Rabies encephalitis in humans: pathology, pathogenesis and pathophysiology.
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Animals↗
Biomedical subjects
R E Mrak
Publications and source records attributed to R E Mrak.
Glial cytokines as neuropathogenic factors in HIV infection: pathogenic similarities to Alzheimer's disease.
The mechanisms by which human immunodeficiency virus (HIV) infection provokes progressive neurodegeneration and dementia in acquired immunodeficiency syndrome (AIDS) remain obscure. In HIV-infected (HIV+) individuals, we found that the brain cells preferentially infected by HIV, viz. the microglia, were abundant, activated, and intensely immunopositive for interleukin-1 alpha (IL-1 alpha), an immune response-generated cytokine that increases the synthesis and processing of beta-amyloid precursor proteins (beta-APP) and promotes proliferation and activation of astroglia. We also found an increase in the number of activated astroglia expressing elevated levels of S100 beta, a cytokine that increases intraneuronal calcium levels and promotes excessive growth of neuronal processes (neurites). These glial changes were accompanied by increased expression of beta-APP immunoreaction product in neurons and overgrown (dystrophic) neurites. In addition, some neurons contained monoclonal antibody Tau-2 immunopositive, neurofibrillary tangle-like structures. Our findings provide evidence that glial activation with increased expression of IL-1 alpha and S100 beta may be important in the neuropathogenesis of AIDS dementia. We propose that HIV infection promotes excessive microglial IL-1 alpha expression with consequent astrogliosis and increased expression of S100 beta. Overexpression of these two cytokines may then be involved in AIDS neuropathogenesis by inducing gliosis, growth of dystrophic neurites, and calcium-mediated neuronal cell loss in AIDS.
Adult↗
Malignant acoustic schwannoma.
An unusual pleomorphic tumor was resected from the cerebellopontine angle of a 40-year-old man with no stigmata of neurofibromatosis. The tumor showed multinucleated giant cells scattered amid smaller, slightly elongated cells. The tumor showed a rudimentary fascicular pattern containing some looser areas but no nuclear palisading. A diagnosis of Schwann cell tumor was made based on ultrastructural findings and on immunoreactivity for S100 protein. Malignancy was suggested by the extreme pleomorphism of the tumor, by the presence of tripolar mitotic figures, and by flow cytometric demonstration of aneuploidy and of a significant proportion of S-phase tetraploid nuclei (9%). Ten months after the first operation, the tumor had regrown to its original size, and was again resected. The histologic and ultrastructural appearances were similar to those of the first specimen, but flow cytometric analysis now showed a double aneuploid population of nuclei and showed 12% of the nuclei in tetraploid S phase. Within 11 months of the second operation, the tumor had regrown to an estimated size of 22 cm3. Four months of radiotherapy subsequently halted tumor growth, but additional lesions appeared in the cervical and high thoracic areas.
Adult↗
Rabies encephalitis in a patient with no history of exposure.
A 29-year-old man died of a rapidly progressive encephalitis without a clinical diagnosis and without a history of exposure to the rabies virus. A diagnosis of rabies was established postmortem by histologic and ultrastructural demonstration of rabies virus inclusions, by fluorescent antibody reaction, and by viral culture. Viral inclusions were sparse, were generally irregular and poorly demarcated, and were confined almost exclusively to the cerebellar Purkinje cells. A history of exposure was obtained only in retrospect on detailed questioning of friends and relatives. Rabies encephalitis is now seen most frequently in patients without a history of exposure and may be easily overlooked both clinically and pathologically.
Adult↗
Broad A bands of striated muscle in Leber's congenital amaurosis: a new congenital myopathy?
A 2-year-old boy with Leber's congenital amaurosis, hypotonia, depressed myotatic reflexes, and delayed motor development had numerous foci of broadened or smeared A bands, loss of distinct I bands, and near-normal Z lines in biopsied muscle. The thick filaments in these lesions appeared misaligned, suggesting an abnormality of the M line or of the structural protein connectin. This unique alteration represents the first described morphologic abnormality of muscle in a patient with Leber's congenital amaurosis.
Biopsy↗
Origins of adenocarcinomas presenting as intracranial metastases. An ultrastructural study.
Adenocarcinomas of unknown origin are a common neurosurgical problem. In many such cases, the primary tumor remains clinically obscure. A series of 28 adenocarcinomas of unknown origin, presenting as intracranial metastases and examined with electron microscopy, was reviewed blindly in a "retrospective prospective" fashion. Distinguishing ultrastructural features allowed prediction of site of origin in 26 cases (93%). Clinical and postmortem follow-up allowed the identification of likely primary tumor sites in 13 cases, with confirmation of the ultrastructural diagnosis in all 13 cases. The great majority of adenocarcinomas of unknown origin were found to originate in the lung (22/26 [85%]), while a few originated in the colon (2/26 [8%]) or kidney (2/26 [8%]). The predominance of pulmonary tumors among intracranial metastatic adenocarcinomas of unknown origin is much greater than the reported 45% to 55% predominance of pulmonary tumors among all intracranial metastatic carcinomas of unknown origin. Electron microscopy is a useful technique to either confirm a bronchogenic origin or to suggest an alternative primary site for these tumors.
Adenocarcinoma↗
The brain stem reticular formation in schizophrenia.
Post-mortem brain tissue was obtained from four patients with schizophrenia and five controls to study cell groups in the brain stem reticular formation. Cholinergic neurons in the pedunculopontine nucleus (PPN) and lateral dorsal tegmental nucleus (LDT) were labeled using nicotinamide adenosine dinucleotide phosphate (NADPH)-diaphorase histochemistry, while catecholaminergic neurons of the locus ceruleus (LC) were labeled immunocytochemically using an antibody to tyrosine hydroxylase. In schizophrenic patients, there were increased numbers of neurons in the PPN labeled by NADPH-diaphorase and reduced cell size in the LC. These results implicate the reticular formation as a possible pathophysiological site for at least some patients with schizophrenia. This also suggests that some of the deficits observed may be based on faulty neurodevelopment.
Aged↗
Supraciliary hemangiopericytoma.
A 10-year-old black girl complaining of pain and decreased vision in the left eye was found to have a smoothly elevated ciliochoroidal mass involving the superonasal quadrant of the left eye. The mass appeared circumscribed and uniformly dense by computed tomography. The tumor was hyperintense to vitreous and cerebral white matter on T1-weighted magnetic resonance imaging but was hypointense to vitreous and hyperintense to white matter on T2-weighted magnetic resonance imaging. Results of gross examination of the enucleated eye showed a sharply circumscribed, tan, intraocular mass arising equatorially. Results of histopathologic examination showed a well-vascularized spindle cell proliferation with a sinusoidal pattern characteristic of hemangiopericytoma. This is the third reported case of intraocular hemangiopericytoma and the first in a pediatric patient.
Child↗
Orbital intramuscular schwannoma.
In an 8-year-old girl with asymptomatic proptosis, computed tomographic scans showed a large medial orbital mass that contoured the globe anteriorly, bowed the optic nerve laterally, and extended posteriorly to the orbital apex. T1-weighted coronal magnetic resonance images showed the mass to be a diffusely enlarged medial rectus muscle. Histopathologic examination of a medial rectus muscle biopsy specimen disclosed a multinodular, intramuscular schwannoma, separating and infiltrating normal skeletal muscle fibers. The intramuscular location and multinodular configuration of this tumor, together with its occurrence in a child, distinguish it from previous orbital schwannomas.
Biopsy↗
Reperfusion injury in ischemic myocardium: protective effect of controlled reperfusion.
Restoration of coronary artery flow following a period of ischemia often results in further ultrastructural damage to cardiac fibers, a phenomenon known as reperfusion injury. We have compared the ultrastructural effects of uncontrolled reperfusion in vivo of ischemic pig myocardium with the ultrastructural effects of reperfusion controlled at flow rates comparable to preischemia levels. Myocardial ischemia was produced for 60 minutes in 9 pigs by means of a reversible coronary artery occlusion, after which coronary artery flow was restored for 120 minutes. This restoration of flow was complete in four pigs (resulting in uncontrolled reperfusion) and partial in five pigs, with constant monitoring and adjustment of flow to maintain rates near preischemia values (controlled reperfusion). Myocardial samples from the ischemic, reperfused region were examined by electron microscopy. Ischemic damage to nuclei, mitochondria, and myofibrils and ischemic depletion of glycogen were graded independently and blindly by two investigators using a simple, nonparametric three-point scale. Ischemic damage was greater in pigs receiving uncontrolled reperfusion than in animals receiving controlled reperfusion, and these differences were significant for ischemic effects on nuclei (p less than 0.01), glycogen (p less than 0.02), and myofibrils (p less than 0.05) but not for ischemic effects on mitochondria (p = 0.095). We conclude that uncontrolled, hyperemic flow during reperfusion of ischemic myocardium is responsible, in part, for the phenomenon of reperfusion injury.
Animals↗
Microvasculature sparing with controlled reperfusion of ischemic myocardium.
Reperfusion of ischemic myocardium may result in further ultrastructural damage to cardiac fibers, a phenomenon known as reperfusion injury. We have recently shown that controlled reperfusion, with maintenance of reperfusion flow rates near preischemia levels, prevents much of this reperfusion damage. This observation suggests that mechanical damage to the myocardial microvasculature is important in the pathogenesis of reperfusion injury. In this study, we have used electron microscopy to examine the microcirculation of ischemic, reperfused pig myocardium under conditions of uncontrolled and controlled reperfusion. Animals receiving uncontrolled reperfusion (reperfusion flow 3-4 times preischemia levels) showed ultrastructural damage to myocardial capillaries after 1 hour of ischemia and 2 hours of reperfusion. This damage was manifested as depletion of endothelial cell pinocytotic vesicles, plugging of capillaries by erythrocytes, leukocytes, and fibrin-containing microthrombi, and perivascular microhemorrhages. None of these changes were found in animals receiving controlled coronary artery reperfusion. We conclude that mechanical damage to the myocardial microvasculature is important in the pathogenesis of reperfusion injury and that such damage is obviated under conditions of controlled coronary artery flow during reperfusion.
Animals↗
Ethanol inhibition of spontaneous calcium release from isolated sarcoplasmic reticulum of alcoholic rats.
Ethanol is a well-recognized cause of muscle damage in humans. In vitro, ethanol decreases muscle fiber twitch tension by a mechanism unrelated to the electrical events of the motor endplates or muscle surface membranes. One possible explanation for this effect is a primary ethanol effect on calcium release from the sarcoplasmic reticulum (SR). Ethanol has been shown to progressively decrease a form of calcium release from isolated SR vesicles seen in vitro in the presence of high phosphate concentrations ("spontaneous calcium release"). In this study, ethanol is shown to have similar inhibiting effects on spontaneous calcium release from sarcoplasmic reticulum isolated from alcoholic rats and from pair-fed controls. This suggests that membrane adaptation to chronic ethanol exposure, such as has been described for brain and liver membranes, does not produce tolerance to ethanol effects on spontaneous calcium release in sarcoplasmic reticulum.
Alcoholism↗
Ultrastructure of metastatic rete testis adenocarcinoma.
Adenocarcinoma of the rete testis is a rare tumor. We describe the ultrastructural appearance of a retroperitoneal adenocarcinoma metastatic from the rete testis, and compare this appearance with that of normal human rete testis. Both normal rete epithelium and the tumor showed deep, narrow nuclear invaginations with apparent nuclear lobulation; small, pleomorphic, electron-dense, membrane-bound granules in the basal cytoplasm; lipid droplets in the apical cytoplasm; and distinctive bulbous cytoplasmic projections along the apical surfaces of the cells. In addition, more general features of glandular tissue were seen. Features notable for their absence were mucin granules, microvilli containing filamentous cores, glycocalyx, and glycocalyceal bodies. The ultrastructural appearance was sufficiently distinctive to suggest that, in the proper clinical context, electron microscopy may serve to support a diagnosis of adenocarcinoma of the rete testis.
Adenocarcinoma↗
Reperfusion injury in ischemic myocardium: effects of nifedipine and verapamil.
Coronary reperfusion following myocardial ischemia may result in further damage to injured myocytes, as judged by their ultrastructural appearance. Calcium entry into myocytes has been implicated in this effect, and calcium channel-blocking agents have been used in attempts to prevent or limit such damage. In this study, we produced myocardial ischemia in pigs by means of reversible coronary artery occlusion. The pigs were infused with either nifedipine or verapamil (both clinically employed calcium channel-blocking agents) prior to and during coronary reperfusion. During reperfusion, nifedipine produced a lowering of mean arterial pressure, while mean arterial pressure was constant in verapamil-treated pigs and rose in pigs not receiving drugs. Myocardial samples from the ischemic, reperfused region were examined by electron microscopy. Ischemic damage to nuclei, mitochondria, and myofibrils and glycogen depletion were independently graded on a three-point scale by two investigators. For each of the organelles studied, ischemic damage was significantly less for nifedipine-treated animals than for controls. Ischemic damage in verapamil-treated pigs was not different from that seen in control animals, except for a slight improvement in myofibrillar appearance. We conclude that nifedipine, administered prior to and during reperfusion of myocardium, protects against reperfusion injury. The mechanism of this protective effect may be attributable, in part, to afterload reduction and, in part, to inhibition of transmembrane calcium flux in cardiac fibers.
Animals↗
Triphasic effects of short chain n-alcohols on synaptic membrane transport of choline and of gamma-aminobutyric acid.
n-Alcohols, when added in increasing concentrations, had an unusual triphasic effect on the uptake of choline and of gamma-aminobutyric acid by isolated synaptosomes. There was slight inhibition of these uptakes at low n-alcohol concentrations, followed by a sharp peak of uptake enhancement, and then greater inhibition. The n-alcohol concentrations required for these effects were proportional to published n-alcohol membrane/buffer partition coefficients, with the peaks of uptake enhancement occurring at 60 mM n-propanol, 20 mM n-butanol and 7.5 mM n-pentanol. Synaptosomal membrane potential, as estimated from synaptosomal accumulation of the permeant cation [3H]tetraphenylphosphonium, was not affected by n-alcohols in the concentrations used in this study, suggesting that neither the inhibitory or enhancing effects of these n-alcohols were attributable to changes in trans-synaptosomal membrane ion gradients. The inhibiting and enhancing effects of n-alcohols could be reproduced in determinations of gamma-aminobutyric acid uptake by isolated synaptic plasma membranes, suggesting that the observed effects are due to a direct action of the n-alcohols on the synaptosomal plasma membrane. These effects may be attributable to a change in membrane binding of these alcohols from the membrane core to the membrane surface as alcohol concentration is increased.
Alcohols↗
An orbital hemangiopericytoma recurrent after 33 years.
A middle-aged woman developed a recurrent orbital hemangiopericytoma 33 years following its initial removal. Preoperative computed tomographic and magnetic resonance imaging scans revealed a well-circumscribed superotemporal orbital mass. A tumor that appeared grossly encapsulated was removed intact via a lateral orbitotomy. Histopathological examination showed a hemangiopericytoma with hypercellularity and a moderate number of mitotic figures. A review of the initial pathologic report confirmed the diagnosis of hemangiopericytoma with histological features similar to those of the recurrent mass. To our knowledge, this case represents the longest reported interval to recurrence of any hemangiopericytoma and demonstrates the extended follow-up needed in patients with hemangiopericytoma.
Female↗
Reperfusion injury in ischemic myocardium: protective effects of ruthenium red and of nitroprusside.
Coronary reperfusion following myocardial ischemia may result in further damage to injured myocytes, as judged by their ultrastructural appearance. Ruthenium red is an inorganic dye with calcium flux-inhibiting properties which protects ischemic myocardium against reperfusion damage, as judged by biochemical indices of mitochondrial function. In this study, we produced myocardial ischemia in pigs by means of reversible coronary artery occlusion. The pigs were infused with either ruthenium red or nitroprusside (an after-load reducing agent with no known calcium flux-inhibiting properties) prior to and during coronary reperfusion. During reperfusion, both ruthenium red and nitroprusside produced similar lowering of mean arterial pressure, while mean arterial pressure rose in pigs not receiving these drugs. Myocardial samples from the ischemic reperfused region were examined by electron microscopy. Ischemic damage to nuclei, mitochondria, and myofibrils and glycogen depletion were graded independently on a three-point scale by two investigators. For each of the organelles studied, ischemic damage was significantly less for treated animals than for controls. This protective effect was similar for both ruthenium red-treated animals and nitroprusside-treated animals. These results suggest that the protective effects of ruthenium red treatment are attributable to its afterload reducing properties rather than to inhibition of transmembrane calcium flux in cardiac fibers.
Animals↗
Ethanol inhibition of spontaneous calcium release from isolated sarcoplasmic reticulum.
Ethanol, in vitro, decreases muscle fiber twitch tension by a mechanism unrelated to the electrical events of the motor end-plate or muscle surface membranes, an effect which may be attributable to a primary ethanol effect on the calcium release process of the sarcoplasmic reticulum. In this study, ethanol was found to progressively decrease a form of calcium release from isolated sarcoplasmic reticulum vesicles seen after calcium loading in high-phosphate media (spontaneous calcium release). Elevated extravesicular free calcium concentrations are known to inhibit spontaneous calcium release, and the ability of sarcoplasmic reticulum to achieve and maintain submicromolar extravesicular free calcium concentrations in the presence of ethanol was therefore determined. Ethanol had no effect on the low extravesicular free calcium concentrations achieved by isolated sarcoplasmic reticulum, and had no effect on residual ATPase activity remaining after cessation of calcium pumping. This latter result suggests that efflux of vesicular calcium and persistent calcium reaccumulation do not occur in the presence of ethanol. These results suggest that ethanol-induced depression of spontaneous calcium release is not attributable to ethanol effects on sarcoplasmic reticulum membrane calcium leakage or on sarcoplasmic reticulum calcium pumping. Ethanol inhibition of spontaneous calcium release from isolated sarcopasmic reticulum may reflect an effect of ethanol on the calcium release process in intact muscle fibers responsible for ethanol-induced decreases in muscle fiber twitch tension.
Adenosine Triphosphatases↗