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Biomedical subjects

J Widmer

Publications and source records attributed to J Widmer.

At least 37 records · Page 2Linked to original sources
PubMed1993

Brain acetyl-CoA carboxylase: isozymic identification and studies of its regulation during development and altered nutrition.

Acetyl-CoA carboxylase, the rate-limiting enzyme of fatty acid synthesis, exists as an oligodendrocyte-associated enzyme in brain and plays an important role in supplying fatty acid for myelination. Rat brain acetyl-CoA carboxylase (ACC) has been identified as a single isozyme of M(r) = 265,000 daltons, indistinguishable immunologically from the isozyme in rat adipose tissue and liver. Total activity of brain ACC declines from birth to 4 weeks of age in the newborn rat. This change in activity can entirely be accounted for by changes in enzyme content, not enzyme specific activity, and is paralleled by decreases in ACC mRNA. In contrast, cardiac, skeletal muscle and liver ACC does not change in content over this developmental period. Unlike ACC in liver and adipose tissue, the enzyme content and specific activity of brain ACC is invariant during various states of nutrition. These data indicate that the brain ACC is subject to unique regulation, as compared to non-neural enzyme. The mechanisms underlying the control of neural ACC activity may be important to understanding the process of myelination during development and to a more general understanding of the factors regulating ACC expression/activity in other tissues.

Acetyl-CoA Carboxylase↗
PubMed1993

Blood magnesium, potassium, sodium, calcium and cortisol in drug-free depressed patients.

Many biochemical variables, including plasma and erythrocyte magnesium, were simultaneously measured in drug-free depressed patients (n = 34), compared to healthy controls (n = 35). Higher plasma and erythrocyte magnesium concentrations were observed in patients than in controls (+12 per cent, P < 0.0001 and 14 per cent, P < 0.0001, respectively). In contrast, patients showed a lower plasma potassium level (-10 per cent; P < 0.007). Cortisol secretion was much higher in patients (+35 per cent; P < 0.02), particularly in females, showing overactivity of the hypothalamo-hypophyseo-adrenal axis in the patients. Except in a few cases, plasma sodium and calcium in patients did not differ from control values. Significant differences in magnesium and cortisol levels were observed between patients classified in diagnostic groups and by sex, whereas little variation in the other biochemical indices was noted. The increase in blood magnesaemia and its possible association with central hypocatecholaminergic deficiency in affective disorders are discussed.

Calcium↗
PubMed1992

Platelet membrane alpha 2-adrenergic receptors in depression.

The platelet membrane was used as a model system to examine alpha 2-adrenergic receptors in 30 depressed patients and 30 healthy control subjects. The number of binding sites and their affinity for 3H-UK 14304 (5-bromo-6-(2-imidazoline-2-ylamino)-quinoxaline), a potent, highly selective alpha 2-adrenergic receptor agonist, was measured. Plasma magnesium and free 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations were assayed in the same sample. A decreased agonist-receptor affinity was found in depressed patients, whereas receptor density was not significantly altered compared with that in control subjects. In bipolar depressed and dysthymic patients, there was a tendency toward a higher density of alpha 2-adrenergic receptors. This trend was not apparent in unipolar, recurrent depressed subjects. Moreover, a positive correlation between Bmax and Kd values was observed in patients but not in control subjects--a finding that suggests that a compensatory phenomenon occurs in depression. After the patients were treated with antidepressant drugs, an increased affinity (decrease in Kd) was observed, together with a decrease in binding sites. Plasma magnesium concentrations were higher in drug-free depressed patients than in control subjects. In addition, magnesium concentrations were negatively correlated with the density of alpha 2-adrenergic receptor binding sites in depressed patients, both before and during treatment. Lastly, a trend toward a negative correlation between plasma MHPG concentration and the number of binding sites was also observed. These results suggest a complex multifactorial regulation of alpha 2-adrenergic receptors, which are probably hyposensitive in depressive syndromes.

Adrenergic alpha-Agonists↗
PubMed1992

Effect of specific growth rates on productivity in continuous open and partial cell retention animal cell bioreactors.

A clonal derivative of a transfectant of the SP2/0 myeloma cell line producing a chimeric monoclonal antibody was cultivated in both continuous open and continuous partially-closed bioreactors. Using an open system for the determination of kinetic parameters, we showed that the production of this chimeric mAb was growth associated. As such, the volumetric productivity increased linearly with increasing dilution rate up to the maximum dilution rate. Three continuous cultivations employing partial cell retention were conducted. In agreement with mathematical predictions, the product titer and volumetric productivity were independent of the degree of cell retention when the total dilution was held constant. When cells were maintained at a low specific growth rate, the product titer was independent of dilution rate and the volumetric productivity increased with increasing dilution rate, again in agreement with mathematical predictions. Since the partially-closed bioreactor could be operated at dilution rates in excess of the maximum specific cellular growth rate, volumetric productivities were greater than those achievable in the open bioreactor. However, when cells were maintained at a high specific growth rate, cell accumulation was limited and product titers decreased at high dilution rates. Therefore, the volumetric productivity in this latter case did not increase at higher dilution rates.

Animals↗
PubMed1992

Decrease in epinephrine-induced attenuation of platelet adenylate cyclase activity in depressed patients: relation with plasma electrolytes.

We have measured the alpha 2-adrenoceptor-mediated inhibition of platelet membrane adenylate cyclase in depressed patients and control subjects. The results showed a decrease in the forskolin-stimulated adenylate cyclase inhibition of depressed patients compared to the healthy subjects. This suggests a subsensitivity of alpha 2-adrenoceptor in depression. However, this subsensitivity was not correlated to the severity of depression as both severely and moderately depressed patients exhibited the same percent of adenylate cyclase inhibition. The antidepressant drugs treatment induced an increase in the percent of adenylate cyclase inhibition with a trend towards the control values. However, this increase did not equal control value, and moreover both remitted and unremitted patients presented a similar change in their alpha 2-adrenoceptor-mediated adenylate cyclase inhibition. This result raises the question about a simple and direct relation between the clinical status of depression and the power of alpha 2-adrenoceptor-mediated adenylate cyclase inhibition. Plasma magnesium and sodium yielded correlations to this alpha 2-adrenoceptor-mediated adenylate cyclase inhibition suggesting a relation between the platelet adrenergic function and plasma electrolytes.

Adenylyl Cyclase Inhibitors↗
PubMed1992

Evolution of blood magnesium, sodium and potassium in depressed patients followed for three months.

No consensus has been obtained about blood electrolyte status, especially about magnesium, in affective disorders. This is mainly due to the lack of information about the distribution of the patients in clinical subgroups, sex, type of treatment and about the severity of their illnesses. Most of these studies concerned treated patients. We confirmed in this study that drug-free depressed patients have higher erythrocyte and plasma magnesium than controls, as shown in previous reports. Significant differences are observed in as shown in previous reports. Significant differences are observed in patients for sex and between clinical subgroups. Low plasma potassium levels are described in both male and female depressed patients. The erythrocyte magnesium level tends to normalize in parallel with clinical improvement, depending on sex and clinical subgroup, and seems then to be related to the intensity of the depression. Plasma magnesium in male and female patients, except for female unipolars, remains higher than controls in all conditions and might be related to the diagnosis of affective disorders.

Adult↗
PubMed1990

L-tyrosine and L-tryptophan membrane transport in erythrocytes and antidepressant drug choice.

In the treatment of depression, when antidepressant drug choice is made according to alterations of erythrocyte membrane transport of L-tyrosine and L-tryptophan in the individual patient, the clinical results are superior to those obtained when drugs are prescribed according to the physician's judgment. This is demonstrated by comparing three experimental groups: I, 100 patients treated in relation to their L-tyrosine and L-tryptophan transport; II, 30 patients treated according to the clinician's experience; III, 38 subjects treated against the L-tyrosine and L-tryptophan transport indications. In these groups, the frequency of patients improved by more than 70% is 77%, 47%, and 16%, respectively.

Adult↗
PubMed1990

A multivariate analysis of red blood cell membrane transports and plasma levels of L-tyrosine and L-tryptophan in depressed patients before treatment and after clinical improvement.

The purpose of this study was to examine whether biological variables, such as erythrocyte membrane transports and plasma levels of monoamine precursor amino acids (tyrosine, tryptophan and phenylalanine), exhibit a particular pattern relatively to DSM-III depressive subgroups (dysthymic disorders, major recurrent depression and biopolar depression), when they are treated synthetically by a stepwise discriminant analysis. We conducted two tests in 97 subjects (64 depressed patients vs. 33 controls): the first before any antidepressant treatment, and the second after pharmacotherapy and clinical improvement. Our results clearly indicate a satisfying homogeneity for the controls and bipolar depressed patients as opposed to dysthymic disorders and major recurrent depression in both tests. The most informative biological variables are the erythrocyte membrane transports before treatment, tryptophan parameters after clinical improvement. Evidence is provided that multivariate analysis constitutes an interesting approach in biological psychiatry.

Adult↗
PubMed1989

Histological and clinical parameters of human gingiva following 3 weeks of chemical (chlorhexidine) or mechanical plaque control.

The aim of the present study was to compare stereologically the histopathologic variations following 3 weeks of chemical (chlorhexidine) or mechanical plaque control. 18 students and dental hygienists volunteered for this investigation. After prophylaxis, they performed optimal oral hygiene to reach mean plaque and gingival indices approaching 0. Six of them then performed mechanical plaque control of 3 weeks (control), while the other 12 rinsed 3 times daily with a 0.12% chlorhexidine solution (test). At days 0 and 21, the plaque index (PlI), the gingival index (Gl) and the gingival exudate flow rate (GEFR) were assessed and biopsies were obtained from buccal sites. Point-counting procedures were performed at 2 different levels of magnification on light microscopic sections to estimate the volume fractions of epithelium, infiltrated and non-infiltrated connective tissue, and collagen. The relative numbers of fibroblasts, polymorphonuclear neutrophils, lymphocytes, plasma cells, macrophages and mast cells were estimated by counting the number of nuclear profiles of these cells in a specific connective tissue area adjacent to the apical termination of the junctional epithelium. After 21 days, the PlIs of the test subjects were significantly higher than the PlIs of the controls, but their Gl were similar. At the end of the experimental period, the various volume fractions and %s of cell profiles remained stable with the exception of an increase in the %s of lymphocytes in the test group. This study has shown that, clinically as well as histologically, the daily use of chlorhexidine for a 3-week period is equally efficient as optimal mechanical tooth cleaning in maintaining a healthy gingiva in the buccal sites investigated.

Chlorhexidine↗
PubMed1989

Involvement of sulfhydryl groups in the transport of L-tyrosine and L-tryptophan across the human red cell membrane in vitro.

In previous papers, we reported a deficit in tyrosine (TYR) and tryptophan (TRP) transport across the erythrocyte membrane in depressed patients. To investigate further the transport mechanism of the two precursors of monoamines, we tested in healthy subjects the role played by sulfhydryl groups (SH). These groups, cysteine residues, are localized on the intrinsic domain such as the transporters of chloride or sugars. We found that all sulfhydryl reagents that inactivated the SH induced a strong inhibition of the transport of amino acid across the red cell membrane when incubated in the plasma as medium. We concluded that a relationship might exist between these neutral amino acids and D-glucose transport.

4-Chloromercuribenzenesulfonate↗
PubMed1988

Individuality and stability in the transport of precursors of monoamines across the erythrocyte membrane of mentally normal subjects.

We evaluated to what extent the tyrosine (TYR) and tryptophan (TRP) transport by the red cells was stable in normal subjects during divers clinical conditions. Twenty-two normal subjects were studied. The values of TYR and TRP transport were found to be individually determined, showed no circadian oscillations and no changes during the menstrual cycle, but varied somewhat more during the postpartum period. A few normal subjects had low TYR and TRP transport values, as observed in patients with affective disorders.

Adult↗
PubMed1988

Evolution of red blood cell membrane transport and plasma level of L-tyrosine and L-tryptophan in depressed treated patients according to clinical improvement.

The erythrocyte membrane transport (MT) of L-tyrosine (TYR) and L-tryptophan (TRP) and their plasma concentration showed abnormal mean values in 37 depressed patients compared to control subjects before treatment. The pattern of these abnormal values differed according to the clinical subgroup (DSM III criteria). In bipolar disorders the TYR values were all low and the TRP values showed little change, except a low level of plasma TRP. In major depression, MT were abnormal (MT TYR low, MT TRP high) with a very low plasma TRP. In dysthymic disorders the TYR and TRP values were normal. The normalization of the above biochemical variables was significantly correlated with the clinical improvement; however, the plasma concentration of TRP remained abnormal in some patients who had recovered. In contrast, only plasma TYR and TRP were significantly increased in patients without recovery.

Adult↗
PubMed1987

In vitro effects of short-chain aliphatic alcohols, benzyl alcohol and chlorpromazine on the transport of precursors of monoamines across the human erythrocyte membrane.

In previous papers we reported a deficit of tyrosine (TYR) and tryptophan (TRP) transport across the erythrocyte membrane in depressed patients. To investigate further the transport mechanism of both monoamine precursors, we tested in healthy subjects the role played by membrane fluidity, using different fluidizing agents such as alcohols and the neuroleptic chlorpromazine. We found that the transport of both amino acids depended on the length of the chain of each alcohol tested (number of carbon atoms = C). No inhibition was observed after methanol (C1) preincubation, in contrast to benzyl alcohol (C6), which produced an inhibition of about 80% of amino acid basal transport. In a condition of incubation by suspension of cells in an artificial medium, we observed a dose response of these transports with ethanol used at doses of 0.1-1.3 M. Finally we found in this study that the effect of ethanol on membrane fluidity, and therefore on inhibition of basal amino acid transport, was totally reversible after having washed the suspended cells, suggesting a superficial, noncovalent ethanol binding on such biological membranes.

Adult↗
PubMed1986

Influence of the time of administration of dexamethasone 0.25 mg on cortisol secretion in normal humans.

Single low doses (0.25 mg) of dexamethasone were given at 11 p.m., 2, 5 and 8 a.m. on separate days to five normal subjects. The concentrations of cortisol in plasma on the next day were significantly decreased compared to results after placebo administration, and cortisol suppression was maximal after dexamethasone had been given at 8 a.m. Our findings suggests that the postulated phase-advance of circadian rhythms is not a major cause of cortisol non-suppression in depressives given dexamethasone.

Adult↗
PubMed1986

L-tyrosine and L-tryptophan transport in red blood cells in normal subjects. Effects of other amino acids, temperature and medium of incubation.

Blood cells may be used as a model in the central transport mechanisms of amino acids, precursors of amines, implicated in some hypotheses of psychiatric diseases. In a previous paper, we showed a deficit of tyrosine transport by red cells incubated in the plasma of depressed patients. In the present study, we have investigated the interaction of these peripheral transport mechanisms for tyrosine and tryptophan with other amino acid transports, such as the L and ASC systems, and the role of sodium ions in the extracellular medium. We also describe the inhibition induced by incubation at a low temperature, and a probable role of the membrane viscosity. The interest of incubating the cells in their own plasma, in order to have physiological conditions, is also discussed.

Alanine↗
PubMed1986

In vitro effects of ionophores and inhibitors of main sodium and calcium movements on tyrosine and tryptophan transport by human erythrocytes.

Peripheral models using blood cells might be biochemical markers in various psychiatric illnesses. In previous papers we reported a deficit of tyrosine and tryptophan transport in red cells incubated in plasma from depressed patients. In the present study we investigated the role played by sodium and calcium in these transports by using inhibitors and ionophores of the main movements of these electrolytes. We also studied the contribution of phloretin-sensitive countertransport, which has been described as low in psychiatric conditions.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1982

Exchange mechanism of tyrosine between plasma and red blood cells in normal subjects and psychiatric patients.

The saturable mechanism of tyrosine (TYR) uptake by the membrane of red blood cells incubated at 37 degrees C has been studied in normal subjects and psychiatric patients. This uptake is markedly inhibited by incubation at 0 degree C, and weakly inhibited by iodoacetic acid and ouabain. The uptake of TYR is significantly lower in unipolar- and bipolar-depressed patients, and significantly higher in schizophrenics compared to normal controls. These results indicate a possible disturbance of functional capacity of membrane transport in some psychiatric diseases.

Biological Transport↗