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M Meier

Publications and source records attributed to M Meier.

At least 37 records · Page 2Linked to original sources
PubMed2000

Design of a minimal protein oligomerization domain by a structural approach.

Because of the simplicity and regularity of the alpha-helical coiled coil relative to other structural motifs, it can be conveniently used to clarify the molecular interactions responsible for protein folding and stability. Here we describe the de novo design and characterization of a two heptad-repeat peptide stabilized by a complex network of inter- and intrahelical salt bridges. Circular dichroism spectroscopy and analytical ultracentrifugation show that this peptide is highly alpha-helical and 100% dimeric tinder physiological buffer conditions. Interestingly, the peptide was shown to switch its oligomerization state from a dimer to a trimer upon increasing ionic strength. The correctness of the rational design principles used here is supported by details of the atomic structure of the peptide deduced from X-ray crystallography. The structure of the peptide shows that it is not a molten globule but assumes a unique, native-like conformation. This de novo peptide thus represents an attractive model system for the design of a molecular recognition system.

Amino Acid Sequence↗
PubMed2000

Protein kinase C activation and its pharmacological inhibition in vascular disease.

Vascular complications in diabetes mellitus are known to be associated with the activation of the protein kinase C (PKC) pathway through the de novo synthesis of diacylglycerol (DAG) from glycolytic intermediates. Specific PKC isoforms, mainly the beta- and delta-isoforms, have been shown to be persistently activated in diabetic mellitus. Multiple studies have reported that the activation of PKC leads to increased production of extracellular matrix and cytokines, enhances contractility, permeability and vascular cell proliferation, induces the activation of cytosolic phospholipase A2 and inhibits the activity of Na+-K+-ATPase. These events are not only frequently observed in diabetes mellitus but are also involved in the actions of vasoactive agents or oxidative stress. Inhibition of PKC by two different kinds of PKC inhibitors - LY333531, a selective PKC-beta-isoform inhibitor, and vitamin E, d-alpha-tocopheron - were able to prevent or reverse the various vascular dysfunctions in vitro and in vivo. Clinical studies using these compounds are now ongoing to evaluate the significance of DAG-PKC pathway activation in the development of vascular complications in diabetic patients.

Animals↗
PubMed2000

Induction of endothelin-1 expression by glucose: an effect of protein kinase C activation.

Enhanced actions or levels of endothelin-1 (ET-1), a potent vasoconstrictor, have been associated with decreased blood flow in the retina and peripheral nerves of diabetic animals and may be related to the development of pathologies in these tissues. Hyperglycemia has been postulated to increase ET-1 secretion in endothelial cells. We have characterized the mechanism by which elevation of glucose is increasing ET-1 mRNA expression in capillary bovine retinal endothelial cells (BREC) and bovine retinal pericytes (BRPC). Elevation of glucose, but not mannitol, from 5.5 to 25 mmol/l for 3 days increased membranous protein kinase C (PKC) activities and ET-1 mRNA in parallel levels by 2-fold in BREC and BRPC. These effects were reversed by decreasing glucose levels to 5.5 mmol/l for an additional 2 days. Glucose-induced ET-1 overexpression was inhibited by a general PKC inhibitor, GF109203X, and a mitogen-activated protein kinase kinase inhibitor, PD98059, but not by wortmannin, a phosphatidylinositol 3-kinase inhibitor. By immunoblot analysis, PKC-beta2 and -delta isoforms in BREC were significantly increased relative to other isoforms in the membranous fractions when glucose level was increased. Overexpression of PKC-beta1 and -delta isoforms but not PKC-zeta isoform by adenovirus vectors containing the respective cDNA enhanced in parallel PKC activities, proteins, and basal and glucose-induced ET-1 mRNA expression by at least 2-fold. These results showed that enhanced ET-1 expression induced by hyperglycemia in diabetes is partly due to activation of PKC-beta and -delta isoforms, suggesting that inhibition of these PKC isoforms may prevent early changes in diabetic retinopathy and neuropathy.

Animals↗
PubMed2000

Beta-hydroxybutyric acid--an indicator for an alcoholic ketoacidosis as cause of death in deceased alcohol abusers.

We analyzed the postmortem blood of a total of 100 fatal cases for beta-hydroxybutyric acid (BHBA). In 25 cases of sudden and unexpected death of alcoholics we found pathologically increased levels of BHBA of 1260 to 47200 (median 8000) micromol/L. This led us to the diagnosis of an alcoholic ketoacidosis (AKA) as cause of death in these cases. The control group of 69 postmortem cases revealed that BHBA concentrations below 500 can be regarded as normal, and values up to 2500 micromol/L as elevated. Our study shows that BHBA values over 2500 micromol/L could lead to death, if no medical attention is sought. During storage we did not find any indication of postmortem formation or decomposition of BHBA in blood in vitro or in the corpses. In our opinion, BHBA should be considered the diagnostic marker of choice for the postmortem determination of alcoholic ketoacidosis (AKA) as the cause of death. The classical indications of such deaths are: unexpected death of a chronic alcoholic; none or only traces of ethanol in the blood; increased acetone blood concentration; and neither autopsy, histology, microbiology, nor toxicology reveal the cause of death. In six further cases a diabetic ketoacidosis (DKA) was diagnosed as the cause of death.

3-Hydroxybutyric Acid↗
PubMed2000

[Reconstruction of mutism. Studies of subjective experiences of former patients with the modified Landfield categories].

OBJECTIVE: The subjective experience of catatonic patients was investigated with the repertory grid-technique after recovery from the acute state of disease and compared with non-catatonic schizoaffective and depressive patients. METHODS: The sample consists of 18 catatonic patients, 22 schizoaffective, 16 unipolar depressive, 8 unipolar manic and 23 patients with bipolar affective disorder as well as of 32 psychiatrically healthy orthopaedic controls. Interviews were held well before discharge. The contents of personal constructs was analyzed by means of modified Landfield categories. RESULTS: "Self" of catatonic patients did not differ significantly from the other groups. The "Idealself" of catatonic patients differed significantly in the categories "high self esteem" (from the controls and the non-catatonic group) and "high empathy" (from the controls). The "disease-self" ("In the acute catatonic state") was construed as isolated (lack of social contact). The results underline the importance of an active therapeutical interaction in the acute catatonic state. The modified Landfield Categories proved to be a useful psychodiagnostic instrument for the idiographic assessment of personality in particular, and for psychiatric therapy research in general.

Adult↗
PubMed1999

Megalin in normal tissues and carcinoma cells carries oligo/poly alpha2,8 deaminoneuraminic acid as a unique posttranslational modification.

In rat kidney, megalin, a member of the low density lipoprotein receptor gene family, is the sole glycoprotein which carries oligo/poly alpha2,8 deaminoneuraminic acid (KDN) as a posttranslational modification. We have investigated immunoprecipitated megalin from rat brain, lung and placenta, mouse yolk sac carcinoma and megalin synthesizing carcinoma cell lines, for presence of this unique glycan structure. Our immunoblot analysis revealed the presence of oligo/poly alpha2,8 KDN on megalin in all the studied normal tissues and carcinoma cells. Furthermore, it is demonstrated to be part of oligosaccharides O-glycosidically linked to megalin.

Animals↗
PubMed1999

Glucose or diabetes activates p38 mitogen-activated protein kinase via different pathways.

Hyperglycemia can cause vascular dysfunctions by multiple factors including hyperosmolarity, oxidant formation, and protein kinase C (PKC) activation. We have characterized the effect of hyperglycemia on p38 mitogen-activated protein (p38) kinase activation, which can be induced by oxidants, hyperosmolarity, and proinflammatory cytokines, leading to apoptosis, cell growth, and gene regulation. Glucose at 16.5 mM increased p38 kinase activity in a time-dependent manner compared with 5.5 mM in rat aortic smooth muscle cells (SMC). Mannitol activated p38 kinase only at or greater than 22 mM. High glucose levels and a PKC agonist activated p38 kinase, and a PKC inhibitor, GF109203X, prevented its activation. However, p38 kinase activation by mannitol or tumor necrosis factor-alpha was not inhibited by GF109203X. Changes in PKC isoform distribution after exposure to 16.5 mM glucose in SMC suggested that both PKC-beta2 and PKC-delta isoforms were increased. Activities of p38 kinase in PKC-delta- but not PKC-beta1-overexpressed SMC were increased compared with control cells. Activation of p38 kinase was also observed and characterized in various vascular cells in culture and aorta from diabetic rats. Thus, moderate hyperglycemia can activate p38 kinase by a PKC-delta isoform-dependent pathway, but glucose at extremely elevated levels can also activate p38 kinase by hyperosmolarity via a PKC-independent pathway.

Adenoviridae↗
PubMed1998

[Erroneous intravenous injection of adrenaline].

HISTORY AND CLINICAL FINDINGS: Since a car accident a 29-year-old man had been suffering from chronic pain treated with injections of morphine and tilidine. Because of renewed worsening of pain he went to the emergency doctor who by mistake intravenously injected 1 mg of undiluted adrenaline. The patients immediately collapsed and pulmonary oedema developed. INVESTIGATIONS: On admission he was hypotensive (85/45 mmHg) and tachycardic (135/min), respiratory rate 36/min. Moist rales were heard throughout the lung. The white cell count was elevated and serum potassium low (3.5 mmol/l). but other routine laboratory tests were unremarkable. TREATMENT AND COURSE: Furosemide, nitroglycerin and morphine were injected at once and his general state improved over the subsequent few hours. Chest radiogram on the next day demonstrated marked reduction of the pulmonary oedema. CONCLUSION: To prevent similar, potentially lethal, accidents, before every i.v. injection two persons should check the name of the drug on the label of the vial or bottle, both on drawing up and before injecting the drug.

Adult↗
PubMed1998

An automated training device for pattern discrimination learning of group-housed gerbils.

The setup, designed for the rodent Meriones unguiculatus (gerbil), allows flexible stimulus presentations and rewarding as well as on-line data registration. It consists of a spacious housing where the animals have free access to water. Food is supplied exclusively in the y-maze training compartment and serves as a reinforcer in an operant conditioning paradigm.

Animals↗
PubMed1998

[Health-related quality of life. Long-term survival in patients with ARDS following extracorporeal membrane oxygenation (ECMO)].

UNLABELLED: Treatment of severe acute respiratory distress syndrome (ARDS) with extracorporeal membrane oxygenation (ECMO) can be lifesaving but requires maximal use of intensive care resources over prolonged periods of time, resulting in high costs. Little is known about the health-related quality of life (HRQL) in long-term survivors. This case-controlled retrospective study was designed to assess the health-related quality of life in long-term survivors of ARDS and ECMO-therapy. METHODS: 14 long-term survivors of ARDS (APACHE II score = 24, Lung Injury Score = 3.25, median values) treated using ECMO between 1992 and 1995 (median time interval between data collection and discharge from the ICU 16 months) and 14 ARDS-patients conventionally treated during the same period (group I) were identified and completed the SF-36 Health Status Questionnaire (Medical Outcome Trust, Boston, USA). 14 healthy subjects (group II) were drawn at random from a large data base generated to provide normal values for the SF-36 in a German population. All three groups were comparable with respect to sex and age. RESULTS: Long-term survivors of ECMO-therapy reported significant reductions in physical functioning when compared with patients treated by mechanical ventilation alone (group I, -12.5%, p < 0.05) and with healthy controls (group II, -50%, p < 0.05) and showed a higher incidence of chronic physical pain (+5% and +24%, respectively, p < 0.05). There were no differences with regard to the mental health dimensions of the SF-36 (e.g. vitality, mental health index or social functioning) between ECMO-patients and all controls. Nine patients (64.3%) from the ECMO group versus all patients treated conventionally (group I) had full-time employment (p = 0.46, Chi2 test). CONCLUSIONS: The majority of long-term survivors of ECMO-treatment show good physical and social functioning, including a high rate of employment. The more aggressive approach of ECMO-therapy and a possibly more severe underlying disease process may explain impairments in health-related quality of life outcomes after ECMO-treatment. Despite these limitations, long-term survivors of ECMO-therapy are able to reach a highly satisfactory health-related quality of life.

APACHE↗
PubMed1998

Paraspinal muscle fibre type alterations associated with scoliosis: an old problem revisited with new evidence.

To establish the extent to which the paraspinal muscles are affected in idiopathic scoliosis, samples from patients must be compared with controls of a similar gender and age. To date, insufficient control data has been available for these purposes. The aim of this study was to re-dress this tissue, in order to identify whether one side of the apex of the scoliotic curve showed greater muscular abnormalities than the other. Bilateral samples of the paraspinal muscles were obtained during surgery from 14 female scoliosis patients, at the apex of the scoliotic curve at T9-T11. Percutaneous muscle biopsy samples were obtained from nine female volunteers, on the left side of the spine at T10. Samples were prepared for routine histochemistry for the identification of muscle fibre types. Fibre size was measured using computerised image analysis. Compared with control muscle, there was a significantly lower proportion of type I (slow-twitch oxidative) fibres in the muscle on the concave side of the scoliotic curve, but no difference on the convex side. The proportion of type IIB (fast-twitch, glycolytic) fibres was higher on both sides of the curve compared with controls, with the effect being significantly more marked on the concave side. The percentage of type IIA (slow-twitch, oxidative-glycolytic) fibres did not differ between the groups, and neither did fibre size (although there was a tendency for the controls to have larger type IIA fibres than the patients). Collectively, the differences in fibre type size and distribution meant that on the concave side the relative area of the muscle occupied by type I fibres was smaller, and on both sides of the curve the relative area occupied by type IIB fibres was greater and by type IIA fibres smaller, in comparison with controls. In scoliosis, the spinal musculature is most affected on the concave side of the curve's apex. The muscle adopts a 'faster', or more 'glycolytic' profile, which would be consistent with a reduced low-level tonic activity of the muscle, perhaps consequent to a local change in activity on this side of the spine following progression of the curve. Less marked changes, in the same direction, are also evident on the convex side; these may be the result of general disuse of the paraspinal muscles associated with the spinal deformity.

Adult↗
PubMed1998

The Zurich long-term outcome study of child and adolescent psychiatric disorders in males.

BACKGROUND: Within the framework of developmental psychopathology the outcome of male former child and adolescent psychiatric patients at age 36 or 38 was studied in order to add to the limited knowledge in this field. METHODS: A total of 269 former child psychiatric patients of male sex and a control group of more than 2700 men, who were all born in 1952, were compared with regard to mortality, delinquency and adult psychiatric disorders. The study was based on case-file data from assessments conducted with the child and adolescent psychiatric patients and on adults, derived from either federal registers (mortality, delinquency) or army health records and records of the psychiatric facilities of the canton. The study is based on lifetime prevalence rates. RESULTS: The two samples did not differ with regard to mortality rates. Delinquency tended to be more prevalent and psychiatric disorders were significantly more prevalent among the former child psychiatric patients. Close to 10% of the latter group showed major delinquency, one-quarter was psychiatrically disturbed and 30% displayed one of these two indicators or maladjustment at least once during the follow-up period. A correspondence in pattern of varying between child and adult psychiatric spectrum disorders was observed. Whereas the type of child and adolescent psychiatric disorders did not predict adult maladjustment, there was some indication that deprived environments, broken homes and parental psychiatric disorders during childhood increased the likelihood of poor adult outcome. CONCLUSIONS: This study clearly underlines the long-term negative effects of child and adolescent mental abnormalities in males.

Adolescent↗
PubMed1998

Health-related quality of life and posttraumatic stress disorder in survivors of the acute respiratory distress syndrome.

OBJECTIVES: Despite considerable progress in intensive care management of the acute respiratory distress syndrome (ARDS), little is known about health-related quality of life in long-term survivors. In addition, intensive care treatment can be extremely stressful, and many survivors of ARDS report adverse experiences such as respiratory distress, anxiety, or pain during intensive care unit (ICU) treatment. This study was performed to assess health-related quality of life in survivors of ARDS and to test the hypothesis that adverse experiences during ICU treatment result in posttraumatic stress disorder (PTSD) and negative effects on health-related quality of life. DESIGN: Retrospective, cohort, case-controlled analyses. SETTING: A 12-bed multidisciplinary ICU of a tertiary care university hospital, capable of providing extracorporeal life support for adults with severe ARDS. PATIENTS: We studied 80 patients who were admitted to our hospital from 1985 to 1995 and who survived an episode of ARDS. ARDS was defined according to the criteria of the American-European Consensus Conference on ARDS. INTERVENTIONS: Health-related quality of life was measured using the Health Status Questionnaire of the self-administered Medical Outcomes Study Short Form Survey that consists of 36 questions (SF-36) and the German version of the Post Traumatic Stress Syndrome 10-Questions Inventory (PTSS-10), a self-report scale for the diagnosis of posttraumatic stress disorder based on the Diagnostic and Statistical Manual (Third Edition) criteria (American Psychiatric Association). The number of adverse experiences (anxiety, respiratory distress, pain, and nightmares) during intensive care was evaluated by means of a structured questionnaire. For each patient with ARDS, three age- and gender-comparable controls were randomly selected from databases providing normal values for the SF-36 and PTSS-10 scores in populations at risk for posttraumatic stress disorder. MEASUREMENTS AND MAIN RESULTS: Survivors of ARDS showed statistically significant impairments in all eight health dimensions of the SF-36 when compared with normal controls (median reduction 21.3%, p < .006) with maximal impairments in physical function (median reduction 28.9%, p = .000) and a 38% higher frequency of chronic pain (p = .0001). Three of 34 patients reporting none, or one, adverse experience had evidence of posttraumatic stress disorder vs. 19 of 46 patients remembering multiple traumatic episodes (p = .007). Patients reporting multiple adverse experiences described the lowest health-related quality of life, with maximal impairments in psychosocial functioning (p < .005) and only small limitations in physical function. CONCLUSIONS: Long-term survivors of ARDS describe a good overall health-related quality of life. Major impairments in mental health domains of health-related quality of life are associated with the development of posttraumatic stress disorder and are a possible result of traumatic experiences during ICU therapy.

Adolescent↗
PubMed1998

Prevalence of child and adolescent psychiatric disorders: the Zürich Epidemiological Study.

Psychiatric disorders were studied in an epidemiological and representative sample of 1964 pupils attending the first to ninth grade in various types of schools in the Canton of Zürich, Switzerland. Using a two-stage procedure, parents were asked to respond to a standardized behaviour problem checklist in the screening phase. In the second stage, structured interviews were performed with 399 parents representing both screen positive and control children. DSM-III-R diagnoses were derived from the interviews. The total prevalence figure for any disorder amounted to 22.5%. Prevalence rates were influenced by the multi-screen procedure. Among various correlates, sex, nationality, age and residence were to some extent significant. Comorbid disorders were present in 12.5% of the subjects.

Adolescent↗
PubMed1998

Successful treatment with insulin analog lispro in IDDM with delayed absorption of subcutaneously applied human regular insulin and complicated intraperitoneal insulin infusion. A case report.

OBJECTIVE: To subcutaneously administer the insulin analog lispro in a patient with delayed absorption of subcutaneously applied human regular insulin whose continuous intraperitoneal insulin infusion (CIPII) with a percutaneous access device had required multiple surgical interventions because of complications. RESEARCH DESIGN AND METHODS: In a 35-year-old woman with long-term IDDM and delayed absorption of subcutaneously applied human regular insulin, a 3-year CIPII with human regular insulin via a percutaneous access device was complicated by three catheter obstructions and one subcutaneous abscess. Each complication required the implantation of a new percutaneous access device. During a 2-day trial with continuous subcutaneous insulin infusion (CSII) of the insulin analog lispro at basal infusion rates of 0.5-1.1 U/h, stable metabolic control was achieved. A 5-h intermediate attempt with human regular insulin in CSII, however, increased blood glucose concentrations from 6.0 to 28.8 mmol/l, despite identical basal rates and additional injection of 16 U of human regular insulin. Restarting with CSII of the insulin analog lispro reinforced stable metabolic control. CONCLUSIONS: It is suggested that the insulin analog lispro is a promising approach in the treatment of IDDM with delayed absorption of subcutaneously applied human regular insulin and a suitable alternative therapy for patients with complications attributed to percutaneous access devices for CIPII.

Administration, Cutaneous↗
PubMed1998

[Child and adolescent psychiatric services in the canton of Zurich: a comparison of outpatients, day clinic, and inpatient referral populations].

Findings in intervention research are an important basis for the discussion of issues pertaining to quality control. In Switzerland such findings have been rare. The present study of the entire 1988-1995 referred child and adolescent population of the Child and Adolescent Psychiatric Service of the Canton of Zurich (N = 7538 treated patients) concentrated on the demographic, diagnostic, and therapeutic attributes of the outpatient, day clinic, and inpatient populations that comprised the referred population. Marked differences are found in comparable studies from Germany with regard to patients treated in an inpatient setting. For example, the mean age of the patients in the Zurich sample is lower and patients with conduct disorders are more frequently represented. On the other hand, patients with psychotic illness are missing and, on the average, the duration of treatment is considerably longer. The reasons for these differences are to be found in the various structural attributes of the cantonal services that are provided in Zurich. In the area of inpatient care, where in comparison to outpatient settings and also day care settings patients with severe disorders are treated, there is a lack of places for the short-term care of acutely ill patients--for example, psychotic patients. This is especially true for adolescent patients. The limitations of traditional outpatient settings are frequently marked by unsatisfactory treatment results in outpatients with conduct disorders, developmental disorders, and a high impact of abnormal psychosocial circumstances.

Adolescent↗