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R Schwab

Publications and source records attributed to R Schwab.

At least 19 recordsLinked to original sources
PubMed1992

Altered major histocompatibility complex-restricted antigen recognition by T cells from elderly humans.

Positive selection of T cells within the thymus gland leads to major histocompatibility complex (MHC)-restricted recognition of antigen by T lymphocytes. As the thymus gland involutes with age, altered MHC-restricted antigen recognition by T cells from elderly humans would be expected. We have tested this hypothesis by comparing the proliferative response of T cells and T cell clones from aged and young subjects to influenza determinants presented by autologous or allogeneic antigen-presenting cells (APC). Under conditions in which the allogeneic mixed lymphocyte reaction was minimal, T cells from six of seven aged donors but only one of seven young donors were stimulated by influenza vaccine presented by allogeneic APC. More importantly, one-half of the influenza-specific T cell clones derived from aged donors, but none of the clones derived from young donors, were activated by influenza vaccine presented by allogeneic APC. While 80% of the MHC-nonrestricted influenza-specific T cell clones expressed the gamma/delta T cell receptor, 20% of these clones expressed the alpha/beta T cell receptor. Thus, changes in MHC-restricted antigen recognition by T cells and in altered distribution of alpha/beta versus the gamma/delta T cell receptor bearing antigen-specific T cell clones occur with aging.

Adult↗
PubMed1992

The origin and fate of beta 2m-free MHC class I molecules induced on activated T cells.

We report here that the expression of major histocompatibility complex (MHC) class I heavy chains not associated with beta 2-microglobulin is induced on resting human T cells by a variety of stimuli. These beta 2m-free class I heavy chains are not transported as such from the endoplasmic reticulum but originate from surface beta 2m-associated MHC class I molecules. beta 2m-free class I heavy chains are spontaneously released from the surface of activated cells. Cross-linking of beta 2m-free class I heavy chains with specific monoclonal antibodies results in the rapid down-regulation and internalization of these molecules. In contrast, beta 2m-associated MHC class I molecules display a different pattern of modulation. Previously, we reported that beta 2m-free class I heavy chains interact with CD8 molecules expressed on the same activated T cells. We propose that interactions between these molecules are involved in a mechanism regulating the function of activated T cells.

Brefeldin A↗
PubMed1992

The immunogenetics of immune senescence.

Immune senescence is characterized by a dysregulation of the immune system. With respect to humoral immunity, aging is associated with an increased level of many autoantibodies and a decreased antibody response to most foreign antigens. This observation reflects a decreased capacity to activate antibody production by CD5-negative B cells despite a normal or increased capacity to generate antibodies produced by the CD5-positive B cells. A similar dysregulation of cell-mediated immunity is manifested by an altered balance in cytokine production by T cells from old as compared to young subjects. Thus, the production of interleukin-2 (IL-2), IL-3 and granulocyte-macrophage colony-stimulating factor by T cells from old subjects is decreased although the production of IL-4, IL-5 and IL-6 is undiminished or actually increased.

Aged↗
PubMed1991

"Cross-wiring" of the immune response in old mice: increased autoantibody response despite reduced antibody response to nominal antigen.

Older humans and experimental animals have been repeatedly found to have higher titers of autoantibodies than do younger individuals despite the impaired responses of older individuals to foreign antigens. The studies reported here were designed to examine the relationship between these two age-related changes in antibody responses. Antibody response to foreign antigen was measured concurrently with autoantibody response in the same mice. Old mice (18-24 months old) had decreased responses to foreign antigens and increased responses to bromelain-treated syngeneic erythrocytes, compared to young mice (2 months old). In vitro mixing experiments were consistent with the possibility that suppressor cell activity in spleen cells from old mice reduce the antibody response to foreign antigen but not to autologous antigen. The results support an emerging view that age-associated changes in immune responses are the result of dysregulation rather than exhaustion of the immune system.

Aging↗
PubMed1991

Cryptococcal pleural effusion preceding cryptococcal meningitis in AIDS.

The authors report a case in which a small cryptococcal pleural effusion preceded the development of severe cryptococcal meningitis in an HIV-positive patient. The appearance of an isolated transient pleural effusion is a very unusual presentation for AIDS-related complications. The authors suggest that cryptococcal infection be considered in this setting.

Acquired Immunodeficiency Syndrome↗
PubMed1991

[Parent-child relations as a predisposition for psychogenic pain syndrome in adulthood. A controlled, retrospective study in relation to G. L. Engel's "pain-proneness"].

In a retrospective study on 151 chronic pain patients the relevance of childhood factors as described by G. L. Engel ("pain-proneness") are empirically investigated. All patients are studied by a structured interview developed for pain patients. Two groups were clinically differentiated and compared regarding childhood development: A psychogenic pain group (PP) without any somatic pathology (IASP-classification axis 5: 09; n = 75) and a group of chronic pain patients with somatic pathology (OP; n = 35). A "psychosomatic group" (IASP-axis 5: 07, e.g. migraine; n = 41) was excluded from further investigation. There are significant differences between PP and OP regarding the emotional quality of the relationship to both parents, physical abuse by the parents, a higher strain of both parents by the job (often a family enterprise), frequent aggressive conflicts between parents and their separation or divorce. Often a favorite toy or animal replaced the missing object. Pain or complaints with same localisation of significant others are significantly more frequent. No significant differences between the two pain groups are found as to loss of parent by death and the number of hospitalisation during childhood.

Adult↗
PubMed1990

Decreased steady state c-myc mRNA in activated T cell cultures from old humans is caused by a smaller proportion of T cells that transcribe the c-myc gene.

The proliferative response of T cells is known to decrease with age of the T cell donor. We now report that this proliferative defect affects both major subsets (CD4+, CD8- and CD4-, CD8+) of peripheral T cells from old humans. Furthermore, this proliferative defect can be detected within the first hours after addition of mitogen by a reduction in the steady state levels of c-myc mRNA in T cell cultures from old donors. Lymphocytes from old humans cultured with PHA have less than 50% of the level of c-myc message than do such cultures from young donors. Nuclear run-on assays suggest that the decreased steady state level of c-myc mRNA in cultures from old donors is caused by reduced transcription of the c-myc gene in T cells from old donors. The age-associated defect in transcription of the c-myc gene affects the second exon to a greater extent than the first, noncoding exon. Individual T lymphocytes from old donors that do express c-myc message, detected by in situ hybridization, have the same intracellular level of c-myc message as T lymphocytes from young donors. These data add additional support for the hypothesis that the proliferative defect of T lymphocytes from old humans is caused by the smaller fraction of T cells from old as compared with young humans that can be activated by mitogens to enter the G1 phase of the cell cycle.

Aging↗
PubMed1990

Defective expression of high affinity IL-2 receptors on activated T cells from aged humans.

The proliferative response of T cells from aged humans to a number of mitogens is significantly reduced. We report here that there is a decrease in high affinity IL-2 receptor (IL-2R) expression on activated T cells from aged humans. Scatchard analysis of the binding of [125I]IL-2 demonstrates fewer high affinity IL-2 binding sites. Autoradiographic techniques demonstrate that this results from there being fewer activated T cells from old as compared to young donors that express high affinity IL-2R. However, T cells from old donors that do not express high affinity IL-2 binding sites express both the IL-2 binding 55 and 75 kd chains. Thus, although the two IL-2 binding peptides are expressed on activated T cells from old donors, expression of the high affinity IL-2R is reduced. This may explain the decreased ability of T cells from old donors to respond to IL-2. The impaired ability of activated T cells from old donors to express high affinity IL-2R while expressing the 55 and 75 kd chains may provide insights into the mechanisms of IL-2 interactions with its receptor.

Adult↗
PubMed1990

Cellular basis for the age-associated increase in autoimmune reactions.

The mechanisms that lead to the increased expression of autoantibodies with age are poorly understood. We have studied the number, size, and density of spleen and peritoneal cells from young and old BALB/c and C57BL/6 mice as well as the frequency of clonal precursors for antibodies to mouse erythrocytes, thyroglobulin, and IgG in these lymphoid preparations. Old mice have a 6-fold increase in the number of resident peritoneal cells and a 2-fold increase in the absolute number of Ly1-bearing B cells in this population. Furthermore, old mice have twice as many large, low density splenic B cells as young mice. The frequencies of B cell clonal precursors for anti-BrMRBC and anti-thyroglobulin antibody-forming cells in old mice were 3-10 times greater than in young mice. In the same cultures, however, no increase in the frequencies of B cell clonal precursors for anti-IgG or anti-DNA antibody forming cells was detected in old compared to young mice. These findings and other data suggest that there are at least two families of B cell autoantibody precursors, one including anti-BrMRBC and anti-thyroglobulin autoantibodies, the other including anti-IgG and anti-DNA antibodies. Studies of the differential regulation of these two families of autoantibody precursors might contribute to a greater understanding of autoimmune phenomena in age and disease.

Aging↗
PubMed1989

A new technique for removing foreign bodies of the external auditory canal.

Foreign bodies of the external auditory canal are a common and challenging problem. Several techniques have been described and utilized to remove the many objects placed in ears. The tightly wedged smooth round foreign body remains one of the most difficult to remove. A new method, using a cyanoacrylate adhesive (Super Glue) was used successfully to remove a soy bean in a 16-year-old male. The glue was placed on the blunt end of a cotton swab, which was then introduced into the canal to make contact with the bean. Removal was easy, safe, and effective. This procedure avoided the morbidity associated with many well known techniques, eg, the use of forceps, and may have prevented removal under general anesthesia.

Adhesives↗
PubMed1988

CD3 pathway of T-cell activation. II. Role of HLA-class I molecules in early events.

The role of distinct regions of HLA class I molecules in regulating T-cell activation via the CD3-antigen receptor complex was investigated. Monoclonal antibodies (MoAbs) which recognize monomorphic and polymorphic epitopes on HLA Class I molecules were shown to inhibit T-cell proliferation to OKT3. These MoAbs have differential effects on the synthesis of interleukin-2 (IL-2) and IL-2 receptor expression. Cell cycle analysis demonstrated that these MoAbs function both in inhibiting cell cycle entry (G0-G1 shift) and in blocking cell cycle progression (G1-S shift) of activated T cells. Furthermore, these MoAbs have regulatory effects on the alternate pathway of T-cell activation via the CD2 molecule, T-cell activation induced by PHA, and activation induced by the phorbol ester PMA in conjunction with the calcium ionophore Ionomycin. Thus these MoAbs have different effects depending upon the pathway of T-cell activation. The results indicate that HLA class I molecules are selectively involved in the sequence of intracellular events leading to T-cell activation and proliferation.

Antibodies, Monoclonal↗
PubMed1988

Physical association between the CD8 and HLA class I molecules on the surface of activated human T lymphocytes.

Immune recognition by cytotoxic effector T cells requires participation of the CD8 and major histocompatibility complex class I antigens. We found that the CD8 molecule is noncovalently associated with the HLA class I heavy chain on the surface of human T cells activated by Con A. Accordingly, anti-CD8 monoclonal antibodies precipitated a heterodimer containing polypeptides of 32 and 43 kDa from the lysates of activated T cells. The 43-kDa chain of this heterodimer can be adsorbed from cell lysates with anti-HLA-A, -B, and -C antibodies. Endoglycosidase F treatment and chymotryptic peptide mapping identified a structural similarity between this 43-kDa molecule and the HLA class I heavy chain precipitated by the anti-HLA-A, -B, and -C antibody W6/32. Analysis of anti-CD8 precipitates under nonreducing and reducing conditions indicated a lack of interchain disulfide bonding between the CD8 and HLA heavy chain molecules. The CD8-HLA heavy chain complex was also detected in mixed lymphocyte cultures and a cloned cytotoxic T-lymphocyte line but not in purified natural killer cells. The present study indicates that CD8 is complexed with HLA heavy chain on the same cells, and the complex may have functional relevance in the T-cell recognition process.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

[Quality of life and time of survival following diagnosis of a bronchus carcinoma in 267 patients from 1977 to 1984].

The data of all patients diagnosed and/or treated for lung cancer at the Zürcher Höhenklinik Wald in the years 1977 to 1984 were analyzed retrospectively. In 1986 follow-up interviews were conducted with surviving patients and physicians of all patients. Quality of life was assessed by a performance scale in three stages, adapted from Karnofsky. Overall survival in the 267 patients (age 65 +/- 10 years, 85% males, 91% smokers) was 18 months. 14 patients have thus far lived longer than 5 years after diagnosis, resulting in a 5-year survival (Kaplan-Meier) of 9.6%. Statistical analysis showed survival to be significantly influenced by the performance scale and stage of disease at the time of diagnosis. Decision trees or algorithms calculated with a new computer program (CART) established the importance of performance scale, stage of disease and patients' age, followed by histology and patient's sex for therapeutic decisions and prognosis in lung cancer. Surgical resection in stage I and II was feasible in 20% of all patients only, with a 5-year survival rate of 36%.

Adult↗