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G Gosztonyi

Publications and source records attributed to G Gosztonyi.

At least 37 records · Page 2Linked to original sources
PubMed1995

Borna disease--neuropathology and pathogenesis.

Natural BD is a nonpurulent acute/subacute encephalitis of horses and sheep with a propensity to involve the olfactory and limbic systems, and the brain stem. The inflammation is concentrated primarily in the gray matter, but subcortical white matter may also be affected. Experimental BD can be produced in a series of animals from birds to primates. The neuropathology after experimental infection is similar to that in natural disease but the inflammatory changes are more diffuse. In the rat and mouse, a persistent/tolerant infection can also be induced, in which inflammatory changes are conspicuously absent. In the course of persistent infection of the rat, an elective, focal degeneration ensues that involves the dentate gyrus, retina, and, less frequently, the magnocellular part of the hippocampus. The cytopathic destruction of the dentate gyrus is the likely anatomical substrate of learning deficiencies and behavioral changes, prominent features of chronic infection. Later in infection, more diffuse and random degeneration of neurons can be found. In all species infected, viral antigens are produced in excess and fill all neuronal processes. Beside neurons, glial cells are infected as well. The agent spreads in the nervous system axonally and transsynaptically (transneuronally). The type of neurotransmitter receptors in the synapse and their interaction with viral proteins may modulate the spread of infection (Gosztonyi et al. 1994). Virus particles have not been visualized in the brain in any phase of the disease. During persistent infection of the rat, production of viral proteins has a phasic character. Some rats survive acute infection and develop an obesity syndrome. The anatomical basis of this syndrome is not fully clarified; inflammatory destruction of the infundibular region, vacuolar degeneration of the paraventricular nucleus of the hypothalamus and severe, progressive involution of the hippocampal formation most probably play an important role in the production of this neuroendocrine syndrome. In the acute disease, inflammatory reaction can severely aggravate virus-induced cytopathology, but cannot be the sole cause of the neurological disease, since infection with high passage virus can lead to a similarly severe disease in the absence of inflammatory changes.

Animals↗
PubMed1994

Reproduction of lyssaviruses: ultrastructural composition of lyssavirus and functional aspects of pathogenesis.

Lyssaviruses are considerably adapted to neural tissue, although they can also be replicated in muscle and glandular cells. In neural tissue their reproduction takes place almost exclusively in neurons, and in the course of their dissemination they make use of the structural peculiarities of this highly differentiated cell type. The replication takes place completely in the cytoplasm, although rhabdovirus leader RNA enters the nucleus and by blocking host DNA and RNA synthesis promotes viral synthetic processes. In the cytoplasm the two phases of viral reproduction, the synthesis of nucleocapsids and the formation of the envelope together with the assembly of the virion, are separate in time and space. By this separation the transmission of infection by the incomplete form of the virus, i.e., by the synaptic transfer of ribonucleoprotein-transcriptase complexes is also possible. The formation of viral envelope and assembly of full viruses on the cisternal system of the host neurons is a highly complex process, as presented here in a three-dimensional analysis. Due to the high complexity of virus assembly, defects in construction are frequent, accounting for the high yield of defective interfering particles in the course of the reproduction of lyssaviruses.

Adsorption↗
PubMed1994

Vasculitic, hypoxic-ischemic leukoencephalopathy.

The case of a 67-year-old woman with terminal renal insufficiency, who developed extensive encephalopathy with predominant involvement of the white matter is reported. The encephalopathy was the consequence of preexisting hypertensive alterations, acidosis, hypoxia, ischemia, bacteremia and varicella-zoster meningoencephalitis. The vasculitic alterations associated with meningoencephalitis had a major influence on the development and the extent of the leukoencephalopathy.

Aged↗
PubMed1994

Human immunodeficiency virus (HIV) distribution in HIV encephalitis: study of 19 cases with combined use of in situ hybridization and immunocytochemistry.

Brains of 19 AIDS patients with HIV encephalitis were examined by immunohistochemistry and in situ hybridization using antisense HIV DNA and RNA probes. Double immunohistochemical labeling, using antibodies against viral and cell-type specific antigens, was utilized to study lesions in some brains. Other combined studies included use of in situ hybridization and immunohistochemical labeling of the same section, using antibodies against either viral or cell-type specific antigens. Hybridization signals were abundant and were concentrated mainly in the white matter. Heavy labeling was found in the subcortical white matter, the corpus callosum, the internal capsule, and white matter regions of the brainstem and cerebellum. Deeper cortical layers often contained cells with hybridized probe when the subcortical white matter was intensely labeled. HIV nucleic acid sequences were found almost exclusively in macrophages. Counts showed that 16-25% of macrophages contained viral antigens and exhibited hybridized HIV probe. Almost all of these macrophages contained proviral DNA, viral RNA and viral proteins; i.e. they were actively replicating HIV. We also examined brains from three AIDS cases without clinical or pathological evidence of HIV encephalitis; no HIV sequences or immunoreactive proteins were detected.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Neuropathologic analysis of postmortal brain samples of HIV-seropositive and -seronegative i.v. drug addicts.

Between 1987 and 1992 we performed forensic-pathologic and neuropathologic examinations on 70 cases of i.v. drug addicts who died of an overdose. In almost 25% of the cases HIV-positivity was revealed by serological examinations. In all the cases, irrespective of the result of the serological examination, a diffuse, reactive astrocytosis was the most prominent histologic alteration, accompanied by more or less pronounced regressive changes of this cell type in the deep layers of the white matter. Furthermore, also in all the cases, a slight to moderate, reactive proliferation of microglia could be assessed. In a few cases of the HIV-seropositive group a lymphocytic meningitis, viz. meningoencephalitis was found; these changes may indicate an early invasion of the central nervous system (CNS) by the HIV. In spite of these inflammatory alterations, in the latter cases no HIV-specific antigens (p24 and gp41) could be demonstrated in the brain, most probably because of the small number of infectious particles. In order to reveal the earliest phase of invasion of the CNS by the HIV, we performed a search for HIV-specific nucleic acid sequences by the aid of the polymerase chain reaction (PCR) in 8 HIV-seronegative and 8 normal control cases. Although, most probably due to contamination, also the control cases exhibited some PCR-signals, these were more pronounced and appeared with more primer-pairs within the group of HIV-seronegative drug addicts. It is conceivable that HIV penetrates the CNS and is harboured in it in latent form shortly after the primary infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Diseases↗
PubMed1993

Rabies and borna disease. A comparative pathogenetic study of two neurovirulent agents.

BACKGROUND: Rabies and Borna disease viruses have been regarded as classical neurotropic agents. Many pathogenetic similarities are shared by these two negative strand RNA viruses. In view of recently gained data on the virology and pathology of these two diseases, and up-to-date comparative pathogenetic study seems to be justified. EXPERIMENTAL DESIGN: This study is based on a survey of experimental and natural infections of laboratory animals and natural hosts. The morphologic damage to the nervous system has been evaluated by light and electron microscopy, with special emphasis on immunocytochemical methods. RESULTS: This comparative study disclosed that both viruses are transported inside axons, pass synapses and propagate along neuronal networks. At the sites of synaptic transfer, full virus particles can never be detected in the early phase of rabies virus infection; in Borna disease virus (BDV) infection, virus particles cannot be found in any phase of disease progression. Thus, a major difference exists between the two agents insofar as rabies virus is morphologically well characterized, whereas BDV has never been visualized in tissue sections. Furthermore, rabies virus infects only neurons, whereas BDV also infects glial cells. The host range and the scale of infection of extraneural tissues by both agents is extremely similar. CONCLUSIONS: These observations allow us to postulate that the synaptic transfer of both viruses likely ensures in the form of bare nucleocapsids (ribonucleoprotein-transcriptase complexes). While in the later phases of replication complete rabies virions are regularly assembled, BDV propagates within the central nervous system in an incomplete form, so that it remains morphologically imperceptible. Thus, BDV may appear in a complete, enveloped form only when exiting the host organism. The dissemination patterns of the two agents may be influenced by specific affinities to neurotransmitter receptor sites. It remains unresolved, why BDV readily infects non-neuronal central nervous system cells, while rabies virus remains restricted to neuronal elements.

Animals↗
PubMed1992

Stereotactic brain biopsy in AIDS.

In the hope of finding a treatable condition, the need for rapid diagnosis in HIV-seropositive patients with brain lesions is apparent. In order to evaluate the efficacy of stereotactic brain biopsy in AIDS patients, we retrospectively studied 25 HIV-infected patients undergoing stereotactic biopsy. Brain lesions were identified with gadolinium-enhanced MRI and/or contrast CT. Brain biopsy was performed using the system of Riechert. From 8 up to 15 small tissue samples from one or two targets were obtained in every patient. The biopsy material was examined cytologically, histologically (including electron microscopy), immunohistochemically and, in part, by animal test and polymerase chain reaction (PCR). A definite diagnosis was achieved in 92%. Diagnosis included primary central nervous system lymphoma (PCNSL) (10), toxoplasmosis (10), progressive multifocal leukoencephalopathy (2) and one case of co-existing toxoplasmosis and cytomegalovirus infection. Two biopsies were non-diagnostic. All PCNSLs showed polymorphic B-cell populations of high malignancy; accurate classification according to the Kiel classification was not possible. In 3 lymphomas Epstein-Barr nuclear antigen (EBNA) 2-mRNA could be detected by PCR and confirmed immunohistochemically by EBNA 2 expression. In 6 cases autopsy confirmed the biopsy diagnosis. Conventional histology was not sufficiently decisive for toxoplasmosis and progressive multifocal leukoencephalopathy, so that immunohistochemistry and animal tests became very important for a final diagnosis. With the help of different morphological and molecular biological techniques stereotactic brain biopsy appears to be an effective method in the diagnosis of HIV-associated brain lesions. In view of the marked radio- and chemosensitivity of PCNSLs it is mandatory to establish an early and accurate histological diagnosis for adequate treatment.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Neuropathy with lysosomal changes in Marinesco-Sjögren syndrome: fine structural findings in skeletal muscle and conjunctiva.

The light- and electron-microscopical findings in the skeletal muscle and conjunctiva of 6 patients with Marinesco-Sjögren syndrome (MSS) were presented. All patients were related and showed the cardinal clinical symptoms of the syndrome: congenital cataracts, mental retardation, delayed statomotor development, and cerebellar ataxia. The most prominent alteration found in the skeletal muscle of four patients was extensive neurogenic atrophy with conspicuous groups of atrophic muscle fibers. Additional findings were vacuolar degeneration and secondary, unspecific changes like slight mitochondrial alterations and increased variability in muscle fiber calibers. The ultrastructural examination revealed double-membrane structures near to, but not in direct contact with the nucleus. The nuclear changes described earlier (7, 20) were not found in any of the cases. Conjunctival biopsies revealed a marked increase in the number of lysosomes in fibroblasts. In summary, to the well known myopathic damage of muscles in MSS a neurogenic component should be added. Disturbed lysosomal function is to be considered as the basic abnormality, though the enzyme defect has not yet been identified. In cases of clinically suspected MSS, examination of a conjunctival biopsy is highly recommended.

Conjunctiva↗
PubMed1992

Axonal and transsynaptic (transneuronal) spread of Herpesvirus simiae (B virus) in experimentally infected mice.

In order to study the pathogenesis of B virus infection of the nervous system, newborn and young mice were inoculated by four different routes: 1. Intramuscular (i.m.) in the forelimb; 2. I.m. in the hindlimb; 3. Subcutaneous (s.c.) in the abdominal wall; 4. Intraperitoneal (i.p.). Spread of virus was followed by immunohistochemical demonstration of viral antigen in tissue sections of the peripheral and central nervous system. Three distinct patterns emerged: 1. After i.m. limb inoculations, virus progressed along the ipsilateral dorsal column, the bilateral spinothalamic and bilateral spinoreticular systems and along central autonomic pathways. 2. After s.c. inoculation, the dorsal column was spared, otherwise the spread was similar to that following i.m. inoculations. 3. After i.p. inoculation, virus spread in the spinal cord bilaterally, mainly along spinothalamic and central autonomic pathways. The peripheral motoneurons were conspicuously spared, even in the i.m. inoculation mode. In the brain stem, B virus antigen appeared bilaterally, at multiple sites. In the cerebrum, virus infected cells appeared first in the thalamus, hypothalamus and the motor cortex. The mode of spread from spinal levels was mainly orthograde along the ascending systems (dorsal columns, spinothalamic, spinoreticular tracts), but also retrograde along descending systems (pyramidal tract, central autonomic pathways). Oligosynaptic systems transmitted virus more quickly than the polysynaptic ones. In the involvement of various neuronal systems in virus spread, a certain selectivity, sparing the peripheral motoneuron and the cerebellar systems, could be assessed.

Aging↗
PubMed1992

In situ hybridization histochemistry in the diagnosis of viral infections of the central nervous system.

In situ hybridization histochemistry opened new perspectives for the study of viral infections of the central nervous system. Immunohistochemistry can give information about the presence of a viral infection only, if the specific viral proteins are expressed in the infected cells, while in situ hybridization can detect viral genes also in case of a latent, non-productive infection. The basic technique has to be modified according to the kind of viral nucleic acid to be displayed (genomic DNA, plus or minus strand genomic RNA, viral mRNA). For detection, the highly sensitive radioactive or the less sensitive non-radioactive (enzyme-) labels can be applied. For the determination of the cell type harbouring the virus and for correlation of viral nucleic acids with viral proteins, in situ hybridization techniques and immunohistochemistry have to be combined.

Animals↗
PubMed1991

Type 2a fibre rhabdomyolysis in myoadenylate deaminase deficiency.

A 31-year-old woman developed an acute, potentially fatal rhabdomyolysis of undetermined origin. Muscle biopsy revealed selective lysis involving exclusively type 2a fibers. Myoadenylate-deaminase (MAD) deficiency was proven by a negative histochemical reaction as well as by an enzymatic biochemical determination. The significantly greater energetic dependence of type 2a fibres on MAD explains their selective damage. The patient's mother also suffers from a similar muscle disease of still unclarified origin.

AMP Deaminase↗
PubMed1990

Wernicke's encephalopathy in two patients with acquired immunodeficiency syndrome.

Two non-alcoholic homosexual patients with acquired immunodeficiency syndrome (AIDS) are reported who developed acute Wernicke's encephalopathy in the terminal stage of their illness. The first patient presented with vascular congestion, minute haemorrhages, proliferation of microglia and of the vessel walls at the predilection sites of the Wernicke-Korsakoff process. In the second patient only the mamillary bodies were involved. Besides Wernicke's encephalopathy, a primary cerebral immunoblastoma and cerebral toxoplasmosis were found in the first patient, whereas the second showed severe encephalitis with numerous microglial and multinucleated giant cells reacting positively with anti-HIV antibody. Just as in the development of Wernicke's encephalopathy in malignant diseases, the catabolic trend of the metabolism of the immunodeficient patients with consecutive thiamine deficiency must be considered the principal pathogenetic mechanism.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Hot knife microtomy for large area sectioning and combined light and electron microscopy in neuroanatomy and neuropathology.

The technical details given in this paper meet the demand in neuroanatomy and neuropathology for methods which combine broad light microscopical surveys with detailed ultrastructural studies of logically selected areas in well perfused brain material, and emerge directly from experiences in Palay's laboratory at the National Institutes of Health in 1956. Using the procedures recommended will give good sections of exceptionally large areas (up to, and above 1 cm x 1 cm) of fully hardened blocks available at all points for electron microscopy. On such large blocks fully correlative, combined light and electron microscopy may be carried out easily. The process is termed 'hot knife microtomy'. In three different laboratories, primary aldehyde fixation by perfusion and hot knife microtomy have given uniformly excellent data from normal, diseased, and virus-infected brain tissues. These techniques permit full neuroanatomical control and orientation, make comprehensive correlative mapping throughout the CNS feasible, and allow study of the time course of infective processes.

Animals↗
PubMed1990

Focal-unilateral accentuation of changes observed in the early stage of Creutzfeldt-Jakob disease.

We report on a 67-year-old male patient with progressive right-sided hemiparesis predominating in the arm and right-sided myoclonias. The EEG showed periodic delta activity in the left hemisphere. The patient died of pulmonary embolism 10 weeks after the onset of the symptoms. The neuropathological examination was indicative of Creutzfeldt-Jakob disease: distinct spongiform changes, nerve cell loss and proliferation of astroglia in the left hemisphere were found; in the right hemisphere, however, only a few circumscribed spongiform foci were seen. There was a clear correlation between the unilateral predominance of the EEG abnormality and neuropathological changes. The hypothesized spread of infection along commissural projection pathways is supported by this pattern of lesions.

Aged↗
PubMed1989

Morphometric study of muscle in congenital idiopathic club foot.

In congenital idiopathic club foot gross morphological changes cannot be assessed in muscle tissue by conventional histopathological techniques. Since, however, recent studies have indicated the presence of neuromuscular anomalies with preponderance of Type 1 fibres in this condition, we have performed histochemical, morphometric and electron microscopic examinations in muscle biopsies of 23 patients with congenital idiopathic club foot deformity. The age of the patients varied between 6 weeks and 12 years, respectively. Muscle biopsy was taken mainly from the flexor group of the affected leg(s) during the surgical correction of the anomaly. No gross pathological changes could be found by histochemical analysis. Morphometric study, however, disclosed abnormalities in the composition of the fibre types. The most prominent change was the percentual increase in Type 1 and decrease in Type 2 fibres in almost all the cases. Electron microscopically, only minor fine structural changes could be found. Since these changes could be assessed soon after birth just as in the later course, they cannot be regarded as the consequence of the abnormal position of the leg. More probably, Type 1 fibre predominance is related etiologically to the congenital club foot deformity.

Biopsy↗
PubMed1989

Spongiform encephalopathy in AIDS dementia complex: report of five cases.

We describe the morphological findings in the brain of five AIDS patients who died with a clinical diagnosis of dementia. We have found a spongiform change (small rounded vacuoles) in different parts of the brain and a similar but morphologically different sponginess, the status spongiosus, characterized by looser and coarser microcystic cavitations of the grey matter in which the tiny cysts and vacuoles are enmeshed by glial fibrils. At the ultrastructural level, round and oval clear spaces, divided by septae into several smaller ones, appeared in the neuropil. The pathogenesis of the majority of the vacuoles and cavitations is not clear yet but a focal loss of cortical neurons was evident and furthermore some of the vacuoles were identified as remnants of dendrites. The light and electron microscopic findings can not be interpreted as artefacts or as a simple edema of the brain and also can not be explained by the different infective complications. We have found spongiform alterations in all cases of clinically diagnosed dementia and therefore it seems obvious that these findings are quite frequent in AIDS dementia.

Acquired Immunodeficiency Syndrome↗