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H V Vinters

Publications and source records attributed to H V Vinters.

At least 19 recordsLinked to original sources
PubMed1992

Differential expression of arachidonate 5-lipoxygenase transcripts in human brain tumors: evidence for the expression of a multitranscript family.

In addition to the important role of leukotrienes as mediators in allergy and inflammation, these compounds are also linked to pathophysiological events in the brain including cerebral ischemia, brain edema, and increased permeability of the blood-brain barrier in brain tumors. Although brain tumors have been shown to secrete leukotrienes, no studies to date have provided evidence for the tumor expression of genes encoding enzymes involved in leukotriene production. Therefore, the present study determined the abundance of the mRNA for arachidonate 5-lipoxygenase (5-LO; arachidonate:oxygen 5-oxidoreductase, EC 1.13.11.34), which is the rate-limiting enzyme in leukotriene synthesis, in a series of human brain tumors. Macrophage/monocyte infiltration of the tumor was estimated by measuring the abundance of the transcript for the 91-kDa glycoprotein phagocyte-specific oxidase (gp91-phox), which is the phagocyte-specific cytochrome b heavy chain. The present study shows that (i) the 5-LO transcript is expressed in normal bovine brain and in human brain tumors; (ii) the 5-LO gene in human brain tumors and in the dimethyl sulfoxide-induced promyelocytic human leukemic HL-60 cells is expressed as a multitranscript family (2.7, 3.1, 4.8, 6.4, 8.6 kilobases); and (iii) the abundance of 5-LO transcripts, the expression of the larger transcripts, and the 5-LO/gp91-phox ratio correlate with the tumor malignancy. Overall, the present study supports the hypothesis that the 5-LO gene product may play a role in human tumor-induced brain edemas and provides evidence for tumor-associated expression of high molecular weight 5-LO transcripts in human brain tumors.

Arachidonate 5-Lipoxygenase↗
PubMed1992

Reversible in vitro growth of Alzheimer disease beta-amyloid plaques by deposition of labeled amyloid peptide.

The salient pathological feature of Alzheimer disease (AD) is the presence of a high density of amyloid plaques in the brain tissue of victims. The plaques are predominantly composed of human beta-amyloid peptide (beta A4), a 40-mer whose neurotoxicity is related to its aggregation. Radioiodinated human beta A4 is rapidly deposited in vitro from a dilute (less than 10 pM) solution onto neuritic and diffuse plaques and cerebrovascular amyloid in AD brain tissue, whereas no deposition is detectable in tissue without performed plaques. This growth of plaques by deposition of radiolabeled beta A4 to plaques is reversible, with a dissociation half-time of approximately 1 h. The fraction of grey matter occupied by plaques that bind radiolabeled beta A4 in vitro is dramatically larger in AD cortex (23 +/- 11%) than in age-matched normal controls (less than 2%). In contrast to the human peptide, rat/mouse beta A4 (differing at three positions from human beta A4) does not affect the deposition of radiolabeled human beta A4. beta A4 has no detectable interaction with tachykinin receptors in rat or human brain. The use of radioiodinated beta A4 provides an in vitro system for the quantitative evaluation of agents or conditions that may inhibit or enhance the growth or dissolution of AD plaques. This reagent also provides an extremely sensitive method for visualizing various types of amyloid deposits and a means for characterizing and locating sites of amyloid peptide binding to cells and tissues.

Aged↗
PubMed1992

Cerebral hemorrhage with biopsy-proved amyloid angiopathy.

Clinical, radiological, and immunohistochemical findings in brain biopsy specimens from six patients with cerebral amyloid angiopathy-associated intracerebral hemorrhage were reviewed. Acute clinical presentations included headache, nausea and vomiting, loss of consciousness, and focal neurological deficits such as hemiplegia and blindness. Transient ischemic attacks experienced by one patient and referable to one hemisphere did not indicate impending hemorrhage in that region. Computed tomographic scans revealed acute, irregular, superficial, lobar hemorrhage with occasional ring enhancement. Immunohistochemical studies were performed on biopsy specimens using primary antibodies against portions of the Alzheimer A4 (beta-) peptide or gamma-trace peptide (the vascular amyloid protein in patients with hereditary cerebral hemorrhage with amyloidosis-Icelandic type). In all patients, anti-A4 and anti-gamma-trace labeled cerebral microvessels. Immunoreactive senile plaques were few compared with the numbers of stained microvessels. Reactive astrocytes in some patients were labeled by both antiserum samples, suggesting uptake or production of these proteins by the astrocytes. This study demonstrates the heterogeneous clinical and radiological features of cerebral amyloid angiopathy-related brain hemorrhage and the value of anti-A4 and anti-gamma-trace immunohistochemical study of biopsy material from patients with suspected cerebral amyloid angiopathy-related intraparenchymal bleeding.

Aged↗
PubMed1992

Neuropathologic findings in surgically treated hemimegalencephaly: immunohistochemical, morphometric, and ultrastructural study.

Tissues from three cases of hemimegalencephaly (HME) causing intractable seizures treated by cortical resection were studied using immunohistochemical, ultrastructural, and morphometric techniques. Severe cortical dysplasia was seen in all cases and included lesions best characterized as hemilissencephaly and polymicrogyria. Blurring of the cortex-white matter junction, the presence of large neuronal heterotopias, and neuronal cytomegaly were frequent observations. Immunohistochemical analysis demonstrated cellular colocalization of astrocytic markers glial fibrillary acidic protein and vimentin in one case of hemilissencephaly. Morphometric data showed significant increases over controls in neuronal profile area in all cases of HME. Neuronal cell density was increased significantly above controls in one of the cases. The study shows that HME results from severe cortical dysplasia which may be caused by multiple insults, manifest in one of several ways, and reflects abnormal or altered signals that regulate cortical morphogenesis.

Brain↗
PubMed1992

Neuropathologic findings in cortical resections (including hemispherectomies) performed for the treatment of intractable childhood epilepsy.

Despite the use of hemispherectomy in the treatment of medically refractory seizures since the early 1950's, few studies published have documented neuropathologic findings in the resected specimens. This report describes the neuropathologic findings in 38 children who underwent either hemispherectomy or multilobar cortical resection as treatment for medically intractable epilepsy between 1986 and 1990. Examination of the resected specimens revealed a variety of abnormalities which fell into four broad categories. Malformations or hamartomatous lesions were the dominant finding in 15 patients, whereas encephalomalacic lesions were the most prominent abnormality in 16; chronic pathogen-free encephalitits (Rasmussen's encephalitis) was present in 3 and an additional 3 children had Sturge-Weber-Dimitri syndrome. There were no gross or microscopic abnormalities in 1 patient. This report provides the first comprehensive description of the pathologic findings in a series of children with refractory epilepsy of varying types treated by hemispherectomy-multilobar resection.

Brain Ischemia↗
PubMed1992

Correlation of neuromuscular pathology in acquired immune deficiency syndrome patients with cytomegalovirus infection and zidovudine treatment.

Peripheral nerve and skeletal muscle specimens from 115 autopsied adult AIDS patients were examined for types and incidence of histological abnormalities. Focal perivascular chronic inflammatory infiltrates featuring plasma cells were found in 85% of nerve and muscle specimens. These foci were specifically associated with cytomegalovirus (CMV)-infected capillary or venous endothelial cells in neuromuscular specimens of 31/115 patients, with increasing incidence in patients surviving longer with the diagnosis of AIDS. Neuromuscular CMV was identified histologically in 19% of AIDS patients with an AIDS-defining illness for 3 months or less, with the incidence increasing to 46% of patients who had the diagnosis for 2 years or longer. Vascular damage from CMV endothelial infection may result in regional ischemic and/or inflammatory damage to nerves, producing myelinated fiber loss and axonal degeneration, leading to denervation atrophy of myofibers found in skeletal muscle specimens in a majority of the patients. Myelinated fiber loss within the sural nerve was determined by morphometric quantitation for a subset of 50 patients, and correlated with the presence of histologically identifiable neuromuscular CMV, clinical history of zidovudine administration, and chemotherapy for alleviation of Kaposi's sarcoma. CMV infection and zidovudine treatment were both positively correlated with myelinated fiber loss, while Kaposi's sarcoma chemotherapy did not independently increase the incidence of myelinated fiber loss.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Morphological substrates of infantile spasms: studies based on surgically resected cerebral tissue.

Extensive surgical resections of neocortical cerebral tissue (including hemispherectomies) from 13 infants and children with infantile spasms showed that 12 of 13 specimens contained either malformative and dysplastic lesions of the cortex and white matter (sometimes with associated hamartomatous proliferation of globular cells), or destructive lesions possibly acquired as a result of anoxic-ischemic injury, or a combination of the two. In brain tissue from 4 patients, coarse neuronal cytoplasmic fibrils resembling neurofibrillary tangles were seen in areas of dysplastic brain on silver-stained (Bielschowsky technique) sections. Immunohistochemical (immunoperoxidase) study of cortical lesions containing globular cells employing primary antibodies to glial fibrillary acidic protein and synaptophysin as markers of astrocytic and neuronal differentiation, respectively, revealed that many cells showed astrocytic and/or neuronal features, suggesting the local proliferation of primitive or multipotential neuroectodermal cells as one substrate for this seizure disorder. Morphological abnormalities of a severe degree and wide extent in the resected tissue (e.g., in one patient with hemimegalencephaly) often showed features to suggest that they may represent variants of tuberous sclerosis. These most likely result from abnormal movement and/or local proliferation of neuroectodermal precursors that have migrated from the germinal matrix to the cortical mantle. Cellular, molecular and neurophysiological study of these abnormalities is likely to yield information about basic molecular mechanisms of brain malformation and injury important in the pathogenesis of infantile spasms and other forms of focal or generalized epilepsy.

Cerebral Cortex↗
PubMed1992

Neuropathologic findings after liver transplantation.

Neuropathologic findings are described in 37 patients autopsied after one or more orthotopic liver transplants. Gross or microscopic lesions were observed in almost all patients, including anoxic-ischemic change, hemorrhages and/or infarcts, and opportunistic infections by fungi (most commonly Aspergillus) and rarely viruses (cytomegalovirus). Central pontine and extra-pontine myelinolysis was commonly observed, and appeared to result from severe multifactorial metabolic abnormalities in the perioperative period. Low-grade (microglial nodule) encephalitis without an obvious pathogen was often encountered. Common clinical neurologic abnormalities included encephalopathy, seizures (myoclonic, focal or generalized), obtundation and coma. These were found more commonly than focal findings, but clinical features in a given patient were not uniformly predictive of underlying neuropathologic change.

Brain Diseases↗
PubMed1992

An assessment of the proliferative potential of 'balloon cells' in focal cortical resections performed for childhood epilepsy.

Cerebral cortical dysplasia is an uncommon pathological substrate of severe intractable childhood epilepsy, sometimes treated by hemispherectomy. Neuropathological findings include abnormal gyrus formation, loss of cortical lamination, unusual giant neurons and 'balloon cells' of indeterminate histogenesis similar in appearance to neoplastic gemistocytic astrocytes. In order to investigate the proliferative potential of 'balloon cells', we used Crocker's silver impregnation technique to demonstrate nucleolar organizer regions (AgNORs) involved in cellular proliferation, together with immunohistochemical evaluation of proliferating cell nuclear antigen (PCNA) expression. Balloon cells (5.56 +/- 0.24) had significantly (P < 0.001) greater AgNOR numbers than reactive astrocytes (3.89 +/- 0.15), neurons (2.30 +/- 0.13) or giant neurons (4.26 +/- 0.20). However, when corrected for nuclear size, results showed that 'balloon cells' (0.093 +/- 0.006) had significantly (P < 0.001) fewer AgNORs/square micrometre of nuclear area than reactive astrocytes (0.225 +/- 0.016) and had significantly (P < 0.001) more AgNORs/square micrometre of nuclear area than normal (0.048 +/- 0.003) or giant neurons (0.054 +/- 0.003). On the assumption that astrocytes are typical interphase cells and that normal neurons are post-mitotic, the results suggest that 'balloon cells' are unlikely to be undergoing proliferative activity and, when adjusted for nuclear size, the number of AgNORs/unit of nuclear area is more reflective of cellular ploidy than of proliferative activity in non-neoplastic neural tissues. The virtual absence of PCNA expression by 'balloon cell' nuclei supports such an interpretation of the AgNOR results.

Cell Count↗
PubMed1992

Temporal and extended temporal resections for the treatment of intractable seizures in early childhood.

In our series of 33 children who underwent temporal and extended temporal lobe resections because of seizures, the average age at surgery was 7 years, 11 months. Sixteen cases (48%) were diagnosed as having tumors: low-grade astrocytoma (6), hamartoma (5), and ganglioglioma/neuroma (5). Other pathologic diagnoses included one or more cytoarchitectural abnormalities and/or reactive changes. Due to a more aggressive and early radiologic and electrophysiologic investigation of children with seizures, a resectable focus, e.g. neoplasm or structural abnormality, was found in a much younger age group of patients than previously reported. In children who had intractable seizures but normal radiologic studies, positron emission tomography was of great value in localizing the seizure focus. In a group of children with infantile spasms, seizures were controlled following the identification and resection of a focal lesion. Prompt detection and precise localization of lesions in the temporal lobe in the pediatric population may lead to surgical management and seizure control.

Adolescent↗
PubMed1992

A rat model of severe neonatal hypoxic-ischemic brain injury.

BACKGROUND AND PURPOSE: Perinatal hypoxic-ischemic brain injury is a common problem with severe neurological sequelae. In this report we describe in detail a simple model of hypoxia-ischemia in the neonatal rat that gives rise to severe neocortical infarction and to selective hippocampal neuronal necrosis. METHODS: Seven-day-old Simonsen Wistar rat pups underwent bilateral carotid artery ligation under methoxyflurane anesthesia and, after a 4 to 6-hour recovery, were exposed to 60 minutes of hypoxia (6.5% O2); they were perfusion-fixed 3 days later for histological study. Brain temperature was monitored throughout this treatment. RESULTS: We found that 64 +/- 3% of neocortex above the rhinal sulcus was infarcted; this infarction was evenly distributed through the cerebral hemispheres. In the hippocampus, neuronal necrosis was selective for the internal (hilar) layers of granule cells of the dentate gyrus, with relative sparing of CA1 pyramidal cells. In addition, brain temperature was tightly controlled throughout the experimental manipulations. CONCLUSIONS: The present model is easy and sensitive and provides an infarct of sufficient severity and homogeneity to make it well suited for pharmacological and biochemical studies directed toward therapeutic amelioration and mechanisms of hypoxic-ischemic brain damage, respectively. In addition, the pattern of damage in the hippocampus is quite different from that seen in the adult brain, which should be helpful in studying the ontogeny of selective vulnerability.

Animals↗
PubMed1992

Neuropathology of the acquired immune deficiency syndrome (AIDS): report of 39 autopsies from Vancouver, British Columbia.

Neuropathological findings from 39 acquired immune deficiency syndrome (AIDS) autopsies of primarily neurologically symptomatic patients and 7 brain biopsies from AIDS patients performed at St. Paul's Hospital, Vancouver, British Columbia are reported. Autopsy findings included human immunodeficiency virus-1 (HIV)-type multinucleated giant cell (MNGC)-associated encephalitis seen in 17 patients, toxoplasmosis in 7 patients, and cytomegalovirus encephalitis and/or microglial nodule-associated nuclear inclusions in brain parenchyma in 9 patients. Central nervous system lymphoma was identified in 11 autopsy patients and in 4 of 7 brain biopsies. Infectious processes including HIV encephalitis were seen in 10 of 11 autopsied patients with lymphoproliferative lesions in the brain parenchyma, while 40% of patients without lymphoma had HIV-type MNGC or opportunistic infections. CNS lymphoma was not significantly increased in incidence in patients with a clinical history of zidovudine treatment, but increased duration of survival after the diagnosis of AIDS was associated with increased incidence of lymphoma in both untreated and zidovudine-treated patients. Patients displaying HIV MNGC within microglial nodules had a shorter mean duration of survival after diagnosis of AIDS than those patients with HIV encephalitis with dispersed MNGC, white matter vacuolation, and gliosis.

AIDS Dementia Complex↗
PubMed1992

Early onset intractable seizures: nonverbal communication after hemispherectomy.

The nonverbal communication skills of 10 children (mean age = 44.2 months) who underwent hemispherectomy for early onset intractable seizures were tested before and after surgery. A within-group analysis suggests that the 10 seizure-free children used more nonverbal communication after a mean follow-up period of 11.2 months than before surgery. Young normal language age matches were available for the 4 older and higher functioning subjects in the sample. Before surgery, the surgical subjects used less requesting gestures than did the normal children. After surgery, these differences were no longer apparent. The patients also employed more gestures to focus an adult's attention on objects and events than language-age-matched normal children. The children who underwent left or right hemispherectomy used similar nonverbal communication behaviors. The study's findings suggest that children with early onset intractable seizures have impaired early social communication that improves to some extent after hemispherectomy.

Child, Preschool↗
PubMed1992

A morphometric study of the blood-brain barrier in Alzheimer's disease.

BACKGROUND: Abnormalities in the human blood-brain barrier may contribute to the pathogenesis of Alzheimer disease (AD). EXPERIMENTAL DESIGN: Morphometric parameters relevant to integrity of the blood-brain barrier (cerebral capillary endothelium) were assessed in brain biopsies from patients with AD and compared with values from age-matched nondemented controls. RESULTS: Alzheimer patients showed diminished mitochondrial density and area within cerebral capillary endothelium, an increased number of capillary profiles containing pericytes (a possible second line of defense when the capillary endothelium fails), and features of inter-endothelial junctions that suggest 'leakiness' of the blood-brain barrier. CONCLUSIONS: The data indicate subtle but definite abnormalities suggesting compromise of the blood-brain barrier in AD that may contribute to its pathogenesis, and support neuropharmacologic and morphologic studies that suggest that a form of denervation microangiopathy may occur in AD brain, possibly secondary to loss of neurons from the pontine locus ceruleus. The changes may also play a role in the deposition of A4 Alzheimer amyloid within cerebral microvessel walls.

Alzheimer Disease↗
PubMed1992

Chronic lymphocytic leukemia presenting as a pituitary mass lesion.

We describe a unique case of chronic lymphocytic leukemia (CLL) in a patient who presented with bitemporal hemianopsia, adrenal insufficiency, and gonadotrophin deficiency. Studies revealed an enhancing intrasellar mass with suprasellar extension and displacement of the optic chiasm. Peripheral blood and cerebrospinal fluid (CSF) studies disclosed a monoclonal IgM kappa expressing B-cell CLL. Biopsy of the pituitary mass revealed dense infiltration of the pituitary gland by leukemic cells. This is, to our knowledge, the first reported case of CLL presenting as a pituitary mass lesion.

Brain↗