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Biomedical subjects

B Weiss

Publications and source records attributed to B Weiss.

At least 343 records · Page 19Linked to original sources
PubMed1978

Specificity of the binding of trifluoperazine to the calcium-dependent activator of phosphodiesterase and to a series of other calcium-binding proteins.

Trifluoperazine inhibits the activation of phosphodiesterase by binding to the calcium-dependent activator. To determine further the specificity by which trifluoperazine binds to activator, we compared the binding of trifluoperazine to activator prepared from several species and tissues and to a number of other calcium-binding proteins devoid of activator activity. Trifluoperazine binds to activator prepared from human, bovine, rat and rabbit brain and from chick embryo fibroblasts. In each case, the binding of trifluoperazine to activator was qualitatively similar and related quantitatively to the ability of the preparation to activate phosphodiesterase. Of the other calcium-binding proteins examined, namely, troponin-C, S-100 protein, phospholipase A, phospholipase B and myosin light chain, only troponin-C displayed any significant calcium-specific binding of trifluoperazine. The binding to troponin-C, however, appeared to be different from the binding to activator; whereas the binding of trifluoperazine to actovator showed no cooperativity, the binding to troponin-C showed positive cooperatively. These results and earlier data showing that trifluoperazine fails to bind to a variety of other proteins, indicate that the binding of trifluoperazine to the calcium-dependent activator of phosphodiesterase is selective and suggest that this binding may explain some of the biochemical and pharmacological actions of this antipsychotic agent.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1978

Indirect induction of differentiation in myeloid leukemic cells by lipid A.

Normal myeloid and MGI(+)D(+) clones of myeloid leukemic cells can be induced for Fc and complement component 3 rosettes, lysozme, and mature macrophages and granulocytes by a protein with macrophage- and granulocyte-inducing (MGI) activity, whereas MGI(+)D(-) clones can be induced by this protein for rosettes and lysozme but not mature cells. Lipopolysaccharides (LPS) from different bacteria induced the appearance of rosettes, lysozyme, and macrophages in some MGI(+)D(+) clones but did not induce any of these changes in MGI(+)D(-) clones. Lipid A gave the same results as LPS. Incubation of MGI(+)D(+) cells with LPS also induced an MGI activity detectable in the culture medium. This activity behaved like MGI in inducing (i) rosettes, lysozyme, and mature cells in MGI(+)D(+) leukemic cells including a clone resistant to LPS, (ii) rosettes and lysozyme in MGI(+)D(-) leukemic cells, and (iii) differentiation of normal myeloid cells to mature macrophages and granulocytes. This activity was induced in MGI(+)D(+) cells by LPS before the induction of rosettes or lysozyme. The results indicate that the lipid A portion of LPS indirectly induces differentiation of MGI(+)D(+) myeloid leukemic cells by inducing MGI protein. It is suggested that induction of specific regulatory proteins may be a more general mechanism for the induction of differentiation by surface-acting compounds.

Animals↗
PubMed1978

Escherichia coli mutants deficient in deoxyuridine triphosphatase.

Mutants deficient in deoxyuridine triphosphatase (dUTPase) were identified by enzyme assays of randomly chosen heavily mutagenized clones. Five mutants of independent origin were obtained. One mutant produced a thermolabile enzyme, and it was presumed to have a mutation in the structural gene for dUTPase, designated dut. The most deficient mutant had the following associated phenotypes: less than 1% of parental dUTPase activity, prolonged generation time, increased sensitivity to 5'-fluorodeoxyuridine, increased rate of spontaneous mutation, increased rate of recombination (hyper-Rec), an inhibition of growth in the presence of 2 mM uracil, and a decreased ability to support the growth of phage P1 (but not T4 or lambda). This mutation also appeared to be incompatible with pyrE mutations. A revertant selected by its faster growth had regained dUTPase activity and lost its hyper-Rec phenotype. Many of the properties of the dut mutants are compatible with their presumed increased incorporation of uracil into DNA and the subsequent transient breakage of the DNA by excision repair.

Coliphages↗
PubMed1978

IV. Covalent coupling of rat liver phenylalanine hydroxylase.

Rat liver phenylalanine hydroxylase (PheH) was covalently coupled to AH-Sepharose 4B, CH-Sepharose 4B, alginic acid and polygalacturonic acid. The activities of the bound enzyme from the ethanol and ammonium sulfate fractions were studied under a variety of conditions. The ethanol enzyme coupled to AH-Sepharose 4B showed the best thermal stability from 20 degrees to 50 degrees after heating for 15 min. It retained more than 15% of its initial activity after storage at 25 degrees for 9 days. The covalently linked enzymes generally had a broader range of optimal activity from pH 5.8 to 7.5. The presence of a positive or negative microenvironment on the matrix had no effect on the activity of the enzyme coupled to AH- or CH-Sepharose 4B. The failure to obtain hydroxylase activity with enzyme linked to alginic acid or polygalacturonic acid was attributed to the acidic microenvironment of the matrices.

Animals↗
PubMed1978

The behavioral toxicology of metals.

Many metals express their toxic actions through behavioral disturbances. Such disturbances most often reflect impairment of central nervous system function, but also may arise from deleterious effects in other systems. Numerous factors influence behavioral toxicity. Uptake into brain obviously is important; the chemical form of the metal (e.g., inorganic versus organic) and route of exposure are key determinants of brain penetration. Species differences in toxicity may arise from differences in kinetics (e.g., blood-brain ratio) and affinity to target brain structures. Developmental stage is still another crucial variable, but the young organism is not necessarily the most susceptible, and nutritional considerations confound the standard paradigms. Furthermore, parametric variations of behavioral functions can no more be ignored than dose-effect functions, a principle exemplified in research on methylmercury. Unwarranted loyalties to traditional psychological tests may be one source of the current dispute about safe levels of lead simply because parametric variations of clearly specified functions are beyond the scope of such instruments.

Aging↗
PubMed1977

Movement disorders induced in monkeys by chronic haloperidol treatment.

After several months of treatment, Cebus apella, Cebus albifrons, and Saimiri sciurea monkeys maintained on haloperidol, in doses of 0.5 or 1.0 mg/kg orally 5 days per week, began to display severe movement disorders, typically 1-6 h post-drug. Cebus monkeys exhibited violent, uncontrolled movements that flung the animals about the cage. Such episodes usually lasted only a few minutes, recurring several times during the period following drug ingestion. Writhing and bizarre postures dominated the response in S. sciurea. Cessation of drug treatment produced no distinctive after-effects. When tested as long as 508 days after the last administration, however, Cebus monkeys responded to haloperidol with several episodes of hyperkinesis, even at challenge doses considerably lower than those in the original treatment.

Animals↗
PubMed1977

Characteristics of the cyclic nucleotide phosphodiesterases of normal and leukemic lymphocytes.

The specific activity of cyclic AMP phosphodiesterase and cyclic GMP phosphodiesterase of leukemic lymphocytes was 5-10-fold greater than that of purified normal lymphocytes or of homogenates of spleen, thymus or lymph nodes of normal mice. This rise was demonstrable over a wide range of substrate concentrations. Both normal and leukemic lymphocytes contained a heat-stable, calcium-dependent activator of phosphodiesterase. However, the increased activity of phosphodiesterase in leukemic lymphocytes was not due to this protein activator since (a) phosphodiesterase activity from these cells was not stimulated by this activator and (b) phosphodiesterase activity of leukemic lymphocytes was not inhibited by the calcium chelater, ethylene-glycol-bis,(beta-aminoethylether)-N,N'-tetraacetic acid, suggesting that the enzyme was not already maximally activated. A comparison of several other properties of phosphodiesterase from normal and leukemic lymphocytes showed that the enzymes have similar pH optima, similar stabilities to freezing and thawing and similar sensitivities to inhibition by the phosphodiesterase inhibitors, chlorpromazine, papaverine and isobutylmethylxanthine. However, the subcellular distribution of the phosphodiesterases was different, and the phosphodiesterase of leukemic lymphocytes was significantly more resistant to heat than that of normal lymphocytes. Although no differences were found between the phosphodiesterases of normal and leukemic lymphocytes in their sensitivities to drugs, there were marked differences in drug sensitivity between the phosphodiesterase of lymphocytes and that of other tissue. For example, concentrations of chlorpromazine which inhibited phosphodiesterase of cerebrum by 70% had no effect on phosphodiesterase activity of lymphocytes. On the othere hand, the papaverine-induced inhibition of phosphodiesterase was similar in lymphocytes and cerebrum. Since an optimal concentration of cyclic nucleotides is essential to maintain normal cell growth, these results suggest that the abnormal growth characteristics of leukemic lymphocytes may be explained by their high activity of phosphodiesterase. Furthermore, the qualitative and quantitiative differences between the phosphodiesterases of leukemic lymphocytes and other tissues raise the possibility of selectively inhibiting the phosphodiesterase of the leukemic lymphocytes, thereby reducing their rate of growth, without affecting other tissues.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1977

Differences in surface membrane ecto-ATPase and ecto-AMPase in normal and malignant cells. I. Decrease in ecto-ATPase in myeloid leukemic cells and the independent regulation of ecto-ATPase and ecto-AMPase.

The hydrolysis of ATP and AMP by enzymes located on the external side of the plasma membrane (ecto-ATPase and ecto-AMPase) was studied in mouse myeloid leukemic cells, normal early myeloid cells, and normal mature granulocytes and macrophages. Nine clones of myeloid leukemic cells were used belonging to three groups that differ in their ability to be induced to differentiate by the differentiation-inducing protein MGI. These three groups consisted of MGI+D+ that can be induced to undergo complete differentiation, MGI+D- that can be induced to partially differentiate and MGI-D- with no induction of differentiation. The ecto-ATPase activity of normal early myeloid cells was similar to that of normal mature granulocytes and macrophages and higher than that of any of the leukemic cells. Among the leukemic cells, the MGI-D- cells had the highest level of ecto-ATPase activity. The behaviour of ecto-AMPase differed from that of ecto-ATPase. Some MGI-D- clones had a higher ecto-AMPase activity than normal cells and MGI+D- and MGI+D+ cells showed no detectable activity. Neither the ecto-ATP-ase nor ecto-AMPase activities changed after induction of differentiation in normal early myeloid or MGI+D+ leukemic cells. The results indicate that the myeloid leukemic cells had a decreased ability to hydrolyse external ATP, that there can be an independent regulation of ecto-ATPase and ecto-AMPase and that neither of these enzyme activities changed during differentiation.

Adenosine Monophosphate↗
PubMed1977

Covalent coupling of calf brain prolidase.

Calf brain prolidase covalently bound to CNBr-Sepharose 4B, retained about 32% of the activity of the uncoupled enzyme. The free enzyme showed slightly greater stability than the bound preparation when stored at 20 degrees C or at 0 degrees C. However, in either case the free and bound enzymes were more stable at the lower temperature. Greater thermal stability was shown by the free enzyme than by the bound preparation over a temperature range of 25 degrees C-60 degrees C. The free and bound prolidase, with and without Mn+2, had maximal activity at pH 4.0. Although the bound enzyme showed a single maximum, the free preparation exhibited three pH maxima of 4.0, 9.0, and 6.5, in decreasing order of activity. The ions Ag+, Cu+, Hg+2, and Zn+2 were strongly inhibitory on the free enzyme, whereas inhibition of the bound enzyme, with the exception of Zn+2 , was less. Unlike the coupled enzyme, a stimulatory effect was obtained on the free preparation with Co+3, Mg+2, and Mn+2. Various other compounds were studied and their effects were noted.

Animals↗
PubMed1977

Cerebroside analogues from 3-phenylserines.

Cerebroside analogues were synthesized from DL-threo-and DL-erythro-3-phenylserines by the following sequence of reactions: esterification, N-acylation, reduction with sodium bis (2-methoxyethoxy)-aluminum hydride (SMEAH), and condensation with acetobromoglucose followed by deacetylation. Mass spectrometry disclosed that the glycosidic bond was formed at the primary hydroxyl group.

Cerebrosides↗