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Biomedical subjects

M J Schmidt

Publications and source records attributed to M J Schmidt.

At least 37 records · Page 2Linked to original sources
PubMed1984

Testosterone and dihydrotestosterone concentrations in elephant serum and temporal gland secretions.

Serum and temporal gland secretions (TGS) were obtained from mature wild African (Loxodonta africana) and captive Asian elephants (Elephas maximus). Samples were obtained from five cows and eight bulls culled for management purposes in Kruger National Park, South Africa, and from four females and two males residing at the Washington Park Zoo, Portland, Oregon. Our purpose was to describe the levels of the androgens, testosterone (T), and dihydrotestosterone (DHT), and to correlate these observations with sex, species and behavioral status. Male-female differences in serum T were pronounced in the Asian species, whereas male and female concentrations overlapped in the African elephant serum. Serum T concentrations in African females were greater than in Asian females. Serum DHT reflected T levels, except that the striking elevation of testosterone in Asian bulls during musth was not paralleled by equal increases in DHT levels. A species difference observed among males was higher serum T levels in nonmusth Asian bulls (1.84-5.35 ng/ml) compared to the levels in African bulls (0.38-0.68 ng/ml), except for one dominant African bull (6.64 ng/ml). This single African value was still considerably lower than the serum T values of the Asian males during musth. These musth values were the highest serum androgen concentrations: T was between 19 and 40 ng/ml (average 26.10 ng/ml). The TSG values of T and DHT were much higher than serum levels except in the Asian female. T/DHT ratios in TGS were more similar than in serum. One dominant African bull had a T TGS value of 78 ng/ml, which was much higher than the rest of the African males or females, but considerably lower than as Asian bull in musth (547 ng/ml). It seems apparent that a change in androgen status as reflected in serum and TGS levels of T and DHT precedes or is concomitant with overt alteration in behavior in the Asian male. The temporal gland appears to actively concentrate androgens in both African males and females, but in the Asian male the gland secretes only during musth when the greatest concentration of both T and DHT were observed. The apparent difference in the degree of temporal gland secretory activity between the two species suggests a more specific communicative function within the Asian male.

Animals↗
PubMed1984

Pharmacologic analysis of two novel inhibitors of leukotriene (slow reacting substance) release.

LY83583 , a quinolinedione , and LY151364 , a quinoxalinedione , were developed as inhibitors of leukotriene (slow reacting substance of anaphylaxis) release. They preferentially inhibited the release of leukotrienes over histamine from fragmented guinea-pig lung and rat peritoneal cells in vitro, regardless of whether the mediators were released immunologically by antigen or chemically by the divalent cationic ionophore, A23187. Similar results were obtained with rat peritoneal cells in vivo. In that system, comparison of LY83583 with disodium cromoglycate showed the former to preferentially inhibit release of leukotrienes, whereas the latter favored inhibition of histamine release. LY83583 did not significantly decrease antigen-induced bronchospasm in guinea pigs after i.v. administration of doses that approached toxic levels. In addition, LY83583 did not antagonize contractions to carbachol or histamine on guinea-pig trachea, prostaglandin F2 alpha-elicited contraction on guinea-pig ileum or contractions produced by serotonin on guinea-pig aorta. This agent, at 1 X 10(-5) M, reduced the maximal responses to bradykinin on ileum and caused a rightward displacement with a reduction in the maximal response to norepinephrine on guinea-pig aorta. In summary, LY83583 and LY151364 have interesting pharmacologic profiles which make them useful as tools in understanding the role of the leukotrienes in isolated tissue systems.

Aminoquinolines↗
PubMed1983

Dopamine agonist-induced hyperglycemia in rats: structure-activity relationships and mechanisms of action.

The concentration of blood glucose was measured in rats after administration of a number of drugs characterized as dopamine agonists. Compounds that cause release of dopamine, or agents that block the reuptake of dopamine, did not elevate blood glucose. Some direct dopamine receptor stimulants (lergotrile, bromocriptine, apomorphine) caused hyperglycemia, but other agonists (e.g. pergolide) did not. Further experiments with lergotrile, the most active hyperglycemic dopamine agonist, revealed that the blood glucose increase was accompanied by a marked elevation in liver glycogen, indicating a gluconeogenic effect of the compound. This hypothesis was supported by using inhibitors of gluconeogenesis (L-tryptophan or 3-mercaptopicolinic acid) to block lergotrile's hyperglycemic action. Structure-activity relationships among close analogues of lergotrile suggest that the cyano moiety in the lergotrile molecule may be of importance in the hyperglycemic action of lergotrile. These results indicate that central dopamine stimulation per se does not cause hyperglycemia in rats.

Animals↗
PubMed1982

Dopamine deficiency in the weaver mutant mouse.

The dopamine system in weaver mutant mice (B6CBA-Aw-J/A background) was studied. Dopamine was 27% lower in the olfactory tubercle, 77% lower in the frontal cortex, and 75% lower in the striatum of 6-month-old weaver mice compared to control mice of the same age. Norepinephrine and serotonin were not lower in these brain areas. Tyrosine hydroxylase activity in the striatum was measured with a radiometric assay and was 70% lower in weaver mice. Examination of mice from 11 to 180 days of age revealed that the dopamine system failed to develop in weaver mice. Motor activity in individual animals was assessed using circular photocell activity cages with minimal illumination. Apomorphine and pergolide, direct dopamine agonists, increased activity more in weaver mice than in normal littermates. Amphetamine, which releases endogenous stores of dopamine, was less active in mutant mice. These findings provide suggestive evidence that postsynaptic dopamine receptors in weaver mutants might have become supersensitive as a result of lower levels of dopamine in motor areas of the brain. Anatomical evidence of dopamine system abnormalities was found in weaver mice by examination of serial sections cut from the midbrain of mutant and normal mice. The pars compacta of the substantia nigra in weaver mice appeared hypocellular when compared with the corresponding sections from controls. Fewer large neurons were seen in the affected animals. This study illustrates that weaver mice have specific deficiencies in the dopamine system. The weaver mouse might provide a way of examining the biochemical and behavioral effects of long term dopamine deficiency and a way to examine drugs to treat dopamine-deficient states in vivo.

Animals↗
PubMed1981

Human brain protein phosphorylation in vitro: cyclic AMP stimulation of electrophoretically-separated substrates.

In vitro phosphorylation of electrophoretically-separated brain proteins was studied in human frontal cortex obtained 3-16 h post-mortem from 13 patients ages 3 days-82 years with extensive, mild or no neuropathological involvement. In 12 of the 13 cases, cyclic AMP increased incorporation of phosphate into acid-precipitable protein. Analysis of the autoradiographic profiles of separate proteins indicated that phosphorylation of the doublet of molecular weight 86-80,000 was stimulated by cyclic AMP in certain samples. This doublet corresponded to the cyclic AMP stimulated doublet from rat frontal cortex we have termed band D-1,2 (proteins Ia and Ib of Ueda and Greengard). Of special interest was the fact that, while co-migration was observed in the other phosphoprotein bands studied, band D-1,2 of humans consistently migrated slightly less than rat protein band D-1,2. This difference was not a function of post-mortem time, subcellular fraction or buffer used in the reaction phosphorylation assay. The use of post-mortem tissue was not a contributing factor as the retardation in band D-1,2 migration was still observed when post-mortem rat brain was used for comparison. In two human post-mortem samples, there was no measureable band D-1,2 phosphorylation even in the presence of cyclic AMP. This was the case in both homogenate and crude synaptosome/mitochondrial preparations. Band F-1 (mol. wt. = 47,000) was not observed in any of the human samples studied. This is consistent with prior studies in rat which show that band F-1 phosphorylation is not detected in post-mortem brain, Band F-2 (mol. wt. 41,000) recently identified as pyruvate dehydrogenase, was lightly phosphorylated under the reaction conditions used in this study.

Aged↗
PubMed1981

Purkinje cell loss and the noradrenergic system in the cerebellum of pcd mutant mice.

Purkinje cells in the cerebellum receive inhibitory noradrenergic input from the locus coeruleus. In pcd mutant mice all Purkinje cells degenerate by 45 days of age. The purpose of the present studies was to determine if the loss of these cerebellar neurons affects the amounts of norepinephrine in the cerebellum of mice 25-280 days of age. No significant changes in norepinephrine content were detected during or after Purkinje cell degeneration. However, since degeneration led to a reduction in cerebellar weight, the norepinephrine concentration was increased in pcd mutants. These results indicate that despite the loss of a major postsynaptic target (Purkinje cells), the cerebellar noradrenergic input remains stable.

Age Factors↗
PubMed1981

The uptake of carnitine by slices of rat cerebral cortex.

The properties of carnitine transport were studied in rat brain slices. A rapid uptake system for carnitine was observed, with tissue-medium gradients of 38 +/- 3 for L-[14CH3]carnitine and 27 +/- 3 for D-[14CH3]carnitine after 180 min incubation at 37 degrees C in 0.64 mM substrate. Uptake of L- and D-carnitine showed saturability. The estimated values of Km for L- and D-carnitine were 2.85 mM and 10.0 mM, respectively; but values of Vmax (1 mumol/min/ml intracellular fluid) were the same for the two isomers. The transport system showed stereospecificity for L-carnitine. Carnitine uptake was inhibited by structurally related compounds with a four-carbon backbone containing a terminal carboxyl group. L-Carnitine uptake was competitively inhibited by gamma-butyrobetaine (Ki = 3.22 mM), acetylcarnitine (Ki = 6.36 mM), and gamma-aminobutyric acid (Ki = 0.63 mM). The data suggest that carnitine and gamma-aminobutyric acid interact at a common carrier site. Transport was not significantly reduced by choline or lysine. Carnitine uptake was inhibited by an N2 atmosphere, 2,4-dinitrophenol, carbonylcyanide-N-chlorophenylhydrazone, potassium cyanide, n-ethylmaleimide, and ouabain. Transport was abolished by low temperature (4 degrees C) and absence of glucose from the medium. Carnitine uptake was Na+-dependent, but did not require K4+ or Ca2+.

Animals↗
PubMed1980

Exaggerated norepinephrine-stimulated accumulation of cyclic AMP in vitro in cerebellar slices from pcd mutant mice following Purkinje cell loss.

Norepinephrine caused in vitro an accumulation of cylic AMP in slices of the cerebellum from pcd mice which was 300 percent greater than in cerebella from age-matched, heterozygous, normal mice. Purkinje cells had disappeared in the pcd mice at the time when the exaggerated hormonal response was seen. The data indicate that high cyclic AMP accumulation can take place in cerebellar cells other than Purkinje cells.

Animals↗
PubMed1980

3H-amphetamine concentrations in the brains of young and aged rats: implications for assessment of drug effects in aged animals.

The distribution of amphetamine in the brain, liver, and fat of 3-month-old Wistar rats was compared to the distribution in 24-month-old rats. Animals were killed 20 or 65 min after IP administration of 2.5 mg/kg of 3H-amphetamine. Amphetamine levels in tissues were measured by homogenizing organs in acid and extracting radioactive amphetamine into toluene. Amounts were quantified by scintillation counting. Amphetamine concentrations were twice as high in the brains of the old rats as in young animals at both time points. The liver and fat of old rats also contained more amphetamine. These findings lead us to question the common practice in aging studies of administering compounds using total body weight as the reference point.

Adipose Tissue↗
PubMed1980

Cyclic AMP-dependent protein kinase activity in human brain across age.

Cyclic AMP-dependent protein kinase activity was measured in the cerebral cortex of humans 2 days to 83 years of age and in the cortex of F344 rats 3, 22, or 30 months of age. Protein kinase activity was detected in the human brain, but no age-related differences in activity were observed in the presence or absence of cyclic AMP. Age differences were also not seen in protein kinase in the rat cerebral cortex. Enzyme activities in rat and human brain were similar.

Adult↗
PubMed1979

Dopamine agonist-induced hyperglycemia in rats: effects of lergotrile mesylate.

Lergotrile and apomorphine, two direct-acting dopamine agonists, caused marked hyperglycemia in fasted rats, while compounds which release endogenous dopamine (amphetamine, methylphenidate) or inhibit dopamine reuptake (LR5182), failed to elevate blood glucose. The effect of lergotrile was dose dependent, causing blood glucose to rise 3-fold above resting levels at 5 mg/kg (i.p.). Blood glucose increased prior to the onset of the behavioral signs of dopamine stimulation. The effect of lergotrile was attenuated by phentolamine, propranolol or butaclamol. Adrenalectomy also prevented lergotrile-induced hyperglycemia. These data indicate that hyperglycemia is not a property of all compounds that cause dopaminergic effects. The action of lergotrile might be indirect, perhaps mediated through release of catecholamines from the adrenal glands.

Adrenalectomy↗