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Biomedical subjects

C Ruby

Publications and source records attributed to C Ruby.

13 recordsLinked to original sources

Discovery of a small molecule insulin mimetic with antidiabetic activity in mice.

Insulin elicits a spectrum of biological responses by binding to its cell surface receptor. In a screen for small molecules that activate the human insulin receptor tyrosine kinase, a nonpeptidyl fungal metabolite (L-783,281) was identified that acted as an insulin mimetic in several biochemical and cellular assays. The compound was selective for insulin receptor versus insulin-like growth factor I (IGFI) receptor and other receptor tyrosine kinases. Oral administration of L-783,281 to two mouse models of diabetes resulted in significant lowering in blood glucose levels. These results demonstrate the feasibility of discovering novel insulin receptor activators that may lead to new therapies for diabetes.

Adenosine Triphosphate↗

Mutants of Streptomyces cattleya defective in the synthesis of a factor required for thienamycin production.

Thienamycin non-producing mutants of Streptomydes cattleya were identified that displayed a cross-feeding relationship. A diffusible product from one of these mutants (RK-11) resulted in restoration of thienamycin production when fed to cultures of another mutant (RK-4). In vivo radiolabeling experiments were conducted to test whether the RK-11 mutant produced a late biosynthetic intermediate which contained a carbapenem ring and a cysteaminyl and/or a hydroxyethyl side chain. Both [35S]cystine and [methyl-3H]methionine were used to label the RK-11 product which was then fed to RK-4 cultures. None of the thienamycin subsequently produced by RK-4 converter cells was labeled, implying the lack of either side chain of the thienamycin molecule in the RK-11 product. Further stability studies suggested that the RK-11 product does not contain a carbapenem ring. Additional feeding experiments with RK-4 cells also ruled out the possibility that the RK-11 product is a co-factor necessary for thienamycin production. It is concluded that the RK-11 product may regulate expression of the thienamycin gene cluster.

Chromatography, High Pressure Liquid↗

A health/patient education database for family practice.

Using pilot project funding from the W. K. Kellogg Foundation, the American Academy of Family Physicians Foundation (AAFP/F) developed a program by which health/patient education print materials were reviewed. Favorably reviewed materials were entered into a database accessible through the AAFP/F's Huffington Library. The review service and resulting database were designed to help the busy clinician identify scientifically accurate, reliable materials for use in patient education. The review process developed for the project is described, as is the database and its use by family physicians. Research findings from the pilot project are discussed, some of which assisted in planning the self-supporting second phase of the program.

Databases, Bibliographic↗

[beta-Thromboglobulin concentration, thrombocyte count and thrombocyte volume from four selected sample collections].

beta-Thromboglobulin, blood platelet count and blood platelet volume are presented by a reference group (N = 30) and are compared with a group of patients having mild thrombocytopenia, migraine and renal disease before, during as well as after dialysis. Patients with migraine have statistically significant differences regarding these three parameters in comparison to the reference group. Renal patients demonstrate a marked increase of the beta-thromboglobulin values during dialysis and a rapid decrease two hours afterwards.

Adult↗

Simultaneous determination of functional coagulation factors and competitive (PIVKA-) inhibitors based on enzyme kinetics.

For a plasma containing the competitive (PIVKA-) inhibitors induced by anticoagulant treatment the coagulation time t is related to the concentrations of functional coagulation factors S (substrates) and competitive inhibitors I by t = tmin + el/S + gamma I/S with tmin being the minimum possible coagulation time and e and gamma the sensitivities of the test procedure towards a change in the concentration of functional coagulation factors and competitive inhibitors, respectively. The calibration of the test procedure can be achieved by performing a series of dilutions on an inhibitor-free plasma (determination of tmin and e) and, after that, on a plasma of known inhibitor content (determination of gamma) in both cases recording the parametrizing straight line which results from multiplying the respective equation by S. The content of functional coagulation factors and competitive inhibitors in the plasmas of anticoagulated patients then can be determined simultaneously by treating the patient's plasma like in the calibration for gamma. The proposed method should allow the complete metrological characterization of thromboplastin time reagents without any need for reference thromboplastins.

Biomarkers↗

"Streptomyces avermitilis" mutants defective in methylation of avermectins.

"Streptomyces avermitilis" mutants defective in the methylation of the avermectins have been isolated and characterized. Four mutant strains, CR-1, CR-2, CR-3, and CR-4, were unable to methylate the oxygen at C5 of the macrolide moiety and produced essentially only the avermectin B components. These four strains lack avermectin B2 O-methyltransferase (B2OMT) activity. Two mutant strains were unable to methylate the oleandrose moiety at the oxygens at C3' and C3'' and produced essentially only demethylavermectin components. One of these mutants, strain CR-5 (derived from wild-type "S. avermitilis"), produced demethylavermectin A and B components and possessed normal B2OMT levels. The other mutant, strain CR-6 (derived from strain CR-1, which lacks B2OMT activity), produced only demethylavermectin B components. Reaction of 3"-O-demethylavermectin B2a and S-adenosylmethionine with either cell extracts or purified B2OMT resulted in the methylation of the oxygen at C5 of the macrolide moiety and yielded only 3''-O-demethylavermectin A2a as the product. These experiments indicate that different enzymes are required for methylation of the macrolide (the oxygen at C5) and the oleandrose (oxygen at C3) and that methylation of the oleandrose occurs before attachment to the macrolide ring.

Adenosine↗

Methylation of demethylavermectins.

Demethylavermectins, which lack methyl groups on the oleandrose moiety, were fed to wild-type "Streptomyces avermitilis," which produces the normal avermectin components, and the bioconversion products were identified. The oleandrose units of the demethylavermectins were not methylated by the wild-type strain, but the C-5 of the macrolide ring was methylated. This demonstrates that methylation of the oleandrose units is not a terminal step in avermectin biosynthesis and that it occurs before attachment of the sugars to the macrolide ring. Avermectin biosynthesis thus differs from that of tylosin and erythromycin, in which methylation of the hexose moieties is a terminal reaction.

Biotransformation↗

[Thrombocyte counting with the Laborscale (PSL-1/PSA-1) particle-counting instrument by Medicor (Budapest/Hungary) and thrombocyte volume analysis in the diagnosis of selected thrombocytopathies].

A thrombocyte counting technique is presented in comparison with the chambre counting according to the German Book of Medicaments (DAB 7 D.L.) GDR on the particle counting device "Laborscale" (PSL-1/PSA-1) of Medicor by using a thrombofuge (70 g). The composition of reagents accounts for problems of measurement which are caused by the device and influences the separation of particles. The possibility of recording the curve of thrombocyte volume distribution and calculating the average thrombocyte volume (VM) is demonstrated by means of a normal collective of test persons as well as by intravascular disorders of haemostasis and during cytostatic therapy.

Adult↗

Plasmid interactions in Staphylococcus aureus: nonadditivity of compatible plasmid DNA pools.

Six different Staphylococcus aureus plasmids have been examined for compatibility relationships and their intracellular DNA pools have been measured singly and in various combinations. All six were mutually compatible, but contrary to expectation, their intracellular DNA pools were not additive; instead, there appeared to be a maximum level of extrachromosomal DNA that could be supported by the cell, and the plasmids studied approached this level individually as well as in varous combinations. One exception was encountered: a plasmid encoding kanamycin/neomycin resistance was present in a small but constant number of copies regardless of the presence of other plasmids.

DNA, Bacterial↗