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Biomedical subjects

M T Smith

Publications and source records attributed to M T Smith.

At least 289 records · Page 16Linked to original sources
PubMed1982

Scanning electronmicroscopy of experimental anencephaly development.

The scanning electronmicroscope was used to study the development of anencephaly in an experimental model. Anencephaly was produced consistently, using vitamin A as the teratogen. Embryos destined to become anencephalic displayed failure of opposing sides of the rostral neural tube to fuse. Subsequently, the neural folds of the experimental embryos progressively curved laterally away from the midline, whereas the neutral folds of the control embryos fused in the midline by day 12. The anlage of the choroid plexus could be identified on the surface of the everting brain folds as early as gestational day 13. Thus, the abnormal eversion of the neural tube occurred before development of the choroid plexus. This study supports the view that anencephaly ultimately results from neural tube nonclosure.

Anencephaly↗
PubMed1981

The effects of dietary lipid and phenobarbitone on the production and utilization of NADPH in the liver. A combined biochemical and quantitative cytochemical study.

The validity of the concept that cellular NADPH utilization in the cytoplasm can, by quantitative cytochemical procedures, be classified into two pathways (Pathway I, in which NADPH is oxidized via the microsomal electron-transport system, and Pathway II, in which NADPH supplies reducing equivalents for biosynthetic processes) was tested. The amount of NADPH, generated by glucose 6-phosphate dehydrogenase, entering Pathways I and II in the centrilobular and periportal regions was measured by quantitative cytochemistry, and the values obtained were compared with biochemical measurements of mixed-function oxidase and fatty acid synthetase activity after the administration of sodium phenobarbitone or by altering the quantity and nature of the dietary lipid. Phenobarbitone stimulates hepatic mixed-function oxidation measured biochemically and Pathway I, but not Pathway II. Variation in the type and quantity of dietary lipid can also regulate the activity in mixed-function oxidation and alter the amount of NADPH entering Pathways I and II. It is concluded that, in general, the concept of two main pathways of NADPH utilization in the liver is valid, but that the ratios of NADPH utilization in the two pathways gives a better indication of the use of NADPH in vivo than is obtained for absolute values for the two pathways. Moreover, the centrilobular and periportal hepatocytes showed different patterns in their response to changes in dietary lipid and the administration of phenobarbitone. These results indicate the different metabolic roles that these two groups of cells may play in the metabolism of foreign compounds.

Animals↗
PubMed1981

Toxic injury to isolated hepatocytes is not dependent on extracellular calcium.

Freshly isolated hepatocytes from phenobarbital-treated rats were incubated in the presence or absence of extracellular calcium with three differently acting liver cell toxins, namely carbon tetrachloride, bromobenzene, and ethylmethanesulfonate. In the absence of extracellular calcium these three compounds were far more toxic to the cells than in its presence. This result is inconsistent with the hypothesis that an influx of extracellular calcium is required as the final step in toxic liver cell injury.

Animals↗
PubMed1981

Diffuse meningeal rhabdomyosarcoma.

Pure rhabdomyosarcomas are extremely rare as primary tumors in the cranial vault. In this instance, a 25-year-old man had symptoms and signs of chronically increased intracranial pressure. A biopsy of the meninges of his posterior fossa was performed revealing a spindle-cell sarcoma. Ultrastructural evidence of striated muscle differentiation and cross striations was present. The patient died of pulmonary emboli. Complete autopsy failed to disclose tumor anywhere except the leptomeninges. The presence of this tumor indicates that a rhabdomyosarcoma can arise from the meninges without a preexisting glioma or teratoma.

Adult↗
PubMed1981

The influence on enzyme activity of storage of tissue blocks at -70 degrees C.

Blocks of tissue from various organs of the rat have been chilled by precipitate immersion in n-hexane cooled to -70 degrees C, and then stored at -70 degrees C. At various intervals (up to 14 days) after chilling, cryostat sections were prepared from these blocks and assayed for the activity of a variety of enzymes. Enzyme activity was measured by scanning and integration microdensitometry. With the exception of acid phosphatase and cytochrome oxidase, all enzymes assayed were stable for at least 7 days after storage at -70 degrees C and most were stable for 14 days, Storage of fresh-frozen sections at -30 degrees C in the cabinet of the cryostat, for up to 24 h, had little effect on enzyme activity.

Animals↗
PubMed1981

The pharmacokinetics of midazolam in man.

Midazolam, a new water-soluble benzodiazepine, was administered as: i) 5 mg intravenously, ii) a 10-mg oral solution and iii) a 10-mg oral tablet, to six volunteers whose informed consent had been obtained. Midazolam plasma concentrations were measured using an electron-capture gas-liquid chromatographic assay. After 5-mg intravenous midazolam, subjects fell asleep within 1-2 min and continued to sleep for an average of 1.33 h. After oral midazolam intake (solution or tablets), drowsiness appeared after a average of 0.38 h (range 0.25-0.55 h) and sleep continued for an average of 1.17 h. The time to reach peak plasma midazolam concentration after the 10-mg solution dose (0.37 +/- 0.45 h) did not differ significantly ('t' = 2.04, df = 10, p greater than 0.05) from the time to reach peak plasma midazolam level after the 10-mg tablet dose (0.74 +/- 0.45 h). The terminal half-life, (t 1/2), of midazolam in plasma was 1.77 +/- 0.83 h and there was no significant difference between the mean terminal half-life values obtained for the three midazolam formulations. The mean total clearance (Cl), of midazolam after 5-mg intravenous administration was 0.383 +/- 0.0941 . kg-1 . h-1. The first pass effect, F, determined experimentally (0.36 +/- 0.09) indicated the substantial first pass metabolism of midazolam. The percentage of the midazolam dose excreted unchanged in urine in four subjects during the 0-8-h urine collection interval was very small (0.011%-0.028%).

Adult↗
PubMed1981

The unsteady model. An alternative approach to nonlinear pharmacokinetics.

In this paper an alternative approach to nonlinear pharmacokinetics modelling has been developed from first principles. This "Unsteady Model" is able to describe the situation whereby one or more independent drugs and their metabolites compete for free attachment sites in liver, tissue, red blood cells etc. The Unsteady model collapses to well-known existing models viz: Michaelis-Menten, Langmuir tissue binding and the linear compartment models, under certain well-defined, limiting conditions. The Unsteady model and its collapse to existing models is derived mathematically and illustrated with simulations. For several reasons the Unsteady model would appear to have many advantages and wide application.

Kinetics↗
PubMed1981

Morphogenesis of experimental anencephaly.

The sequential morphological development of anencephaly was studied in an experimental model. Vitamin A was administered to pregnant rats on gestational days 8, 9, and 10. When the litters were allowed to proceed to term, the treatment resulted in fetuses with anencephalic features. The progressive morphological development of the malformation was then established by histological and gross study of embryos and fetuses of different ages. The earliest lesion identified was a microfocal necrosis located in the head fold epithelium near the anterior neuropore on day 9; it was lateral to the normal position of physiological necrotic foci seen in control embryos. Subsequent to the appearance of the initial lesion, the malformation developed as everted brain folds extending vertically from the diencephalon in the pattern of exencephaly. The neural tube in the region of the malformation never closed, and the exencephaly arose as a progressive development of non-closed neural tube. Finally, the classical anencephalic resulted from the spontaneous necrosis of the exencephalic malformation. This study indicates that anencephaly in an experimental model arises from microscopic foci of necrosis near the anterior neuropore and develops through non-closure of the neural tube.

Abnormalities, Drug-Induced↗
PubMed1980

The use of an inexpensive, general purpose microcomputer in quantitative cytochemistry.

A 32K Commodore Pet microcomputer has been interfaced with two Vickers microdensitometers. This system allows for the simultaneous logging of data from two densitometers being operated independently of each other. Software for the statistical analysis of data generated by the densitometers, and for use with the cytochemical bioassay of hormones, is described. The densitometer/Pet system is relatively cheap, reliable, and readily adaptable to other applications.

Computers↗
PubMed1980

Periarteritis nodosa in pregnancy: report of a case and review of the literature.

This article presents a case report and review of the literature on periarteritis nodosa. The purpose is to alert physicians that there are causes of hypertension in pregnancy other than preeclampsia and chronic essential hypertension. Periarteritis nodosa is rare in pregnancy and is usually fatal in the gravid patient.

Adult↗
PubMed1979

The distribution of glutathione in the rat liver lobule.

A quantitative cytochemical method was developed for measuring the GSH (reduced glutathione) content of hepatocytes in different regions of the rat liver lobule. Use of this method enabled us to show that GSH is not evenly distributed within the rat liver lobule. The hepatocytes located within 100 micrometer of the central vein contain much less GSH than do those in other regions of the rat liver lobule. We suggest that this partially explains the peculiar susceptibility of these cells to electrophilic attack by toxic metabolites formed via the microsomal cytochrome P-450 system.

Animals↗