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Biomedical subjects

R E Walker

Publications and source records attributed to R E Walker.

At least 19 recordsLinked to original sources
PubMed1995

Increases in CD4 T lymphocytes with intermittent courses of interleukin-2 in patients with human immunodeficiency virus infection. A preliminary study.

BACKGROUND: Interleukin-2 is an important regulatory cytokine of the immune system, with potent effects on T cells, B cells, and natural killer cells. In vitro, interleukin-2 can induce the proliferation and differentiation of peripheral-blood mononuclear cells from patients infected with the human immunodeficiency virus (HIV). METHODS: We treated 25 HIV-infected patients with interleukin-2 administered as a continuous infusion at a dosage of 6 to 18 million IU per day for 5 days every 8 weeks during a period of 7 to 25 months. All patients also received at least one approved antiviral agent. Immunologic and virologic variables were monitored monthly. RESULTS: In 6 of 10 patients with base-line CD4 counts higher than 200 per cubic millimeter, interleukin-2 therapy was associated with at least a 50 percent increase in the number of CD4 cells. Changes ranged from -81 to +2211 cells per cubic millimeter. Interleukin-2 therapy resulted in a decline in the percentage of CD8 lymphocytes expressing HLA-DR and an increase in the percentage of CD4 lymphocytes that were positive for the p55 chain of the interleukin-2 receptor. Four patients had a transient but consistent increase in the plasma HIV RNA level at the end of each infusion. In the remaining 15 patients, who had CD4 counts of 200 or fewer cells per cubic millimeter, interleukin-2 therapy was associated with increased viral activation, few immunologic improvements, and substantial toxic effects. CONCLUSIONS: Intermittent courses of interleukin-2 can improve some of the immunologic abnormalities associated with HIV infection in patients with more than 200 CD4 cells per cubic millimeter.

Adult↗
PubMed1995

Anticytomegaloviral activity and safety of cidofovir in patients with human immunodeficiency virus infection and cytomegalovirus viruria.

Cidofovir (HPMPC; (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine) is a nucleotide analog with activity against human cytomegalovirus (CMV). A phase I/II dose escalation trial was conducted with asymptomatic human immunodeficiency virus (HIV)-infected patients with CMV viruria to determine its pharmacokinetics, maximally tolerated dose, and preliminary antiviral activity against CMV. Qualitative CMV blood and urine cultures were monitored weekly to assess anti-CMV activity. Twenty-one HIV-infected persons with CD4 counts from 0 to 389 cells per microliters (median, 39) were enrolled in six dose-ranging groups. The first five groups enrolled four patients each to receive cidofovir infusions either weekly or biweekly for 4 weeks or every 3 weeks for 12 weeks. The sixth group enrolled one patient who received infusions of 5 mg/kg of body weight every other week. Patients receiving 0.5 or 1.5 mg/kg twice weekly experienced no serious toxicity. The first two patients who received 5 mg/kg twice weekly developed glycosuria and 2+ proteinuria. Subsequent patients received concomitant probenecid to attempt to ameliorate renal toxicity. Seventeen patients experienced proteinuria on one or more occasions; 6 of them experienced at least 2+ proteinuria. Four patients did not complete the study as planned because of renal toxicity. Positive CMV urine cultures reverted to negative in 2 of 8 patients receiving doses of < or = 1.5 mg/kg twice weekly and 11 of 13 patients receiving higher doses. Cidofovir has in vivo anti-CMV activity demonstrated by prolonged clearing of CMV viruria, although this observation is tempered by the fact that clearance of viremia could not be demonstrated. The dose-limiting toxicity is renal; however, concurrent administration of probenecid may be protective. The maximally tolerated weekly intravenous dose with probenecid is approximately 5 mg/kg. Efficacy trials with CMV disease will define the therapeutic utility and optimal dosing interval for cidofovir.

Adult↗
PubMed1995

Hyperglycemia-induced changes in Na+/myo-inositol transport, Na(+)-K(+)-ATPase, and protein kinase C activity in proximal tubule cells.

In many tissues, hyperglycemia alters the activities of the Na(+)-dependent myo-inositol (Na/MI) transporter, Na(+)-K(+)-ATPase, and protein kinase C (PKC). However, little is known concerning adaptive changes in renal proximal tubular function after acute or chronic hyperglycemia. We examined hyperglycemia-induced changes in Na/MI transport, Na(+)-K(+)-ATPase activity, and PKC activity using three proximal tubule-like cell lines (JTC12, LLC-PK1, and OK/E cells) and primary cultures of human proximal tubular epithelium (HK cells) cultured for varying periods in low- or high-glucose media, myo-Inositol (MI) transport was mediated by a high-affinity (Km approximately 50 mumol/l) Na(+)-dependent saturable process in the four cell lines. Hyperglycemia produced a time-dependent and persistent increase in Na/MI transport in all cell lines. Chronic hyperglycemia increased the Km for MI transport in LLC-PK1 cells and increased the Vmax in both LLC-PK1 and JTC12 cells. Glucose competitively inhibited Na/MI transport in all low-glucose cells and in high-glucose HK, JTC12, and OK/E cells but had no effect on transport in high-glucose LLC-PK1 cells. Acute hyperglycemia also produced time-dependent increases in Na(+)-K(+)-ATPase activity in all cell lines, a change that persisted only in HK cells. A 24-h exposure to high glucose had no effect on PKC activity in any of the cell lines but increased Ca/phospholipid-dependent PKC activity in membrane fractions from chronically high-glucose LLC-PK1 and OK/E cells. These data suggest that hyperglycemia causes acute changes in proximal tubule function and long-lived adaptive responses in Na/MI transport and the PKC signaling pathway.

Biological Transport↗
PubMed1994

Check chains.

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Animals↗
PubMed1994

Analysis of the T-cell receptor beta-chain variable-region (V beta) repertoire in monozygotic twins discordant for human immunodeficiency virus: evidence for perturbations of specific V beta segments in CD4+ T cells of the virus-positive twins.

We analyzed the T-cell receptor (TCR) V beta repertoire in human immunodeficiency virus type 1 (HIV-1)-infected individuals at different stages of disease. To circumvent the effect of HLA and other loci on the expressed TCR repertoire, we compared the TCR repertoire in nine pairs of monozygotic twins who were discordant for HIV infection. A semiquantitative polymerase chain reaction (PCR) assay and flow cytometry enabled us to show distinct differences in the V beta repertoire in the HIV-positive twin compared with the HIV-negative twin. By combining PCR and cytofluorometry, these differences were restricted to a specific set of TCR V beta segments, with members of the V beta 13 family perturbed in six out of seven cases and those of the V beta 21 family perturbed in four out of seven cases studied. Most of the other V beta families remained unchanged. Our results provide direct evidence for a skewed TCR repertoire in HIV infection.

Antibodies, Monoclonal↗
PubMed1994

Molecular and serologic analysis of HLA genes and immunoglobulin allotypes in IgA nephropathy.

We studied a large North American Caucasian population of patients with biopsy proven IgA nephropathy for polymorphisms of HLA-A,B,C, HLA-DR, HLA-DQ and HLA-DP using a combination of serologic phenotyping and polymerase chain reaction sequence specific oligonucleotide probe (PCR-SSOP) hybridization genotyping. We also examined patients for polymorphisms of immunoglobulin by determining Gm and Km allotypes. When compared to healthy local controls there was an apparent decrease in HLA-DR5 (DRw11, DRw12) suggesting that this allele had a protective effect on disease susceptibility. None of the previously reported HLA-DQ associations found among Japanese or british Caucasian patients were found among this large North American Caucasian population. The HLA-DPB1*0601 genotype was increased among patients, but this was not significant when corrected for multiple comparisons. There were no differences in the distribution of Gm or Km allotypes among patients versus controls, regardless of whether they were stratified into those with progressive or non-progressive renal disease. Taken together, these findings suggest that there is substantial genetics heterogeneity in susceptibility to IgA nephropathy among different ethnic and/or geographically distinct populations.

Alleles↗
PubMed1989

Zidovudine in patients with human immunodeficiency virus (HIV) infection and Kaposi sarcoma. A phase II randomized, placebo-controlled trial.

STUDY OBJECTIVE: To evaluate the toxicity, effects on immune function, antitumor effects, antiretroviral effects, and pharmacokinetics of zidovudine therapy in patients with early human immunodeficiency virus (HIV) infection and Kaposi sarcoma. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: National Institutes of Health, a referral-based research institution (single site). PATIENTS: Physician-referred volunteer patients with HIV infection, Kaposi sarcoma, CD4+ lymphocyte counts greater than 0.2 x 10(9)/L, and no systemic symptoms or history of opportunistic infection. Of 41 patients enrolled, 4 had not met all entry criteria and were therefore not evaluable. INTERVENTIONS: Patients were randomized to one of four treatment groups for an initial 12-week treatment period: oral placebo (9 patients); zidovudine, 250 mg orally every 4 hours (9 patients); zidovudine, 0.5 mg/kg body weight intravenously every 4 hours (9 patients); and zidovudine, 2.5 mg/kg intravenously every 4 hours (10 patients). After at least 12 weeks of therapy at their assigned dose, patients were treated with oral zidovudine, generally 250 mg every 4 hours, with a mean 42-week follow-up. MEASUREMENTS AND MAIN RESULTS: Anemia and granulocytopenia were the major toxicities. Significant increases in platelet counts and declines in serum HIV antigen and IgG and IgM levels occurred in treated patients. Treated patients were more likely than those on placebo to clear HIV from the cerebrospinal fluid. There were no differences in tumor progression or CD4+ or CD8+ lymphocyte counts among the groups. CONCLUSIONS: Zidovudine was well tolerated and had antiretroviral activity in patients with early HIV infection and Kaposi sarcoma but it had no significant effect on the extent of Kaposi sarcoma or on immune function.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Safari to Kenya.

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Canada↗
PubMed1988

Disseminated Mycobacterium haemophilum infection in two patients with the acquired immunodeficiency syndrome.

In two patients with the acquired immunodeficiency syndrome (AIDS), multiple erythematous cutaneous lesions developed, revealing acid-fast organisms on Fite's stain. Initial culture results on the first patient were negative; however, repeat cultures on hemin-enriched media were positive for Mycobacterium haemophilum. Despite antimycobacterial therapy, lesions persisted until the patients' death. M. haemophilum should be a diagnostic consideration when smears of peripheral (especially skin) lesions from AIDS patients show acid-fast organisms. Cultures in such patients should be done with iron hemin- or ferric ammonium citrate-enriched media.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Anemia and erythropoiesis in patients with the acquired immunodeficiency syndrome (AIDS) and Kaposi sarcoma treated with zidovudine.

We evaluated the development of anemia as part of a trial of zidovudine therapy in patients with the acquired immunodeficiency syndrome (AIDS) with Kaposi sarcoma. Patients were randomized to one of three treatment groups or a placebo group. Transfusion-requiring anemia (hemoglobin less than 100 g/L) developed in 6 of 15 patients on zidovudine therapy at a mean of 6 weeks after starting treatment. A fall in the reticulocyte count was the earliest peripheral blood indicator of toxicity. Mean corpuscular volume increased markedly in patients on zidovudine therapy not developing anemia yet remained stable or only slightly increased in those who became anemic. Bone marrow examination showed pure red cell aplasia in 2 patients, erythroid maturation arrest in 1, and erythroid hypoplasia in 3. Megaloblastic erythropoiesis was present in 2 of the 6 anemic patients. Erythropoietin levels measured at the time of first transfusion were increased. Thus, the anemia associated with zidovudine therapy is due to red cell hypoplasia or aplasia.

Acquired Immunodeficiency Syndrome↗
PubMed1984

High-density-lipoprotein cholesterol in heparin-MnCl2 supernates determined with the Dow enzymic method after precipitation of Mn2+ with HCO3-.

Manganese interferes with enzymic cholesterol methods. In this study, we enzymically measured high-density-lipoprotein (HDL) cholesterol in heparin-Mn2+ supernates that had been treated with NaHCO3 (91 mmol/L) to precipitate Mn2+, and compared results with those by an automated Liebermann- Burchard method. For untreated supernates of 96 fresh plasma samples, the enzymic values were 10.4% higher than comparison-method values, a bias that declined to +2.3% for treated supernates. For 72 sera promptly frozen and stored after collection, the enzymic values for untreated and treated supernates were, respectively, 6.0% and 0.5% higher than comparison-method values. In all cases, the magnitude of the bias was independent of the concentrations of cholesterol, triglyceride, and HDL-cholesterol. Enzymic HDL-cholesterol measurements in NaHCO3-treated heparin-Mn2+ supernates prepared from four pooled serum controls agreed within 21 mg/L with values established for these pools by the Centers for Disease Control. We conclude that the accuracy of enzymic HDL cholesterol measurements in heparin-Mn2+ supernates in considerably increased by treatment with NaHCO3.

Bicarbonates↗
PubMed1983

Malignant melanoma of the foot.

This discussion and case presentation demonstrate the importance of proper diagnostic procedures when a suspect lesion presents. Biopsy and examination by a pathologist in the field of malignant melanoma revealed an immediate definitive diagnosis. Any delay of such measures will increase the chance of metastasis and the degree of necessary surgical excision.

Aged↗
PubMed1982

Evaluation of five enzymic kits for determination of triglyceride concentrations in plasma.

We evaluated five commercial enzymic kit methods (methods A-E) for the determination of triglyceride concentrations in plasma, by comparing each with the automated fluorometric procedure of the Lipid Research Clinics Program. Aliquots of 91 to 97 samples were analyzed with each kit and with the comparison method. The results obtained with all five kits were highly correlated with those of the comparison method (r = 0.97-0.99). Group mean triglyceride concentrations as determined with kits A and D did not differ significantly from those assayed with the comparison method. The other three kits gave values 6.5-7.5% higher than those by the comparison method (p less than 0.001). The relative biases between the kit and reference methods did not vary with triglyceride concentration for kits B, D, and E; kits A and C had concentration-dependent biases. Kits D and E were the most nearly precise and had coefficients of variation (CVs) of 3.1% or less. Kit B had CVs of 3.8-4.4%; the remaining two kits had CVs of 5.4-6.7%. On the basis of these results, we judged kits B, D, and E to perform most satisfactorily, from the standpoint of their precision and their concentration-independent relationships to the comparison method.

Cholesterol↗
PubMed1982

Determination of high density lipoprotein-cholesterol in human plasma stored at -70 degrees C.

We determined the effect of storage at -70 degrees C on the determination of plasma high density lipoprotein (HDL)-cholesterol. Plasma from 106 subjects was stored for 1, 6, and 12 months, then treated with heparin and MnCl2 to remove other lipoproteins, and HDL-cholesterol was measured. The mean HDL-cholesterol level decreased by 2.9% after 1 month, and by 5.1% after 12 months. The magnitude and direction of the changes were not constant, but were correlated primarily with HDL-cholesterol concentration. After 1 month, samples with HDL-cholesterol levels below 40 mg/dl tended to increase, and those above this value tended to decrease. By 12 months, only those samples with HDL-cholesterol below 22 mg/dl tended to increase. Linear regression analysis indicated changes of 0.9-1.5 mg/dl for each 10 mg/dl initial HDL-cholesterol concentration. Storage of heparin-MnCl2 supernatants, rather than unfractionated plasma, minimized these changes. The mean HDL-cholesterol of stored heparin-MnCl2 supernatants was 3.3% lower after 12 months, and the change was constant regardless of lipoprotein concentration. The findings suggest the possible occurrence of changes in the heparin-MnCl2 precipitability of lipoproteins during storage, which produce errors in HDL-cholesterol analyses, and indicate that samples can be stored more satisfactorily if the other lipoproteins are removed first.

Cholesterol↗