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Biomedical subjects

R B Bhalla

Publications and source records attributed to R B Bhalla.

18 recordsLinked to original sources
PubMed1992

Inter-relationships between quinolinic acid, neuroactive kynurenines, neopterin and beta 2-microglobulin in cerebrospinal fluid and serum of HIV-1-infected patients.

Quinolinic acid (QUIN) is an neurotoxic N-methyl-D-aspartate receptor agonist and an L-tryptophan metabolite of the kynurenine pathway. Increased concentrations of QUIN occur in both cerebrospinal fluid (CSF) and blood of patients infected with human immunodeficiency virus (HIV)-1, particularly those with neurologic disturbances. In the present study of HIV-1 infected patients in Walter Reed stages 4, 5 and 6, reductions in L-tryptophan accompanied proportional increases in L-kynurenine and QUIN in both serum and CSF. Further, close inter-correlations exist between QUIN kynurenic acid and L-kynurenine with both beta 2-microglobulin and neopterin in CSF and serum. These correlations support the hypotheses that the kynurenine pathway is activated in association with inflammation and induction of indoleamine-2,3-dioxygenase. There were no relationships between CSF QUIN, L-kynurenine or kynurenic acid with the ratio of serum:CSF albumin concentrations, which indicates that the increases in CSF QUIN, L-kynurenine or kynurenic acid were not dependent on a breakdown of the blood-brain barrier. Kynurenic acid is also a kynurenine pathway metabolite that can attenuate the excitotoxic effects of QUIN when present in higher molar concentrations. While CSF kynurenic acid levels were increased in HIV-1-infected patients, the magnitude of the increases were smaller than those of QUIN and the molar concentrations of kynurenic acid were consistently lower than QUIN by at least one order of magnitude. We conclude that immune activation increases the levels of neuroactive kynurenines within the central nervous system of HIV-1-infected patients secondary to activation of indoleamine-2,3-dioxygenase.

AIDS Dementia Complex↗
PubMed1992

Cerebrospinal fluid beta 2-microglobulin in patients with AIDS dementia complex: an expanded series including response to zidovudine treatment.

OBJECTIVE: To determine the relationship between cerebrospinal fluid (CSF) beta 2-microglobulin (beta 2M) and severity of AIDS dementia complex (ADC), and between CSF beta 2M and response of ADC to zidovudine. DESIGN: A prospective study. SETTING: Tertiary referral hospital. PATIENTS, PARTICIPANTS: Seventy-eight patients with varying stages of ADC were selected from a subgroup of a cohort of HIV-seropositive patients who are being studied prospectively for the neurological complications of HIV-1 infection. To enter our study, patients had to have an ADC stage of at least 0.5 (equivocal symptoms or abnormal neurological signs in the absence of functional impairment). A control group of 11 HIV-1-seropositive, neurologically normal patients was chosen randomly from the patients followed in the Multicenter AIDS Cohort Study. INTERVENTIONS: Patients were assessed neurologically and neuropsychologically and computed tomography of the brain and CSF studies were performed. MAIN OUTCOME MEASURES: Patients were staged according to severity of ADC on clinical criteria. Neuropsychological test scores were converted to an impairment score. CSF beta 2M was quantified in both serum and CSF of all patients and in 10 patients with pre- and post-zidovudine assessments. RESULTS: There was a high correlation between CSF beta 2M concentration and severity of ADC (P less than 0.0001); treatment with zidovudine significantly reduced these concentrations (P = 0.013). CSF beta 2M concentration was independent of CSF white-cell count and blood-brain barrier impairment. Other CSF changes in the same patients (including blood-brain barrier permeability to albumin, intrathecal synthesis of immunoglobulin G and HIV-1-p24-antigen levels) were less useful as objective correlates of ADC severity and response to zidovudine therapy. CONCLUSIONS: CSF beta 2M may be a valuable marker of ADC severity and response to antiviral therapy.

AIDS Dementia Complex↗
PubMed1991

Relationship and prognostic value of endogenous interferon-alpha, beta 2-microglobulin, and neopterin serum levels in patients with Kaposi sarcoma and AIDS.

We investigated whether elevated serum levels of beta 2-microglobulin and neopterin were related to the abnormal in vivo production of interferon described in patients with human immunodeficiency virus (HIV) infection, and whether these factors might add to measurements of CD4+ T cells in predicting survival and tumor regression in patients with Kaposi sarcoma associated with AIDS. beta 2-Microglobulin and neopterin levels were strongly correlated (r = 0.82), and were each significantly higher in patients with detectable serum interferon-alpha activity. Inverse correlations were observed between prognosis and levels of these serum products. Prediction by CD4+ T-cell count of tumor regression after treatment with interferon-alpha and zidovudine was improved by each of two factors: (a) the presence or absence of endogenous interferon-alpha activity, and (b) a combined variable reflecting relative levels of the interferon-inducible products, beta 2-microglobulin and neopterin. The level of beta 2-microglobulin was the single best predictor of survival. When beta 2-microglobulin was not considered, the endogenous interferon-alpha variable was the best predictor of survival, and the prediction was enhanced by addition of the combined variable, or the neopterin value alone. We conclude that serologic markers, which directly or indirectly reflect activation of the endogenous interferon system, may be valuable adjuncts to CD4+ T-cell counts in assessing prognosis and selecting and evaluating treatments for patients with Kaposi sarcoma and AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Cerebrospinal fluid neopterin in human immunodeficiency virus type 1 infection.

We evaluated cerebrospinal fluid (CSF) concentrations of neopterin, a putative marker of activated macrophages, in 97 subjects infected with human immunodeficiency virus type 1 who had a spectrum of neurological complications. The highest CSF neopterin concentrations occurred in those with neurological opportunistic infections, primary central nervous systems lymphoma, and acquired immunodeficiency syndrome (AIDS) dementia complex. In general, the CSF concentration of neopterin was independent of CSF cell count and blood-brain barrier disruption to albumin. In the patients with AIDS dementia complex, CSF neopterin concentrations correlated with severity of disease and decreased in conjunction with clinical improvement following treatment with zidovudine. These results suggest that CSF neopterin, although not disease-specific, may be useful as a surrogate marker for the presence of AIDS dementia complex and its response to antiviral therapy.

AIDS Dementia Complex↗
PubMed1989

Cerebrospinal fluid beta 2 microglobulin in patients infected with human immunodeficiency virus.

We prospectively evaluated CSF concentrations of beta 2 microglobulin (beta 2M) in 65 human immunodeficiency virus type 1 seropositive patients. The highest concentrations occurred in those with lymphoma, neurologic opportunistic infections, and acquired immune deficiency syndrome dementia complex (ADC). There was a high correlation between the CSF beta 2M concentration and ADC severity, suggesting that CSF beta 2M may be useful as a marker for the development, progression, and perhaps response to treatment of ADC. Elevated CSF beta 2M was not due to CSF pleocytosis and was usually independent of blood-brain barrier dysfunction.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Ferritin in neuroblastoma. Impact of tumor load and blood transfusions.

Serial serum ferritin (SF) levels were measured in 36 patients with neuroblastoma seen at Memorial Sloan-Kettering Cancer Center (MSKCC) between January 1981 and December 1982. The significance of the associations among SF, stage and extent of disease, number of blood transfusions, liver function, serum iron (Fe), total iron-binding capacity (TIBC), and transferrin saturation was investigated. Although a dominant statistical correlation was found between SF and number of blood transfusions, the results suggest that amount of disease contributes to increasing SF levels. Serum ferritin levels increased on average in a linear fashion with number of blood transfusions in patients free of disease or with minimal disease. In patients with bulky disease, this increase was exponential (p value less than 0.01). Application of a reverse hemolytic plaque assay to the analysis of ferritin secretion by cells demonstrates that tumor cells do secrete ferritin in vitro.

Adolescent↗
PubMed1984

Correlation between maternal and fetal immunoglobulin E levels.

Immunoglobulin E (IgE) concentrations were measured in 157 paired samples of maternal-fetal sera. A correlation was found between maternal and fetal IgE levels, in contrast to earlier reports dealing with smaller series. The correlation is probably not due to placental transfer of maternal IgE but rather to genetic factors. The possible role of IgE in the fetal immune response is discussed.

Female↗
PubMed1983

Administration of gallium nitrate by continuous infusion: lack of chronic nephrotoxicity confirmed by studies of enzymuria and beta 2-microglobulinuria.

Enzymuria and beta 2-microglobulinuria are sensitive markers of injury to renal tubular cells. We evaluated these markers in 41 patients with advanced malignant lymphoma who received gallium nitrate administered as a continuous infusion during a recent phase I-II study. In contrast to our findings with cisplatin, we observed no significant increase in enzyme excretion or beta 2-microglobulinuria in these patients even after long-term treatment. Our results indicate that gallium nitrate administered by infusion does not produce cumulative renal tubular toxicity.

Acetylglucosaminidase↗
PubMed1980

Comparison of methods of evaluating nephrotoxicity of cis-platinum.

The urinary excretion of leucine aminopeptidase (LAP), N-acetyl-beta-glucosaminidase (NAG), and beta 2-microglobulin was measured in 12 cancer patients receiving cis-platinum to evaluate the sensitivity of these indices for renal tubular damage. NAG and LAP excretion rose markedly in all patients, and beta 2-microglobulin rose in 11. Seven of the 9 patients who had received cis-platinum 6 wk before the study had prestudy dose elevations of one or more of these indices. We conclude that these urinary proteins are sensitive indicators of proximal renal tubular injury and may provide greater sensitivity for comparison of the nephrotoxic potential of future platinum analogs or for assessing the efficacy of regimens designed to protect the kidney from platinum nephrotoxicity than other measurements. The persistence of high excretion vales for these indices 6 wk after a dose demonstrates the persistent renal injury by cis-platinum.

Acetylglucosaminidase↗
PubMed1977

The size and location of the poly(A) tract in EMC virus RNA.

Encephalomyocarditis (EMC) virus RNA, selected by its affinity for oligo(dT)-cellulose, contains poly(A) of size : (i) about 14 nucleotide residues long, based on the percentage of radioactivity in the RNA resistant to digestion by a mixture of pancreatic and T1 RNases; (ii) about 15 residues long, as measured by the ratio of the amount of terminal adenosine to internal adenylic acid in isolated poly(A); and (III) in the range 12 to 45 residues, the majority of tracts being about 16 to 18 residues long, based upon electrophoretic mobility on polyacrylamide gels using poly(A) molecules of known size as mol. wt. markers. The poly(A) appears to be located at the 3'-terminus of the virus genome since the tract, liberated by digestion with a mixture of pancreatic and T1 RNases, was shown by compositional analysis to contain a non-phosphorylated 3'-terminus and only adenine residues. The size heterogeneity in the poly(A) tracts revealed by gel electrophoresis is also consistent with a terminal location. Comparison of our data for EMC virus with published data for other picornaviruses suggests that the sizes of poly(A) tracts in polio- and Mengovirus RNA have been overestimated; poly(A) tracts in cardioviruses appear to be smaller than those in poliovirus; the minimum size of poly(A) required for full infectivity of picornavirus RNA has also been overestimated; a tract of at least 13 adenine residues long is required for full infectivity of EMC virus RNA.

Base Sequence↗