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Biomedical subjects

M N Hart

Publications and source records attributed to M N Hart.

At least 37 records · Page 2Linked to original sources
PubMed1991

Adhesion of splenocytes to brain microvascular endothelium in the BALB/c and SJL/j mouse systems.

Adhesion of hematopoietic cells to endothelial (En) cells plays an important role in their migration into extravascular tissue. This report characterizes the adhesion properties of naive splenocytes to syngeneic and allogeneic mouse brain microvascular endothelium isolated from the BALB/c or SJL/j mouse strains. Syngeneic adhesion reaches maximum levels by 60 min at 37 degrees C, but is more pronounced in the BALB/c system (mean adhesion = 10.7% +/- 1.0) compared to adhesion seen in the SJL/j (mean adhesion = 4.3% +/- 0.6). BALB/c, but not SJL/j adhesion, seems to be mediated, at least in part, by the interaction of CD11a/CD18 (lymphocyte function-associated antigen 1 (LFA-1] with one of its ligands, because BALB/c adhesion is partially inhibited when the assay is carried out either in the presence of chelating agents or with antibodies to the CD11a/CD18 molecule. Activation of the endothelium with recombinant interferon-gamma (rIFN-gamma), recombinant interleukin-1 alpha (rIL-1 alpha), and recombinant tumor necrosis factor-alpha (rTNF-alpha), enhances adhesion in both BALB/c and SJL/j. IFN-gamma and IL-1 alpha mediated adhesion enhancement is abrogated by antibodies to the CD11a/CD18 molecules in the BALB/c but not in the SJL/j system. The adhesion of splenocytes to mouse brain En clearly has unique properties, and whether or not the differences seen in the SJL/j system in any way influences its susceptibility to the autoimmune demyelinating disease, experimental autoimmune encephalitis, remains to be determined.

Animals↗
PubMed1991

Medulloblastoma: a population-based study of 532 cases.

Five hundred thirty-two cases of medulloblastoma (males n = 327 and females n = 205), aged 0 to 86 years diagnosed between 1973 and 1986 were studied to determine the incidence in different geographic regions of the United States and to evaluate the effect of various factors on survival. The median age was 9 years and average follow-up time was 45 months. The overall incidence rate was 1.8 per one million person-years. Variables that were statistically significant (p less than 0.05) in a multivariate model determining survival in rank order were treatment group, sex, geographic region, year group and age. This observational study found that 1) age and sex were statistically significant factors in describing the incidence rates, whereas year group and geographic region were not; 2) no incidence peak in the third decade of life was observed; 3) a significant improvement in survival was observed in the combined 1978 to 1986 year groups relative to the 1973 to 1977 year group; 4) the overall 5-year survival probability was 45%; and 5) there has been an increase over time in the use of more than two modalities of treatment.

Adolescent↗
PubMed1990

Activation of CD4+ lymphocytes by syngeneic brain microvascular smooth muscle cells.

Splenocyte proliferation as measured by [3H]thymidine incorporation was detected when brain microvessel smooth muscle cells (SM) were cocultured with syngeneic spleen cells. This report focuses on the role of different lymphocyte populations in this activation. The central role of CD4+ T cells in the proliferation response has been established by different sets of experiments. The phenotypic characterization of splenic lymphocytes before and after the co-culture showed that the only cell type present in higher number after the co-culture than before is the CD4+ T cell. When CD4+ cells were purified by flow microfluorimetry and co-cultured with SM a strong proliferative response was detected. In contrast, purified CD8+ cells in co-culture with SM cells did not proliferate. The activation of CD4+ cells by SM required direct cell-to-cell contact and could be detected on the fourth day, reaching maximal levels at the 6th and 7th days of the co-culture. The activation is more pronounced in the syngeneic system than under allogeneic conditions and is inhibited by anti-MHC II mAb, but not by anti-MHC II mAb. The finding that vascular smooth muscle cells can activate syngeneic T cells may have important implications concerning the mechanism of induction of vasculitis.

Animals↗
PubMed1990

Antigen presentation by brain microvessel smooth muscle and endothelium.

It has been previously reported that cultured brain microvessel smooth muscle cells (SM) express major histocompatibility complex (MHC) class II antigen. Here we report that SM is able to present ovalbumin (OVA) antigen to an OVA-specific T cell hybridoma (A2.2E10) and also presents keyhole limpet hemocyanin (KLH) to a KLH-specific T cell clone (HDK-1). Both the class II expression and the antigen-presenting capacity of SM cells is increased by interferon-gamma stimulation. Antigen presentation by SM is also MHC restricted as it is blocked by anti-Ia monoclonal antibodies. In contrast to SM, brain endothelium (En) presents whole OVA, digested OVA and KLH poorly, to a much lesser degree than SM, to the same antigen-specific T cells.

Animals↗
PubMed1990

Carcinoma metastatic to a cerebellar vascular malformation: case report.

A 73-year-old woman with a spontaneous intracerebellar hemorrhage was seen and was found to have metastatic adenocarcinoma within a vascular malformation. There was no evidence of other metastatic disease. The association of these two lesions is uncommon and has rarely been reported. The rich vascularity of the malformation may explain the hematogenous deposition of metastatic neoplasm at this site.

Adenocarcinoma↗
PubMed1990

Permeability of neutral vs. anionic dextrans in cultured brain microvascular endothelium.

The luminal surface of vascular endothelium contains glycocalyx residues that establish an overall negative charge. Recent evidence has suggested that local endothelial surface charge properties may account for the permeability properties of various macromolecules. It has also been suggested that altered membrane charge on the luminal side may play a role in thrombogenesis and atherogenesis. The relationship of macromolecule charge to endothelial cell permeability was examined in vitro using mouse brain microvessel endothelial cells grown to confluence on a nitrocellulose filter separating a double-chamber system. Endothelial permeability to 4K and 10K fluorescein-labeled neutral dextrans was compared with the permeability to 4K and 10K fluorescein-labeled anionic dextrans (sulfated). After 1 h, there was significantly greater permeability of neutral fluorescein-labeled dextran than of anionic fluorescein-labeled dextran in each particle size. In addition, there was significantly greater permeability of 4K than 10K fluorescein-labeled dextrans of either charge. The findings indicate that charge in addition to size plays an important role in the movement of macromolecules across cultured microvascular endothelial cells.

Animals↗
PubMed1990

Surgical experience with cerebral amyloid angiopathy.

Cerebral amyloid angiopathy can present as lobar intracerebral hemorrhage in an elderly person, presumably due to increased fragility of the vessels affected by amyloid deposition. For this reason, patients presenting with intracerebral hemorrhage and suspected of having cerebral amyloid angiopathy have often been treated nonsurgically. Since 1983 we have evaluated 11 patients with cerebral amyloid angiopathy (nine women and two men, mean age 73 years) who have undergone either intracerebral hematoma evacuation or brain biopsy. Nine of the 11 patients presented with intracerebral hemorrhage, which was unilobar in three patients and multilobar in six and involved the parietal lobes seven times, the frontal lobes four times, the temporal lobes four times, and the occipital lobes twice. These nine patients underwent hematoma removal, with no cases of abnormal intraoperative bleeding or recurrent hemorrhage. Six patients improved neurologically, and two were unchanged after hematoma evacuation; the remaining patient had a fatal cardiopulmonary arrest during the immediate postoperative period. During follow-up in seven patients (median 11 months, range 1 week to 74 months) none experienced a recurrent intracerebral hemorrhage and four continued to improve. Two of the 11 patients had cerebral amyloid angiopathy diagnosed by brain biopsy as part of an evaluation for dementia, also without surgical complications. This series suggests that patients with cerebral amyloid angiopathy may safely undergo operative procedures, and patients presenting with intracerebral hemorrhage may show neurologic improvement following evacuation of the hematoma.

Aged↗
PubMed1990

Progressive aphasia in a patient with Pick's disease: a neuropsychological, radiologic, and anatomic study.

Although Pick's disease is generally considered as a dementia characterized by signs of frontal lobe dysfunction, it can present with selective language defects rather than with cognitive decline. In this study, we report prospective and serial clinical, neuropsychological, and neuroradiologic observations in a 59-year-old man whose prominent disturbance was in the retrieval and learning of names denoting concrete entities and actions. Postmortem study confirmed the diagnosis of Pick's disease and revealed that neuronal loss and gliosis were most prominent in left anterior temporal cortices. The findings are in keeping with evidence that the left anterior temporal cortices and interconnected hippocampal system are critically involved in the learning and retrieval of verbal lexical items. The evidence from this patient, along with similar evidence from the literature we reviewed, suggests that when patients present with a progressive aphasia characterized by anomia, Pick's disease should be considered as the probable diagnosis.

Aphasia↗
PubMed1990

Leukoencephalopathy in cerebral amyloid angiopathy: MR imaging in four cases.

We report four cases of biopsy proved cerebral amyloid angiopathy demonstrated by MR imaging. White matter signal hyperintensities on T2-weighted spin-echo pulse sequences were present in three patients. We believe the white matter lesions associated with cerebral amyloid angiopathy are not specific to this disorder but rather reflect hypoperfusion of distal white matter resulting from vascular disease.

Aged↗
PubMed1989

Differential modulation of MHC class I antigen expression on mouse brain endothelial cells by MHV-4 infection.

Virus-induced modulation of mouse cerebral endothelial cell class I and class II antigens by the neurotropic coronavirus, MHV-4 (JHM), was examined by flow cytometry. In susceptible BALB/c, H-2Kd was downregulated, while H-2Dd was upregulated following infection by MHV-4. In contrast, H-2K and H-2D antigens were both upregulated in either MHV-4-susceptible B10.S and (BALB/c x SJL) F1, or MHV-4-resistant SJL-derived cerebral endothelial cells following infection with this virus. Class II antigen expression was unchanged following MHV-4 infection. Virus-induced MHC class I modulation is genetically regulated, and may influence virus clearance by class I-dependent CTL.

Animals↗
PubMed1989

Brain microvessels produce 12-hydroxyeicosatetraenoic acid.

Cerebral microvessels isolated from perfused, adult murine brain produce a compound with the chromatographic properties of a monohydroxyeicosatetraenoic acid when incubated with arachidonic acid or stimulated with calcium ionophore A23187. The formation of this arachidonic acid metabolite is not reduced in the presence of the cyclooxygenase inhibitor ibuprofen, but it is abolished by the lipoxygenase inhibitor nordihydroguaiaretic acid. Analysis by gas chromatography combined with chemical ionization and electron impact mass spectrometry of reduced and nonreduced derivatives of the metabolite, indicate that the compound is 12-hydroxyeicosatetraenoic acid. Fractions of isolated microvessels enriched with capillaries produce 2.1 times more 12-hydroxyeicosatetraenoic acid per microgram of protein than do fractions of microvessels enriched with arterioles. These studies confirm that brain microvessels can produce 12-hydroxyeicosatetraenoic acid and strongly suggest that cerebral endothelia are the primary source of microvessel-derived 12-hydroxyeicosatetraenoic acid. They further suggest that in brain injury, the liberation and accumulation of arachidonic acid in cerebral tissues may lead to the production of 12-hydroxyeicosatetraenoic acid within microvessels. The 12-hydroxyeicosatetraenoic acid formed in this way may mediate some of the blood-brain barrier and cerebrovascular dysfunction that occurs following stroke, brain trauma, or seizures.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1989

The effects of platelet-derived growth factor in cultured microvessel endothelial cells.

The effects of platelet-derived growth factor (PDGF) on thymidine incorporation into DNA and glucose and neutral amino acid uptake were studied in endothelial cells cultured from macrovessels (bovine aorta and pulmonary artery) and microvessels (bovine fat and mouse brain). Similar to previous studies, PDGF did not bind to macrovessel cells, nor did it influence their metabolic function. In contrast, PDGF bound specifically to the two types of microvessel cell culture and in these cells also stimulated the uptake of glucose and neutral amino acids as well as the incorporation of thymidine into DNA. Stimulatory effects of PDGF occurred at concentrations of 2 ng/ml, with maximal stimulation up to 5-fold of the control value for amino isobutyric acid and glucose uptake and up to 8- to 10-fold for thymidine incorporation. The maximal effects of PDGF were additive to those of insulin-like growth factor, I, a known stimulator of all three metabolic processes in microvessel endothelial cells. The binding of PDGF to the endothelial cells was, in general, equivalent to PDGF binding to human foreskin fibroblasts, both in the magnitude of tracer binding and in the affinity of binding. Similar effects were found with recombinant and platelet-derived PDGF. We conclude that these two cultured microvessel endothelial cells not only produce PDGF-like material, but are capable of binding and responding to PDGF.

Adipose Tissue↗
PubMed1989

Downbeating nystagmus and other ocular motor defects caused by lithium toxicity.

We report the clinical and neuropathologic findings of a 63-year-old woman who died following an accidental lithium overdose that produced coma, respiratory depression, horizontal gaze palsy, and downbeating nystagmus. She also had mild hypomagnesemia. The pathology was cytotoxicity, predominantly in the regions of the nuclei prepositus hypoglossi and medial vestibular nucleus. Damage to this area with kainate and ibotenate in rhesus monkeys has produced horizontal gaze palsy and downbeating nystagmus. In addition, we report our clinical experience during the past 6 years with other examples of downbeating nystagmus in patients receiving lithium.

Cranial Nerve Diseases↗
PubMed1989

Purification of murine endothelial cell cultures by flow cytometry using fluorescein-labeled griffonia simplicifolia agglutinin.

Griffonia simplicifolia agglutinin (GSA) is a valuable histochemical tool in the identification of endothelium. In this study GSA labeled with fluorescein isothiocyanate (GSA-FITC) was used to purify cultures of murine cerebral microvascular endothelium. Cultures were stained with GSA-FITC, then sorted using a fluorescence-activated cell sorter (FACS). GSA-positive endothelial cells were collected, re-cultured, and subsequently re-analyzed by FACS using GSA-FITC. Cultures that initially contained 80 +/- 3 to 89 +/- 3% (X +/- SE) GSA-positive cells were purified to 98 +/- 1% positivity. Immunohistochemistry with an anti-muscle-action antibody confirmed that FACS sorting of GSA-FITC-stained cells effectively removed contaminating smooth muscle cells from endothelial cell cultures. Viability, proliferation, and prostaglandin production of the cells was unaltered by lectin staining and FACS sorting. Thus, GSA-FITC can be used in conjunction with flow cytometry to enhance the purity of murine endothelial cell cultures without adversely affecting cell viability, growth, or metabolism.

Actins↗
PubMed1988

Murine cerebral microvascular endothelium incorporate and metabolize 12-hydroxyeicosatetraenoic acid.

Cultured murine cerebromicrovascular endothelial cells were employed to study the metabolism of 12-hydroxyeicosatetraenoic acid (12-HETE) in an in vitro model of the blood-brain barrier. These endothelial cells convert 12-HETE to at least four, more polar compounds. Analysis of the least polar and predominant metabolite by gas chromatography combined with chemical ionization and electron impact mass spectrometry of reduced and nonreduced derivatives indicate that the compound is 8-hydroxyhexadecatrienoic acid (8-HHDTrE). The uptake of 12-HETE into cell phospholipids peaks at 2 hr, and is not saturable up to the highest concentration tested, 5 microM. Seventy-five to 92% of this 12-HETE is incorporated into phosphatidylcholine, while the remainder is divided between the inositol and ethanolamine phospholipids. Incorporation into neutral lipids is slower, with radioactivity gradually accumulating in triglycerides over 24 hr. Saponification of cell lipids demonstrated that not only 12-HETE, but also its major metabolite, 8-HHDTrE, is incorporated into the cell lipids. Prostacyclin and prostaglandin E2 production by the cerebral endothelial cells is inhibited by up to 56% with 1 microM and 90% with 5 microM 12-HETE. These data demonstrate that 12-HETE is actively metabolized by cerebral endothelium and suggest at least two mechanisms through which 12-HETE may alter cerebromicrovascular function: 1) incorporation into cerebral endothelial membranes and 2) inhibition of cerebral endothelial prostaglandin production. Conversion of 12-HETE to more polar compounds, particularly 8-HHDTrE, may be interpreted as either the inactivation of 12-HETE or the production of additional, biological mediators.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1988

Eicosanoid metabolism in cerebromicrovascular endothelium.

Cultured murine cerebral microvessel endothelia produce predominantly prostacyclin and prostaglandin (PG) E2 when exposed to trace amounts of arachidonic acid. At higher concentrations of arachidonate or with ionophore A23187, they produce more PGE2 than prostacyclin and additionally make PGF2 alpha and small amounts of eicosanoids comigrating with hydroxylated derivatives of arachidonate. Endothelia grown on micropore filters release prostaglandins from both apical and basal surfaces; however, the ratio of basal to apical release is as high as 4:1. This polarity suggests that cerebral endothelial prostaglandins can interact with neighboring cells of the vessel wall and brain parenchyma, where they may play important roles in the control of cerebrovascular tone and neuroglial function. These eicosanoids also are produced by mouse brain microvessels, but the major microvessel product is 12-hydroxyeicosatetraenoic acid. This suggests that 12-hydroxyeicosatetraenoic acid may be abundant in brain injuries after arachidonate release. Cultured cerebral endothelia rapidly convert 12-hydroxyeicosatetraenoic to more polar metabolites and thus may prevent the accumulation of this potentially deleterious hydroxyacid.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗