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Biomedical subjects

M M Ward

Publications and source records attributed to M M Ward.

At least 91 records · Page 5Linked to original sources
PubMed1991

Genetic effects on cardiovascular responses to cold and mental activity in late adulthood.

The purpose of the present investigation was to examine the genetic contributions to cardiovascular reactivity in an adult cohort of male twins. A total of 47 monozygotic (MZ) twin pairs and 54 dizygotic (DZ) twin pairs, aged 59 to 69 years, were laboratory tested at four sites as part of the third examination of the National Heart, Lung, and Blood Institute Twin Study. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were recorded during two tasks, a mental arithmetic task involving serial subtraction and the cold pressor test. Significant cardiovascular responsivity was observed during both tasks as measured by substantial elevations in SBP, DBP, and HR from resting periods to task periods. Heritability estimates were statistically significant for SBP and DBP but not HR levels during pretask baseline periods and during both tasks. Genetic variance was maintained for blood pressure reactivity to the mental arithmetic task after adjustments for baseline and performance. No genetic variance for SBP or DBP reactivity to the cold pressor test was evident.

Aged↗
PubMed1991

Soluble interleukin-2 receptor levels in patients with dermatitis herpetiformis.

To determine the role of T-cell activation in dermatitis herpetiformis (DH), soluble IL-2R levels were measured by enzyme-linked immunosorbent assay (ELISA) in the sera of 30 patients with DH. Levels of this shed receptor are considered to be a measure of in vivo T-lymphocyte activation, and are elevated in the sera of many patients with inflammatory and immune-mediated diseases. Fifteen of the thirty (50%) patients with DH had elevated levels of soluble IL-2R compared to one of 31 (3%) healthy HLA-B8 or HLA-DR3 control subjects (p less than 0.00001) and one of 10 (10%) healthy non-HLA-B8/-DR3 subjects (p less than 0.0018). In addition, the mean soluble IL-2R level in the patients with DH (744 +/- 381 U/ml) was also significantly higher than that seen in 31 healthy HLA B8 or HLA DR3 individuals (388 +/- 160 U/ml, p = 0.0001) and 10 healthy non-HLA-B8/DR3 individuals (397 +/- 201 U/ml, p = 0.002). Only two of the 30 patients with DH had active skin lesions at the time of serum sampling, one of whom had elevated levels of IL-2R. Measurement of soluble IL-2R levels in sequential serum samples, available in four patients with DH at times of active and inactive skin disease, demonstrated a temporal association between soluble IL-2R level elevations and active skin disease in two patients and no association in two patients. In one patient a marked elevation in soluble IL-2R levels occurred with the onset of gastrointestinal symptoms, which decreased by 14% with institution of a gluten-free diet. In order to determine if soluble IL-2R levels are related to the mucosal immune response, the IL-2R levels were compared to the level of IgA antibodies directed against the dietary antigen beta-lactoglobulin. Ten of eleven (91%) patients with circulating IgA anti-beta lactoglobulin antibodies were also found to have elevated levels of IL-2R. In contrast, in the patients with no detectable IgA anti-beta lactoglobulin antibodies, only four of 16 (25%) had elevated levels of IL-2R (p = 0.001). Because IL-2R levels are not related to activity of the skin disease in patients with DH but are associated with the presence of IgA antibodies against the dietary antigen beta-lactoglobulin, these results suggest that some of the T-cell activation commonly present in DH reflects an ongoing immune response in the gastrointestinal tract.

Antibodies↗
PubMed1991

The relationship between soluble interleukin 2 receptor levels and antidouble stranded DNA antibody levels in patients with systemic lupus erythematosus.

Levels of soluble interleukin 2 receptors (IL-2R) have been found to be elevated in the serum of patients with systemic lupus erythematosus (SLE) and are considered an indication of immune system activation in this disease. To assess the relationship between soluble IL-2R levels and other serological markers, we compared levels of soluble IL-2R and anti-double stranded DNA (anti-dsDNA) antibodies in SLE sera. In a cross sectional study of 34 patients with SLE, soluble IL-2R levels were elevated compared with healthy individuals (1126 U/ml vs 235 U/ml, p less than 0.0001), and a significant correlation between levels of soluble IL-2R and anti-dsDNA antibodies was present (r = 0.543, p = 0.0009). In a longitudinal study of 10 additional patients, the time courses of soluble IL-2R levels and anti-dsDNA antibody measurements were similar in 3 patients. In 7 patients, substantial differences in the levels of soluble IL-2R and anti-dsDNA antibodies over time were observed, including marked changes in anti-dsDNA antibody levels that were accompanied by only minor changes in soluble IL-2R levels, and soluble IL-2R measurements that were persistently elevated despite generally low anti-dsDNA antibody levels. Our results indicate that soluble IL-2R levels may not always parallel other serological markers of SLE, suggesting measurement of different facets of immune system activation by various assays.

Adult↗
PubMed1991

The time course of acute psychiatric episodes in systemic lupus erythematosus.

Acute psychotic manifestations in systemic lupus erythematosus (SLE) have been considered usually to occur early in the course of illness, although these findings are primarily based on studies with few patients and limited lengths of observation. To further investigate the chronology of acute psychiatric disturbances in SLE, the time course of these episodes was examined in 36 patients over a median duration of observation of 72 months. Twenty-two of 36 (61.1%) initial psychiatric episodes occurred within the first year of diagnosis of SLE, although several patients experienced the initial onset of psychiatric manifestations several years after the onset of SLE. Recurrent episodes occurred in 10 of 36 patients at a median of 8 months after the initial episode. Although tending to occur early in SLE, primary acute psychiatric events may first occur in patients with long durations of illness, and the time of onset of these episodes does not appear helpful in their differential diagnosis.

Acute Disease↗
PubMed1991

Serum immunoglobulin levels in systemic lupus erythematosus: the effects of age, sex, race and disease duration.

To determine whether factors other than disease activity influence immunoglobulin levels in patients with systemic lupus erythematosus (SLE), the effect of age, sex, race, and duration of disease on serum IgG and IgM levels in 170 patients with SLE were investigated. Serum IgM and IgG levels did not differ between men and women, while IgM levels were higher in whites. Serum IgG levels did not vary with age or duration of SLE. In contrast, serum IgM levels were negatively correlated with both age (r = -0.236; p = 0.002) and duration of SLE (r = 0.248; p = 0.001), and demonstrated a U-shaped age relationship, being higher in children and older patients. These patterns of immunoglobulin expression in patients with SLE contrast with those exhibited in populations of healthy individuals, suggesting that the immunoregulatory disturbances of SLE predominate over the normal mechanisms regulating levels of IgM and IgG.

Adult↗
PubMed1990

Analysis of the immune response to lipopolysaccharide. Existence of an interspecies cross-reactive idiotype associated with anti-lipid A antibodies.

LPS is the major surface glycolipid on gram-negative bacteria. In this work, we have idiotypically characterized the antibody response against LPS in different species. To do this, we have produced mAb against LPS. Binding of many of these antibodies to LPS could be inhibited by LPS and lipid A, indicating that the monoclonals are specific for lipid A, the toxic moiety of the LPS molecule. One anti-lipid A antibody, IC9, proved protective against gram-negative bacteremia and endotoxic shock in murine protection models. We generated anti-idiotypic antibodies against IC9. The binding of several of these anti-Id to IC9 was specifically inhibited by lipid A. We used these anti-Id to characterize the anti-LPS response, and the results revealed that the IC9 Id is conserved in different species. The importance of an interspecies cross-reactive Id in the response to endotoxin and its relevance in vaccine development for septic shock are discussed.

Animals↗
PubMed1990

Serum interleukin-2 receptor responses to immunization.

Serum interleukin-2 receptor (sIL-2R) levels have been used to assess immune activation in inflammatory and infectious illnesses, although the cellular origin of these receptors and the dynamics of their production are not well defined. To investigate the relationship between sIL-2R levels and the degree of immune activation in antigen-specific responses, sIL-2R were measured in healthy individuals after both primary and secondary immunization with keyhole limpet hemocyanin (KLH). Despite induction of strong antibody responses, KLH immunization did not result in consistent elevations of sIL-2R levels, with only one of six subjects developing a substantial (twofold) increase in sIL-2R levels. The absence of sIL-2R elevation after a discrete antigenic stimulus suggests that inflammatory illnesses in which elevated sIL-2R levels have been noted involve more extensive stimulation of immune cells, either in number or in degree, than that present after simple immunization in healthy individuals.

Adult↗
PubMed1990

Heavy and light chain utilization in autoantibodies of elderly patients with systemic lupus erythematosus.

To determine whether age-related changes in immune function affect patterns of autoantibody production, we have examined the isotype and light chain utilization in autoantibodies of elderly patients with systemic lupus erythematosus (SLE). Enzyme-linked immunosorbent assays (ELISA) were used to determine the frequencies of IgG and IgM antibodies to single-stranded DNA (ssDNA), Sm, and the 70K protein component of RNP in the sera of 53 patients with SLE older than age 60. The IgG subclass distributions and kappa/lambda ratios for each of these autoantibodies were also determined and compared to measurements performed on the sera of 53 young adult patients with SLE. The frequencies of autoantibodies of each specificity, except IgM anti-ss DNA antibodies, were higher among the young adult patients, although the magnitudes of the responses were similar in both age groups. IgG anti-Sm antibodies were composed of both IgG1 and IgG2 subclasses, while IgG anti-70K RNP and IgG anti-ssDNA were predominantly of the IgG1 subclass. There were no differences in the IgG subclass distributions of any of the three autoantibodies between the elderly and young adult patient sera. The kappa/lambda ratios for each of the three autoantibodies were similar to that present in total serum immunoglobulins, and kappa/lambda ratios of autoantibodies, standardized to the kappa/lambda ratios of serum, were not different between elderly and young adult groups. Few patient sera of either age group (9 elderly, 7 young adult) demonstrated even midly skewed light chain ratios in their autoantibody responses. Thus, despite developing in an immunological environment that may have altered the clonality and isotype distribution of their responses, the autoantibodies produced by elderly patients with SLE were qualitatively similar to autoantibodies of younger patients.

Adolescent↗
PubMed1990

Expression of IgM and IgG autoantibodies in pediatric and adult systemic lupus erythematosus.

To compare patterns of autoantibody responses in pediatric and adult patients with systemic lupus erythematosus (SLE). IgG and IgM antibodies to single-stranded DNA (ssDNA), Sm, and the 70-kDa protein component of the RNP antigen (70-kDa RNP) were measured in 29 pediatric and 36 adult patients by enzyme-linked immunosorbent assays. Antibodies of either isotype to ssDNA, Sm, and 70-kDa RNP were present in 64, 58, and 79% of pediatric patients, respectively, comparable to prevalences of these autoantibodies in the adult SLE patients. Pediatric SLE patients were more likely than adult patients to have IgM anti-Sm antibodies (41.4% vs 13.9%, P = 0.02) and tended to more commonly express IgM anti-70-kDa RNP and IgM anti-ssDNA antibodies. The prominence of IgM autoantibody responses among pediatric SLE patients was shown by multiple logistic regression analysis to be related to total IgM concentrations and not related to age or duration of disease. Sequential serum samples available from several pediatric patients revealed the maintenance of similar patterns of isotype responses over time in approximately one-half of patients. In those patients whose responses changed over time, the variations in isotype expression were consistent with maturation of antibody responses of each specificity. While these results demonstrate similarities in autoimmune reactivities between pediatric and adult SLE patients, the serologic study of pediatric patients may provide an opportunity to more readily investigate the evolution of autoantibody responses.

Adolescent↗
PubMed1990

Temporal correlation of antibody responses to different epitopes of the human La autoantigen.

To investigate the temporal relationship of antibody responses to different La epitopes, sequential sera from nine patients with systemic lupus erythematosus and Sjogren's syndrome were tested by enzyme-linked immunosorbent assay for antibody binding to a series of recombinant fusion proteins containing different regions of the La molecule. The results of this analysis indicate that antibody responses to four different La fragments vary in parallel over time. This finding is supported by a statistical analysis indicating that the changes in antibody levels between the six pairs of responses were highly correlated (P less than 0.001). Furthermore, we show by immunoaffinity purification that antibodies to the three nonoverlapping La protein fragments do not cross-react with other fragments and, hence, represent independent populations. These results suggest that anti-La antibodies are coordinately produced to different epitopes on the La molecule, possibly reflecting an antigen-driven mechanism.

Antibodies, Antinuclear↗
PubMed1990

Systemic lupus erythematosus in men: a multivariate analysis of gender differences in clinical manifestations.

The marked gender influence on the occurrence of systemic lupus erythematosus (SLE) indicates that genetic and hormonal factors may be important in the etiology of this illness. However, few differences in clinical manifestations between males and females have been reported. To further investigate gender differences in SLE, the prevalence of 23 clinical manifestations of SLE were compared in a cohort of 62 men and 299 women. After adjusting for differences in age, race, and duration of followup, men were found to more commonly have seizures (odds ratio = 1.65; 95% confidence interval = 1.09, 2.49), and showed a trend to progress to renal failure more often (odds ratio = 1.40; 95% confidence interval = 0.96, 2.03) than women. Gender differences were not evident for the remaining 21 clinical features. The clinical similarity between men and women with SLE represents a circumstance in which the use of clinically defined patient subsets does not appear to facilitate the investigation of potential pathogenetic or etiologic factors.

Adult↗
PubMed1990

Clinical manifestations of systemic lupus erythematosus. Identification of racial and socioeconomic influences.

The identification of differences in the clinical manifestations of systemic lupus erythematosus (SLE) due to racial and socioeconomic factors has been hampered in previous studies by limitations in the numbers of black patients examined. We sought to define racial differences in the cumulative clinical manifestations of SLE in a large, racially balanced cohort (184 black patients and 174 white patients). Differences in the cumulative disease manifestations of SLE between black and white patients were evaluated by multivariate regression techniques, controlling for socioeconomic status and the potential confounding factors of age, gender, duration of follow-up, and treatments. Race was found to be an important factor influencing the prevalence of 9 of 24 clinical features of SLE. As a group, blacks more commonly manifested anti-Sm and anti-RNP antibodies, discoid skin lesions, and proteinuria, and less commonly manifested photosensitivity, than whites. Among specific age, gender, and socioeconomic subgroups, blacks were more likely than whites to have had psychosis, serositis, and urinary cellular casts, and less likely to have had sicca syndrome. Racial differences in the prevalence of renal failure were due to socioeconomic effects. These results suggest that race is under-recognized as a factor influencing the clinical heterogeneity of SLE.

Adult↗
PubMed1990

Age associated clinical manifestations of systemic lupus erythematosus: a multivariate regression analysis.

The influence of age on the prevalence of individual clinical manifestations of systemic lupus erythematosus (SLE) has not been adequately distinguished from racial or gender influences. Therefore, we examined variations in the clinical manifestations of SLE with age in a group of 361 patients. Multivariate regression techniques, including logistic regression and analysis of covariance, were used to identify clinical features associated with age, while controlling for important confounding factors, including race, gender, duration of followup, and treatment effects. Lymphopenia was found more frequently with increasing age, while malar rash, seizures, false-positive VDRL, thrombocytopenia (in whites), proteinuria (0.5-3.5 g/day), elevated antidouble stranded DNA antibodies, and hypocomplementemia were found less frequently. No age relationship was found for the prevalence of 16 of 24 clinical features examined, including the important disease manifestations of arthritis, serositis, psychosis, nephrotic-range proteinuria, renal failure, autoimmune hemolytic anemia, and leukopenia. The use of regression analysis allows the recognition of similarities and differences in cumulative clinical features of SLE due to age in isolation from the effects of other demographic factors.

Adult↗
PubMed1989

A meta-analysis of the clinical manifestations of older-onset systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) with onset in later life has been reported to have a clinical presentation different from that in younger individuals; however, the disease manifestations typical of older-onset SLE patients are known to vary widely among published studies. Meta-analysis is a statistical process capable of quantitatively combining the results of these reports. This meta-analysis examines the methodologic features of studies investigating age-associated manifestations of SLE, and pools estimates of association between clinical features of SLE and age across these studies. Serositis, interstitial pulmonary disease, anti-La antibodies, and Sjögren's syndrome were most strongly and consistently associated with older-onset SLE, while alopecia, Raynaud's phenomenon, fever, lymphadenopathy, hypocomplementemia, and neuropsychiatric illness were present less frequently in this group. The extent to which information bias, selection bias, and uncontrolled confounding effects potentially influence these results is discussed. The available information in the literature does not describe the spectrum of clinical manifestations of SLE in the elderly sufficiently to allow its categorization as a distinct entity.

Age Factors↗
PubMed1989

Antidouble stranded DNA antibody assays in systemic lupus erythematosus: correlations of longitudinal antibody measurements.

To determine whether different assays of antidouble stranded DNA (anti-dsDNA) antibodies provide comparable information in quantitative antibody assessment over time, longitudinal correlations between 3 anti-dsDNA antibody methods were derived. Determinations of anti-dsDNA antibody levels on serial samples from 9 patients with systemic lupus erythematosus (SLE) were performed by filter binding radioimmunoassay, enzyme linked immunosorbent assay, and Crithidia indirect immunofluorescence. Substantial pairwise correlations among assay methods were found (r = 0.544 to 0.804; p less than 0.001). In addition, anti-dsDNA antibody levels as measured by each assay were inversely correlated with levels of the 3rd component of complement. Our results indicate that changes in antibody levels as determined by these 3 methods closely parallel each other over time, and suggest that the array of anti-dsDNA antibodies detected in patient sera remains relatively constant over time.

Adolescent↗
PubMed1988

Factors predictive of acute renal failure in rhabdomyolysis.

In a historical cohort study, acute renal failure developed in 16.5% of 157 patients with rhabdomyolysis over a two-year study period. Underlying clinical, laboratory, and causative factors associated with the development of acute renal failure were examined. Factors predictive of renal failure in this setting, determined by multiple logistic regression analysis, included the degree of serum creatine kinase, serum potassium, and serum phosphorus level elevation; the degree of depression of serum albumin level; and the presence of dehydration at presentation or sepsis as the underlying cause. The predictive model that was developed correctly classified 93% of subjects and was statistically validated.

Acute Kidney Injury↗
PubMed1987

Idiotope vaccine against Streptococcus pneumoniae. A precursor study.

An analysis of nominal vs idiotope antigen-induced B cell precursors was performed in A/St mice. With the use of the splenic fragment culture system, the quantity and quality of B cell precursors responding to two anti-idiotope carrier antigens (4C11 hemocyanin and F6 hemocyanin) and nominal antigen (phosphorylcholine-hemocyanin) were compared. In addition, the effect of priming with anti-idiotope-carrier antigens on B cell precursors responding to phosphorylcholine-hemocyanin was determined. We found that one anti-idiotope-carrier antigen, 4C11-hemocyanin, and phosphorylcholine-hemocyanin stimulated similar subpopulations of primary B cells. However, the B cell population stimulated by F6-hemocyanin, the other anti-idiotype complex, was distinct. Furthermore, priming with certain idiotope antigens can direct the phosphorylcholine-hemocyanin response into the expression of idiotypes that may be the most effective in protective immunity. Our results provide essential information for the rational design of idiotype vaccines by clarifying the dynamic relationship of the B cell precursor repertoire with the in vivo antibody response in the response to nominal and idiotope antigens.

Animals↗