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Biomedical subjects

M Simon

Publications and source records attributed to M Simon.

At least 253 records · Page 14Linked to original sources
PubMed1995

Variational expression of functionally different macrophage markers (27E10, 25F9, RM3/1) in normal gingiva and inflammatory periodontal disease.

Keratinocytes and macrophages share under immunologically activated conditions several surface proteins. We investigated immunohistochemically with monoclonal antibodies and the APAAP technique the expression pattern of 27E10 antigen (inflammatory macrophages), 25F9 antigen (resident macrophages) and RM3/1 antigen (intermediate macrophages in healing tissue) in 29 specimen biopsies of different stages of gingivitis and periodontitis. Macrophages of each subtype exhibited a different localization pattern depending on the stage of inflammation. Furthermore, suprabasal oral gingival epithelia showed a constant 27E10 expression, independent of the stage of inflammation. In contrast, all layers of the sulcus and pocket epithelia in gingivitis and periodontitis were strongly 27E10-positive, indicating immunological activation. 25F9 antigen was expressed on basal keratinocytes independent of the stage of inflammation, whereas RM3/1 was constantly negative on keratinocytes. The expression pattern of these functionally different macrophage markers on lesional macrophages and keratinocytes indicates varying differentiation and activation and suggests a participation of these cells in the local immune response in periodontal infection.

Adult↗
PubMed1995

Significance of bacteriophages for controlling bacterioplankton growth in a mesotrophic lake.

Bacterium-specific viruses have attracted much interest in aquatic microbial ecology because they have been shown to be about 10 times more abundant than planktonic bacteria. So far most of the studies of interactions of planktonic bacteria and viruses have been done in marine environments, and very little is known about these interactions in lakes. Therefore, we studied phage proliferation in Lake Constance, a large mesotrophic lake in Germany. We enumerated bacteria and quantified the fraction of bacteria with mature intracellular phage particles and the number of free viruses by transmission electron microscopy. Between the end of March and early August 1992, peaks of bacterial abundance were followed in 1 to 2 weeks by peaks in the fraction of bacteria containing visible phage particles (0 to 1.7%) and in the number of free viruses (1 x 10(sup7) to 4 x 10(sup7) ml(sup-1)). We estimated that 1 to 17% +/- 12% of all bacteria were phage infected, implying that phage-induced mortality was <34% +/- 24% of total mortality. A direct comparison between phage-induced mortality, the net decrease of bacterial numbers, and bacterial growth rates indicated that phage-induced mortality accounted for <11% of total bacterial mortality during the phytoplankton spring bloom and 18 to 21% following the bloom. Estimated burst sizes ranged from 21 to 121 phages. Phage production rates of 0.5 x 10(sup6) to 2.5 x 10(sup6) ml(sup-1) day(sup-1) accounted for 70 to 380% of the observed net increase rates of free phages, implying high rates of simultaneous phage decay. The cyclic dynamics between bacteria and phages and the varying size structure of the intracellular mature phage particles suggested that phage infection was important in structuring the bacterial host assemblage during the study period.

Journal Article↗
PubMed1995

Expression of vascular endothelial growth factor and its receptors in human renal ontogenesis and in adult kidney.

Vascular endothelial growth factor (VEGF) may modulate vascular permeability, chemotaxis for monocytes, and protease activity. In addition, VEGF may play a role in embryonic and tumor angiogenesis. In fetal mouse kidney, VEGF mRNA and protein expression have been demonstrated. This finding led to the hypothesis that VEGF might be involved in renal growth and development. To further elucidate the role of VEGF in human kidney, expression of VEGF and its receptors, the specific tyrosine kinase receptors, fit-1 and KDR, were studied. In fetal (6-24 gestational wk; mesonephros and metanephros) and adult kidney, VEGF mRNA and protein could be colocalized in glomerular epithelia and collecting duct cells by in situ hybridization and immunohistology. By reverse transcription-polymerase chain reaction, mRNA of three VEGF isoforms, VEGF121, VEGF165, and VEGF189, were found in fetal kidney and cortex, isolated glomeruli, and medulla of adult human kidney. KDR and flt-1 mRNA were coexpressed in endothelia of glomeruli and in peritubular capillaries in fetal and adult kidney. These data support the assumption that VEGF and its receptors may influence renal ontogenesis. We speculate that the constitutive expression of VEGF in adult kidney may be required for the function of VEGF receptor positive-fenestrated endothelia in glomeruli and postglomerular vessels. The expression of VEGF in collecting duct and of its receptors in medullary capillaries may in addition be relevant for maintaining medullary osmolality.

Aged↗
PubMed1995

The antiperinuclear factor and the so-called antikeratin antibodies are the same rheumatoid arthritis-specific autoantibodies.

The so-called antikeratin antibodies (AKA) and the antiperinuclear factor (APF) are the most specific serological markers of RA. Using indirect immunofluorescence, AKA label the stratum corneum of various cornified epithelia and APF the keratohyalin granules of human buccal mucosa epithelium. We recently demonstrated that AKA recognize human epidermal filaggrin. Here, we report the identification of the major APF antigen as a diffuse protein band of 200-400 kD. This protein is seen to be closely related to human epidermal (pro) filaggrin since it was recognized by four antifilaggrin mAbs specific for different epitopes, and since the APF titers of RA sera were found to be correlated to their AKA titers and to their immunoblotting reactivities to filaggrin. Immunoabsorption of RA sera on purified epidermal filaggrin abolished their reactivities to the granules of buccal epithelial cells and to the 200-400-kD antigen. Moreover, antifilaggrin autoantibodies, i.e., AKA, affinity purified from RA sera, were shown to immunodetect the 200-400-kD antigen and to stain these granules. These results indicate that AKA and APF are largely the same autoantibodies. They recognize human epidermal filaggrin and (pro) filaggrin-related proteins of buccal epithelial cells. Identification of the epitopes recognized by these autoantibodies, which we propose to name antifilaggrin autoantibodies, will certainly open new paths of research into the pathophysiology of RA.

Antibodies, Antinuclear↗
PubMed1995

TGF beta promotes the basal phenotype of epidermal keratinocytes: transcriptional induction of K#5 and K#14 keratin genes.

TGFbeta is an important regulator of epidermal keratinocyte function because it suppresses cell proliferation, while it induces synthesis of extracellular matrix proteins and their cells surface receptors. To examine whether TGFbeta affects synthesis of intracellular proteins as well, specifically the transcription of keratin genes, we transfected a series of DNA constructs that contain keratin gene promoters into human epidermal keratinocytes. The transfected cells were grown in the presence and absence of TGFbeta. We found that TGFbeta specifically induces transcription controlled by the promoters of K#5 and K#14 keratin genes, markers of basal cells. No other keratin gene promoters were induced. The effect of TGFbeta is concentration-dependent, can be demonstrated in HeLa cells, does not depend on keratinocyte growth conditions and can be elicited by both TGFbeta1 and TGFbeta2. We conclude that TGFbeta promotes the basal cell phenotype in stratified epithelia such as the epidermis.

3T3 Cells↗
PubMed1995

Evidence for clonal spread in the development of multiple meningiomas.

Meningiomas are common intracranial tumors that arise from the arachnoid cells of the meninges. Occasionally patients develop multiple meningiomas. Because the underlying mechanism of multiple meningioma formation is unknown, the authors examined the pattern of X chromosome inactivation in multiple meningiomas. Fifteen intracranial meningiomas were resected in four patients with multiple meningiomas to determine whether the tumors in patients with multiple meningiomas originate from a common progenitor cell or arise independently. Specimens were examined using polymerase chain reaction assays to detect the pattern of X chromosome inactivation. In each patient, all tumors showed inactivation of the same X chromosome, suggesting that tumors arose from the same clone of cells (p < 0.0005). The authors conclude that multiple meningiomas arise from the uncontrolled spread of a single progenitor cell.

Alleles↗
PubMed1995

Operations improvement and reengineering at Ohio State University Medical Center.

Rising costs and increasing competition have forced hospitals to respond to the needs of their customers. At Ohio State University Medical Center, operations improvement and reengineering are being used to redesign processes and to position the medical center competitively in today's changing environment. An operations improvement team identified business processes with the greatest opportunity for positive impact based on the goals of the medical center. Next, these areas were prioritized and teams appointed to begin the reengineering process. Reengineering methods focused on specific outcomes, including improved patient satisfaction, reduced cost, and improved clinical and service quality. Throughout the process, the goals and successes of reengineering were communicated to the organization and community.

Academic Medical Centers↗
PubMed1995

Genetic instability of a dinucleotide repeat-rich region in three hematologic malignancies.

Microsatellite instability is a newly identified mechanism of mutation that occurs in some heritable neurological and muscular disorders, as well as in an increasing number of human cancers. To extend previous data, we examined the genetic instability of a human genomic region, termed S3/1, which we isolated from a human DNA library. The S3/1 sequence contains a stretch with exceptionally high numbers of (GA)n and (CA)n dinucleotide repeats. An interesting rearranged pattern emerged from Southern blot analysis of genomic DNA from three patients with different hematopoietic proliferative diseases out of 69 analyzed (one case of essential thrombocytosis (ET), one of chronic myelogenous leukemia (CML) and one of acute myelogenous leukemia (AML)). The CML and ET patients showed a deletion of 300 to 400 base pairs (bp), and the AML an insertion of about 600 bp, involving the S3/1 locus. Amplification of the rearranged fragments confirmed these observations, and enabled a precise analysis of the region involved. In normal individuals, no gross rearrangements involving this region could be detected. Analysis of DNA from three consecutive bone marrow biopsies of the CML patient disclosed that the genetic alteration affecting S3/1 was no longer detectable following alpha 2-interferon therapy, neither by Southern blot nor by polymerase chain reaction (PCR), thus confirming the tumor-specificity of the alteration; in the same patient, moreover, two out of five other analyzed microsatellites showed tumor-specific alleles, suggesting a more generalized genetic instability in the leukemic cells. These results demonstrate genetic instability of a region containing high numbers of short dinucleotide repeats in a small percentage (4%) of human hematopoietic proliferative disorders.

Acute Disease↗
PubMed1995

[Association between BoLA antigens and bovine mastitis].

The association between BoLA class I antigens and mastitis was studied in Bohemian Pied breed (n = 17) and its crosses--Bohemian Pied x Red Pied Holstein (n = 161), Bohemian Pied x Red Pied Holstein x Ayrshire (37). The diagnostics of mastitis was followed in the course of two years and two diagnostic parameters were included: 1. a modified California Mastitis Test (CMT) was performed once a month; 2. a bacteriological infection was examined once quarterly using biochemical and serological methods. BoLA class I antigens were determined by specific antisera in the standard microlymphocytotoxicity test. During testing the majority of cows had at least one positive reaction of CMT test. The bacterial findings were detected in 31.63% of animals. The antigen A16 was found to be significantly associated with susceptibility to mastitis in both diagnostic tests. Animals A16 positive showed the highest CMT values and repeated bacterial infections (Fig. 1). The high values observed in A2 positive animals were not significant due to the very low frequency of this allele in the population under study. There was a slight increase of CMT values and the infection frequency in animals with higher parity number (Fig. 2). However, the order of lactations did not influence the relationship of BoLA A16 and mastitis. This association was not significantly affected by the breed. The increased bacterial infection observed in the Bohemian Pied breed is likely due to relatively high incidence of A16 allele rather than to breed differences (Fig. 3).

Animals↗
PubMed1994

[Skin as an immune system].

Skin consists of three structurally and functionally distinct compartments containing resident and nonresident cells. These cells cooperative with humoral pathway of immune system in defence of healthy skin. Resident and nonresident cells are able to initiate inflammatory or immune processes of skin, although interstitial reactions (activation by bacteria, immunoglobulin or complement) also take place in such processes. In normal conditions nonresident cells can migrate through vascular endothel, however, PMN granulocytes and B lymphocytes cannot. Resident and nonresident cells of skin are capable of exerting a wide range of immunomodulatory effects, among them keratinocytes are of distinguished significance producing arachidon metabolites and IL-1 as well. Activated skin cells might induce chemotactic migration of distinct white blood cells normally absent or only a few cells being present in healthy skin. Cell migration into the interstitial space of skin is mediated by adhesion molecules expressed on cell surface of migrating cells, vascular endothel cells and on keratinocytes. Composition and density of adhesion molecules vary by type of stimuli, therefore various cytokines might induce distinct reactions mediated by certain population of cells. In addition, initiation and progress of immune- or inflammatory reactions are determined by the involved cell-populations as well. Normal regulation provides appropriate control and termination of the reaction, however, uncontrolled regulation results in development of pathological state.

Adjuvants, Immunologic↗
PubMed1994

[Complete remission in acute promyelocytic leukemia. The advantages of all-trans-retinoic acid compared to conventional chemotherapy].

In all of seven patients (six men, one woman; mean age 43 [24-55] years) with newly diagnosed acute promyelocytic leukaemia, treated between 1989 and 1993, complete remission was achieved. In three of these patients, treated between 1989 and 1991, remission was induced with conventional chemotherapy (cytarabine and anthracycline), after this in four patients with all-trans retinoic acid (tretinoin). The seventh patient who had a very rapid increase in leucocytes during tretinoin administration, was as a precaution also given conventional chemotherapy. All seven patients received consolidating chemotherapy with an intensive treatment cycle. Retrospective analysis indicated that induction with tretinoin had marked advantages: quicker regression of the clotting abnormalities (mean of 9 vs 25 days), shorter period of leukopenia (mean of 3.5 vs 30 days), shorter time until complete remission (mean of 38 vs 48 days). There were no specific side effects ascribable to tretinoin. Toxicity after chemotherapy corresponded to WHO grades 2-4. The results indicate that tretinoin markedly reduces the two main risks in the treatment of acute promyelocytic leukaemia: bleeding and infection.

Adult↗
PubMed1994

Sequence and functional expression of an amphibian water channel, FA-CHIP: a new member of the MIP family.

A new member of the family of water channel proteins (aquaporin-CHIP) related to the major intrinsic protein (MIP) family is described. The cDNA coding for this amphibian CHIP was cloned from frog (Rana esculenta) urinary bladder, a model for the kidney collecting duct, using a RT-PCR cloning strategy. The encoded protein, designated FA-CHIP (frog aquaporin-CHIP), shows 77.4%, 42.4% and 35.6% identity with the three proteins now referred to as the aquaporins of the MIP family, i.e., human CHIP28, WCH-CD and gamma-TIP, respectively. Xenopus leavis injected with FA-CHIP cRNA exhibited a marked increase of the osmotic water permeability.

Amino Acid Sequence↗
PubMed1994

Laryngeal carcinoma in a 12-year-old child. Association with human papillomavirus 18 and 33.

OBJECTIVE: A laryngeal squamous cell carcinoma was observed in a 12-year-old child. There was no history of preceding papillomatosis or radiotherapy. We searched for an association with human papillomavirus (HPV). METHODS: The resected specimens were assayed for infection with HPV types 11, 16, 18, 31, 33, 35, 39, 42 by in situ hybridization, and for HPV types 6, 16, 18, 33 by Southern blotting. In addition, cervical swabs of the mother were examined for HPV infection by filter in situ hybridization. RESULTS: Coinfection by HPV types 18 and 33 could be demonstrated by in situ hybridization, with homogeneous infection of both tumor and adjacent epithelial cells by HPV 33 and focal infection of only invasive cancer by HPV 18. Southern blot testing confirmed a high viral copy number of HPV 18 DNA. Examination of the mother at the time of tumor diagnosis revealed no evidence of HPV-related lesion in the lower genital tract. CONCLUSIONS: In this child, coinfection by at least two HPV types is the only evaluable risk factor for laryngeal carcinoma. Coinfection by two HPV types might substitute for carcinogenic cofactors normally present in adult laryngeal carcinomas.

Blotting, Southern↗
PubMed1994

[The expression pattern of adhesion molecules in PUVA treated lichen planus patients].

Biopsy specimens of involved and uninvolved skin were studied in four patients suffering from generalized lichen planus (LP) before and after successful oral PUVA treatment with murine monoclonal antibodies against several cellular adhesion molecules. In contrast to untreated LP lesions, in biopsies obtained after PUVA therapy from healed involved skin we found markedly diminished to completely absent expression of CD54(ICAM-1), HLA-DR, CD11a/18(LFA-1) and CD49f(VLA-6) on keratinocytes and an effective loss of CD49a(VLA-1)-, CD49c(VLA-3)-, CD49d(VLA-4)-, CD49f(VLA-6)-, CD3- and CD8-positive infiltrating cells. Our data demonstrate the influence of PUVA on cell-cell and cell-matrix adhesion in patients with LP.

Adult↗
PubMed1994

["Granulomatous slack skin"--cutaneous elastolytic lymphoma].

The term "granulomatous slack skin" (GSS) was introduced by Ackerman for a disease first described by Convit et al. in 1973. GSS represents a rare cutaneous lymphoma characterized by localized elastolytic lesions with a granulomatous infiltrate. We recently observed two male patients with the characteristic features of this disease. Both patients responded well to therapy with interferon-alpha 2b. In one patient clinical remission was stable under long-term treatment with clofazimine. We report on common features of these two patients and give a review of the cases published in the literature.

Biopsy↗