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Biomedical subjects

M Simon

Publications and source records attributed to M Simon.

At least 217 records · Page 12Linked to original sources
PubMed1996

all-trans-retinoic acid regulates retinol and 3,4-didehydroretinol metabolism in cultured human epidermal keratinocytes.

The potential for all-trans-retinoic acid to regulate the metabolism of 3H-retinol and 3H-3,4-didehydroretinol was examined in cultured human epidermal keratinocytes. Confluent cultures were treated daily with medium containing 5% fetal bovine serum or the same medium supplemented with nanomolar concentrations of all-trans-retinoic acid for up to 3 d. During the last 24 of treatment, cells were incubated with 3H-retinol or 3H-3,4-didehydroretinol for 24 h (isotopic steady state) to label the endogenous retinoids. After the labeling period, one group of cells was harvested and another group was allowed to incubate for an additional 24 h in the absence of medium retinol for the determination of endogenous 3H-retinoid utilization. The 3H-retinoids present in cells were extracted and quantitated by reverse-phased high-pressure liquid chromatography. Keratinocytes treated with retinoic acid and labeled with 3H-retinol exhibited time- and concentration-dependent (i) increases in retinyl ester mass, (ii) increases in the rate of retinyl ester synthesis, (iii) decreases in retinyl ester utilization, and (iv) decreases in the cellular concentrations of retinoic and 3,4-didehydroretinoic acids. There was no effect of exogenous retinoic acid on its own metabolism. Cells labeled with 3H-3,4-didehydroretinol exhibited exclusive labeling of vitamin A2-related retinoids suggesting that the A1 to A2 conversion is not reversible. Treatment of cells with low nanomolar concentrations of retinoic acid decreased the utilization of 3,4-didehydroretinyl esters, decreased the production of 3,4-didehydroretinoic acid but had no effect on the synthesis of 3,4-didehydroretinol or its esters. The results demonstrate that keratinocytes respond to extracellular retinoic acid by decreasing endogenous production of active retinoids, sequestering extracellular substrate retinol as retinyl ester, and decreasing ester utilization.

Adult↗
PubMed1996

Thrombospondin receptor (CD36) expression of human keratinocytes during wound healing in a SCID mouse/human skin repair model.

Using a human skin/severe combined immunodeficient (SCID) chimeric mouse model, we examined the keratinocyte expression of the thrombospondin receptor (CD36) and its ligand thrombospondin-1 (TSP1) in acute uninflamed wounds. Positive suprabasal keratinocyte expression of CD36 was observed as early as 30 minutes after wounding in the adjacent, intact epidermis; it disappeared 4 days later. Keratinocytes of the freshly re-epithelised wounds and those of the surrounding epidermis remained TSP1-negative throughout the whole observation period of 7 days. Our results indicate that CD36-positive keratinocytes, probably in connection with activated, TSP1-positive thrombocytes, may play an important role in the early phase of wound healing.

Animals↗
PubMed1996

T-cell-rich B-cell lymphoma presenting in skin. A clinicopathologic analysis of six cases.

We reviewed our experience with six T-cell-rich B-cell lymphomas (TRBL) presenting in skin. Immunohistochemical studies were performed on all biopsies. The lymphoid population consisted mainly of CD3 and/or UCHL-1 (CD45RO) positive T cells. 5 to 15% of the lymphoid cells stained for the B-cell marker L26 (CD20). Monoclonality of the B-cell component was demonstrated in all cases, utilizing either light chain restriction (5 cases) or clonal immunoglobulin heavy chain gene rearrangement by polymerase chain reaction (PCR) (2 cases). One case was confirmed to be monoclonal by both techniques. Additionally, no clonal rearrangements of the T-cell receptor gamma gene were observed. There was considerable morphological variety in these cases. In H&E stained sections, the differential diagnosis included pseudolymphoma, peripheral T-cell lymphoma, Hodgkin's disease, Lennert's lymphoma and a MALT lymphoma. A significant component of monoclonal plasma cells was present in 3 of 6 cases, suggesting a possible origin from cutaneous immunocytoma. In fact, one of our cases was a biphasic lymphoma displaying TRBL with a small focus of immunocytoma. We conclude that immunophenotypic analysis is necessary for the diagnosis of TRBL. Pathologists should be aware of this type of cutaneous B-cell lymphoma to avoid misinterpretation as a pseudolymphoma.

Adult↗
PubMed1996

Identification in situ and dynamics of bacteria on limnetic organic aggregates (lake snow).

Microbial assemblages on large organic aggregates (lake snow) of Lake Constance, Germany, were analyzed with rRNA-directed fluorescent oligonucleotide probes specific for the domain Bacteria and the alpha-, beta-, and gamma-subclasses of the class Proteobacteria. Lake snow aggregates were either collected in situ by SCUBA diving or in a sediment trap at 50 m or formed of natural lake water incubated in rolling cylinders under simulated in situ conditions. For the latter aggregates, the time course of the microbial colonization was also examined. The natural aggregates and those made in rolling cylinders were composed of the particulate organic material present in the lake and thus reflected the composition of the ambient plankton community. All types of lake snow aggregates examined were heavily colonized by microbial cells and harbored between 0.5 x 10(6) and > 2 x 10(6) cells aggregate -1. Between 55 and 100% of the microbial cells stained with 4', 6-diamidino-2-phenylindole (DAPI) could be visualized with the domain Bacteria-specific probe. In most samples, beta-subclass proteobacteria dominated the microbial community, constituting 27 to 42% of total cells as counted by DAPI staining, irrespective of the composition of the aggregates. During the time course experiments with the laboratory-made aggregates, the fraction of beta-subclass proteobacteria usually increased over time. Except for a few samples, alpha- and gamma-subclass proteobacteria were far less abundant than beta-subclass proteobacteria, constituting 11 to 25 and 9 to 33% of total cells, respectively. Therefore, we assume that a specific aggregate-adapted microbial community was established on the aggregates. Because the compositions of the microbial assemblages on natural and laboratory-made aggregates were similar, we conclude that aggregates made in rolling cylinders are good model system with which to examine the formation and microbial colonization of macroscopic organic aggregates.

Bacteria↗
PubMed1996

Epstein-Barr-virus-associated lymphoproliferative syndrome in severe combined immunodeficiency: establishment of a lymphoblastoid cell line as an in vitro model for biological and therapeutic studies.

Patients with primary or secondary immunodeficiency are at high risk for B cell lymphoproliferative syndromes (LPS) that are generally Epstein-Barr virus (EBV)-associated. We established a cell line, termed JuWa, from an immunoblastic lymphoma that developed in a child with severe combined immunodeficiency. JuWa cells were representative of the original lymph node as shown by a similar IgH gene rearrangement pattern. The cell line exhibited the typical features of a lymphoblastoid cell line (LCL): (1) growth pattern in large clumps, (2) lack of structural chromosome abnormalities, (3) type III latency with expression of EBV-associated EBNA2 and LMP, as well as B cell activation markers CD23 and CD30, thereby showing characteristics of an EBV producer cell line, i.e. a latent infection with a small subpopulation of cells spontaneously entering the lytic cycle, (4) inducibility of the lytic cycle by IdU and TPA, leading to an increase of early antigen and viral capsid antigen-positive cells from 1 to 15-20%, and (5) elimination of the linear viral genomes by treatment with acyclovir (ACV), without affecting the circular episomal genomes. After withdrawal of ACV, viral replication resumed within 7 days. Thus, JuWa cells support the concept of the LCL-like features of LPS and lymphomas occurring in the setting of immunodeficiency. In our in vitro model, ACV treatment could effectively suppress the viral replication but not cure EBV infection of B cells.

Acyclovir↗
PubMed1996

Outcome of risperidone therapy in elderly patients with chronic psychosis.

OBJECTIVE: This report reviews the efficacy and tolerability of risperidone therapy in elderly patients with chronic psychosis. METHODS: A computer search was conducted for all patients who were sixty-five years or older at the time of risperidone therapy at the Cleveland VAMC. Data collected included psychiatric diagnosis, risperidone dosage/side effects, concurrent medications, comorbid medical diagnosis, and response to treatment. Treatment response was quantified on a graduated scale. RESULTS: Twenty-six patients age sixty-five or older were included in this sample. Mean age of the group was 70.4 years. Mean risperidone dosage was 3.8 mg/day for a mean duration of 251 days. Eighteen of twenty-six patients (69%) had schizophrenia, two of twenty-six (8%) had schizoaffective disorder, two of twenty-six (8%) had bipolar disorder, and four of twenty-six (15%) had other psychotic disorders. Patients had a mean of 2.4 medical diagnoses in addition to their primary psychiatric diagnosis. Twenty-two of twenty-six patients (85%) had clinical improvement on risperidone, and twenty of twenty-six (77%) had improvement that was either marked or moderate. Risperidone therapy was very well tolerated in this elderly population with nineteen of twenty-six patients (73%) remaining on risperidone therapy at completion of this study. Medical illness did not appear to be worsened or complicated by risperidone therapy. CONCLUSION: Risperidone appears to be an effective and well tolerated antipsychotic for elderly patients with chronic psychosis.

Aged↗
PubMed1996

Breech infants: vaginal or cesarean delivery?

BACKGROUND: This study was undertaken to determine whether planned vaginal or elective cesarean delivery is better for singleton term breech infants and their mothers. METHODS: We studied deliveries of 388 singleton term breech infants that were born in our teaching hospital in Vienna. We follow well defined criteria for vaginal delivery versus cesarean section of term breech fetuses. We thus compared 280 (72%) cases scheduled for vaginal delivery with 108 (28%) scheduled cesarean sections with regard to neonatal mortality and morbidity, including Apgar score, umbilical artery pH, and postpartum maternal morbidity. RESULTS: Vaginally delivered fetuses of primiparas had lower five-minute Apgar scores (5% < Apgar 7) and a lower umbilical artery pH (39% below 7.2). This is significantly different from the abdominally delivered primiparas (no Apgar below 7, only 11% with an artery pH below 7.2). Multiparas did not show significantly different results with regard to Apgar scores and umbilical artery pH between the different modes of delivery. Postpartum maternal morbidity was not different between the two groups. CONCLUSION: The results suggest that planned vaginal delivery of singleton breech infants of primiparas result in newborns with lower Apgar-scores, a lower umbilical artery pH and a poorer fetal outcome. On the other hand, it seems that singleton term infants of multiparas do not profit from cesarean delivery.

Adolescent↗
PubMed1996

Protein and messenger RNA expression of connexin43 in astrocytomas: implications in brain tumor gene therapy.

The expression of connexin43, the primary gap-junction constituent of glial cells, was evaluated at the messenger RNA and protein levels in different grades of astrocytoma to investigate the relevance of gap junctions in herpes simplex virus-thymidine kinase (HSV-tk)-mediated gene therapy of brain tumors. Transduction of the retroviral-mediated HSV-tk gene into tumor cells with subsequent administration of ganciclovir has recently been used as an experimental therapeutic strategy for treatment of brain tumors. One aspect of this approach is the bystander effect, which augments the efficacy of this therapeutic approach. Glioblastoma cells with minimum levels of connexin43 protein were transfected with a connexin43 complementary DNA. These cells manifested a marked increase in the in vitro bystander effect, supporting the contention that the in vitro bystander effect is a consequence of metabolic cooperation between cells mediated by gap junctions. To assess relative levels of gap-junction protein expression in the relevant tumor type, we examined primary astrocytomas, primary astrocytoma cell cultures, and glioblastoma cell lines. Although most astrocytoma tumor samples expressed connexin43, they differed in the level of expression, with the greatest variation exhibited in high-grade astrocytomas. Primary glioblastoma cell cultures and established glioblastoma cell lines also displayed some variability in connexin43 levels. In aggregate, our results anticipate that glioblastomas will have a varied bystander effect during HSV-tk gene therapy depending on the level of connexin43 expression.

Astrocytoma↗
PubMed1996

Ultrastructural instability of paired helical filaments from corticobasal degeneration as examined by scanning transmission electron microscopy.

Paired helical filaments (PHFs) accumulate in the brains of subjects affected with Alzheimer's disease (AD) and certain other neurodegenerative disorders, including corticobasal degeneration (CBD). Electron microscope studies have shown that PHFs from CBD differ from those of AD by being wider and having a longer periodicity of the helical twist. Moreover, PHFs from CBD have been shown to be primarily composed of two rather than three highly phosphorylated polypeptides of tau (PHF-tau), with these polypeptides expressing no exons 3 and 10. To further explore the relationship between the heterogeneity of PHF-tau and the appearance of abnormal filaments, the ultrastructure and physical parameters such as mass per unit length and dimensions were compared in filaments from CBD and AD using high resolution scanning transmission electron microscopy (STEM). Filament-enriched fractions were isolated as Sarcosyl-insoluble pellets and for STEM studies, samples were freeze-dried without prior fixation or staining. Ultrastructurally, PHFs from CBD were shown to be a heterogeneous population as double- and single-stranded filaments could be identified based on their width and physical mass per unit length expressed in kilodaltons (kd) per nanometer (nm). Less abundant, double-stranded filaments had a maximal width of 29 nm and a mass per unit length of 133 kd/nm, whereas three times more abundant single-stranded filaments were 15 nm wide and bad a mass per unit length of 62 kd/nm. Double-stranded filaments also displayed a distinct axial region of less dense mass, which appeared to divide the PHFs into two protofilament-like strands. Furthermore, these filaments were frequently observed to physically separate along the long axis into two single strands or to break longitudinally. In contrast, PHFs from AD were ultrastructurally stable and uniform both in their width (22 nm) and physical mass per unit length (104 kd/nm). The ultrastructural features indicate that filaments of CBD and AD differ both in stability and packing of tau and that CBD filaments, composed of two distinct protofilaments, are more labile under STEM conditions. As fixed and stained filaments from CBD have been shown to be stable and uniform in size by conventional transmission electron microscopy, STEM studies may be particularly suitable for detecting instability of unstained and unfixed filaments. The results also suggest that molecular heterogeneity and/or post-translational modifications of tau may strongly influence the morphology and stability of abnormal filaments.

Aged↗
PubMed1996

[Evaluation of psychiatric treatment teams by relatives].

262 members of the Austrian relatives' self-help organisation HPE evaluated their experience with 12 types of psychiatric professionals and judged their satisfaction with the behaviour of these professionals on a 5-point scale corresponding to the Austrian school mark system (1 = the best mark, 5 = the worst mark). Overall the core group of psychiatric professionals-psychiatrists, psychologists and nurses-had the worst rating, while non-core professionals like occupational therapists, social workers and ambulance aids received the highest satisfaction ratings. One possible explanation for the dissatisfaction with the core psychiatric professionals is the unmet needs of the relatives for information, which 93% complained of. It is suggested to teach professionals systematically how to evaluate the needs of relatives and how to communicate with them in a more satisfying way.

Adult↗
PubMed1996

Mesenchymal cell activation is the rate-limiting step of granulation tissue induction.

During wound repair a 3-day lag occurs between injury and granulation tissue development. When full-thickness, 8-mm-round, excisional wounds were made in the paravertebral skin of outbred Yorkshire pigs and harvested at various times, no granulation tissue was observed before day 4. Day 4 wounds were 3% filled with granulation tissue, day 5 wounds 48% filled, and day 7 wounds 88% filled. The prerequisites for granulation tissue induction are not known but hypothetically include fibrin matrix maturation or cell activation. To examine whether matrix maturation was necessary, wounds were allowed to heal for 5 or 7 days and then aggressively curetted, resulting in the formation of fresh fibrin clots in the newly formed wound spaces. In contrast to original wounds, no lag phase was observed; wounds curetted on day 5 were 23% filled with granulation tissue 1 day later and 99% filled 3 days later, whereas wounds curetted on day 7 were 47% filled 1 day later and completely filled within 2 days. Thus, granulation tissue formation resumed promptly and independently of fibrin clot matrix maturation. This observation suggested that mesenchymal cell activation might be the rate-limiting step in granulation tissue formation. To address this hypothesis more directly, cultured porcine or human fibroblasts, grown to 80% confluence in Dulbecco's minimal essential medium plus 10% fetal calf serum, were added to new wounds. These wounds were sealed with a freshly made exogenous fibrin clot. In some wounds, platelet releasate was added to the fibrin clot. Granulation tissue did not form in day 3 wounds, which had received either fibrin alone, fibrin and platelet releasate, or fibrin and fibroblasts. In contrast, granulation tissue was observed in wounds receiving fibrin, human fibroblasts, and platelet releasate. By day 4, wounds receiving cultured human fibroblasts, fibrin, and platelet releasate were 14% filled with granulation tissue compared with less than 4% granulation tissue in control wounds. Thus, fibroblast activation is a limiting step of granulation tissue formation, and continued cell stimulation is required for accelerated development.

Animals↗
PubMed1996

From R&D to the mouth--a viable roadmap for the technology era.

This article serves as an overview of the status of dental technology as the profession approaches a new century. Its purpose is to define various ways in which dental manufacturers and marketers can better understand the thinking of the dental professional, those factors that influence their thought processes and how to use this information to develop more effective and predictive marketing strategies. With the advent of more complex and expensive dental technologies, e.g., video imaging, digitized radiology, electronic data transmission, etc., the dentist is faced with a variety of decisions relating to purchasing, implementation and costs/benefits analysis that go beyond the normal daily concerns of delivering competent dental care. It is no longer enough for a manufacturer to make a good product; successful marketing strategies must also include a means for guiding the dentist in the successful integration of these technologies into their offices. In order for dental marketers to meet the competitive demands of this advanced technology era, there must be a commitment to the development of strategic information through the use of third party, customized marketing research. Too much of the input currently used to develop marketing strategies is anecdotal, inherently biased and often not representative of the target market as a whole. It is hoped that this article will effectively challenge the reader to look at the development of dental products and services from a somewhat different, less traditional perspective and that it will provide the impetus and direction for creating better targeted and more rewarding marketing strategies.

Cost-Benefit Analysis↗
PubMed1996

A longitudinal study of a harlequin infant presenting clinically as non-bullous congenital ichthyosiform erythroderma.

Over the past 8 years, we have followed a child born as a harlequin baby, who survived due to treatment with retinoids. His condition evolved clinically towards the erythrodermic form of lamellar ichthyosis (non-bullous congenital ichthyosiform erythroderma, NBCIE). According to ultrastructural and biochemical criteria, our patient originally presented with type II harlequin ichthyosis. Investigations showed an abnormal keratinosome structure and extrusion, a keratin pattern characteristic for epidermal hyperproliferation, and an absence of conversion of profilaggrin to filaggrin. Persisting keratinocyte hyperproliferation, associated with the presence of a dermal infiltrate, is in agreement with the present clinical picture of severe NBCIE. However, abnormal lamellar body production and defective filaggrin processing, which is not one of the diagnostic criteria of NBCIE, persist in the patient's skin. Further studies of the epidermal lipid composition, and of possible mutations of the keratinocyte transglutaminase gene performed on epidermal cell cultures of harlequin ichthyosis, will be necessary before type II harlequin ichthyosis can be accepted as an extremely severe form of NBCIE.

Etretinate↗
PubMed1996

[Determination of physicochemical characteristics and evaluation of decontaminating efficacy and in vitro safety of cleaning products for contact lenses].

PURPOSE: This work aims to characterize products designed for cleaning contact lenses and particularly their physicochemical properties, their efficiency and their ocular irritancy potential compared to the main requirements of eye-washes. MATERIAL AND METHODS: The physicochemical controls include pH determination, viscosity and freezing point depression. In addition, we carried out the hydrogen peroxide assay for products containing this active substance. A microbiological control was performed when opening the product and after simulation of a 21-day aging. We determined the decontaminating efficacy of the products on four bacterial strains and a fungal strain. Finally, we tested their ocular allowance by an in vitro test. RESULTS: The pH values obtained ranged from 3.2 (oxygenated water solutions) to 7.6. The viscosity was close to a water solution one (about 1 centipoise). The different assays showed hydrogen peroxide content similar to that stated on the package: rate averaged to 3% and was negligible after neutralization. At opening and after simulation the bacteriological quality was excellent. Finally, decontaminating efficiency against germs was very good for the products tested. The products were classified as non-irritant by the ocular irritancy test. CONCLUSION: The results obtained show that the products tested met the reference criteria, particularly eye-wash criteria.

Bacteria↗
PubMed1996

[Cardioactive hormones: bradykinin].

Kinins are autacoids affecting B2-receptors of many organs. They are involved in autocrine and paracrine mechanisms which are crucial in organ protection. Because of rapid degradation their effects are only short acting. Therefore, inhibition of degradation by ACE-inhibitors increases their pharmacological effects, and is of significant importance for therapy of cardiovascular diseases. Blood pressure lowering and cardioprotective effects are most important and can be explained by actions on the endothelium. The participation of kinins in blood pressure decrease during ACE inhibitor treatment can be estimated from animal experiments at about 50%. With respect to regression of cardiovascular hypertrophy or increase in insulin sensitivity their participation might be even more significant. The role of kinins in cardiovascular diseases as a pathophysiologic correlate has to be elucidated in further investigations.

Angiotensin-Converting Enzyme Inhibitors↗