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Biomedical subjects

M Köster

Publications and source records attributed to M Köster.

At least 19 recordsLinked to original sources

Sickness behavior of rats with abdominal sepsis can be improved by antibiotic and G-CSF prophylaxis in clinic modeling randomized trials.

BACKGROUND AND AIM: In clinical sepsis research nearly all immune-modulators have demonstrated no benefit in regard to the 28-day mortality rate. Other endpoints such as quality of life have become more attractive, but clinically relevant animal models analyzing an equivalent to quality of life by measurement of sickness behavior are extremely rare. The concept of clinic modeling randomized trials was used in an animal trial to model clinical complexity and conditions of a randomized clinical trial. METHODS: 80 adult male Wistar rats were randomly assigned to (1) control: anesthesia and sham operation, (2) sepsis: laparotomy and peritoneal infection with human stool bacteria, (3) sepsis with antibiotic prophylaxis: cefuroxime/metronidazole and (4) sepsis with antibiotic plus a cytokine prophylaxis with granulocyte-colony stimulating factor (GCSF). Endpoints were physiological and behavioral parameters. RESULTS: The combination of antibiotics plus G-CSF was most effective in reducing mortality. All infected animals showed reduced open field activity acutely after infection, and recovery was improved during the 9 day follow-up in rats with prophylactic treatments. In the social interaction test, but not in the elevated plus-maze anxiety test, prophylaxis was also efficient, especially with antibiotics and G-CSF. CONCLUSIONS: The results show that improving sickness behavior in septic rats with G-CSF plus antibiotics may be a promising approach.

Animals↗

Changing sex ratio in acute coronary heart disease: data from Swedish national registers 1984-99.

OBJECTIVES: To examine trends in sex ratios for different manifestations of coronary disease. DESIGN: National Swedish registers on hospital discharges and cause-specific deaths were used to calculate age- and sex-specific trends and sex ratios for coronary admissions and deaths. SETTING: Nineteen Swedish counties, average population 4.8-5.1 million in the investigated age groups. SUBJECTS: All patients aged 25-84 years with first hospital admissions or deaths as a result of coronary heart disease in 1984-99, in total 432,871 cases. MAIN OUTCOME MEASURES: Ratio men/women and rates (per 100,000) of acute myocardial infarction (AMI), acute admissions for angina and total of all acute admissions for any coronary disease. RESULTS: Below age of 65 years AMI incidence decreased more for men than for women and rates of acute admissions for angina increased more in women than in men. In men and women above 65 years trends were almost identical. In 1984-87 the ratio men/women with respect to myocardial infarction was 5.6 at age 25-44 years, but decreased to 3.7 in 1996-99. Corresponding sex ratios for angina decreased from 3.2 to 1.8 and for total coronary heart disease from 4.7 to 2.8. Amongst men and women aged 45-54 years, the sex ratio with respect to myocardial infarction decreased from 5.6 to 4.1, for angina from 2.4 to 1.7 and for total acute coronary disease from 4.2 to 2.7. Ratios men/women decreased less at higher ages and remained unchanged throughout the period in the oldest age group. CONCLUSIONS: Overall, we found decreasing sex ratios at ages below 65, but above age 65 years trends in men and women were similar. These developments could be due to changing criteria for admission and diagnosis, but true differences in the clinical manifestation of coronary disease, possibly in response to secular trends in risk factor levels, cannot be excluded.

Adult↗

[Concepts in early planning for vocational rehabilitation in schizophrenia patients during acute care].

The particular relevance of employment for financial independence, acquisition of social skills and, hence, an increase in self-confidence is undeniable, and has for several years now been increasingly considered an essential component of care notably in psychiatric disorders. Vice versa, unemployment is deemed a potential risk factor with regard to poorer therapeutic response and social integration as well as a higher incidence of crises in persons with mental illness. Schizophrenia is among the psychiatric disorders very often resulting in unemployment and subsequent early pensioning. Planning for vocational rehabilitation early-on during acute care therefore is considered of greatest importance especially in this patient group. This article gives a brief overview of the main concepts drawn on in preparing the vocational rehabilitation of patients with Schizophrenia, focussing in particular on their relevance for daily practice and the possibilities for evaluating their effectiveness.

Activities of Daily Living↗

Neurological sequelae in children born after in-vitro fertilisation: a population-based study.

BACKGROUND: There is an absence of population-based long-term studies on the risk of neurological sequelae in children born after in-vitro fertilisation (IVF). Our aim was to compare the frequency of such problems between IVF-born children and controls. METHODS: We did a population-based retrospective cohort study in which we compared development of neurological problems in 5680 children born after IVF, with 11360 matched controls. For 2060 twins born after IVF, a second set of controls (n=4120), all twins, were selected. We obtained data on neurological problems from the records of the Swedish habilitation centres. FINDINGS: Children born after IVF are more likely to need habilitation services than controls (odds ratio 1.7, 95% CI 1.3-2.2). For singletons, the risk was 1.4 (1.0-2.1). The most common neurological diagnosis was cerebral palsy, for which children born after IVF had an increased risk of 3.7(2.0-6.6), and IVF singletons of 2.8 (1.3-5.8). Suspected developmental delay was increased four-fold (1.9-8.3) in children born after IVF. Twins born after IVF did not differ from control twins with respect to risk of neurological sequelae. Low-birthweight and premature infants were more likely to need habilitation than fullterm babies. Maternal age did not affect risk. INTERPRETATION: Our study suggests that children born after IVF have an increased risk of developing neurological problems, especially cerebral palsy. These risks are largely due to the high frequency of twin pregnancies, low birthweight, and prematurity among babies born after IVF. To limit these risks, we recommend that only one embryo should be transferred during IVF.

Adolescent↗

STAT1 from the cell membrane to the DNA.

The binding of interferons (IFNs) to their receptors leads to the phosphorylation and activation of signal transducers and activators of transcription (STATs), and their translocation from the cytoplasm to the nucleus. The mechanisms by which the STATs move to the nuclear pore are not, however, known. Here it is shown that IFN-alpha and -gamma signalling and STAT1 translocation are independent of the actin cytoskeleton or microtubules. Using fluorescence loss in photobleaching (FLIP) and fluorescence recovery after photobleaching (FRAP) experiments, the mobility of a fusion protein of STAT1 with green fluorescent protein (STAT1-GFP) was compared with that of GFP and protein kinase C-GFP. In IFN-gamma-treated and control cells, cytoplasmic STAT1-GFP shows high, energy-independent, mobility comparable to that of freely diffusible GFP. A random walk model for movement of STAT1 from the plasma membrane to the nuclear pore is, therefore, indicated. Nuclear STAT1-GFP showed similar high mobility, with exclusion from nucleoli, consistent with high rates of association and dissociation of STAT1-DNA and/or STAT1-protein complexes in the nucleoplasm of the cell.

Biological Transport↗

Structure and expression of Xenopus tropicalis BMP-2 and BMP-4 genes.

The Xenopus tropicalis BMP-2 and BMP-4 genes have been cloned and sequenced. A comparison with the corresponding genes from X. laevis reveals that the BMP-4 genes are conserved at a higher extent than the BMP-2 genes. This is especially evident for the intron sequences, but is also reflected by the exon sequences. While the amino acids of X. tropicalis and X. laevis BMP-4 proteins diverge at about 4%, those of BMP-2 proteins diverge at about 7%. By reverse transcriptase polymerase chain reaction analyses and whole mount in situ hybridizations, we demonstrate the temporal and spatial expression patterns of X. tropicalis BMP-2 and BMP-4 genes. BMP-2 is found to be expressed maternally, and later in development, in migrating heart progenitor cells as well as in the final heart, within the pineal gland and the olfactory placodes. BMP-4 is zygotically activated within the ventral marginal zone and later found in the eye, the otic vesicle, the heart and within blood islands. Although the overall patterns are very similar to those found in X. laevis, there is some distinct difference which might result from the accelerated development in X. tropicalis.

Amino Acid Sequence↗

Sex differences in survival after myocardial infarction in Sweden; data from the Swedish National Acute Myocardial Infarction Register.

AIMS: Women, particularly younger women, hospitalized with acute myocardial infarction have been found to have poorer prognosis than men. A large proportion of deaths due to myocardial infarction, however, occur in the pre-hospital phase. We set out to analyse age-specific sex differences in survival after myocardial infarction at different time intervals from the onset of acute myocardial infarction, including pre-hospital deaths and 1-year overall survival. METHODS AND RESULTS: The National Acute Myocardial Infarction Register in Sweden was used to analyse age-specific sex differences in mortality outside hospital, 28-day mortality and 1-year mortality in 353 905 cases occurring between 1987 and 1995 in Swedish men and women aged 30 to 89 years. Overall, one in four of all myocardial infarction victims died outside hospital. At all ages, except in individuals younger than 50 years, men had higher pre-hospital mortality. The odds of dying within 28 days for women below 50 years of age, compared to men, was 1.84 (1.56--2.18) in hospitalized patients and 1.31 (1.18--1.46) in all infarction patients. Above the age of 65, in the total population with myocardial infarction, women had a better prognosis, with odds ratios ranging from 0.83 to 0.89. In patients surviving the first 28 days, 4.0% of the women and 2.9% of the men below the age of 50 were dead within a year after the infarction, odds ratio 1.37 (1.06--1.76). This excess mortality was mainly due to diabetes and non-cardiac causes. Only women younger than 50 years had a significantly poorer overall 1-year survival than men of the same age. At the age of 70 or more, women had a small survival advantage. CONCLUSION: In the total acute myocardial infarction population, only women under 50 years of age have a consistently worse prognosis than men. Much of the excess mortality in young women seems to be associated with diabetes.

Aged↗

The Golgi matrix protein GM130: a specific interacting partner of the small GTPase rab1b.

To detect specific partners of the small Golgi-localized GTPase rab1b we generated rab1b mutants and used them as bait proteins in yeast two-hybrid screens. We isolated several specifically interacting clones. Two of them encode large protein fragments highly homologous to rat GM130 and to human Golgin95. The full-length human GM130 cDNA was cloned and its interaction with rab1b was characterized in detail by yeast two-hybrid and in vitro binding assays. Here we report for the first time that the rab1b protein interacts specifically with GM130 in a GTP-dependent manner and therefore needs the hypervariable regions of the N- and C-termini. We mapped the rab1b binding site of GM130 and provide evidence that it is different to the previously described p115 and Grasp65 binding sites of the GM130 protein.

Amino Acid Sequence↗

Bacterial populations and processes involved in acetate and propionate consumption in anoxic brackish sediment.

Bacterial populations and pathways involved in acetate and propionate consumption were studied in anoxic brackish sediment from the Grosser Jasmunder Bodden, German Baltic Sea. Uptake of acetate and propionate from the porewater was studied using stable carbon isotope-labeled compounds. Labeled acetate was not produced as an intermediate during propionate uptake experiments, and propionate consumption was not affected by the addition of acetate. In parallel, incorporation of labeled acetate and propionate into phospholipid-derived fatty acids (PLFA) was studied to indicate bacterial populations involved in the consumption of these substrates. The (13)C-acetate label was mainly recovered in even-numbered PLFA (16:1omega7c, 16:0 and 18:1omega7c). In contrast, primarily odd-numbered PLFA (a15:0, 15:0, 17:1omega6 and 17:0) and the even-numbered i16:0 were labeled after incubation with (13)C-propionate. Although single PLFA labeled with propionate are commonly found in sulfate reducers, the complete PLFA-labeling pattern does not resemble any of the know strains. However, the acetate-labeling pattern is similar to Desulfotomaculum acetoxidans and Desulfofrigus spp., two acetate-consuming, sulfate reducers. In conclusion, our data suggest that acetate and propionate were predominantly consumed by different, specialized groups of sulfate-reducing bacteria.

Journal Article↗

Activin A signaling directly activates Xenopus winged helix factors XFD-4/4', the orthologues to mammalian MFH-1.

We investigated the Xenopus winged helix gene XFD-4, its cDNA, and a pseudoallelic cDNA, termed XFD-4', representing Xenopus orthologues to chicken CWH-2 and mammalian MFH-1. XFD-4/4' genes are activated after midblastula transition in dorsolateral mesoderm but not within the dorsal lip. Later, expression is found in two segmented lines of cells bordering the somites, in head mesenchyme, in ventral abdominal muscle, and in the tail tip. Smad2 RNA injection leads to ectopic expression of XFD-4'. Since activation is also observed in activin A treated animal cap explants in the presence of cycloheximide, XFD-4/4' genes represent direct targets of activin signaling. Note that the future nomenclature for XFD-4 will be FoxC2a and for XFD-4' will be FoxC2b (Fox Nomenclature Committee).

Activins↗

[Trial employment: a provisional work setting for psychiatric patients].

OBJECTIVE: This study investigates the effects of probationary work for psychiatric patients in community-based small businesses during their inpatient or day care. METHODS: Patients were evaluated for working capacity, psychopathology, motivation for work and patient satisfaction (n = 69). RESULTS: The results confirm a high degree of acceptance of this approach as well as significant improvements on various clinical scales such as the Brief Psychiatric Rating Scale (BPRS), the Beck Depression Inventory (BDI), the Global Assessment of Functioning Scale (GAF), choice reaction time (Wiener Determinationsgerät, WDG), attention (Revisionstest) and self-rating of work-relevant skills. CONCLUSIONS: This approach, with its complex demand characteristics, may be an effective alternative to occupational therapy, at least for small therapeutic units.

Adult↗

Obstetric complications and the risk of schizophrenia: a longitudinal study of a national birth cohort.

BACKGROUND: Numerous epidemiological studies found an increased risk of schizophrenia among persons exposed to various obstetric complications. The underlying mechanisms are unknown. OBJECTIVE: To study specific risk factors, as well as sets of risk factors, representing 3 different etiologic mechanisms: (1) malnutrition during fetal life; (2) extreme prematurity; and (3) hypoxia or ischemia. METHODS: In this longitudinal cohort study, information in the National Birth Register was linked to the National Inpatient Register. We followed up 507516 children born between 1973 and 1977 with regard to a diagnosis of schizophrenia between 1987 and 1995 (238 cases). By record linkage, we also had access to data on psychiatric illness in the mother. Occurrence of schizophrenia was measured by the Mantel-Haenszel test and logistic regression. RESULTS: A number of specific risk factors were associated with an increased risk of schizophrenia. The relative risk (95% confidence interval) for preeclampsia was 2.5 (1.4-4.5); vacuum extraction, 1.7 (1.1-2.6); and malformations, 2.4 (1.2-5.1). In logistic regression models, we found that indicators of all 3 etiologic mechanisms were associated with increased point estimates of schizophrenia, although at lower risk levels. Preeclampsia, an indicator of fetal malnutrition, was the only risk factor with statistically significant increased risk after control for all potentially confounding factors. CONCLUSION: This study supports the theory of an association between obstetric complications and schizophrenia. Although preeclampsia was the strongest individual risk factor, there was evidence of increased risk associated with all 3 etiologic mechanisms.

Adult↗

Genomic structure and embryonic expression of the Xenopus winged helix factors XFD-13/13'.

We have isolated the gene, its corresponding cDNA and a closely related cDNA encoding the Xenopus winged helix factors XFD-13' and XFD-13, respectively. XFD-13/13' are regarded as pseudo-alleles and, based upon a comparison of sequences and genomic structures, represent the Xenopus orthologues to mammalian FREAC-1/HFH-8. XFD-13/13' genes are not transcribed during oogenesis, zygotic transcription starts at late gastrula/early neurula and transcripts persist throughout embryogenesis. Expression is found within head derived neural crest cells and the dorsolateral plate (DLP). At later developmental stages, cell populations of the DLP migrate to the ventral region but exclude the most posterior part. Since they are subsequently found to accumulate in vessel like structures, we suggest that these cells represent hematopoietic/endothelial progenitor cells.

Amino Acid Sequence↗

Characterization of a subfamily of related winged helix genes, XFD-12/12'/12" (XFLIP), during Xenopus embryogenesis.

The fork head domain family of genes defines a growing group of proteins that serve important regulatory functions in pattern-forming events of both invertebrates and vertebrates. Here we add three closely related, novel members to this family in Xenopus laevis, termed XFD-12, XFD-12' and XFD-12". All three genes reveal indistinguishable expression patterns during Xenopus embryogenesis. During gastrulation, XFD-12 type transcripts are detected exclusively in the superficial layer of cells within the Spemann organizer territory. In the open neural plate, XFD-12 type expression defines a row of cells located along the dorsal midline and destined to become the floor plate of the neural tube. After closure of the neural tube, XFD-12 type encoding mRNAs are only detected in the tailtip and a small area located at the midbrain/hindbrain boundary. Within the Spemann organizer and in the floor plate area, expression of XFD-12 type genes is only partially overlapping with XFD-1 expression.

Amino Acid Sequence↗

Dynamic redistribution of STAT1 protein in IFN signaling visualized by GFP fusion proteins.

STAT proteins (signal transducers and activators of transcription) are a family of transcription factors which are used by many cytokines and cell growth factors for initiating gene expression. They are activated by tyrosine phosphorylation through the cytoplasmic domain of stimulated receptors. Upon phosphorylation STAT proteins dimerize, translocate to the nucleus and activate transcription by binding to specific recognition sites. Different cytokines activate different subsets of STATs and other signaling proteins. We have made use of green fluoresencent protein (GFP) fusion proteins to visualize the subcellular localization and trafficking of STAT1, STAT2 and p48 during interferon (IFN) stimulation and have analysed in detail STAT1-GFP trafficking in living cells. Analysis of GFP fusion proteins allowed the determination of time kinetics of subcellular trafficking in individual living cells. STAT1-GFP is indistinguishable from its wild-type protein displaying strong activity as transcriptional activator as well as the same time kinetics of transport to the nucleus and retreat to the cytoplasm. After prolonged exposure to IFN, STAT1-GFP is no longer retained in the nucleus and relocation to the cytoplasm is observed. Restimulation with the same type of IFN does not lead to repeated nuclear translocation of STAT1-GFP. STAT1 is not subject of inhibition, as restimulation with another type of IFN allows immediate reuse of previously activated STAT1-GFP. However, restimulation with the same type of IFN can be achieved when the primary stimulus is removed after a short induction period. This method of visualizing signal transduction reveals a considerable inhomogeneity with respect to the extent of STAT1-GFP shuttling within a clonal cell population, indicating that competence for full-blasted IFN response is restricted to a cellular subpopulation whereas other cells respond incompletely, retarded or not at all.

Animals↗

Risk factors for neck and upper limb disorders: results from 24 years of follow up.

OBJECTIVES: To investigate associations between different potential risk factors, related and not related to work, and disorders of the neck and upper extremities occurring up to 24 years later. METHODS: The study comprised 252 women and 232 men, Swedish citizens, 42-59 years of age and in a broad range of occupations. Information about potential risk factors was available from a former study conducted in 1969. Data on disorders of the neck, shoulder, and hand-wrist disorders were obtained retrospectively for the period 1970-93. RESULTS: Risk factors were found to differ between the sexes. Among women over-time work, high mental workload, and unsatisfactory leisure time were associated with disorders in the neck-shoulder region. Interaction was found between high mental workload and unsatisfactory leisure time. Neck symptoms earlier in life were associated with recurrent disorders. Hand and wrist disorders were associated mainly with physical demands at work. Among men blue collar work and a simultaneous presence of high mental workload and additional domestic workload predicted disorders in the neck-shoulder region. CONCLUSIONS: Factors related and not related to work were associated with disorders of the neck, shoulders, and hands and wrist up to 24 years later in life. These included factors related to working hours which previously have not been noted in this context. Interactions between risk factors both related and not related to work were commonly found.

Adult↗