Biomedical subjects

D W Dickson

Publications and source records attributed to D W Dickson.

At least 163 records · Page 9Linked to original sources

PubMed1992

Characterization of primary human fetal dissociated central nervous system cultures with an emphasis on microglia.

BACKGROUND: We undertook a systematic examination of human fetal central nervous system dissociated cell cultures, particularly with respect to microglia and their dynamic interactions with other central nervous system cell components. EXPERIMENTAL DESIGN: The growth and differentiation of astrocytes, microglia, and small immature neuronal cells in mixed and single cell type-enriched cultures were followed by phase contrast microscopy, immunocytochemistry, flow cytometry, electron microscopy and immunoelectron microscopy, in regard to their phenotype change, proliferation and class II major histocompatibility complex antigen expression. RESULTS: Both astrocytes and microglia expressed marked phenotype heterogeneity, but they were consistently positive for glial fibrillary acidic protein and CD68, respectively. Highly enriched astrocyte and microglial cultures suitable for biochemical or molecular biologic studies were obtained. Using double immunocytochemical labeling techniques with the proliferating cell nuclear antigen and cell-type specific markers, astrocytes grown in serum-containing media showed a high labeling index, whereas microglia seldom exhibited a similar degree of proliferative activity. Microglia, however, proliferated in response to certain growth factors, such as granulocyte macrophage colony-stimulating factor. Both microglia and astrocytes expressed high basal levels of class II MHC antigens, which further increased with addition of interferon-gamma. The microglia in dissociated cultures existed in two forms, ameboid and ramified. Microglial ramification was induced when ameboid microglia were co-cultured with a monolayer of astrocytes, suggesting a role for astrocytes in microglial differentiation. In addition, lipopolysaccharide in nanogram amounts consistently enhanced microglial survival and morphologic differentiation. The small bipolar cells, the most frequent cell type in mixed culture, were glial fibrillary acidic protein (-) and CD68 (-), and their size and shape remained unchanged under our culture conditions. A subpopulation of small bipolar cells was stained positive with an antibody to surface ganglioside, A2B5. Electron microscopic examination showed that their processes contained parallel microtubules bearing side arms consistent with immature neurons. CONCLUSIONS: Highly purified astrocyte and microglial cultures are obtained using the currently described technique. The current culture system is a valuable tool in studying human central nervous system biology and disease.

Astrocytes↗

PubMed1991

Primary central nervous system lymphoma in acquired immune deficiency syndrome. A clinical and pathologic study with results of treatment with radiation.

Primary central nervous system (CNS) lymphoma occurs frequently in patients with the acquired immune deficiency syndrome (AIDS). Seventeen patients with AIDS and biopsy-proven CNS lymphoma were treated with whole-brain radiation. At presentation, most patients were severely debilitated from previous AIDS-related illnesses. Patients generally had focal neurologic symptoms such as seizures and paralysis. Headaches and mental status changes, often noticed after hospital admission, seldom brought our patients to seek medical attention. Computed tomography (CT) scan showed low-density, contrast-enhancing, mass lesions with variable amounts of peritumor edema. Size, location, and pattern of contrast enhancement of the lesions varied. No specific pattern was seen that could be used to distinguish between CNS lymphoma, toxoplasmosis, or other CNS diseases that occur in patients with AIDS. Biopsy results showed angiocentric, high-grade, large cell tumors with frequent necrosis. Immunohistochemical analysis showed B-cell phenotype with small amounts of T-cells, presumably reactive. All patients received irradiation to the whole brain with parallel opposed fields. A variety of doses and treatment regimens were used. Mean survival was only 72 days. Survival was longer in patients with higher pretreatment Karnofsky scores. The correlation between dose and survival was not significant. At completion of therapy, most patients showed improvement in Karnofsky score and had partial improvement in neurologic symptoms. CNS lymphomas in patients with AIDS are responsive to radiation. Posttreatment CT scans showed regression of tumors. Autopsy examinations showed regression of tumors, but also showed concurrent CNS infections, AIDS encephalopathy, and radiation-induced changes within the normal CNS tissue. Opportunistic infections rather than cerebral herniation or uncontrolled lymphoma was the most common cause of death.

Acquired Immunodeficiency Syndrome↗

PubMed1991

Meningioangiomatosis: an immunocytochemical study.

Meningioangiomatosis (MA) is a rare malformative lesion of the central nervous system. It has generally been thought that the main cells forming this lesion are derived from arachnoidal cap cells. We report a case of MA in which histochemical, immunoperoxidase and electron microscopic studies did not support a meningothelial origin of this lesion. Rather, the lesion in this case appears to be a vascular malformation with the dominant cells being fibroblastic, derived from vessel walls; however, their origin from arachnoid cap cells that differentiated into fibroblast-like cells could not be totally ruled out. Residual neurons within the lesion contained neurofibrillary tangles with ultrastructural and immunostaining properties identical to those seen in Alzheimer's disease except for the absence of A4 amyloid.

Adolescent↗

PubMed1991

Striatonigral degeneration, olivopontocerebellar atrophy and "atypical" Pick disease.

A 75-year-old woman with parkinsonism plus was found at autopsy to have striatonigral degeneration (SND), olivopontocerebellar atrophy (OPCA) and intracytoplasmic neuronal inclusions, mostly confined to the hippocampus and pontine nuclei. These inclusions were intensely argyrophilic, ubiquitinated and expressed variable immunoreactivity for neurofilament but not for tau-1 and Alz 50 proteins. Ultrastructurally, they were formed of skeins of intermediate filaments averaging 11 nm in diameter. They were considered to represent Pick bodies. There was no cortical atrophy, gliosis or sponginess. To our knowledge, SND and OPCA in association with Pick's disease has not been previously reported. In addition, intracytoplasmic oligodendroglial inclusions were present in the deeper layers of the cortex, especially the pericentral gyri, the striatum and the white matter of certain regions of the cerebral hemispheres, as well as in the cerebellum. These inclusions which have been previously reported in multisystem atrophy, had to be distinguished from cortical Lewy bodies, Pick bodies, and the nonspecific ubiquitinated bodies in the white matter of the aged brain, mainly by their topographical distribution and immunostaining properties.

Aged↗

PubMed1991

Human immunodeficiency virus-1 infection of the nervous system: an autopsy study of 268 adult, pediatric, and fetal brains.

The central nervous system (CNS) of 221 adults and 31 infants or children with the acquired immunodeficiency syndrome (AIDS) was examined with immunocytochemistry for infectious agents and for human immunodeficiency virus-1 (HIV-1) antigen (gp41). Since the major risk factor in this population was intravenous drug abuse, there were more female and pediatric patients than in other neuropathology autopsy series. Although children had a different spectrum of pathologic changes, including less frequent opportunistic infections, women did not differ from men in terms of types or incidence of opportunistic infections, vascular disease, neoplasia, and subacute AIDS encephalitis (SAE). Subacute AIDS encephalitis was detected in 26% of adult and 48% of pediatric brains. Immunocytochemical analysis of 100 adult and 20 pediatric brains revealed gp41 immunoreactivity in 78% and 40%, respectively. Virtually all adult brains with SAE had gp41 immunoreactivity in macrophages and microglia. Even brains with no significant pathology had frequent gp41 immunoreactivity, especially in the basal ganglia. In pediatric brains, including cases with SAE, gp41 immunoreactivity was less abundant, suggesting the possibility of latent infection or viral clearance. Spinal cords with vacuolar myelopathy or corticospinal tract degeneration had only rare gp41-positive cells. Brains from 16 aborted fetuses from HIV-1-seropositive women were all negative for gp41 immunoreactivity, but 12 brains were positive for HIV-1 by the polymerase chain reaction. These results may indicate that HIV-1 infection in fetal brains is below the limits of detection of immunocytochemistry. The differences noted between adults and children suggest that adults more often have productive CNS HIV-1 infection.

AIDS Dementia Complex↗

PubMed1991

Ubiquitin-immunoreactive dystrophic neurites in Down's syndrome brains.

Ubiquitin-immunoreactivity was studied in Down's syndrome brains ranging in age from two days to sixty years. Numerous randomly distributed ubiquitin-immunoreactive dot-like structures in the white matter were shown to correspond to granular degeneration of myelin. Granular degeneration of myelin was first detected at age 21 and increased thereafter with age. Other larger and more coarsely granular ubiquitin-immunoreactive structures, most numerous in the middle and upper cortical layers, were consistent with dystrophic neurites. Immunoelectron microscopy demonstrated that the dystrophic neurites contained non-filamentous, membranous, dense bodies. In Down's syndrome, ubiquitin-immunoreactive dystrophic neurites were first detected at age six in the hippocampus, and were consistently more numerous in comparison to age-matched control subjects. In the presence of amyloid, either as diffuse or as compact deposits, ubiquitin-immunoreactive dystrophic neurites frequently formed aggregates consistent with senile plaques. Although apparently independent events, these data suggest that amyloid deposition is associated with local accentuation of ubiquitin-immunoreactive neuritic dystrophy. In addition, since dystrophic neurites appeared substantially earlier in the grey matter in Down's syndrome than in age-matched normals, this may be further evidence that selective aspects of aging are accelerated in Down's syndrome.

Adolescent↗

PubMed1991

Hippocampal degeneration differentiates diffuse Lewy body disease (DLBD) from Alzheimer's disease: light and electron microscopic immunocytochemistry of CA2-3 neurites specific to DLBD.

Immunocytochemistry with antibodies to ubiquitin is currently the most sensitive method for detecting cortical Lewy bodies, which are a sine qua non for the diagnosis of diffuse Lewy body disease (DLBD), an increasingly recognized form of primary degenerative dementia. In the systematic application of ubiquitin immunocytochemistry to sections of hippocampus from control subjects and patients with a wide spectrum of neurodegenerative diseases, we noted the frequent occurrence of ubiquitin-immunoreactive neurites in the CA2-3 region in DLBD. The nature of these neurites was investigated with immunocytochemistry in DLBD, Alzheimer's disease (AD), normal elderly subjects, and Parkinson's disease (PD). Although the number of neurites varied from case to case, they were virtually always detected in DLBD but not in normal, AD, or PD brains. Double immunolabeling studies with anti-ubiquitin demonstrated a small fraction of double-stained neurites with antibodies to neurofilament or Alz-50, but no double staining with an antibody to Alzheimer neurofibrillary tangles. These results are different from those for neurites in AD, which are rarely seen in CA2-3 and which are immunoreactive with all these antibodies. Neuritic degeneration in the CA2-3 region of the hippocampus appears to be a specific histopathologic feature of DLBD.

Adolescent↗

PubMed1991

The N terminal region of human tau is present in Alzheimer's disease protein A68 and is incorporated into paired helical filaments.

Antibody (Ab) E-1 was raised to the amino terminus (19 to 33 amino acid residues) of human tau. It recognized Alzheimer's disease proteins A68 (MW 60, 64, 68 kd), labeled paired helical filaments, and had no reactivity with tau from rat, mouse, and bovine brains. The results indicate that the N terminus of tau is incorporated in A68 proteins and paired helical filaments and that human tau proteins contain species-specific amino acid sequences.

Alzheimer Disease↗

PubMed1991

Microglia in human disease, with an emphasis on acquired immune deficiency syndrome.

In conclusion, there is overwhelming evidence that within the CNS the primary sites of active HIV-1 infection are microglia. CNS infection may be related to the normal repopulation of the CNS by monocytes (microglial turnover) that carry latent infection into the CNS. Activation of viral infection may depend upon microglial differentiation, soluble factors (cytokines), and/or coexistent infections. Infection of microglia may disturb the normal hemostatic balance that exists between microglia and other glia, and between microglia and neurons, processes that are only recently being explored at the molecular level. The impact that HIV infection of microglia may have on synaptic integrity is unknown. Cytokines appear to be prime candidates as mediators of some of the adverse effects of microglial infection on other CNS cells, myelin and endothelial cells.

AIDS Dementia Complex↗

PubMed1990

Primary central nervous system lymphoma in a pediatric patient with acquired immune deficiency syndrome. Treatment with radiation therapy.

Primary central nervous system (CNS) lymphoma, an otherwise rare pediatric tumor, has been reported with increasing frequency in children with acquired immune deficiency syndrome (AIDS). With current therapy, the outcome of this disease is invariably fatal. The authors present a case of primary CNS lymphoma in a 3.5-year-old girl with AIDS who received treatment with total brain irradiation. After treatment, the patient's mental status improved, the seizures resolved, and she had no further progression of her neurologic symptoms until she died of pneumonia 6 months later. The autopsy revealed a necrotic mass at the site of the original tumor. The brain stem and spinal cord, unirradiated, contained lymphomatous lesions. The patient had extensive fibrinoid necrosis and leukoencephalopathy that were consistent with radiation-induced CNS damage. Coexisting AIDS encephalopathy also contributed to the patient's CNS injury. Effective palliation of CNS lymphoma in children with AIDS may be obtained with cranial irradiation. Pediatric AIDS patients may show more severe tissue effects from irradiation than unaffected children.

Acquired Immunodeficiency Syndrome↗

PubMed1990

Localization of morphologically distinct microglial populations in the developing human fetal brain: implications for ontogeny.

Although 70 years have elapsed since del Rio Hortega's initial description of microglia, the ontogeny of these cells remains enigmatic. In addition to the general scientific importance of clarifying this issue, a more complete characterization of microglia is dictated by their apparent pivotal role in the pathophysiology of central nervous system (CNS) disease associated with the acquired immunodeficiency syndrome (AIDS) in adults and, especially, in children. To accomplish this goal, fetal central nervous system tissue was collected at the time of elective pregnancy terminations. Coronal vibratome sections of Bouin's-fixed cerebrum were either stained with Ricinus communis agglutinin-1 (RCA-1) or analyzed by immunohistochemistry using monoclonal antibodies that recognize human tissue macrophages and microglia. By at least 13 weeks of gestation, microglia were detected in fetal brain. In the 13-18 week gestational age cerebrum, there was variability in the morphology of microglia within the developing white matter and cortex. However, there was less variability within these areas in the 19-24 week gestational age group. At all ages the greatest number of labeled cells per field was in the germinal matrix with decreasing numbers in the developing white matter and cortex. Cells in the germinal matrix were round with short processes ('ameboid microglia') while cortical cells were more ramified ('resting microglia'). These results suggest that microglia may originate in the germinal matrix rather than in the pial mesenchyme as originally hypothesized by del Rio Hortega.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗

PubMed1990

Ubiquitin immunoreactivity in kuru plaques in Creutzfeldt-Jakob disease.

Cerebellar kuru plaques in 2 cases of Creutzfeldt-Jakob disease were studied immunohistochemically. Similar to cerebellar senile plaques in Alzheimer's disease, many kuru plaques contained ubiquitin-positive, tau-negative small granular elements, presumably representing dystrophic neurites. Our results suggest that similar mechanisms are involved in neuritic changes in cerebellar plaques in Creutzfeldt-Jakob and Alzheimer's diseases despite differences of amyloid proteins in the plaques.

Aged↗

PubMed1990

Stroke in pediatric acquired immunodeficiency syndrome.

In a 4 1/2-year period, 4 of 68 children in a longitudinal study of neurological complications of human immunodeficiency virus (HIV) infection had clinical and/or neuroradiological evidence of stroke, yielding a clinical incidence of stroke in this population of 1.3% per year. During this period, 32 subjects died, and permission for autopsy was granted in 18 of the patients, including 3 of 4 who had clinical evidence of stroke. The prevalence of cerebrovascular pathological features in our consecutive autopsy series was higher than the clinical incidence. At autopsy cerebrovascular disease was documented in 6 (24%) of 25 children with HIV infection, including all 3 children who had clinical evidence of stroke. Four patients had intracerebral hemorrhages, 6 patients had nonhemorrhagic infarcts, and 3 had both. Hemorrhage was catastrophic in 1 child and clinically silent in 3 children, all of whom had immune thrombocytopenia. One child had an arteriopathy that affected meningocerebral arteries. In another child, the arteries of the circle of Willis were aneurysmally dilated. Two children had coexisting cardiomyopathy and subacute necrotizing encephalomyelopathy with vascular proliferation. These results suggest that stroke should be considered when children with HIV infection develop focal neurological signs.

Acquired Immunodeficiency Syndrome↗

PubMed1990

Microglia in cerebellar plaques in Alzheimer's disease.

Cerebellar amyloid deposits in Alzheimer's disease were studied by immunocytochemistry and with a series of antibodies that recognize human microglia, including anti-HLA-DR, LN-1, Leu-M5 and leukocyte common antigen. Microglia formed a dense reticular array throughout the cerebellum in areas with and without amyloid deposits. In areas with compact and reticular amyloid deposits, microglia had morphological features consistent with activation, such as cytoplasmic swelling and shortening and thickening of cell processes. In areas with diffuse amyloid deposits, microglia had delicate and highly ramified processes. Nevertheless, microglial cells or their processes were detected in association with amyloid deposits of all morphological types. These results raise the possibility that microglia may play a fundamental role in the pathogenesis of amyloid deposition in the cerebellum in Alzheimer's disease.

Aged↗

PubMed1990

Modified Bielschowsky stain and immunohistochemical studies on striatal plaques in Alzheimer's disease.

The nature of senile plaques (SP) in the striatum in 14 cases of Alzheimer's disease (AD) was investigated with the modified Bielschowsky stain and immunohistochemistry using antibodies to a beta amyloid synthetic peptide, ubiquitin, tau protein, and paired helical filaments (PHF). Striatal SP, composed of beta amyloid deposits with or without neuritic elements, were demonstrated in all AD cases examined. Compact and perivascular amyloid deposits were concentrated in the ventral striatum, including the nucleus accumbens. Many diffuse amyloid deposits in the ventral striatum contained ubiquitin-positive granular elements, presumably representing dystrophic neurites, whereas most of those in the dorsal striatum did not have such elements. On the other hand, most compact amyloid deposits in both ventral and dorsal striatum had ubiquitin immunoreactivity. Dystrophic neurites with tau or PHF immunoreactivity were detected particularly around compact amyloid deposits. Our results indicate that the ventral striatum, which is closely affiliated with the limbic system, is frequently affected by amyloid deposits with dystrophic neurites, and suggest that the ventral striatum is particularly vulnerable to AD. Furthermore, our results suggest that amyloid deposits, especially compact deposits, may induce dystrophic neurites.

Aged↗

PubMed1990

Ubiquitin immunoelectron microscopy of dystrophic neurites in cerebellar senile plaques of Alzheimer's disease.

Senile plaques are present in the cerebellum of most Alzheimer patients. They are composed of beta-amyloid deposits lacking neurites detectable with immunocytochemistry for neurofilament, tau and paired helical filament proteins. Recent studies, however, have shown that cerebellar plaques usually contain round structures that are reactive with ubiquitin antibodies. In this immunoelectron microscopic study, the nature of these structures is explored. Ubiquitin-positive structures in cerebellar senile plaques were composed of degenerating neurites that contained membranous and vesicular dense bodies, but no paired helical filaments. A minority of the neurites contained finely granular material. Thus, cerebellar plaques are associated with neuritic degeneration, and the neurites in cerebellar plaques resemble dystrophic neurites in senile plaques of non-demented elderly subjects and subjects with non-Alzheimer dementias. They differ from some of the neurites in senile plaques in the neocortex in Alzheimer's disease by the absence of paired helical filaments. These results suggest that the same mechanisms involved in the generation of dystrophic neurites in pathological aging are involved in generating dystrophic neurites in the cerebellum in Alzheimer's disease.

Aged↗

PubMed1990

Morphology and distribution of HIV-1 gp41-positive microglia in subacute AIDS encephalitis. Pattern of involvement resembling a multisystem degeneration.

Among 100 brains from patients with acquired immunodeficiency syndrome (AIDS), 33 brains (21 adults and 12 children) with histological evidence of subacute AIDS encephalitis were immunostained with one of the most sensitive antibodies to HIV-1 antigen, anti-gp41. Twenty-six (20/21 adults, 6/12 children) of the 33 brains showed pg41 positivity. Brains from children had fewer gp41-positive cells than brains from adults. The distribution of gp41-positive cells was characteristic. They were frequently detected and most numerous in the globus pallidus (medial greater than lateral). Although gp41-positive cells were prevalent, fewer were detected in the corpus striatum and thalamus. Of infratentorial areas involved, the ventral midbrain, especially the substantia nigra, and the dentate nucleus contained many positive cells. Lower levels of infections, often patchy, were noted in the cerebral and cerebellar white matter and pontine base. Gp41-positive cells were rarely seen in the cerebral cortex, medulla, spinal cord, leptomeninges, choroid plexus, ependyma, subependymal areas and endothelia. Besides immunoreactive macrophages and multinucleated cells, gp41-positive microglia with various morphological alterations were abundant in the deep cerebral gray matter, ventral midbrain and dentate nucleus. Most of these microglia were undetectable with conventional histological methods. We discuss the significance of the distribution of HIV-1-infected cells, especially microglia, with respect to cellular tropism and involvement of deep gray matter nuclei in a pattern reminiscent of a multisystem atrophy.

Acquired Immunodeficiency Syndrome↗

PubMed1990

Aprosencephaly: review of the literature and report of a case with cerebellar hypoplasia, pigmented epithelial cyst and Rathke's cleft cyst.

Aprosencephaly is a very rare brain malformation that occurs in isolated and sydromatic forms. The syndromatic form has been named "XK-aprosencephaly", and is characterized by near total absence of prosencephalon with a midline oculofacial defect similar to the most severe forms of holoprosencephaly, in association with limb and genital anomalies. We present a case of syndromatic aprosencephaly with absence of thumb and abnormal external genitalia. A previously undescribed finding was a Rathke's cleft cyst. Two other cystic structure were also identified--an ependymal cyst, which may represent a dorsal cyst as in holoprosencephaly, and a pigmented epithelial cyst, which may represent a rudimentary eye. Additional findings were extensive calcific vasculopathy in the rudimentary prosencephalon, absence of pituitary gland, forking of the aqueduct of Sylvius and marked cerebellar hypoplasia. Since calcific vasculopathy is a common accompaniment of other inflammatory diseases of the central nervous system, its presence in this case suggests that destructive processes may be involved in the genesis of some cases of aprosencephaly.

Abnormalities, Multiple↗