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Biomedical subjects

R Anand

Publications and source records attributed to R Anand.

At least 181 records · Page 10Linked to original sources
PubMed1989

Biological and molecular characterization of human immunodeficiency virus (HIV-1BR) from the brain of a patient with progressive dementia.

HIV-1BR was isolated from the autopsied brain tissue of a 57-year-old man who died of progressive dementing illness. This virus was shown to be HIV-1 by hybridization to HIV-specific DNA probes. The expression of viral proteins as tested by radioimmunoprecipitation assay revealed the presence of HIV-1-specific proteins. HIV-1BR replicated in cultures of CD4+ T-lymphoid cells and induced cytopathic effects in these cells. HIV-1BR also replicated in monocytoid cell lines. The genetic nature of this isolate was determined by molecular cloning and sequencing of the 3'-half of the genome. DNA sequence information established that HIV-1BR is a unique HIV-1 isolate. A stretch of approximately 30 bases in the nef gene of HIV-1BR was found duplicated when compared with the other sequenced HIV-1 genomes. The functional significance of this duplication remains to be determined.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Efficacy of rifabutin in the treatment of AIDS-related complex.

We performed a phase 1-2 antiviral dose escalation trial of rifabutin, a rifamycin antibiotic with anti-HIV-1 activity in vitro. We followed 16 men with AIDS-related complex (ARC) for a mean duration of 29 weeks; the maximum toxicity-limited dose of rifabutin was 2400 mg/day, which was achieved in two patients. There was some evidence of anti-HIV-1 activity in two patients, one of whom had an improvement in immune status, but 11 of the 16 patients showed a deterioration in either virologic or immunologic status. The majority of the patients under study remained clinically stable during the trial, but there was clinical deterioration in the three who entered with CD4 cell counts of less than 100 x 10(6)/l. On the basis of this trial, rifabutin as a single antiviral agent does not appear to be beneficial to ARC patients.

AIDS-Related Complex↗
PubMed1989

Augmentation of helper virus replication in the presence of defective retrovirus.

The interaction between defective spleen focus-forming virus (SFFV) and helper virus(es) in Friend virus (FV) complex has been assumed to be one-way, with the helper virus complementing SFFV by supplying necessary virion components. To test this assumption the expression of both SFFV and helper virus in partially congenic mice which differ at the Fv-2 locus, a gene that specifically controls susceptibility to SFFV, was analysed. When the mice were infected with LLV (a strain of Friend SFFV-free helper virus), there was no detectable effect of Fv-2 genotype on LLV expression as tested by virus infectivity in the XC plaque assay or by quantitative viral antigen analysis in an immunoprecipitation assay. However, after infection with FV complex there was an amplification of LLV (as well as SFFV) synthesis in Fv-2s as compared with Fv-2r hosts. To determine whether the increased LLV synthesis in Fv-2s mice was due to an increased population of susceptible target cells as a result of SFFV infection and/or transformation, the ratios of LLV-infected cells in the spleens of LLV- and FV-infected Fv-2s hosts in an infectious centre assay, were compared. Since the percentage of LLV-infected cells was equivalent in both instances, the higher rate of LLV synthesis after infection with FV complex was presumably due to intrinsic properties of SFFV-infected erythroid cells.

Animals↗
PubMed1989

The effects of moclobemide on cognition.

The mental ability of the elderly is frequently compromised by age-associated cognitive declines, which may be result of cholinergic deterioration. Depression is accompanied by cognitive performance impairments, and recent work suggests these may be more severe in the elderly. Antidepressants with anticholinergic side-effects, such as the tricyclics, should thus be used with caution in the elderly. A potential advantage of new antidepressants which are relatively free of anticholinergic effects, may be in a reduced liability to impair cognition, whilst maintaining at least equal antidepressant potency. The effects of moclobemide, a novel reversible monoamine oxidase inhibitor, have been studied in both young and elderly volunteers using computerized assessment of a variety of aspects of cognition. In the young the drug was studied within a scopolamine model of the cognitive effects of aging and dementia, while, in the elderly, the cognitive effects of the drug were compared to those of trazodone. In the scopolamine model, moclobemide was significantly superior to placebo and other compounds in antagonizing the cognitive impairments resulting from cholinergic blockade. In the elderly, some improvements were found with moclobemide, particularly in memory, and while an impairment to vigilance was observed, this effect was considerably less marked than with trazodone. Moclobemide would thus appear to have an advantage over antidepressant compounds such as the tricyclics of having a lower liability to impair cognitive efficiency. However, to establish this in depressed patients it will be necessary to incorporate sensitive assessments of cognitive efficiency into trials of the drug in young and elderly populations.

Benzamides↗
PubMed1989

"Top of the basilar" syndrome: a clinical and CT analysis.

Fifteen patients presenting with visual, oculomotor and behavioural disturbances were diagnosed to be suffering from "top of the basilar" syndrome. Computed tomography confirmed the distribution of infarctions in the vascular territory of the rostral basilar artery. The clinical profile comprised cortical blindness and visual field defects, vertical gaze paresis, memory and behavioural disturbances and in one patient, the paramedian diencephalic syndrome.

Adult↗
PubMed1989

Surgical dilation of the pupil during pars plana vitrectomy.

Adequate pupillary dilation is essential to dissect and excise peripheral tractional proliferative tissue during vitreous surgery. Most surgical dilating procedures involve an incision or excision of iris tissue, that is either inadequate or irreversible. We describe a modification of a previously devised technique for stretching the pupil that ensures an excellent view of the peripheral retina. The technique has been used in aphakic and pseudophakic eyes in over 50 cases with no postoperative morbidity or problems with glare or poor cosmesis.

Dilatation↗
PubMed1988

Extensive deletions and insertions in different MHC supratypes detected by pusled field gel electrophoresis.

The genomic organization of the human MHC was examined in multiple examples of six different supratypes using pulsed field electrophoresis (PFGE) after digestion of genomic DNA with infrequency cutting restriction endonucleases. Differences in restriction fragment length and band intensity were shown to be specific for each supratype. Mapping of the MHC revealed that each supratype contains previously undescribed deletions and insertions between HLA B and DQ regions.

Chromosome Deletion↗
PubMed1988

Complete structure of the glycosyl phosphatidylinositol membrane anchor of rat brain Thy-1 glycoprotein.

Glycosyl-phosphatidylinositol (GPI) anchors have recently been identified as alternatives to hydrophobic amino acid sequences for the attachment of a variety of eukaryotic cell surface molecules to the lipid bilayer. In single cell eukaryotes the GPI group appears to be the predominant form of membrane attachment, and in vertebrates a substantial minority of molecules have this anchor including cell surface hydrolytic enzymes, antigens and cell adhesion molecules. Analysis of different GPI anchors suggests they share common structural features including linkage to the COOH group of the terminal amino acid via ethanolamine phosphate, the presence of phosphatidylinositol lipid and a glycan between the bridging ethanolamine phosphate and the lipid. In the case of the Trypanosoma brucie variant surface glycoprotein (VSG) the full structure of the GPI anchor has been determined and this provides a prototype for comparison with other molecules. We now report the structure of the GPI anchor of rat brain Thy-1 glycoprotein. It has an identical backbone to the VSG anchor but shows significant differences in side chain moieties.

Animals↗
PubMed1988

Preliminary molecular characterization of a human immunodeficiency virus (HIV-I) associated with neuropathology.

A human immunodeficiency virus (HIV-I) was isolated from the brain of a patient with progressive dementia but no obvious immunosuppression. This isolate, designated as HIV-IBR, was molecularly cloned and sequenced, and its long terminal repeat (LTR) and envelope sequences were compared with those of other HIV isolates not uniquely associated with dementia. The HIV-IBR LTR showed marked homology with the LTR sequences of the other HIV-I isolates. The predicted amino acid sequence of the external glycoprotein (gp120) of HIV-IBR revealed a pattern of conserved and variable regions similar to that of other HIV isolates. The sequence of the transmembrane portion of envelope, gp 41, was highly homologous to the counterpart region of other isolates. Further analysis is required to determine whether specific sequence variation can account for neurological manifestations of HIV-IBR infection.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Natural variants of human immunodeficiency virus from patients with neurological disorders do not kill T4+ cells.

Human immunodeficiency virus (HIV) has selective T4-cell tropism and is cytocidal to cells with the helper-inducer phenotype. Central nervous system dysfunctions can complicate full-blown acquired immunodeficiency syndrome (AIDS) but can also be present either in isolation or in the context of AIDS-related complex. Remarkably bland histopathological findings have been reported in some patients with AIDS dementia in the presence of severe clinical dysfunction. Thus, to understand the cytopathic properties of HIV, we recovered five viral isolates from 4 patients with neurological symptoms of AIDS and identified them as HIVs. The replication and cytocidal properties of these isolates were compared with lymphadenopathy-associated virus in vitro. All five isolates exhibited replication efficiency equivalent to lymphadenopathy-associated virus, but four isolates did not kill CD4 (T4+) cells. These findings provide evidence for the existence of replication-competent noncytocidal natural variants of HIV and raise the possibility that, in some AIDS patients, neurological disorders might be caused by HIV variants that are noncytocidal to T4 cells.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Laser balloon angioplasty: effect of tissue temperature on weld strength of human postmortem intima-media separations.

Dehiscence of portions of atheromatous plaques fractured during percutaneous transluminal coronary angioplasty may contribute to both abrupt reclosure and gradual restenosis. Laser balloon angioplasty has been shown to be effective in welding human plaque-arterial wall separations in vitro by heating tissues with a Nd:YAG laser during balloon inflation. To define the potentially useful therapeutic range of tissue temperature required to achieve thermal welds, 220 1-cm diameter discs of human postmortem atheromatous aortic tissue, the intimal plaque of which had been separated from the media, were exposed to 3-25 watts of Nd:YAG laser radiation delivered over a 12-mm2 nominal spot size for 20 seconds via a 400-micron core optical fiber. As measured with a thermistor, adventitial temperature reflected the temperature at the plaque-media junction to within 10 degrees C. The degree of tissue temperature elevation was related to delivered energy, while effective tissue penetration increased to maximum depth of 3 mm at the highest power density. Strength of tissue welds was defined as the force required to shear opposing layers of welded segments. Adventitial tissue temperatures below 80 degrees C were not associated with appreciable welds, while equilibrium temperatures between 95 degrees C and 140 degrees C were consistently associated with effective mean weld strengths, which increased linearly from 25 to 110 g, respectively. Temperatures greater than 150 degrees C were associated with rapid tissue dehydration and charring. These data suggest that the therapeutic range of tissue temperature that provides effective thermal fusion of intima-media separations is broad and that the depth and degree of thermal coagulation can be controlled by manipulation of laser energy delivery.

Angioplasty, Balloon↗
PubMed1988

Studies on human immunodeficiency virus-induced cytopathic effects: use of human rhabdomyosarcoma (RD) cells.

A full-length molecular clone of human immunodeficiency virus (HIV) proviral DNA was transferred to human rhabdomyosarcoma (RD) cells by gene transfer method. RD cells released infectious virus within 12 hours after transfection and the viral particles present in the culture medium could be quantitated by monitoring reverse transcriptase activity. Chronic low level viral producer cell lines of RD were also established. Southern hybridization analysis revealed the presence of HIV sequences in transfected RD cells. Electron microscopic studies of the transfected cell revealed intracellular budding of HIV and also showed structural abnormalities such as giant cell phenotype and vacuolation. These features qualify RD cells as a useful system for studying the regulation and cytopathic effects of HIV.

Cytopathogenic Effect, Viral↗
PubMed1988

Human immunodeficiency virus replication in human brain cells. Brief report.

Human immunodeficiency virus (HIV), the etiologic agent of AIDS, was found to infect and replicate in human brain cells. The extent of HIV replication was minimal in human brain-derived cells in comparison to T4 lymphoid cells. These results suggest that direct infection of glial/neuronal cells by HIV may contribute to the CNS dysfunction frequently observed in HIV infected individuals.

Brain↗
PubMed1988

Clones from an 840-kb fragment containing the 5' region of the DMD locus enriched by pulsed field gel electrophoresis.

Detailed analysis of a large region of genomic DNA is facilitated by generating overlapping clones covering the entire region. These clones are usually obtained by bidirectional "walking" using either bacteriophage lambda or cosmid cloning vectors. This is a slow procedure when starting from a single start site. Multiple start sites are an advantage, and here we describe a method of generating clones from an extensive region of the Duchenne muscular dystrophy locus by preparative pulsed field gel electrophoresis using the chromosome of interest isolated in a cell hybrid. We have generated 12 clones mapping to an 840-kb SfiI fragment of DNA from the Xp2.1 region of the X chromosome, where the DMD gene has been localized. Further localization of these clones to the four subregions of the 840-kb fragment indicates that the clones are distributed throughout the fragment. The feasibility of using this approach to generate probes close to other loci is discussed.

Animals↗
PubMed1988

Mapping of Xp21 translocation breakpoints in and around the DMD gene by pulsed field gel electrophoresis.

Balanced translocations with a breakpoint in the Xp21 region are likely to disrupt the giant Duchenne muscular dystrophy (DMD) locus and can be demonstrated in females suffering from the disease. Pulsed field gel electrophoresis allows the positioning of these breakpoints by detecting junction fragments on the derived chromosomes; DNA probes hybridizing to these fragments may be located as many as several hundred kilobases away from the breakpoints. By using this approach, 11 translocation breakpoints from the Xp21 region have been analyzed. The localization of three previously examined breakpoints was confirmed. Six other breakpoints, including a breakpoint flanking the DMD gene and not associated with the DMD phenotype, could be positioned relative to SfiI sites on a 3.5-Mb restriction map of the region.

Cell Line↗
PubMed1988

Interaction between rifabutin and human immunodeficiency virus type 1: inhibition of replication, cytopathic effect, and reverse transcriptase in vitro.

Rifabutin (ansamycin; LM427), a semisynthetic rifamycin derivative, inhibits the replication of human immunodeficiency virus type 1, the virus etiologically linked to acquired immunodeficiency syndrome. The inhibition of virus production was observed in human immunodeficiency virus type 1-infected peripheral blood mononuclear cells both by reverse transcriptase assay and virus-antigen assay. In addition, rifabutin effectively reduced human immunodeficiency virus type 1-associated cytopathic effect to OKT4-positive cells. Virion-associated reverse transcriptase was also markedly inhibited by rifabutin. The inhibitory dose of rifabutin was nontoxic to lymphoid cells, which further suggests that it might serve as a useful agent in the therapeutic modalities of acquired immunodeficiency syndrome.

Cell Line↗