Biomedical subjects
H V Vinters
Publications and source records attributed to H V Vinters.
Collagen microbeads: experimental evaluation of an embolic agent in the rete mirabile of the swine.
PURPOSE: To evaluate the histologic and angiographic effects of collagen microbeads as an embolic agent in the swine rete mirabile. METHODS: Human collagen particles (380 +/- 100 microns) of spheroidal shape and smooth surface were used to embolize the rete mirabile in five swine. Control angiograms and pathologic examinations were obtained immediately and sequentially from 3 to 35 days after embolization. RESULTS: The collagen particles were easy to inject through microcatheters. Embolization was always angiographically complete and persistent for at least 5 weeks. Histologic studies showed occlusion of 25% to 50% of the rete vessels. After 3 and 5 weeks' follow-up, transmural and adventitial chronic inflammation was present. Inflammatory infiltrates included lymphohistiocytic cells and scattered eosinophils. The foreign-body giant-cell reaction was pronounced. No evidence of angionecrosis or focal hemorrhage was shown. CONCLUSIONS: Collagen microbeads are a promising experimental embolic agent, with potential future applications in humans.
Neuropathology.
The surgical neuropathologist who examines corticectomy specimens from infants and children with epilepsy is in a unique position to make observations of fundamental importance in understanding the pathogenesis of seizures as well as the basic neurobiology of brain lesions that are associated with epilepsy. Findings on the resected human tissue using novel immunocytochemical and molecular probes can supplement and even build on relevant findings in experimental models, the goal of which is an understanding of epilepsy at cellular and subcellular levels.
Evidence for fibromuscular pulleys of the recti extraocular muscles.
PURPOSE: Magnetic resonance imaging (MRI) shows that the paths of recti extraocular muscle (EOM) bellies remain fixed in the orbit during large ocular rotations and across large surgical transpositions of their insertions. These findings imply that recti EOMs pass through pulleys coupled to the orbit and anterior to the muscle bellies, because the insertions must move with the globe. The present study was conducted to locate anatomically and to characterize histologically the pulley tissues. METHODS: High-resolution MRI images were collected from volunteers, using multiple gaze directions to infer the locations of, and occasionally to visualize, recti EOM pulleys. Fresh cadaver orbits were exenterated and dissected to evaluate mechanical and structural properties of the orbital connective tissues. Lipid was cleared from whole specimens to reveal tissue relationships. Other specimens were selectively step- and serial-sectioned for histochemical and immunohistochemical staining. RESULTS: Magnetic resonance imaging demonstrated dense connective tissue structures within posterior Tenon's fascia near the equator of the globe adjacent to the recti EOMs. Histochemistry showed these structures to be pulleys--fibroelastic EOM sleeves consisting of dense bands of collagen and elastin, suspended from the orbit and adjacent EOM sleeves by bands of similar composition. A monoclonal antibody to human smooth muscle alpha-actin demonstrated substantial smooth muscle in the pulley suspensions and in posterior Tenon's fascia. Tenon's fascia itself was seen to be suspended at its periphery from the orbital walls like a drumhead. CONCLUSIONS: The human orbit contains specialized musculofibroelastic tissues in and just posterior to Tenon's fascia that serve as compliant pulleys and determine the pulling directions of recti EOMs. In this sense, the pulleys are the functional origins of the recti EOMs and are determinants of ocular motility.
Polyclonals to beta-amyloid(1-42) identify most plaque and vascular deposits in Alzheimer cortex, but not striatum.
Alzheimer's beta-peptides (A beta) aggregation rates depend on A beta length. We made synthetic peptide antisera to A beta 34-40 and 37-42. Purified anti-34-40 preferentially recognizes beta 1-40, vascular amyloid and a subset of plaques while purified anti-37-42 recognizes A beta 1-42 and not A beta 1-40 in dot and Western blots and immunoprecipitates; 37-42 precipitates a small percentage of fibroblast secreted A beta and strongly stains all deposits identified by monoclonals to A beta on adjacent sections from frontal cortex, but not in dorsal striatum.
Monoclonal antibody to the C-terminus of beta-amyloid.
Soluble amyloid beta-protein (A beta) is normally produced, but forms deposits in the brain of Alzheimer's (AD) patients. The length of isolated A beta in SDS-insoluble amyloid from AD brain is reported to vary between plaques and vessels ranging from 28 to 43, with major species being 40 and 42 residues. Because the A beta C-terminus determines aggregation rates, we made an A beta monoclonal antibody distinguishing beta 1-42 from beta 1-40. In AD cortex, the beta 1-42 antibody recognizes all the structures identified by monoclonal to beta 1-40 on adjacent sections: plaque cores, diffuse A beta deposits and vascular amyloid. These antibodies help define variation in A beta length between different deposits, regions and autopsied brains.
Posterior cortical atrophy. Neuropathologic correlations.
OBJECTIVE: A subgroup of patients with progressive dementia has been reported with a marked predominance of symptoms attributed to the dysfunction of the posterior parieto-occipital cortex. These cases have been referred to as posterior cortical atrophy. The objective of this study was to determine whether posterior cortical atrophy is associated with distinct, uniform neuropathologic findings. DESIGN: Three individuals with progressive dementia that began with higher visual dysfunction (posterior cortical atrophy) were followed up to definitive neuropathologic diagnosis. RESULTS: Three separate neuropathologic entities were discovered: subcortical gliosis, Alzheimer's disease, and Creutzfeldt-Jakob disease. CONCLUSION: Posterior cortical atrophy is a clinically homogeneous but pathologically heterogeneous syndrome.
Neuronal cytoskeletal abnormalities in human cerebral cortical dysplasia.
The cytoskeletal abnormalities of cortical neurons in human cerebral cortical dysplasia were compared by immunohistochemical methods to the neurofibrillary tangles of Alzheimer's disease (AD). Surgical specimens from cortical resections performed for the treatment of intractable childhood seizures as well as autopsied samples from AD patients were analyzed with different antibodies directed against high- or medium-molecular mass neurofilament epitopes, phosphorylated or non-phosphorylated forms of neurofilaments, ubiquitin, the microtubule-associated protein tau, and paired helical filaments (PHF), a defining feature of AD tangles. A strong abnormal increase in immunoreactivity to the high and medium molecular mass neurofilament epitopes was seen in hypertrophic neurons of cortical dysplasia. These neurofilamentous accumulations of cortical dysplasia as well as AD tangles also displayed immunoreactivity with antibodies against phosphorylated and non-phosphorylated neuro-filament epitopes, tau and ubiquitin. Only the AD tangles, however, were immunoreactive to the antiserum to PHF. These results replicate and extend our previous findings that the neurofibrillary accumulations in cerebral cortical dysplasia share some common antigens with the neurofibrillary tangles of AD but do not demonstrate immunoreactivity to PHF antiserum. The results also suggest that the cytoskeletal abnormalities observed in neurons of cortical dysplasia may result in part from alterations in the level of expression, in phosphorylation state or in transport of cytoskeletal components.
Copper deficiency secondary to a copper transport defect: a new copper metabolic disturbance.
We describe a 21-year-old man who developed copper deficiency manifested as a demyelinating neuropathy, chronic intestinal pseudo-obstruction, osteoporosis, testicular failure, retinal degeneration, and cardiomyopathy with a tortuous aorta. His serum copper was low and did not increase despite administration of large doses of intravenous copper sulfate. The ceruloplasmin level as measured by an antibody technique was normal, yet ceruloplasmin (Cp) oxidase activity was very low. The Cp amino acid sequence was normal. This suggests that the copper deficiency was caused by a defect in hepatic processing of copper for incorporation into Cp.
Autosomal dominant arteriopathic leuko-encephalopathy and Alzheimer's disease.
A 49-year-old man suffered from progressive dementia and seizures leading to death after 2 years. CT scans showed severe cortical-subcortical atrophy and hypodensity of the white matter. His father had died at about the same age with similar clinical signs. Two sisters and one brother were also affected. Neuropathological study revealed predominant involvement of the cerebral white matter with myelin loss, gliosis and type I lacunes. The small arteries and arterioles of the white matter and basal ganglia, and, to a lesser extent those of the subarachnoidal space, displayed fibrosis and replacement of the media by an eosinophilic, PAS positive, Congo Red negative, granular substance. Electron microscopy showed swollen myocytes surrounded by collagen, elastin and a compact electron-dense material. Immunofluorescence using antibodies against IgA, IgG, IgM, C1q and C3 stained the abnormal media weakly. In the cortex, there were diffuse senile plaques and neurofibrillary tangles. Immunohistochemistry demonstrated beta/A4 positive material in cortical senile plaques but not in arterial walls. Adventitial macrophages were, however, immunoreactive for gamma-trace. Systemic arterioles were normal. The vascular changes and leukoencephalopathy are comparable to those described in 'Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy' (CADASIL). Similar vascular changes were also observed in nonfamilial cases. An association with Alzheimer changes in the cortex has not been described previously. The relationship between both diseases and the role of each in the causation of the dementia is unclear.
Neuropathology of Rett syndrome: case report with neuronal and mitochondrial abnormalities in the brain.
Neuronal changes in the brain of a Rett syndrome patient were examined in a frontal lobe biopsy performed at age 3 years and in the postmortem brain at age 15 years. In the brain biopsy, frontal cortex contained numerous scattered pyramidal neurons with cytoplasmic vacuolation and increased cytoplasmic density, with no neuronophagia or inflammation detected; electron microscopy showed these neurons to have large, lucent-appearing mitochondria, very abundant ribosomal content, and some lipofuscin granules. Postmortem brain 12 years later showed scattered neurons in frontal cortex, substantia nigra, and cerebellar folia, with increased electron density of the cytoplasm, stacks of ribosomal endoplasmic reticulum, and large amounts of disorganized membranous material, including autophagic-type organelles. Mitochondria of these neurons contained electron-dense, finely granular matrix inclusions; in the substantia nigra, some spherical mitochondrial inclusions completely filled the matrix space. Golgi preparations of (autopsy) frontal cortex and cerebellar folia showed truncation and thickening of dendrites and a degenerate appearance of cortical pyramidal neurons, similar to changes found in aged brain. Synaptophysin immunohistochemistry indicated that the density of synapses was not greatly altered compared to controls in frontal cortex and cerebellum. The patient also had a second genetic defect, severe combined immunodeficiency with thymic aplasia, which may be X-linked.
Potential toxic effects of superselective injection of amobarbital sodium on microvasculature: a study in an animal model.
PURPOSE: To determine whether microvascular damage occurs from superselective intraarterial injection of amobarbital sodium using the swine endovascular embolization model. METHODS: Thirty-four swine underwent percutaneous femoral puncture for superselective catheterization of the proximal artery of the rete. Varying concentrations of amobarbital sodium were prepared (12.5 to 100 mg/mL solution) in either normal saline or sterile water (105 mOsm/L to 1138 mOsm/L) of which one concentration was infused slowly into one ipsilateral rete. Control infusions were also performed. Histopathologic changes were evaluated at 30 minutes and 10 days after infusion, using standard light and electron microscopy techniques. RESULTS: Moderate vasospasm occurred only in three swine at 100 mg/mL amobarbital sodium in normal saline. Light microscopy showed no significant histologic changes in the retia at any of the tested concentrations of amobarbital sodium. Electron microscopy showed ultrastructural alterations in the intima only at the higher amobarbital sodium concentrations. CONCLUSIONS: Concerns for inducing significant damage to cerebral microvasculature by superselective injection of amobarbital sodium at the usually recommended concentrations and doses are probably not justified.
Technical feasibility and histopathologic studies of ethylene vinyl copolymer (EVAL) using a swine endovascular embolization model.
PURPOSE: To study the safety, technical efficacy, and histopathology of the ethylene vinyl alcohol copolymer (EVAL) embolic mixture in an animal model. METHODS: Microcatheterization of the rete was performed in 29 swine. The clinical, angiographic, and histopathologic consequences of superselective injection of the two principal embolic mixture components (EVAL and dimethyl sulfoxide [DMSO]) were evaluated. Necropsy and standard histologic preparation were used for pathologic analysis. RESULTS: Significant technical difficulties and adverse outcomes occurred. The EVAL mixture was difficult to see under fluoroscopy and prematurely polymerized during one embolization, resulting in catheter occlusion. However, polymerized EVAL did not adhere to the catheter. DMSO damaged the plastic hubs of the microcatheters. Infusions of DMSO always caused immediate, moderate to severe vasospasm and frequently caused either subarachnoid hemorrhage or stroke. Histopathologic findings of both DMSO and DMSO plus EVAL were similar, producing variable endothelial denuding, thrombosis, and disruption of internal elastic lamina in the acute stage. An intense, mixed inflammatory response, organized thrombus, and transmural necrosis with extravasation were seen in the subacute and chronic stages. CONCLUSIONS: Despite having some desirable features as an embolic agent, significant problems were encountered with EVAL; the most important of which is that one of the principal components of the embolic mixture, DMSO, seems to be very angiotoxic.
Expression of oligodendrocyte-associated genes in cell lines derived from human gliomas and neuroblastomas.
Two putative human oligodendroglioma cell lines were examined for the expression of the oligodendrocyte-associated genes, 2',3'-cyclic nucleotide-3'-phosphodiesterase, myelin basic protein, myelin proteolipid proteins, and myelin-associated glycoprotein. The expression of these genes also was examined in control astrocytoma and neuroblastoma cell lines. In addition, the expression of the non-oligodendrocyte-specific genes, glial fibrillary acidic protein (GFAP), neuron-specific enolase and neurofilaments (NF) NF-L and NF-M also were examined. All the cell lines expressed 2',3'-cyclic nucleotide 3'-phosphodiesterase, neuron-specific enolase, and vimentin, and none expressed myelin-associated glycoprotein. The "oligodendrocyte-specific" myelin proteolipid protein mRNAs and the "neuron-specific" NF-L mRNA were expressed in the two astrocytoma cell lines, which also expressed GFAP. Expression of intermediate filament protein genes was more restricted. The astrocytoma, neuroblastoma, and oligodendroglioma cell lines expressed only GFAP, NF-M, and cytokeratin K7, respectively. These results: (a) provide molecular data confirming the classification of the two cell lines as oligodendrogliomal and suggest that their molecular profiles are indicative of immature oligodendrocytes; (b) demonstrate the expression of cytokeratins in oligodendrogliomal cell lines and suggest that apparent GFAP expression in oligodendrogliomas detected by immunocytochemical methods may be due to cross-reactivity with cytokeratins, with which they share common polypeptide sequence; and (c) indicate that astrocytoma cell lines can exhibit a "mixed" phenotype, expressing genes associated with fully differentiated oligodendrocytes and neurons.
Acute varicella-zoster virus ventriculitis and meningo-myelo-radiculitis in acquired immunodeficiency syndrome.
A 30-year-old AIDS patient with no history of cutaneous eruption, presented with rapidly progressive flaccid paraplegia, hypoesthesia, urinary retention, moderate psychomotor slowing and fever (39.8 degrees C), leading to death within 1 week. CD4 count was 290/mm3. Cerebrospinal fluid contained 210 white blood cells and 238 mg/100 ml protein. Neuropathology revealed HIV encephalitis and diffuse ventriculitis with Cowdry type A inclusions in the ependymal cells. Extensive necrotic and hemorrhagic changes with marked recrotizing vasculitis involved the entire spinal cord and spinal roots. Immunocytochemistry revealed numerous inclusion bodies positive for varicella-zoster virus (VZV) and negative for cytomegalovirus (CMV) and herpes simplex virus type 1 and 2, in ependymal cells, subpial glial cells, endothelial cells and Schwann cells. Electron microscopy confirmed herpes virus-like particles. In situ hybridization confirmed VZV genome in leptomeninges, brain, spinal cord and spinal roots. Comparable neuropathological findings and numerous VZV inclusion bodies were also found in the brain, spinal cord, and spinal roots of a 40-year-old AIDS patient who died from a fulminant ascending myeloradiculopathy previously reported as "necrotizing vasculitis of the nervous system". Direct infection of the brain by VZV, in AIDS patients, has been shown to cause leukoencephalitis and cerebral non-inflammatory vasculopathies. Our observations demonstrate that, in AIDS patients, VZV infection of the central nervous system may also be responsible for meningo-myelo-radiculitis possibly secondary to ventriculitis as in CMV infection. The role of VZV in the pathogenesis of some AIDS-related vasculitides seems also very likely.
Pathologic findings in a patient with a vein of Galen aneurysm treated by staged endovascular embolization.
Vein of Galen aneurysms are uncommon malformations that can be treated with a combination of endovascular embolization and surgery. Since the relevant techniques are new and innovative, their pathologic sequelae are not yet well described. A patient treated with staged embolization over a 15-month period developed evidence of cerebral venous hypertension on angiography. At necropsy, we observed marked myointimal proliferation of the aneurysm wall, dura, and cerebral vessels in addition to severe widespread encephalomalacia, calcinosis, and rare mural thrombi. These vascular changes have not been previously described in cases of vein of Galen aneurysm, and may, in part, be a consequence of embolization therapy.
The pathology of arteriovenous malformations of the brain treated by embolotherapy. II. Results of embolization with multiple agents.
Light microscopic and immunohistochemical examination was undertaken of intracranial arteriovenous malformations (AVMs) surgically resected from 18 patients, each of whom had undergone preoperative angiographic embolization with multiple agents. Distinct patterns of tissue reaction to these agents were noted, even when more than one substance was present in a vascular lumen. Avitene produced the mildest tissue response but resulted in relatively early endothelialization and recanalization. Cyanoacrylates were longer-lasting but associated with more acute and chronic (including granulomatous) inflammation and vessel wall changes. Polyvinyl alcohol foam/ethanol mixture had intermediate properties. Endothelial proliferation over embolization material was confirmed using immunohistochemical application of an antibody to cell proliferation-specific proteins. The significance of these findings for combined endovascular and surgical treatment of cerebral vascular malformations is discussed.