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M Julius

Publications and source records attributed to M Julius.

At least 37 records · Page 2Linked to original sources
PubMed1994

Glutathione and morbidity in a community-based sample of elderly.

This study examined the association of blood glutathione level, a potential marker of physiological/functional aging, with a number of biomedical/psychological traits in a subgroup (N = 33) of a representative sample of community-based elderly. Higher glutathione levels were associated with fewer number of illnesses (p < 0.05), higher levels of self-rated health (p < 0.01), lower cholesterol (p < 0.05), lower body mass index, and lower blood pressures. Subjects with diagnoses of arthritis, diabetes, or heart disease (as assessed by physicians) had at least marginally significant lower glutathione levels than those who were disease free. Glutathione, together with age and a measure of suppressed anger, accounted for 39% of the variance of an index of morbidity. Glutathione, by itself, accounted for 24% of the variance. To our knowledge, this is the first evidence of an association of higher glutathione levels with higher levels of physical health in a sample of community-based elderly. Further studies in large samples are needed to investigate glutathione as a potential overall health risk factor for morbidity among the elderly.

Aged↗
PubMed1994

Thymus independent T cell development and selection in the intestinal epithelium.

The presence of intestinal intra-epithelial lymphocytes (IEL) has been appreciated for over 100 years. However, until recently, the IEL were thought to be simply another specialized component of the gut-associated lymphoid tissue (GALT), sharing the same origin as lymphocytes found in other GALT compartments such as the lamina propria, the Peyer's patches, and the mesenteric lymph nodes. While the IEL remain functionally enigmatic, over the last ten years increasing evidence, originally based on the phenotypic complexity of IEL, has led to the conclusion that the intestinal epithelium comprises a distinct and unique lymphoid compartment within the organism. The recent discovery that the intestinal epithelium is a primary T lymphopoietic organ provides obvious potential explanations for the phenotypic peculiarities of IEL. The following discussion reviews the experiments that established that the intestinal epithelium is a site of T cell development and selection, and the discussion correlates phenotypic and functional heterogeneity of IEL within this context.

Animals↗
PubMed1993

Thymus-independent positive and negative selection of T cells expressing a major histocompatibility complex class I restricted transgenic T cell receptor alpha/beta in the intestinal epithelium.

We demonstrate that in the mouse intestinal epithelium the selection of T lymphocytes expressing a transgenic T cell receptor alpha/beta (TCR-alpha/beta) specific for male antigen (H-Y) in the context of H-2Db depends on the differential expression of H-Y and H-2Db in situ. In H-2Db transgenic males, there is no reduction in the number of intestinal intraepithelial lymphocytes (IEL), and the four main subsets of IEL expressing TCR-alpha/beta, defined by the differential expression of CD4, CD8 alpha, and CD8 beta, are present. Moreover, the level of expression of CD8 alpha and CD8 beta on CD8+ IEL subsets is unaltered. The frequency of CD8 alpha+ IEL expressing CD8 beta, in H-2Db male mice, however, is significantly decreased and these cells do not express the transgenic TCR. In contrast, virtually all CD8 alpha+beta- IEL in the same animals express the transgenic TCR. Still, these potentially autoreactive cells are refractile to H-Y/H-2Db stimulation in vitro. Both H-2Db and H-2Dd transgenic females contain high frequencies of cells expressing the transgenic TCR among CD8 alpha+beta- and CD8 alpha+beta+ IEL. However, two possibly related phenotypic features are peculiar to H-2Db female mice. The frequency of CD8 alpha+ IEL expressing CD8 beta is increased in these mice and, while in H-2Dd females the level of the transgenic TCR alpha chain expressed on CD8 alpha+beta+ IEL is uniformly low, some of the CD8 alpha+beta+ IEL in H-2Db females express a high level of both transgenic TCR chains. It is important to note, the ability of CD8 alpha+beta+ IEL to respond to H-Y/H-2Db stimulation in vitro is restricted to those coexpressing a high level of both transgenic TCR chains. The analysis of athymic radiation chimeras using adult thymectomized recipients of distinct H-Y/H-2 haplotypes, reconstituted with bone marrow from H-2Db transgenic females, demonstrates that all IEL subsets present in unmanipulated transgenic animals develop in the absence of a thymus. These IEL are phenotypically identical to those found in unmanipulated transgenic animals sharing the H-Y/H-2 haplotype of athymic recipients. Taken together, these results demonstrate that in the absence of male antigen, expression of H-2Db in the intestinal epithelium results in the positive selection of functional IEL specific for male antigen, in situ. When both H-Y and H-2Db are expressed in the intestinal epithelium, CD8 alpha+beta+ IEL expressing the transgenic TCR are negatively selected, while the frequency of nonfunctional CD8 alpha+beta- IEL expressing the transgenic CR is increased.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Follicular dendritic cells help resting B cells to become effective antigen-presenting cells: induction of B7/BB1 and upregulation of major histocompatibility complex class II molecules.

This study was designed to investigate whether follicular dendritic cells (FDC) can activate B cells to a state in which they can function as effective antigen-presenting cells (APC). High buoyant density (i.e., resting) B cells specific for 2,4-dinitro-fluorobenzene (DNP) were incubated with DNP-ovalbumin (OVA) bearing FDC, after which their capacity to process and present to an OVA-specific T cell clone was assessed. The efficacies of alternative sources of antigen and activation signals in the induction of B cell APC function were compared with those provided by FDC. Only FDC and Sepharose beads coated with anti-immunoglobulin (Ig)kappa monoclonal antibody provided the necessary stimulus. FDC carrying inappropriate antigens also induced B cell APC function in the presence of exogenous DNP-OVA. However, in circumstances where soluble DNP-OVA was limiting, FDC bearing complexes containing DNP, which could crosslink B cell Ig receptors, induced the most potent APC function. Analysis by flow cytometry revealed that within 24 h of coculture with FDC, a significant percentage of B cells increased in size and expressed higher levels of major histocompatibility complex class II. By 48 h, an upregulation of the costimulatory molecule, B7/BB1, occurred, but only when exposed to the FDC bearing DNP. Taken together, the results demonstrate that FDC have the capacity to activate resting B cells to a state in which they can function as APC for T cells. The stimuli that FDC provide may include: (a) an antigen-dependent signal that influences the upregulation of B7/BB1; and (b) possibly a signal independent of crosslinking mIg that results in Ig internalization. The relevance of these findings to the formation of germinal centers and maintenance of the humoral response is discussed.

Animals↗
PubMed1993

Distinct roles for CD4 and CD8 as co-receptors in antigen receptor signalling.

The co-ordinated interactions of multiple membrane molecules with the T-cell receptor for antigen (the TCR-CD3) are prerequisite for T-cell activation. In this review we consider the involvement of CD4, CD8, and CD45 on the two lymphocyte lineages. Experiments from many laboratories have provided concordant results leading to the consensus that CD4 and CD8 are functional analogues, providing similar supplementary signals to those generated through the TCR-CD3 complex on MHC class-II- and MHC class-I-restricted T cells, respectively. However, recent results demonstrate striking differences in the coreceptor functions of CD4 and CD8. These differences reflect the distinct properties of the molecules themselves, which in turn are associated with CD45 involvement in the activation of CD4+ and CD8+ T cells.

Animals↗
PubMed1992

Association of tyrosine kinase p56lck with CD4 inhibits the induction of growth through the alpha beta T-cell receptor.

The membrane glycoprotein CD4 enhances antigen-mediated activation of T cells restricted by class II molecules of the major histocompatibility complex (MHC). This positive function has been attributed to the protein tyrosine kinase p56lck (ref. 4), which is noncovalently associated with the cytoplasmic portion of CD4, and is activated on CD4 aggregation. Antigen presentation by MHC class II molecules coaggregates CD4 and the T-cell antigen receptor (TCR alpha beta-CD3). Thus, the mutual specificity of CD4 and TCR alpha beta for the MHC-antigen complex results in the juxtaposition of p56lck and TCR alpha beta-CD3. In contrast, anti-CD4 antibodies can abrogate antigen-induced, as well as anti-TCR-induced T-cell activation, indicating that CD4 might also transduce negative signals. The molecular basis for this opposing function remains unclear. Here we show that the CD4-p56lck complex prohibits the induction of activation signals through the TCR-CD3 complex when not specifically included in the signalling process. This negative effect does not require anti-CD4 treatment, indicating that the induction of distinct negative signals is probably not involved. Rather, the results demonstrate that the CD4-p56lck complex provides prerequisite signals for antigen-receptor-induced T-cell growth and thus characterize a molecular mechanism for functional constraints imposed on T-cell activation by the MHC.

Animals↗
PubMed1992

Thymus-independent development and negative selection of T cells expressing T cell receptor alpha/beta in the intestinal epithelium: evidence for distinct circulation patterns of gut- and thymus-derived T lymphocytes.

We demonstrate that mouse intestinal intraepithelial lymphocytes (IEL) can be divided into subsets based on the differential expression of functional T cell receptor alpha/beta (TCR-alpha/beta) signaling complexes. Two subsets, CD4+ 8 alpha + beta - and CD8 alpha + beta -, are refractory to stimulation with anti-TCR-alpha/beta and contain high frequencies of potentially self-reactive cells. In contrast, the CD4+ and CD8 alpha + beta + IEL subsets are responsive to anti-TCR-alpha/beta and depleted of potentially self-reactive cells. The analysis of fetal liver radiation chimeras using adult thymectomized recipients demonstrates that the four TCR-alpha/beta + IEL subsets are generated in normal numbers in the absence of the thymus. Moreover, expression of the major histocompatibility complex class II-encoded I-E molecule and Mls1a in the gut of the athymic host results in the negative selection of potentially self-reactive T cells expressing V beta 11 and V beta 6, respectively, from those IEL subsets that express functional TCR-alpha/beta signaling complexes. Neither the spleen nor the Peyer's patches of athymic recipients contain T cells of donor origin. In contrast, normal numbers of phenotypically and functionally mature CD4+ and CD8 alpha + beta + T cells of donor origin are found in the lamina propria of chimeric animals. The phenotypic analysis of lymphocytes obtained from Ly5 congenic parabionts reveals that peripheral T cells migrate rapidly to the Peyer's patches and lamina propria, but not to the intestinal epithelium. Taken together, these results demonstrate that the intestinal epithelium is a thymus-independent site of T lymphopoiesis, where selection of the T cell repertoire involves the deletion of potentially self-reactive cells in situ. Moreover, the appearance of donor-derived, phenotypically mature T cells, exclusively in the lamina propria of athymic radiation chimeras, suggests that mature IEL expressing functional TCR-alpha/beta migrate to this site.

Alleles↗
PubMed1992

The induction of resting B cell differentiation does not require T cell contact.

A T cell clone as well as immediately ex vivo CD4+ lymph node T cells are shown to support the differentiation of co-cultured resting B cells in the absence of T cell-B cell contact. Antibodies specific for class II products of the major histocompatibility complex inhibit the transactivation of resting but not activated B cells. This differential inhibition pattern indicates that the responses obtained from resting B cell populations are not due to their contamination with B cell blasts. Further, supernatants prepared from an activated T cell clone induce resting B cell differentiation. Two lines of evidence suggest that the activity contained in these supernatants can be attributed to interleukin (IL)-5. Activity is neutralized by monoclonal anti-IL-5; and both recombinant and affinity-purified IL-5 induce the differentiation of immediately ex vivo resting and activated B cells with comparable efficiency. Taken together, these results demonstrate that contact with T cells does not provide prerequisite signals for the induction of resting B cell differentiation.

Animals↗
PubMed1991

Functional consequences of CD4-TCR/CD3 interactions.

The relative positions of CD4 and of the T cell receptor complex for antigen (TCR/CD3) determine whether signalling through the antigen receptor results in T cell growth. The following discussion focusses on those central observations which demonstrate that CD4 and the associated protein tyrosine kinase p56lck provide critical signals modulating the biological responses induced through the TCR/CD3 complex. Based on the available evidence, we suggest that antigen-mediated co-aggregation of CD4/Lck and TCR/CD3 is an obligate activation signal and that, in its absence, signalling through TCR alpha beta induces T cell death. The role of CD4 in self-non-self discrimination would therefore be critical and would provide a mechanism for the maintenance of peripheral T cell tolerance to non-major histocompatibility complex-related self-antigens.

Animals↗
PubMed1990

Structure of germ line immunoglobulin alpha heavy-chain RNA and its location on polysomes.

We describe the structure of the major germ line RNA transcribed from unrearranged immunoglobulin alpha heavy-chain genes in immunoglobulin M-expressing cells of the I.29 mu B-cell lymphoma, a cell line capable of switching to immunoglobulin A expression upon lipopolysaccharide treatment. This germ line alpha RNA has a small open reading frame that does not include the C alpha domain, and this RNA appears to be present on polysomes in I.29 mu cells.

Animals↗
PubMed1989

Independence in activities of daily living for end-stage renal disease patients: biomedical and demographic correlates.

Factors associated with physical well-being were examined in a population-based sample of adult end-stage renal disease (ESRD) patients in Michigan (n = 459). The dependent variables were two measures of physical functioning: (1) a ten-item measure of activities of daily living (ADL), and (2) the 45-item physical dysfunction dimension of the Sickness Impact Profile (SIP). Independent variables included four modalities of treatment (in-center hemodialysis, continuous ambulatory peritoneal dialysis [CAPD], related transplant, and cadaver transplant); primary cause of ESRD (eg, diabetes, glomerulonephritis); comorbidity (other illnesses besides primary cause of ESRD); and demographic characteristics (sex, race, age, marital status, education). ADL and SIP unadjusted mean scores differed significantly by category for each of the eight study factors (analysis of variance [ANOVA], P less than 0.0001), with the exception of sex for SIP means. The highest levels of dependency in ADL were reported by patients who were older, female, black, widowed, less educated, treated with in-center hemodialysis, had diabetes as the primary cause of ESRD, and/or reported more comorbidity. The partial effect of each factor on the dependent measures with adjustment for the seven other factors was assessed using analysis of covariance (ANCOVA). In the ADL analysis, sex, race, age, primary cause of kidney failure, and comorbidity were significant factors (probability values ranging from 0.05 for race to 0.0001 for sex, primary cause of ESRD, and comorbidity). The SIP physical dysfunction measure gave slightly different results. Race, age, primary cause of ESRD, comorbid status, and modality of treatment were significantly related to physical dysfunction (P less than 0.05 to P less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗
PubMed1989

A comparison of employment rates of patients treated with continuous ambulatory peritoneal dialysis vs in-center hemodialysis (Michigan End-Stage Renal Disease Study).

This study examines factors associated with employment status in a stratified subsample of the Michigan End-Stage Renal Disease Study population. To reduce the variation in employment potential, the subsample consisted of nondiabetic patients aged 20 to 64 years. The patients were stratified on the basis of their treatment histories as follows: (1) treated by in-center hemodialysis only; (2) primarily treated by continuous ambulatory peritoneal dialysis; and (3) failed continuous ambulatory peritoneal dialysis, substituted by another form of dialysis. A significantly higher percentage of the patients undergoing stable continuous ambulatory peritoneal dialysis were in the labor force than were those undergoing in-center hemodialysis (27.4% vs 9.6%). Using logistic regression, even when adjusted for sex, race, age, education, marital status, primary diagnosis, and duration of end-stage renal disease, the stable continuous ambulatory peritoneal dialysis group was significantly more likely to be employed than the group undergoing either in-center hemodialysis only or the group that failed continuous ambulatory peritoneal dialysis.

Adult↗
PubMed1988

Daily symptoms and behavioral responses. Results of a health diary with older adults.

Research on the health care behavior of older adults in response to symptoms will benefit from having data collection methods that can monitor health actions as they occur on a daily basis. In the present study, symptom experiences over a 2-week period and the actions taken in response to them were studied with a self-kept daily diary. Participants were 142 community-resident older persons, aged 62-94. Diary information about number of daily symptoms and the accompanying pain/discomfort was correlated with health perceptions and psychosocial indices obtained in an interview prior to the diary period. Women tended to take a more active response to symptoms than men, particularly in the area of personal care actions. Preventive health behaviors were not strongly related to symptom-related actions. Satisfaction with one's income was the only predictor of seeking professional assistance. Overall, the diary method is feasible to use with older adults, although certain groups may require special consideration (e.g., the visually impaired, persons with multiple symptoms per day, or those with a limitation on writing ability).

Age Factors↗
PubMed1986

Anger-coping types, blood pressure, and all-cause mortality: a follow-up in Tecumseh, Michigan (1971-1983).

This study examined prospectively (1971-1983) the relationship between anger-coping types, blood pressure, and all-cause mortality in a sample of men and women aged 30-69 (n = 696) of the Tecumseh Community Health Study. Subjects who indicated that they were likely to suppress their anger in response to two hypothetical anger-provoking situations had 1.7 times the mortality risk of those who expressed their anger (95% confidence interval (CI) = 1.03-3.05). Subjects who suppressed their anger when unjustifiably confronted by their spouse had twice the mortality risk of those who expressed their anger (95% CI = 1.13-3.38). For high vs. low suppressed anger towards a policeman, the mortality risk was 1.24 (95% CI = 0.72-2.14). These relationships were invariant across age, sex, and education groups, even when medical risk factors were adjusted for, i.e., smoking, relative weight, blood pressure, coronary heart disease status, forced expiratory volume at one second (FEV1), and chronic bronchitis. However, suppressed anger measures significantly interacted with elevated blood pressure to predict the highest mortality risk. These results suggest that persons with high mortality risk can be identified in part by how they cope with anger, and by the joint effect of anger-coping type (a behavioral trait) and elevated blood pressure (a biologic trait).

Adaptation, Psychological↗