Search PubMed⌕ Search

Biomedical subjects

M A Bell

Publications and source records attributed to M A Bell.

At least 37 records · Page 2Linked to original sources

Relationship of flavonoid oxidation potential and effect on rat hepatic microsomal metabolism of benzene and phenol.

The effect of several flavonoids on the benzene hydroxylase and phenol hydroxylase activity of rat hepatic microsomes was determined. The electrochemical characteristics of the flavonoids were also determined. The effect of flavonoids on microsomal phenol hydroxylase activity was found to correlate well with the oxidation potential for flavonoid aglycones. Easily oxidized flavonoids inhibited phenol hydroxylase activity with the extent of inhibition correlated to the ease of oxidation. This inhibition exhibited dose-dependent behaviour, with concentrations below 1 microM having no effect. On the other hand, flavonoids with high oxidation potentials increased phenol hydroxylase activity in a dose-independent manner. Hydroxyl substitution at C-7 was required for inhibition of phenol hydroxylase activity independently of the oxidation potential. Glycosylation at either C-7 or C-3 was found to moderate the inhibition of phenol hydroxylase activity. A linear relation was found between the degree of inhibition and the number of sugar residues for glycosylated flavonoids. There was no correlation between electrochemical properties and effect on microsomal benzene hydroxylase activity.

Animals↗

Arteriolar tortuosity of the white matter in aging and hypertension. A microradiographic study.

Previous studies have shown tortuous arteries and arterioles in the brains of older people, but the effects of age and other factors have not been studied. To examine the effects of hypertension, age, race and sex on white matter (WM) arteriolar tortuosity (AT), we performed high-resolution microradiography and morphometry of human brains taken at autopsy from 44 subjects of various ages (range 30-96 years; 31 hypertensives/13 normotensives). About 70% of tortuosities in the WM were found at the gray-white interfaces of the insular region and adjacent subcortical-WM of the inferior frontal and superior temporal gyri. Six morphologic types of tortuous profiles were identified. The number of tortuous profiles increased with age, but not significantly. Hypertension, sex and race had no effect on tortuosity. Our findings also suggest that 1) WM AT is found mostly at the interfaces between gray matter and WM and, therefore, 2) the physical properties of the WM somehow predispose to the development of AT; 3) AT is not associated with tortuosity in the veins; and 4) the location of complex arteriolar coils supports a recent claim that they can be mistaken for the Charcôt-Bouchard microaneurysms if injection of contrast media and low-magnification radiography of the brain slices are employed for that purpose.

Adult↗

Microvascular density of the human paraventricular nucleus decreases with aging but not hypertension.

Microvascular density was determined in the supraoptic nuclei (SON) and paraventricular nuclei (PVN) of fixed brain tissue from 19 human subjects ranging in age from 30 to 85 years. Eight of these patients had hypertension. No sex- or hypertension-related differences in microvascular density were found in either the SON or PVN. However, capillary density decreased in the PVN with aging. These results indicate a differential pattern of microvascular loss in the human hypothalamus with aging.

Adult↗

A pilot scheme for improving the accuracy of serum cholesterol measurement in Scotland and Northern Ireland.

The measurement of plasma cholesterol is subject to particularly stringent requirements of bias and imprecision because clinically important action limits lie within the bulk of the population distribution. A pilot scheme was conducted with the aim of improving the accuracy of the assay of cholesterol in 26 laboratories in Scotland and Northern Ireland. This involved the distribution of three sets of authentic human sera with varying cholesterol concentrations assigned by the reference Abell-Kendall method which was established and validated in a central laboratory. The precision (coefficient of variation) of cholesterol testing was 1.71% across all laboratories at the first distribution and this did not alter subsequently. Mean bias was initially 4.07% (median 4.14%) relative to the Abell-Kendall assigned values and this figure had fallen to 1.12% (median 0.92%) by the third distribution. We conclude that through a standardization scheme it is possible in a relatively short time to improve bias significantly and meet the criterion of < 2-3% bias required for optimum cholesterol measurement.

Bias↗

Regulation of the phosphorylation of histones and glycogen synthase.

The phosphorylation of histones and glycogen synthase by protein kinases was analysed by SDS-polyacrylamide gel electrophoresis and autoradiography. The phosphorylation of histone III-S by the catalytic subunit of cyclic AMP-dependent protein kinase (A-PK) or cGMP-dependent protein kinase (G-PK) was inhibited by archidonic acid, sphingosine and staurosporine. Using the catalytic subunit of A-PK, the phosphorylation of histone VIII-S was inhibited by Ca2+, arachidonic acid and staurosporine; the phosphorylation of histone II-S was inhibited by phosphatidyl ethanolamine, phosphatidyl inositol, arachidonic acid and staurosporine; and the phosphorylation of glycogen synthase was inhibited by arachidonic acid and staurosporine. After being phosphorylated by the catalytic subunit of A-PK, calpain II with 4 microM Ca2+ was less effective in degrading histone III-S, which had been prephosphorylated by PK-C.

AMP-Activated Protein Kinases↗

The Charcôt-Bouchard aneurysm controversy: impact of a new histologic technique.

For over a century a controversy has existed about the prevalence and significance of Charcôt-Bouchard (C-B) aneurysms, especially regarding their relationship to intracerebral hemorrhage (ICH) in man. We reassessed C-B aneurysms by staining thick brain sections from 35 hypertensives and 20 normotensives with the alkaline phosphatase (AP) endothelial stain followed by light microscopy and high-resolution microradiography. Charcôt-Bouchard aneurysms were conspicuously absent in both groups which included four cases of hypertensive ICH. The three-dimensional perspective and enhanced ability to trace vessels with these techniques helped to identify arteriolar coils and twists that can be mistaken for aneurysms when demonstrated by injection methods. Routine brain pathologic sections from 2,800 autopsies over a decade showed rare examples of parenchymal aneurysms. We conclude that elimination in our study of a) injection artifacts and b) misinterpretations shows that C-B aneurysms are uncommon and have little relationship to ICH. Despite this, and in view of the original contribution of Charcôt and Bouchard, the occasional examples of brain parenchymal aneurysms should continue to bear their names.

Aged↗

The relations between frontal brain electrical activity and cognitive development during infancy.

The relations between changes in the scalp-recorded electroencephalogram (EEG) and the development of the ability to perform successfully 2 cognitive tasks attributed to frontal lobe functioning were examined in 13 infants from 7 to 12 months of age. Infants successful in performing the A-not-B task with increasingly longer delays across the second half of the first year of life showed changes in power in scalp-recorded brain electrical activity in the frontal region and an increase in anterior/posterior EEG coherence. Infants with rapid mastery of object retrieval did not differ in frontal EEG development from infants who exhibited the normal developmental progression in object retrieval performance. In a task examining inhibition of reaching to a novel toy, there were no differences in frontal EEG as a function of performance. Results from a cross-sectional sample revealed similar findings. These data confirm work with nonhuman primates on the importance of maturation of frontal cortex in the successful performance on certain tasks (A-not-B), but do not confirm nonhuman primate data on the importance of frontal cortex for other tasks (object retrieval). The data also suggest that the electroencephalogram may be useful as a noninvasive measure of central nervous system development during the first year of life.

Brain↗

Does tortuosity in cerebral arterioles impair down-autoregulation in hypertensives and elderly normotensives? A hypothesis and computer model.

A mathematical model of pressure/flow relationships in straight and tortuous intracerebral arterioles is presented. Using this model, it is predicted that patients with severe tortuosity would never be able to tolerate an appreciable decrease in MAP. This morphological alteration may explain the inability of a few hypertensive and normotensive elderly patients to tolerate periods of mild reductions in blood pressure. The alkaline phosphatase histochemical staining technique is potentially an excellent method of establishing the identity of deep white matter signal alterations seen on MRI because of its ability to trace the vascular supply from the brain surface to the lesion.

Aging↗

Brain microemboli during cardiac surgery or aortography.

We have observed many focal dilatations or very small aneurysms in terminal arterioles and capillaries of 4 of 5 patients and 6 dogs who had recently undergone cardiopulmonary bypass. A smaller number of sausagelike dilatations distended medium-sized arterioles. Two other patients had a small number of the same microvascular changes following proximal aortography. Thirty-four patients and 6 dogs not undergoing cardiopulmonary bypass had none. (A 35th patient who had not undergone cardiopulmonary bypass or aortography showed a small number of dilatations; mediastinal air was a suggested source.) Some of the dilatations exhibited various forms of birefringence. Because most of the dilatations appear empty, we speculate that they are the sites of gas bubbles or fat emboli that have been removed by the solvents used in processing. These microvascular events, occurring only in conjunction with major arterial interventions, may be the anatomical correlate of the neurological deficits or moderate to severe intellectual dysfunction seen in at least 24% of patients after cardiac surgical procedures assisted by cardiopulmonary bypass.

Adult↗

Electrophysiological indices of frontal lobe development. Relations to cognitive and affective behavior in human infants over the first year of life.

Over the past 8 years we have been involved in a study of the psychophysiological correlates of cognitive and affective behaviors during the first year of life. We have utilized recordings of brain electrical activity (the EEG) to describe differences in regional activation as well as, more recently, changes in regional connectivity. Our studies have indicated an important role for the frontal region in the expression of positive and negative emotions and in the regulation of emotional distress. In addition, individual differences in frontal EEG maturation seem to be associated with improved performance on tasks known to involve specific regions of frontal cortex. The corroborative data from different areas of study (studies of brain-damaged adults; studies of lesions in nonhuman primates) give us confidence that our measures of regional electrical activity are indeed reflecting true brain processes. Our continuing task is to understand the skills that are involved in these complex behaviors (such as AB performance or expression of affect) so as to better understand these important brain-behavior relationships.

Aging↗

Features of the cerebral vascular pattern that predict vulnerability to perfusion or oxygenation deficiency: an anatomic study.

In an ongoing study of brain microvasculature in humans at autopsy, we had the opportunity to analyze the overall scheme of this vascular supply. The native endothelial membrane enzyme, alkaline phosphatase, is used to precipitate black lead sulfide salt in the vessel wall, rendering the brain microvasculature visible by both light microscopy and microradiography. There are six distinct patterns of intraparenchymal afferent blood supply to the supratentorial brain: short arterioles from a single source (e.g., those in the cortex); short- to intermediate-length arterioles, single source (anterior two-thirds of the corpus callosum); short- to intermediate length arterioles and arteries, dual source (subcortical U fibers); intermediate-length arterioles and arteries, triple source (extreme/external capsule and claustrum); long arteries and arterioles, single source (centrum semiovale); and large, long muscular arteries, single source (thalamus and basal ganglia). The nature of this arrangement offers some protection to certain regions of the cerebrum from circulatory challenges such as hypotension, while leaving other areas vulnerable. The distal arterioles supplying two of these protected regions, the U-fiber area and the extreme/external capsule and claustrum area, also exhibit the feature of interdigitation, which can offer additional collateral potential from one arteriolar territory to the next. Aging, hypertension, diabetes mellitus, and atherosclerosis can have a significant impact on brain microcirculation. The way in which vascular patterns dictate the distribution of these effects is discussed. The ability to stain the cerebral microvessels and demonstrate the finer points of their patterns in sections and microradiographs has enabled us to resolve some long-standing questions about vascular connections and directions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Microdialysis-perfusion sampling for the investigation of phenol metabolism.

In vivo methods provide several advantages for the study of metabolism relative to the commonly used in vitro techniques. The integrity of the organism and actual physiological conditions are maintained to reflect more accurately the processes occurring on exposure to a xenobiotic compound. Experimental precision is improved because each animal serves as its own control and can be used to generate a complete pharmacokinetic experiment. This may result in the added benefit that fewer experimental animals will be needed for a metabolic investigation using in vivo techniques. The technique of microdialysis perfusion was characterized for the in vivo study of the hepatic metabolism of phenol and conjugation by glutathione. In this study, in vivo experiments were conducted by implanting a microdialysis probe into the intact, in-place liver of a killed rat. These results were compared to in vitro experiments using liver homogenate and liver-microsomal protein. Substantial differences were observed between the in situ experiments and those performed in vitro.

Animals↗

Lucilia cuprina induced hyperammonaemia and alkalosis associated with pathology in sheep.

Gross and microscopical examinations were done in 12 sheep infested with Lucilia cuprina larvae. All the sheep became hyperammonaemic and alkalotic. Six sheep died and 6 survived, one being moribund before euthanasia. Necropsy revealed severe acute dermatitis and congestion of the liver, heart, kidney, spleen and lungs. Ecchymotic haemorrhages were present in the heart, kidneys and adrenal glands of severely infested sheep. Microscopical examination showed mild to severe vacuolation of the central nervous system in all sheep. In severely infested sheep, skin, lung, heart, kidney, and liver tissues were infiltrated by mononuclear cells, neutrophiles or lymphocytes. Fibrin thrombi were present in vessels. Elevated concentrations of lipid soluble ammonia in blood were positively correlated with tissue abnormality and early death.

Alkalosis↗

Changing practice habits of King County obstetricians.

In 1987, all practicing King County, Washington obstetricians (N = 181) were surveyed to determine the impact of rising malpractice premium rates and the threat of litigation on their obstetric practices. Six percent of respondents anticipated closing their practices over the next year, which means an additional 520 deliveries will have to be absorbed into existing obstetric practices. Of the 71% who increased their professional fees in 1986, 90% attributed the increase to higher malpractice premiums and increased risk of litigation.

Adult↗

Localized fibrous tumour of serosal surfaces. Immunohistochemical and ultrastructural evidence for a type of mesothelioma.

It is uncertain whether localized lesions of serosal membranes have a kinship to mesotheliomas or are truly fibromatous in nature. Ultrastructural and immunohistochemical investigations were carried out on 12 localized benign and malignant pleural and peritoneal tumours from 10 patients. Electron microscopic findings, including the consistent and non-fibroblastic cellular organization of localized neoplasms, the presence of some form of intercellular junctions in 7 of 10 cases, basal lamina deposition in 3 cases, and polarized microvilli in one case indicated a form of mesothelial differentiation. Using monoclonal and polyclonal antibodies, positive immunostaining of tumour cells for cytokeratin peptides was detected in one case, while antibody to vimentin stained four cases. Light microscopic, ultrastructural and immunohistochemical features of one benign localized serosal tumour, with a unique blend of epithelial and spindle cells, provided further evidence for a histogenic link between localized serosal tumours and diffuse epithelial mesotheliomas. On the basis of the current findings and reports in the literature, it would appear that the majority of localized tumours of serosal membranes are a subset of mesothelioma, while a minority are fibromas.

Adult↗

The correlation of vascular capacity with the parenchymal lesions of Alzheimer's disease.

Hippocampal capillary and arteriolar measurements showed a significant reduction in capacity with normal aging. Alzheimer's dementia was not associated with any further reduction; in fact regional variations suggested that the zones of Ammon's horn most severely affected by tangles and granulovacuoles retained the best vascular capacity. The arterial system supplying the hippocampus, from the posterior cerebral artery to the series of small hippocampal arteries, was also assessed. Its capacity, as judged by arterial diameters, was similarly found to decrease significantly with age; the arterial diameters of Alzheimer cases were (insignificantly) greater than those of the normal old. Calcarine capillary and arteriolar measurements also indicated a marked reduction of capacity with normal aging, and, as before, in Alzheimer's dementia there was no further significant change. All three phases of the study thus suggest that cerebrovascular capacity in Alzheimer's dementia is at least as good as in the normal old, if not better. Senile (neuritic) plaques with amyloid cores and their relationship to the microvasculature were examined in the calcarine cortex. In both normal old and Alzheimer cases the plaques tended to congregate where capillaries were densest. Their correlation with capillary density was however better in the normal old, raising the question of whether their pathogenesis might differ in the two conditions.

Adult↗

Encephalic microvascular abnormalities in hypertension. A light and X-ray microscopic study.

Brain and cervical spinal cord removed at autopsy from hypertensive humans have been subjected to 4 levels of microscopic study, 3 being first histochemically prepared so as to stain the arterial and capillary system. Thick (100 microns) sections for light microscopy and thicker (500-1000 microns) for x-ray microscopy facilitate the study of long, complex anatomic units. Arterial and arteriolar microaneurysms have not been found. In addition to the usual age related vascular changes in normal people we have found: moniliform capillary dilatations, focal segments of arteriolar narrowing, état pre-criblé, and lacunar infarcts. Few changes have been encountered in the corpus callosum. While the segmental arteriolar narrowing occurs in the cortex as well as deep white matter, the effects of resultant poor perfusion might be expected to be more profound in the deep white matter.

Animals↗