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Biomedical subjects

M Simon

Publications and source records attributed to M Simon.

At least 163 records · Page 9Linked to original sources

Expression of corneodesmosin in the granular layer and stratum corneum of normal and diseased epidermis.

The stratum corneum (SC) has long been considered as a sort of inert membrane destined to be shed at the surface of the epidermis. During the last two decades, however, several lines of evidence have been reported, suggesting that active physical and chemical changes take place in the horny layer despite the absence of intracytoplasmic organelles. In particular, processing of filaggrin, replacement of the plasma membrane by a ceramide envelope and constant, progressive modification of extracellular lipid multilayers have been put forward. Recently, attention has focused on the intercellular junctions, which may be involved in the regulation of SC desquamation. Corneodesmosin, a newly discovered protein of s.c. desmosomes (corneodesmosomes), is synthesized at the latest stages of keratinocyte differentiation and persists between the horny cells until desquamation occurs. In the present study, we performed immunohistochemical and immuno-ultrastructural investigations on corneodesmosin expression in various skin lesions characterized by abnormal production and/or retention of the horny layer. Our results suggest that corneodesmosin expression is independent from profilaggrin synthesis. We found corneodesmosin in almost all morphologically recognizable corneodesmosomal structures and specifically those which persisted up to the SC surface. Hyperkeratotic lesions which are characterized by an increased number of junctions showed intense immunoreactivity with anticorneodesmosin antibody. A complete absence of corneodesmosin was not observed in any disease. This finding, together with our previous biochemical studies, suggests that corneodesmosin may exert a protective function against proteolytic degradation of corneodesmosomes both in normal skin and in the pathological horny layer.

Antibodies, Monoclonal↗

An optimization study on unprogrammed cryopreservation of human CD34+ bone marrow cells and their subsequent storage in an -80 degrees C mechanical freezer.

Among the factors which enable successful bone marrow transplantation, the ability to store and subsequently recover sufficient viable marrow cells to reestablish hematopoiesis is crucial. In most centers, marrow is typically prepared for long term storage by programmed, controlled rate freezing with subsequent placement into the vapor phase of liquid nitrogen. Though clearly effective, this procedure is time consuming and equipment intensive. Since cost containment is an important issue for all medical procedures, we evaluated the utility of a faster and less costly method to accomplish the same purpose. We found that when CD34+ bone marrow cells are immediately frozen and stored at -80 degrees C, the number and quality of stem/progenitor cells recovered after thawing was comparable to those reported recovered after conventional processing. Herein we report optimized conditions for cryopreserving and storing CD34+ bone marrow cells at -80 degrees C and for subsequent thawing of the stored product. With these methods post-thaw recovery of CFU-Mix, for example, equaled or exceeded 80% of predicted numbers, even after six months of storage. Further, though progenitor cell recovery does not necessarily correlate with speed of engraftment, these results nonetheless suggest that storage of human CD34+ cells at -80 degrees C in a mechanical freezer is a convenient, inexpensive, and reliable method for storing marrow for transplantation.

Antigens, CD34↗

Prognostic factors in agnogenic myeloid metaplasia: a report on 195 cases with a new scoring system.

We studied the survival of 195 patients with agnogenic myeloid metaplasia (AMM) diagnosed between 1962 and 1992 in an attempt to stratify patients into risk groups. Median survival was 42 months. Adverse prognostic factors for survival were age > 60 years, hepatomegaly, weight loss, low hemoglobin level (Hb), low or very high leukocyte count (WBC), high percentage of circulating blasts, male sex, and low platelet count. A new scoring system based on two adverse prognostic factors, namely Hb < 10 g/dL and WBC < 4 or > 30 x 10(9)/L, was able to separate patients in three groups with low (0 factor), intermediate (1 factor), and high (2 factors) risks, associated with a median survival of 93, 26, and 13 months, respectively. An abnormal karyotype (32 cases of 94 tested patients) was associated with a short survival, especially in the low-risk group (median survival of 50 v 112 months in patients with normal karyotype). The prognostic factors for acute conversion were WBC > 30 x 10(9)/L and abnormal karyotype. Thus, hemoglobin level and leukocyte count provide a simple prognostic model for survival in AMM, and the adverse prognostic value of abnormal karyotype may be related to a higher rate of acute conversion.

Adult↗

Evidence that filaggrin is a component of cornified cell envelopes in human plantar epidermis.

Cornified cell envelope (CE) is generated during the late stages of epidermal differentiation and is made up of proteins covalently linked together by transglutaminases. To determine whether filaggrin is a component of this structure in humans, we analysed highly purified CE from plantar stratum corneum. An immunoelectron microscopy analysis showed specific binding of four different anti-(pro)filaggrin monoclonal antibodies to the surface of the CE, proved previously to be free of non-covalently linked proteins. Moreover, the anti-filaggrin activity of one of the antibodies was absorbed by preincubation with the plantar CE, as determined by ELISA. Convincingly, fragments of CE produced by proteolytic digestion of the structures were stained by this antibody on immunoblots. These data provide direct evidence that filaggrin is a component of CE purified from human plantar stratum corneum. Cross-linking between CE and the filaggrin-containing fibrous matrix may enhance the structural cohesion of the corneocytes and thus the resistance of the stratum corneum.

Antibodies, Monoclonal↗

Role of genomic instability in meningioma progression.

Microsatellite length instability, probably resulting from defective DNA mismatch repair mechanisms, has been described in a variety of cancers. Such genetic instability may play a significant role in tumor formation and progression. To investigate the role of microsatellite alterations in meningioma tumorigenesis and progression, we examined 33 microsatellite markers on nine chromosomes for abnormalities in 18 benign, 15 atypical, and 11 malignant meningiomas. In each tumor, at least 15 markers were investigated. Microsatellite instability was not detected in any of the cases examined. However, loss of heterozygosity for markers from various chromosomes was seen frequently among atypical and malignant meningiomas. Although some of these chromosomal losses might represent random events, our data also indicate a role for specific loci on chromosome arms 14q, 1p, 10q, and possibly 9p in the development of malignancy in meningiomas. Our results argue against a significant role for a generalized microsatellite instability phenotype in meningiomas, but they suggest that genomic instability resulting in frequent allelic deletions may contribute to meningioma progression.

Alleles↗

The impact of the Medicare Influenza Demonstration Project on influenza vaccination in a county in Massachusetts, 1988-1992.

Influenza and related pneumonia continue to cause significant amounts of morbidity and mortality despite the availability of effective vaccines. Two comparable counties in Massachusetts served as project areas of a national trial to see if reimbursement for immunizing Medicare-B eligible recipients against influenza would increase the use of the vaccine and reduce the costs attributed to related morbidity. Providers of health and social services to elders were recruited to participate in one county. A variety of professional and public education campaigns and media were used to promote influenza immunizations. Laboratory-based surveillance was instituted in both counties to assess the extent of circulating virus in each. Vaccine was made available to medical providers in both counties. While the amount of vaccine used in the comparison county increased by 6% from pre-project time (16,000 to 17,000 doses administered), vaccine use increased 219% in the intervention county (21,250 to 46,494 doses administered). In a post-project survey of participating physicians, 88% of 238 respondents reported administering less than 100 doses of influenza vaccine per year prior to the project. By the end of the project, only 32% administered less than 100 in the previous year. This project demonstrated the need for educating both the provider and the public in order to successfully promote immunizations. It was not clear, however, if reimbursement was a more important factor for promoting influenza immunizations than was universal distribution of free vaccine.

Aged↗

[Detection of clonality of cutaneous T-cell lymphomas using polymerase chain reaction].

Differentiation of a cutaneous lymphoma from a reactive lymphoid infiltrate is a demanding challenge for the pathologist. In this retrospective study we examined 24 paraffin-embedded tissue samples from lesions diagnosed as lymphomas and 7 control samples of skin affected by benign changes and with pronounced lymphoid infiltrates for clonal rearrangement of the gamma T-cell-receptor. Using PCR technology we demonstrated clonality in 22 cases of lymphoma (92%). Thus, the primer combination used in this study covering the four main groups (I-IV) of the variable region of the gamma T-cell receptor gene allows high sensitivity. No clonality was demonstrable in any of the 7 control cases. This study demonstrates the growing importance of PCR technology for the diagnosis of lymphoma.

Cell Transformation, Neoplastic↗

Ruminant cluster WC13.

Five monoclonal antibodies (mAbs) belonged to preliminary cluster 27; however, only two mAbs, Buf13 (3W-506) and Co-3D1D4 (3W-202), were shown to detect the same surface antigen and belong to WC13. The other three mAbs, IVA120 (3W-323), IVA197 (3W-533) and IVA198 (3W-290), detected a 45 kDa molecule that could be fibrinogen (Mateo A., Perez de la Lastra, J., Moreno, A., Dusinsky, R., Bilka, F., Simon, M., Horovska, L., Naessens, J. and Llanes, D., 1996. Biochemical characterization of antigens detected with anti-platelet monoclonal antibodies. Vet. Immunol. Immunopathol., 52: 363-370; Perez de la Lastra, J.M., Mateo, Dusinsky, R., Bilka, Simon, M., Horovska, L. and Llanes, D., 1996. Two monoclonal antibodies from the platelet panel recognize sheep plasma fibronigen. Vet. Immunol. Immunopathol., 52:).

Animals↗

Biochemical characterization of antigens detected with anti-platelet monoclonal antibodies.

A panel of 18 monoclonal antibodies (mAbs) defined by the third workshop as specific for platelets, clustered in three preliminary groups: PC7, PC13 and PC27. These mAbs were further analysed by immunoprecipitation using extracts of iodinated and biotinylated peripheral blood mononucleated cells (PBMC) and platelets. We could confirm the existence of mAbs with specificities to WC9 (in PC7) and CD41/61 (in PC13). Two mAbs formed a new cluster, WC13, which may be homologous to human CD31 (in PC27). The influence of EDTA and thrombin on the expression of the different antigens on the platelet membrane was assessed by flow cytometry (FCM) analysis, as well as cross-reactivity with platelets from different species.

Animals↗

Two monoclonal antibodies from the platelet panel recognize sheep plasma fibrinogen.

Among the monoclonal antibodies (mAbs) submitted to the third Workshop, two mAbs, IVA120 (3W-323) and IVA198 (3W-290), could be identified to recognize the sheep fibrinogen molecule. The apparent molecular weight of the immunoprecipitated 48-60 kDa cell surface protein under reducing conditions suggested this antigen could be the fibrinogen molecule. ELISA and immunoblotting assays, performed with commercially available sheep plasma fibrinogen, confirmed that these two mAbs recognize two different epitopes present on the sheep fibrinogen molecule.

Animals↗