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Biomedical subjects

M Steiner

Publications and source records attributed to M Steiner.

At least 109 records · Page 6Linked to original sources

Circulating endothelial cell markers in peripheral vascular disease: relationship to the location and extent of atherosclerotic disease.

We examined the relationship between specific endothelial cell markers soluble E-selectin, von Willebrand factor and soluble thrombomodulin and the location or extent of atherosclerosis by analysing plasma samples from 200 patients with symptomatic peripheral vascular disease and 213 age- and sex-matched asymptomatic control subjects. Using ELISAS, we found increased von Willebrand factor and thrombomodulin (both P < 0.0001) in the patients relative to the control subjects, but no significant change in soluble E-selectin. Soluble thrombomodulin was increased in patients with disease at one locus (i.e. of the carotid or iliac/femoral arteries), with an additional significant increase in patients with disease at multiple loci (i.e. any combination of carotid, coronary or iliac/femoral artery disease). No marker differentiated carotid artery disease from iliac/femoral artery disease. We conclude that von Willebrand factor is a marker of generalized atherosclerosis, but that soluble thrombomodulin is related to the extent of disease. Further research into these endothelial cell products are warranted to explore their diagnostic and/or prognostic potential.

ABO Blood-Group System↗

S-allylmercaptocysteine inhibits cell proliferation and reduces the viability of erythroleukemia, breast, and prostate cancer cell lines.

Organosulfur compounds are the biologically active components of allium vegetables. Many health benefits have been ascribed to them, including inhibition of carcinogenesis. Inasmuch as several of these thioallyl compounds are quite unstable and others are rapidly inactivated in the body, we have investigated one of the stable components present in aged garlic extract, S-allylmercaptocysteine (SAMC), in an effort to determine whether it can inhibit proliferation of cancer cells. Proliferation and viability of two erythroleukemia cell lines, HEL and OCIM-1, two hormone-responsive breast and prostate cancer cell lines, MCF-7 and CRL-1740, respectively, and normal human umbilical vein endothelial cells in response to different concentrations of SAMC were studied for up to two weeks. There were variations in sensitivity to this organosulfur compound in the different cell lines examined, but the two hormone-responsive cancer cell lines of breast and prostate clearly were far more susceptible to the growth-inhibitory influence of the thioallyl compound. The antiproliferative effect of SAMC was limited to actively growing cells. Human umbilical vein endothelial cells that had reached confluence escaped the reduction in viability so noticeable in the cancer cell lines tested. Our studies thus give evidence of a direct effect of SAMC on established cancer cells.

Antineoplastic Agents↗

dl-alpha-tocopherol induces apoptosis in erythroleukemia, prostate, and breast cancer cells.

Vitamin E, best known as a potent antioxidant, has been shown to have other functions that are not mediated by this activity. Recent reports have suggested that vitamin E may inhibit smooth muscle cell and also cancer cell growth. We have studied the effect of dl-alpha-tocopherol (vitamin E) on a series of well-established cancer cell lines that included two erythroleukemia cell lines and a hormone-responsive breast and prostate cancer cell line. Cell proliferation was examined in these cell lines, which were maintained at optimal growth conditions. A dose-dependent inhibition of cell growth was found in all cell lines examined, with the MCF-7 breast and CRL-1740 prostate cancer cell lines showing potent suppression of growth at 0.1 mM vitamin E, whereas the erythroleukemia cell lines, HEL and OCIM-1, responded only at > 0.25 mM vitamin E with inhibition of proliferation. Studies of [3H]thymidine incorporation showed that vitamin E supplementation reduced DNA synthesis in all cell lines. Analysis of high-molecular-weight DNA revealed extensive fragmentation, indicating apoptosis of all cell lines supplemented with vitamin E. Our studies thus give evidence of a general inhibition of cell proliferation by dl-alpha-tocopherol, with breast and prostate cancer cells distinctly more sensitive than erythroleukemia cells.

Apoptosis↗

S-allylmercaptocysteine, a stable thioallyl compound, induces apoptosis in erythroleukemia cell lines.

The antiproliferative potential of S-allylmercaptocysteine (SAMC), a stable organosulfur compound of aged garlic extract, has been investigated using two erythroleukemia cell lines, HEL and OCIM-1. It induces a dose-dependent inhibition of cell growth with a 50% lethal dose of 0.046 mM for OCIM-1 cells and 0.093 mM for HEL cells. [3H]thymidine incorporation was reduced in cells treated with this thioallyl compound, and analysis of high-molecular-weight DNA showed fragmentation compatible with apoptosis. Flow cytometric analyses of DNA revealed an abnormal cell cycle progression in both types of erythroleukemia cells, with the major portion of the unsynchronized cells in the G2/M phase. Measurement of acid-soluble free sulfhydryl groups showed an initial increase in response to SAMC followed by a progressive dose-dependent decrease with extended incubation of cells. We conclude from these studies that SAMC is an effective antiproliferative agent against erythroleukemia cells that induces cell death by apoptosis.

Apoptosis↗

Premenstrual syndromes.

Premenstrual syndrome research has made a great deal of progress since 1983 when the criteria for the diagnosis were clearly defined. Confirming the diagnosis prospectively and ruling out other disorders was a major methodologic advance. The DSM-IV criteria for PMDD now help us identify and classify women who have severe psychologic symptoms during the premenstruum. Although we do not have a definitive cause for PMDD, the consensus is that it is the end result of a complex series of events mediated partly by the serotonin system and triggered by ovulation. Women who meet criteria for PMS, do not meet the criteria for PMDD, and do not have a concurrent disorder should be treated conservatively. Women who meet criteria for PMDD can be treated successfully with low-dose clomipramine, SSRIs, or GnRH-as with "add back" estrogen and progestins.

Evidence-Based Medicine↗

Premenstrual syndromes.

The recent inclusion of research criteria for premenstrual dysphoric disorder in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders should help physicians recognize women with symptoms of irritability, tension, dysphoria, and lability of mood that seriously interfere with their lifestyle. Premenstrual dysphoric disorder can be differentiated from premenstrual syndrome, which is primarily reserved for milder physical symptoms and minor mood changes. The use of criteria from the Diagnostic and Statistical Manual in conjunction with prospective daily charting for at least two menstrual cycles is now accepted as common practice in confirming the diagnosis. Treatment options range from the conservative (lifestyle and stress management) to treatment with psychotropic medications and hormonal or surgical interventions to eliminate ovulation for the more extreme cases. Results from several randomized, placebo-controlled trials have clearly demonstrated that selective serotonin reuptake inhibitors, as well as medical or surgical oophorectomy, are effective in treating premenstrual dysphoric disorder. Taken together, these data indicate that treatment may be accomplished by either eliminating the hormonal trigger or by reversing the sensitivity of the serotonergic system.

Diagnosis, Differential↗

Synergism of hemopoietic growth factors on endothelial cell proliferation.

Endothelial cells, which are nonhemopoietic cells, express and/or produce most of the known hemopoietic receptors and cytokines. The biological role of these factors, and their respective receptors, on endothelial cells is still unknown. In this study, the authors assessed the effect of different hemopoietic growth factors, ie, interleukin-3 (IL-3), erythropoietin (EPO), macrophage-colony stimulating factor (M-CSF), granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), singly or in conjunction with others, on proliferation and chemotaxis of human umbilical vein endothelial cells (HUVECs). They found growth stimulatory activity with IL-3, EPO, and GM-CSF and potent synergism between EPO and IL-3, less with IL-3 and GM-CSF, and none with EPO and either GM-CSF or G-CSF. All the singly tested hemopoietic growth factors stimulated the migration of HUVECs, but in conjunction with other factors, they did not show any additive or synergistic effect.

Cell Division↗

[Modification of risk factors after cerebral infarct: results of the Klosterneuburg Stroke Databank].

A number of studies have shown that reduction of elevated blood pressure and other major risk factors are essential for the primary prevention of stroke. In contrast, only sparce data exist as to the reduction of risk factors in secondary prevention although many patients are only ready to modify their lifestyle after having suffered a stroke. This study reports the results of the one-year follow-up examinations from the Klosterneuburg Stroke Data Bank, a prospective, hospital-based registry. Out of 870 stroke survivors (97.4% follow-up rate) registered between 1988 and 1994 575 patients (69%) had been hypertensive before their index stroke. Out of these, 112 hypertensives (19.7% of all hypertensives) had not received antihypertensive treatment before their index stroke. Compared to all other hypertensive stroke patients they were significantly younger (p = 0.01), more often regular drinkers (p = 0.01), and regular smokers (p = 0.007). They showed significantly less heart diseases (p = 0.03) as well as prior strokes (p = 0.006). 12 months after the index-stroke the rate of untreated hypertension in this group fell to 6.0% (34 patients). In the latter group there were more frequent prior strokes compared to those hypertensives who started regular treatment after their index stroke (p = 0.003). Out of 221 smokers only 115 (52%) had quit smoking within one year after the index-stroke and 110 out of 270 (40.7%) stroke patients that had had regular alcohol intake had stopped drinking. 42 out of 118 (36%) patients who had been regular drinkers and smokers continued to drink and smoke. Regular intake of aspirin was noted more often in those patients who also had regular blood pressure checks (p = 0.009) and regular antihypertensive treatment (p = 0.001). It is concluded that there is insufficient modification of risk factors after stroke and controlled interventional studies in secondary stroke prevention are an important issue.

Aged↗

BIBP 3226, suramin and prazosin identify neuropeptide Y, adenosine 5'-triphosphate and noradrenaline as sympathetic cotransmitters in the rat arterial mesenteric bed.

The physiological role of neuropeptide Y (NPY) and extracellular adenosine 5'-triphosphate (ATP) in sympathetic neurotransmission is becoming increasingly clear. To assess whether NPY and ATP act as cotransmitters together with noradrenaline (NA) in the sympathetic nerves of the superior mesenteric artery, the changes in perfusion pressure of the arterial mesenteric bed caused by nerve stimulation were recorded. Depolarization of the perivascular superior mesenteric arterial nerves caused frequency- and time-dependent increases in the perfusion pressure that were abolished by guanethidine, which implied the sympathetic origin of these responses. Independent perfusion with either 500 nM BIBP 3226, an NPY Y1 antagonist; 3 microM suramin, a competitive purinoceptor antagonist; or 0.1 nM prazosin, a competitive alpha-1 adrenoceptor antagonist, evoked approximately a 30% reduction in the rise in perfusion pressure caused by the 20- to 30-Hz electrical depolarization of the perimesenteric arterial nerves. Prazosin (0.1 nM) blocked the increases in perfusion pressure caused by electrical stimulation of the perimesenteric nerves but did not significantly reduce the vasomotor effect of exogenous NA. Likewise, 5-methyl urapidil and chloroethylclonidine, alpha-1 adrenoceptor antagonists with selectivity for the alpha-1A and alpha-1B receptor subtypes, respectively, concentration-dependently decreased the increase in perfusion pressure elicited by electrical stimulation of the perimesenteric nerves at concentrations lower than that required to block the vasoconstriction elicited by exogenous NA. The combined perfusion of 3 microM suramin plus 0.1 nM prazosin did not result in a complete inhibition of the physiological response. Only upon the simultaneous application of BIBP plus suramin plus prazosin was the rise in perfusion pressure abolished. These results support the working hypothesis that the sympathetic nerves of the rat mesenteric bed release NPY, ATP and NA that act as postjunctional cotransmitters in this neuroeffector junction.

Adenosine Triphosphate↗

The use of generalised additive models (GAM) in dentistry.

BACKGROUND: Ordinary multiple regression and logistic multiple regression are widely applied statistical methods which allow a researcher to 'explain' or 'predict' a response variable from a set of explanatory variables or predictors. In these models it is usually assumed that quantitative predictors such as age enter linearly into the model. OBJECTIVE AND METHOD: During recent years these methods have been further developed to allow more flexibility in the way explanatory variables 'act' on a response variable. The methods are called 'generalised additive models' (GAM). The rigid linear terms characterising the association between response and predictors are replaced in an optimal way by flexible curved functions of the predictors (the 'profiles'). Plotting the 'profiles' allows the researcher to visualise easily the shape by which predictors 'act' over the whole range of values. The method facilitates detection of particular shapes such as 'bumps', 'U-shapes', 'J-shapes, 'threshold values' etc. Information about the shape of the association is not revealed by traditional methods. The shapes of the profiles may be checked by performing a Monte Carlo simulation ('bootstrapping'). CASE STUDY: After the presentation of the GAM a relevant case study is presented in order to demonstrate application and use of the method. The dependence of caries in primary teeth on a set of explanatory variables is investigated. Since GAMs may not be easily accessible to dentists, this article presents them in an introductory condensed form. It was thought that a nonmathematical summary and a worked example might encourage readers to consider the methods described. CONCLUSION: GAMs may be of great value to dentists in allowing visualisation of the shape by which predictors 'act' and obtaining a better understanding of the complex relationships between predictors and response.

Age Factors↗

Intermittent fluoxetine dosing in the treatment of women with premenstrual dysphoria.

Some women experience premenstrual mood symptoms that severely disrupt their lives and relationships. These women often require pharmacologic treatment. Selective serotonin reuptake inhibitors, particularly daily fluoxetine, have been proven superior to placebo in several randomized controlled trials. Twenty-four women with confirmed premenstrual dysphoric disorder (PMDD) and with a history of affective disorders or alcoholism were treated with fluoxetine 20 mg/day (continuous), and 24 women with PMDD and no psychiatric history were treated with fluoxetine 20 mg/day for 14 days premenstrually only (intermittent). Both groups received treatment for three menstrual cycles. Sixteen women (66.7%) in the continuous dosing group and 18 women (75.0%) in the intermittent group were classified as treatment responders. Intermittent dosing of fluoxetine seems to be effective and mostly free of side effects in women with PMDD and, therefore, may offer an attractive treatment option for a disorder that is itself intermittent.

Adult↗

Effects of in vivo cocaine administration on human platelet aggregation.

To evaluate whether cocaine administration to human volunteers in vivo increases platelet aggregation, 12 healthy male volunteers were studied twice in a prospective, double-blinded fashion. There was a decrease in aggregation following cocaine exposure compared to placebo, which was most prominent at high doses of adenosine diphosphate.

Adult↗

Plasma from patients with idiopathic and human immunodeficiency virus-associated thrombotic thrombocytopenic purpura induces apoptosis in microvascular endothelial cells.

The pathogenesis of thrombotic thrombocytopenic purpura (TTP) is obscure. It is manifested classically by platelet thrombi and localized microvascular endothelial cell (EC) proliferation, in the absence of an inflammatory response. It is statistically associated with human retroviral disease, but pathological studies of TTP lesions have been unable to establish whether perturbation of the endothelium is a primary or secondary event, irrespective of the presence of retroviral infection. We document that plasma from all of four acute TTP patients, with or without human immunodeficiency virus infection, can induce apoptosis in cultured ECs of microvascular but not large vessel origin. This process was documented by three different methods, (1) laser-illuminated light scatter, (2) quantitation of the pre-G1 Ao peak on DNA histograms and direct visualization of chromatin fragmentation by acridine orange and 4'6-diamidino-2-phenylindole staining, and (3) agarose gel electrophoresis of low molecular weight cellular DNA. Apoptosis was independent of tumor necrosis factor-alpha secretion or the presence of CD36 on microvascular ECs but was linked to the rapid induction of Fas (CD95) on these cells. Soluble anti-Fas antibody, normal plasma depleted of cryoprecipitate, and low concentrations (< or = 0.1 micromol/L) of aurintricarboxylic acid were capable of suppressing TPP plasma-mediated EC apoptosis. In conclusion, microvascular EC apoptosis may be of pathophysiological importance in TTP may be susceptible to interruption by blockade of initiating signals for, or final common enzyme pathways leading to, programmed cell death.

Acridine Orange↗