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Biomedical subjects

M Steiner

Publications and source records attributed to M Steiner.

At least 37 records · Page 2Linked to original sources
PubMed2002

[Biological markers in epidemiology: concepts, applications, perspectives (part I)].

The inclusion of biomarkers in epidemiological research provides new possibilities for exposure assessment and the study of early structural or functional changes and pre-clinical stages of diseases. At the same time issues of validity, reliability, and quality control as well as logistics require special attention. Usually epidemiological studies become more expensive with regard to time and cost. Interdisciplinary collaboration between epidemiology, basic research, and laboratory research is crucial. A prerequisite for this collaboration are agreements on definitions, methods and procedures. The definition of "biomarker" and a description of previous uses of biomarkers in epidemiological studies are presented in the first part of this paper. The second part addresses genetic markers and markers of individual sensitivity and susceptibility. We will end with a discussion about the possible future of biomarkers in epidemiology.

Biomarkers↗
PubMed2002

[Biological Markers in Epidemiology: Concepts, applications, Perspectives (Part II)].

The first part of this paper outlined terms and definitions in the context of the application of biological markers in epidemiological studies. Cardiovascular epidemiology served as an example for their historical development. The second part focusses on DNA-based biomarkers, practical and methodological dimensions of the use of biomarkers in analytic epidemiological studies as well as requirements in respect of validity and quality assurance. Most genetic polymorphisms have no impact on health. However, some can be used as biomarkers for individual sensitvity to exposures and susceptibility for specific diseases. The Human Genome Project has brought about a quantum leap in the development of genetic markers. The practical implications cannot presently be assessed with certainty. However, present and future research programmes of gene-environment interactions depend on "traditional" epidemiological study designs, methods, and concepts. Ethical principles and data protection requirements apply equally to genetic and molecular epidemiology as do the "Guidelines for Good Epidemiological Practice".

Biomarkers↗
PubMed2002

Etoposide, doxorubicin and cisplatin alternating with 5-fluorouracil, doxorubicin and high-dose methotrexate in patients with advanced adenocarcinoma of the stomach or the gastroesophageal junction.

Both the etoposide, doxorubicin, cisplatin (EAP) and 5-fluorouracil, doxorubicin, high-dose methotrexate (FAMTX) schedules have been reported to be active in advanced gastric cancer. Since these regimens include non-cross resistant agents, a regimen that consists of EAP alternating with FAMTX may have an advantage over each regimen alone. We undertook a phase II trial to evaluate EAP/FAMTX in patients with advanced adenocarcinoma of the stomach or gastroesophageal junction. Of the 56 patients treated, an objective response was observed in 34%, including complete response in 7%. Median response duration was 8 months and median survival for the entire group was 9 months. The main toxicity was myelosuppression. Hospitalization for granulocytopenic fever was required in 32% of patients and 34% required red blood cells (RBC) transfusion. Non-hematological toxicity was moderate. There were three drug-related deaths associated with granulocytopenic fever. We conclude that the alternating EAP/FAMTX regimen is associated with occasional lethal events and has no obvious advantage over either regimen alone.

Adenocarcinoma↗
PubMed2002

Paroxysmal nocturnal hemoglobinuria in a 63-year-old patient.

Intermittently occuring hemolytic anemia can be the expression of paroxysmal nocturnal hemoglobinuria (PNH). Diagnosis is made via the detection of decreased resistance of the erythrocytes to acidified serum or osmotic hemolysis. Furthermore, diagnostic proof is provided by the cytometric detection of several erythrocyte populations caused by the altered expression of an anchor protein (PIG-A protein) of the cell membrane. This report is of a case where "black morning urine" has been in existence for more than 10 years and in which the additional occurrence of icterus led to the diagnosis. The patient's spleen had been removed in 1964 because of idiopathic thrombopenia, in retrospect, however, thrombopenia within the framework of PNH should be considered.

Antigens, CD↗
PubMed2002

Diffuse emission and control of copper in urban surface runoff.

Copper washed off from roofs and roads is considered to be a major contribution to diffuse copper pollution of urban environments. In order to guarantee sustainable protection of soils and water, the long-term strategy is to avoid or replace copper containing materials on roofs and fagades. Until achievement of this goal, a special adsorber system is suggested to control the diffuse copper fluxes by retention of copper by a mixture of granulated iron-hydroxide (GEH) and calcium carbonate. Since future stormwater runoff concepts are based on decentralised runoff infiltration into the underground, solutions are proposed which provide for copper retention in infiltration sites using GEH adsorption layers. The example of a large copper façade of which the runoff is treated in an adsorption trench reveals the first full-scale data on façade runoff and adsorber performance. During the first year of investigation average façade runoff concentrations in the range of 1-10 mg Cu/l are reduced by 96-99% in the adsorption ditch.

Adsorption↗
PubMed2001

Arrangement of ribosomal genes in nucleolar domains revealed by detection of "Christmas tree" components.

We investigated how the transcribing ribosomal genes ("Christmas trees") of HeLa cells are arranged in the nucleolus. Hypotonic conditions let the granular component disperse, while fibrillar centres and parts of the dense fibrillar component were resistant to low ionic strength conditions. Both remained within the former nucleolar territory. We used immunocytochemistry and in situ hybridisation at the light microscopic and ultrastructural level for the analysis of the internal nucleolar structures. The 5' ends of ribosomal RNA and ribosomal DNA sequences were found associated with the periphery of fibrillar centres. The hypotony-resistant parts of the dense fibrillar component did not contain the 5' end of the transcript or the gene. The downstream ribosomal DNA sequences were found in the nucleolar territory but not associated with any hypotony-resistant structures. The downstream ribosomal RNA revealed a similar distribution. We show that transcription initiation and transcript elongation occur in different molecular and structural environments. Transcription initiation is located at the periphery of fibrillar centres. Evidently the dense fibrillar component is non-homogeneous in molecular composition. Transcript elongation is continued in a part of the dense fibrillar component which is dissolved under intermediate hypotonic conditions. A structural model of nucleolar transcription is suggested.

3' Flanking Region↗
PubMed2001

Current management of premenstrual syndrome and premenstrual dysphoric disorder.

About 5% of women of reproductive age experience affective or physical premenstrual symptoms that markedly influence work, social activities, or relationships. Prospective charting of symptoms for at least two menstrual cycles is required to facilitate an accurate diagnosis of premenstrual syndrome or premenstrual dysphoric disorder. The optimal treatment plan begins with lifestyle modifications, followed by pharmacotherapy. Evidence from numerous controlled trials has clearly demonstrated that low-dose serotonin reuptake inhibitors, using intermittent or continuous administration, have excellent efficacy with minimal side effects. Modification of the menstrual cycle should be considered only after all other treatment options have failed.

Antidepressive Agents↗
PubMed2001

Carnosic acid inhibits proliferation and augments differentiation of human leukemic cells induced by 1,25-dihydroxyvitamin D3 and retinoic acid.

Carnosic acid, the polyphenolic diterpene derived from rosemary, is a strong dietary antioxidant that exhibits antimutagenic properties in bacteria and anticarcinogenic activity in various cell and animal models. In the present study, we show that carnosic acid (2.5-10 microM) inhibits proliferation of HL-60 and U937 human myeloid leukemia cells (half-maximal inhibitory concentration = 6-7 microM) without induction of apoptotic or necrotic cell death. Growth arrest occurred concomitantly with a transient cell cycle block in the G1 phase, which was accompanied by an increase in the immunodetectable levels of the universal cyclin-dependent kinase inhibitors p21WAFI and p27Kipl. Carnosic acid caused only a marginal induction of differentiation, as monitored by the capacity to generate superoxide radicals and the expression of cell surface antigens (CD11b and CD14) and receptors for the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine. However, at low concentrations, this polyphenol substantially augmented (100- to 1,000-fold) the differentiating effects of 1,25-dihydroxyvitamin D3 and all-trans retinoic acid. Furthermore, such combinations of carnosic acid and any of these differentiation inducers synergistically inhibited proliferation and cell cycle progression. These results indicate that carnosic acid is capable of antiproliferative action in leukemic cells and can cooperate with other natural anticancer compounds in growth-inhibitory and differentiating effects.

Abietanes↗
PubMed2001

Aged garlic extract, a modulator of cardiovascular risk factors: a dose-finding study on the effects of AGE on platelet functions.

Aged garlic extract (AGE) has been shown previously to have moderate cholesterol-lowering and blood pressure-reducing effects. We have now investigated whether platelet function, a potential risk factor for cardiovascular disease, can be inhibited by AGE administration. In a randomized, double-blind study of normal healthy individuals (n = 34), both men and women, the effect of AGE was evaluated in doses between 2.4 and 7.2 g/d vs. equal amounts of placebo. Platelet aggregation and adhesion were measured at 2-wk intervals throughout the study. Threshold concentrations for epinephrine and collagen increased moderately during AGE administration compared with the placebo and baseline periods. Only at the highest supplementation level did AGE show a slight increase in the threshold level of ADP-induced aggregation. Platelet adhesion to collagen, fibrinogen and von Willebrand factor was investigated by perfusing whole blood through a laminar flow chamber under controlled flow conditions. Adherence of platelets was inhibited by AGE in a dose-dependent manner when collagen was the adhesive surface perfused at low shear rates ( approximately 30 s(-1)). At high shear rates (1200 s(-1)), AGE also inhibited platelet adhesion to collagen but only at higher intake levels. Adhesion to von Willebrand factor was reduced only at 7.2 g/d AGE, but adherence to fibrinogen was potently inhibited at all levels of supplementation. Thus, AGE exerts selective inhibition on platelet aggregation and adhesion, platelet functions that may be important for the development of cardiovascular events such as myocardial infarction and ischemic stroke. We briefly review the effect of garlic preparations in general on cardiovascular risk factors and point out differences between AGE and other garlic preparations that we feel are important to explain the efficacy of AGE.

Cardiovascular Diseases↗
PubMed2001

Protein crystallography with neutrons--status and perspectives.

The current state of the art and future perspectives for protein crystallography with neutrons have been reviewed and discussed at an international workshop recently organized by the Hahn-Meitner-Institut (HMI) and Max-Delbrück-Center (MDC) in Berlin, and supported by the Neutron Round Table activity. The main topics discussed and the conclusions drawn are presented in this paper. While the available flux from even the most powerful neutron sources is much lower than that available at a modern synchrotron-radiation source, there is no doubt that neutrons can additionally provide vital information in structural biology that is difficult to obtain using other methods. One of the overriding themes at the workshop was the fact that the current instrumentation and facilities do not fully exploit the neutron beams that are available. Current trends indicate that many of the problems that have limited the efficiency of biological neutron scattering have been recognized and with new technological advances important efforts are under way to tackle these problems. It is clear that the use of neutrons in biology will become increasingly significant at existing and new neutron sources.

Crystallography, X-Ray↗
PubMed2001

The efficacy of fluoxetine in improving physical symptoms associated with premenstrual dysphoric disorder.

OBJECTIVE: To determine the effectiveness of fluoxetine in alleviating physical symptoms of premenstrual dysphoric disorder. DESIGN: Randomised, double-blind, placebo controlled, parallel study. SETTING: Canadian University based outpatient clinics. Participants Four hundred and five subjects, of whom 320 with prospectively determined premenstrual dysphoric disorder were randomised. METHODS: Randomised women were assigned to fluoxetine 20 or 60 mg/day or placebo. Common physical symptoms associated with premenstrual dysphoric disorder including breast tenderness, bloating, and headache were evaluated by visual analog scales and the self-rated and observer premenstrual tension syndrome scales. OUTCOME MEASURES: Luteal phase change from mean baseline scores to mean treatment scores for all scales. RESULTS: Fluoxetine treatment was statistically superior to placebo, with no significant differences between the two fluoxetine dosages in their effects on physical symptoms. CONCLUSION: Daily fluoxetine treatment is superior to placebo in improving the most common physical symptoms associated with premenstrual dysphoric disorder.

Adult↗
PubMed2001

The selective serotonin reuptake inhibitor sertraline: its profile and use in psychiatric disorders.

The naphthylamine derivative sertraline is a potent and selective inhibitor of serotonin reuptake into presynaptic terminals. Sertraline has a linear pharmacokinetic profile and a half-life of about 26 h. Its major metabolite, desmethylsertraline does not appear to inhibit serotonin reuptake. Sertraline mildly inhibits the CYP2D6 isoform of the cytochrome P450 system but has little effect on CYP1A2, CYP3A3/4, CYP2C9, or CYP2C19. It is, however, highly protein bound and may alter blood levels of other highly protein bound agents. Sertraline is a widely used serotonin reuptake inhibitor that has been shown to have both antidepressant and antianxiety effects. Many clinical trials have demonstrated its efficacy in depression compared with both placebo and other antidepressant drugs. Its efficacy has also been demonstrated in randomized, controlled trials of patients with obsessive-compulsive disorder, panic disorder, social phobia, and premenstrual dysphoric disorder. In short-term, open-label studies it has appeared efficacious and tolerable in children and adolescents and in the elderly, and data are positive for its use in pregnant or lactating women. Typical side effects include gastrointestinal and central nervous system effects as well as treatment-emergent sexual dysfunction; withdrawal reactions may be associated with abrupt discontinuation of the agent. The safety profile of sertraline in overdose is very favorable. Sertraline's efficacy for both mood and anxiety disorders, relatively weak effect on the cytochrome P450 system, and tolerability profile and safety in overdose are factors that contribute to make it a first-line agent for treatment in both primary and tertiary care settings.

Aging↗
PubMed2001

[Decline of caries prevalence in Swiss military recruits between 1970 and 1996].

In 1996, 416 military recruits (aged 20.4) were dentally examined. The mean DMFT based on clinical findings was 4,8 (including extracted premolars). The mean DMFT based on clinical and radiological findings was 5.3 (DT=l.2; MT=0.4: almost all of them premolars; FT=3.7. 13% of the recruits were caries-free (DMFT=0). On average, 8.7 affected sites (DFS) were counted; 1.4 were untreated (DS). The caries declined by 70% (DMFT) between 1970 and 1996 and by 46% (DMFT) and 54% (DFS) respectively between 1985 and 1996. In the latter period of time, the mean number of untreated lesions (DS) decreased by 71%, in approximal surfaces of molars and premolars even by 78%. The ratio FS/DFS was 51% in 1985 and 71% in 1996,. This means an improvement in restorative care. 56% of all DFS were found in pits and fissures, 36% in approximal surfaces of molars and premolars. 62% of all untreated lesions (DS) were observed in approximal surfaces of molars and premolars; this percentage was 83% in 1985. The estimated caries increment between age of 15 and 20 was approximately 1.6 DFS/year in the early eighties and 1.3 DFS/year in the early nineties. In 1996 , the former difference in caries prevalence between the recruits from the Canton of Vaud and those from other Western Cantons did not persist. This is probably due to an alignment of the nation-wide supply with fluoridated salt since 1983.

Adolescent↗
PubMed2000

Intestinal absorption of cholesterol is mediated by a saturable, inhibitable transporter.

Although the mechanism by which dietary cholesterol is absorbed from the intestine is poorly understood, it is generally accepted that cholesterol is absorbed from bile acid micelles in the jejunum. Once inside the enterocytes, cholesterol is esterified by the action of acyl-coenzyme A:cholesterol acyltransferase (ACAT), assembled into chylomicrons, and secreted into the lymph. In this work, mechanistic aspects of cholesterol absorption were probed using compounds that block cholesterol absorption in hamsters. Sterol glycoside cholesterol absorption inhibitors, exemplified by L-166,143, (3 beta, 5 alpha,25R)-3-[(4", 6"-bis[2-fluoro-phenylcarbamoyl]-B-D-cellobiosyl)oxy]-spirostan -11-on e, potently blocked absorption of radioactive cholesterol, and the potencies of several analogs correlated with their ability to lower plasma cholesterol. Each molecule of L-166,143 blocked the uptake of 500 molecules of cholesterol, rendering it unlikely that the inhibitor interacts directly with the cholesterol or bile acid. Radiolabeled L-166,143 bound to the mucosa and binding was blocked by active, but not inactive, cholesterol absorption inhibitors. Subtle changes in the structure of sterol glycosides yielded large changes in their ability to block both cholesterol absorption and binding of radiolabeled L-166,143. Large species-to-species variation in potency was also observed. These lines of evidence support the interpretation that dietary cholesterol is absorbed via a specific transporter found in the intestinal mucosa.

Animals↗
PubMed2000

A target for cholesterol absorption inhibitors in the enterocyte brush border membrane.

Uptake of cholesterol by the intestinal absorptive epithelium can be selectively blocked by specific small molecules, like the sterol glycoside, L-166,143. Furthermore, (3)H-labeled L-166,143 administered orally to hamsters binds specifically to the intestinal mucosa, suggesting the existence of a cholesterol transporter. Using autoradiography, the binding site of (3)H-L-166,143 in the hamster small intestine was localized to the very apical aspect of the absorptive epithelial cells. Label was competed by non-radioactive L-166,143 and two structurally distinct cholesterol absorption inhibitors, suggesting a common site of action for these compounds. L-166,143 blocked uptake of (3)H-cholesterol into enterocytes in vivo, as demonstrated by autoradiography, suggesting that it inhibits a very early step of cholesterol absorption, incorporation into the brush border membrane. This conclusion was confirmed by studies in which intestinal brush borders were isolated from hamsters dosed with (3)H-cholesterol in the presence or absence of L-166,143. Uptake of (3)H-cholesterol into the membranes was substantially inhibited by the compound. In contrast, an inhibitor of acyl CoA:cholesterol acyltransferase, did not affect uptake of (3)H-cholesterol into the brush border membranes. These results strongly support the existence of a specific transporter that facilitates the movement of cholesterol from bile acid micelles into the brush border membranes of enterocytes.

Animals↗
PubMed2000

Direct evidence for the breakdown of the N = 8 shell closure in 12Be

Partial cross sections and corresponding momentum distributions have been studied in the one-neutron knockout reaction ( 12Be,11Be+gamma) on a 9Be target at 78 MeV/nucleon. The resulting spectroscopic factors for the only two bound states of 11Be are 0.42+/-0.06 ( 1/2(+)) and 0.37+/-0.06 ( 1/2(-)), where the errors are experimental only. This result shows that N = 8 is not a good closed shell in the neutron-rich 12Be and that the last neutron pair is two-thirds in the ( 1s(2)+0d(2)) intruder configuration.

Journal Article↗