PubMed Health⌕ Search

Biomedical subjects

M Ochsner

Publications and source records attributed to M Ochsner.

At least 19 recordsLinked to original sources
PubMed1999

Safety and health conditions, practices, and priorities for OSHA reform: a comparison of views of New Jersey union members and safety and health professionals.

This article draws on survey and interview data from New Jersey occupational health and safety professionals and union members to provide insights into the interactions among workers, management, unions, and health and safety professionals that shape work place conditions and practices. A substantial number of both professionals and union members reported: serious or very serious health and safety problems; limited access to effective resources for addressing these problems; and the presence of serious barriers to resolving these problems. Fewer than half of the union and professional respondents reported that effective participatory mechanisms such as union/management health and safety committees existed at their work sites, and many interview respondents described situations in which serious problems might be aired but seldom resolved.

Journal Article↗
PubMed1998

A survey of New Jersey industrial hygienists and safety engineers: health and safety conditions, practices, and priorities for OSHA reform.

This study reports the results of an analysis of responses from more than 400 New Jersey industrial hygienists and safety engineers to a survey examining a wide range of health and safety conditions and practices. Findings are reported on a number of variables including the types and seriousness of safety and health hazards encountered at the respondents' work sites, perceived improvements in health and safety conditions, compliance with right-to-know requirements, the effectiveness of resources used in correcting hazards, and the barriers encountered in addressing hazardous conditions. The respondents were also asked to rank their priorities regarding 14 proposals for Occupational Safety and Health Administration (OSHA) reform. Opinion questions were scaled to reflect the respondent's sense of the importance of each variable. One finding of particular interest is that worker involvement in health and safety committees was perceived as an "effective" or "very effective" resource by more than one-half of the respondents. Changes in the Occupational Safety and Health Act that would strengthen requirements for worker participation were among the respondents' top priorities for OSHA reform.

Attitude of Health Personnel↗
PubMed1998

Factors which support effective worker participation in health and safety: a survey of New Jersey industrial hygienists and safety engineers.

Strategies for increasing worker involvement in health and safety are widespread and have received emphasis in various OSHA reform proposals; however, much remains unknown about the effectiveness of these strategies. This paper draws on a survey of more than 400 New Jersey members of the American Industrial Hygiene Association (AIHA) and the American Society of Safety Engineers (ASSE) which addressed a broad range of issues relating to health and safety conditions and practices, including the use of worker or labor/management health and safety committees (HSCs) and worker health and safety representatives. Stepwise discriminant analysis was used to explore the relationships between effective participation and variables which describe worksites and potential health and safety resources and barriers. Effective strategies for involving workers appear to be conditional on a number of variables, most importantly on worker activism and the effective use of formal union negotiations. Findings are consistent with studies from both the U.S. and abroad which emphasize the role of unions in shaping opportunities for effective worker participation.

Community Participation↗
PubMed1997

Ca2+ transient, cell volume, and microviscosity of the plasma membrane in smooth muscle.

Despite pronounced differences by which membrane-depolarizing or phospholipase C-activating stimuli initiate contractile responses, a rise in [Ca2+]i is considered the primary mechanism for induction of smooth muscle contractions. Subsequent to the formation of the well-characterized Ca(2+)4-calmodulin complex, interaction with the catalytic subunit of myosin light chain kinase triggers phosphorylation of 20 kDa myosin light chain and activates actin-dependent Mg2+-ATPase activity, which ultimately leads to the development of tension. The present article reviews the fundamental mechanisms leading to an increase in [Ca2+]i and discusses the biochemical processes involved in the transient and sustained phases of contraction. Moreover, the commentary summarizes current knowledge on the modulatory effect of changes in the microviscosity of the plasma membrane on the Ca2+ transient as well as the contractile response of smooth muscle. Evidence has accumulated that these changes in microviscosity alter the activity of membrane-bound enzymes and affect the generation of endogenous mediators responsible for the regulation of cytosolic Ca2+ concentrations and for the [Ca2+]i-sensitivity of myosin light chain phosphorylation.

Animals↗
PubMed1997

Photophysical and photobiological processes in the photodynamic therapy of tumours.

Photodynamic therapy (PDT) is an innovative and attractive modality for the treatment of small and superficial tumours. PDT, as a multimodality treatment procedure, requires both a selective photosensitizer and a powerful light source which matches the absorption spectrum of the photosensitizer. Quadra Logic's Photofrin, a purified haematoporphyrin derivative, is so far the only sensitizer approved for phase III and IV clinical trials. The major drawbacks of this product are the lack of chemical homogeneity and stability, skin phototoxicity, unfavourable physicochemical properties and low selectivity with regard to uptake and retention by tumour vs. normal cells. Second-generation photosensitizers, including the phthalocyanines, show an increased photodynamic efficiency in the treatment of animal tumours and reduced phototoxic side effects. At the time of writing of this article, there were more than half a dozen new sensitizers in or about to start clinical trials. Most available data suggest a common mechanism of action. Following excitation of photosensitizers to long-lived excited singlet and/ or triplet states, the tumour is destroyed either by reactive singlet oxygen species (type II mechanism) and/or radical products (type I mechanism) generated in an energy transfer reaction. The major biological targets of the radicals produced and of singlet oxygen are well known today. Nucleic acids, enzymes and cellular membranes are rapidly attacked and cause the release of a wide variety of pathophysiologically highly reactive products, such as prostaglandins, thromboxanes and leukotrienes. Activation of the complement system and infiltration of immunologically active blood cells into the tumorous region enhance the damaging effect of these aggressive intermediates and ultimately initiate tumour necrosis. The purpose of this review article is to summarize the up-to-date knowledge on the mechanisms responsible for the induction of tumour necrotic reactions.

Animals↗
PubMed1997

Photodynamic therapy: the clinical perspective. Review on applications for control of diverse tumorous and non-tumorous diseases.

Photodynamic therapy (PDT) is an innovative and attractive modality for the treatment of small and superficial tumours. PDT, as a multi-modality treatment procedure, needs both, a photosensitizer with distinct tumour selectivity and a powerful light source that matches the absorption spectrum of the photosensitizer. The purified haematoporphyrin derivative Photofrin is so far the only sensitizer approved for phase III/IV clinical trials. Major drawbacks of this product are: lack of chemical homogeneity, skin phototoxicity, unfavourable physicochemical properties and poor selectivity in terms of uptake and retention by tumour versus normal cells. Most second generation photosensitizers, including the phthalocyanines, show an increased photodynamic efficiency in the treatment of animal tumours and reduced phototoxic side effects. In 1997, there were more than half a dozen new sensitizers in or about to start clinical trials. To introduce the basic principles of photodynamic therapy, the current review article discusses in some more detail the treatment of endobronchial lung cancer, one of the leading indications of PDT. Moreover, a broad overview is given on the use of PDT for treatment of a wide variety of tumorous and nontumorous diseases, including new strategies for control of rheumatoid arthritis and application of PDT for extracorporeal bone marrow purging.

Animals↗
PubMed1996

The action of the peptidoleukotriene LTD4 on intracellular calcium in rat mesangial cells.

The dose-dependent effect of CGP 45715A on the LTD4-induced Ca2+ response of glomerular mesangial cells has been studied. Our results demonstrate that the LTD4-dependent increase in the cytosolic Ca2+ concentration primarily involves an InsP3-mediated release of Ca2+ from intracellular storage sites and to a minor extent an enhanced influx of Ca2+ through receptor-operated Ca2+ channels located in the plasma membrane. The action of CGP 45715A on the Ca2+ response is an inhibitory one and is convincingly explained by a displacement of LTD4 from its receptor site(s). The contractile effect of LTD4 on pulmonary smooth muscle is proposed to be mainly caused by a receptor-mediated hydrolysis of phosphatidylinositol-4,5-bisphosphate.

Animals↗
PubMed1996

Simultaneous measurement of Ca2+ transients and changes in the cell volume and microviscosity of the plasma membrane in smooth muscle cells. Evaluation of the effect of formoterol.

The effects of the beta 2-adrenoceptor agonist formoterol (50 nM) on the angiotensin II (20 nM)-induced Ca2+ response and changes in the cell volume and microviscosity of the plasma membrane of vascular smooth muscle cells were studied. Applied as a model substance for the stimulation of the phosphoinositide-phospholipase C pathway, angiotensin II has been used to simulate the bronchospasm of smooth muscle in asthma. Our results demonstrated that angiotensin II-induced smooth muscle contraction primarily involves an InsP3-mediated release of Ca2+ from intracellular stores and, to a minor extent, an enhanced influx of Ca2+ through the plasma membrane. Both the Ca2+ response and the contractile reaction were strongly antagonized by pretreatment of the cells with 50 nM formoterol. The protective effect of formoterol on smooth muscle contractions is proposed to be mainly related to a direct stimulation of beta 2-adrenoceptor-coupled cAMP generation. Moreover, it is predicted that the interaction between the beta 2-adrenoceptor glycoprotein and adenylate cyclase will be enhanced following a formoterol-associated decrease in the microviscosity of the plasma membrane.

Adrenergic beta-2 Receptor Agonists↗
PubMed1996

Light scattering of human skin: a comparison between zinc (II)-phthalocyanine and photofrin II.

Zinc(II)-phthalocyanine is the active component of the liposomal formulation CGP 55847 which showed a highly activity in photodynamic therapy studies on a variety of animal tumours (K. Schieweck et al., SPIE Conf. Proc., 2078 (1994) 107-118). The photophysical properties of zinc(II)-phthalocyanine have been studied in detail and compared with those of Photofrin II(R), the only sensitizing agent approved so far for Phase III and IV clinical trials (M. Ochsner-Bruderer, Inaugural Dissertation, University of Basle, 1994). As will be shown in a series of papers, the main photophysical properties of zinc(II)-phthalocyanine are significantly better than those of Photofrin II(R) (M. Ochsner-Bruderer, Inaugural Dissertation, University of Basle, 1994). In this paper we especially consider the effect of the absorption wavelength on the penetration of light into the human skin. The results clearly show that the longer absorption wavelength of zinc(II)-phthalocyanine causes a deeper penetration of light into the human skin as compared with Photofrin II(R). In addition to this, the higher extinction coefficient (epsilon S) lowers the zinc(II)-phthalocyanine dose required to induce a tumour necrosis.

Animals↗
PubMed1993

Protein kinase C inhibitors potentiate angiotensin II-induced phosphoinositide hydrolysis and intracellular Ca2+ mobilization in renal mesangial cells.

Stimulation of mesangial cells with angiotensin II leads to rapid phosphoinositide hydrolysis and subsequent mobilization of intracellular Ca2+. Previous studies indicated that activation of protein kinase C (PKC) triggers a negative-feedback signal, which limits phosphoinositide turnover. By comparing the relative susceptibility of PKC isoenzymes to phorbol ester-induced down-regulation with the down-regulation of the functional cell response, i.e. feedback inhibition of inositol trisphosphate production, we inferred that PKC-alpha and PKC-delta are candidates for regulating phosphoinositide hydrolysis in mesangial cells. To test this hypothesis further, we examined the effects of inhibitors of PKC, that are reportedly not active on PKC-delta, on angiotensin II-stimulated phosphoinositide degradation and Ca2+ mobilization. Pretreatment of mesangial cells with the PKC inhibitors staurosporine and K252a potently augmented inositol trisphosphate and 1,2-diacylglycerol formation as well as Ca2+ mobilization in response to angiotensin II. These results suggest that PKC-alpha, but not PKC-delta, is the most likely candidate mediating feedback inhibition of angiotensin II-stimulated phosphoinositide turnover in mesangial cells.

Alkaloids↗
PubMed1991

Simultaneous measurement of Ca2+ transients and of membrane depolarizations in synaptosomes.

Calcium and membrane potential sensitive dyes have been widely used to study the biochemical effects of the intracellular calcium concentration and of the membrane potential on diverse biochemical processes. However, due to the discontinuous measurement techniques applied, it was until now impossible to get an insight into the sequence and dynamics of the induced biological reactions. In order to study the relationship between the intracellular calcium concentration and the membrane potential, an apparatus was developed capable of measuring both biological processes simultaneously. Potassium chloride induced changes of the synaptosomal membrane potential and of the intracellular calcium concentration are presented.

Aniline Compounds↗
PubMed1990

Nafenopin, a hypolipidemic and non-genotoxic hepatocarcinogen increases intracellular calcium and transiently decreases intracellular pH in hepatocytes without generation of inositol phosphates.

Addition of nafenopin (30-300 microM to 45Ca2+ preloaded cultured hepatocytes caused a rapid and concentration-dependent increase in 45Ca2+ efflux in a manner similar to vasopressin, as evidenced by the loss of radioactivity from the cells. In contrast to vasopressin, addition of nafenopin to [3H]inositol prelabelled hepatocytes in culture did not increase [3H]inositol phosphate production. When added simultaneously with vasopressin, nafenopin inhibited the vasopressin-stimulated [3H]inositol phosphate production. In hepatocyte suspensions isolated from rats treated for 1 week with a carcinogenic dose of nafenopin (1000 ppm in their daily food) the incorporation of [3H]inositol into the phosphoinositide fraction, particularly phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate, was much less than that in hepatocytes isolated from untreated rats. The vasopressin-stimulated [3H]inositol phosphate production was also decreased. Experiments with hepatocyte suspensions preloaded with Ca2+ or pH sensitive fluorescent indicators demonstrated that addition of nafenopin caused an increase in intracellular free Ca2+ and transient acidification of the cells. The increase in [Ca2+]i was decreased by only about 25% when extracellular calcium was removed indicating that nafenopin mainly mobilizes Ca2+ from intracellular stores. The recovery to basal pH was amiloride-sensitive indicating the importance of Na+/H+ exchange in pH recovery after intracellular acidification. Amiloride also inhibited DNA synthesis induced by nafenopin and by epidermal growth factor in cultured hepatocytes; but this effect occurred concomitantly with inhibition of basal DNA synthesis. We suggest that hepatic Ca2+ mobilization induced by nafenopin may play an important role in the mechanism by which nafenopin exerts its physiological as well as its tumour promotive activity upon chronic treatment with carcinogenic doses.

Animals↗
PubMed1990

Potentiation of angiotensin II-stimulated phosphoinositide hydrolysis, calcium mobilization and contraction of renal mesangial cells upon down-regulation of protein kinase C.

Long-term pretreatment of rat mesangial cells with 12-O-tetradecanoylphorbol 13-acetate (TPA) down-regulated protein kinase C activity and potentiated the angiotensin II-induced inositol trisphosphate (InsP3) formation. This increased response to angiotensin II occurred without a significant change in the receptor number or Kd value of angiotensin II binding to the cells. The biologically inactive phorbol ester 4 alpha-phorbol 12,13-didecanoate was without effect on angiotensin II-stimulated InsP3 generation. Long-term pretreatment with TPA also increased the angiotensin II-induced mobilization of Ca2+ and the subsequent contraction of mesangial cells.

Angiotensin II↗
PubMed1989

Down-regulation of protein kinase C potentiates angiotensin II-stimulated polyphosphoinositide hydrolysis in vascular smooth-muscle cells.

In smooth-muscle cells (SMC) isolated from rat aorta, angiotensin II stimulates a phospholipase C with subsequent formation of inositol trisphosphate (InsP3). Short-term (10 min) pretreatment of SMC with 12-O-tetradecanoylphorbol 13-acetate (TPA; 100 nM) decreases the angiotensin II-induced InsP3 formation. However, this inhibition is not observed after incubating the cells for 2 h with TPA. Longer-term pretreatments even lead to an enhanced generation of InsP3. This increased response to angiotensin II occurs without a significant change in the receptor number or Kd value of angiotensin II binding to the cells. The biologically inactive phorbol ester 4 alpha-phorbol 12,13-didecanoate was without effect on angiotensin II-stimulated InsP3 generation, irrespective of the time of preincubation. In parallel with this potentiation of angiotensin II-induced generation of InsP3 by TPA, a down-regulation of protein kinase C activity is observed. A 24 h pretreatment of SMC with TPA decreases protein kinase C activity to less than 10% of that of control cells. Longer-term pretreatment also increases the angiotensin II-induced release of Ca2+ and delays the decay of the transient Ca2+ increase. All these data suggest that protein kinase C exerts a negative feedback control on angiotensin II-stimulated polyphosphoinositide turnover, and that protein kinase C is an important factor in limiting the production of InsP3 in stimulated cells.

Angiotensin II↗
PubMed1982

Improvement of the radioallergosorbent test (RAST) sensitivity by using an antibody specific for the determinant D epsilon 2.

A technical modification was introduced by the manufacturer (Pharmacia) of a commercially available RAST, with the use of an anti-IgE antibody specific for the domain epsilon 2 of the IgE molecule. Results of the previous and of the new RAST were compared in 100 patients suffering from bronchial asthma or chronic rhinitis. When the same serum was assayed by both techniques, the new RAST technique disclosed a higher positivity in 26% of the comparisons. The new RAST improved the overall correlation between RAST and skin-tests by 6%: individually by 12% for house dust, 8% for Dermatophagoides pteronyssinus and 15% for animal danders. However, the level of correlation was decreased by 8% for the moulds. In patients with a total IgE concentration larger than 100 PRIST units, the new RAST allowed the demonstration of specific IgE in a number of cases twice as large as the previous technique. Thus, the modification of the RAST provides a more sensitive test, the results of which better correlate with those of other diagnostic methods.

Adolescent↗
PubMed1981

Critical evaluation of 1-stage cystectomy--reducing morbidity and mortality.

Although it is a major surgical effort removal of the bladder can be done with reasonable safety. In our opinion cystectomy and urinary diversion by an ileal conduit can be performed as a conjoined procedure without need for staging to reduce risks. Mortality up to 3 months postoperatively was 3.9 per cent and the major complication rate for surviving patients was 18.6 per cent. Minor complications occurred in 28.7 per cent of all patients but were treated easily. We did not note increased morbidity after radical cystectomy compared to other types of cystectomy. A higher complication rate was noted in patients who had undergone preoperative radiation treatment, and wound infection rate was higher in patients with neurogenic bladder dysfunction and chronic cystitis. The advantages of 1-stage compared to 2-stage cystectomy would include the fact that it eliminates the need for a second operation, saves considerable expense by virtue of shortened hospitalization and an earlier resumption of the patient's productivity, achieves early removal of the malignancy, decreases the chances of infection by avoiding a second laparotomy in the presence of a stoma and allows better exposure in the absence of previous ureteroileal anastomoses.

Adolescent↗
PubMed1975

[Chemotaxis of human polymorphonuclear cells in vitro. Study of inflammatory rheumatic diseases].

Sixty-eight determinations of leukocyte chemotaxis were performed in 42 patients suffering from systemic lupus erythematodes (17 cases), rheumatoid arthritis (15 cases) and scleroderma (10 cases). In contrast to the results of others, this study showed a deficiency in only 15 of 42 cases (35.7%). Impairment of chemotaxis was always transitory and demonstrable only during acute phases of disease. Intrinsic deficiency of PMN leukocytes as well as deficiency of plasma factors were related to the clinical and biological course of the disease and to the treatment.

Antibodies, Antinuclear↗