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Biomedical subjects

H J Martin

Publications and source records attributed to H J Martin.

At least 19 recordsLinked to original sources
PubMed2006

Is hand-held dynamometry useful for the measurement of quadriceps strength in older people? A comparison with the gold standard Bodex dynamometry.

BACKGROUND: The lower limb muscle strength is an important determinant of physical function in older people. However, measurement in clinical and epidemiological settings has been limited because of the requirement for large-scale equipment. A protocol using a novel, versatile hand-held dynamometer (HHD) has been developed to measure the quadriceps strength in a supine position. OBJECTIVE: The objective of this study was to assess the validity of this new methodology for measuring the lower limb muscle strength compared to the gold standard Biodex dynamometer. METHODS: The supine quadriceps strength was measured twice with each of the Biodex and the HHD in 20 men and women, aged 61-81 years, on their non-dominant leg. The agreement between the peak torques obtained by Biodex and HHD was analyzed. RESULTS: The mean peak Biodex and HHD results were 83.4 +/- (SD) 28.0 Nm and 68.9 +/- 19.6 Nm, respectively. The HHD undermeasured the quadriceps strength by an average of 14.5 Nm (95% CI 8.5, 20.6) compared to the Biodex, and this effect was most marked in the strongest participants. Nevertheless, there was a good correlation between the measures (r = 0.91, p < 0.0001). Classification of individuals into tertiles of muscle strength showed good agreement between the two methods (Kappa = 0.69, p < 0.0001). CONCLUSIONS: Our findings suggest that the HHD using a supine positioning offers a feasible, inexpensive, and portable test of quadriceps muscle strength for use in healthy older people. It underestimates the absolute quadriceps strength compared to the Biodex particularly in stronger people, but is a useful tool for ranking muscle strength of older people in epidemiological studies. It may also be of value for quick and objective assessment of physical function in the clinical setting.

Age Factors↗
PubMed2001

The 12,13-diol cyclization approach for a truly stereocontrolled total synthesis of epothilone B and the synthesis of a conformationally restrained analogue.

A highly convergent and stereocontrolled synthesis of epothilone B (1) has been developed. The epoxide moiety in 1 was generated by regioselective mesylation and base treatment of the 12,13-diol 30 which was formed by a chelate Cram controlled Grignard addition of 14 and methyl ketone 13. Both fragments were synthesized from the chiral carbon pool precursors (S)-citronellol and (S)-lactic acid, respectively. A highly diastereoselective aldol addition of epoxy-aldehyde 7 and the known Southern hemisphere ketone 8 delivered the full carbon skeleton, containing all the stereogenic centers of 1. Functional group manipulation, macrolactonization and removal of two protecting groups then yielded 1. The spatial closeness of the C4-beta-methyl and C6-methyl group in the crystal structure of 1 inspired us to connect them through a methylene bridge to give a cyclohexanone derivative. Thus, the Northern hemisphere aldehyde 7 was added to the enolate of the cyclohexanone 47. Further manipulations and macrolactonization delivered the conformationally restrained epothilone derivative 42.

Antineoplastic Agents↗
PubMed2000

Human 11beta-hydroxysteroid dehydrogenase type 1 is enzymatically active in its nonglycosylated form.

11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD 1) is a microsomal enzyme responsible for the reversible interconversion of active 11beta-hydroxyglucocorticoids into inactive 11-ketosteroids and by this mechanism regulates access of glucocorticoids to the glucocorticoid receptor. The enzyme has also been proven to participate in xenobiotic carbonyl compound detoxification. 11beta-HSD 1 is anchored within the membranes of the endoplasmic reticulum (ER) by its N-terminus, whereby its active site protrudes into the lumen of the ER. In the primary structure of 11beta-HSD 1 three Asn-X-Ser glycosylation motifs have been identified. However, the importance of N-linked glycosylation of 11beta-HSD 1 for catalytic activity has been controversely discussed. To clarify if glycosylation is essential for enzyme activity, we performed deglycosylation experiments of native 11beta-HSD 1 from human liver as well as site-directed mutagenesis to remove potential glycosylation sites upon overexpression in Pichia pastoris. The altered proteins were examined regarding their catalytic activity towards their physiological glucocorticoid substrates. The molecular size of the various 11beta-HSD 1 forms was analyzed by immunoblotting with a polyclonal antibody raised against 11beta-HSD 1 protein from human liver. By stepwise enzymatic deglycosylation of native 11beta-HSD 1 we could demonstrate that all potential glycosylation sites carry N-linked oligosaccharide residues under physiological conditions. Interestingly, complete deglycosylation did not affect enzyme activity, neither in the reductive (cortisone) nor in the oxidative (cortisol) direction. Upon overexpression in the yeast P. pastoris, 11beta-HSD 1 did not undergo glycosylation, but, in spite of this, yielded a fully active enzyme. Our results conclusively demonstrate that 11beta-HSD 1 does not need to be glycosylated to perform its physiological role as glucocorticoid oxidoreductase.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed2000

Human 11beta-hydroxysteroid dehydrogenase 1/carbonyl reductase: recombinant expression in the yeast Pichia pastoris and Escherichia coli.

Detoxification of aldehydes and ketones generally proceeds via reduction to their corresponding alcohols, which are then conjugated and eliminated. We focused our interest on 11beta-hydroxysteroid-dehydrogenase type 1 (11beta-HSD 1), a pluripotent enzyme which physiologically performs the interconversion of active and inactive glucocorticoid hormones, and which also participates in xenobiotic carbonyl compound detoxification. 11beta-HSD 1 belongs to the protein superfamily of the short-chain dehydrogenases/reductases (SDR), and has been structurally and functionally characterized. 11beta-HSD 1 is a glycosylated membrane protein which is very difficult to purify in an active state. In addition, expression levels in humans differ in a wide range. In order to facilitate biochemical and molecular studies on the significance of human 11beta-HSD 1 in detoxification processes, we have successfully performed the overexpression of recombinant human 11beta-HSD 1 in the yeast Pichia pastoris and in Escherichia coli. Recombinant 11beta-HSD 1 from E. coli was purified to homogeneity and used to generate a polyclonal antibody. The enzyme had no enzymatic activity, possibly due to the lack of glycosylation and/or incorrect folding in E. coli. In contrast, 11beta-HSD 1 overexpressed in P. pastoris was enzymatically active towards its physiological glucocorticoid substrates as well as towards xenobiotic carbonyl compounds. In western blot experiments the antibody crossreacted with both recombinant 11beta-HSD 1 forms and with the native enzyme from mouse and human liver. In conclusion, recombinant 11beta-HSD 1 from P. pastoris serves as a valuable tool for future studies on carbonyl compound detoxification.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed2000

The photodegradation of vitamins A and E in parenteral nutrition mixtures during infusion.

BACKGROUND & AIMS: Vitamins A and E are the most light-sensitive vitamins. Vitamin A is degraded by photolysis, while vitamin E degrades by photo-oxidation. The composition of the parenteral nutrition mixture and the container could therefore influence degradation during daylight administration. The aim of this study was therefore to determine the influence of fat emulsion and the type of bag on the photo-degradation of vitamins A and E in Parenteral Nutrition (PN) mixtures during simulated infusion in daylight. METHODS: Representative adult PN mixtures, with and without fat emulsion, were prepared. Samples for analysis were taken from infusates and each bag during simulated infusion. Degradation of vitamins A and E was determined by stability-indicating HPLC analysis. RESULTS: Results indicated that vitamin A loss proceeded rapidly during infusion, resulting in up to 80% loss in 6 hours, even with light protection of the bag. The presence of fat emulsion did not provide significant light protection. Vitamin E degradation was substantial if mixtures were prepared in EVA bags but was largely prevented if PN mixtures were compounded and stored in multi-layered bags. CONCLUSIONS: It is recommended that all PN bags should be light-protected during infusion in daylight. The use of multi-layered bags will prevent vitamin E losses during infusion.

Chromatography, High Pressure Liquid↗
PubMed1997

Different activation energies in glucose uptake in Saccharomyces cerevisiae DFY1 suggest two transport systems.

The analysis of initial glucose uptake in Saccharomyces cerevisiae at 25 degrees, 20 degrees, 15 degrees and 10 degrees C by computer-assisted nonlinear regression analysis predicts two transport systems. The first demonstrates Michaelis-Menten kinetics and the second shows first order behaviour. The activation energies of these two systems were calculated by the Arrhenius equation at four different growth phases, namely early exponential (EE), middle exponential (ME2), late exponential (LE) and early stationary (ES) with 2% glucose in the batch medium. The activation energies calculated from the V(m) values in EE, ME, LE and ES growth phases were 15.8 +/- 1.7, 13.5 +/- 1.0, 15.1 +/- 0.8 and 13.5 +/- 0.7 kcal/mol. These values are in agreement with activation energies calculated for the first mechanism, facilitated diffusion, which is the mechanism deduced from countertransport experiments. The activation energies derived for the second transport system from the first order rate constants in cells grown to EE, ME2, LE and ES were 8.0 +/- 2.1, 8.1 +/- 1.3, 9.6 +/- 3.0 and 7.5 +/- 2.6 kcal/mol. These values are still significantly higher than for free diffusion of glucose in water and lower as predicted for passage of glucose through the lipid phase. Therefore, we assume in addition to carrier-mediated facilitated diffusion the entrance of glucose into the cell through a pore.

Biological Transport↗
PubMed1996

Long-term stability of cimetidine in total parenteral nutrition.

The stability of cimetidine (Tagamet) was investigated in total parenteral nutrition (TPN) mixtures containing different amino acid sources. TPN mixtures were stored at 5 degrees C in ethylvinyl acetate bags for 28 days and analysed by stability-indicating high-pressure liquid chromatography. Results indicated that cimetidine was physically compatible and chemically stable (less than 5% degradation) for at least 28 days in TPN mixtures containing either Freamine III, Vamin 14 or Aminoplex 12 as the amino acid source.

Amino Acids↗
PubMed1990

Control and support: what physicians want from hospitals.

It has been asserted that physicians hold the key to success in hospital efforts to increase admissions and contain costs. While there is a great need to forge a partnership with the medical staff in achieving mutual goals, little is known about what physicians want from hospitals. A survey was completed by 177 physicians in two Cleveland-area hospitals that assessed their preferences on issues concerning hospital governance and control, hospital services, and hospital employment of physicians. Results showed that physicians want greater involvement in hospital decision making and desire services that facilitate their practice of medicine. Responses varied significantly according to physician age, specialty, HMO participation, and multiple-staff membership. Greater effort on the part of hospital administrators to assess and understand medical staff needs is suggested.

Age Factors↗
PubMed1984

A revised measure of approval motivation and its relationship to social desirability.

Existing measures of approval motivation attempt to assess this dimension of personality indirectly through evaluation of socially desirable response tendencies. The Martin-Larsen Approval Motivation (MLAM) Scale takes a more direct approach by focusing on individual differences in need for social approval. Since the original version of the MLAM scale is subject to acquiescence response bias, fully balanced and partially balanced scales were created to minimize this response style. Results indicated that the revised measures arc equivalent to the original version and that balancing affects the magnitude but not the pattern of correlates with other scales. Comparisons with the Marlowe-Crowne Social Desirability (MCSD) Scale revealed a divergent pattern of correlates with several measures of personality suggesting a basic difference between the MLAM and MCSD in their conceptualization of approval motivation.

Journal Article↗