Biomedical subjects

W R Valenski

Publications and source records attributed to W R Valenski.

13 recordsLinked to original sources

PubMed1995

Cell-mediated immune status of children with recurrent infection.

OBJECTIVE: To evaluate the cell-mediated immune status of children with recurrent respiratory tract infections. DESIGN: We evaluated the cell-mediated immune status of 76 patients referred because of recurrent infection. Patients were divided into those with serologic abnormalities and those without such findings. Twenty-three healthy children served as control subjects. Studies of lymphocyte phenotype included CD4+ CD29+ cells (an immunologically mature phenotype), lymphocyte proliferation studies, cytokine production including interleukin-2 (IL-2), IL-4, IL-6, and interferon gamma), and measurement of in vitro IgM and IgG synthesis. RESULTS: Lymphocyte proliferation and T-cell phenotype were similar in both patient groups as well as in control subjects. The proportions of CD4+ CD29+ cells at different ages were similar in all groups. Patients with serologic abnormalities (e.g., partial IgA deficiency, partial IgG subclass deficiency) produced more IL-2 and IL-4 than did other patients. The control population had greater spontaneous IgM and IgG synthesis than the patient groups. CONCLUSION: Routine studies of T-cell function of patients with recurrent infection provide little information useful in making clinical decisions.

Antigens, Bacterial↗

PubMed1994

Elevated in vitro IL-4 production in a patient with elevated serum IgE.

BACKGROUND: We have cared for an unusual patient with serum IgE concentrations of up to 150,000 IU/mL who did not have the hyper-IgE syndrome. OBJECTIVE: Our objective in this study was to compare the regulation of in vitro IgE synthesis in this patient with results reported for in vitro IgE production by patients with the hyper-IgE syndrome. METHODS: We utilized an enzyme-linked immunosorbent assay to measure in vitro IgE production under varying conditions. In vitro cytokine production including IL-2, IL-4, IL-6, and interferon-gamma also was evaluated as was expression of the IgE receptor molecule CD23. RESULTS: B cells from this patient produced high concentrations of IgE. The patient was found to produce very high levels of interleukin-4 (IL-4) in vitro, to have high levels of soluble CD23 in his serum, and to have cells that were inconsistently responsive to the effect of IL-4 on IgE synthesis. CONCLUSIONS: Patients with elevated production of IL-4 may have increased serum IgE concentrations without having the hyper-IgE syndrome syndrome.

Adult↗

PubMed1992

Natural killer cell activity in very low birth weight infants.

The exact role of natural killer (NK) cells in host defense is unclear, but they may be important as an early response to certain infections. We evaluated NK cell phenotype and activity in premature very low birth weight infants (VLBWI) (n = 52) with an average gestational age of 29.3 wk (24-35 wk) and an average birth weight of 1124 g (537-1480 g). All patients initially were evaluated within 7 d of birth. Samples also were obtained at 2, 4, and 6 wk in some infants. The proportion of mononuclear cells expressing the phenotypic marker of NK cells (NKH-1; CD56) was significantly lower in VLBWI than in adults (2.5 +/- 1.4 versus, 12.5 +/- 7.8%, p less than 0.0001) or term infants (2.5 +/- 1.4 versus 9.5 +/- 7.1%, p less than 0.0001). VLBWI also had significantly diminished NK activity expressed as the percentage of specific lysis compared with adults (4.7 +/- 4.4 versus 32.3 +/- 14.5%, p less than 0.0001) or term infants (4.7 +/- 4.4 versus 15.5 +/- 10.8%, p less than 0.0001). Both the number of cells expressing the NK phenotype and the NK lytic activity in VLBWI increased in the 6 wk after birth. NK activity in VLBWI was enhanced by IL-2 and in most cases by interferon-gamma.

Adult↗

PubMed1991

Evaluation of lymphocyte phenotype and phytohemagglutinin response in healthy very low birth weight infants.

Sixteen healthy very low birth weight infants (VLBWI) were studied in a serial fashion over a 3-week period. Subjects were evaluated for lymphocyte phenotype, phytohemagglutinin (PHA) response, and metabolic status including weight, blood urea nitrogen, creatinine, albumin, pH, calcium, phosphorus, and ammonia. Lymphocyte phenotype determination showed a decreased proportion of CD3+ cells (66.8 +/- 10.4 vs 75.9 +/- 6.1, P less than 0.02) in VLBWI. When subsets of the CD4+ population were examined, VLBWI had a lower proportion of CD4+/CD29+ cells (8.2 +/- 5.8% vs 23.5 +/- 8.0%, P less than 0.0001) than adults and a higher proportion of CD4+/CD45R+ cells (35.6 +/- 12.4% vs 22.2 +/- 7.4%, P less than 0.03). The CD4+ subsets in VLBWI were similar to those seen in term infants. The peak PHA response in VLBWI was greater than that of adults (P less than 0.01). There was little change in the immune measurements over the 3-week study period. There were no strong correlations between any of the immunological measurements and the metabolic measurements except that the proportion of CD8+ cells increased with birth weight. Our findings demonstrate that immune measurements in healthy VLBWI differ from values found in adults but are similar to those of full-term infants. Lower proportions of the CD4+/CD29+ cells (the helper/inducer subset for antibody production) may contribute to some of the differences in immune function reported in neonates.

Ammonia↗

PubMed1989

In vitro evidence for B cell dysfunction in patients with chronic liver disease.

Patients with chronic liver disease have been reported to have multiple immunologic abnormalities. We evaluated immune function in 40 such patients. The patient group had a decreased proportion of CD3 positive cells compared to controls (54.2 +/- 13.2 vs 67.9 +/- 5.7, p less than 0.01), CD4 positive cells (38.4 +/- 10.0 vs 44.3 +/- 4.9, p less than 0.01) and CD8 positive cells (17.7 +/- 8.2 vs 26.3 +/- 3.9, p less than 0.05). B cells were increased over controls (8.3 +/- 4.0 vs 6.0 +/- 1.9, p less than 0.01). In vitro immunoglobulin synthesis studies demonstrated decreased production in both IgM (632 +/- 482 ng/ml vs 2,050 +/- 1,720 ng/ml, p less than 0.01) and IgG synthesis (726 +/- 640 ng/ml vs 1,117 +/- 1,012 ng/ml, p less than 0.05) by patients as compared to controls. Coculture of fractionated populations of lymphocytes indicated that the patients had adequate T helper cell activity and no evidence for enhanced T suppressor cell activity. B cells of patients with chronic liver disease appear to have an impaired capacity to produce immunoglobulin in vitro.

Adult↗

PubMed1988

Lymphocyte and complement abnormalities in splenectomized patients with hematologic disorders.

Twenty-two patients, splenectomized 1 to 26 years earlier for hematologic disorders, were studied to determine possible defects in immunologic function or complement levels. Quantitation of B cells and T-cell subsets revealed slight decreases in the proportions of CD3 and CD4 cells but normal or increased absolute numbers of all cell populations. IgM synthesis in vitro by peripheral blood mononuclear cells was markedly diminished, but IgG synthesis was normal. Fractionation studies, in which various B-cell- and T-cell-enriched populations from controls and patients were combined, demonstrated diminished B-cell function in the patients. Sickle cell patients, who were functionally asplenic, showed similar deficits. Complement levels in splenectomized and sickle cell patients in both the classical and alternative pathways were generally normal. A modest decrease in component H in the alternative pathway in splenectomized and sickle cell patients probably was not clinically significant. In summary, splenectomized patients have a diminished capacity for IgM synthesis that can be attributed primarily to defective B-cell function. This may be partially responsible for their increased susceptibility to infection by encapsulated organisms.

Adolescent↗

PubMed1988

Immunoregulatory studies in patients with IgA nephropathy.

Numerous studies have evaluated T cell subsets and in vitro IgA synthesis in patients with IgA nephropathy. These reports have resulted in the hypothesis that defective regulation of IgA synthesis is important in the pathogenesis of IgA nephropathy. Baseline immunologic measurements were performed in a clinically well characterized group of 19 pediatric and 13 adult (greater than or equal to 18 years) patients with no macrohematuria or intercurrent infection at the time of study. Mean percentages of OKT3 and OKT4 subsets were significantly decreased for the patients as compared to healthy adult controls. Mean T4:T8 ratios were similar for control and patient groups although 7 patients had T4:T8 ratios greater than 2 SD above the control mean. Unstimulated and pokeweed mitogen stimulated in vitro IgA synthesis was similar for patients and controls. During six episodes of macrohematuria in five patients no significant changes occurred for T cell subset percentages, while mean T4:T8 ratios decreased from baseline. Mean serum concentration of IgA increased during these episodes, although in vitro IgA synthesis remained normal. Our data fail to demonstrate a consistent immunoregulatory abnormality for patients with IgA nephropathy.

Adolescent↗

PubMed1987

Characterization of mononuclear cell-derived histamine release enhancing factor.

Histamine release enhancing factor (HREF) is a product of phytohemagglutinin-stimulated mononuclear cells that substantially augments in vitro IgE-mediated basophil histamine release. The factor is stable at 56 degrees C and has a molecular weight in the 10,000 to 30,000 dalton range. The magnitude of HREF activity produced is dependent on the concentration of mononuclear cells cultured and the final concentration of HREF during basophil challenge. The HREF phenomenon could not be attributed to phytohemagglutinin, alpha- or gamma-interferon, arachidonic acid metabolites, or interleukin-1 or 2. HREF appears to be a unique cytokine of potential importance in the immunology of inflammatory and atopic processes.

Adult↗

PubMed1986

Serial immunologic studies in recipients of hepatic allografts.

Thirty recipients of hepatic allografts had serial immunologic evaluations. Prior to transplant, patients had marked depression of lymphocyte subsets and impaired in vitro immunoglobulin synthesis, while phytohemagglutinin responsiveness was similar to that of controls. Following transplantation and introduction of cyclosporine and low-dose steroid therapy, there was a significant decline in both T cell subsets, but only the T4 population remained significantly depressed throughout the entire study period. The T4:T8 ratio in 5 patients who experienced acute rejection episodes was 1.4 +/- 0.6 prior to transplant. It increased to a mean of 2.0 +/- 0.6 by the time the diagnosis of rejection was made. By contrast, 12 subjects transplanted during a similar time period who did not demonstrate rejection had a T4:T8 ratio of 4.0 +/- 3.9 prior to transplant which fell to 1.5 +/- 0.6 (P less than 0.01) by 1 week post-transplant. In all 12 of these, the T4:T8 ratio fell in the 7 days post-transplant. The results indicate that monitoring the T4:T8 ratio in hepatic allograft recipients may be a useful marker for determining patients at risk for a rejection episode.

Antibody Formation↗

PubMed1984

Use of the T lymphocyte colony-forming assay to study human lymphocyte interactions.

The role of various mononuclear cell subpopulations necessary for T lymphocyte colony formation was investigated. Neither T cell-enriched nor T cell-depleted populations formed colonies as readily as did unfractionated cells. Addition of small numbers of the T cell-depleted pool greatly enhanced the capacity of the T cell-enriched pool to form colonies. Populations depleted of cells bearing the OKT4 phenotype were deficient in their colony-forming capacity. This assay may prove useful in evaluating patients with subtle abnormalities of mononuclear cell function.

Antibodies, Monoclonal↗

PubMed1982

Impaired T-lymphocyte colony formation by cord blood mononuclear cells.

When compared to adult mononuclear cells, cord blood mononuclear cells demonstrated significantly decreased T-lymphocyte colony formation (1351 +/- 643 vs 592 +/- 862, P less than 0.01). This diminished colony-forming activity did not appear to be associated with impaired responsiveness to the stimulant phytohemagglutinin or with excessive suppressor-cell activity. Irradiation reduced the colony-forming capacity of cord blood mononuclear cells more than it did that of adult mononuclear cells. Depletion of adherent cells reduced cord blood mononuclear-cell colony-forming capacity by 40%, while similar treatment reduced adult colony formation by 10%. Lymphocyte proliferation in liquid culture of cord and adult cells was minimally affected by these procedures. The colony-forming capacity of cord blood could be enhanced by the addition of irradiated adult cells (284 +/- 72 vs 752 +/- 78, P less than 0.01). This enhancement was demonstrated to be due to a soluble factor produced by a population of irradiated adult cells depleted of the OKT8+ subpopulation of lymphocytes. These results indicate that the progenitor cells of T-lymphocyte colonies in cord blood have distinct biologic characteristics when compared to colony progenitors present in adult blood. This assay may prove to be useful in our efforts to understand the differentiation of T-cell function in man.

Adult↗

PubMed1981

The in vitro response of human lymphocytes to Pneumocystis carinii antigen.

Pneumocystis carinii pneumonitis (PCP) is a major complication in the immunocompromised host. Recent evidence suggests that most normal individuals have detectable antibody against this organism. The role of the various components of the immune system in protecting the host from acute PCP is unclear. We have examined the in vitro proliferative response of lymphocytes from normal adults to P. carinii antigen. Fourteen of 16 subjects had a positive response with stimulation indices greater than 3. This response was due primarily to thymus-derived (T cell) lymphocytes and was dependent upon the presence of adherent cells. The response was most likely not due to a mitogenic component in our antigen preparation, since lymphocytes from only 2 of 16 cord blood specimens had stimulation indices greater than 3.

Adult↗

PubMed1981

T lymphocyte colony-forming capacity of patients with immunodeficiency diseases: relationship of colony formation to E rosette formation and lymphocyte proliferation.

The formation of T lymphocyte colonies was studied in 30 normal subjects and 12 patients with suspected abnormalities in immune function. The mean number of colonies per plate in normal subjects was 1.159 +/- 411 which represented a plating efficiency of 0.5-1.0%. When individual cells from colonies of these normal subjects were studied for membrane markers, greater than 90% were E rosette-positive and less than 1% were positive for surface immunoglobulins. Blood lymphocytes obtained from all 12 patients showed diminished colony-forming capacity when compared to normal subjects with a range of 0-311 colonies. Six patients had less than 50 colonies/plate. Colony formation was diminished in some patients who had normal E rosette formation and lymphocyte proliferation in liquid culture. Because of these discrepancies it appears that colony formation is not a direct reflection of E rosette formation and lymphocyte proliferation. Evaluation of T lymphocyte colony-forming capacity may prove useful as an additional in vitro assessment of lymphocyte function.

Cell Division↗