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Biomedical subjects

J Adams

Publications and source records attributed to J Adams.

At least 397 records · Page 22Linked to original sources

Conjugated alpha-keto acids as mechanism-based inactivators of brewer's yeast pyruvate decarboxylase: electronic effects of substituents and detection of a long-lived intermediate.

A series of phenyl substituted E-4-phenyl-2-keto-3-butenoic acid derivatives were synthesized (p-Cl, m-Cl, p-NO2, m-NO2, o-NO2, 3,4-Cl2, 2,6-Cl2, p-CH3O, p-(CH3)2N) and tested as potential irreversible inhibitors of brewer's yeast pyruvate decarboxylase (EC 4.1.1.1). All those derivatives with electron withdrawing substituents were found to be time-dependent inactivators of the enzyme, unlike the p-CH3O- and p-(CH3)2N derivatives. Detailed kinetic studies with the m-nitro derivative (the most potent inhibitor) indicated that this compound formed reversible complexes with the enzyme at two sites (supposed regulatory and catalytic with Ki values of 0.026 and 0.13 mM, respectively) prior to irreversible inactivation of the enzyme. In addition, concurrently with the inactivation, addition of the m-NO2 derivative to the enzyme produced a new VIS absorbance with lambda max near 430 nm. This absorbance was attributed to the enzyme-bound enamine intermediate. The time course of formation and disappearance of the intermediate could be determined and provided detailed information about the mechanism of the enzyme.

Carboxy-Lyases↗

Cinnamoylation of the sugar hydroxyls of 3-methylthymidine. Formation of a relatively stable ester derivative.

A trace amount (51 ng) of 3-methylthymidine is derivatized with cinnamic anhydride in the presence of the acylation catalyst 4-dimethylaminopyridine. The yield of the diacylated product, 3'-5'-bis-(O-cinnamoyl)-3-methylthymidine, is 102 +/- 3.6%. The product is stable at pH 4-8 in aqueous acetonitrile for 16 days and can be determined at the low pg level by gas chromatography with electron-capture detection. These results encourage the further development of alpha,beta-unsaturated acylating reagents for use in this and related chromatographic analyses.

Chemical Phenomena↗

The lipoxins. Stereochemical identification and determination of their biosynthesis.

The stereochemistry and double bond geometry of a novel series of leukocyte-derived arachidonic acid metabolites, the lipoxins, was determined by comparison to pure unambiguous synthetic standards. The lipoxins were found to be a mixture of four lipoxin A isomers and two lipoxin B isomers. In determining the biosynthesis of these compounds, they were shown to be formed via a tetraene epoxide. In addition, it was shown that all of the lipoxin isomers formed by the incubation of 15-hydroperoxyeicosatetraenoic acid with human leukocytes were also formed by nonenzymatic hydrolysis of this tetraene epoxide.

Arachidonic Acid↗

The Philadelphia (Ph) chromosome in leukemia. I. A new mechanism due to interstitial deletion and insertion in chronic myelocytic leukemia.

The Philadelphia (Ph) chromosome in leukemia is invariably derived from chromosome #22. A break occurs in the long (q) arm of chromosome #22 and, in every case observed until now, all of the material from that breakpoint through the telomere of chromosome #22 has been reciprocally translocated to another chromosome, most often chromosome #9. With the t(9;22) translocation, the oncogene c-sis moves from chromosome #22 onto 9q and the oncogene c-abl moves reciprocally from chromosome #9 onto 22q. We report a new mechanism for the genesis of the Ph chromosome in chronic myelocytic leukemia (CML) involving interstitial deletion of chromosome #22 with insertion of the deleted material into another chromosome: 46,XX,dir ins(11;22)(q13;q11q13). The distal portion of chromosome #22, including the telomere, appeared to have been retained in the Ph chromosome. There was no visible involvement of chromosome #9. This insertional deletion is of potential importance in evaluating the roles of oncogenes such as c-abl and c-sis in the Ph rearrangement in the origin of leukemia.

Bone Marrow↗

The investigation of female gonadal dysfunction.

An approach to the investigation of ovarian dysfunction has been presented here with a particular emphasis on the importance of effective imaging of the ovary and uterus by ultrasonography. Essential endocrine investigations in the various clinical manifestations of altered ovarian function have been placed in the context of recent research on the control of female reproduction.

Adult↗

Physiological characterization of adaptive clones in evolving populations of the yeast, Saccharomyces cerevisiae.

Populations of a diploid strain of S. cerevisiae were grown in glucose-limited continuous culture for more than 260 generations. A series of seven sequential adaptive changes were identified by monitoring the frequency of cycloheximide resistance in these populations. Samples were taken from the continuous cultures following each adaptive shift and characterized physiologically to determine (1) the range of phenotypes that can be selected in a precisely defined constant environment and (2) the order and predictability of the occurrence of the adaptive mutations in evolving populations. The clones were characterized with respect to the growth parameters, maximum growth rate, saturation coefficient and yield, as well as for changes in cell size and geometry and rate of glucose uptake. The maximum growth rates of the seven adaptive clones were very similar, but in contrast the saturation coefficients differed substantially. Surprisingly, not all clones showed reductions in the saturation coefficients, in comparison to the immediately preceding clones, as would be predicted from classical continuous culture kinetics. In addition, yield estimates first increased and then decreased for later isolated adaptive clones. In general, the results suggest epistatic interactions between the adaptive clones, consistent with earlier published results. The rate of glucose uptake, as measured by 14C-xylose uptake, increased dramatically after the selection and fixation of seven adaptive clones. Progressive decreases in cell volume and changes in cell geometry, resulting in increased surface area to volume ratios, were also observed in the adaptive clones, but these changes were not always seen in other haploid and diploid yeast populations evolving under the same conditions. Such changes may be easily explainable in terms of the characteristics of the glucose-limited environment. The significance of the results to the evolution of microorganisms under nutrient-limiting conditions is discussed.

Biological Transport↗

The treatment of central precocious puberty using an intranasal LHRH analogue (buserelin).

Eight girls and one boy with precocious puberty were treated with intranasal (D-Ser6)-LHRH (buserelin) for 0.5-2.3 years (mean 1.2 years). Treatment regimen varied between 17 and 40 microgram/kg/d in the girls to 10 micrograms/kg/d in the boy in two or three divided doses. Gonadotrophin-dependent clinical signs showed arrest or regression whereas those of adrenarche progressed. Serial pelvic ultrasound assessment was used to monitor treatment in four girls. Although peak stimulated gonadotrophins reduced to prepubertal levels, basal gonadotrophins became elevated on treatment. The mode of action of buserelin was the abolition of gonadotrophin pulsatility. Initial data suggest an improved growth prognosis. We concluded that intranasal therapy is an alternative route of administration of LHRH analogue in the treatment of precocious puberty.

Administration, Intranasal↗