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Biomedical subjects

G W Goldstein

Publications and source records attributed to G W Goldstein.

At least 55 records · Page 3Linked to original sources
PubMed1988

Heparin inhibits the growth of astrocytes in vitro.

Heparin at a concentration of 100 micrograms/ml, inhibits neonatal rat astrocyte proliferation by 45%, and [3H]thymidine incorporation into DNA by 55% when they are stimulated with 2% fetal bovine serum (FBS) in culture. Higher serum concentrations up to 10% FBS decreased this inhibition to 20% and 29% respectively. Inhibition of [3H]thymidine incorporation by heparin is dose-dependent with maximal inhibition at 100 micrograms/ml, but 39% inhibition is still seen at 1 microgram/ml on stimulation by 5% FBS. Heparin or heparin-like molecules in the extracellular matrix of brain capillary walls may be important in the regulation of astrocyte growth in vivo.

Animals↗
PubMed1988

Transforming growth factor beta activates protein kinase C in microvessels isolated from immature rat brain.

We investigated the activation of protein kinase C in microvessels isolated from rat brain. We found that unstimulated kinase activity in microvessels from immature animals is soluble while that from adults is particulate. The tumor promoter, phorbol 12-myristate 13-acetate, and the diacylglycerol analog, 1-oleoyl-2-acetyl-sn-glycerol, caused the redistribution of protein kinase C activity to the membrane fraction in microvessels from immature rats. Exposure to transforming growth factor beta resulted in similar redistribution of kinase activity. To our knowledge, this is the first report of an effect of transforming growth factor beta on protein kinase C. The kinase activity in microvessels from adult animals was unaffected by exposure to these agonists. We suggest that protein kinase C activation promotes differentiation of the brain microvasculature. Transforming growth factor beta may mediate this process.

Aging↗
PubMed1988

Stroke associated with obstructive sleep apnea in a child with sickle cell anemia.

We describe a child with sickle cell anemia and multiple ischemic infarctions who was found to have severe obstructive sleep apnea and hypoxemia, secondary to adenotonsillar enlargement. The apnea-associated hypoxemia likely contributed to the development of the strokes in this child. Moreover, because stroke in patients with sickle cell anemia, and maximal tonsillar enlargement (the most common cause of obstructive apnea in children) both have peak incidence at the same age (6-7 years), obstructive sleep apnea may be an important factor in the development of stroke in other children with sickle cell anemia.

Adenoidectomy↗
PubMed1988

Lead activates protein kinase C in immature rat brain microvessels.

We investigated the effects of inorganic lead upon calcium-, phospholipid-dependent protein kinase (protein kinase C) in brain microvessels isolated from 6-day-old rat pups. We found that (a) in broken cell preparations, lead at micromolar concentrations activates this enzyme to an extent equivalent to that of micromolar calcium (10.3 +/- 1.3 and 9.2 +/- 1.6 pmol/mg/min, respectively) and (b) preincubation of intact microvessels with lead results in a translocation of protein kinase C from the soluble to the particulate fraction. The cytosolic kinase activity stimulated by lead has the same requirements for diacylglycerol and phospholipid as the calcium-stimulated enzyme, suggesting that lead activates the kinase by mimicking calcium. The hypothesis that lead affects protein kinase C activity through a mechanism similar to that of calcium is supported by the similar time courses of substrate phosphorylation and dephosphorylation mediated by lead and calcium. When intact microvessels are preincubated with micromolar concentrations of lead, the translocation of protein kinase C occurs in a dose- and time-dependent manner. The relocalization is virtually complete at 0.1 microM lead and by 30 min of exposure. We propose that the sensitivity of protein kinase C to lead, described here in immature brain microvessels, makes this regulatory enzyme a potential mediator of lead toxicity.

Animals↗
PubMed1988

Endothelial cell-astrocyte interactions. A cellular model of the blood-brain barrier.

Microvascular endothelial cells in the brain have a number of special properties that underlie formation of the blood-brain barrier (BBB) and contribute to control of the neuronal microenvironment. Evidence from transplantation experiments indicates that signals arising within brain rather than a programmed commitment of the endothelial cells are responsible for the expression of blood-brain barrier properties. The close anatomic relationship between brain endothelial cells and the foot processes of astrocytes suggests a role for astrocytes as a source of the differentiation signals. It is now possible to isolate and separately culture populations of brain-derived endothelial cells and astrocytes. When the two cell types are grown together, a characteristic morphologic organization occurs that is associated with induction of enzymes and tight junctions similar to those found in vivo. Endothelial cells and astrocytes in culture differ in their production of and response to specific polypeptide growth factors. These findings provide the basis for a model of endothelial cell-astrocyte interaction that may explain several aspects of BBB behavior.

Animals↗
PubMed1988

Neonatal hypoxic-ischemic encephalopathy: current management practices.

A national survey of training programs in neonatal-perinatal medicine was undertaken to determine neurologic management practices in dealing with the asphyxiated, term newborn. Seventy-two of 105 responses (68.6 per cent) were returned. Commonly used diagnostic tests include routine electroencephalography, cranial sonography, and determinations of arterial blood gases and serum calcium. Fluid restriction and treatment of seizures with phenobarbital are widely used therapies. Many available techniques for both diagnosis and treatment show wide variability in utilization. These results demonstrate a lack of a "standard" approach to the problem and suggest the need for well-designed clinical trials to assess efficacy and safety of treatment measures inconsistently applied to the asphyxiated, term newborn.

Academic Medical Centers↗
PubMed1987

Hyperosmotic urea reversibly opens the tight junctions between brain capillary endothelial cells in cell culture.

The effect of hyperosmotic solutions of urea on primary cultures of bovine brain microvessel endothelial cells was examined. Confluent monolayers of cells positive for Factor VIII-related antigen were obtained by seven days in culture. The cells were: incubated in media containing 1 M, 2 M or 3 M urea and horseradish peroxidase (HRP) for various periods of time and then examined by transmission electron microscopy. Exposed to hypertonic urea solutions and 14C-3-O-methyl-D-glucose for determination of the intracellular water space. In control cultures endothelial cells were bound together by tight junctional complexes over 91% of which excluded HRP. In experimental cultures 82% of the interendothelial clefts became permeable to HRP after one minute of incubation with 3 M urea. The degree of cell shrinkage corresponded well with the extent of junctional opening. In monolayers examined 24 hours following removal of urea from the media more than 63% of the intercellular clefts were impermeable to HRP. These observations indicate that hyperosmotic solutions of urea reversibly open the tight junctions between brain microvessel endothelial cells in tissue culture. Decrease in cell volume appears to be linked to the increased junctional permeability.

Animals↗
PubMed1987

Formation of a barrier by brain microvessel endothelial cells in culture.

Endothelial cells (EC) isolated from bovine brain microvessels produce a continuous monolayer when grown in primary culture. The EC are joined together by tight junctions and contain few pinocytotic vesicles. Horseradish peroxidase (HRP) is unable to penetrate this in vitro barrier system. Exposure of the cells to 1.6 M arabinose produces a reversible separation of the tight junctions with penetration of HRP across the monolayer in a pattern similar to that observed in animals after infusion of hyperosmotic solutions into the carotid artery. The behavior of brain microvascular cells in culture suggest that they retain properties important to the formation of the blood-brain barrier.

Animals↗
PubMed1986

In vitro studies of the blood-brain barrier using isolated brain capillaries and cultured endothelial cells.

The endothelial cells in brain capillaries are the anatomic site of the blood-brain barrier. To learn more about the biology of these specialized cells, we developed methods to prepare suspensions of purified brain microvessels as well as primary cultures of endothelial cells in monolayer. These two preparations allow for direct investigation of the metabolism, transport properties, and receptor content of the brain capillary. We used isolated brain microvessels to study distribution of membrane carriers between the luminal and the abluminal plasma membrane of endothelial cells. We found that Na+K+-ATPase and the A-system amino-acid transport system are located predominantly on the abluminal surface of brain capillary endothelial cells. This distribution of transport carriers is consistent with the low permeability of potassium and small neutral amino acids in the blood-to-brain direction. It suggests, however, that both solutes can be actively transported across brain capillaries from the brain interstitial fluid to the blood. In tissue culture, the endothelial cells form continuous tight junctions with their neighbors. This results in a cellular layer impermeable to protein tracers. When exposed to hyperosmolar solutions, in an attempt to mimic the conditions that open the blood-brain barrier in vivo, we found a reversible separation of the tight junctions between contiguous endothelial cells. No indication of activation of pinocytosis was observed. In vitro systems provide a novel approach for studying the function of the blood-brain barrier and allow for observations not possible with intact animals.

Animals↗
PubMed1985

Cell proliferation after ischemic infarction in gerbil brain.

In order to study cell proliferation after ischemic infarction, a model of bilateral common carotid artery occlusion in the gerbil was developed. A comparison of survival rates after 15, 30, 45 and 60 min of occlusion revealed that 45 min was the maximum duration of ischemia after which most (72%) of the gerbils were alive at 1 week. The administration of pentobarbital (single dose, 30 mg/kg) postoperatively to badly seizing animals increased survival to 100%. Large, well-demarcated infarcts were present in posterior thalamus or midbrain in 62% of gerbils subjected to 45 min bilateral occlusion. In 60% of these animals the infarcts were unilateral; in 40% they were bilateral. To quantitate cell proliferation in the infarcts from 12 h to 25 days after ischemia, gerbils were injected with [3H]thymidine 4 h prior to sacrifice, and autoradiographs were prepared from sectioned brains. Proliferation took place from 2 to 7 days after occlusion, with a maximum of 24% labeled cells at 6 days.

Animals↗
PubMed1985

Steroid-responsive ophthalmoplegia in a child. Diagnostic considerations.

Among the painful ophthalmoplegias, ophthalmoplegic migraine and Tolosa-Hunt syndrome share many features. Our 6-year-old patient had three episodes of ophthalmoplegia. Two episodes were painful and promptly resolved with oral prednisone. She had no evidence of parasellar or systemic disease. A review of published cases of ophthalmoplegic migraine demonstrated that the clinical history, the cornerstone of diagnosis in migraine, does not differentiate ophthalmoplegic migraine from Tolosa-Hunt syndrome. Other features helpful in the diagnosis of Tolosa-Hunt syndrome were not usually investigated in reports of ophthalmoplegic migraine. Until better criteria are available for differentiating the two entities, we suggest that children who fulfill the clinical criteria for Tolosa-Hunt syndrome receive a trial of steroid therapy.

Child↗
PubMed1985

Primary culture of capillary endothelial cells from the spiral ligament and stria vascularis of bovine inner ear. Retention of several endothelial cell properties in vitro.

Methods for isolation and culture of microvascular endothelial cells of the inner ear were devised to provide an in-vitro system for studying endothelial functions in this tissue. Capillaries from the stria vascularis and spiral ligament were treated enzymatically to free them from surrounding tissue. Contamination by extraneous tissue was minimized by banding capillary segments in Percoll gradients and culture in plasma-derived serum on a fibronectin-coated substrate. Although only small amounts of inner ear tissue were available, tritiated thymidine autoradiography demonstrated that considerable growth in culture was possible. Addition of heparin and endothelial cell growth supplement to the medium enhanced proliferation. The endothelial origin of the cultured cells was confirmed by immunofluorescent demonstration of the presence of Factor VIII-related antigen and angiotensin-converting enzyme. In addition, tight junctions between cells were observed in both thin sections and platinum replicas obtained by freeze-fracture techniques. Endothelial cells from neither the stria vascularis nor the spiral ligament allowed passage of horseradish peroxidase across the monolayer during a 5-min period. However, endothelial cells from the stria vascularis exhibited a greater amount of pinocytotic activity than those of the spiral ligament, a difference that is also observed in vivo. Methods for expanding a small population of endothelial cells with retention of specialized properties into one of sufficient size for morphologic and biochemical studies have been demonstrated for the inner ear.

Animals↗