Biomedical subjects
Publications and source records attributed to S Morgello.
A case of OS of the T6 vertebra in a 58-year-old man is presented. Diagnosis was obtained by an open biopsy. The clinical and radiographic findings were described. The topic of vertebral OS was discussed at length. We emphasize the fact that OS of the spine is rare and that those cases not associated with Paget's disease or previous radiation therapy are even rarer.
The prevalence of Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV) in acquired immunodeficiency syndrome (AIDS)-related primary central nervous system (CNS) lymphoma was examined. Deoxyribonucleic acid (DNA) extracted from 12 formalin-fixed, paraffin-embedded tumors was used as substrate for the polymerase chain reaction (PCR). Targets for amplification were the EBNA-1 region of EBV, the gag region of HIV, and a single copy cellular sequence as a control. The cases studied were autopsy and surgical specimens collected between the years 1985 and 1989. By the working formulation for non-Hodgkin's lymphomas, five had large cell, four had mixed large and small cleaved cell, two had small cleaved cell, and one had an unclassified histology. Epstein-Barr virus was detected in 6 of 12 tumors studied. Human immunodeficiency virus was not detected in any of the tumors. The presence of EBV was not correlated with any particular histologic tumor type. It is concluded that EBV, not HIV, can be detected in a large percentage (50%) of AIDS-related primary central nervous system (CNS) lymphomas. This viral association may be significant in light of the demonstrated ability of EBV to induce lymphoid tumors in experimental mammalian systems.
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Macrophages are essential for normal wound repair and many of their effects on healing wounds are likely to be mediated by the secretion of cytokines. This study examines the appearance of messenger RNA (mRNA) for cachectin/tumor necrosis factor (TNF), IL 1, and macrophage inflammatory proteins 1 and 2 (MIP-1 and MIP-2), as well as the mature peptides, in a model of wound healing using wound chambers. RNA for all four cytokines can be detected in wound inflammatory cells by polymerase chain reaction amplification throughout the first 7 days. Cachectin/TNF and IL 1 protein levels peaked on the first day after wound chamber implantation, and MIP-1 and MIP-2 were detected only on day 3. The data suggest that these cytokines participate in the early inflammatory response to wounding.
The distribution and time course of postischemic astrocyte hypertrophy and hyperplasia and the relationship to neuronal viability or necrosis was studied in rats subjected to 30 min of carotid and vertebral artery occlusion followed by reperfusion from 3 h to 5 weeks. Intermediate filaments (IFs) were evaluated by electron microscopy, IF proteins by immunohistochemistry, and astrocyte division by [3H]thymidine uptake. Glial fibrillary acidic protein (GFAP) increased in damaged and nondamaged brain regions by 2 days and was associated with cell enlargement, increases in IF, and transformation of GFAP-negative into GFAP-positive glia. Cell hypertrophy and increased GFAP persisted only in regions of neuronal necrosis whereas the number and size of GFAP-positive astrocytes returned to control levels in nondamaged regions by 2 weeks. Astrocyte hyperplasia was not seen until 3 days and was confined to damaged brain regions. Vimentin-positive astrocytes were numerous by 2 days in damaged brain and remained only in those regions at 5 weeks. The data demonstrate that reactive astrocytosis develops in undamaged brain, but is reversible with prolonged survival, whereas reactive astrocytosis that accompanies structural brain damage persists for prolonged periods and is associated with hyperplasia, as well as hypertrophy. In addition, the results show that astrocyte expression of vimentin is more specific than GFAP in identifying regions of permanent ischemic injury during the early postischemic period.
Fourier-transform infrared spectroscopy (FT-IR) was applied to the study of tissue sections of human colorectal cancer. Pairs of tissue samples from colorectal cancer and histologically normal mucosa 5-10 cm away from the tumor were obtained from 11 patients who underwent partial colectomy. All cancer specimens displayed abnormal spectra compared with the corresponding normal tissues. These changes involved the phosphate and C-O stretching bands, the CH stretch region, and the pressure dependence of the CH2 bending and C = O stretching modes. Our findings indicate that in colonic malignant tissue, there are changes in the degree of hydrogen-bonding of (i) oxygen atoms of the backbone of nucleic acids (increased); (ii) OH groups of serine, tyrosine, and threonine residues (any or all of them) of cell proteins (decreased); and (iii) the C = O groups of the acyl chains of membrane lipids (increased). In addition, they indicate changes in the structure of proteins and membrane lipids (as judged by the changes in their ratio of methyl to methylene groups) and in the packing and the conformational structure of the methylene chains of membrane lipids. The cell(s) of the malignant colon tissues responsible for these spectral abnormalities is unknown. Cultured colon adenocarcinoma cell lines displayed similarly abnormal FT-IR spectra. The diagnostic potential of the observed changes is discussed.
Forty-two patients with large pituitary tumors were studied with magnetic resonance imaging scans. Based on the operative findings, the tumors were divided into two groups. Tumors in Group 1 (n = 35) were soft or partially necrotic and were easily removed by suction and curettage. Tumors in Group 2 (n = 7) were firm and required sharp dissection or use of the laser for removal. Tumors were divided into two groups based on the long TR signal: a) isointense in comparison with white matter, or b) hyperintense in comparison with white matter. All 7 firm tumors (Group 2) had an isointense signal on long TR sequences. Thirty-two of 35 soft tumors showed a hyperintense signal on long TR sequences, and 3 an isointense signal. Based on these results, we recommend a transsphenoidal approach for the initial operation in patients with large pituitary tumors. If the tumor is largely isointense on the magnetic resonance imaging scan, we discuss with the patient preoperatively the possibility (70% in this series) that the tumor may be too firm to remove in a single transsphenoidal procedure. In these circumstances, a second, transcranial, procedure may be required to decompress the suprasellar structures adequately.
We have developed a murine model of wasting by injecting intracerebrally cells which continuously secrete h-cachectin/TNF (CHO-TNF) to: (a) determine the effects of cachectin/TNF produced continuously in the central nervous system (CNS), and (b) compare the metabolic effects of cachectin/TNF-secreting tumor in the brain to the cachexia caused by CHO-TNF tumor in peripheral tissue (IM). Intracerebral CHO-TNF tumors produced increased serum h-cachectin/TNF levels with lethal hypophagia and weight loss (mean survival time of 11 d); these changes were not observed in association with nonsecretory control brain tumors. The metabolic consequences of intracerebral cachectin/TNF production were indistinguishable from acute, lethal starvation: whole-body lipid content was decreased significantly but protein was conserved. Although intramuscular cachectin/TNF-secreting tumors caused similar increases of serum h-cachectin/TNF levels, profound anorexia did not develop; wasting developed after a longer period of tumor burden (50 d) with classical signs of cachexia (i.e., anemia and depletion of both protein and lipid). These studies provide a reproducible animal model of site-specific cytokine production and suggest that, regardless of serum levels, cachectin/TNF produced locally in brain influences both the rate of development of wasting and its net metabolic effects.
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A 22-year-old Haitian man had a 15-month course of progressive meningitis accompanied by multiple cerebral infarcts. Multiple areas of stenosis and occlusion in all branches of the circle of Willis, and hypertrophy of collateral perforating vessels at the base of the brain in a "puff of smoke" appearance typical of moyamoya disease were seen on cerebral angiogram 5 months before the patient died. At autopsy, the patient had meningovascular syphilis and a necrotizing encephalitis with massive treponemal invasion of the brain, the pathology of late-stage degenerative, "quaternary", neurosyphilis. The patient was also infected with human immunodeficiency virus (HIV). Retrovirus-like particles 100 nm in diameter with dense cores were seen by electron microscopy. Nucleic acid obtained from the patient's brain contained sequences homologous to HIV DNA as determined by dot blot hybridization. The moyamoya-like radiologic appearance of neurosyphilis has not been previously described. The autopsy finding of quaternary neurosyphilis in a patient with HIV infection supports the hypothesis that retrovirus may alter the natural history of syphilitic infection.
T-cell lymphoma may involve the CNS as either a primary or secondary neoplasm. This report describes 8 patients with either primary or secondary T-cell malignancies in the CNS. Five patients presented with symptoms and signs of CNS disease that included seizures, visual impairment, cranial nerve palsies, sensory and motor deficits, gait ataxia, and paraparesis. Three of them had primary parenchymal CNS lymphoma, and 2 had epidural lymphoma that originated in adjacent bone marrow. Three patients were neurologically asymptomatic, but had leptomeningeal tumor and focal parenchymal infiltration at postmortem examination. Histologically, 4 lymphomas were large cell, 3 were mixed large and small cell, and 1 could not be classified by the working formulation for non-Hodgkin's lymphomas. The clinical and pathologic manifestations of T-cell lymphoma in the CNS may be diverse. This report demonstrates that neurologic abnormalities may be the presenting signs of either primary CNS or systemic T-cell lymphoma.
The MR images and CT scans of 14 patients with surgically verified pyogenic cerebral abscesses were reviewed. The MR findings correlated well with those seen on CT and were believed to be sufficiently characteristic to allow early and accurate diagnosis with MR alone. These features include (1) peripheral edema producing mild hypointensity on short TR/short TE and marked hyperintensity on long TR/intermediate to long TE scans; (2) central necrosis with abscess fluid hypointense relative to white matter and hyperintense relative to CSF on short TR/short TE scans and hyperintense relative to gray matter on long TR/intermediate to long TE scans (the fluid had concentric zones of varying intensity in seven cases, a finding not previously identified in other lesions); (3) extraparenchymal spread (intraventricular or subarachnoid), which was detected more easily on MR than on CT and was manifested by increased intensity relative to normal CSF on both short TR/short TE and long TR/intermediate TE scans; and (4) visualization of the abscess capsule, which was iso- to mildly hyperintense relative to brain on short TR/short TE scans and iso- to hypointense relative to white matter on long TR/intermediate to long TE scans. On the long TR scans, the relative hypointensity of the rim allowed for visualization of the typical morphologic features of the capsule, which in turn aided in differentiation of abscesses from other lesions (as it does on CT). To investigate the cause of the capsular intensity, pathologic studies of the capsules were reviewed when available (10 cases). Fibrosis was identified in all mature abscess capsules, but the combination of the intensities seen on short TR/short TE and long TR/intermediate to long TE scans as well as the temporal changes in intensity were believed to be incompatible with fibrosis as a cause of the capsular changes. Intensity patterns were suggestive of hemorrhage, but neither acute nor chronic hemorrhage was identified on routine H and E stains, while iron stain revealed scant hemorrhage in only two of the eight patients in whom these stains were used. We believe the capsular intensity (in particular the hypointense rims on long TR scans) may reflect paramagnetic T1, and to a greater extent T2, shortening, possibly due to the presence of heterogeneously distributed free radicals that are products of the respiratory burst produced by actively phagocytosing macrophages in the capsule wall. Distinctive MR features of pyogenic abscesses should afford early and accurate diagnosis.
Bacterial endotoxins (LPS) causes placental injury and fetal demise in pregnant animals. Because several biological effects of LPS are mediated by interleukin-1 (IL-1) and tumor necrosis factor (TNF), the hypothesis that these cytokines could cause placental injury similar to that seen in LPS-treated pregnant rats was tested. On day 12 of gestation, rats were injected intraperitoneally with saline, LPS, native or heat-inactivated (HI) rHIL 1 alpha, or rH-TNF alpha. Seven days later, grossly abnormal implantation sites and fetal demise were observed in rats injected with rHIL-1, rHTNF, or LPS but not in those injected with saline or HI-cytokines. Necrosis of placental, decidual, and fetal tissues was observed in cytokine-treated animals. The necrosis was more severe in LPS-treated rats, in which no fetal remains were identifiable. These data suggest that IL-1 and TNF may play a role in the fetoplacental injury observed in LPS-treated pregnant rats.
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An insulin-containing ovarian carcinoid was found at the autopsy of a 63-year-old woman with a 12-year history of episodic hyperinsulinemic hypoglycemia. In terms of histology, the carcinoid displayed both insular and trabecular patterns and contained a small focus of mucinous cystadenoma. Beta secretory granules were demonstrated by electron microscopy, and immunoreactivity for insulin was demonstrated in tumor cell cytoplasm by immunohistochemistry. Additional autopsy findings included a solitary parathyroid adenoma and a microscopic focus of pituitary hyperplasia. This is the first recorded case of insulin production by a primary ovarian neoplasm. The patient's constellation of endocrine findings may represent a variant of the syndrome of type I multiple endocrine neoplasia.
A 30-month-old infant with Menkes kinky-hair disease died, with prominent vascular, cerebral and cerebellar degeneration. Increased numbers of mitochondria containing homogeneous dense bodies were seen on electron-microscopic examination of Purkinje cells. Subsarcolemmal aggregates of mitochondria ('ragged red' fibers) were present in skeletal muscle. These mitochondrial alterations support the hypothesis that copper deficiency results in mitochondrial encephalomyopathy.
Two patients with varicella-zoster virus leukoencephalitis and acquired immunodeficiency syndrome are described. Neither patient had cutaneous or disseminated varicella-zoster virus infection within the last six months of life. Demyelinated lesions resembling those of progressive multifocal leukoencephalopathy were seen in their brains at autopsy. Numerous cells with Cowdry type A intranuclear inclusions surrounded the lesions; these cells stained positively for varicella-zoster virus with immunohistochemistry and contained herpesvirus nucleocapsids by electron microscopy. Leptomeningeal vessels accompanying the lesions displayed a zoster-induced vasculopathy in one of the two patients. Vascular and parenchymal central nervous system infections with varicella-zoster virus are rare in the absence of cutaneous lesions, and to our knowledge, the presence of both in one patient has not yet been described.
Three patients with the acquired immunodeficiency syndrome (AIDS) had combined infections of the central nervous system, with both herpes simplex virus (HSV) and cytomegalovirus (CMV). All three had a diffuse ventriculoencephalitis documented at postmortem examination. The presence of HSV type 1 and CMV was confirmed microscopically with immunohistochemistry. The clinical importance of these three patients is that they establish the presence of concomitant HSV and CMV encephalitis in acquired immunodeficiency syndrome, and suggests the possibility of therapeutic intervention with antiviral drugs that have activity against HSV and/or CMV.