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Biomedical subjects

J Wittmann

Publications and source records attributed to J Wittmann.

At least 19 recordsLinked to original sources
PubMed2006

Endoscopic ultrasound-guided tissue sampling by combined fine needle aspiration and trucut needle biopsy: a prospective study.

BACKGROUND AND AIMS: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has a diagnostic accuracy of 70-90%, depending on the site under evaluation. In order to improve EUS-guided tissue sampling a novel 19-gauge trucut-type needle has been designed to obtain core biopsies during EUS. We prospectively evaluated the safety and accuracy of EUS-FNA alone versus combined EUS-FNA and trucut needle biopsy (TNB) in patients referred to our Unit over a 3-year period. PATIENTS AND METHODS: A total of 159 patients underwent EUS-FNA alone (lesions<2 cm) or the combination of both sampling modalities (lesions>or=2 cm). The adequacy of sampling, sensitivity, specificity and overall accuracies of EUS-FNA or EUS-TNB alone and combined EUS-FNA/TNB were determined. RESULTS: Adequate samples were obtained by EUS-FNA, EUS-TNB and EUS-FNA/TNB in 91%, 88% and 97% of patients, respectively. From the pancreas (n=83), adequate samples were obtained by FNA in 94% and by TNB in 81%, compared with 87% and 92% from non-pancreatic sites (n=76), respectively. The combination of both techniques resulted in more adequate samples from non-pancreatic cases than EUS-FNA alone (P=0.044). The specificity was 100%. Overall accuracy for EUS-FNA alone was 77%, for EUS-TNB alone 73% and for EUS-FNA/TNB 91% (P=0.008). For pancreatic sampling, the accuracy of EUS-FNA alone was 77%, for EUS-TNB alone 56% and for EUS-FNA/TNB 83%. For non-pancreatic sampling, the accuracy for EUS-FNA alone was 78%, for EUS-TNB alone 83% and for EUS-FNA/TNB 95% (P=0.006). The complication rate was 0.6%. CONCLUSIONS: Combined EUS-FNA/TNB for lesions>or=2 cm improves adequacy of sampling and diagnostic accuracy compared with either technique alone and is safe.

Aged↗
PubMed2001

Are antidepressants less effective in the acute treatment of bipolar I compared to unipolar depression?

BACKGROUND: Using our routine documentation system we evaluated the hypothesis that antidepressants may be less effective in the acute treatment of bipolar I depressed patients compared to unipolar depressed patients. METHOD: Based on the data from 2032 consecutively admitted inpatients with unipolar or bipolar I depression we compared the efficacy of antidepressants in both groups. The outcome was assessed by the Global assessment scale (GAS), the duration of hospitalisation and the Apathic-, Depressive- and Manic Syndrome subscales of the Association for Methodology and Documentation in Psychiatry system. RESULTS: Cohorts were comparable in treatment regimens and severity of depression at admission. At discharge, there were no statistically significant differences between bipolar I and unipolar depression for the outcome criteria Depressive Syndrome scale, GAS score and days in hospital. Bipolar patients showed a slightly decreased score of the Apathic Syndrome scale at discharge, also reflected by a slightly elevated score of the Manic Syndrome scale. LIMITATIONS: This study did not check for differences in side effects such as switching or cycling commonly attributed to the use of tricyclic antidepressants in bipolar patients. Naturalistic data were obtained prospectively, analysis, however, was done retrospectively, thus limiting, but not completely excluding a possible selection bias. CONCLUSION: Evaluating different outcome criteria, our naturalistic data of a large cohort seem to reject the hypothesis that antidepressants may be less effective in the acute treatment of bipolar I compared to unipolar depressed patients.

Adult↗
PubMed2001

The negative regulator Opi1 of phospholipid biosynthesis in yeast contacts the pleiotropic repressor Sin3 and the transcriptional activator Ino2.

Structural genes of phospholipid biosynthesis in the yeast Saccharomyces cerevisiae are transcriptionally co-regulated by ICRE (inositol/choline-responsive element) promoter motifs. Gene activation by an ICRE is mediated by binding of the Ino2/Ino4 transcription factor, whereas repression in the presence of high concentrations of inositol and choline (IC) requires an intact Opi1 repressor. However, the mechanism of specific repression and the functional interplay among these regulators remained unclear from previous work. Using in vivo as well as in vitro interaction assays, we show binding of the pleiotropic repressor Sin3 to the pathway-specific regulator Opi1. The paired amphipathic helix 1 (PAH1) within Sin3 and OSID (Opi1-Sin3 interaction domain) in the N-terminus of Opi1 were mapped as contact sites. The regulatory significance of the Opi1-Sin3 interaction was shown by the obvious deregulation of an ICRE-dependent reporter gene in a sin3 mutant. Opi1 also interacts with a newly identified functional domain of the transcriptional activator Ino2 (RID, repressor interaction domain). These results define the molecular composition of the transcription complex mediating control of ICRE-dependent genes and allow a hypothesis on the flow of regulatory information in response to phospholipid precursors.

Amino Acid Sequence↗
PubMed2000

Long-term course of schizophrenic, affective and schizoaffective psychosis: focus on negative symptoms and their impact on global indicators of outcome.

OBJECTIVE: The aim of this study was to compare indicators of outcome between different types of psychosis and to verify whether or not negative symptoms (NS) have a special relevance for schizophrenia. METHOD: This is a follow-up study on functional psychosis according to ICD-9. Patients were assessed standardized at the time of first hospitalization and about 12.5 years later. RESULTS: Comparison of global outcome parameters and NS revealed that schizophrenia had the poorest outcome of all types of psychosis. NS had the highest impact on global functioning and the severity of illness in schizophrenia. NS assessed at the first hospitalization were associated with the different outcome parameters only in schizophrenia at follow-up. CONCLUSION: The course of schizophrenia is a more deteriorating one than that of affective or schizoaffective psychosis. The findings point to the special relevance of NS for the outcome and their relative specificity for schizophrenia.

Adult↗
PubMed1999

Deficit syndromes in schizophrenic patients 15 years after their first hospitalisation: preliminary results of a follow-up study.

This study is a follow-up study on broadly defined schizophrenic disorders. Patients were assessed standardized at the time of their first hospitalization (admission and discharge) and reassessed in an standardized manner 15 years later. The aim of the analyses presented here was to evaluate the frequency of patients with markedly expressed negative symptoms in terms of deficit syndrome and to analyze which of the variables assessed at the time of first hospitalization were predictive concerning deficit syndromes at follow-up. Results indicate that nearly one third of patients have developed a deficit syndrome 15 years after their first hospitalization. These patients are characterized by severe impairments in important areas of life, such as partnership or employment. Furthermore, apart from more pronounced negative symptoms, these patients also have more paranoid-hallucinatory symptoms than schizophrenic patients without deficit syndromes. Predictive signs for non-development of a deficit syndrome 15 years later were good global functioning, female gender, pronounced depressive symptoms and good treatment response concerning negative and paranoid-hallucinatory symptoms at first hospitalization. A longer duration of symptoms prior to first hospitalization, lack of a partnership, pronounced negative symptoms at admission and at discharge were predictive of developing a deficit syndrome. Results are discussed with regard to the literature and to methodological limitations.

Adult↗
PubMed1999

Proteolytic activity in the yolk sac membrane of quail eggs.

Extraembryonal degradation of yolk protein is necessary to provide the avian embryo with required free amino acids during early embryogenesis. Screening of proteolytic activity in different compartments of quail eggs revealed an increasing activity in the yolk sac membrane during the first week of embryogenesis. In this tissue, the occurrence of cathepsin B, a lysosomal cysteine proteinase, and cathepsin D, a lysosomal aspartic proteinase, has been described recently (Gerhartz et al., Comp Biochem Physiol, 118B:159-166, 1997). Determination of cathepsin B-like and cathepsin D-like proteolytic activity in the yolk sac membrane indicated a significant correlation between growth of the yolk sac membrane and proteolytic activity, shown by an almost constant specific activity. Both proteinases could be localized in the endodermal cells, which are in direct contact to the yolk. The concentration of proteinases in the endodermal cells appears to be almost unaltered in the investigated early stage of quail development, whereas the amount of endodermal cells increases rapidly, seen by a complicated folding of the yolk sac membrane. In the same cells quail cystatin, a potent inhibitor of quail cathepsin B (Ki 0.6 nM), has been localized at day 8 of embryonic development. Approximately at this stage of development, the quail embryo stops metabolizing yolk. In conclusion, it is strongly indicated that the amount of available free amino acids, produced by proteolytic degradation and supporting embryonic growth, is regulated by the growth of the yolk sac membrane.

Animals↗
PubMed1998

Longitudinal study of bone turnover after acute spinal cord injury.

Increased bone turnover is a sequel of spinal cord injury (SCI) and predisposes to a number of clinically relevant complications, including osteoporosis and fractures. There are limited data available regarding the changes in modern markers of bone metabolism after SCI. We report a 6-month longitudinal follow-up of biochemical markers of bone metabolism (free and total deoxypyridinoline, total pyridinoline, N-telopeptide, osteocalcin, and total alkaline phosphatase) and bone mineral densitometry in 30 subjects with acute SCI. Markers of bone formation showed only a minor rise, remaining within the reference range. In contrast, markers of bone resorption showed a significant rise after acute SCI, peaking around weeks 10-16, with values up to 10 times the upper limit of normal. Paired bone mineral densities (n = 11; on the average, determined 14 weeks apart) showed no change at the hip, lumbar spine, or radius, but demonstrated a decrement in the entire lower limbs. changes in biochemical markers of bone formation and resorption were comparable in patients with quadriplegia and paraplegia, except for a greater increase in quadriplegics in pyridinoline, expressed as a percentage of baseline. In conclusion, a marked increase in bone resorption and modest changes in bone formation occur after SCI, and possibly increased bone resorption occurs in quadriplegia.

Adolescent↗
PubMed1997

Quail cystatin: isolation and characterisation of a new member of the cystatin family and its hypothetical interaction with cathepsin B.

Quail cystatin, a new cysteine proteinase inhibitor protein of the cystatin superfamily, was purified from egg albumen of Japanese quail Coturnix coturnix japonica. Amino acid sequencing and mass spectrometry revealed the complete 116 amino acid residue primary structure of a phosphorylated form (13,173 Da). The inhibitor has a 90% sequence identity with chicken cystatin. Its interaction with papain is rapid and tight (Ki = 4.4 pM; k(on) = 1.8x10(7) M(-1) s(-1); k(off) = 0.8x10(-4) s(-1)) and very similar to that of chicken cystatin. Surprisingly, however, cathepsin B was inhibited 15-fold more strongly by quail cystatin (Ki = 47 pM; k(on) = 19x10(7) M(-1) s(-1); k(off) = 9x10(-4) s(-1)) than by chicken cystatin (Ki = 784 pM; k(on) = 2.9x10(7) M(-1) s(-1); k(off) = 24x10(-4) s(-1)). Intuitive comparative conformational inspection of related inhibitors and of cognate enzymes suggest that: (i) the 3D structure of quail cystatin is nearly identical to that of chicken cystatin, (ii) quail cystatin can interact with cathepsin B analogous to the stefin B-papain interaction, if the 'occluding loop' of cathepsin B possesses an 'open' conformation, (iii) the greater inhibition of cathepsin B by quail cystatin compared to chicken cystatins probably arises from two additional ionic interactions between residues Arg15 and Lys112 of the inhibitor and Glu194 and Asp124 of the enzyme, respectively. The two potential salt bridges are located outside of the known contact regions between cystatins and peptidases of the papain family.

Amino Acid Sequence↗
PubMed1997

Proteolytic enzymes in yolk-sac membrane of quail egg. Purification and enzymatic characterisation.

Degradation of yolk protein is essential for the early development of the avian embryo. In Japanese quail (Coturnix coturnix japonica), proteolysis in the surrounding tissue of the yolk, the yolk-sac membrane, can be inhibited by class-specific inhibitors of cysteine proteinases as well as of aspartic proteinases. Purification of the enzymes leads to one cysteine proteinase and one aspartic proteinase with an apparent molecular mass of 29 kD and 44 kD, respectively. Both enzymes were purified in a two-chain form, although a single-chain form is also present in the homogenate of yolk-sac membrane. The cysteine proteinase was identified by NH2-terminal sequence analysis as well as by kinetic studies as a new cathepsin B from quail. Like mammalian cathepsin B, this avian cathepsin B exhibits two different kinds of proteolytic activity, an endopeptidase activity and a dipeptidyl carboxypeptidase activity. Chicken egg white cystatin, a protein-aceous cysteine proteinase inhibitor, inhibits quail cathepsin B with an equilibrium dissociation constant (Ki) of 3.3 nM. Likewise the aspartic proteinase was identified as a new cathepsin D from quail. This avian cathepsin D has a different processing site to all known mammalian cathepsins D. In quail cathepsin D one NH2-termini is homologous to amino acids 211-230 in mammalian cathepsin D. This is more than 100 amino acids downstream of the mammalian processing site. Comparison of the enzymatic properties of quail and bovine cathepsin D indicate that the different processing site has no influence on the enzymatic properties.

Amino Acid Sequence↗
PubMed1995

[Simulation as a method for solving medical technical problems].

The present paper first presents a comprehensive overview of the methodological aspects of simulation. It lists the various approaches to the modelling of real-world systems and emphasizes the respective constraints on the interpretation of model data. For this purpose, a classification of typical applications of simulation models is given, and is followed by a discussion of three structurally different ways of constructing a model. The correct matching of these modelling concepts to the particular application problem in hand is discussed, with special consideration being given to the drawing of conclusions from, and the interpretation of, the simulation results. To round of the classification, the simulation models are differentiated in accordance with the nature of their implementation. By defining application type, modelling concept and model implementation, an understanding of the validity and appropriate application of any industrial model is derived.

Computer Simulation↗
PubMed1993

Activity of cholinesterases in the Japanese quail embryo. Effects of dichlorphos on the embryonic development.

Cholinesterase activity is detectable in the Japanese quail embryo, in the yolk and subembryonic liquid, but not in the albumen. Obviously, this enzyme is deposited by the hen into the yolk and from there it is transferred to the subembryonic liquid. In contrast, in the embryo the enzyme is synthesized by itself and the amount increases with the age of the embryo. By using BW284c51 1,5-bis-(4-allyldimethylammoniumphenyl)pentan-3-one bromide and ISO-OMPA tetraisoprophylpyrophosphoramide as inhibitors, it was found that the enzyme in the embryo is predominantly acetylcholinesterase (EC 3.1.1.7), whereas that in the yolk and subembryonic liquid is butyrylcholinesterase (EC 3.1.1.8). Both types are inhibited by dichlorphos. However, the embryonic enzyme activity is restored within 8 hr, whereas that in the subembryonic liquid remained inactive at least for 72 hr after inhibition. Enzyme inhibition leads to retardation of the development, to reduced accumulation of glucose and amino acids in the subembryonic liquid and finally to death of the embryo, suggesting that the developmental retardation is due to the restricted supply of glucose and amino acids. Surprisingly, most of the embryos die when the embryonic enzyme activity has again been restored.

Amino Acids↗
PubMed1993

Developmental retardation of the Japanese quail embryo under the influence of dexamethasone.

Cultured Japanese quail embryos were treated with various doses of dexamethasone on day 2 and in part also on day 5. The treatment lead to a significant delay of development. This was demonstrated by means of developmental (growth rate, developmental stage), histological and metabolic (excreted uric acid, protein synthesis) parameters. The effect was intensified when the agent was administered into the subembryonic liquid instead of the albumen. This is due to the fact that a higher dilution is expected when the agent is deposited into the albumen. In conclusion Japanese quail embryos respond to exogenous glucocorticoids, at a very early stage of development and at a comparatively low concentration with a depression of development.

Animals↗
PubMed1991

Respiratory function of catecholamines during the late period of avian development.

To study the function of catecholamines in the late period of avian embryogenesis, the time course of plasma catecholamines, the release of catecholamines by hypoxia and finally the effect of adrenergic agents on blood parameters and on circulation were recorded. The experiments reveal a temporary increase in plasma adrenaline and noradrenaline shortly before internal pipping occurs. On the other hand a premature increase of plasma catecholamines is induced by hypoxia. Furthermore, treating the embryo with adrenergic agents such as adrenaline, noradrenaline and phenylephrine resulted in changes of blood gas parameters: increase of PO2, O2-saturation and negative base excess, decrease of PCO2 and HCO3-. In addition, exogenous adrenaline and noradrenaline released an increase in the blood flow and an enhanced hemoglobin content in the chorioallantoic membrane, but not in the kidneys. Finally, adrenaline caused a decrease of 2,3 DPG and an increase of lactate in the plasma. The data indicate that hypoxia, which is formed normally towards the end of embryogenesis, induces an increased secretion of catecholamines which in turn improves the blood gas status. In this way the embryo is protected from deleterious hypoxic damages. This conclusion has been derived from experiments, in which the release of catecholamines was blocked under hypoxia. Under these conditions a significant increase in the mortality rate was observed.

2,3-Diphosphoglycerate↗
PubMed1991

The influence of thiourea on the development of the cultured quail embryo.

Although thyroid hormones are known to promote embryonic development, it is still questionable whether the hormones of the thyroid gland exert a stimulatory effect on the early embryo. In attempting to elucidate the thyroid function in this period, we tried to block the synthesis of thyroid hormones by thiourea and followed the embryogenesis under these conditions. The experiments were performed with cultured quail embryos (Coturnix coturnix japonica), which seemed especially suitable for those studies. The results demonstrate that thiourea causes a decrease of the survival rate, DNA-synthesis and of the excretion of uric acid into the allantoic liquid. Furthermore, it exerts an inhibitory effect on weight gain and developmental stages. On the basis of these results it seems very likely, that thyroid hormones exert a stimulatory effect on the development of quail embryos earlier than assumed previously.

Animals↗
PubMed1989

Accelerating and retarding effects of dexamethasone on the development of the avian lung.

Fertile eggs from Bovans hybrid were treated with dexamethasone on day 17 of incubation. This treatment resulted in a stimulation of the surfactant synthesis as recorded by the increased uptake of 14C-choline into the pulmonary phosphatidylcholine and the accumulation of lipoid vacuoles. On the other hand, dexamethasone caused a delay in pulmonary fluid absorption till day 19. This delay seems to be caused by a retarded onset of lung circulation. This conclusion has been derived from the lowered pulmonary hemoglobin content at this developmental stage. On the basis of the activities of ornithokallikrein and the angiotensin converting enzyme, ornithokinin may be involved in the retarded onset of circulation.

Animals↗
PubMed1988

Formation and changes of the subembryonic liquid from turned, unturned, and cultured Japanese quail eggs.

Japanese quail eggs belonging to the same flock of hens were incubated under different conditions: group 1 eggs were turned 3 times a day, group 2 eggs were left unturned, and group 3 eggs were cultured and left unturned. The results indicate that failure to turn eggs results in a delayed efflux of liquid and glucose from albumen and from the subembryonic liquid. Furthermore, the major difference between unturned and cultured eggs was that in the first group the glucose levels and in the second group the lactate levels of the subembryonic liquid were increased. It is suggested that reduced glucose supply may be involved in the disturbance of development of unturned and cultured eggs.

Animals↗
PubMed1987

Activity of putative pulmonary ornithokallikrein and angiotensin-converting enzyme during the onset of lung respiration in the chick embryo.

We have assayed a proteinase from chicken lungs, the properties of which were comparable to those of ornithokallikrein, the enzyme that catalyzes the formation of ornithokinin. The activity of this pulmonary proteinase showed an accelerated increase during the development of lung respiration (paranatal period). In contrast, the increase in the activity of angiotensin-converting enzyme (ACE), which degrades kinin, was not enhanced at this developmental stage. L-thyroxine administration accelerated the onset of lung respiration and the associated changes in the activities of ornithokallikrein and ACE. Thiourea, on the other hand, retarded the onset of lung respiration. Concomitantly, there was no pronounced increase in ornithokallikrein activity and no attenuation of the increase in ACE activity. Furthermore, the development of lung circulation, as measured by pulmonary hemoglobin concentration, paralleled the ornithokallikrein activity. The results suggest that the increase in ornithokallikrein activity and the suppression of ACE activation during the paranatal period help adapt the embryo to the neonatal period.

Animals↗