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Biomedical subjects

M Morris

Publications and source records attributed to M Morris.

At least 433 records · Page 24Linked to original sources

Neurohypophyseal dopamine biosynthesis in the spontaneously hypertensive rat.

A study was performed to investigate the neurohypophyseal dopaminergic axis in terms of its biosynthetic activity and possible changes associated with spontaneous hypertension (SHR). An in vitro system was used in which isolated neuro-intermediate lobes were incubated with the catecholamine precursor, 3H-tyrosine. Dopamine (DA) content and 3H-DA were monitored using electrochemical detection coupled with high pressure liquid chromatographic separation. A time course study showed that there was significant incorporation of 3H-tyrosine into 3H-DA. In the SHR, both neurohypophyseal DA content and biosynthetic activity were reduced. Tissue levels of 3H-DA decreased from 651 to 297 dpm/posterior pituitary. A test of the effect of dehydration on neurohypophyseal dopaminergic activity revealed that water deprivation (48 hrs) caused an increase in DA biosynthesis in the hypertensive, but not the normotensive animal. This may have been due to a greater stimulation of the neurohypophyseal axis in the SHR since these animals showed significantly higher plasma vasopressin levels and hematocrits in response to dehydration. These results demonstrate that the neurohypophysis contains an active dopaminergic system which is altered in genetic hypertension.

Animals↗

Gross and histological studies of immediate, Arthus, and delayed skin test responses to schistosome antigen, and of delayed response to ubiquitous antigens in Egyptians.

Gross studies of skin reactions to adult antigen of Schistosoma mansoni were made on 156 hospitalized patients with schistosomiasis and 114 subjects from the nonendemic area of Hurghada in Egypt. Wheal areas equal to or greater than 1.0 cm2 indicated a positive immediate (15-min) reaction to adult worm antigen; the criterion of positivity for both 24-hour and 48-hour delayed reactions was an area of induration equal to or greater than 0.6 cm2. Immediate reactions with adult worm antigen were observed in 99% of the patients with schistosomiasis and 11% of the subjects from Hurghada: the percentages with delayed reaction were 58% and 2%, respectively. Biopsies of skin test sites at various intervals after antigen injection were done on 87 individuals. Eosinophilic and mononuclear infiltrates were characteristic of immediate and delayed skin responses, respectively. Biopsies from 22 patients with marked skin reactions 5 hours after antigen injection showed that a neutrophilic response indicative of Arthus reactivity was present in only 18. Thus, Arthus reactivity could not be determined on gross appearance alone. The studies did not show any evidence of delayed basophilic hypersensitivity to schistosome antigen. Immunofluorescent studies on a small number of biopsies suggested that a late phase (5-hour) reaction due to IgE may occur in some patients. Delayed reactivity to mumps and/or monilia skin test antigens was observed in 91% of Egyptians in a nonendemic area of schistosomiasis. Delayed hypersensitivity to PPD was detected in 44% of the same group.

Adolescent↗

The effect of delay on the expression of the t6/t6 genotype.

In vivo, t6/t6 embryos are developmentally arrested between gestation days 5.5 (short-egg-cylinder stage) and 6.75 (long-egg-cylinder stage). In the present series of studies we used both in vivo and in vitro blastocyst delay followed by in vitro outgrowth to determine whether the t6/t6 lethality is time- or stage-specific. The results show that the t6/t6 genome is expressed differently in vivo and in vitro and that the in vitro expression of the homozygous t6 genome differs with different methods of effecting developmental delay. Although delay increases the life span of t6/t6 embryos it does not alter the stage of lethality. One method used to effect delay (ovariectomy) causes the t6/t6 embryos to remain as blastocysts for a significantly longer period of time than their wild-type littermates when placed into outgrowth medium. This distinction provides a unique method for obtaining a sample composed entirely of t6/t6 embryos at a stage prior to the lethal period.

Animals↗

Direct detection of the vasopressin precursor.

Cysteine-rich proteins were isolated from the hypothalamo-neurohypophyseal tract of dogs by high performance molecular weight chromatography. Trypsin digestion of these proteins produced a low molecular weight (LMW) peptide which was identified, by chemical and immunological assays, as (Arg8) vasopressin. There appear to be two forms of the precursor protein, one which has vasopressin immunoreactivity, and one which does not. Trypsin digestion of this latter protein produces high as well as LMW immunoreactivity. This suggests that the non-immunoreactive protein may be the precursor to the immunoreactive protein.

Animals↗

Inhibition of microsomal metabolism and chemical oncogenesis in culture by naphthalene quinones.

A series of naphthalene diols, quinones, and related compounds were examined for their ability to inhibit mixed-function oxidase in liver microsomes obtained from rats which had been pretreated with 3-methylcholanthrene (3-Mc) or phenobarbital (PB). Using benzo(a)pyrene monooxygenase as a measure of mixed-function oxidase activity, it was found that phenanthrene-9, 10-quinone was the most active compound tested with a K1 = 0.79 microM. Phenanthrene-9, 10-quinone did not affect cytochrome c reductase but did inhibit aminopyrine N-demethylase and p-nitroanisole-O-demethylase in both 3-MC and PB-induced microsome with almost identical inhibition constants. 1,2-Naphthoquinone exerted similar effects as phenanthrene-9,10-quinone on cytochrome c reductase, aminopyrine N-demethylase and p-nitroanisole-O-demethylase. Both quinones stimulated NADPH oxidase activity but the extent of this stimulation did not explain their inhibition of microsomal oxidation. Kinetic studies using benzo(a)-pyrene monooxygenase with phenanthrene-9, 10-quinone and 1,2-naphthoquinone indicated that they were noncompetitive with benzo(a)pyrene and mixed noncompetitive with NADPH. Both of these quinones inhibited benzo(a)pyrene induced oncogenic transformation in C3H10T1/2CL8 cells in culture in a dose response manner, presumably by inhibition of the cellular microsomal enzyme which activate benzo(a)pyrene. Phenanthrene-9, 10-quinone and 1,2-naphthoquinone seem to inhibit microsomal oxidative processes by interaction at the level of cytochrome P-450 possibly with a cytochrome P-450-substrate-oxygen complex.

Aminopyrine N-Demethylase↗

Hypothalamic catecholamine biosynthesis in vitro as measured by liquid chromatography and electrochemical detection.

A procedure is described for monitoring the biosynthesis of hypothalamic catecholamines in vitro, using the incorporation of the labeled precursor, 3H-tyrosine, into norepinephrine (NE), L-DOPAS and dopamine (DA). The technique involves separation of amines by high performance liquid chromatography, quantiation by electrochemical detection (LCEC), and the collection and measurement of labeled eluant. Rat hypothalami incubated in vitro were found to rapidly synthesize labeled DA while L-DOPA and NE synthesis were less apparent. The monoamine oxidase inhibitor, iproniazid, reduced incorporation. The tyrosine hydroxylase inhibitor, alpha methyl para-tyrosine (alpha mpt), virtually abolished DA synthesis while not appreciably affecting tissue content. The advantages of this technique over others is that it allows for the concurrent quantitation of tissue catecholamine levels, as well as their biosynthetic rate.

Animals↗

Methylmalonic acidemia: 6 years' clinical experience with two variants unresponsive to vitamin B12 therapy.

Two infants with lethargy, vomiting, convulsions, coma and marked metabolic acidosis were found to have very high concentrations of methylmalonic acid in their serum and urine. In vitro studies of fibroblasts demonstrated that the infants had different variants of methylmalonic acidemia.Vitamin B(12) was given in two different forms at 1 month of age and at 12 months of age. Each trial continued for 4 months but neither infant showed a clinical or biochemical response.In both infants hyperglycinemia, neutropenia and thrombocytopenia developed during acute metabolic crises only. Hypoglycemia was found in patient 2. Hyperammonemia was severe in patient 2 during acute crises but never appeared in patient 1. When clinically well, both infants continued to excrete abnormal amounts of methylmalonic acid in the urine and both had persistent compensated metabolic acidosis.Marked hyperuricemia developed in patient 1 at 18 months of age and led to progressive renal failure. Allopurinol therapy was necessary to keep the uric acid concentration within the normal range. Renal function returned to normal, as indicated by a marked increase in the renal clearance of creatinine and uric acid.Patient 1 is physically and mentally retarded, and has moderate hypotonia, hepatomegaly and persistent vomiting. Patient 2 has developed normally.The urine concentrations of methylmalonic acid in the four parents were normal.

Amino Acid Metabolism, Inborn Errors↗

Renin, antidiuretic hormone and the kidney in water restriction and rehydration.

1. The effect of restricted water intake followed by voluntary rehydration with water or 10 mM-KCl was studied in four conscious sheep with respect to plasma concentrations of renin, antidiuretic hormone (ADH), protein and electrolytes, and urine flow rate, osmolality and osmolal excretion. 2. Water restriction increased the plasma renin concentration and the plasma ADH concentration. 3. Rehydration with water caused a further rise in plasma renin, but plasma ADH returned to basal levels in less than 2 hr. 4. Rehydration with 10 mM-KCl in order to stabilize plasma K concentration greatly attenuated the post-drinking rise in plasma renin concentration, while plasma ADH levels fell as before. 5. Urine flow rates after rehydration with water and 10 mM-KCl remained low for at least 6 hr in most experiments despite low plasma ADH levels. The effect on urine osmolality ranged from no change to a large drop. 6. The post-drinking antidiuresis was associated with a reduction in solute excretion rate. However, free water clearance usually remained negative. 7. These experiments do not support the existence of a direct nexus between plasma ADH levels and plasma renin concentration.

Animals↗

Serum levels of prolactin, LH and LH-RH after ablation of the medial basal hypothalamus.

4 weeks after surgical ablation (MHA) of the medial basal hypothalamus (MBH) in adult male rats, serum levels of prolactin, LH, and LH-RH were determined by radioimmunoassay. Blood samples were obtained by jugular venipuncture under ether anesthesia (designated 'stress' samples) and 30 min after the ether stress by rapid decapitation (designated 'resting samples). 30 min after ether, serum levels of prolactin, LH, and LH-RH in MHA rats were comparable to those of intact and sham-operated controls. Among intact and sham-operated rats, ether elicited an initial increased in prolactin but not in LH or LH-RH. In the MHA group, prolactin levels were also acutely increased, although the increment was not as great as in control groups. The data indicate that considerable basal prolactin and LH secretion persists after MHA, and that this continued secretion may be regulated by neurohoromones such as LH-RH which arise from areas outside the MBH.

Animals↗