Biomedical subjects

M N Hart

Publications and source records attributed to M N Hart.

At least 55 records · Page 3Linked to original sources

PubMed1988

Mechanics of cerebral arterioles in hypertensive rats.

Chronic hypertension is associated with hypertrophy of cerebral blood vessels. Previous studies of the mechanical properties of cerebral vessels in chronic hypertension have examined large cerebral arteries. The goals of this study were first to develop a method to examine vascular mechanics of cerebral arterioles in vivo and second to determine whether the stiffness of cerebral arterioles is altered in the presence of chronic hypertension. We calculated circumferential stress and strain of pial arterioles in age-matched, anesthetized stroke-prone spontaneously hypertensive rats (SHRSP) and in Wistar Kyoto rats (WKY) from measurements of pial arteriolar pressure, inner diameter, and wall thickness. Pial arteriolar pressure was measured with a servonull system. Smooth muscle of pial arterioles was deactivated with ethylenediaminetetraacetic acid (EDTA), and pressure-diameter relations were examined during step-wise reductions in pressure. Prior to deactivation of smooth muscle in 3-4-month-old rats, pial arteriolar pressure was greater in SHRSP than in WKY (110 +/- 4 versus 75 +/- 2 mm Hg [mean +/- SE]; p less than 0.05). Pial arteriolar diameter, which was measured at prevailing levels of pial arteriolar pressure, was less in SHRSP than in WKY (52 +/- 5 versus 63 +/- 3 microns; p less than 0.05). Following deactivation of smooth muscle, diameter of pial arterioles at 70 mm Hg of pial arteriolar pressure was similar in the two groups: 104 +/- 6 microns in SHRSP and 109 +/- 3 microns in WKY (p greater than 0.05). Wall thickness was 4.5 +/- 0.2 microns in SHRSP and 4.1 +/- 0.1 microns in WKY (p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Composition and mechanics of cerebral arterioles in hypertensive rats.

It was demonstrated recently that, in contrast to large cerebral arteries, distensibility of cerebral arterioles is increased in stroke-prone spontaneously hypertensive rats (SHRSP). The goals of this study were to examine composition of normal cerebral arterioles, and to determine whether chronic hypertension alters relative composition of the arteriolar wall. Pial arterioles in normotensive Wistar Kyoto rats contain large amounts of smooth muscle, small amounts of elastin and basement membrane, and very little collagen. Hypertrophy of pial arterioles in SHRSP is characterized by increases in the elastic components, smooth muscle and elastin. The stiffer components, collagen and basement membrane either did not change or decreased. It is concluded that cerebral arterioles contain proportionately more smooth muscle and less collagen than large arteries, and that hypertrophy of cerebral arterioles in SHRSP is accompanied by a relative increase in the more elastic components of the arteriolar wall, which probably contributes to the increase in arteriolar distensibility.

Animals↗

PubMed1988

beta-amyloid protein of Alzheimer's disease is found in cerebral and spinal cord vascular malformations.

Congo/Red deposition with birefringence to polarized light was demonstrated focally in cerebrovascular malformations removed surgically from 4 older patients (ages 85, 74, 74, and 63), and in a spinal cord vascular malformation in a 76-year-old patient. Lesser degrees of Congophilic change were observed in cerebrovascular malformations screened from 4 of 10 patients between the ages of 30 and 59. No Congophilic change was seen in 10 cerebrovascular malformations removed from patients under 30 years of age. Congophilic areas in all cases decorated with W-2 and 85/45 polyclonal antibodies raised to peptide sequences of cerebrovascular beta-amyloid and beta-amyloid of senile plaques from patients with Alzheimer's disease. Thus, the amyloid in these vascular malformations is immunologically related to beta-amyloid protein. This finding provides another indication that vascular beta-amyloid deposition is not specific for Alzheimer's disease and suggests that an existing abnormality of vessels may be a predisposing factor.

Adolescent↗

PubMed1987

Brain microvascular smooth muscle expresses class II antigens.

Mouse (BALB/c) splenic lymphocytes co-cultured in vitro with syngeneic brain-derived microvascular smooth muscle (SM) proliferate and become activated. After subsequent transfer of the activated lymphocytes to a syngeneic host, a vasculitis develops in the host. Investigation of the possible antigen-presenting properties of the cultured SM has resulted in the demonstration of class II (Ia) antigens on the SM. Fluorescence-activated cell sorter analysis has shown that an average of 31% of unstimulated SM cells in culture were positive when stained with an anti-IE of the appropriate haplotype (H2d), and an average of 20% were positive with an anti-IA of the H2d haplotype. Controls consisting of irrelevant antibodies of the same isotype, as well as an anti-IA of the H2s haplotype, were negative. In contrast, BALB/c-derived brain microvascular endothelial cells showed considerably less class II antigen expression (7% for both IA and IE).

Animals↗

PubMed1987

Management of radiation-induced accelerated carotid atherosclerosis.

Patients with long survival following cervical irradiation are at risk for accelerated carotid atherosclerosis. The neurologic presentation in these patients mimics naturally occurring atheromatous disease, but patients often present at younger ages and with less concurrent coronary or systemic vascular disease. Hypercholesterolemia also contributes to this accelerated arteriosclerosis. Angiographic findings in this disorder include disproportionate involvement of the distal common carotid artery and unusually long carotid lesions. Pathologic findings include destruction of the internal elastic lamina and replacement of the normal intima and media with fibrous tissue. This article describes two surgical patients with radiation-induced accelerated carotid atherosclerosis who typify the presentation and characteristics of this disease.

Adult↗

PubMed1987

Dominantly inherited dilated cardiomyopathy.

We describe a family in which there is segregating an autosomal dominant gene determining a cardiomyopathy. The pathodynamics is that of pump failure associated with dilatation of the heart, generally having an overt clinical onset from the fourth through seventh decades. Dysrhythmia is a frequent concomitant feature. There may be an associated skeletal myopathy, either producing a very mild proximal weakness or proving detectable only upon biopsy. This family is similar to other reported cases of familial dominant "idiopathic" dilated cardiomyopathy, but the nature of the heterogeneity within this category remains to be elucidated. The roles of echocardiography, cardiac biopsy, and skeletal muscle biopsy in the presymptomatic detection of the heterozygote are noted.

Adolescent↗

PubMed1987

Alpha-glucosidase deficiency and basilar artery aneurysm: report of a sibship.

Glycogen deposition in vascular smooth muscle has been demonstrated previously in alpha-glucosidase deficiency but has not been clinically significant. Three sons of healthy, nonconsanguineous parents developed progressive proximal muscular weakness secondary to alpha-glucosidase deficiency. Each patient developed a fusiform basilar artery aneurysm, which was complicated by fatal rupture in two patients and a cerebellar infarction in the third. Postmortem examination demonstrated severe vacuolation of skeletal muscle, liver, and vascular smooth muscle with accumulation of periodic acid-Schiff-positive, diastase-sensitive material. In the surviving brother, similar glycogen deposition was demonstrated in the smooth muscle of the superficial temporal artery. Basilar artery aneurysm formation in this sibship may be a consequence of alpha-glucosidase deficiency.

Adolescent↗

PubMed1987

Pneumocystis carinii. Taxonomy as viewed by electron microscopy.

Pneumocystis carinii is an opportunistic unicellular organism that can cause serious pulmonary infection in immunosuppressed patients. The taxonomy and classification of P. carinii has not yet been settled. The authors present transmission and scanning electron microscopic (TEM and SEM) observations of tissue from two patients with pulmonary Pneumocystis infections. The infectious organisms display marked variability in shape and size. They appear to divide by binary fission and lack motility organelles, Golgi apparatus, phagosomes, and lysosomes. The mitochondria and endoplasmic reticulum were poorly developed. The nucleus was rather ill defined, and there appeared to be asynchrony in the development of nuclear membranes and cytoplasm. The authors contend that there are firm ultrastructural evidences against the claim for a protozoan nature of Pneumocystis and in favor of its being a fungus, albeit of a primitive form, in which the mycelium is reduced to a unicellular state but the ability to sporulate is preserved.

Cell Nucleus↗

PubMed1987

Differential opening of the brain endothelial barrier following neutralization of the endothelial luminal anionic charge in vitro.

This study was undertaken to determine the effect of neutralization of brain endothelial cell luminal membrane anionic charge on endothelial permeability properties. Mouse brain microvessel endothelial cells were grown to confluence on a nitrocellulose filter. The permeability of the endothelium to Evan's blue dye (EBD) (molecular weight 960) and fluoresceinated dextran (FITC-D) (molecular weight 20,000), both polar molecules, was assessed before and after the exposure of the endothelium to cationic ferritin (CF) or native ferritin (NF). The use of CF resulted in a significant increase in permeability of the endothelium to EBD compared to NF. This result indicates that ablation of endothelial surface anionic charge enhances endothelial transport of a small, polar-charged molecule. Cationic ferritin did not increase the permeability of FITC-D compared to NF. This negative result is not surprising because FITC-D differs from EBD in terms of charge and solubility as well as in size. The electrical resistance of the endothelial cell layer after the application of CF was unchanged from baseline values suggesting a transcellular rather than a paracellular route of the EBD leakage.

Animals↗

PubMed1987

Experimental autoimmune inflammatory myopathy.

We report an experimental model of autoimmune inflammatory myopathy. Splenic cells from two inbred murine strains (BALB/c and SJL/J) are activated (immunized) in vitro by co-culture with their respective syngeneic skeletal muscle myotubes. Subsequent injection of the activated splenocytes with or without B. pertussis into the respective syngeneic hosts results in inflammatory myopathy in the SJL/J mice but never in the BALB/c mice. The muscle inflammation is very similar in appearance to human autoimmune inflammatory myopathies. The myositis is not effector cell-skeletal muscle specific because splenocytes activated by co-culture with smooth muscle will also elicit skeletal muscle lesions. Both strains of skeletal muscle appear to express class II (Ia) antigens and the splenocytes from both strains appear to be equally activated. Thus we postulate that the difference in the expression of myositis between the two strains is in the effector phase of the disease. Since SJL/J mice have vasoactive amine sensitive vascular systems and BALB/c do not, it is likely that activated splenocytes emigrate from muscle microvessels in the SJL/J strain whereas they cannot do so in the BALB/c strain. The most significant contribution of this model may be in its potential for addressing a sine qua non of cellular autoimmune disease, i.e. lymphocyte migration from the vascular compartment into the target tissue. Finally, the data support a cellular more than a humoral pathogenesis in this model.

Animals↗

PubMed1987

Response to immunosuppressive therapy in patients with hereditary motor and sensory neuropathy and associated dysimmune neuromuscular disorders.

We encountered 2 patients with hereditary motor and sensory neuropathy (HMSN) type I who had marked weakness developing during several months superimposed on chronic peroneal muscular atrophy. Further studies disclosed a chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in one patient and CIDP associated with polymyositis in the other. Both patients responded to prednisone and azathioprine with substantial improvement. Patients with HMSN who develop rapid progression of weakness should be evaluated for superimposed, potentially treatable dysimmune neuromuscular disorders.

Adult↗

PubMed1986

Growth control in cerebral microvessel-derived endothelial cells.

Endothelial (En) cells derived from the cerebral microvasculature were examined for their growth control properties. These cells were shown to be growth responsive to fetal bovine serum and arrested growth if serum was removed. They lend themselves to studies in chemically defined media since they survive well in serum-free medium with little or no proliferation. These cerebral microvessel En cells also respond to epidermal growth factor (EGF) and platelet-derived growth factor (PDGF), unlike some other endothelial cells. Similar to other endothelial cells, the En cells responded to fibroblast growth factor (FGF). The response to EGF and PDGF occurred in serum-free media, but only if both agents were present. The cells further responded mitogenically to conditioned media obtained from transformed endothelial cells. The En cells were found to bind EGF and displayed two orders of affinity as determined by Scatchard analysis, depending upon whether the cells were in confluent or subconfluent conditions. The data indicate that some endothelial cells respond to EGF and PDGF and that one mechanism for growth control of endothelial cells may be an ability to regulate high-affinity growth factor receptors for epidermal growth factor.

Animals↗

PubMed1986

Movement disorders associated with chronic GM2 gangliosidosis. Case report and review of the literature.

A 24-year-old man presented with dystonia, dementia, amyotrophy, choreoathetosis, and ataxia. Partial hexosaminidase A deficiency was documented in serum and leukocytes and confirmed by rectal biopsy with ganglion cells containing membranous cytoplasmic bodies. A brief review of the literature reveals that tremor, dystonia and choreoathetosis are common but neglected symptoms associated with chronic GM2 gangliosidosis.

Adult↗

PubMed1986

Establishment and preliminary growth characteristics of a transformed mouse cerebral microvessel endothelial cell line.

A clone of spontaneously transformed mouse cerebral microvessel endothelial cells has been characterized and its growth characteristics have been investigated. The clone has been designated TEn and has been derived from parent nontransformed cerebral microvessel endothelial cells after multiple passages in culture. These transformed endothelial cells maintained characteristics of other transformed cells: anchorage-independent growth in soft agar, nude mouse tumorigenicity, and growth to high saturation density in culture with lack of contact inhibition. Although transformed, these cells still maintained endothelial functions and markers. These cells respond to both epidermal growth factor and platelet-derived growth factor. Although the TEn cells utilize serum factors for growth, they have maintained in completely serum-free media for up to 3 months. Additionally, serum-free media conditioned by these cells contained a growth factor-like activity that was mitogenic for the nontransformed parent endothelial cells. The TEn cells' maintenance of endothelial functions, growth in serum-free media, production of growth factor-like activity, and the response to well-characterized purified mitogens (epidermal growth factor and platelet-derived growth factor) suggest that these cells may be useful in studying growth control of cerebral microvessel-derived endothelial cells as well as in studies of growth factor production by transformed cells.

Animals↗

PubMed1985

Uptake of glucose analogues into cultured cerebral microvessel endothelium.

Tritiated glucose analogues 3-O-methylglucose (3-OMG) and 2-deoxyglucose (2-DG) were used to study glucose uptake properties in established lines of cultured mouse cerebral microvessel endothelium. Uptake of both analogues was similar in terms of rate and absolute amount for the first two minutes. Thereafter, intracellular accumulation of 2-DG continued at a more rapid rate because of intracellular phosphorylation of this substrate. The uptake of 3-OMG uptake was temperature-dependent, independent of Na+, and not inhibited by ouabain or 2,4-dinitrophenol. Phloretin and cytochalasin B both significantly inhibited 3-OMG uptake. Other hexoses in high concentration acted as competitive inhibitors at the endothelial cell membrane. Pre-incubation of cells with 50 mM D-glucose resulted in higher levels of 3-OMG accumulation than in control cells (counter-transport phenomenon). In contrast to findings at the blood-brain barrier in vivo, insulin was found to stimulate 3-OMG uptake. Maximal stimulation of approximately 3-fold was found at ambient insulin concentrations of 1,000 ng/ml or higher. The findings provide support at the cellular level for some components of the model of carrier-mediated glucose transport across the blood-brain barrier which has been postulated to exist in vivo. The effect of insulin is discussed in the light of new data that show stimulation of glucose analogue transport into isolated cerebral capillaries.

3-O-Methylglucose↗

PubMed1985

Autoimmune vasculitis resulting from in vitro immunization of lymphocytes to smooth muscle.

Lymphocytes sensitized in vitro to syngenic microvascular smooth muscle and transferred to syngeneic recipients produced in vivo microvessel vasculitis characterized by mononuclear cells which adhered to endothelium, infiltrated the vessel wall, and formed a perivascular cuff. A granulomatous type of vascular inflammation was seen in 20% of the affected recipients in which the vessel smooth muscle appeared to be preferentially attacked. These lesions bear a striking resemblance to certain human vasculitides, and the model provides an important means of studying vasculitis as well as general cellular autoimmune disease mechanisms.

Animals↗

PubMed1984

Cerebral microvascular smooth muscle in tissue culture.

Cerebral endothelium is being studied rather extensively in tissue culture, but no reports are available describing the tissue culture of cerebral microvascular smooth muscle. The present paper describes for the first time the isolation and culture of non-neoplastic mouse cerebral vascular smooth muscle. Microvessels from a dounce homogenate of mouse brain are plated onto plastic culture dishes in Dulbecco's modified Eagle media plus 20% fetal bovine serum and treated briefly with collagenase. Cells migrate from vessels and proliferate sufficiently to be transferred out of primary culture in 2 to 3 wk. Light microscopy reveals generally broad, polygonal cells that grow collectively in a "hill and valley" pattern. By transmission electron microscopy the cells possess many characteristics of smooth muscle: basal laminas, clusters of pinocytotic vesicles, and bundles of thin filaments. Several ill-defined cell-to-cell junctions are also present. Isoelectric focusing and sodium dodecyl sulfate-electrophoresis of cellular proteins on polyacrylamide gels after pulse labeling cultures with [S-35]methionine demonstrate that these cells actively synthesize a smooth-muscle-specific isoactin, alpha-actin. The identity of alpha-actin is confirmed by analysis of NH2-terminal peptides after actin digestion with trypsin and subsequent peptide cleavage with thermolysin. Both their morphology and active synthesis of alpha-actin strongly suggest that these cells are of smooth-muscle origin. Future studies of their metabolism and interactions with endothelium and astrocytes should provide a better understanding of the cerebral microcirculation.

Actins↗

PubMed1984

Glial cells influence polarity of the blood-brain barrier.

Polarity has been shown to exist at the blood-brain barrier (BBB) with respect to Na+-dependent neutral amino acid transport. A situation similar to the endothelial-astrocyte relationship existing at the BBB can be produced by growing cultured cerebral endothelium on one side of a filter and C6 glial cells on the other in an enclosed double chamber. In this setting 3H-alpha-methylaminoisobutyric acid transport can be demonstrated and is more rapid from the glial surface across the endothelium, as compared with transport in the opposite direction. The observation supports a glial influence on BBB polarity in this system.

Aminoisobutyric Acids↗