Biomedical subjects

S Morgello

Publications and source records attributed to S Morgello.

At least 37 records · Page 2Linked to original sources

PubMed1998

Cerebellar degeneration associated with human immunodeficiency virus infection.

Cerebellar disorders associated with HIV infection are typically the result of discrete cerebellar lesions resulting from opportunistic infections such as toxoplasmosis and progressive multifocal leukoencephalopathy or primary CNS lymphoma. Clinical symptoms and pathologic abnormalities related to the cerebellum may also be observed with HIV dementia. A primary cerebellar degeneration with HIV has not previously been reported. Ten patients were identified over an 8-year period at five medical centers. All patients had clinical, laboratory, and radiologic evaluations, and three had neuropathologic examinations. Patients presented with progressively unsteady gait, slurred speech, and limb clumsiness. Examination revealed gait ataxia, impaired limb coordination, dysarthria, and abnormal eye movements. Cognition, strength, and sensory function remained normal. CD4 lymphocyte counts varied between 10 and 437 cells/mm3. Neuroimaging studies showed prominent cerebellar atrophy. Neuropathology showed focal degeneration of the cerebellar granular cell layer and unusual focal axonal swellings in the brainstem and spinal cord. Cultures, histopathology, and immunochemical studies showed no conclusive evidence of infection. We report a syndrome of unexplained degeneration of the cerebellum occurring in association with HIV infection.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Idiopathic progressive hyalinizing and calcifying CNS vasculopathy.

We present a female adolescent with intermittently progressive neurologic deficits over a period of 7 years. Serial imaging studies showed a calcifying lesion with increasing enhancement, signal abnormalities from the subcortex to the medulla, and hemispheric volume loss. Stereotactic biopsies disclosed a hyalinizing and calcifying vasculopathy involving the penetrating vessels. The vasculopathy may result in ischemic lesions responsible for the severe deficits.

Adolescent↗

PubMed1997

Cerebral glucose transporter expression in HIV infection.

Abnormalities in cerebral glucose metabolism have been demonstrated in patients with AIDS dementia complex (ADC), with increased consumption in early disease and decreased utilization in late stages. The basis of these changes is unknown. Accordingly, a pilot study was undertaken to determine whether levels of cerebral glucose transporters GLUT1 and GLUT3 were altered by HIV disease. Frontal gray and white matter membrane preparations from patients with HIV encephalitis (HIVE), HIV infection without parenchymal neuropathology, and non-infected controls were utilized in quantitative immunoblots to measure GLUT1 and GLUT3. Results were expressed as a ratio of glucose transporter to structural protein actin. Within-group patient variability was great, precluding statistically significant differences between groups for any one brain region. However, when data for gray and white matter was pooled, results obtained statistical significance, with levels of GLUT1 increasing in HIV infection without neuropathology, and declining with HIVE. Increased GLUT1 in HIV infection without parenchymal neuropathology may be important in the biology of increased glucose consumption described with early ADC. With progression to HIVE, reduced levels of glucose transporters may contribute to late stage hypometabolism.

AIDS Dementia Complex↗

PubMed1997

The distribution of Lewy bodies in pure autonomic failure: autopsy findings and review of the literature.

Pure autonomic failure (PAF; also known as idiopathic orthostatic hypotension or Bradbury-Eggleston syndrome) is an uncommon sporadic disorder, characterized by autonomic failure without other neurological deficits and histopathologically by cell loss in intermediolateral columns and sympathetic ganglia. Few postmortem studies of patients with PAF have been reported in the literature, and none have demonstrated Lewy bodies in distal axons, although this has been described as a feature in Parkinson's disease with autonomic failure. We report a patient with PAF who had orthostatic hypotension and urinary symptoms for 15 years prior to death at the age of 63 years. Postmortem findings included typical and atypical Lewy bodies in the substantia nigra, locus ceruleus, substantia innominata, and sympathetic ganglia, as well as in autonomic axons in the epicardial fat, autonomic nerve fascicles in periadrenal adipose tissue, and autonomic nerves in the muscularis of the urinary bladder. Sites of autonomic nerve involvement correlated with clinical symptomatology, and thus were a valuable observation in the complete autopsy. Systemic autopsy results should be reviewed carefully in patients with PAF, as Lewy bodies in this disease may be seen in distal axons at a great length from their primary cell bodies.

Autonomic Nervous System Diseases↗

PubMed1997

HHV-8 and AIDS-related CNS lymphoma.

Human herpesvirus 8 (HHV-8), the Kaposi's sarcoma (KS)-associated herpesvirus, is closely related to the transforming Epstein-Barr virus (EBV) and may be detected in AIDS-related, EBV-containing, body-cavity-based lymphomas. Accordingly, we analyzed 27 EBV-positive, AIDS-related CNS lymphomas for HHV-8 sequences. Only one tumor yielded HHV-8 sequences; this tumor arose in a patient with concomitant systemic lymphoma and a history of KS. We conclude that HHV-8 is unlikely to have a major role in the pathogenesis of AIDS-related, EBV-associated CNS lymphomas.

Central Nervous System Neoplasms↗

PubMed1997

Epstein-Barr virus-associated dural leiomyosarcoma in a man infected with human immunodeficiency virus. Case report.

A 35-year-old man infected with human immunodeficiency virus presented with cervical myelopathy of 2 months duration. Clinical and radiographic evaluation revealed a discrete, subdural mass at C-6. At surgery, the mass proved to have a dural attachment and thus clinically, radiographically, and grossly, it resembled meningioma. Histopathological analysis revealed a leiomyosarcoma that stained diffusely for muscle-specific actin. Electron microscopy revealed basal lamina surrounding the tumor cells and intracytoplasmic bundles of myofilaments. Epstein-Barr virus (EBV) was demonstrated within tumor cell nuclei by in situ hybridization for EBER1 messenger RNA and immunohistochemical staining for EBNA2 protein. Epstein-Barr virus latent membrane protein (LMP1) was not detected. This is the first documentation of an EBV-associated smooth-muscle tumor of the dura, and the first demonstration that tumors in this location contain EBV in an unusual form of latency not seen in lymphoid cell lines. With increasing numbers of individuals being afflicted with long-term immunosuppression, EBV-associated dural leiomyoma and leiomyosarcoma may be encountered more frequently in the future.

Adult↗

PubMed1996

Idiopathic granulomatous hypophysitis.

A case is described of an elderly woman who presented with headaches, hypopituitarism, and visual disturbances and was found to have idiopathic granulomatous hypophysitis, a rare lesion of the pituitary gland. Preoperative magnetic resonance imaging demonstrated a well-circumscribed lesion, which was isointense on both T1- and T2-weighted imaging and enhanced uniformly with administration of gadolinium contrast enhancement, not unlike a macroadenoma. The present case and 12 other cases from the literature are reviewed.

Journal Article↗

PubMed1996

Undifferentiated carcinoma of the parotid gland in a white patient: detection of Epstein-Barr virus by in situ hybridization.

Paraffin sections of an undifferentiated salivary gland carcinoma of lymphoepithelioma type, arising in a white (Greek) patient and confirmed by immunohistochemistry, were examined for the presence of Epstein-Barr virus (EBV), using in situ hybridization to detect EBV-specific EBER1 message. Epstein-Barr virus was detected in malignant epithelial cells, but was not found in lymphoid stroma or in residual benign salivary epithelium. These results confirm the existence of an association between EBV and tumor cells of undifferentiated carcinoma of parotid gland. This is the first demonstration of EBV in a salivary gland lymphoepithelioma arising in a non-Eskimo, white patient. This finding suggests that the association of EBV with undifferentiated salivary gland carcinoma may exist in geographic regions remote from Greenland.

Carcinoma↗

PubMed1995

The human blood-brain barrier glucose transporter (GLUT1) is a glucose transporter of gray matter astrocytes.

Human and monkey brain sections were examined by immunohistochemical light and electron microscopy to determine the distribution of GLUT1, a glucose transporter isoform associated with erythrocytes and endothelial cells of the human blood-brain barrier. Protein immunoblotting of fractionated human brain membranes was performed to determine the distribution of molecular forms of the transporter. GLUT1 staining was abundant in erythrocytes and cerebral endothelium of gray and white matter but was also present diffusely in gray matter neuropil when viewed by light microscopy. Immunoelectron microscopy confirmed the gray matter and vascular localization of GLUT1, with specific GLUT1 staining seen in erythrocytes, gray and white matter endothelial cells, astrocyte foot processes surrounding gray matter blood vessels, and in astrocyte processes adjacent to synaptic contacts. No astrocytic staining was identified in white matter. Astrocyte GLUT1 staining was identified only in mature gray matter regions; undifferentiated regions of preterm (22-23 weeks gestation) cortex had GLUT1 staining only in blood vessels and erythrocytes, as did germinal matrix. Immunoblots of adult human frontal cortex revealed that two forms of GLUT1 (45 and 52 kDa) were present in unfractionated brain homogenates. Immunoblots of vessel-depleted frontal lobe revealed only the 45 kDa form in gray matter fractions, and depleted in membranes prepared from white matter regions. We conclude that the GLUT1 isoform of glucose transporter is present both in endothelium of the blood-brain barrier and in astrocytes surrounding gray matter blood vessels and synapses. Furthermore, the form present in astrocytes is likely to have a lower molecular weight than the form found in cerebral endothelium. The GLUT1 transporter may play an important role not only in astrocyte metabolism, but also in astrocyte-associated pathways supporting neuronal energy metabolism.

Animals↗

PubMed1995

Mitochondrial abnormalities in human immunodeficiency virus-associated myopathy.

There is controversy as to whether zidovudine (ZDV) induces a mitochondrial myopathy that is distinguishable from human immunodeficiency virus (HIV)-associated myopathy in ZDV-naive patients. Mitochondrial abnormalities were evaluated in skeletal muscle obtained from 18 HIV-positive, ZDV-exposed patients, and 9 who were drug naive. All patients had clinical myopathy, and underwent neuromuscular evaluation with information recorded on timing and dosage of ZDV. All underwent muscle biopsies and samples were examined without knowledge of clinical history or ZDV status. Biopsy samples were evaluated by light and electron microscopy. Mitochondrial abnormalities were seen in ZDV-treated and -naive groups, and did not correlate with ZDV exposure or cumulative ZDV dosage. Mitochondrial abnormalities displayed significant correlation with the presence and severity of myofiber degeneration on biopsy, regardless of ZDV status. As mitochondrial abnormalities reflect myofiber degeneration, present in both patient groups, they may not be used as evidence of primary mitochondrial dysfunction. The etiology of myofiber degeneration in patients with HIV infection, whether ZDV-exposed or -naive, remains unclear.

Adult↗

PubMed1995

Pathogenesis and classification of primary central nervous system lymphoma: an update.

Primary central nervous system lymphoma has undergone a remarkable increase in incidence over the last decade, both in immunosuppressed and immunocompetent individuals. Its clinicopathologic evaluation requires knowledge of current hematopathologic systems for lymphoma classification, as well as specific understanding of unique central nervous system determinants. In immunocompromised individuals, the tumor has a constant association with Epstein-Barr virus. The form of Epstein-Barr virus in these tumors appears to be predominantly latent, however, the precise mechanism relating virus to tumor pathogenesis is still unclear. In immunocompetent patients, risk factors and oncogenic associations are completely unknown. Critical to the formation of these tumors is the trafficking of B-cells, whether pre- or post-transformation, across the blood-brain barrier. These B-cell migrations may require perturbations to the barrier that originate in or around neural parenchyma, such as localized injury or infection.

Blood-Brain Barrier↗

PubMed1994

Multifocal cytomegalovirus demyelinative polyneuropathy associated with AIDS.

A 47-year-old man with acquired immunodeficiency syndrome presented 3 months antemortem with the onset of lower extremity sensory abnormalities. A progressive course of multifocal weakness and sensory disturbances ensued. Electrophysiologic studies revealed a generalized asymmetric demyelinating polyneuropathy with secondary axonal loss. The patient was sequentially treated with plasmapheresis, high dose corticosteroids, intravenous immune globulin, and ganciclovir. His neuropathy progressed, and he died of a fulminant bronchopneumonia. At autopsy the patient had a multifocal cytomegalovirus polyradiculoneuropathy, with both demyelinative and necrotizing features. While cytomegalovirus may be associated with a variety of peripheral nerve syndromes, its clinical presentation as a primary demyelinating polyneuropathy is unusual. Its importance vis-à-vis potential therapy for AIDS-associated neuropathies is discussed.

Acquired Immunodeficiency Syndrome↗

PubMed1994

Cerebral demyelination with 5-fluorouracil and levamisole.

We report a patient who developed multifocal cerebral demyelination with the use of 5-fluorouracil, levamisole, and leucovorin as adjuvant treatment for intestinal adenocarcinoma. The clinical features were acute confusion, restlessness, ataxia, and slurred speech. Magnetic resonance imaging revealed multifocal enhancing white matter lesions. Brain biopsy showed a well-demarcated area of demyelination in cerebral white matter. The patient improved clinically and radiologically after cessation of chemotherapy and a short course of steroids. There have been only 4 previously reported cases of multifocal leukoencephalopathy related to the use of combination 5-fluorouracil and levamisole. The extensive use of these agents as adjuvant treatment for colorectal carcinoma may result in more frequent recognition of this form of neurological toxicity.

Adenocarcinoma↗

PubMed1994

Epithelial cystic lesions of the sellar and parasellar region: a continuum of ectodermal derivatives?

Cystic epithelial lesions of the sellar and parasellar region are classified on the basis of histology and location into Rathke's cleft cysts, epithelial cysts, epidermoid cysts, dermoid cysts, and craniopharyngiomas. A retrospective review of the clinical presentation, radiological findings, and histology was performed on 19 such lesions, and a survey of the literature pertinent to the classification, clinical presentation, and embryology of these lesions was conducted. Presentation was nonspecific and not predictive of histology. Imaging studies were generally useful in distinguishing these tumors, with the exception of Rathke's cleft cysts, suprasellar epidermoid cysts, and craniopharyngiomas, which frequently could not be differentiated. On microscopic examination, most lesions fit into distinct categories; however, overlap was common among all and some could not be definitively categorized by histological criteria. Evidence supportive of an ectodermal ancestry for sellar and parasellar epithelial-lined cystic lesions is presented. Based on the current findings and a review of the literature, it is suggested that these lesions represent a continuum of ectodermally derived cystic epithelial lesions.

Adolescent↗

PubMed1993

Central nervous system Strongyloides stercoralis in acquired immunodeficiency syndrome: a report of two cases and review of the literature.

Hyperinfection with Strongyloides stercoralis is rare in acquired immunodeficiency syndrome (AIDS), despite endemicity in areas where infection with human immunodeficiency virus is highly prevalent. We autopsied two patients with AIDS and disseminated Strongyloides and describe their central nervous system findings. The microscopic patterns of brain infection were dissimilar in the two patients, and reflected histology in systemic viscera. In one patient, a granulomatous response accompanied filariform larvae in all locations, including granulomatous ependymitis in brain. Additionally in the brain, larvae without tissue reaction were seen. In the second patient, the absence of tissue response to larvae was body wide, and isolated parasites were found in centrum semiovale. The occurrence of these patients in a region where Strongyloides is not endemic suggests that this infection may be more prevalent in AIDS than formerly suspected.

Acquired Immunodeficiency Syndrome↗

PubMed1993

Tissue distribution of the human GLUT3 glucose transporter.

The tissue distribution of the GLUT3 glucose transporter protein was examined in human tissues using a rabbit antiserum directed against the C-terminal peptide sequence of human GLUT3. This anti-serum was shown to recognize the human GLUT3 protein in Chinese hamster ovary cells transfected with GLUT3 cDNA and to immunoprecipitate an authentic glucose transport protein in brain and testis membranes, as assessed by glucose-inhibitable photolabeling with [3H] cytochalasin-B. The GLUT3 protein, migrating with an apparent mol wt of approximately 48 kilodaltons, was strongly expressed in brain and testis membranes as well as in spermatozoa. It was not detectable in membranes from erythrocytes, adipocytes, heart, skeletal muscle, liver, kidney, spleen, thyroid, and prostate. Very low levels may be present in placenta. In brain, GLUT3 protein was strongly expressed in grey matter regions and was only weakly expressed in white matter, suggesting that it may be important in providing glucose to regions of high metabolic activity, i.e. to areas associated with synaptic transmission. None was found in peripheral (femoral) nerve. It appeared to be stable for up to 47 h in autopsy brain tissue kept at 4 C. The tissue distribution of human GLUT3 protein thus appears to be highly restricted (brain and testis/spermatozoa), in contrast with a previous report. Its function may be to provide a high affinity glucose transport system in cells that are highly dependent on glucose as a fuel source.

Affinity Labels↗

PubMed1993

The histopathological effects of the CO2 versus the KTP laser on the brain and spinal cord: a canine model.

Because no data are available concerning the histopathological effects of the potassium titanyl phosphate (KTP) laser on central nervous tissue, a study was performed using a canine model to compare the histopathological effects of a commonly used laser (CO2) and the KTP laser on brain and spinal cord tissue. Exposed brain and spinal cord tissue were irradiated with 0.1-s pulses (x10), with spot sizes of 1 mm (in focus) over a range of 1 to 10 W. Wedge-shaped lesions were produced with the CO2 laser, while more blunt, semilunar-shaped lesions were produced by the KTP laser. The depth and width of the lesions were proportional to the energy applied. The lesions ranged in surface diameter from 0.6 to 1.3 mm for CO2 and 0.8 to 1.6 mm for KTP lasers, respectively. The depth of the lesions varied from 0.4 to 2.0 mm for CO2 and 0.3 to 1.1 mm for KTP lesions. Histopathologically, a central zone of tissue destruction and vaporization was surrounded by a zone of coagulative necrosis, in turn surrounded peripherally by a zone of pallor. CO2-induced lesions were histologically more hemorrhagic than KTP-induced lesions. In view of the histopathological findings, the KTP laser appears as safe as the CO2 laser in terms of tissue lateral thermal change (penetration) and tissue absorption. The additional hemostatic advantage observed clinically for the KTP laser is demonstrated histologically as well. Although the wavelength of the KTP and argon laser light are similar, the histopathological effects seem to be less pigment dependent. The KTP laser seems well suited for neurosurgery and has the versatility provided by a fiberoptic delivery system.

Animals↗

PubMed1993

Epstein-Barr virus and primary lung lymphoma: a study utilizing the polymerase chain reaction.

Seven cases of primary lung lymphoma were analyzed for the presence of Epstein-Barr virus DNA sequences by the polymerase chain reaction. The series included: four cases of diffuse, small lymphocytic lymphoma; one case of diffuse, intermediate lymphocytic lymphoma; one case of diffuse, small cleaved cell lymphoma; and one case of large cell, immunoblastic lymphoma. The latter occurred in a patient with acquired immunodeficiency syndrome. A 200-bp sequence of the Epstein-Barr nuclear antigen 1 gene was used as a template for PCR amplification. The only tumor that contained Epstein-Barr virus sequences was the immunoblastic lymphoma. These findings support previous observations that small lymphocytic lymphomas of the lung are not related to Epstein-Barr virus infection. In contrast, some large cell lymphomas may represent Epstein-Barr-virus--associated lymphoproliferative disorders.

Adult↗