The AIDS dementia complex.
Explore the source record for details and available documents.
Acquired Immunodeficiency Syndrome↗
Biomedical subjects
H V Vinters
Publications and source records attributed to H V Vinters.
Isolation and culture of cells derived from human cerebral microvessels.
Microvessels were isolated from non-neoplastic human cerebral cortical fragments resected for treatment of intractable seizure disorder. The microvessels were incubated in modified Lewis medium with 20 or 30% fetal bovine serum. Within 1-2 weeks, two cell populations emerged from the isolates. One type of cells had polygonal morphology, showed density-dependent contact inhibition at confluence in vitro, showed lectin-binding characteristics of endothelium (but only moderate positivity for factor VIII antigen), demonstrated induction of gamma-glutamyl transpeptidase when exposed to astrocyte-conditioned media, and responded to insulin by a pronounced increase in DNA synthesis. The other variety of cells grew in vitro more slowly in irregular strands separated by clear zones, showed ultrastructural features of smooth muscle, and isoelectric focusing of cell proteins revealed the presence of smooth-muscle-specific alpha-isoactin. Both types of cells could be serially subcultured. The ability to isolate and grow the two cell types, tentatively identified as human cerebral microvascular endothelium and smooth muscle, may facilitate studies of human blood-brain barrier function as well as the pathogenesis of cerebral microangiopathies unique to the human brain.
Adolescent↗
A quantitative analysis of blood-brain barrier ultrastructure in the aging human.
The unique ultrastructure of brain endothelial cells restricts nonspecific leakage of blood-borne molecules across the blood-brain barrier (bbb). Human barrier ultrastructure has not been studied extensively because of the rapid ultrastructural degeneration that takes place after death. We have obtained living, structurally normal neocortex and underlying white matter at biopsy from patients of various ages, and have quantitated ultrastructural features that are associated with the bbb so that we could characterize human barrier ultrastructure and determine whether it changes with age. We found that gray matter capillaries have thinner walls than white matter capillaries, and that during aging white matter capillary walls became thinner until they approached the dimensions of those in gray matter. Thinning is due to loss of pericytes and thinning of the endothelial cytoplasm. The mitochondrial density was found to be higher in gray matter than in white matter, but this is a consequence of there being a smaller cytoplasmic volume and not more (or larger) mitochondria. The mitochondrial population did not change with age. Presumptive nonspecific permeability routes (endothelial vesicles, junctional gaps) did not change with age; therefore we found no morphological substrate for increased nonspecific bbb permeability in the aging human. The loss of pericytes, however, suggests that the bbb in the elderly may be less able to compensate for transient leaks.
Aging↗
Amyloid angiopathy of Alzheimer's disease: amino acid composition and partial sequence of a 4,200-dalton peptide isolated from cortical microvessels.
The cardinal lesions of Alzheimer's disease are neurofibrillary tangles, senile neuritic plaques, and vascular amyloid, the latter generally involving cortical arteries and small arterioles. All three lesions are composed of amyloid-like, beta-pleated sheet fibrils. Recently, a 4,200-dalton peptide has been isolated from extraparenchymal meningeal vessels, neuritic plaques, and neurofibrillary tangles. The assumption of N-terminal homogeneity in vascular amyloid has been used as an argument for a neuronal (versus blood) origin of the peptide. However, intracortical microvessels from Alzheimer's disease have not been previously isolated. The present studies describe the isolation of a microvessel fraction from Alzheimer's disease and control fresh autopsy human brain. Alzheimer's disease isolated brain microvessels that were extensively laden with amyloid and control microvessels were solubilized in 90% formic acid and analyzed by urea sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The arteriole fraction from the Alzheimer's subject with extensive amyloid angiopathy contained a unique 4,200-dalton peptide, whereas the arterioles or capillaries isolated from two controls and two Alzheimer's disease subjects without angiopathy did not. This peptide was purified by HPLC and amino acid composition analysis showed the peptide is nearly identical to the 4,200-dalton peptide recently isolated from neuritic plaques or from neurofibrillary tangles. Sequence analysis revealed N-terminal heterogeneity. The N-terminal sequence was: Asp-Ala-Glu-Phe-Arg-His-Asp-Ser-Gly-Tyr, which is identical to the N-terminal sequence of the 4,200-dalton peptide isolated previously from extraparenchymal meningeal vessels and neuritic plaques.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Lymphomatoid granulomatosis and the acquired immunodeficiency syndrome (AIDS)
Explore the source record for details and available documents.
Acquired Immunodeficiency Syndrome↗
Focal pontine leukoencephalopathy in a patient with the Shwachman-Diamond syndrome.
A 35-year-old woman who died after a long history of an illness consistent with Shwachman-Diamond Syndrome, was found to have extensive calcified necrotizing lesions confined to the pontocerebellar fibers of the basis pontis. The possible relationship of this recently described lesion to the patient's immunosuppressed state and/or other systemic metabolic disturbances is discussed.
Adult↗
Dementia and ataxia in a patient with AIDS.
Explore the source record for details and available documents.
Acquired Immunodeficiency Syndrome↗
The blood vessel wall as an insulin target tissue.
Study of the effects of insulin and insulin-like growth factors on blood vessel walls has been expedited by the ability to isolate and grow components of large and small blood vessels in pure culture. This paper summarizes current knowledge about the effects of insulin and related molecules on blood vessel derived cells, with an emphasis on: (1) peptide receptors, their regulation, and transport and processing of molecules through the endothelium; (2) metabolic and (3) mitogenic effects of insulin and related peptides on the blood vessel wall, with a discussion of major differences between large and small vessel endothelia; and (4) interactions of insulin with barrier endothelia, for example cerebral microvascular endothelium, site of the blood-brain barrier.
Aminoisobutyric Acids↗
Focal pontine leukoencephalopathy in immunosuppressed patients.
In three patients who died of immunodeficiency syndromes, including two patients with acquired immunodeficiency syndrome (AIDS), foci of necrotizing leukoencephalopathy were found in the basis pontis. The lesions were identical in location and morphology to those previously described in patients who received chemotherapy and central nervous system radiotherapy for various malignancies, and (except for their restricted anatomic location) resembled the disseminated necrotizing leukoencephalopathy that complicates central nervous system leukemia and lymphoma. The lesions are to be distinguished from central pontine myelinolysis, are confined to pontocerebellar tracts, and are not specific for the immunodeficient state, but may reflect preterminal metabolic derangements, since they seem unrelated in this clinical setting to malignancy and/or its treatment. Alternatively, they may be a consequence of the immunosuppressed state. The presence of this morphologic abnormality in two AIDS patients is especially intriguing, in view of the frequency with which white matter lesions are seen in the AIDS population.
Acquired Immunodeficiency Syndrome↗
Effect of inorganic lead on some functions of the cerebral microvessel endothelium.
The effect of inorganic lead on two functions of cerebral microvessel endothelium, cell division and glucose analog uptake, was investigated. Lead concentrations considered to be toxic in humans inhibited both functions in cultured endothelial cells. Both effects were dependent on the length of lead exposure and dose over the range of 10(-4) to 10(-6) M lead acetate. After 4 days of exposure there were 76% fewer cells in 10(-4) M lead-exposed cultures relative to control cultures. After 4 days of exposure to 10(-5) M lead there were 55% fewer cells, and after 10(-6) M lead exposure there were 15% fewer cells. Two days after 10(-4) M lead exposure [methyl-3H]thymidine incorporation into endothelial cells was inhibited by 71%. Incorporation was inhibited 47% by 10(-5) M lead but 10(-6) M lead did not inhibit incorporation after 2 days of exposure. Glucose analog uptake was inhibited in both contact-inhibited and log-phase cells; however, the latter were more sensitive to lead and this increased sensitivity correlated with a higher lead content in this cell population. Both the specific carrier-mediated and the nonspecific components of glucose analog uptake were inhibited by exposure of the endothelial cells to lead. A lead exposure of 40 min produced a significant effect on the uptake mechanism. In order to manifest its effects the lead had to be present in serum-containing medium, suggesting that some serum component was necessary to present the lead to the endothelial cells. These findings imply that the initial target of inorganic lead in the CNS may be the plasma membrane of the capillary endothelial cells, and that lead may act by altering the physiological function of these membranes.
3-O-Methylglucose↗
Long-term pathological follow-up of cerebral arteriovenous malformations treated by embolization with bucrylate.
We examined 17 intracranial arteriovenous malformations that were resected after treatment by embolization using bucrylate (isobutyl-2-cyanoacrylate). In nine specimens removed 5 days to 16 months after embolization therapy, a series of pathologic changes was seen, including patchy mural angionecrosis (adjacent to bucrylate fragments) up to six weeks after embolization, the presence of bucrylate in vessel walls and fibromuscular intimal cushions, and the occurrence (after several months) of entirely extravascular bucrylate. Occasional parts of recanalized vascular malformations were identified. Bucrylate was present within arteriovenous malformations as late as 16 months after embolization, although the amount appeared to be diminished. These findings suggest a specific sequence of events in the interaction between bucrylate and mural components within the malformations and may explain some important complications of embolization therapy (e.g., delayed hemorrhage after embolization).
Adolescent↗
Gerstmann-Sträussler-Scheinker disease: autopsy study of a familial case.
Postmortem neuropathological findings in a patient with biopsy-proved familial Gerstmann-Sträussler-Scheinker disease of eight years' duration included severe spongy change in the neocortex, extensive and often large amyloid deposits throughout the cerebral hemispheres and cerebellum, and severe astrocytic gliosis throughout all areas of gray and white matter within the brain. The degree of cortical spongy change was much greater than that in relatives who died with a similar clinical history, indicating the phenotypic heterogeneity in this familial disorder.
Central Nervous System↗
Severe cerebellar degeneration in a patient with T-cell lymphoma.
A 53-year-old man with an aggressive T-cell lymphoma was found at autopsy to have severe cerebellar degeneration, presumably as a 'remote' effect of malignancy. The degree of cerebellar atrophy was unusually pronounced and widespread, involving both Purkinje cell and granule cell layers, although patches of preserved and essentially normal cerebellar cortex were identified. This case is of particular interest in view of data which indicate that cerebellar Purkinje cells and T-lymphocytes share antigenic surface markers.
Atrophy↗
An unusual form of motor neuron disease following a cat bite.
A case of motor neuron disease with clinical and pathological resemblance to amyotrophic lateral sclerosis (ALS) in a woman who was severely bitten on the ankle by a cat is described. Weakness first appeared at the ankles and relentlessly advanced proximally, terminating in death from pulmonary failure in a year. A number of unusual features that are uncharacteristic of ALS were found that included a markedly elevated antinuclear antibody titre in the serum and the presence of prominent oligoclonal bands in the cerebrospinal fluid. The spinal cord showed loss of anterior horn cells and pyramidal degeneration that are characteristic of ALS, but an extraordinary finding was the presence of transmural granulomatous inflammation of numerous small and medium sized vessels, especially veins, in the subarachnoid space around the cord. There were also inflammatory changes in the brainstem and spinal cord consisting of microglial and astrocytic nodules and perivenous cuffing by mononuclear cells. Ill-defined hyaline eosinophilic cytoplasmic inclusions were seen in some remaining anterior horn cells. No viral particles were found by electron microscopy despite an extensive search. Virological studies were inconclusive but there is reason to believe that this patient's illness was caused by an as yet unidentified virus.
Amyotrophic Lateral Sclerosis↗
The blood-brain barrier in Alzheimer's disease.
The current evidence for and against abnormalities of the blood-brain barrier in "normal" aging and Alzheimer's disease is reviewed. Recent studies of cerebral amyloid angiopathy, a microangiopathy commonly observed in Alzheimer's disease and one suggested to result from blood-brain barrier derangement, are discussed with particular attention to the biochemical nature of the vascular amyloid material, and features it shares with the amyloid found in senile plaque cores and with neurofibrillary tangles. Modern techniques that will probably clarify blood-brain barrier pathophysiology are reviewed.
Aging↗
Insulin binding to the blood-brain barrier in the streptozotocin diabetic rat.
125I-Insulin binding to isolated brain microvessels from control, streptozotocin diabetic, and insulin-treated diabetic rats was measured. The binding was highest in the control (21.1 +/- 1.8%/mg capillary protein) and lowest in the diabetic (14.8 +/- 1.9%, p less than 0.01) animals. Administration of 2 U of protamine zinc insulin per day increased the maximum binding in the diabetic rats to 17.2 +/- 2.1%. Scatchard analyses of the binding showed that the major difference between the diabetic and the control animals was a decrease in the number of both high- and low-affinity sites in the diabetic animals. To test whether the failure of up-regulation in the hypoinsulinemic diabetic animal was related to an inherent defect in the endothelial cell or resulted from the diabetic milieu, cultured brain endothelial cells were tested for their capacity to up- and down-regulate their insulin receptors in vitro. In response to 100 ng/ml insulin for 12 h, these cells down-regulated their insulin receptors. When the insulin was removed, the insulin receptors returned to control levels. These studies showed that in vitro brain capillary endothelial cells have the capacity to increase their insulin receptors in response to a low-insulin environment, whereas in vivo the microvessels decrease their insulin receptors in response to diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
The neuropathology of AIDS. UCLA experience and review.
The central nervous system (CNS) has been examined at autopsy in 89 patients who died of the acquired immune deficiency syndrome (AIDS), including 14 patients who died primarily of neurologic complications of the disease. A total of 66 brains (74%) showed significant pathologic abnormalities, with opportunistic infections including cytomegalovirus (14) and cryptococcal (11) infections, progressive multifocal leukoencephalopathy (6), toxoplasmosis (6), and histoplasma microabscesses (1). Incidental Mycobacterium avium-intracellulare infection was found in 4 cases. Simultaneous CNS infection by more than one microorganism was encountered in 5 patients. Subacute (microglial nodule) encephalitis-related to cytomegalovirus infection or possibly brain infection by the causative agent of AIDS was present in 56 cases. Primary CNS lymphoma was noted in 3 patients. Secondary CNS deposits of lymphoma were found in 1 patient, and another patient had lymphomatoid granulomatosis. Vascular complications were not infrequently seen, and included infarcts secondary to vessel occlusion and disseminated intravascular coagulation in 4 patients and intracranial hemorrhage of variable severity in 13. White matter changes included vacuolar myelopathy (3 cases), central pontine myelinolysis (1 case), and foci of calcified, necrotizing leukoencephalopathy in pontocerebellar fibers of the basis pontis (2 cases). These findings highlight the variety of CNS complications in AIDS, some of which are not associated with clinical manifestations. Nevertheless, characterization of all lesions may be important in understanding the neurologic sequelae of AIDS.
Adult↗
Arteriovenous malformation and multiple anomalies of the circle of Willis.
A case is presented of subarachnoid hemorrhage from an arteriovenous malformation (AVM) involving the left middle cerebral artery in the circle of Willis, seen in association with multiple anomalies of the circle. This is an extremely unusual location for such a malformation. The possible etiology of the AVM and its relationship to the associated anomalies is discussed.
Circle of Willis↗