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Biomedical subjects

J F Dunn

Publications and source records attributed to J F Dunn.

At least 91 records · Page 5Linked to original sources
PubMed1984

Plasma testosterone transport in primates.

All primate species, including Old and New World primates and prosimians have a plasma testosterone-estradiol binding globulin (TeBG), which is a glycoprotein and has a similar mobility in polyacrylamide gel electrophoresis. In New World primates the TeBG binding capacity for [3H]testosterone was higher and its affinity lower than in Old World primates. These changes were associated with high unbound plasma testosterone concentrations in these species. Binding parameters of TeBG in prosimian species varied markedly. Thus, in primate evolution TeBG was conserved despite marked differences in binding characteristics. In New World primates changes are associated with high total and unbound testosterone, a finding concordant with alterations of other steroid hormones concentration in these species with "generalized steroid hormone resistance".

Animals↗
PubMed1984

Leydig cell hypoplasia causing male pseudohermaphroditism: diagnosis 13 years after prepubertal castration.

An 11-yr-old patient with male pseudohermaphroditism who was castrated at nine days of age and raised thereafter as a female was evaluated to determine the cause of abnormal sexual differentiation. Stimulation with ACTH for 8 h revealed no abnormality in the biosynthesis of cortisol or adrenal androgens. The administration of fluoxymesterone (10 mg, orally, daily) for 5 weeks at age 13 yr led to significant decrements in serum levels of sex steroid-binding globulin and T4-binding globulin to a degree similar to that found in 2 normal men, but no change in the basally elevated levels of FSH and LH. LH bioactivity was normal in the rat Leydig cell bioassay. Skin fibroblasts cultured from a labial skin biopsy revealed normal 5 alpha-reductase activity and normal androgen receptors. Reexamination of the original testis specimens by light microscopy failed to reveal Leydig cells. Furthermore, when immunoperoxidase staining for testosterone was performed on the tissue sections, only 30-35 positive cells/10 high power fields were seen. In contrast, examination of testis sections from 4 male infants who died of other causes revealed 94-836 cells/10 high power fields that stained positively for testosterone. Although hCG stimulation testing to confirm Leydig cell hypoplasia could not be done in this patient because of previous castration, this patient demonstrates that the diagnosis can be made without it by the use of immunohistochemical stains and in vivo and in vitro tests to exclude other disorders of androgen biosynthesis or androgen action.

Adrenocorticotropic Hormone↗
PubMed1983

Metabolic adjustments to diving and recovery in the African lungfish.

The metabolic potentials of the heart, brain, white muscle, and liver in the African lungfish were estimated by enzymatic data. Metabolic effects of a 12-h submergence were monitored using metabolite measurements. Heart was the most oxidative tissue but also showed the greatest anaerobic potential. The brain displayed relatively low oxidative capabilities. White muscle remained almost inert. Although high-energy phosphate concentrations in brain and heart did not fall during submergence, glycolysis was activated as indicated by crossover plots, depletion of endogenous glycogen stores, and lactate accumulation. Blood-tissue lactate and glucose gradients indicated 1) that the heart and brain released lactate throughout submergence, 2) that after 12 h of submersion the brain and heart were probably obtaining all their required glucose from the blood, 3) that the liver released glucose throughout submergence, and 4) that white muscle was metabolically isolated from the rest of the body during submergence. It appeared that perfusion adjustments occurring during submergence were directed more toward regulating intertissue exchange of metabolites than toward oxygen conservation. Comparisons are made to diving responses in mammals.

Anaerobiosis↗
PubMed1982

Familial thyroid hormone resistance.

Three phenotypically normal family members were discovered to have elevated thyroid function (T4, free T4, T3, 123I uptake), but were clinically euthyroid. Further evaluation of pituitary and peripheral indices of thyroid hormone action was consistent with the diagnosis of peripheral resistance to thyroid hormone. Basal metabolic rate, serum cholesterol, pulse wave arrival time (QKd), and serum sex hormone binding globulin levels were all normal. Serum TSH was inappropriately elevated for the degree of thyroid hormone excess, while serum alpha subunit levels were normal. TSH responses to TRH (200 micrograms) were commensurate with the basal TSH levels, and decreases in TSH were observed after T3, dexamethasone, and bromocriptine administration. Analysis of thyroid hormone binding to an extract of mononuclear leukocyte nuclei disclosed no abnormalities. The reason for these patients' resistance to thyroid hormones remains to be elucidated. The proper diagnosis of this syndrome may be difficult. Assessment of pituitary TSH secretory dynamics and peripheral indices of thyroid hormone action should be performed in all hyperthyroxinemic patients who do not have obvious symptoms and signs of thyrotoxicosis.

Adolescent↗
PubMed1981

An ultrastructural and histochemical study of the axial musculature in the African lungfish.

Red, intermediate, and white axial muscle fibres of African lungfish were studied using histochemical techniques and electron microscopy. Gross dissection revealed the presence of a small wedge of red coloured muscle along the lateral line. This wedge was shown by histochemical demonstrations of lactate and succinate dehydrogenases, of adenosine triphosphatases, and of lipid to be composed of a mosaic of red and intermediate fibres measuring 23.63 and 34.30 micrometer in average diameter, respectively. The bulk of the myotome was composed of white fibres having an average diameter of 67.35 micrometer. Mitochondrial density, capillarity and lipid content were very low for all fibres. These data suggest that the axial musculature is geared primarily for anaerobic function. The mosaic arrangement of fibres, and the lack of a subsarcolemmal band of mitochondria suggests that the lungfish have a muscle organisation that is transitional between lower vertebrates and amphibians.

Adenosine Triphosphatases↗
PubMed1981

Transport of steroid hormones: binding of 21 endogenous steroids to both testosterone-binding globulin and corticosteroid-binding globulin in human plasma.

This report describes a model of steroid transport in human plasma. The binding affinities of 21 endogenous steroids for both testosterone-binding globulin (TeBG) and corticosteroid-binding globulin (CBG) were determined under equilibrium conditions using a solid phase method at physiological pH and temperature. A computer program was used to solve the complex equilibrium interactions between these steroids and TeBG, CBG, and albumin. In this manner, we calculated the plasma distribution of each steroid into TeBG-bound, CBG-bound, albumin-bound, and unbound fractions in normal men, normal women during both the follicular and luteal phases of the ovarian cycle, and women during the third trimester of a normal pregnancy.

Adrenal Cortex Hormones↗
PubMed1981

Transport of steroid hormones: interaction of 70 drugs with testosterone-binding globulin and corticosteroid-binding globulin in human plasma.

This report describes the binding of 70 synthetic compounds to both testosterone-binding globulin (TeBG) and corticosteroid-binding globulin (CBG). The ability of each compound to displace [3H]testosterone from TeBG and [3H]cortisol from CBG adsorbed from a plasma pool onto a solid phase matrix of Concanavalin A-Sepharose was determined under equilibrium conditions at physiological pH and temperature. From these data, the association constants of the compounds for binding to both TeBG and CBG were calculated and used to predict whether endogenous steroid transport would be altered by the therapeutic administration of the drug. Computer simulation predicted that by interacting with TeBG, therapeutic levels of danazol, methyltestosterone, fluoxymesterone, and norgestrel could displace 83%, 48%, 43%, and 16%, respectively, of the concentration of testosterone bound to TeBG in a normal man. Similarly, by interacting with CBG, therapeutic levels of prednisolone could decrease the concentration of cortisol bound to CBG by approximately 32% in both men and women, and despite relatively low affinity binding to TeBG (5 X 10(5) M-1), prednisolone could also displace small amounts of testosterone from TeBG. These results indicate that binding to steroid transport proteins should be considered among the in vivo effects of drugs on endogenous steroid hormone levels.

Binding, Competitive↗
PubMed1980

Testosterone-estradiol binding globulin binds to 2-methoxyestradiol with greater affinity than to testosterone.

This report describes the unexpected observation that testosterone-estradiol binding globulin (TeBG) binds 2-methoxyestradiol better than it binds either testosterone or 17 beta-estradiol. As determined by competitive displacement of 3H-testosterone from TeBG adsorbed onto a solid phase matrix of Con A-Sepharose, the relative binding activities of 2-methoxyestradiol, testosterone and 17 beta-estradiol for TeBG were 2.0, 1.0 and 0.32, respectively. In contrast, 2-methoxyestradiol, which is known to bind with low affinity to estrogen receptors, had only low affinity binding to the androgen receptor, as determined by competitive displacement of 3H-dihydrotestosterone using 64-24 rat mammary tumor cells. 2-Methoxyestradiol is the first example of a naturally occurring steroid which binds with high affinity to TeBG but with low affinity to both androgen and estrogen receptors.

2-Methoxyestradiol↗
PubMed1979

Measurement of the testosterone binding parameters for both testosterone-estradiol binding globulin and albumin in individual serum samples.

This report describes a solid phase method for the characterization of testosterone binding to both albumin and testosterone-estradiol binding globulin (TeBG). TeBG is adsorbed from serum samples onto a solid phase matrix of concanavalin A covalently linked to 4B Sepharose. The binding of testosterone is then examined both in the presence and absence of the endogenous serum albumin. Analysis of the resulting Scatchard plots permits determination of the TeBG binding capacity, TeBG association constant and a parameter of albumin binding equivalent to the product of its affinity and capacity for binding testosterone. Results showed that the TeBG capacity was lower in men than in women (18.4 +/- 5.8 vs. 33.1 +/- 19.2 nM, p less than 0.01). The association constant was greater in men (1.59 +/- 0.35 vs. 1.19 +/- 0.32 x 10(9)M-1, 10(9)M-1, p less than 0.01). There was no difference in the albumin binding parameter (43.8 +/- 18.3 vs. 46.6 +/- 15.5, NS). These parameters can then be used to calculate the distribution of the circulating testosterone into albumin bound, TeBG bound and unbound fractions.

Adult↗
PubMed1977

Genetic control of renin activity in the submaxillary gland of the mouse.

Administration of androgen to female mice is known to increase the level of several proteins in the submaxillary gland, including nerve growth factor, epidermal growth factor, esteroproteolytic activity, and renin. In the present study, renin activity has been assessed in extracts of submaxillary gland of female mice from two inbred strains (SWR/J and C57BL/10J), from F1 and F2 hybrids, and from backcrosses between F1 and parental strains. In both uninduced and induced mice, renin activity of submaxillary gland was more than 100-fold greater in SWR/J than in C57BL/10J mice as measured by either an enzymatic assay or an immunodiffusion method. This difference was not due to differences in plasma testosterone levels between the strains, and the enzymes from the two strains had similar pH optima, substrate specificities, heat stabilities, and apparent Michaelis constants. In the submaxillary gland the difference was relatively specific for renin because increases in esteroproteolytic activity, nerve growth factor, and epidermal growth factor after androgen treatment appeared to be similar in both strains. Studies with the various hybrids indicate that the difference in renin activity between the two strains is apparently due to a single regulatory gene.

Animals↗
PubMed1975

Consistency and change in styles of mothering.

The idea that the immediate postpartum period is particularly important for the developing relationship between mother and child is being increasingly discussed; however, little is known of the long-term significance of the individual differences in adjustment found in this period. A longitudinal study of 70 mother-baby pairs showed that difficulities during feeds were related to longer labour and to measures of the baby's state at birth. Differences between babies in the latency with which they responded by crying to interruption of sucking (in tests of non-nutritive sucking) were also related to the smoothness of the feed. Measures of affectionate maternal behaviour were associated with differences between babies in sucking rate, and were not influenced by labour and delivery. During later observations (8-30 weeks), strong consistency in individual differences across age was found in the levels of maternal touching, vocalizing, and responsiveness to baby's vocalizing. Maternal affectionate contact during early feeds (babies up to 10 days old) was related to these later maternal measures for breast-fed babies. Other aspects of coordination and warmth in the early feeds did not correlate with later measures, which suggested that predictions based on observations early in the neonatal period should be made with caution. Measures of maternal response to crying showed little consistency across the first seven months and were influenced by how much the baby cried at earlier ages.

Age Factors↗
PubMed1975

Developmental study of androgen responsiveness in the submandibular gland of the mouse.

The development of androgen responsiveness in the submandibular gland of normal and androgen-resistant (Tfm) mice of different ages was studied after varying hormonal treatments. Total esteroproteolytic (tamase) activity of submandibular gland homogenates was used as a marker for androgen action. Newborn mice of all four genotypes (normal male, normal female, carrier Tfm females, and Tfm males) were resistant to androgen. However, at 3 weeks of age the capacity to develop a tamase response appears in normal and carrier Tfm animals given androgen and rapidly rise to maximal levels. The level in the normal animal is regulated thereafter primarly by the level of circulating androgen. In contrast, the tamase response in the Tfm male of all ages and under all androgen regimens was minimal.

Aging↗
PubMedDate not supplied

Fat suppression at 7T using a surface coil: application of an adiabatic half-passage chemical shift selective radiofrequency pulse.

The selective suppression of fat using chemical shift selective (CHESS) sinc, gaussian presaturation, or binomial radiofrequency pulses are widely implemented techniques in magnetic resonance imaging. For applications wherein transmitter coils that generate inhomogeneous magnetic (B1), fields are used (e.g., surface coils), adiabatic radiofrequency pulses that are less susceptible to spatial variations in B1 amplitude will improve the spatial homogeneity of spin excitation angle. Herein, we describe the application of an adiabatic half-passage hyperbolic secant CHESS pulse suitable for acquiring fat-suppressed magnetic resonance images with surface coils on high-field systems. Images obtained from a water/fat phantom and from the abdominal region of a rat are presented indicating excellent suppression of fat signal from the entire coil-sensitive volume.

Abdomen↗
PubMedDate not supplied

Depth selective quantification of phosphorus metabolites in human calf muscle.

We have used phase modulated rotating frame imaging, a depth selective NMR technique, in conjunction with two methods of calibration, in order to determine the feasibility of quantifying phosphorus compounds in selected regions of a biological sample. In one method, we related peak areas obtained from a sample to the peak area of an external reference located within the receiver coil, previously calibrated against a standard. In the second method we measured peak areas from a standard separately and related them directly to the area of the sample peak. We examined the calf muscles of male volunteers, positioning the coil to obtain signal mainly from the gastrocnemius in the shallow slices and soleus in the deep slices. The concentrations of Pi, phosphocreatine and ATP (in mmol/kg tissue) were 3.0 +/- 0.5, 18 +/- 2 and 4.8 +/- 0.2 at 2 cm depth (mean +/- SD; n = 5). These results are similar to published biopsy data. A comparison with published values obtained from other NMR quantification methods suggests that, while it is possible to obtain consistent results within one laboratory, it is not currently possible to obtain similar results between laboratories. This is evident from the fact that different laboratories report different phosphocreatine/ATP ratios, indicating that the techniques are limited by variations in the processes of data collection and peak area measurement.

Adenosine Triphosphate↗