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Biomedical subjects
Publications and source records attributed to E Jacobson.
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The uptake of carboxyfluorescein diacetate (CFDA) into live cells was used as the basis for a simple, rapid and fully automated micromethod for determination of cell growth. The aim of the investigation was to adapt the CFDA method for detection of cell growth factors from cell culture supernatants. Thus, the biological activities of the growth factors IL-2 or IL-1 could be detected and quantitated at the same level of sensitivity as with the conventional [3H]thymidine incorporation. Similarly, the method was well suited to assay inhibition of IL-2-dependent lymphocyte growth by the monoclonal antibody anti-Tac, binding to the human lymphocyte membrane receptor for IL-2. The CFDA method proved to be rapid, reliable and well suited for several applications involving limiting numbers of cells and biological reagents.
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The synthesis and uptake of taurine were studied in isolated human granulocytes. It was found that granulocytes were capable to metabolize L-cysteine to taurine, and to take up taurine from the incubation medium. The taurine uptake appeared to be temperature dependent, sodium dependent and competitively inhibited by beta--alanine.
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Of 500 red-footed tortoises imported to southern Florida, approximately 200 died during a 2-month period. Clinical signs were nonspecific and included anorexia, listlessness, and watery diarrhea, with lingering death. Necropsy consistently revealed thickened duodenum, with necrotic mucosa and multifocal to diffuse areas of hepatic necrosis. Histologic evaluation of tissues demonstrated numerous amebae in intestinal and hepatic lesions.
Cultured human lymphoblastoid cells take up taurine from the medium by two processes: 1) a temperature-dependent, Na+-dependent, saturable "active"-transport system and 2) diffusion. The active transport has properties similar to those reported for taurine transport by other tissues. Apparent Km is about 25 microM and Vmax about 7.2 pmol/min/10(6) cells; saturation occurs at 100 microM taurine. Uptake is competitively inhibited by the beta-amino acids hypotaurine (50% inhibition at 44 microM) and beta-alanine (50% at 152 microM), as measured at 50 microM taurine. Taurocyamine inhibits 50% at 260 microM. Chlorpromazine and imipramine are strong uncompetitive inhibitors, giving 50% inhibition at 26 microM and 115 microM, respectively; at these concentrations cellular viability per se is not affected. Ouabain inhibits 40-50% over a concentration range of 4-500 microM. Diffusion of taurine into the cells is proportional to concentration up to 20 mM. However, at the concentration of taurine in human plasma, 40-100 microM, active transport would provide 90% of the taurine taken up.
The safety and efficacy of intravenous quinidine were evaluated in a patient population with a high prevalence of left ventricular dysfunction and intraventricular conduction delays. Quinidine gluconate (mean dose 9.1 +/- 1.6 mg/kg) was administered during electrophysiologic study to 100 patients with ventricular or supraventricular tachyarrhythmias. Clinical heart failure was present in 68 percent of the patients. Left ventricular end-diastolic pressure, cardiac index, and left ventricular ejection fraction were abnormal in 62, 48, and 70 percent, respectively. Major intraventricular conduction delays (QRS of 120 msec or more) were present in 27 percent, and the H-V interval was prolonged (over 55 msec) in 28 percent. Despite the prevalence of these abnormalities, quinidine was discontinued because of hypotension in only 10 patients. Saline solution was infused to maintain preload in 37 percent, and hypotension responded promptly to saline solution infusion or discontinuation of quinidine infusion in all subjects. Hypotension was not more common in patients with more severe left ventricular dysfunction. QRS duration, H-V interval, QTc, and right ventricular effective refractory period increased significantly (p less than 0.001) after quinidine administration. Heart block or QRS widening of 50 percent or more did not occur. Quinidine prevented arrhythmia induction in 26 percent of patients who received full doses. Ventricular tachycardia cycle length increased in all 41 patients in whom identical forms were induced before and after quinidine (287 +/- 71 msec versus 361 +/- 93 msec, p less than 0.001). Intravenous quinidine may be administered safely to patients with intraventricular conduction delays and moderate heart failure. When antiarrhythmic efficacy is assessed by electrophysiologic study, quinidine compares favorably with other antiarrhythmic agents.
An antemortem diagnosis of lymphosarcoma was made in a captive Eastern king snake and a rhinoceros viper. The Eastern king snake died on the 1st day after biopsy of a liver nodule, and necropsy revealed multiple tumor nodules throughout all major organ systems. The rhinoceros viper died after chemotherapy with cytosine arabinoside. The major gross lesion was a large paracolonic coelomic tumor that extended into the adjacent musculature and subcutaneous tissue of the lateral abdominal wall. The immediate cause of death of the rhinoceros viper was believed to be severe renal tubular necrosis.
Of 438 snakes in a zoologic collection, 35 died during a 3-month period; all were members of the family Viperidae. Clinical signs consisted of gaping of the mouth followed within 1 day by convulsions. All necropsied animals had a mucoid exudate throughout the respiratory tract. Histologic evaluation of lung revealed evidence of interstitial pneumonia, with occasional eosinophilic intracytoplasmic inclusions in epithelial cells. A paramyxo-like virus, isolated in viper heart cells from lung tissue, was observed by electron microscopy to be budding from cell membranes. The virus hemagglutinated chicken red blood cells at 5 C, and antibody titers were assayed by hemagglutination inhibition. In a random survey of 22 snakes from the zoologic collection, antibody titers to the virus ranged from 1/20 to 1/2,560.
The 3T3 cells were treated with 50 mu g/ml lysolecithin (LL) followed by the addition of exogenously supplied radiolabelled sugar nucleotides to serve as direct glycosyl donors. These were found to be 1.5 to 3.0 times more active than untreated cells in their glycosyl transferase activities depending on the particular sugar nucleotide used. Mannosyl transferase activity was not inhibited by 2-deoxyglucose or mannose-1-phosphate, indicating that the sugar nucleotide remained intact throughout the assay period. Preincubation of the cells with tunicamycin caused an 85% decrease in mannosyl transfer, which suggested that the normal pathway of glycosylation via lipid intermediates was still operable in the treated cells. Fractionation of control and LL-treated cells after incubation with UDP[3H]galactose revealed that only microsomal and cytosolic proteins from the treated cells were radioactive. Thus, intracellular labelling of permeabilized cells was allowed. About 80% of the radiolabeled product was glycoprotein in nature, based upon its solubilization with pronase.
During temperature-induced transition of the dimorphic pathogenic fungus Histoplasma capsulatum from the single yeast cell form to the multicellular mycelial form, there was an increase in intracellular cyclic adenosine 3',5'-monophosphate (cAMP) levels as well as a striking accumulation of cAMP in the medium. cAMP levels also changed during the reverse mycelium-to-yeast transition.
A patient with advanced chronic renal failure secondary to polycystic kidney disease suffered an episode of volume contraction during which his urinary sodium concentration fell to less than 5 mEq daily. Urine sodium excretion remained at this level when later in his course he became clinically volume expanded. The patient also suffered from Crohn's disease and had an ileostomy from which he excreted from 100 to 150 mEq sodium daily. We propose that this patient's capacity to produce urine virtually free of sodium despite advanced renal failure was a result of the persistent loss of sodium from his ileostomy. This sodium loss obviated the development of the adaptive natriuresis that usually occurs in the functioning nephrons of the diseased kidney and prevented the development of a 'salt-losing' tendency.
A rock rattlesnake (Crotalus lepidus) with a history of progressive central nervous disease was submitted for necropsy. The histopathologic findings included evidence of interstitial pneumonia, multifocal areas of gliosis in the brain, and ballooning degeneration and demyelination of brainstem and upper spinal cord axons. By electron microscopy, brainstem tissue was found to contain numerous virus particles in the extracellular spaces. A paramyxo-like virus, isolated in viper heart cells from lung tissue, was observed by electron microscopy to be similar in size and shape to the particles seen in nerve tissue.
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All living and most fossil representatives of the reptilian subclass Archosauria lack pineal bodies. Arrhythmic, low-level, nonpineal melatonin is present, however, in the blood of Alligator mississippiensis. Although pineal bodies have been implicated in circadian phenomena, these results suggest that arrhytmic melatonin in alligators may not be involved incircadian events and indicate that the pineal is not the only source of the hormone melatonin. The evolutionary loss of the pineal in Archosauria occurred during the Mesozoic, and era noted for its seasonal stability. Arrhythmic melatonin titers inalligators and pineal loss in alligators and other archosaurs may be related to Mesozoic seasonal stability.