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G Schaeffer

Publications and source records attributed to G Schaeffer.

At least 19 recordsLinked to original sources
PubMed2003

Intercellular signalling within vascular cells under high D-glucose involves free radical-triggered tyrosine kinase activation.

AIMS/HYPOTHESIS: Diabetes mellitus is associated with endothelial dysfunction in human arteries due to the release of superoxide anions (*O(2)(-)) that was found to occur predominantly in smooth muscle cells (SMC). This study was designed to elucidate the impact of high glucose concentration mediated radical production in SMC on EC. Pre-treatment of vascular SMC with increased D-glucose enhanced release of *O(2)(-). METHODS: Microscope-based analyses of intracellular free Ca(2+) concentration (fura-2), immunohistochemistry (f-actin) and tyrosine kinase activity were performed. Furthermore, RT-PCR and Western blots were carried out. RESULTS: Interaction of EC with SMC pre-exposed to high glucose concentration yielded changes in endothelial Ca(2+) signalling and polymerization of f-actin in a concentration-dependent and superoxide dismutase (SOD) sensitive manner. This interaction activated endothelial tyrosine kinase(s) but not NFkappaB and AP-1, while SOD prevented tyrosine kinase stimulation but facilitated NFkappaB and AP-1 activation. Erbstatin, herbimycin A and the src family specific kinase inhibitor PP-1 but not the protein kinase C inhibitor GF109203X prevented changes in endothelial Ca(2+) signalling and cytoskeleton organization induced by pre-exposure of SMC to high glucose concentration. Adenovirus-mediated expression of kinase-inactive c-src blunted the effect of pre-exposure of SMC to high glucose concentration on EC. CONCLUSIONS/INTERPRETATION: These data suggest that SMC-derived *O(2)(-) alter endothelial cytoskeleton organization and Ca(2+) signalling via activation of c-src. The activation of c-src by SMC-derived radicals is a new concept of the mechanisms underlying vascular dysfunction in diabetes.

Animals↗
PubMed2003

Pathways database system: an integrated system for biological pathways.

MOTIVATION: During the next phase of the Human Genome Project, research will focus on functional studies of attributing functions to genes, their regulatory elements, and other DNA sequences. To facilitate the use of genomic information in such studies, a new modeling perspective is needed to examine and study genome sequences in the context of many kinds of biological information. Pathways are the logical format for modeling and presenting such information in a manner that is familiar to biological researchers. RESULTS: In this paper we present an integrated system, called Pathways Database System, with a set of software tools for modeling, storing, analyzing, visualizing, and querying biological pathways data at different levels of genetic, molecular, biochemical and organismal detail. The novel features of the system include: (a) genomic information integrated with other biological data and presented from a pathway, rather than from the DNA sequence, perspective; (b) design for biologists who are possibly unfamiliar with genomics, but whose research is essential for annotating gene and genome sequences with biological functions; (c) database design, implementation and graphical tools which enable users to visualize pathways data in multiple abstraction levels, and to pose predetermined queries; and (d) an implementation that allows for web(XML)-based dissemination of query outputs (i.e. pathways data) to researchers in the community, giving them control on the use of pathways data. AVAILABILITY: Available on request from the authors.

Database Management Systems↗
PubMed1999

Alterations in platelet Ca2+ signalling in diabetic patients is due to increased formation of superoxide anions and reduced nitric oxide production.

Increased aggregation of platelets might contribute to the development of vascular complication in diabetes mellitus. In this study release of superoxide anions, intracellular Ca2+ signalling and nitric oxide formation stimulated by the receptor-dependent agonist adenosine 5 '-diphosphate (ADP) and the receptor-independent stimulus thapsigargin, were compared in platelets isolated from patients with Type II (non-insulin-dependent) diabetes mellitus and healthy control subjects. Diabetes augmented intracellular Ca2+ release and Ca2+ entry to ADP by 40 and 44% (control subjects: n = 11; diabetic: n = 6), while the median effective concentration (EC50) of ADP to initiate Ca2+ signalling was similar in both groups. The effect of thapsigargin on Ca2+ concentration was increased by 69% in diabetic patients (control subjects: n = 22; diabetic patients: n = 9). In addition, release of superoxide anions was 70% greater in diabetic patients (control subjects: n = 9; diabetic patients: n = 6). Treatment of platelets from control subjects with the superoxide anion-generating mixture xanthine oxidase and hypoxanthine or buthioninesulphoximine (BSO) mimicked the effect of diabetes on platelet Ca2+ signalling. The antioxidant glutathione normalized enhanced Ca2+ response in the diabetic group (control subjects: n = 5: diabetic patients: n = 6). Basal and thapsigargin-evoked nitric oxide synthase activity was reduced in the diabetic group by 85 and 64%, respectively (control subjects: n = 13; diabetic subjects: n = 13). The nitric oxide-donor 2-(N,N-diethylamino)-diazenolate-2-oxide sodium (DEA/NO) normalized enhanced Ca2+ signalling in platelets preincubated with xanthine oxidase and hypoxanthine (n = 12) and in those from diabetics (control subjects: n = 6; diabetic patients: n = 6). Inhibition of nitric oxide synthase by N-nitro-L-arginine (L-NA) augmented thapsigargin-induced Ca2+ signalling by 51% (n = 8). These data indicate that in diabetes platelet Ca2+ signalling might be enhanced by excessive superoxide production and an attenuated negative direct or indirect feedback control by nitric oxide, due to its reduced production.

Adenosine Diphosphate↗
PubMed1999

Anandamide-induced mobilization of cytosolic Ca2+ in endothelial cells.

1. Experiments were designed to determine whether anandamide affects cytosolic Ca2+ concentrations in endothelial cells and, if so, whether CB1 cannabinoid receptors are involved. To this effect, human umbilical vein-derived EA.hy926 endothelial cells were loaded with fura-2 to monitor changes in cytosolic Ca2+ using conventional fluorescence spectrometry methods. 2. Anandamide induced an increase in Ca2+ in endothelial cells which, in contrast to histamine, developed slowly and was transient. Anandamide caused a concentration-dependent release of Ca2+ from intracellular stores without triggering capacitative Ca2+ entry, contrary to histamine or the endoplasmic reticulum Ca2+ -ATPase inhibitor thapsigargin. 3. Anandamide pretreatment slightly reduced the mobilization of Ca2+ from intracellular stores that was evoked by histamine. The mobilization of Ca2+ from intracellular stores evoked by anandamide was impaired by 10 mM caffeine. 4. Anandamide and histamine each significantly increased NO synthase activity in EA.hy926 cells, as determined by the enhanced conversion of L-[3H]-arginine to L-[3H]-citruline. 5. The CB1 cannabinoid receptor antagonist SR141716A (1 microM) only produced a marginal reduction of the mobilization of Ca2+ produced by 5 microM anandamide. However, at 5 microM SR141716A elicited the release of Ca2+ from intracellular stores. This concentration strongly impaired the mobilization of cytosolic Ca2+ evoked by either anandamide, histamine or thapsigargin. 6. Pretreatment of the cells with either 200 microM phenylmethylsulphonyl fluoride (to inhibit the conversion of anandamide into arachidonic acid) or 400 ng ml(-1) pertussis toxin (to uncouple CB1 cannabinoid receptors from Gi/o proteins) had no significant effect on the mobilization of cytosolic Ca2+ evoked by either anandamide, or histamine. 7. Taken together the results demonstrate that anandamide mobilizes Ca2+ from a caffeine-sensitive intracellular Ca2+ store that functionally overlaps in part with the internal stores mobilized by histamine. However, a classical CB1 cannabinoid receptor-mediated and pertussis toxin-sensitive mechanism does not mediate this novel effect of anandamide in endothelial cells. 8. The mobilization of cytosolic Ca2+ in endothelial cells may account for the endothelium-dependent and NO-mediated vasodilator actions of anandamide. Due to its non-specific inhibition of Ca2+ signalling in endothelial cells, SR141716A may not be used to assess the physiological involvement of endogenous cannabinoids to endothelium-dependent control of vascular smooth muscle tone.

Arachidonic Acids↗
PubMed1986

Serum free carnitine, carnitine esters and lipids in patients on peritoneal dialysis and hemodialysis.

Serum free and esterified carnitine levels as well as lipids were investigated in patients undergoing regular hemodialysis (HD) treatment before and during 12 weeks of treatment with L-carnitine (1 g i.v.) at the end of each HD. The results were compared with those obtained in patients on continuous ambulatory peritoneal dialysis (CAPD; n = 15) or intermittent peritoneal dialysis (IPD; n = 3) and healthy controls (CO; n = 20). In HD patients (n = 23) total carnitine (TC) was 49.9 +/- 3.9 (CO: 46.0 +/- 2.5; NS), free carnitine (FC) was 31.6 +/- 2.8 (CO: 37.4 +/- 1.3; p less than 0.05), short-chain acylcarnitine (SCC) was 17.0 +/- 1.8 (CO: 7.2 +/- 0.9; p less than 0.0001) and long-chain acylcarnitine (LCC) was 1.2 +/- 0.2 mumol/l (CO: 0.6 +/- 0.1; p less than 0.05). FC was in the normal range in CAPD (35.6 +/- 3.2) and IPD (44.5 +/- 8.0 mumol/l) patients, whereas SCC (30.1 +/- 3.5) and LCC (2.9 +/- 0.2) levels were maximal elevated in IPD patients (11.8 +/- 0.8 and 1.5 +/- 0.2 on CAPD). Therefore, TC was higher in IPD than in CAPD patients (77.5 +/- 5.0 vs. 49.0 +/- 3.5 mumol/l). 12 weeks after L-carnitine supplementation in HD patients, TC was 313.9 +/- 22.6, FC was 207.7 +/- 12.4, SCC was 99.6 +/- 12.1 and LCC was 7.1 +/- 0.6 mumol/l. TC and FC were significantly lower in females compared with males. Total cholesterol and ketone bodies were normal, HDL cholesterol was significantly decreased before and after L-carnitine supplementation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

[Significance of object loss on the course of psychosomatic diseases].

Psychosomatic diseases are organic diseases in the pathogenesis of which a psychic factor has an important significance. They are no nosological unit. Psychotherapeutic experience with such patients causes us to search for the different measure of this psychic disturbance. The authors deal with the research on narcissism and object loss which has again been performed since 10 years. The psychosomatic patient has difficulties with overcoming discouraging events (object losses) which evoke a depressive reaction in him. Pathophysiological connections between the reactive depression and the organic lesion are discussed. The psychotherapy has a double task: actual influence on the depressive reaction as well as the aid of learning a more suitable form of explanation of the discouragement.

Adolescent↗
PubMed1979

[The concept of a dynamic group psychotherapy for patients with psychosomatic diseases].

From a 15-year experience with group psychotherapy in psychosomatic patients a plan of such a treatment is presented. In several points it deviates from the model of an intended dynamic group psychotherapy after Höck. These deviations are based on the peculiarities which differentiate psychosomatic patients and neurotics. In particular these are bodily symptoms of the disease, which show lower abilities for the recognition and verbalisation of emotional courses, and the experiences to be freed as a patient from certain struggles. With the help of several graphs is tried to represent the connection of three phases of treatment and their corresponding points.

Ambulatory Care↗
PubMed1978

[Psychology of ageing and age (author's transl)].

Aging is a biological process being experienced. The experience of ageing is associated with disappointment and renuciation. Thus, aging is a task which can be mastered in different ways.--It is asserted that there is an ageing having a social sense.--It is demonstrated by some parameters which advancements and which hindrances may play a role in ageing as well as which defective developments may be possible. The traditional norms and ideas from former generations as well as the social evaluation of age have to be taken into consideration when an approach to the problems of aging is designed.--The different situation of the sexes is briefly outlined.--The physician can help best if he himself is able to cope with his own ageing.

Adaptation, Psychological↗
PubMed1976

[Investigations into urea elimination in patients with advanced chronic renal failure during forced diuresis].

Controlled balance studies were performed in 12 oedema-free patients with advanced chronic renal failure with optimal dietary pretreatment. Forced water diuresis did not result in a significantly increased urea excretion as compared with spontaneous diuresis. Furosemide diuresis resulted in a significant increase (P less than 0.05) which was irrelevant therapeutically. The serum urea may even increase slightly under furosemide due to massive fluid loss. During thirst-regulated diuresis of advanced chronic renal failure urea back-diffusion is probably already reduced to a minimum. Normal hydration provided, forced water diuresis (oral or parenteral fluid) is useless and irresponsible as it poses additional risks in such patients. Furosemide in high dosage in over-hydrated patients is an effective diuretic even in advanced renal failure. The slightly significant increase in urea excretion during furosemide treatment does not result in important benefits in dietetically well treated patients.

Adult↗
PubMed1975

[Therapy of neuroses].

The therapy of neuroses begins with the creation of a condition of confidence between physician and patient. It is followed by a relevant explanation of pathophysiologic connections, which must effect the removal of anxiety in the patient. A common task leads to the proper process. The use of the various therapeutic methods, which are differed as centered to symptoms and centered to personality above all depends on the degree of severity of the neurosis. Results from the two groups of treatment are reported. The use of autogenic training in bronchial asthma, estimated according to the changes of the maximum expiration speed and the maximum breathing capacity, as an example of a symptom-centered method. As an example of a personality-centered treatment it is reported on a complex group psychotherapy in cases of chronic ulcerative colitis in an in-patient department, estimated according to the frequency of relapses and to the capability to work before and after psychotherapy.

Asthma↗
PubMed1975

Histidines and renal function.

The results of endogenous renal clearances of 3-methylhistidine and histidine in twelve patients with normal and decreased renal functions are reported. Differences in the renal handling of the amino acids have been established. 3-methylhistidine showed a hyperbolic relationship between serum concentration and inulin clearance: histidine a linear relationship. The percentage tubular reabsorption of 3-methylhistidine was found to be about half that of histidine. The possible use of the measurement of serum 3-methylhistidine concentration as an index of renal insufficiency is discussed.

Adult↗
PubMed1975

[Objectifying the effect of autogenic training on disordered ventilation in bronchial asthma].

Forty-one persons suffering from asthma (aged 20 to 55; duration of disease: greater than or equal 2 years) were divided into 2 groups and participated in courses of instruction in autogenic training. The control group was comprised of 14 patients. The effects of autogenic training on the maximum rate of expiration as well as the limiting respiratory value were recorded. The control group showed a seasonal decrease in the maximum rate of expiration and the limiting respiratory value by 10 to 20% in the period extending from April through November. The autogenic-training patients showed a temporally similar increase in the maximum rate of expiration of 27 and 22%, respectively (the difference to the control group being 47 and 42%, respectively). In 35 patients the increase in the limiting respiratory value was equal to or greater than the effect produced by novodrine. Catamnesis after one year (n = 40): Absence from work in a twelve-month period was 663 days prior to autogenic training and 77 days (11.6%) subsequent to autogenic training. Accordingly, autogenic training may be considered to be an objectively effective component of a combination of therapeutical methods used in the treatment of bronchial asthma.

Adult↗
PubMed1975

Amino acid and protein intake in RDT patients. A nutritional and biochemical analysis.

In 40 unselected RDT patients (20 center and 20 home dialysis patients) the intake of nutrients was measured using the precise weighing method of Wirths [1969]. The protein intake was found to be 0.97 plus or minus 0.19 g/kg predialysis body weight, the calorie intake 32.3 plus or minus 6.4 cal/kg. Two thirds (0.65 plus or minus 0.15 g/kg) of the protein consisted of high biological value protein. Despite the fact that according to current recommendations the protein intake should have been adequate, signs of protein malnutrition were found. The mean serum concentrations of total protein, transferrin and valine and the ratio of essential amino acids to nonessential amino acids (EAA/NEAA) were significantly lower than in normal subjects and the glycine level was elevated. Histidine levels were normal indicating that the histidine intake measured at 1.75 plus or minus 0.47 g/day appeared adequate under these conditions. Phenylalanine levels were elevated indicating a blocking of 4-hydroxylase leading to low tyrosine levels. A possible reason for these findings may be that the protein requirements of the RDT patient over a long period of time are higher than those found experimentally in short term studies. An inadequate calorie intake could not be excluded. Additionally a dialysis dependent pathologic variation of the daily intake of nutrients may be responsible for the disturbed nutritional status. In connection with this, three distinct types of intake variation can be described: A stable type in which the variation in the daily protein and calorie intake does not differ by more than 20% from a daily mean value, an unstable type I with significantly lower intake on the day of dialysis and an unstable type II with a significantly higher intake on the day of dialysis. Signs of protein malnutrition occurred significantly more frequently in the unstable groups.

Adult↗