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Biomedical subjects

K Michel

Publications and source records attributed to K Michel.

At least 55 records · Page 3Linked to original sources
PubMed1998

Analysis of the expression pattern of the latent transforming growth factor beta binding protein isoforms in normal and diseased human liver reveals a new splice variant missing the proteinase-sensitive hinge region.

Latent transforming growth factor beta binding protein (LTBP), a component of the extracellular matrix (ECM) of various tissues, is important for the secretion of TGF-beta and, furthermore, for the storage of TGF-beta in ECM. The proteolytic cleavage of LTBP is assumed to be the prerequisite for the activation of TGF-beta. We investigated the mRNA expression pattern of the three LTBP isoforms (LTBP-1, -2, -3) and the protein distribution of the components of the large latent TGF-beta complex, namely LTBP-1 and -2, latency-associated protein (LAP), and TGF-beta, in human liver using reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemical alkaline phosphatase anti-alkaline phosphatase (APAAP) staining. Parts of explanted livers diagnosed as hepatitis B, hepatitis C, primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC) and normal liver tissue were examined. LTBP transcripts were detected in the same manner in all liver specimens. Interestingly, we found a new splice variant of LTBP-1 (LTBP-1D), in which the sequence coding for the proteinase-sensitive hinge region is deleted. The corresponding parts of the human LTBP-2 and LTBP-3 cDNA coding for the hinge region were sequenced and show neither similar proteinase cleavage sites nor deleted cDNA sequences. The proposed proteinase cleavage site of mouse LTBP-3 seems not to be conserved in the human LTBP-3 gene. By immunohistochemistry, LTBP-1, -2, and LAP were detectable in normal and diseased livers and showed a different staining pattern for both LTBP isoforms. By contrast, TGF-beta showed a spotted staining pattern in diseased livers only, predominantly in the area of parenchymal cells that are close to fibrotic tissue. This strongly suggests the release of active TGF-beta from preexisting latent complexes. The LTBP-1D splice variant, which is probably less sensitive against proteolytic degradation and therefore may protect TGF-beta from activation, may have importance for modulating the biological activity of TGF-beta in normal and diseased liver.

Amino Acid Sequence↗
PubMed1998

Isoforms and splice variant of transforming growth factor beta-binding protein in rat hepatic stellate cells.

BACKGROUND & AIMS: Hepatic stellate cells (HSCs) are one important source for transforming growth factor beta (TGF-beta). They produce TGF-beta in a latent form associated with latency-associated peptide and latent TGF-beta-binding protein (LTBP). This study was designed to investigate, on RNA and protein levels, which isoforms of LTBP and TGF-beta are expressed in HSCs and myofibroblasts. METHODS: HSCs isolated from rat liver were analyzed for LTBP and TGF-beta at various times of culture during transdifferentiation into myofibroblasts using immunocytochemical staining, metabolic labeling and immunoprecipitation, reverse-transcription polymerase chain reaction (RT-PCR), and sequencing. RESULTS: Alkaline phosphatase-anti-alkaline phosphatase staining and fluorescence immunostainings indicated the expression of all three components of the large latent TGF-beta complex in HSCs and myofibroblasts. Transcripts of three TGF-beta and LTBP isoforms were detected by RT-PCR and confirmed by sequence analyses. A new LTBP-1 splice form was found lacking part of the hinge region with a potential proteinase cleavage site. Metabolic labeling followed by immunoprecipitation with LTBP antiserum confirmed the synthesis and secretion of various LTBP-related proteins. CONCLUSIONS: The existence of different LTBP isoforms and splice variants in HSCs and myofibroblasts suggests multiple functions of the LTBP family in rat liver, which might not be restricted to the maintenance of TGF-beta latency.

Amino Acid Sequence↗
PubMed1998

Placement of a low-profile duodenostomy and jejunostomy device in five dogs.

Five male crossbred dogs successfully underwent surgical placement of button enterostomy tubes to evaluate the placement technique, maintenance and complications of these tubes. Surgical placement was quick, technically straightforward and similar to techniques used for other feeding tubes. None of the dogs experienced life-threatening complications during the 10 month follow-up period. One device required replacement as it was removed by the dog before a permanent fistula had formed. Open tubes due to loose safety plugs and focal cellulitis surrounding the exit sites of these tubes were noted in all dogs. The button tube may be a feasible option for long-term nutritional support in patients with pancreatic, hepatobiliary or gastrointestinal conditions.

Animals↗
PubMed1998

Relation between attempted suicide and suicide rates among young people in Europe.

STUDY OBJECTIVE: To determine if there are associations between rates of suicide and attempted suicide in 15-24 year olds in different countries in Europe. DESIGN: Attempted suicide rates were based on data collected in centres in Europe between 1989 and 1992 as part of the WHO/EURO Multicentre Study of Parasuicide. Comparison was made with both national suicide rates and local suicide rates for the areas in which the attempted suicide monitoring centres are based. SETTING: 15 centres in 13 European countries. PATIENTS: Young people aged 15-24 years who had taken overdoses or deliberately injured themselves and been identified in health care facilities. MAIN RESULTS: There were positive correlations (Spearman rank order) between rates of attempted suicide and suicide rates in both sexes. The correlations only reached statistical significance for male subjects: regional suicide rates, r = 0.65, p < 0.02; national suicide rates, r = 0.55, p < 0.02. CONCLUSIONS: Rates of attempted suicide and suicide in the young covary. The recent increase in attempted suicide rates in young male subjects in several European countries could herald a further increase in suicide rates.

Adolescent↗
PubMed1998

Structural and functional organization of the enteric nervous system in the stomach.

This report summarises some features of the gastric enteric nervous system in the guinea-pig model. Particular attention has been paid to relations between neurochemical properties, electrophysiological and putative function of enteric neurones. (1) Cholinergic and nitrergic neurones form separate neuronal populations. (2) Ascending neurones outnumbered descending ones. (3) Transmitter-phenotype and projection were related: cholinergic neurones were primarily ascending while nitrergic neurones were mainly descending. (4) The neurochemical code, i.e. the transmitter colocalisation, could be related to the function of enteric neurones. Colocalisation of substance P and/or enkephaline in cholinergic neurones was characteristic for ascending excitatory muscle neurones. Descending inhibitory muscle neurones were nitrergic often colocalising the neuropeptides neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP). In the intrinsic innervation of the gastric mucosa NPY/VIP was abundant and colocalised in ascending cholinergic as well as descending nitrergic neurones. (5) The vast majority of ascending and descending interneurones were cholinergic and often colocalised NPY. (6) The majority of descending mucosa and descending inhibitory muscle neurones were tonically-firing neurones. Our results revealed the characteristics of some neural components within the enteric nervous system of the stomach which are involved in modulation of mucosa and muscle functions. It may be concluded that muscle and mucosa functions are under the control of the enteric nervous system which contains distinct populations responsible for motor and secretory activity.

Animals↗
PubMed1997

Subpopulations of gastric myenteric neurons are differentially activated via distinct serotonin receptors: projection, neurochemical coding, and functional implications.

The enteric nervous system coordinates various gut functions. Functional studies suggested that neurotransmitters and neuromodulators, one of the most prominent among them being 5-HT, may act through a specific modulation of ascending and descending enteric pathways. However, it is still mostly unknown how particular components of enteric reflex circuits are controlled. This report describes experiments aimed at identifying a differential activation of enteric pathways by 5-HT. Electrophysiological and immunohistochemical methods were combined to investigate the projection pattern and the transmitter phenotype of 5-HT-sensitive gastric myenteric neurons. Of 294 intracellularly labeled neurons, 60.5% showed responses mediated via 5-HT3 receptors, 11.3% were 5-HT1P-responsive, 3.7% exhibited both 5-HT3 and 5-HT1P receptor-mediated depolarization, and 24.5% were not responding to 5-HT. The 5-HT3-responsive cells were mainly cholinergic (79%) and had ascending projections, whereas the 5-HT1P-responsive cells had primarily descending projections and were nitrergic (67%). Substance P-positive neurons were cholinergic; most of the cells (75%) exhibited 5-HT3 mediated responses and had ascending projections. Muscle strip recordings supported the functional significance of the differential location of 5-HT receptor subtypes. Thus, contractile responses of gastric circular muscle strips were dose-dependently increased by a 5-HT3 and decreased by a 5-HT1P agonist. Results indicated that excitatory ascending enteric pathways consisting of cholinergic, substance Pergic neurons were activated by 5-HT3 receptors, whereas 5-HT1P receptors were involved in activation of inhibitory descending pathways using nitrergic neurons. This suggested that different effects of 5-HT on gastric functions are related to specific activation of receptors located on different subsets of enteric neurons.

Animals↗
PubMed1997

Complications associated with use of jejunostomy tubes in dogs and cats: 40 cases (1989-1994).

OBJECTIVE: To evaluate complications and outcomes of surgeries in which jejunostomy tubes were used in critically ill dogs and cats. DESIGN: Retrospective review of medical records. ANIMALS: 32 dogs and 8 cats. PROCEDURE: In each animal, a 5-F or 8-F red rubber urethral/feeding catheter was surgically placed in the proximal portion of the jejunum. RESULTS: The most common indication for jejunostomy tube placement in dogs was a gastrointestinal condition (20 dogs; 62.5%). Neoplasms were detected in 11 of the 20 dogs. Pancreatic disease was the most common indication for tube placement in cats (7 cats; 87.5%). Thirty-three animals (27 dogs, 6 cats; 82.5%) did not have complications. Five dogs and 2 cats had 10 tube-related complications, including focal cellulitis (3 dogs), tube dislodgement (2 dogs, 1 cat), and tube occlusion (1 dog, 1 cat). Twenty-four animals (20 dogs, 4 cats; 60%) were discharged from the hospital. Fifteen dogs and 4 cats were alive 2 weeks after discharge, and 5 dogs and 2 cats survived for at least 4 weeks after discharge. Deaths were related to disease and were not associated with jejunostomy tubes. CLINICAL IMPLICATIONS: The complication rate associated with jejunostomy tubes appears to be low. Complications usually are nonfatal.

Animals↗
PubMed1997

Identification of a positive regulatory element responsible for tissue-specific expression of prostate-specific antigen.

The prostate-specific antigen (PSA) promoter (PSA-P) has been identified, characterized, and determined to be tissue specific. Compared with high expression of the genomic PSA gene in prostate cells, expression of the transgene driven by the putative PSA promoter is low. This suggests that the identified promoter may be incomplete or may function optimally with additional regulatory elements. To identify the presence of additional regulatory elements, we screened sequences upstream of the PSA promoter and identified a DNA fragment of 822 bp, which enhances PSA gene expression. Combining the newly identified PSA gene regulatory sequence (PSAR) with our previously identified PSA promoter (PCPSA-P) exhibited enhanced expressional activity in the PSA-producing LNCaP cell line. With the addition of 10 to 100 nM dihydrotestosterone, a more than 1000-fold increase in expression was observed as compared to androgen-negative controls. Furthermore, although the combined regulatory element (PSAR)-PSA promoter (PCPSA-P) sequence resulted in high transgene expression in LNCaP cell lines, the combined regulatory element-promoter sequence resulted in minimal expression in the non-PSA-producing prostate cell line PC-3, renal tumor cell line R11, and cervical adenocarcinoma cell line HeLa. The newly identified 822 bp alone could also function as a promoter. Compared with the combined promoter, however, the 822-bp fragment alone demonstrated lower activity and lower responsiveness to androgen stimulation. Our results suggest that coupling the PSA promoter with an upstream regulatory element results in a marked increase in PSA expression, suggesting that the complete PSA promoter contains two functional domains: a proximal promoter and a distal promoter, which can also function as an enhancer. The enhanced gene expression of the new construct, combined with its tissue specificity and androgen responsiveness, in turn provides a foundation for the development of tissue-specific vectors for prostate cancer gene therapy.

Base Sequence↗
PubMed1997

A repetition-prediction study of European parasuicide populations: a summary of the first report from part II of the WHO/EURO Multicentre Study on Parasuicide in co-operation with the EC concerted action on attempted suicide.

One of the aims of the European Study on Parasuicide, which was initiated by the Regional Office for the European Region of the World Health Organization in the mid-1980s, was to try to identify social and personal characteristics that are predictive of future suicidal behaviour. A follow-up interview study (the Repetition-Prediction Study) was designed, and to date 1145 first-wave interviews have been conducted at nine research centres, representing seven European countries. The present paper provides an abridged version of the first report from the study. The design and the instrument used (The European Parasuicide Study Interview Schedules, EPSIS I and II) are described. Some basic characteristics of the samples from the various centres, such as sex, age, method of suicide attempt, and history of previous attempts, are presented and compared. The male/female sex ratio ranged from 0.41 to 0.85; the mean age range for men was 33-45 years and that for women was 29-45 years. At all of the centres, self-poisoning was the most frequently employed method. On average, more than 50% of all respondents had attempted suicide at least once previously. The representativeness of the samples is discussed. There were differences between the centres in several respects, and also in some cases the representativeness of the different samples varied. Results obtained from analyses based on pooled data should therefore be treated with caution.

Adolescent↗
PubMed1997

Contacts of suicide attempters with GPs prior to the event: a comparison between Stockholm and Bern.

The aim of this study was to investigate patterns of contact made with GPs by subjects in two cities prior to attempting suicide, in order to determine whether differences in the health care systems could be a possible factor influencing the help-seeking behaviour of people experiencing suicidal crises. Structured interviews were conducted with suicide attempters from geographically defined catchment areas in two countries with private and national health care systems, respectively. The subjects were suicide attempters, admitted consecutively, aged > or = 15 years and living either in Stockholm (n=202) or in Bern (n=66). Patients living in Bern had seen their GPs more regularly and more frequently throughout the year. There was an increase in the number of visits to the GP prior to the suicide attempt in both cities, but it was greater in Stockholm than in Bern. However, in Stockholm fewer patients who saw their GP in the week before the attempt talked about their suicidal thoughts. The differences in help-seeking behaviour between the two patient samples may be related to the higher number of practising GPs and a more personal and consistent patient-doctor relationship in Bern. It is possible that the private medical care system in Switzerland lowers the threshold enabling patients to talk to their GP about their suicidal plans. The results suggest that in both cities there is scope for improving communication of the suicidal patient with his or her doctor.

Adolescent↗
PubMed1997

[The suicidal patient].

Suicide prevention in the general practitioner's practice should not only be a topic for patients that are close to putting an end to their lives. It should start with the recognition of an emotional crisis or depressive symptoms. Such patients have to be asked about suicidal thoughts or plans. Depressive states have to be assessed very carefully and treated adequately. The Gotland study has clearly shown that competence in the recognition and treatment of depression can significantly reduce the frequency of suicide.

Combined Modality Therapy↗
PubMed1996

A repetition-prediction study on European parasuicide populations. Part II of the WHO/Euro Multicentre Study on Parasuicide in cooperation with the EC Concerted Action on Attempted Suicide.

One of the aims of the inter-European study on parasuicide, which was initiated by WHO/Euro in the mid-1980s, was to try and identify social and personal characteristics predictive of future suicidal behavior. A follow-up interview study (the Repetition-Prediction Study) was designed, and so far 1145 interviews have been carried out at nine research centers, representing seven European countries. The study and the instrument used (the European Parasuicide Study Interview Schedules, EPSIS I and II) are described here. Some basic characteristics of the material from the various centers are presented and compared, and the representativeness of the samples are discussed. There were differences between the centers in several respects. Results from analyses based on pooled data have to be treated with some caution because of the possible lack of representativeness.

Adult↗
PubMed1996

The WHO-EURO Multicentre Study: risk of parasuicide and the comparability of the areas under study.

The 15 areas under study in the WHO/Euro Multicentre Study on Parasuicide vary considerably with regard to socio-economic factors, culture, life-styles, etc. In this paper, the authors discuss whether the traditional high risk factors for suicidal behavior (such as unemployment, abuse, divorce, etc.) take on different weights depending on local societal and cultural settings. Results from analyzing covariations between various background factors characteristic of the different areas under study and the frequency of attempted suicide showed weak or insignificant correlations, indicating that high-risk factors can only be identified from international pooled data with great care.

Adult↗
PubMed1996

Attempted suicide in Europe: rates, trends and sociodemographic characteristics of suicide attempters during the period 1989-1992. Results of the WHO/EURO Multicentre Study on Parasuicide.

The World Health Organization/EURO Multicentre Project on Parasuicide is part of the action to implement target 12 of the WHO programme, "Health for All by the Year 2000', for the European region. Sixteen centres in 13 European countries are participating in the monitoring aspect of the project, in which trends in the epidemiology of suicide attempts are assessed. The highest average male age-standardized rate of suicide attempts was found for Helsinki, Finland (314/100,000), and the lowest rate (45/100,000) was for Guipuzcoa, Spain, representing a sevenfold difference. The highest average female age-standardized rate was found for Cergy-Pontoise, France (462/100,000), and the lowest (69/100,000) again for Guipuzcoa, Spain. With only one exception (Helsinki), the person-based suicide attempt rates were higher among women than among men. In the majority of centres, the highest person-based rates were found in the younger age groups. The rates among people aged 55 years or over were generally the lowest. For the majority of the centres, the rates for individuals aged 15 years or over decreased between 1989 and 1992. The methods used were primarily "soft' (poisoning) or cutting. More than 50% of the suicide attempters made more than one attempt, and nearly 20% of the second attempts were made within 12 months after the first attempt. Compared with the general population, suicide attempters more often belong to the social categories associated with social destabilization and poverty.

Adolescent↗
PubMed1996

Effect of Rennie Liquid versus Maalox Liquid on intragastric pH in a double-blind, randomized, placebo-controlled, triple cross-over study in healthy volunteers.

OBJECTIVES: Despite years of successful use of calcium-containing antacids in acid-related disease, allegations of gastric rebound following their intake has brought these agents into disrepute. By assessing intragastric acidity over the 24-h period, we evaluated whether antacids induce a clinically relevant acid rebound. METHODS: Twelve healthy volunteers were assigned to a double-blind, placebo-controlled, triple cross-over comparison of placebo, Maalox Liquid, and a calcium-containing antacid, Rennie Liquid. The two antacids had identical neutralizing capacity. Each drug was administered at standard doses q.i.d 1 h after the main meals (at 1000, 1400, and 1900 h) and at bedtime (2300 h). Intragastric acidity was monitored by continuous ambulatory 24-h pH-metry on 3 separate days with a wash-out period of 1 wk. Special attention was given to the acidity of pre-determined postantacid time intervals during the day and night. RESULTS: Both antacids led to a significant increase of the median 24-h pH and the median pH of the first postantacid hour, compared with placebo. Neither Rennie Liquid nor Maalox Liquid led to a drop of intragastric pH during the putative acid rebound time (2nd and 3rd postantacid hr and at night). A marginal increase in serum calcium and gastrin concentration with Rennie Liquid, and magnesium concentration with Maalox Liquid, were observed. CONCLUSIONS: No gastric acid rebound was detected with the calcium carbonate-containing antacid, Rennie Liquid, or with Maalox Liquid at standard doses. An identical increase of intragastric pH was achieved with Rennie Liquid and Maalox Liquid during the first postantacid hour and the entire 24-h period.

Adult↗
PubMed1994

Suicide with psychotropic drugs in Switzerland.

All suicides in Switzerland in 1990 where drugs were involved (179 persons; 12.2% of all suicides) were analyzed by examination of death certificates and direct contacts with physicians and medico-legal institutions. Nearly 50% of these people took overdoses of combinations of different drugs and in 26% of the cases alcohol was reported to have been taken with the drugs. Unexpectedly, we found 29 suicides in which persons had obviously used drug combinations recommended by EXIT, an organization advocating the freedom of the individual to decide about his own time and nature of death. In EXIT-suicides usually barbiturates and anticholinergic drugs were taken together. Interestingly, the barbiturate compound used most often had officially been withdrawn from the market the previous year. Altogether, psychotropic drugs represented 78.7% of all drugs taken, with benzodiazepines being named most often (38.9%), followed by barbiturates (16.6%) and antidepressants (13.6%). Among the benzodiazepines flunitrazepam, diazepam, and triazolam were used most often and surprisingly, benzodiazepines were named as single drugs on 27 death certificates. Among the antidepressants (taken in 20.3% of overdoses) maprotiline was the most common drug used, followed by mianserin and trimipramine. This order of frequency reflects the prescribing habits of Swiss doctors. Two suicides were recorded with neuroleptics alone.

Adult↗