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Biomedical subjects

S Weinreich

Publications and source records attributed to S Weinreich.

At least 19 recordsLinked to original sources
PubMed2003

Off-Pump versus on-pump coronary artery bypass: can OPCAB reduce neurologic injury?

OBJECTIVE: Coronary artery bypass grafting (CABG) with cardiopulmonary bypass is still the gold standard for surgical myocardial revascularization. Despite advances in techniques and technologies, documented evidence indicates that cardiopulmonary bypass remains the major source of intraoperative brain injury. This study was set up to test whether offpump coronary artery bypass (OPCAB) is superior to CABG regarding postoperative neurologic outcome or neurocognitive function. METHODS: Between January 1999 and June 2001, 251 patients scheduled for coronary revascularization were divided into 2 groups, CABG (control) and OPCAB. All patients underwent an extensive neurologic and neurocognitive battery of tests preoperatively and postoperatively at 48 hours, 7 days, and 3 months following surgery. RESULTS: There were no statistically significant differences between the 2 groups regarding the preoperative or intraoperative data. The means for patient age, number of grafts, and number of central anastomoses were, respectively, 65.4 years (CABG) and 64.6 years (OPCAB), 3.0 (CABG) and 2.2 (OPCAB), and 2.0 (CABG) and 1.2 (OPCAB). The occurrence of stroke was 2.3% (CABG) and 0% (OPCAB). CONCLUSION: Neurologic complications and postoperative neurocognitive dysfunction remain major concerns in coronary artery surgery. Besides the occurrence of stroke, which dramatically reduces the success of the heart operation, the importance of neurocognitive disorders for postoperative quality of life is not yet well defined. OPCAB significantly improves postoperative neurocognitive function, which may in turn improve the postoperative quality of life.

Aged↗
PubMed2000

Increased risk of developing ankylosing spondylitis among first-born children.

OBJECTIVE: Studies in mice have demonstrated an increased risk of ankylosing enthesopathy in earlier litters compared with later-born offspring. In humans, birth order and maternal age as risk factors for ankylosing spondylitis (AS) have not been investigated previously. This study was undertaken to investigate whether first-born children have a higher risk of AS than later-born children and whether maternal age at delivery is another risk factor. METHODS: The birth order of 162 AS patients was compared with that of their healthy siblings, both for the total group and with stratification for maternal age at first delivery. Maternal age at the time of delivery of AS patients who were first-born children was compared with the mean maternal age at first delivery in the Dutch population. RESULTS: The number of first-born children with AS was significantly higher than would be expected in case of an equal risk between first-born and later-born children (26 versus 20 for families with 2 children [P = 0.029] and 63 versus 47.6 for all families [P = 0.004]). Also, the mean maternal age at first delivery was lower in mothers of AS patients (24.8 years) compared with mothers of healthy controls (26.1 years). CONCLUSION: Low birth order is a risk factor for AS in humans.

Adolescent↗
PubMed2000

Germ-free mice do not develop ankylosing enthesopathy, a spontaneous joint disease.

Ankylosing enthesopathy (ANKENT) is a naturally occurring joint disease in mice with numerous parallels to human ankylosing spondylitis (AS). Similarities between AS and ANKENT include not only affected tissue (joint entheses) but also association of the disease with genetic background, including MHC genes, gender, and age. Young males with the C57Bl/10 background have been described to suffer from ANKENT and, among H-2 congenic strains, high frequency of afflicted joints has been recorded in B10.BR (H-2(k)) males. Interestingly, the incidence of ANKENT is higher in conventional (CV) males that in their specific-pathogen-free (SPF) counterparts. The latter finding suggests that microbes could play a role as an ANKENT-triggering agent. To further examine this hypothesis we have established a germ-free (GF) colony of B10.BR mice and observed ANKENT incidence in both GF males and their conventionalized (ex-GF) male littermates; 20% of ex-GF males developed ANKENT before 1 year of age. In contrast, no joint disease was observed under GF conditions (p < 0.0001). Our results show that live microflora is required in ANKENT pathogenesis.

Animals↗
PubMed2000

Strong association of HLA-B27 heavy chain with beta 2-microglobulin.

Monoclonal antibody TG1 recognizes specifically antigens HLA-B27, B7, B22 and B17 on cell surface in cytotoxicity and cytofluorometry tests. When cell detergent extracts were subjected to SDS PAGE under mild conditions (no heating and no reduction of the sample) followed by Western blotting, TG1 detected exclusively a complex of B27 heavy chains with beta(2)-microglobulin (as a 50 kDa band) whereas the other B-locus antigens (B7, B22, B17) were detected as free 43 kDa heavy chains under the same conditions. When the samples were boiled prior to SDS PAGE, TG1 detected again the 43 kDa free heavy chains of B7, B22 and B17 but no zone corresponding to B27 could be detected indicating that the epitope in free B27 chains is more sensitive to denaturation by SDS. Thus, our main finding is that the interaction of HLA-B27 heavy chain with beta(2)-microglobulin appears to be stronger than that of the other HLA-B chains. The resistance of the HLA-B27/beta(2)-microglobulin complex to the SDS dissociation is strikingly similar to the behavior of MHC class II molecules under similar conditions. Thus, it may be speculated that HLA-B27 complexes can be also more stable than other MHC class I molecules under more physiological dissociative conditions (e.g. in endosomal compartments). This feature might potentially influence antigen presentation by HLA-B27 and contribute to the well known disease linkage of HLA-B27.

Animals↗
PubMed1998

Histopathology of murine ankylosing enthesopathy.

Ankylosing enthesopathy is a spontaneously occurring progressive stiffening of the ankle and/or tarsal joints in mice of C57Black background. In C57BL/10 mice and mice of the same genetic background that had been made transgenic for HLA-B27, the start of the disease was detected by weekly testing for decreased mobility in the ankle/tarsus region. Ankylosing enthesopathy was found to begin with a short phase of proliferative inflammation of the joints and adjacent tissues, with some fibrinous exsudation, some leucocytic infiltration and slight bone erosion. This inflammation is soon accompanied and followed by proliferation of cartilaginous cells at the bone insertions of joint capsule ligaments (entheses). Ossification of the cartilage proliferations and some desmal ossification lead to large osteophytes that inhibit mobility. Fusion of osteophytes occasionally leads to marginal ankylosis. The histopathology of the successive stages of murine ankylosing enthesopathy and the preponderance in males and HLA-B27 transgenic mice are reminiscent of ankylosing spondylitis in man. The spine, however, was not affected.

Animals↗
PubMed1996

Solitary caging protects mice from ankylosing enthesopathy.

Murine ankylosing enthesopathy (ANKENT) is a spontaneous joint disease with numerous parallels to the human seronegative spondylarthropathies at the level of disease distribution, genetics and pathology. Although several genetic susceptibility factors have been identified previously, there is variation in disease susceptibility among genetically identical individuals, living in a stable environment. Preliminary observations indicate that males housed together with females rarely develop the disease, in contrast to males housed with other males (p < 0.25, p < 0.05, and p < 0.01). Furthermore, males caged under solitary conditions developed no ANKENT, whereas the disease did develop among individuals housed in groups of 4 (p < 0.01). The mechanism through which grouped caging induces a risk for ANKENT requires further study.

Animal Husbandry↗
PubMed1996

Grouped caging predisposes male mice to ankylosing enthesopathy.

OBJECTIVE: To evaluate the number of males per cage as a possible risk factor for murine ankylosing enthesopathy (ANKENT)--a spontaneous joint disease with parallels to human seronegative spondylarthropathies--since ANKENT shows incomplete penetrance of genetic susceptibility factors among individuals living in a stable environment. METHODS: Frequency of ANKENT was compared among males housed with females, with other males, or alone. RESULTS: In three independent cohorts, a trend was observed that males housed with females rarely develop the disease, in contrast to males housed with other males (P < 0.25, P < 0.05, and P < 0.01). Furthermore, no males caged alone developed ANKENT, whereas disease did occur in males grouped together (P < 0.01). When healthy males (retired breeders) were recaged either alone or with other males, ANKENT developed among the grouped males only (P < 0.005). CONCLUSIONS: Caging males together is a relative risk factor for ANKENT. Grouped caging may perturb the immune system through endocrine pathways or modify microbiological load through behaviour (for example, infection due to biting).

Animals↗
PubMed1995

HLA-B27 as a relative risk factor in ankylosing enthesopathy in transgenic mice.

HLA-B27 is a risk factor for several human diseases through a mechanism that is not yet understood. This article describes a naturally occurring joint disease in laboratory mice, ANKENT. ANKENT begins with mild inflammation and culminates in irreversible stiffening of the ankle and/or tarsal joints in one or both hind paws. The macroscopic and histologic features of ANKENT, its relationship to age, gender, and environment, and some immunologic aspects are considered. With respect to genetics, it is demonstrated that an HLA-B27 transgene is a relative risk factor for ANKENT. Its impact depends on the H-2 haplotype, reaching a relative risk value of 9.4 for C57Bl/10, H-2b males (p < 0.025). Several features of ANKENT are reminiscent of human AS: joint pathology, age and gender distribution, the presence of non-MHC as well as MHC risk factors (including HLA-B27), and the suspicion that environmental factors are involved.

Age Factors↗
PubMed1995

Maternal age influences risk for HLA-B27 associated ankylosing enthesopathy in transgenic mice.

OBJECTIVE: To study further the temporal clustering of ankylosing enthesopathy (AE) noted originally during a study of the influence of mouse major histocompatibility complex (MHC) H-2 and transgenic HLA-B27 on the frequency of AE. METHODS: The relationship between maternal age at littering and frequency of AE was analysed. RESULTS: Mice born to mothers aged eight months or older had a significantly lower disease frequency of AE than mice born to mothers younger than eight months of age. This phenomenon was observed in three independent cohorts evaluated to date (p < 0.01, 0.025, and 0.05). CONCLUSION: Maternal age is a novel, non-genetic risk factor as defined in relation to an MHC associated enthesopathy. Its mode of action and relevance to human disease require further investigation.

Animals↗
PubMed1993

New technique for sigmoid colectomy.

A combination of laparoscopic and rectoscopic procedures has enabled complete resection of the sigmoid colon and eliminated the need for minilaparotomy when constructing the anastomosis or withdrawing the specimen. This combined procedure was performed in different ways in a series of animal models until the definitive technique had been standardized. These techniques were then successfully used in 15 consecutive medium-sized pigs. Histological evaluation of the specimens, including the anastomosis (examined 2-3 weeks after operation) confirmed the efficacy and safety of the method.

Anastomosis, Surgical↗
PubMed1990

Pharmacodynamic modeling of lymphocytopenia and whole blood lymphocyte cultures in prednisolone-treated individuals.

In this study, we describe the time course of the influence of a single oral dose of prednisolone (10 mg) in man on the proliferative response of peripheral blood lymphocytes in whole blood. The data were fitted to an integrated pharmacokinetic-pharmacodynamic model, relating the plasma concentrations of prednisolone to its effect. The determination of prednisolone-induced lymphocytopenia and monocytopenia in vivo and the assessment of the influence of varying lymphocyte and monocyte numbers on proliferative responses in vitro enabled us to calculate the relative contributions of several prednisolone-induced effects to the diminished lymphoproliferative responses in whole blood after administration of prednisolone in vivo. We demonstrate that the decrease of the proliferative response in whole blood lymphocyte cultures stimulated with a monoclonal antibody directed against CD3 is mainly determined by the time course of the prednisolone-induced lymphocytopenia. The time course of the monocytopenia and the relative changes in the CD4+ and CD8+ T-cell subpopulations induced by prednisolone and the direct inhibitory effect of the changing plasma concentrations of the drug also contribute to the decrease of aCD3-stimulated whole blood lymphocyte cultures to some extent. The decrease of the proliferative response in whole blood lymphocyte cultures stimulated with a horse anti-human lymphocyte serum closely followed the time course of the lymphocytopenia induced by prednisolone. However, this response remained decreased for a longer period of time than could be expected on the basis of the prednisolone-induced lymphocytopenia in vivo. A possible mechanism which might explain this discrepancy between the prednisolone-induced effects in vivo and in vitro will be discussed.

Administration, Oral↗
PubMed1990

The influence of prednisolone on the recirculation of peripheral blood lymphocytes in vivo.

In humans and in laboratory animals, administration of a single does of glucocorticosteroids induces a rapid and transient decrease in the numbers of peripheral blood lymphocytes through a redistribution of circulating lymphocytes. This lymphocytopenic effect is an important factor in the immunosuppressive capacity of corticosteroids. We have investigated whether the redistribution is due to an increased influx of circulating lymphocytes from the blood into the lymphoid organs or to a decreased efflux from the organs. Fluoresceinated lymphocytes were injected intravenously in unrestrained normal and prednisolone-treated rabbits and the distribution curves in the peripheral blood were analysed on the basis of a two-compartment model (known from pharmacokinetic studies). In this way, it is shown that the rapid fall in peripheral blood lymphocyte numbers induced by prednisolone is due to a decreased efflux of circulating lymphocytes from the lymphoid organs. In addition, it is demonstrated that prolonged infusion of prednisolone leads to an altered distribution pattern of the circulating lymphocytes among the organs.

Animals↗
PubMed1989

The influence of cyclosporin A on the alternative pathways of human T cell activation in vitro.

To gain further insight into the mechanism of action of the immunosuppressant cyclosporin A (CyA), we investigated the influence of CyA on proliferative responses of human T lymphocytes, induced via different membrane molecules. As was previously shown, activation of T cells via the T cell receptor (Ti)/CD3 complex with an anti-CD3 monoclonal antibody was inhibited by CyA. Likewise, triggering of T lymphocytes via the alternative, CD2(T11)-mediated pathway of activation was strongly inhibited. In contrast, responses induced by phorbol myristate 13-acetate (PMA; 100 ng/ml) or the combination of an anti-CD28 monoclonal antibody and a suboptimal concentration of PMA (1 ng/ml) were found to be insensitive to CyA. CyA-induced inhibition of both anti-CD3- and anti-CD2-mediated proliferation could not be reversed by addition of either PMA (1 ng/ml) or anti-CD28. An increase in the intracellular free Ca2+ concentration [( Ca2+]i) is an early event observed after stimulation of T cells via CD3 or CD2, whereas stimulation with PMA and anti-CD28 does not lead to a rise in [Ca2+]i. This suggests that the inhibitory action of CyA is related to Ca2+-dependent signaling pathways. Since we observed that CyA does not interfere with anti-CD3- or anti-CD2-induced increases of [Ca2+]i, our data suggest that CyA-mediated inhibition is related to a later event in these intracellular signaling pathways.

Antibodies, Monoclonal↗
PubMed1989

Studies on the monocyte dependence of T-cell proliferation induced by monoclonal antibodies directed against regions I and II of the CD2 antigen.

We produced three murine monoclonal antibodies (mAb) directed against the human T-cell differentiation antigen CD2 (formerly T11) and analysed their epitope specificity by E-rosette inhibition, cross-blocking and proliferation-induction experiments. When added together, two mAb (both IgG1 kappa) were able to induce proliferation in peripheral blood T cells. This proliferation was found to be strictly dependent on the presence of monocytes. The polymorphism of Fc receptors (FcR) expressed on human monocytes for murine IgG1 antibodies, which is readily demonstrable in anti-CD3-induced T-cell activation, was not found in the anti-CD2-driven system. Moreover, mAb directed against the 40,000 MW FcRII were unable to inhibit proliferation induced by the mitogenic anti-CD2 combination. Still, F(ab')2 fragments of the mitogenic anti-CD2 antibody combination could not initiate T-cell mitogenesis, despite their ability to induce a rise in the free intracellular [Ca2+]. The contributions of monocytes and of antibody Fc moieties to T-cell proliferation, induced by combinations of anti-CD2 mAb, will be discussed.

Antibodies, Monoclonal↗
PubMed1988

Prednisolone and cyclosporin A exert differential inhibitory effects on T-cell proliferation in vitro.

To elucidate the mechanisms of action of prednisolone (pred) and cyclosporin A (CyA), we have investigated the effects of these immunosuppressive drugs on the proliferative response of human peripheral blood lymphocytes (PBMN) induced by various stimulants, well defined with regard to their monocyte dependence. We found that pred-induced inhibition of monocyte-dependent proliferative responses could be reversed by the addition of exogenous interleukin 2 (IL-2). Monocyte-independent proliferative responses were not affected by pred. These findings suggest that pred inhibits IL-2 production and subsequent lymphocyte proliferation at the level of the signal derived from the monocyte. In contrast, CyA inhibited monocyte-dependent as well as monocyte-independent proliferative responses of human PBMN. This inhibition could not be reversed by the addition of exogenous IL-2. We have previously demonstrated that CyA does not affect the expression of receptors for IL-2. Taken together, these data indicate that CyA-mediated inhibition does not primarily occur at the level of the IL-2 system, but rather affects the proliferative mechanism of the T cell itself. These data clearly demonstrate that pred and CyA act at distinct sites of the triggering process.

Antigen-Presenting Cells↗
PubMed1988

Cyclosporin A and prednisolone do not inhibit the expression of high-affinity receptors for interleukin 2.

To elucidate the mechanisms of action of cyclosporin A (CyA) and prednisolone (pred), we investigated the effects of these immunosuppressive drugs on the expression of receptors for interleukin 2 (IL-2) as well as the effect of exogenous IL-2 on CyA-inhibited and pred-inhibited responses. Pred-induced inhibition of T cell proliferative responses could be reversed by addition of exogenous IL-2. In contrast, exogenous IL-2 could not overcome CyA-mediated inhibition of T cell proliferation. Receptors for IL-2, as measured by the expression of Tac antigen, were slightly decreased by CyA and pred. However, expression of the biologically active, high-affinity IL-2 receptors was not diminished. These data suggest that pred-mediated inhibition occurs at the level of the IL-2 system, whereas CyA affects the proliferative mechanism of the T cell itself.

Adult↗