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Biomedical subjects

J McArthur

Publications and source records attributed to J McArthur.

At least 37 records · Page 2Linked to original sources
PubMed1999

Neurology update.

Explore the source record for details and available documents.

AIDS Dementia Complex↗
PubMed1998

Failure of cytarabine in progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. AIDS Clinical Trials Group 243 Team.

BACKGROUND: Progressive multifocal leukoencephalopathy affects about 4 percent of patients with the acquired immunodeficiency syndrome (AIDS), and survival after the diagnosis of leukoencephalopathy averages only about three months. There have been anecdotal reports of improvement but no controlled trials of therapy with antiretroviral treatment plus intravenous or intrathecal cytarabine. METHODS: In this multicenter trial, 57 patients with human immunodeficiency virus (HIV) infection and biopsy-confirmed progressive multifocal leukoencephalopathy were randomly assigned to receive one of three treatments: antiretroviral therapy alone, antiretroviral therapy plus intravenous cytarabine, or antiretroviral therapy plus intrathecal cytarabine. After a lead-in period of 1 to 2 weeks, active treatment was given for 24 weeks. For most patients, antiretroviral therapy consisted of zidovudine plus either didanosine or stavudine. RESULTS: At the time of the last analysis, 14 patients in each treatment group had died, and there were no significant differences in survival among the three groups (P=0.85 by the log-rank test). The median survival times (11, 8, and 15 weeks, respectively) were similar to those in previous studies. Only seven patients completed the 24 weeks of treatment. Anemia and thrombocytopenia were more frequent in patients who received antiretroviral therapy in combination with intravenous cytarabine than in the other groups. CONCLUSIONS: Cytarabine administered either intravenously or intrathecally does not improve the prognosis of HIV-infected patients with progressive multifocal leukoencephalopathy who are treated with the antiretroviral agents we used, nor does high-dose antiretroviral therapy alone appear to improve survival over that reported in untreated patients.

AIDS-Related Opportunistic Infections↗
PubMed1997

The systematic review: an essential element of an evidence based approach to nursing.

Consistent with a move towards evidence based practice, systematic review of research relating to effective health care practices is having an increasing influence on health care decision making at all levels. This paper explains the systematic review as a specific type of literature review, one that contrasts with less rigorous approaches to assessing current best available research evidence. The use of this process to achieve effective nursing practice is discussed in the context of systematic review in medicine and health services in general. It is asserted that, in the 'information age', understanding and being able to assess the quality of systematic reviews is an essential area of nursing research.

Humans↗
PubMed1996

Adequately Treated Remote Syphilis Does Not Augment CNS HIV-1 Expression.

OBJECTIVE: The co-occurence of human immunodeficiency virus (HIV) infection and syphilis may accelerate the course of both infections. We investigated whether remote syphilis infection augmented the activation of central nervous system (CNS) HIV infection and increased the frequency of cerebrospinal fluid (CSF) abnormalities. METHODS: The subjects consist of HIV seropositive men who had CSF as part of prospective neurological studies performed at the Johns Hopkins University. Prior syphilis infection was determined by measuring serum FTA-ABS. All subjects had received adequate treatment for syphilis with negative RPR's or RPR's ≤ 1:8 and completed a full neurological examination and underwent lumbar punctures for analysis of cerebrospinal fluid. A range of CSF tests were performed including HIV culture, p24 antigen, β2 microglobulin (β2M) and CSF/albumin ratios. RESULTS: The FTA positive group was significantly older (p = .005), more advanced in HIV clinical staging (p = .04), had more minor neurological symptoms (p = .03), and was more likely to be on antiretroviral therapy (p = .03). No differences between FTA positive and FTA negative groups were observed either in the frequency of CFS anbormalities or the mean CSF values. CONCLUSIONS: Based on these findings, it appears that adequately treated remote syphilis does not augment HIV-1 expression within the CNS.

Cerebrospinal Fluid↗
PubMed1996

Neuronal pattern correlates with the severity of human immunodeficiency virus-associated dementia complex. Usefulness of spatial pattern analysis in clinicopathological studies.

The spatial distributional pattern of neurons, in the superior frontal gyrus of 32 subjects who died of acquired immune deficiency syndrome, was examined. The patients were classified as nondemented, mildly demented, and severely demented, and some were treated with the anti-retroviral drug zidovudine. Spatial statistical techniques were employed to investigate the degree of clustering in the individual cases and various groups. We found that the cluster pattern of large and small neurons differed significantly with increasing severity of dementia but was not influenced by the duration of zidovudine treatment. We conclude that this is a sensitive technique for clinicopathological correlations and that the differences may result from loss of specific neuronal populations, which could determine the degree of dementia.

AIDS Dementia Complex↗
PubMed1995

Generation of a transcription map at the HSD17B locus centromeric to BRCA1 at 17q21.

A detailed transcription map of the 320-kb region containing the HSD17B locus on chromosome 17 was generated. Thirty unique cDNA fragments, retrieved following the hybridization of immobilized YACs to primary pools of cDNAs prepared from RNA of mammary gland, ovary, placenta, and the Caco-2 cell line, were aligned into 10 transcription units by physical mapping and hybridization to RNAs of a series of tissues. The cDNAs were then further characterized by sequencing and used to screen mammary gland cDNA libraries. Fragments corresponding to the broadly expressed gamma-tubulin and Ki antigen genes were identified. A full-length cDNA clone encoding a 117-amino-acid protein homologous to the rat ribosomal protein L34 was isolated. Portions of genes with restricted patterns of expression were also obtained, including the previously characterized HSD17B1. One new gene, for which a full-length cDNA was isolated, was found to have an interesting tissue-specific pattern of expression with abundant mRNA in both the colon and the testis and in the mammary carcinoma cell line BT-474. This contrasted with the barely detectable level observed in several tissues including normal mammary gland. Of the five additional transcription units identified, one showed no similarity, two showed identity to human expressed sequences, and two displayed similarity to genes of animal species by amino acid alignment. These latter cDNA clones include potential homologues of a rat nuclear tyrosine phosphatase and of a factor of Drosophila that is known to be involved in the negative regulation of transcription of segment identity genes.

Amino Acid Sequence↗
PubMed1995

An epidemiologic analysis of Mycobacterium avium complex disease in homosexual men infected with human immunodeficiency virus type 1.

Cofactors associated with the Mycobacterium avium complex (MAC) disease and its prognosis in incident cases of AIDS in homosexuals were studied. We compared 51 men in whom MAC disease developed as the initial AIDS-defining illness (termed AIDS illness hereafter); 157 men who had MAC disease subsequent to another AIDS illness; and 884 men who had only non-MAC AIDS illnesses. MAC disease was the initially diagnosed AIDS illness more often in Baltimore (6.9%) and Los Angeles (5.6%) than in Chicago (2.6%) and Pittsburgh (0) (P < .01). MAC disease also was a more common subsequent AIDS illness in Baltimore (14.3%) and Los Angeles (22.4%) than in Chicago (8.5%) and Pittsburgh (6.5%) (P < .0001). Prophylaxis for Pneumocystis carinii infection increased the occurrence of MAC disease as the initial AIDS illness (from 2.3% to 12.5%; P < .0001). A low white blood cell (WBC) count was slightly more predictive of MAC disease than was a low CD4+ cell count. At 0-6, 7-12, and 13-18 months before diagnosis, the WBC cell counts of 75.0%, 61.1%, and 50.0%, respectively, of those with MAC disease as the initial AIDS illness were < or = 3,400/microL. Men in whom cytomegalovirus disease developed were at higher risk for subsequent MAC disease (relative hazard = 2.65; P < .0001). MAC disease also increased the risk for subsequent cytomegalovirus disease (relative hazard = 3.96; P < .0001).

AIDS-Related Opportunistic Infections↗
PubMed1994

Role of IL-6, IL-1, and CD28 signaling in responses of mouse CD4+ T cells to immobilized anti-TCR monoclonal antibody.

Purified CD4+ T cells require TCR engagement and Ag-nonspecific co-stimulatory signals to produce IL-2 and proliferate. A number of recent studies have demonstrated that the interaction of the B7 molecule expressed on APC with the T cell-associated CD28 molecule provides a potent co-stimulatory signal to both freshly isolated CD4+ T cells and cloned Th1 cells. Earlier reports have described the role of cytokines, in particular IL-6 and IL-1, as costimulatory molecules for T cell activation. We previously reported that IL-6 and IL-1 synergize to co-stimulate proliferation of purified mouse CD4+ T cells in conjunction with anti-TCR mAb. In this report we explore the interaction of IL-6, IL-1, and CD28 signaling in the activation of mouse CD4+ T cells, and demonstrate that the co-stimulatory requirements of the cells vary depending on the mode of TCR stimulation. CD28 signaling is not sufficient to co-stimulate responses of high buoyant density CD4+ T cells to anti-TCR-conjugated agarose beads; there is an additional requirement that can be supplied by exogenous IL-6 but not by IL-1. In contrast, in responses to anti-TCR mAb that is passively bound to the bottom of culture wells, CD28 stimulation is sufficient to co-stimulate proliferation, resulting in a very high level of IL-2 production; there is no additional requirement for exogenous IL-6 or IL-1. Possible explanations for the differential requirement for IL-6 in the two systems are discussed. Our results are consistent with the notion that CD28 signaling plays a central role in co-stimulating T cell responses. However, the results also suggest that, depending on the nature of the TCR stimulus, T cell activation may also require additional co-stimulatory signals provided by cytokines.

Animals↗
PubMed1994

Neuronal density in the superior frontal and temporal gyri does not correlate with the degree of human immunodeficiency virus-associated dementia.

Human immune deficiency virus (HIV) disease may be associated, neuropathologically, with significant neuronal loss and clinically with a severe dementia. However, the significance of neuronal loss in the development of dementia has not been established. In this study we have undertaken a stereological determination of the neuronal numerical density and neuronal volumes in post mortem tissue from the superior frontal and superior temporal gyri in 32 patients who died of acquired immune deficiency syndrome (AIDS). All were prospectively clinically characterized, with dementia identified or excluded, and antiretroviral medication documented. This study combines morphometric techniques with prospective clinical assessment of dementia. As previously demonstrated, all patients dying with AIDS showed neuronal loss, but this was not related to the presence of HIV-associated dementia.

AIDS Dementia Complex↗
PubMed1993

A transcription map of the region containing the Huntington disease gene.

A transcription map of the Huntington disease gene region was generated by a direct cDNA selection strategy using genomic DNA from the 4p16.3 region surrounding the D4S95 and D4S127 loci. A total of 58 cDNA fragments were obtained from cDNAs derived from fetal brain, frontal cortex, liver and bone marrow following hybridization to overlapping YACs from this region. These cDNA clones were aligned into transcription units by hybridization to specific mRNAs, by sequence overlap and by physical mapping onto overlapping YAC clones. Nine separate transcription units spanning approximately one megabase were detected by RNA hybridization. They represent a minimum number of genes in this region and do not include those genes expressed specifically in tissues not used for the hybridization. The transcription map that is provided by the cDNA segments will lead to the generation of a detailed gene map of this region.

Base Sequence↗
PubMed1992

AIDS and multiple sclerosis: neural and mental features.

The presence of mental disorder and cognitive functioning were examined in groups of 20 multiple sclerosis (MS) and homosexual acquired immunodeficiency syndrome (AIDS) ambulatory male outpatients matched for disability and demographic features. Patients who were somatically ill, had past central nervous system infection or tumours or abused intravenous drugs or alcohol were excluded. The groups significantly differed in mental symptoms and mental disorders (DSM-III classification) seen currently and after the diagnosis of MS or human immunodeficiency virus-1 infection. AIDS patients had pre-existing anxiety disorders that affected their current mental symptoms. MS patients showed more evidence of cognitive impairment than equally disabled AIDS patients. The differing neural and mental features are discussed in relation to the current concepts of subcortical and cortical disorders.

AIDS Dementia Complex↗
PubMed1991

Metacognition in HIV-1 seropositive asymptomatic individuals: self-ratings versus objective neuropsychological performance. Multicenter AIDS Cohort Study (MACS).

This study examined the relationship between actual and self-reported neuropsychological deficits, depression, and HIV-1 serostatus. The subjects, who consisted of 479 individuals, 256 who were HIV seronegative (SN) and 233 who were HIV-1 seropositive though still asymptomatic (ASP), were administered a standardized neuropsychological screening battery consisting of measures of attention, motor speed, psychomotor speed, verbal memory, verbal fluency, and depression. To assess subjects' subjective sense of their cognitive status, the Cognitive Failures Questionnaire (CFQ), a 25-item self-report questionnaire, was also administered. The results of MANOVA failed to reveal group differences between the SN and ASP groups on the measures of neuropsychological function. Similarly, the ASP and SN groups did not differ on the number or severity of reported cognitive failures. However, a positive correlation was found between CFQ scores and level of depression. These results do not support the hypothesis that ASP individuals are aware of cognitive decline prior to detection using standard neuropsychologic screening instruments. The data do suggest that the presence of depressed mood, independent of serostatus or actual neuropsychological impairment, is associated with increased cognitive complaints.

Adult↗