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Biomedical subjects

D J Morton

Publications and source records attributed to D J Morton.

At least 37 records · Page 2Linked to original sources

Thyroid hormone use and bone mineral density in elderly men.

BACKGROUND: Excessive thyroid hormone use reduces bone density in women. Thyroid hormone use is much less common in men, who also have less osteoporosis. We examined bone mineral density in a community-based sample of elderly men who reported long-term thyroid hormone use. METHODS: All 685 white men aged 50 to 98 years from a Southern California community who participated in a study of osteoporosis were examined. Medication use was validated. Height and weight were measured. Bone mineral density was measured at the ultradistal radius and midshaft radius using single photon absorptiometry and at the hip and lumbar spine using dual energy x-ray absorptiometry. RESULTS: Thirty-three men taking a mean thyroxine-equivalent dose of 130 micrograms daily for an average of 15.5 years were compared with 653 nonusers. There were no significant differences in bone density at any site between users and nonusers, before or after controlling for age, body mass index, smoking, thiazide diuretics, and oral corticosteroid use. Bone density also did not differ according to thyroid hormone type, duration of use, or use of suppressive dose adjusted for body weight. CONCLUSIONS: Long-term thyroid hormone use was not associated with adverse effects on bone mineral density in men.

Aged↗

Plasma cortisol as an indicator of stress due to capture and translocation in wildlife species.

Plasma cortisol concentrations were determined by radioimmunoassay in 712 individual animals of 18 wildlife species after either physical or chemical restraint, tranquillisation or trauma, in order to define baseline values and to assess the possibility of using cortisol as an indicator of stress. The cortisol levels appeared to rise after capture in all the species examined except the Cape buffalo. On the basis of the plasma cortisol levels, chemical capture was less stressful than physical restraint. Animals which were tranquillised had lower than 'normal' cortisol levels, whereas animals that had suffered trauma or which died after they were captured had higher than normal cortisol levels.

Animals↗

Inhaled and oral corticosteroids: their effects on bone mineral density in older adults.

Use of oral and inhaled corticosteroids and bone mineral density were examined cross-sectionally in 1673 community-dwelling white subjects aged 56 to 91 years. Bone mineral densities at the ultradistal and midshaft radii, hip, and lumbar spine were compared in users of inhaled (n = 34) and oral (n = 44) corticosteroids and nonusers. Women who used oral corticosteroids had significantly lower bone mineral densities at the midshaft radius, hip, and spine than never users. Women who used inhaled corticosteroids had bone mineral densities at the ultradistal radius, hip, and spine that were intermediate between those of oral corticosteroid users and those of never users. Bone mineral density did not vary significantly according to corticosteroid use in men.

Absorptiometry, Photon↗

Thiazides and bone mineral density in elderly men and women.

The relation of bone mineral density of the ultradistal radius, midshaft radius, hip, and lumbar spine to thiazide use were examined in a community-based sample of 1,696 white men and women aged 44-98 years. Male thiazide users had higher age-adjusted bone mineral density levels only at the midshaft radius (p < 0.05). Among women, thiazide users had significantly higher bone mineral density levels at all four sites (p < 0.05), both before and after controlling for the effects of age, body mass index, smoking, and estrogen use. The association was explained by current thiazide use; no significant association was found between past use or duration of use and bone mineral density levels. Results were similar when hypertensive women were excluded from the analyses, suggesting the effect was drug-related and not due to hypertension or some other factor related to hypertension. At all sites, the highest bone mineral density levels were seen in women currently using both estrogen and thiazide. Overall, these findings suggest that thiazides may be useful in the prevention of osteoporosis in postmenopausal women.

Adult↗

Binding of human hemoglobin by Haemophilus influenzae.

Binding of biotinylated human hemoglobin to Haemophilus influenzae was detected when organisms were grown in heme-deplete, but not heme-replete, conditions. Hemoglobin binding was completely inhibited by a 100-fold excess of unlabelled human hemoglobin or human hemoglobin complexed with human haptoglobin. Binding was only partially inhibited by rat hemoglobin, bovine hemoglobin, human globin, and bovine globin, and not at all by heme, human serum albumin, bovine serum albumin, human transferrin, or myoglobin. Hemoglobin binding was saturable at 16-20 ng of hemoglobin per 10(9) cfu. Binding of human hemoglobin was detected in serotypes a-f and serologically non-typable strains of H. influenzae, as well as Haemophilus haemolyticus but not Haemophilus parainfluenzae, Haemophilus aphrophilus, Haemophilus parahaemolyticus, or Escherichia coli.

Animals↗

Thyroid hormone use and bone mineral density in elderly women. Effects of estrogen.

OBJECTIVE: To determine the effect of long-term use of thyroid hormone on bone mineral density (BMD) in elderly women and the potential mitigating effects of estrogen replacement therapy. DESIGN: Cross-sectional, community-based study. SETTING: Rancho Bernardo, Calif. PARTICIPANTS: A total of 991 white women aged 50 to 98 years who participated in a study of osteoporosis. MAIN OUTCOME MEASURES: Bone mineral density at the ultradistal radius and midshaft radius using single-photon absorptiometry and at the hip and lumbar spine using dual-energy x-ray absorptiometry. RESULTS: A total of 196 women taking thyroid hormone for a mean duration of 20.4 years were compared with 795 women who were not using thyroid hormone. Women taking daily thyroxine-equivalent doses of 200 micrograms or more had significantly lower BMD levels at the midshaft radius and hip compared with those taking less than 200 micrograms. Daily doses of 1.6 micrograms/kg and greater were associated with lower bone mass at all four sites compared with nonuse, whereas doses less than 1.6 micrograms/kg were not associated with lower BMD levels. These associations were independent of age, body mass index, smoking status, and use of thiazides, corticosteroids, and estrogen. Women taking both estrogen and a thyroid hormone dose of 1.6 micrograms/kg or greater had significantly higher BMD levels at all four sites than women taking the same thyroid hormone dose alone. Women taking both thyroid hormone and estrogen had BMD levels comparable with those observed in women taking only estrogen. CONCLUSIONS: Long-term thyroid hormone use at thyroxine-equivalent doses of 1.6 micrograms/kg or greater was associated with significant osteopenia at the ultradistal radius, midshaft radius, hip, and lumbar spine. Estrogen use appears to negate thyroid hormone-associated loss of bone density in postmenopausal women.

Absorptiometry, Photon↗

Hydroxyindole-O-methyltransferase activity in the pineal gland of the muskox (Ovibos moschatus).

Characteristics of hydroxyindole-O-methyltransferase (HIOMT) activity were examined in pineal gland tissue from 10 muskoxen shot by native hunters in November, 1990. The enzyme preferentially methylated N-acetylserotonin, with other hydroxyindole compounds showing relatively low affinities; activity peaked sharply at pH 8.2. HIOMT was noncompetitively inhibited by its substrate, N-acetylserotonin, and competitively inhibited by its product S-adenosylhomocysteine. The catalytic mechanism appeared to be ordered as described in previous studies: S-adenosylmethionine was the obligatory first substrate, followed by N-acetylserotonin; methyl transfer then occurred and the products, melatonin and S-adenosylhomocysteine, were released sequentially. Interestingly, the inhibition constant (Ki) for N-acetylserotonin was relatively close to the Michaelis-Menten constant (Km), which might allow physiological concentrations of N-acetylserotonin to inhibit HIOMT activity in vivo. This effect could be relevant to the ecology of free-living muskoxen during the dramatic seasonal fluctuations in dietary protein and daily photoperiod associated with their arctic habitat.

Acetylserotonin O-Methyltransferase↗

Thiazide-associated metabolic abnormalities and estrogen replacement therapy: an epidemiological analysis of postmenopausal women in Rancho Bernardo, California.

The objective of this study was to identify abnormalities in lipid and carbohydrate metabolism in women taking thiazide diuretics and determine whether these abnormalities are mitigated by concurrent postmenopausal estrogen replacement therapy. The study design was cross-sectional; its setting was Rancho Bernardo, an upper middle-class community in southern California. The subjects included 1047 white nondiabetic postmenopausal women, aged 50-89 yr, categorized by the use of thiazide diuretic, estrogen replacement therapy, both, or neither. Medical history including behavior, verified medication use, height, weight, fasting chemistry and lipid panels, and a standardized oral glucose tolerance test with fasting and 2-h plasma glucose and serum insulin levels were determined. Compared with nonusers, women taking thiazides had significantly lower high density lipoprotein cholesterol levels and significantly higher fasting triglyceride, glucose, and insulin levels. Concomitant use of thiazide and estrogen yielded lipid profiles and fasting glucose and insulin levels similar to those of subjects receiving estrogen alone, i.e. elevated high density lipoproteins, decreased low density lipoproteins, and lower levels of fasting glucose and insulin compared with those in nonusers. However, thiazide-associated postchallenge glucose and insulin elevations were not modified by estrogen. These patterns were not explained by differences in age, body mass index, exercise, smoking, alcohol use, type or dose of thiazide diuretic, type of estrogen replacement, or serum potassium levels. We conclude that postmenopausal estrogen use masks thiazide-associated dyslipidemia and fasting elevations in glucose and insulin levels, but does not improve thiazide-associated postchallenge glucose intolerance and hyperinsulinemia. Modification of most of the untoward metabolic effects of thiazides in women taking postmenopausal estrogen could provide a new incentive for the use of this traditional antihypertensive in elderly women.

Aged↗

The use of evaporative cooling to extend the shelf life of reconstituted oral penicillin solutions.

The relationship between temperature and the degradation of reconstituted penicillin solutions was evaluated. In all cases storage at temperatures of 25 degrees C or less was sufficient to maintain penicillin stability within acceptable pharmacopoeial limits for 5 days. In addition, the relationship between humidity and dry bulb temperature was examined in order to assess the use of evaporative cooling in lowering the temperature of penicillin solutions in those areas of the country where temperatures commonly exceed 25 degrees C. The results of this study suggest that, with the use of evaporative cooling, penicillin solutions can be maintained in a stable state for a 5-day period without the need for refrigeration.

Administration, Oral↗

Comparison of the effectiveness of two oral phenytoin products and chronopharmacokinetics of phenytoin.

A cross-over study was carried out in 14 epileptic patients to compare the steady-state serum phenytoin concentrations produced by two phenytoin formulations (Phenytoin Sodium and Epanutin). Differences in steady-state phenytoin concentrations following a change from one product to the other were not significant, indicating that the two brands manifest equivalent therapeutic efficacy. The results suggest that no overall dosage adjustments are required when switching from one brand to the other. Chronopharmacokinetic parameters of a single 300-mg dose of phenytoin, given at 08.00 and 20.00 hours, were studied in 10 healthy, male volunteers under controlled conditions. No evidence was found that circadian rhythms influenced absorption and disposition.

Administration, Oral↗

Expression of the Haemophilus influenzae transferrin receptor is repressible by hemin but not elemental iron alone.

The absolute requirement for elemental iron and the porphyrin nucleus for growth of Haemophilus influenzae led us to investigate the role of iron and hemin in regulation of expression of the H. influenzae transferrin receptor. H. influenzae type b strain H1689 was grown in brain heart infusion broth supplemented with beta-NAD and either 10 or 0.1 microgram of hemin ml-1. Transferrin-binding ability was determined with a dot blot assay using human transferrin-horseradish peroxidase conjugate. Cells grown in media with 0.1 microgram of hemin ml-1 bound transferrin, but organisms grown in media with 10 micrograms ml-1 did not. In hemin-restricted media, transferrin binding occurred despite addition of up to 10 mM ferric nitrate, ferric citrate, or ferric PPi, whereas addition of 10 micrograms of hemoglobin ml-1 repressed expression. The breadth of species distribution of this mode of regulation was determined with strains previously characterized by multilocus enzyme electrophoresis. When grown in hemin-restricted media, 24 of 28 type b strains and 52 of 57 serologically nontypeable strains exhibited transferrin binding, although none did so in hemin- and iron-sufficient media. Strain H1689 and serologically nontypeable strain HI1423 grown in heat-inactivated pooled normal human serum, human cerebrospinal fluid, or human breast milk exhibited transferrin binding. Growth in these fluids with 10 micrograms of added hemin ml-1 abolished transferrin binding, whereas addition of 10 mM ferric nitrate did not. These data suggest that the transferrin receptor of H. influenzae is regulated by levels of hemin but not elemental iron alone and that this property is widely distributed among several major cloned families in the species.

Haemophilus influenzae↗

Pulsed static magnetic field effects on in-vitro pineal indoleamine metabolism.

In-vitro rat pineal glands stimulated with the beta-adrenergic receptor agonist isoproterenol to induce melatonin synthesis and exposed for 1 h to a pulsed 0.4-G static magnetic field demonstrated significant inhibition of serotonin-N-acetyltransferase activity and melatonin content. 2-h exposure to pulsed magnetic field also resulted in a significant reduction in isoproterenol-induced serotonin-N-acetyltransferase activity. These results support the idea that the cultured pineal gland can be affected directly by artificially generated weak magnetic fields.

Animals↗

Effect of change in vehicle composition on ophthalmic bioavailability of benzylpenicillin.

The stability and bioavailability of benzylpenicillin ophthalmic solutions were determined at pH 5, 6, 6.5, 7 and 8 in citrate buffer. The stability of benzylpenicillin solutions stored at room temperature was greatest at pH 6.6-7 while at 2-4 degrees C stability was greatest at pH 6.5. The uptake by corneal and aqueous humour of benzyl [14-C] penicillin into ovine eyes was greatest at a pH of 6.5, which indicates that for optimum stability and bioavailability benzylpenicillin ophthalmic solutions should be prepared in citrate buffer at pH 6.5. Under these conditions the stability of the refrigerated preparation is acceptable for a normal treatment period.

Animals↗

Primary structure of ovine apolipoprotein C-II and the production of antibodies directed towards a synthetic fragment (residues 46-59).

Two distinct activator proteins for lipoprotein lipase were isolated from ovine plasma and purified to homogeneity by reverse phase HPLC. The two proteins were partially sequenced (up to residue 59) and the results show that they are identical except that 6 residues were missing from the N-terminal of the smaller protein. The complete sequence of the proteins has been deduced from amino acid composition studies and by comparison with the sequence information available from other species. Antibodies were produced in BALB/c mice to a synthetic peptide corresponding to a highly hydrophilic region (residues 46-59) of the activator protein. The antibodies cross-reacted with the two forms of activator and with ovine lipoproteins. This work with a synthetic fragment of ovine activator protein confirms that the technique is useful for investigating antibody production and specificity directed against native lipoproteins.

Amino Acid Sequence↗

Prevalence of alcohol consumption among older persons.

Percent prevalences of alcohol consumption were determined in a cross-sectional study of randomly chosen residents of San Diego County, California aged 45 years and over. The study sample (N = 2,105) showed statistically significant drinking differences between Whites (n = 819), Blacks (n = 629), and Mexican-Americans (n = 657). Overall, the highest prevalence of drinking occurred among the White elderly. The common belief that socioeconomic conditions are inversely associated with a high prevalence of drinking was not supported in this sample. Statistically significant differences in age-specific and sex-specific percent prevalences of alcohol intake were also found. There was a generally decreasing prevalence of alcohol consumption with advancing age, which existed regardless of ethnicity. Initial empirical measures and a better understanding of drinking correlates will identify those elderly persons at risk and provide the basis for future interventions in the areas of applied epidemiology and health promotion.

Black or African American↗

Utilization of enterobactin and other exogenous iron sources by Haemophilus influenzae, H. parainfluenzae and H. paraphrophilus.

The ability of Haemophilus influenzae, H. parainfluenzae and H. paraphrophilus to utilize iron complexes, iron-proteins and exogenous microbial siderophores was evaluated. In a plate bioassay, all three species used not only ferric nitrate but also the iron chelates ferric citrate, ferric nitrilotriacetate and ferric 2,3-dihydroxybenzoate. Each Haemophilus species examined also used haemin, haemoglobin and haem-albumin as iron sources although only H. influenzae could acquire iron from transferrin or from haemoglobin complexed with haptoglobin. None of the haemophili obtained iron from ferritin or lactoferrin or from the microbial siderophores aerobactin or desferrioxamine B. However, the phenolate siderophore enterobactin supplied iron to both H. parainfluenzae and H. paraphrophilus, and DNA isolated from both organisms hybridized with a DNA probe prepared from the Escherichia coli ferric enterobactin receptor gene fepA. In addition, a monospecific polyclonal antiserum raised against the E. coli 81 kDa ferric enterobactin receptor (FepA) recognized an iron-repressible outer membrane protein (OMP) in H. parainfluenzae of between 80 and 82 kDa (depending on the strain). This anti-FepA serum did not cross-react with any of the OMPs of H. paraphrophilus or H. influenzae. The OMPs of each Haemophilus species were also probed with antisera raised against the 74 kDa Cir or 74 kDa IutA (aerobactin receptor) proteins of E. coli. Apart from one H. parainfluenzae strain (NCTC 10665), in which an OMP of about 80 kDa cross-reacted with the anti-IutA sera, no cross-reactivity was observed between Cir, IutA and the OMPs of H. influenzae, H. parainfluenzae or H. paraphrophilus.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Outer Membrane Proteins↗

Siderophore-independent acquisition of transferrin-bound iron by Haemophilus influenzae type b.

The specificity by which Haemophilus species acquired iron from transferrin (TF) was investigated. In a plate bioassay H. influenzae used iron bound to human, bovine and rabbit TFs but not mouse, rat, dog, horse, guinea-pig, pig or ovo- TFs or human and bovine lactoferrins. In contrast, H. pleuropneumoniae used iron only from pig TF whilst H. parainfluenzae was unable to utilize iron bound to any of the human or animal TFs tested. The inhibition of growth imposed on H. influenzae type b strain Eagan by the addition of the synthetic iron chelator EDDA to the culture medium was reversed by 30% iron-saturated human TF added directly to the medium but not when the TF was contained inside a dialysis bag. Dot-blotting of whole cells revealed that human TF bound to the surface of bacteria cultured in iron-restricted but not in iron-plentiful media. Incubation of whole bacterial cells in the presence of the proteolytic enzyme trypsin also abolished TF-binding activity, suggesting that the TF receptor was a protein. In competition dot blotting experiments, human and bovine but not rabbit, dog, mouse or guinea-pig TFs blocked the binding of a horseradish peroxidase--human TF conjugate. SDS-PAGE and Western blotting of outer membranes revealed the presence of a TF-binding protein of approximately 72 kDa. These results suggest that the acquisition of TF-bound iron by H. influenzae type b probably involves a direct interaction with an outer-membrane protein which shows some TF-species specificity.

Animals↗