PubMed Health⌕ Search

Biomedical subjects

L Sharer

Publications and source records attributed to L Sharer.

15 recordsLinked to original sources
PubMed2003

Detection of HIV-1 DNA in microglia/macrophages, astrocytes and neurons isolated from brain tissue with HIV-1 encephalitis by laser capture microdissection.

In HIV-1 encephalitis, HIV-1 replicates predominantly in macrophages and microglia. Astrocytes also carry HIV-1, but the infection of oligodendrocytes and neurons is debated. In this study we examined the presence of HIV-1 DNA in different brain cell types in 6 paraffin embedded, archival post-mortem pediatric and adult brain tissues with HIV-1 encephalitis by Laser Capture Microdissection (LCM). Sections from frontal cortex and basal ganglia were stained by immunohistochemistry for CD68 (microglia), GFAP (astrocytes), MAP2 (neurons), and p24 (HIV-1 positive cells) and different cell types were microdissected by LCM. Individual cells or pools of same type of cells were lysed, the cell lysates were subjected to PCR using HIV-1 gag SK38/SK39 primers, and presence of HIV-1 DNA was confirmed by Southern blotting. HIV-1 gag DNA was consistently detected by this procedure in the frontal cortex and basal ganglia in 1 to 20 p24 HIV-1 capsid positive cells, and in pools of 50 to 100 microglia/macrophage cells, 100 to 200 astrocytes, and 100 to 200 neurons in HIV-1 positive cases but not in HIV-1 negative controls. These findings suggest that in addition to microglia, the infection of astrocytes and neurons by HIV-1 may contribute to the development of HIV-1 disease in the brain.

Adolescent↗
PubMed1998

Surveillance for Creutzfeldt-Jakob disease among persons with hemophilia.

BACKGROUND: Although Creutzfeldt-Jakob disease (CJD) has been shown to be transmissible through blood components in rodent models, no human blood-to-blood transmission has been documented. If blood transmission were possible in humans, persons with hemophilia in the United States would be at higher risk of contracting CJD, because they receive large numbers of blood components. Nearly one-half of the hemophilia population contracted HIV in the 1980s, and many of these people have since died with neurologic complications. This study investigated whether some hemophilia patients with neurologic disorders may have died with CJD. STUDY DESIGN AND METHODS: Hemophilia treatment Centers across the United States were invited to participate in this retrospective surveillance study. The centers were asked to send any available formalin-fixed paraffin block brain samples from hemophilia decedents. Slides were prepared at the Centers for Disease Control and Prevention and reviewed by three expert neuropathologists. Two slides were stained for the prion protein at the request of one of the neuropathologists. RESULTS: Specimens from 24 decedents with genetic bleeding disorders were collected and reviewed.The panel found no evidence of CJD in any of the specimens. CONCLUSIONS: Although the study sample is small, these results support the growing evidence that CJD is not being transmitted in the nation's blood supply.

Adult↗
PubMed1998

Clinical manifestations of mitochondrial DNA depletion.

OBJECTIVE: We studied five new patients with mitochondrial DNA (mtDNA) depletion to better define the clinical spectrum of this disorder. BACKGROUND: mtDNA depletion has been associated with myopathy or hepatopathy, or both, in infants and young children. Involvement of the CNS and peripheral nervous system has not been clearly established. METHODS: We reviewed the clinical course and performed morphologic, biochemical, and genetic analyses of muscle samples from five patients. RESULTS: Age at onset ranged from 3 months to 5 years, and one patient survived until age 10 1/2 years. Two patients had laboratory and clinical features reminiscent of dystrophinopathy, two had evidence of brain involvement, and two had peripheral neuropathy. Muscle biopsy specimens in all patients showed abundant ragged-red fibers. Biochemistry showed cytochrome c oxidase deficiency in all patients tested and decreased activities of other respiratory chain complexes in some. CONCLUSIONS: Inheritance appeared to be autosomal recessive, suggesting that mutations in nuclear DNA are responsible for mtDNA depletion. mtDNA depletion should be considered in children with mitochondrial disorders of uncertain etiology, and criteria for diagnosis are proposed.

Blotting, Southern↗
PubMed1994

A cultured malignant B-1 line serves as a model for Richter's syndrome.

Human chronic lymphocytic leukemia (CLL) is a malignancy of B-1 cells characterized by the accumulation of mature appearing, long lived, slow growing B-1 cells in peripheral blood. CLL occasionally evolves into an aggressive large cell lymphoma termed Richter's syndrome. NZB mice can be used to model the early stage of CLL because aged NZB mice can spontaneously develop slow growing malignant B-1 cell clones. The malignant NZB B-1 clones fail to grow in culture and are typically carried in vivo as passaged lines. During serial passage, an aggressive lymphoma developed as a result of a continued transformation of the original B-1 clone, similar to the development of Richter's syndrome. An in vitro cell line was established from the aggressive lymphoma, which was stromal dependent and could rapidly metastasize when passaged into recipient animals. Analysis of adhesion molecules did not reveal any consistent characteristics that could account for the metastatic potential of the Richter's-like cells. In addition, the aggressive in vitro line had the identical heavy chain sequence as the slow growing NZB malignant B-1 clones. The in vitro and in vivo aggressive B-1 cells had very high levels of IL-10 message, and underwent more apoptosis in response to anti-IgM than did nonaggressive B-1 clones. Taking these characteristics together, we have composed a comprehensive animal model system for human CLL that includes both the aged NZB mice for the early stage and the recipients of the in vitro B-1 line for the late stage or Richter's syndrome. This model system can be used to study, not only the ontogeny and genetic linkage of CLL, but also the regulatory factors involved in transformation and growth both in vivo and in vitro.

Animals↗
PubMed1994

Electrolyte-induced demyelination in rats. 2. Ultrastructural evolution.

This study presents the electron microscopic evolution of lesions in electrolyte-induced demyelination (EID) in rats, a lesion which bears striking histological and clinical similarity to central pontine myelinolysis. The earliest change was observed during the hyponatremic phase and consisted of minimal intracellular edema present throughout the brain. Following the injection of hypertonic saline, additional changes were observed which were restricted to sites previously reported to be frequently involved in EID. Early dilatation of the inner tongue of oligodendrocyte cytoplasm in myelinated nerve fibers was observed at 3 h post hypertonic saline injection (PHS). This was followed, at 48 h PHS, by the appearance of degenerative changes consistent with dying oligodendrocytes. Well-delineated, vacuolar and spongy lesions, seen by light microscopy, were present by 48 h PHS at the same sites as above. Electron microscopically, this appearance was found to be due to striking intramyelinic edema. By 96 h PHS, macrophages containing myelin and other cellular debris were frequently present at these sites. Concomitantly, myelin sheaths underwent vesicular disruption and disintegration. This sequence of events suggests a lesion of the oligodendrocyte-myelin complex, secondary to initial blood-brain barrier damage and edema.

Animals↗
PubMed1993

Multiple sclerosis. Pathology of recurrent lesions.

Recent autopsy studies suggest that remyelinated shadow plaques located in otherwise intact white matter are the outcome of a previous single episode of acute demyelination. In the present study, of 98 remyelinated plaques examined in 15 patients with multiple sclerosis who died between 27 days and 5 years after clinical onset, 15 showed evidence of a superimposed new demyelinating lesion. Inspection of old shadow plaques in a separate series of patients with subacute and long-standing multiple sclerosis revealed that such lesions sometimes exhibit punched-out areas of demyelination and gliosis similar in size and shape to fresh lesions located within or overlapping remyelinated shadow plaques. The findings support magnetic resonance imaging evidence that local recurrence may be as important or more important than progressive edge activity in determining plaque growth and the conversion of nascent lesions into classical demyelinated plaques. The findings also support experimental evidence that recurrent demyelination of the same area of white matter may be one of the factors underlying failed remyelination in multiple sclerosis.

Adult↗
PubMed1993

Cortical astrocytosis in juvenile rhesus monkeys infected with simian immunodeficiency virus.

The pattern of expression of GFAP immunoreactivity in astrocytes of the juvenile rhesus monkey cortex was examined following infection with simian immunodeficiency virus (SIV). Blocks of cerebral cortex plus subjacent white matter from saline- and formalin-perfused brain were examined by peroxidase-linked immunochemical and immunofluorescence staining of deparaffinized sections. Strong GFAP immunoreactivity was found in astrocytic cells in both uninfected and SIV-infected juvenile macaque in the subpial cerebral cortex and in subcortical white matter, where GFAP-positive cells were abundant. GFAP staining of cortical layers 2-6 on the other hand was weak or absent in three uninfected controls and one infected animal without cognitive impairment, but moderate to strong in animals productively infected with SIV that demonstrated cognitive and/or motor impairment. These data demonstrate a cortical locus of astrocytic activation in rhesus monkeys infected with primate immunodeficiency virus isolate SIVB670 which, like HIV-1 in man, causes motor/cognitive impairment as well as immunodeficiency disease.

Animals↗
PubMed1989

HIV-2-associated AIDS in the United States. The first case.

A 41-year-old woman from the Cape Verde Islands, Africa, who had been residing in the United States for 11 months was found to have human immunodeficiency virus type 2 (HIV-2)-associated acquired immunodeficiency syndrome (AIDS). Antibody to HIV-2 was found by enzyme immunoassay and was verified by radioimmunoprecipitation. The patient was being treated for pulmonary tuberculosis at the time of her admission to our institution. Further laboratory and clinical evaluation at our facility revealed depressed CD4 lymphocytes, oral candidiasis, and cryptococcal meningitis with indeterminate results on serologic testing for HIV type 1 (HIV-1). The biopsy specimen of a lesion in the right occipital lobe of the brain documented Toxoplasma gondii, indicating a clinical diagnosis of AIDS. To our knowledge, our study presents the first known patient with HIV-2-associated AIDS in the United States. Our patient provides further evidence that HIV-2 causes severe immunodeficiency and opportunistic infection. The condition should be suspected in the face of normal or repeatedly equivocal HIV-1 antibody test results in the presence of clinically documented AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Arteriopathy in children with acquired immune deficiency syndrome.

Pathologic features of the arteries of different organs (heart, lungs, kidneys, spleen, intestine, brain) seen at autopsy in 6 children with acquired immune deficiency syndrome (AIDS) are described. Small and medium-sized arteries, which were the most commonly involved, showed intimal fibrosis with fragmentation of elastic tissue, fibrosis and calcification of media with variable luminal narrowing, and a vasculitis or perivasculitis that was seen only in the brain in association with AIDS encephalopathy. In 1 case aneurysms of the right coronary artery with thrombosis and myocardial infarction were seen. Vascular inflammation, seen only in the brain, may be related to the agent associated with AIDS encephalopathy. The fibrocalcific arterial lesions most closely resemble idiopathic arterial calcification of infancy, but because of differences in age incidence, clinicopathologic and immunologic features, and the size and distribution of the involved arteries, the arterial lesions of pediatric AIDS appear to constitute a distinctive arteriopathy. Infection, secondary to immunodeficiency and resulting in increased exposure to endogenous and exogenous elastases, may be the pathogenesis. Luminal narrowing caused by arterial lesions may play a contributory role in the pathogenesis of the atrophy, cell depletion, scarring, and necrosis or infarction found in organs of children with AIDS. Pediatricians should be alerted to the possibility of arterial involvement in pediatrics AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1981

Metastasis of intracranial germinoma through a ventriculoperitoneal shunt.

A young man developed a tumor in the pineal region that grew along ventricular surfaces and caused obstructive hydrocephalus. Cytologic examination of cerebrospinal fluid demonstrated malignant cells consistent with germinoma. Following a ventriculoperitoneal shunt and radiotherapy, the tumor and the hydrocephalus regressed. Three years later, an intraperitoneal tumor appeared that was diagnosed by transcutaneous biopsy specimen as a germinoma. The abdominal germinoma also regressed after radiotherapy. While extracranial metastases of intracranial germinomas via shunts are probably rare, their occurrence, as exemplified by this case, argues for including protective filters in the shunts.

Abdominal Neoplasms↗
PubMed1980

Meningeal involvement in IgD myeloma with cerebrospinal fluid paraprotein analysis.

Myelomatous meningitis is a rare occurrence in multiple myeloma. We report 2 cases of documented IgD myeloma with cytologic evidence of meningeal involvement in 1 and detailed paraprotein analysis in both. The occurrence of meningeal involvement in this rare form of plasma cell neoplasm may be more common than previously thought.

Aged↗