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Biomedical subjects

E Jacobson

Publications and source records attributed to E Jacobson.

At least 19 recordsLinked to original sources

Cloning and functional characterization through antisense mapping of a kappa 3-related opioid receptor.

We have identified a putative opioid receptor from mouse brain (KOR-3), belonging to the G protein-coupled receptor family, that is distinct from the previously cloned mu, delta, and kappa 1 receptors. Assignment of the clone to the opioid receptor family derives from both structural and functional studies. Its predicted amino acid sequence is highly homologous to that of the other opioid receptors, particularly in many of the transmembrane regions, where long stretches are identical to mu, delta, and kappa 1 receptors. Both cyclazocine and nalorphine inhibit cAMP accumulation in COS-7 cells stably expressing the clone. Northern analysis shows that the mRNA is present in brain but not in a number of other organs. Southern analysis suggests a single gene encoding the receptor. A highly selective monoclonal antibody directed against the native kappa 3 receptor recognizes, in Western analysis, the clone expressed in COS-7 cells. The in vitro translation product is also labeled by the antibody. Additional clones reveal the presence of several introns, including one in the second extracellular loop and another in the first transmembrane region. Antisense studies with an oligodeoxynucleotide directed against a region of the second extracellular loop reveal a selective blockade of kappa 3 analgesia in vivo that is not observed with a mismatch oligodeoxynucleotide based upon the antisense sequence. The mu, delta, and kappa 1 analgesia is unaffected by this antisense treatment. Antisense mapping of the clone downstream from the splice site in the first transmembrane region reveals that six different antisense oligodeoxynucleotides all block kappa 3 analgesia. In contrast, only one of an additional six different antisense oligodeoxynucleotides directed at regions upstream from this splice site is effective. This strong demarcation between the two regions raises the possibility of splice variants of the receptor. An additional clone reveals an insert in the 3' untranslated region. In conclusion, the antibody and antisense studies strongly associate KOR-3 with the kappa 3-opioid receptor, although it is not clear whether it is the kappa 3 receptor itself or a splice variant.

Amino Acid Sequence

Malignant transformation of angiomyolipoma.

Angiomyolipomas are well recognized but uncommon tumors that can involve the kidney. To our knowledge a well documented case of malignant change of angiomyolipoma has never been reported. We report a case of renal angiomyolipoma and leiomyosarcoma with a clearly identified transition of benign to malignant elements seen in the resected tissue.

Adult

The effects of ambient temperature on amikacin pharmacokinetics in gopher tortoises.

The pharmacokinetics of amikacin were compared in two groups of tortoises, one held at 20 degrees C and the other at 30 degrees C. The mean (+/- SD) residence time for amikacin in the 30 degrees C tortoises was 22.67 +/- 0.50 h; significantly (P less than 0.05) less than those held at 20 degrees C (41.83 +/- 3.23 h). There was no significant difference (P greater than 0.05) in the steady-state volume of distribution (Vd(ss] between the tortoises held at 30 degrees C (0.241 +/- 0.520 l/kg) and those held at 20 degrees C (0.221 +/- 0.019 l/kg). The clearance rate was faster (P less than 0.05) in the warmer tortoises (10.65 +/- 2.42 ml/min/kg at 30 degrees C compared to 5.27 +/- 0.152 ml/min/kg at 20 degrees C). These data indicate that while the volume of distribution was approximately the same, amikacin remained in the colder tortoises longer because of its slower elimination. The oxygen consumption and metabolism were measured and found to be lower in the colder tortoises, almost by the same 2:1 ratio as clearance time (Cl), mean residence time (MRT), and area under the curve (AUC). The data derived from this limited study indicated that an appropriate therapeutic dosage regimen for amikacin in gopher tortoises at 30 degrees C is 5 mg/kg given i.m. every 48 h.

Amikacin

A rapid method for detection of cellular proliferation using carboxyfluorescein. Assay of growth factors (IL-2, IL-1) and growth inhibiting antibodies.

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.

Antibodies, Monoclonal

Synthesis and uptake of taurine by isolated human granulocytes.

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.

Adult

Amebiasis in red-footed tortoises.

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.

Amebiasis

Taurine uptake by cultured human lymphoblastoid cells.

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.

Binding, Competitive

Safety and efficacy of intravenous quinidine.

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.

Arrhythmias, Cardiac