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Biomedical subjects

H V Vinters

Publications and source records attributed to H V Vinters.

At least 145 records · Page 8Linked to original sources
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↗
PubMed1991

Multi-step pathogenesis of AIDS--role of cytomegalovirus.

Human immunodeficiency virus (HIV) has been shown to be the initial aetiological agent of the acquired immune deficiency syndrome (AIDS). The recent clinical, epidemiologic, pathological, immunological and molecular data presented in this review point to a multi-step pathogenesis of AIDS involving HIV as an initial cause leading to reactivation of cytomegalovirus (CMV), human herpesvirus-6 (HH-6) and other immunosuppressive organisms. Although the onset of CMV reactivation is not precisely known, it may be related to the transition from AIDS-related complex to AIDS. The molecular interactions between CMV and HIV occur in both directions. Although transcriptional activation of HIV by CMV infection (possibly via induction of NF chi B) is better known, the enhancement of CMV replication by HIV is clinically as important. The interactions between HIV or simian immunodeficiency virus (SIV) and CMV appear to be more specific than between HIV or SIV and other herpes viruses, and are also cell-type-dependent. CMV-induced immune suppression (possibly of variable magnitude with different strains) may be an additional co-factor in AIDS. In a rhesus monkey model, the interaction of SIV with rhesus CMV appears contributory to the reproduction of the full-blown simian AIDS. Patients with AIDS and disseminated CMV infection display the maximum activation of HIV p24 antigenaemia and the greatest deficiency of CD8+ T lymphocytes. Defects in CD4+ and CD8+ T cells, including HIV- and CMV-specific cytotoxic T cells, are crucially important in the progression to terminal AIDS and are related not only to HIV but also to CMV and HH-6 infections of lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Dementia Complex↗
PubMed1991

Measurement of amyloid peptide precursor of Alzheimer disease in human blood by double antibody immunoradiometric assay.

The dementia of Alzheimer disease (AD) correlates with the deposition of extracellular amyloid, and this amyloid arises from the abnormal processing of a high molecular weight amyloid peptide precursor (APP), which is a normal cellular protein that is found in both brain and in peripheral tissues in humans. Overproduction of the APP in AD could cause increased concentrations of this protein in either human blood or cerebrospinal fluid (CSF). However, thus far no direct demonstration of soluble APP in human blood has been possible, owing to poor assay sensitivity and interfering plasma proteins. These two problems were eliminated with the present development of an extracting two-site immunoradiometric assay (IRMA). Two rabbit polyclonal antisera were prepared reacting to two different sites (amino acids 161-180 and 597-624) of the APP molecule. The near N-terminal antiserum (anti-APP161-180) was covalently coupled to a solid phase support and the near C-terminal directed antiserum (anti-APP597-624) was indirectly labeled using 125I-labeled near C-terminal synthetic peptide corresponding to amino acids 597-624. The IRMA was validated by partial purification of the APP from human serum and demonstration of the protein's molecular weight (112 kDa) by Western immunoblot procedures. Results of the IRMA showed that the APP is present in human plasma (mean +/- SE concentration = 32 +/- 6 pM, n = 25), and there was no significant difference in the APP concentration in 25 controls, 19 patients with AD, and 10 individuals with Down syndrome (DS). Immunoreactive APP was generally not detectable in control or AD CSF volumes as large as 1 ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Heat shock in cultured neurons and astrocytes: correlation of ultrastructure and heat shock protein synthesis.

Cultured cerebral cortical neurons and astrocytes were compared after a brief shock. Morphological findings were correlated with the synthesis of the 68 kD heat shock protein (HSP68). Heat shocked neurons demonstrated many severe morphological changes after exposure to temperatures of 43 degrees C for 15 min and 45 degrees C for 10 min. Nuclear membrane 'blebbing' with lysis of the membrane, chromatin clumping, and disappearance of the nucleolus were prominent after both conditions. Lysis of the cell membrane was noted in severely injured neurons; this was more prominent at the higher temperature. In addition, alterations to polyribosomes, Golgi apparatus, rough endoplasmic reticulum and mitochondria were noted in the cytoplasm of neurons after heat shock. In contrast, no significant changes were noted in either the nucleus or cytoplasm of heat shocked astrocytes. The severity of morphological changes in neurons directly correlated with the low level of induction of HSP68 in neurons. Neurons synthesized much less 68 kD heat shock protein than similarly heat shocked astrocytes. We conclude that cultured cerebral cortical neurons are more susceptible to injury after heat shock than heat resistant astrocytes and that one possible mechanism of injury is failure to synthesize adequate amounts of HSP68 after injury.

Animals↗
PubMed1991

Surgical treatment of limbic epilepsy associated with extrahippocampal lesions: the problem of dual pathology.

The authors present their review of 178 patients who underwent en bloc temporal lobectomies as surgical treatment for intractable epilepsy. Hippocampal cell density was quantitatively analyzed and the histology of the anterior temporal lobe was reviewed. Fifty-four patients (30.3%) had evidence of extrahippocampal lesions in addition to neuronal cell loss within the hippocampus (the dual pathology group). The pattern of cell loss was analyzed in the remaining 124 cases (69.7%) with no extrahippocampal pathology, and compared with that of the dual pathology group and a control group of four nonepileptic patients. Hippocampal cell loss was found in almost all epileptic patients compared to the control group. Severe cell loss greater than 30% of control values was found in 88.7% of patients without extrahippocampal lesions, but in only 51.8% of patients with dual pathology. The difference between these two groups was statistically significant (p less than 0.001). In the dual pathology group, lesions of different pathology had a significant relationship with the degree of hippocampal cell loss: all 12 patients with glioma had mild cell loss, whereas all 13 patients with heterotopia were associated with severe cell loss. Severity of hippocampal cell loss was also analyzed in relation to seizure history: a prior severe head injury was associated with severe cell loss. Other factors such as seizure duration, secondary generalization, or family history of seizures were not associated with hippocampal damage. Dual pathology may produce a combination of neocortical and temporolimbic epilepsies that warrants a precise definition of the true epileptogenic area prior to surgical treatment.

Adolescent↗
PubMed1991

HIV-1 env sequence variation in brain tissue of patients with AIDS-related neurologic disease.

We investigated sequence variation in the human immunodeficiency virus type 1 (HIV-1) env gene region that encodes the fourth disulfide-bonded domain of the external membrane glycoprotein, gp120, among three HIV-1 isolates from patients with AIDS-related neurologic disease. The sequences of HIV-1 isolated directly from brain tissue, blood cells, and in vitro cell cultures were compared. The results suggest that there may be many closely related HIV-1 genomes of several distinct subtypes in an HIV-1-infected individual. Differences were observed in the frequency distribution of sequence variants obtained from brain versus blood of the same individuals. Overall, the proportion of silent mutations is much lower than expected by random occurrence. Taken together, these results favor the possibility that selective forces may play a role in the tissue distribution of certain HIV-1 strains.

AIDS Dementia Complex↗
PubMed1991

Image analysis microspectroscopy shows that neurons participate in the genesis of a subset of early primitive (diffuse) senile plaques.

Amyloid is a component of the senile plaques that characterize one of the major neuropathologic changes in patients with Alzheimer's disease (AD). The sequence of events leading to the accumulation of amyloid precursors in senile plaques is unknown. In previous studies, the authors have shown that congophilic deposits in a subset of mature amyloid plaques are angiocentric. In this study, the authors used image analysis microspectroscopy and an antibody directed against a synthetic beta-protein (beta) or A4 sequence to examine the distribution patterns of this protein in serial sections from brains of patients with AD and in normal aged brains after quantitative immunohistochemistry. Image analysis of early primitive plaques disclosed two main patterns of early beta/A4 deposition, which consisted of neurocentric and angiocentric decreasing concentration gradients. In most instances, these gradients were not recognizable by the naked eye but appeared strikingly conspicuous after image subtraction and pseudocoloring. The described neurocentric gradients suggest that deposition of this protein, in at least some early primitive plaques, is related to neurons and possibly originates from these cells. The opposite viewpoint, i.e., that peripherally synthesized beta/A4 protein would 'sink in' toward neurons, is not supported because in very early plaques the highest immunoreactivity within the gradient was the neuronal body itself. A hypothesis is offered to reconcile the presence of both neurocentric and angiocentric depositions of these substances.

Aged↗
PubMed1991

Ataxia-telangiectasia: an interdisciplinary approach to pathogenesis.

Ataxia-telangiectasia is a syndrome with many facets, involving a progressive cerebellar ataxia, immunodeficiency, cancer susceptibility, radiosensitivity, defects in DNA repair/processing, chromosomal breakage and rearrangements, elevated serum alphafetoprotein, and premature aging. Ataxia-telangiectasia is an autosomal recessive disorder, rare in outbred populations; carriers of the ataxia-telangiectasia gene may be as common as 1 in 60 and have subclinical radiosensitivity and cancer susceptibility. One estimate suggests that 8.8% of patients with breast cancer could be carriers of ataxia-telangiectasia. These carriers may be responsible for underestimating normal tolerance doses for radiation therapy by 15% to 20%; thus by preselecting and excluding carriers of ataxia-telangiectasia from cohorts of patients with cancer, conventional radiation doses might be increased so as to improve greatly the efficacy of radiotherapy. The genes for the 3 most common ataxia-telangiectasia complementation groups, which include 97% of tested families, have recently been localized to the long arm of chromosome 11.

Ataxia Telangiectasia↗
PubMed1991

Immunohistochemical localization of human immunodeficiency virus (HIV) in central nervous system lymphoproliferative disorders of patients with AIDS.

Immunohistochemical localization of human immunodeficiency virus type 1. (HIV-1) in central nervous system lymphoma lesions and uninvolved regions of the brain in seven patients with AIDS revealed evidence of frequent association of HIV-labeled macrophages and multinucleated giant cells with the lesions. Five of seven cases displayed a higher density of labeled cells within and at the periphery of mass lesions and angiocentric infiltrates than in brain parenchyma farther than 1 cm from such lesions. In addition, no label was detected within the neoplastic lymphoid cells in any patient. HIV could not be localized within similarly appearing macrophages associated with destructive lesions (e.g. related to cytomegalovirus encephalitis) or small thrombotic infarcts in brain tissue from the same patients. All lymphomas studied were of a high-grade B-cell type with similar histology in multiple sites. Leptomeningeal spread of the tumor was found in all cases. Facilitation of the development of malignant B-cell clonal proliferation might occur in foci of HIV replication. Alternatively, the development of lymphoma may be due to the generalized immunosuppression; in this case, local activation of macrophages in proximity to the malignant lymphocytes might lead to preferential concentration of disseminated virus by these cells.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Reversible visual loss caused by fibrous dysplasia.

Fibrous dysplasia is a developmental anomaly of bone, often affecting the facial bones. We treated a patient who had fibrous dysplasia involving the right maxillary and sphenoid bones. The patient had a sudden loss of visual acuity to R.E.: counting fingers. Visual fields demonstrated a central scotoma, and retrobulbar neuritis was diagnosed. When vision failed to improve spontaneously, however, radiologic studies were performed. These showed compromise of the optic canal by bony proliferation and an apparent mucocele at the orbital apex. Surgical exploration disclosed fibrous dysplastic bone and a cystic structure overlying the optic nerve. Successful surgical excision of the cyst and debulking of the fibrous dysplasia resulted in visual acuity returning to R.E.: 20/25.

Adult↗