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R H Rhodes

Publications and source records attributed to R H Rhodes.

At least 37 records · Page 2Linked to original sources

Immunohistochemistry of human immunodeficiency virus in the central nervous system and an hypothesis concerning the pathogenesis of AIDS meningoencephalomyelitis.

Early events of HIV infection of the CNS are not yet clear. HIV infection in most recent cases, generally shows a prolonged interval between diagnosis and death. HIV infection, months to years before the patient's death, may or may not result in early neurologic symptoms. AIDS patients with spinal cord symptoms often show a sudden onset of long tract signs and a temporally related altered mental status indicating the appearance of both myelitis and encephalitis. Immunohistochemical localization of the HIV cell-surface receptor protein, CD4, and of HIV antigens in cerebral and lymph node venular endothelial cells suggests that a natural occurrence or induction of CD4 protein in some endothelial cells allows transmission of HIV from circulating infected white blood cells preferentially to certain tissues through endothelial cell infection. HIV immunolocalization is present in perivascular astrocytes, particularly in long white matter tracts, and on the surface of oligodendrocytes. HIV immunoreactivity is mostly in macrophages and multinucleated cells in a typical autopsy case, but this may be due to the clearing of HIV antigen from early sites of infection by the hematogenous cells. Not all immunoreactivity for HIV antigens is necessarily due to HIV gene products. Cross reacting epitopes, such as that of HIV envelope glycoprotein gp120 and neuroleukin, may be "seen" not only by antibodies on tissue sections, but by an AIDS patient's immune system, thus targeting a CNS antigen for immune-complex formation. Evidence for hypersensitivity disease in the CNS in AIDS includes the frequent findings of demyelination, perivenous chronic inflammation, chronic vasculitis, and perivenous hemorrhages. The white matter demyelination so frequently reported in all areas of the CNS in AIDS could be the result of a combination of factors that include direct HIV vasculitis, opportunistic infections, and hypersensitivity responses. The blood-brain barrier is breached when immune-related antigens interact on CNS vascular endothelial cells. Perhaps the CD4 antigen, which responds to interaction with antigen-presenting cells and enhances cellular immune activity, is induced or increased in the CNS in association with immune activity and in the presence of a leaky blood-brain barrier. Therefore, with or without HIV in the CNS, hypersensitivity disease, including demyelination, may be the result of long-standing activity of the immune system in AIDS patients.

Acquired Immunodeficiency Syndrome↗

Deep white matter infarction: correlation of MR imaging and histopathologic findings.

Focal and confluent areas of periventricular hyperintensity have been reported on magnetic resonance (MR) images in 30% of patients over 60 years of age. In order to better understand the pathologic basis of these lesions, the authors studied 14 formalin-fixed brains with MR imaging. Multiple focal areas of hyperintensity were identified in the periventricular white matter in three of the 14 brains studied (21%). Subsequent gross and microscopic pathologic examination of both hyperintense and normal-intensity areas was performed on 87 tissue sections. The larger lesions were characterized centrally by necrosis, axonal loss, and demyelination and therefore represent true infarcts. Reactive astrocytes oriented along the degenerated axons were identified at distances of up to several centimeters from the central infarct. This is called isomorphic gliosis and is associated with increased intensity on T2-weighted images that increases the apparent size of the central lesion.

Aged↗

Progressive multifocal leukoencephalopathy and retroviral encephalitis in acquired immunodeficiency syndrome.

Antigens of human polyomaviruses, the etiologic agents of progressive multifocal leukoencephalopathy (PML), and of human immunodeficiency virus were localized in paraffin sections from brains of six patients who died with the acquired immunodeficiency syndrome. Immunostaining revealed polyomaviral antigens in oligodendrocytes and in some astrocytes. Human immunodeficiency (retro) virus antigens were immunostained in mononuclear macrophages, glial cells, and vascular endothelial cells. Both viral types were found ultrastructurally. The lesions of PML were more destructive than is usually seen in cases without the acquired immunodeficiency syndrome. The retroviral encephalitis could have occurred before the onset of PML. However, a secondary retroviral encephalitis could have resulted if the monocytes responding to an initial polyomaviral lesion were already infected with human immunodeficiency virus before they differentiated into macrophages.

Acquired Immunodeficiency Syndrome↗

Ultrastructure of complex carbohydrates of rodent and monkey ependymal glycocalyx and meninges.

The surfaces of the brain offer metabolic and mechanical support to the underlying parenchyma. Mouse, rat, and monkey brains were fixed by immersion in a glutaraldehyde fixative or glutaraldehyde with cetylpyridinium chloride, followed by block staining for complex carbohydrates using alcian blue with OsO4 postfixation, or OsO4 postfixative solution containing ruthenium red, or alcian blue and then ruthenium red-OsO4 treatment. The ependyma in these species had a glycocalyx extending into the ventricular fluid as a finely filamentous network when stained with alcian blue or with alcian blue followed by ruthenium red-OsO4. Mice in the middle age range had stained material in this glycocalyx resembling the hyaluronic acid reported in the ocular vitreous body. Similar material was seen in the arachnoidal space of these mice and in the inner connective tissue matrix of the dura mater. Both the mouse and monkey had a cell-free zone, termed the inner dural matrix zone, between the thick fibrous dura and its innermost cellular layer. This zone contained filamentous and globular alcian blue-stained material. The complex carbohydrates of the mouse ependymal glycocalyx and inner dural matrix zone underwent changes developmentally. Aged rats were injected intraventricularly with latex beads, which, along with extravasated erythrocytes, were seen to adhere to the ependymal glycocalyx. A similar adhesion of erythrocytes was seen in the mouse and monkey ependymal glycocalyx and in the filamentous network of the mouse and monkey inner dural matrix zone. The ependymal glycocalyx, formed in part of complex carbohydrates, is much thicker than previously demonstrated. Some activities related to the ependymal lining of the ventricles, including the movement of cells or particles, the penetration of metabolites or serum-protein fractions (e.g., immunoglobulins), and cell-surface hydration, probably depend in part on complex carbohydrates that provide a sticky, electrically negative, hydrophilic environment. The complex carbohydrates in the inner dural matrix zone might provide mechanical buffering. Complex carbohydrates in the arachnoidal space may help to maintain a loose tissue that needs not only to be hydrated, but also to be open enough to provide cerebrospinal fluid circulation.

Animals↗

Immunohistochemical demonstration of proteinase inhibitor alpha-1-antichymotrypsin in normal human central nervous system.

The presence of alpha-1-antichymotrypsin, a serine proteinase inhibitor with a high affinity for cathepsin G, is demonstrated in the normal human central nervous system (CNS) by immunohistochemical techniques. Paraffin-embedded normal human CNS tissue from five adult, two fetal, one neonatal and three newborn autopsies were stained with monospecific rabbit antibodies to human alpha-1-antichymotrypsin using biotinylated goat anti-rabbit antibodies and an avidinbiotin-peroxidase complex. Positive immunostaining was seen in neurons and glial cells in the cerebral cortex, basal ganglia, hippocampus, cerebellum, brainstem, and spinal cord of the adults. The epithelium of the adult choroid plexus had the most intense staining in apical granular organelles corresponding in position to lysosomes or secretory granules. Ependymal cells, particularly those near the choroid plexus, were immunostained. The fetal CNS had no alpha-1-antichymotrypsin staining. Limited staining of choroid plexus, ependyma, and frontal lobe was found in the newborns. Immunostaining in the neonatal temporal lobe was only found in the choroid-plexus epithelium. These observations establish a widespread distribution of this proteinase inhibitor in the normal human CNS. Developmental regulation of this inhibitor in the human CNS is also indicated.

Adult↗

Histopathology of the central nervous system in the acquired immunodeficiency syndrome.

Histopathologic findings in the central nervous system in 100 autopsy cases of the acquired immunodeficiency syndrome (AIDS) gave evidence of a variety of opportunistic infections and probably of infection by human immunodeficiency virus (HIV). Gliomesenchymal cell nodules (47 per cent of cases) and spongiform alterations with demyelination were common. Vasculitides (8 per cent) and lesions such as acute hemorrhagic leukoencephalitis may be attributable partly to hypersensitivity reactions. Multinucleated cells, including giant cells that could be a hallmark of HIV encephalitis, were common in normal neuropil, in gliomesenchymal cell nodules, near blood vessels, and in cavitating lesions. Degeneration in long tracts (13 per cent) included posterior column demyelination and spongiform change with or without corticospinal tract degeneration. Some long tract degeneration appeared to originate from bilateral degeneration of the internal capsule, and this may be part of the origin of subacute combined degeneration-like changes in AIDS vacuolar myelopathy. Prominent brainstem inflammatory infiltration suggests that the brainstem is a relatively prominent site of infection or immunopathologic activity. Early ependymal lesions in infants and frequent healed ependymal lesions in adults (16 per cent) could be related to the origin and pathogenesis of HIV lesions in the brain. Some characteristic lesions in AIDS encephalitis may result from immune-mediated responses to HIV antigens on neural cell receptors or from cross-reactivity occurring against epitopes common to neural constituents and to hematopoietic cells, with the latter being under direct antiviral attack.

Acquired Immunodeficiency Syndrome↗

Immunohistochemical localization of human and simian immunodeficiency viral antigens in fixed tissue sections.

Antigens of human (HIV) or simian immunodeficiency viruses (SIV) were identified with polyclonal or monoclonal antibodies and avidin-biotin complex (ABC) immunohistochemistry in fixed surgical pathology and autopsy specimens of humans or monkeys with the acquired immunodeficiency syndrome. With B-5 fixative, viral antigens were readily detected in lymph nodes of 8 of 13 patients with follicular hyperplasia, but in only 1 of 12 patients with follicular atrophy. Antigen was detected in follicular dendritic reticular cells and rare blastlike cells, extracellularly, and in postcapillary venules, medullary lymphocytes, sinus histiocytes, and macrophages in some lymph nodes. In the brain at autopsy, antigen could be found in gliomesenchymal-cell nodules, astrocytes, vascular endothelial cells, multinucleated cells, and astrocytes and macrophages associated with demyelination. In contrast, 4 rhesus monkeys with experimental SIV infection had abundant antigen in sinus histiocytes, macrophages, and multinucleated giant cells of lymph nodes and spleen and in thymic epithelial cells. Brain lesions of monkeys resembled those of humans, with antigen found in macrophages and multinucleated giant cells. Antibodies to HIV also were immunoreactive in formalin-fixed tissue sections of monkeys containing SIV antigens. The ABC technique provided a fast and efficient method for localizing HIV and SIV antigens in fixed surgical and autopsy specimens. These findings are consistent with those found with in situ hybridization, ultrastructural studies, frozen sections of lymph nodes, and permanent sections of brain.

Acquired Immunodeficiency Syndrome↗

An ultrastructural study of complex carbohydrates in the posterior chamber and vitreous base of the mouse.

The fibrillar and mucoid extracellular matrix of the posterior chamber and vitreous base was studied in the mouse by electron microscopy using fixation and staining methods that demonstrated complex carbohydrates. These methods, including block-staining with Alcian Blue, allowed globular and filamentous hyaluronic acid, finely filamentous oligosaccharides, laminated glycolipids or lipophilic glycoproteins and stellate proteoglycan monomers to be identified tentatively. There was much less globular hyaluronic acid along the basement membrane of the peripheral retina and ciliary body than has been observed in the posterior fundus. A finely filamentous network on the basement membrane interconnected with a similar network covering individual collagen fibrils, zonules and meridional fibrillar laminae as well as with a branching fibrillar network that was seen in the posterior chamber and vitreous base. This interconnected system of fibrillar proteins and complex carbohydrates was also connected to the anterior hyaloid membrane. The infoldings of the ciliary epithelium contained stellate densities with characteristics of proteoglycan monomers similar to those reported in the matrix of cartilage. The complex carbohydrates of the posterior chamber and vitreous base are of several types known to affect protein function, provide water binding and assist in mechanical stability.

Animals↗

Respirator retina.

Retinas from 14 comatose patients, who had been sustained with a respirator for one or more days before death, had selective characteristic alterations (ie, autophagy, cell swelling, and coagulation necrosis) of inner nuclear layer in a patchy pattern in posterior fundus. Bipolar cells were most often affected, but amacrine and horizontal cells also were substantially damaged. Cells of Müller and vascular cells were largely spared. These lesions are ascribed to oligemia (ischemia) since the inner nuclear layer is a microscopic vascular watershed (boundary zone) between the choroidal and retinal circulations.

Adolescent↗

Ultrastructure of Müller cells in the developing human retina.

The posterior retina of human embryos from 4 to 200 mm of crown-rump length was studied by electron microscopy. At 20 mm dense inner Müller-cell processes near ganglion cells contained rough endoplasmic reticulum, free ribosomes, small matrix particles, and some intermediate filaments. These processes soon had smooth endoplasmic reticulum. By 71 mm many of these inner processes were lucent and contained many intermediate filaments and glycogen particles. Müller-cell nuclei and outer processes were observed between differentiating cone cells at 66 mm, and these outer radial-cell processes soon contained many dense matrix particles and glycogen particles. As neurons in the inner nuclear layer differentiated by 100 mm, Müller-cell cytoplasm in the mid-retina was identified by its intermediate filaments and glycogen particles. Müller cells have composite glial features that appear in the horizontal retinal layers concomitant with neuronal differentiation and maturation in each layer.

Adolescent↗

The distribution of cathepsin D in rat tissues determined by immunocytochemistry.

The distribution of cathepsin D (CD) was surveyed in rat tissues by light microscopic immunocytochemistry. Although immunoreactive CD was detected in all tissues examined, there was a marked difference in the amount in the cytoplasm of different cell types of the same organ. In the retina large amounts of CD were present in the pigment epithelium, ganglion cells, and Müller cells. Moderate to large amounts of CD were also found in neuronal perikarya of the gastrointestinal tract and adrenal medulla; in macrophages in the lung, liver, and spleen; in some secretory cells of the submandibular and lacrimal glands; in parts of renal distal convoluted and collecting tubules; and in the surface transitional epithelium of the calyx, ureter, and urinary bladder. Other cells adjacent to cells containing large amounts of the enzyme had little or no detectable CD themselves. These included hepatocytes, the proximal tubular cells of the kidney, selected cells of the submandibular gland, cells of the zona glomerulosa of the adrenal cortex, and lymphocytes in lymphoid organs. The localization of CD indicates that its degradative effect is exerted preferentially in certain cell types and suggests that physiological influences on CD may have a variety of effects in different organs.

Animals↗

An ultrastructural study of histochemical staining of complex carbohydrates in the mouse posterior vitreous body.

The vitreous body contains complex carbohydrates that can be demonstrated morphologically. Vitreous hyaluronic acid is very soluble but it can be precipitated by cetylpyridinium chloride (CPC) while being cross-linked by glutaraldehyde. Oligosaccharide chains of vitreous glycoproteins are fixed with glutaraldehyde alone. Mouse eyes were fixed with glutaraldehyde or glutaraldehyde and CPC and the complex carbohydrates of the posterior vitreous cortex were studied by electron microscopy. Cationic dyes were used in the fixative or for block-staining on most fixed tissue blocks to allow detailed observations of complex carbohydrates. Most blocks were postfixed with OsO4. The hyaluronic-acid domain on vitreous collagen fibrils sequentially contracted and expanded in size with various histochemical manipulations. Contraction of the domain of hyaluronic acid generally indicates an increased charge density. OsO4 contributes considerable charge density upon forming osmate esters, but tissue postfixed with OsO4 contained large globular forms of hyaluronic acid rather than the small globules observed in non-osmicated preparations. A model is proposed to explain the seemingly paradoxical findings by reference to suggested mechanisms of polysaccharide-ligand-OsO4 interactions.

Animals↗

A comparative study of vitreous-body and zonular glycoconjugates that bind to the lectin from Ulex europaeus.

Eyes from adult rodents, rabbits and humans were fixed in formalin, embedded in paraffin and incubated with a horseradish peroxidase-conjugated lectin from Ulex europaeus to localize vitreous-body and zonular glycoconjugates. Rodent eyes had reaction product for peroxidase activity in fibrous structures in the posterior chamber, vitreous base and vitreous cortex. The zonules and the internal limiting membrane region of the retina also were stained. Rabbit eyes had more stained fibrous material in the vitreous base than rodent eyes and the attachment region of the zonules on the lens capsule, the anterior hyaloid membrane and tracts in the vitreous cortex were more heavily stained in rabbits. There was heavy staining of the thick vitreous base in the human eyes as well as staining of zonules, anterior hyaloid membrane and vitreous cortex. The localization of this lectin may be specific for fucose in glycoproteins or other glycoconjugates, although this was not demonstrated here. However, the location of lectin binding sites correlates well with known sites of uptake of tritiated fucose and tritiated glucosamine in rabbit eyes. Eyes from the larger species studied had more lectin-binding glycoconjugates in fibrous structures in the vitreous body than those from smaller species. The amount of glycoconjugate identified in some of the lectin-binding sites may be related to some extent to the degree of stress incident upon those sites.

Adult↗

Ocular malformation involving tissue of neural-crest derivation.

A 5-month-old infant had an enlarged left eye removed for a possible intraocular malignancy. The eye had a thin cornea, a superior staphyloma, a completely cupped optic nerve head and no iris or lens. Histopathologic study showed little corneal or uveal stroma, small rudiments of ciliary body superiorly with no smooth muscle, pigment epithelium and nonpigmented neuroepithelium that lined the entire interior of the globe, focal superior retinal dysplasia and a focal superior scleral thickening containing a melanotic malformation. Except for the absence of the lens and the presence of neuroepithelium behind the cornea, all of the findings might be explained by a defect in ocular neural-crest tissue, either as a primary lesion of a portion of the cephalic neural crest (crest embryopathy) or secondary to a local mesodermal malformation.

Choroid↗

Intrasellar neural-adenohypophyseal choristoma. A morphological and immunocytochemical study.

A patient with mild acromegaly had recurrence of symptoms and signs of a chiasmal-area lesion seventeen years after radiation therapy for a presumed pituitary adenoma. A mass was found anterior to the pituitary gland. Abnormal tissue removed from the sphenoid sinus and sella turcica consisted of a predominantly ganglion-cell lesion. A few ganglion cells were immunoreactive for somatostatin. There were some small cysts lined by cells with immunostaining for glial fibrillary acidic protein, growth hormone or prolactin. Some cells with vacuoles and eosinophilic granules showed immunostaining for growth hormone, prolactin, ACTH, and beta-endorphin and, thus, appeared to be of adenohypophyseal origin. Cases of intrasellar ganglion-cell lesions have been reported, most of them associated with pituitary adenomas and acromegaly. The findings in this case are discussed in relation to the hypothesis that displaced, hypothalamic-type ganglion cells may produce a growth hormone-releasing factor that stimulates the development of a growth hormone-secreting pituitary adenoma. An alternative hypothesis is suggested that includes this concept, but also allows for the influence of non-neuronal cells on neuronal differentiation and for the possible influence of adenohypophyseal hormones on the replication of hypothalamic-type neurons in the lesion.

Adult↗

An ultrastructural study of the complex carbohydrates of the mouse posterior vitreoretinal juncture.

The content and distribution of complex carbohydrates of the posterior vitreoretinal juncture of the mouse eye were examined by electron microscopy. Eyes were fixed 24 hr or 192 hr in glutaraldehyde or glutaraldehyde and cetylpyridinium chloride (CPC) and then block-stained with cationic dyes. Globular material of intermediate electron density was found in the basement membrane of the retina and on collagen fibrils in the vitreous cortex with CPC fixation and disappeared after Streptomyces hyaluronidase digestion. More of this material was found at the juncture of the basement membrane and the vitreous body with alcian blue than with the other cationic dyes after the shorter fixation period. After prolonged fixation, all of the cationic dyes revealed a thick layer of globular material on the basement membrane. A finely filamentous network associated with the globular material was revealed by glutaraldehyde fixation and alcian blue staining. Some laminated bodies were found at the vitreoretinal juncture after block-staining. Neither the finely filamentous material nor the laminated material was sensitive to the hyaluronidase. It is suggested that the globular material is hyaluronic acid, which is more labile along the basement membrane than toward the inner vitreous cortex. The finely filamentous network may be formed of oligosaccharide chains associated with vitreous proteins. The laminated bodies may be formed of lipid and complex carbohydrates of an otherwise uncharacterized mixture. The various complex carbohydrates form parts of a vitreoretinal-juncture layer that may participate in the known chemical, cellular, and mechanical barrier functions of this region.

Animals↗