 38% during, and 23% after immunotherapy. Hyperthyroidism occurred in 1%, 4%, and 7% of patients at those time intervals. Among patients initially euthyroid (n = 111), primary hypothyroidism developed in 32% during and 14% after immunotherapy, persisting a median of 54 days. Three patients required levothyroxine. Hyperthyroidism developed in 2% of patients during immunotherapy and 6% after. Thyroid dysfunction was not a function of sex, diagnosis, type of treatment, or response to immunotherapy. Elevated titers of antithyroglobulin and antithyroid microsomal antibodies were detected after treatment in 9% and 7%, respectively, of all patients without prior antibody abnormalities and did not correlate with response to therapy. The high incidence of therapy‐induced thyroid dysfunction suggests that thyroid function should be carefully monitored in all patients receiving IL‐2‐based immunotherapy. Cancer 68:2384–2390, 1991.

URATE CRYSTAL INDUCED INFLAMMATION IN THE RAT: EVIDENCE FOR THE COMBINED ACTIONS OF KININS, HISTAMINE AND COMPONENTS OF COMPLEMENT

The inflammation produced by subplantar injection of sodium urate micro-crystals in the hindpaw of the rat was used as a model of gouty arthritis. Kinins are probably involved since carboxypeptidase B or soybean trypsin inhibitor partially (35%) blocked the edema. Serotonin does not participate since the edema was not prevented by methysergide or cyproheptadine. Histamine is apparently involved since many antihistaminics also partially (40%) suppressed this edema. Two antihistaminics, promethazine and tri-pelennamine, inhibited (75%) the edema as effectively as colchicine by mechanisms as yet not established. Treatment of rats with a combination of soybean trypsin inhibitor and a specific antihistaminic, triprolidine, inhibited the urate edema by 58-66%, which suggested that still another mediator was involved. Complement depletion of the rats also partially (30%) inhibited the edema. The combination of soybean trypsin inhibitor, triprolidine and complement depletion almost completely (80%) suppressed the...

Control of the circadian rhythm in serotonin content of the rat pineal gland

Abstract The circadian rhythm in pineal serotonin content is abolished by removal of the superior cervical ganglia but not by blinding.

Distribution of serum concentrations of creatine kinase MM and BB isoenzymes measured by radioimmunoassay

Because of the recent interest in measuring serum enzyme concentration as opposed to catalytic activity, we measured the serum concentration of creatine kinase isoenzymes BB and MM by radioimmunoassay and the total creatine kinase enzymatic activity in healthy adults. For sex-race subgroups we report mean values and the 2.5, 5, 25, 50, 75, 90, 95 and 97.5 percentiles. Differences among average values of the subgroups were highly significant. Results within subgroups frequently departed from a gaussian distribution.

Increased CK-BB concentrations in serum following cardiac surgery

We measured the BB isoenzyme of creatine kinase by a specific radioimmunoassay in the serum of 47 patients following cardiac surgery. A sharp increase in CK-BB occurred immediately after surgery, with rapid return to baseline by the fourth post-operative day. This data, along with other reports in the literature, suggest that CK-BB is released into the circulation following myocardial insult.

ROC Curves: Assessment of Clinical Test Accuracy

The number and complexity of measurements or indicators of the clinical performance of laboratory tests have increased considerably in recent years. So many different quantities, terms and plots have been suggested that even persons interested in and familiar with the issues find the array confusing. This need not be the case. By defining the fundamental issues and then making logical distinctions, we can identify order in this field. When I first began thinking about test performance and usefulness, I failed to appreciate a simple but important distinction which I now recognize and wish to promote. This is the distinction between accuracy and efficacy. Failure to maintain this simple distinction clouds the fundamental issues, contributes to the complex terms and quantities we are now burdened with, and obscures the source of problems with use of the test.