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Biomedical subjects

M Castell

Publications and source records attributed to M Castell.

At least 19 recordsLinked to original sources

Prevention of adjuvant arthritis by the W3/25 anti-CD4 monoclonal antibody is associated with a decrease of blood CD4(+)CD45RC(high) T cells.

Imbalance between Th1 and Th2 functions is considered to play a key role in the induction and development of several autoimmune diseases, and the correction of that imbalance has led to effective therapies of some experimental pathologies. To examine whether CD4(+)CD45RC(high) (Th1-like) and CD4(+)CD45RC(low) (Th2-like) lymphocytes play a role in the pathogenesis of adjuvant arthritis (AA) and in its prevention by anti-CD4 antibody, CD45RC expression on CD4(+) T cells was determined in arthritic rats and in animals treated with an anti-CD4 MoAb (W3/25) during the latency period of AA. The phenotype of regional lymph node lymphocytes from arthritic rats in the active phase of the disease was determined by flow cytometry. Peripheral blood lymphocytes from rats treated with W3/25 MoAb were also analysed for 2 weeks after immunotherapy finished. IgG2a and IgG1 isotypes of sera antibodies against the AA-inducing mycobacteria, considered to be associated with Th1 and Th2 responses, respectively, were also determined by ELISA techniques. Fourteen days after arthritis induction, regional lymph nodes presented an increase in CD4+CD45RC(high) T cell proportion. Preventive immunotherapy with W3/25 MoAb inhibited the external signs of arthritis and produced a specific decrease in blood CD4(+)CD45RC(high) T cells and a diminution of antibodies against mycobacteria, more marked for IgG2a than for IgG1 isotype. These results indicate a possible role of CD4(+)CD45RC(high) T lymphocytes in the pathogenesis of AA, and suggest that the success of anti-CD4 treatment is due to a specific effect on CD4(+)CD45RC(high) T subset that could be associated with a decrease in Th1 activity.

Animals↗

[Bone metastasis from gastrinoma without hepatic involvement. Utility of the scintigraphy with 111 In-pentetreotide].

The case of a 54 year old patient suffering from gastrinoma (within a type I multiple endocrine neoplasm) is presented. In 1990, she underwent a surgical resection. Eight years later, she suffered from a pain in the left thigh. The 99mTc-MDP bone scintigraphy showed bone metastasis. The CT scan did not show any hepatic involvement and the scintigraphy with 111In-Pentetreotide verified bone metastasis of a neuroendocrine tumor as a single expression of the recidive. In this case, the utility of the scintigraphy with octreotide to facilitate the localization and extent of the neuroendocrine tumors is demonstrated.

Adrenalectomy↗

Immunohistochemical study of lymphoid tissues in adjuvant arthritis (AA) by image analysis; relationship with synovial lesions.

The aim of this study was to examine leucocyte populations in lymphoid organs during AA and to ascertain the relationship with lesions in synovial joints. Popliteal lymph nodes, spleen and knee synovial membranes were removed from both healthy and AA rats at intervals of 3-4 days over a 3-week period. Cryostat sections were stained with MoAbs directed against lymphocyte and macrophage subpopulations, and studied by image analysis. Throughout the arthritic period, high numbers of ED1+ and ED3+ macrophages were seen in both lymphoid compartments and intercellular adhesion molecule-1 (ICAM-1) expression also increased in some zones of lymph nodes and spleen. The percentages of CD4+ and CD8+ cells rose in the splenic zones studied but fell in the lymph node cortex. Very few natural killer (NK) cells were found in lymphoid tissues, but the number rose after AA induction. In synovia from AA rats, ED2+ macrophages proliferated but alpha/beta T cell infiltration was only occasionally observed, accompanied by ED1+ cells and ICAM-1 expression. In conclusion, synovitis developing after AA induction seems to be caused directly by macrophages and indirectly by lymphocytes placed both in popliteal lymph nodes and spleen.

Animals↗

An image analysis strategy to determine the distribution of cell types in spleen sections.

An image analysis strategy was designed to objectively determine distribution patterns of cell types in spleen sections. The strategy was applied to rat spleen cryostat sections that were strained immunohistochemically by means of monoclonal antibodies against different populations of lymphocytes and macrophages. The strategy revealed three segments of the spleen beginning in the middle of a central arteriole and ending within the red pulp. In each of these segments, three consecutive zones were established: the white pulp, the marginal zone, and the red pulp. In each tissue section, three segments were selected starting in two different arterioles. Consequently, six segments were analysed in each section. Special software was used to calculate percentages of positive staining in all zones in each segment. Image analysis data for each monoclonal antibody tested correlated closely with microscopical observations. The proposed strategy allows objective quantification of lymphocyte and macrophage populations and their distribution patterns. It is an useful tool for studying imbalances in cell populations in the spleen due to immune challenges.

Animals↗

Surgical treatment of oligosymptomatic mitral valve incompetence?.

OBJECTIVE: Despite improvements of the surgical technique in NYHA (III)-(IV) mitral valve incompetence (MVI) postoperative long-term results remain poor. As long-term results reflect primarily the ventricular function rather than the quality of the surgical technique the contractile performance of isolated papillary muscles obtained from patients undergoing mitral valve replacement for MVI (n = 25) was analysed in detail. METHODS: Muscle preparations (0.4 x 5.0 mm) obtained from left ventricular papillary muscles (NYHA (I), n = 4; NYHA (II), n = 7; NYHA (III), n = 8; NYHA (IV), n = 6) were loaded for intracellular calcium measurements with FURA-2, stretched to optimal length (Lmax) and electrically stimulated with frequencies ranging from 30 to 180 beats/min (b.p.m.) (10% above threshold, 37 degrees C, Krebs-Henseleit solution). Isometric force development and diastolic intracellular calcium (measured by the 'ratio method'; excitation light: wavelengths alternating 340 and 380 nm, frequency: 250 Hz) were simultaneously recorded as a function of the stimulation frequency. RESULTS: At 60 b.p.m. force development was significantly higher in NYHA (I) myocardium (21.3 +/- 2.8 mN/mm2) than in NYHA (III) myocardium (12.8 +/- 2.2 mN/mm2), (P < 0.0001). In NYHA (I) myocardium force rose with increasing stimulation frequency ('positive staircase'). In contrast the stimulation frequency associated with maximum force was shifted towards lower frequencies in NYHA (II)-(IV) myocardium ('negative staircase'). As compared with NYHA (I) myocardium diastolic intracellular calcium was significantly elevated at 150 b.p.m. in NYHA (II)-(IV) myocardium (P < 0.01). CONCLUSION: The data show, that severe impairment of contractile function ('negative staircase phenomenon', reduced force, elevated diastolic calcium) is present in MVI classified as NYHA (III)-(IV) that may explain the poor long-term results. Most interestingly the data argue for a significant impairment of myocardial function even in NYHA (II) MVI. The results suggest an early surgical treatment of mitral valve incompetence as long as the myocardial function is normal (NYHA (I)) as (1) a reduced perioperative risk, (2) improved long-term results, and (3) a higher probability for mitral valve repair (instead of replacement) may be expected in these early stages of mitral valve disease.

Biopsy, Needle↗

Alterations of lymphocyte populations in lymph nodes but not in spleen during the latency period of adjuvant arthritis.

The aim of this study was to analyze potential imbalances in lymphocyte populations from regional lymph nodes (LN) and spleen occurring before the development of the outer inflammation of adjuvant arthritis (AA). Percentages and absolute numbers of CD5+, CD4+, CD8+, Ig+, I-A+, NKR-P1+ and TCRgammadelta+ cells were determined. No differences in percentages of gammadelta T or NK cells were found either in LN or spleen, thus ruling out an important role of these minor subpopulations in these early stages of AA. While no significant lymphocyte imbalances were observed in spleen, an increase in the percentage of B lymphocytes was found in regional LN. Moreover, a high proliferation of CD8+ cells was observed when measuring absolute numbers of LN lymphocytes, thus producing an imbalance in the CD4/CD8 ratio at very early stages of the inflammatory process. These findings suggest a role for CD8+ and B lymphocytes in the latency period of AA at the LN level. Our results indicate a primary role for lymph nodes in initiating the inflammation of AA, whereas cells from the spleen probably play a secondary role.

Animals↗