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Biomedical subjects

M Maes

Publications and source records attributed to M Maes.

At least 343 records · Page 19Linked to original sources
PubMed1982

Kinetics of the inhibition of plasmin in acidified human plasma.

Acid-treated human plasma is a competitive inhibitor of the hydrolysis of D-Val-Leu-Lys-Nan (S-2251) by plasmin. The rate of hydrolysis is decreased to 50% by 750 fold diluted acidified normal plasma and by 60 fold diluted acidified alpha 2-antiplasmin depleted plasma (alpha 2-antiplasmin concentration less than 2%). These findings suggest that alpha 2-antiplasmin is a contributary but not the main competitive inhibitor of acidified plasma. This interpretation is supported by the finding that alpha 2-antiplasmin depleted plasma reconstituted with purified alpha 2-antiplasmin inhibits the hydrolysis of S-2251 by plasmin at a 125 fold dilution following acidification and by the finding that in a purified system acid inactivated alpha 2-antiplasmin inhibits the hydrolysis of S-2251 by plasmin with a Ki of 25 nM. Thus, besides alpha 2-antiplasmin, other plasma proteins which are at least in part eliminated by the removal of alpha 2-antiplasmin from plasma by immunoadsorption appear to be competitive inhibitors for plasmin in acidified plasma. It is suggested that several competitive inhibitors for plasmin are present and/or generated in acidified plasma and that these inhibitors may at least in part be responsible for the variability in the results of measurements of plasminogen and/or plasmin in plasma following acidification.

Fibrinolysin↗
PubMed1982

Human complete androgen insensitivity with normal dihydrotestosterone receptor binding capacity in cultured genital skin fibroblasts: evidence for a qualitative abnormality of the receptor.

Complete androgen insensitivity syndrome (CAIS), or so-called testicular feminization, results from the lack of androgen action on target organs. Within this syndrome, two major variants have been described. In the first variant, the specific intracellular androgen receptors are undetectable (CAIS, AR-), whereas normal levels of androgen receptors are measured in the second variant (CAIS, AR+). From studies with cultured labial skin fibroblasts of three CAIS, AR+ patients from the same family, we have demonstrated that their androgen receptors present qualitative differences when compared to normal receptors: 1) the apparent affinity constant (Kd) of 5 alpha-dihydrotestosterone for the receptor is higher than normal; 2) the in vitro dissociation rate of the receptor-steroid complex is faster than normal: 3) the cellular androgen receptor is more thermolabile than normal when cells are exposed to superphysiological temperatures; and 4) the relative binding affinity of the androgen receptor for progesterone is greater than normal. These findings suggest the presence of a structural abnormality of the androgen receptor in patients with CAIS, AR+. However, these changes (e.g. slightly decreased affinity of the receptor for 5 alpha-dihydrotestosterone) probably do not explain the total lack of androgen action in these patients. Finally, the present data from this family along with those from the literature suggest the presence of heterogeneity as to the cause of the defect in CAIS, AR+.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1981

Site-specific mutagenesis of Agrobacterium Ti plasmids and transfer of genes to plant cells.

A general method is described for the use of tumor-inducing (Ti) plasmids as experimental gene-vectors for plant cells. Intermediate vectors, containing specific Ti plasmid sequences and capable of replication in both E. coli and Agrobacterium strains, were constructed and used for the in vitro introduction of isolated DNA fragments into predetermined sites of the T-region derived fragments. Site-specific inserts and/or deletions-substitutions in Ti plasmids were produced by exchange of the modified T-region sequences for the wild-type sequence by in vivo recombination between intermediate vectors and resident Ti plasmids. This method was applied for the isolation of mutant Ti plasmids affecting either morphogenetic properties or opine synthesis in crown gall tumors. Foreign DNA, inserted at different sites in the T-region of both octopine and nopaline Ti plasmids, was shown to be cotransferred with the T-DNA and to be stably maintained in the transformed plant cells.

Arginine↗
PubMed1980

Phenotypic variation in a family with partial androgen insensitivity syndrome.

A family with partial androgen insensitivity syndrome exhibited considerable variation in phenotypic expression of their androgen resistance. One subject died at 2 1/2 years of age of a Wilms' tumor. In the two living members, one had a micropenis with otherwise normal genitalia, while the other had a small phallus, perineoscrotal hypospadias, bifid scrotum, and persistence of a vaginoutricular pouch. At puberty, plasma androgens and serum gonadotropins increased to normal or elevated values. However, despite adequate endogenous plasma testosterone levels and testosterone therapy, these patients showed poor virilization and were sterile. Studies of cultured sexual skin fibroblasts showed adequate 5 alpha-reductase activity and normal receptor affinity and capacity for dihydrotestosterone. An X-linked mode of inheritance is postulated, although autosomal dominance cannot be ruled out.

Child↗
PubMed1980

Androgen receptors and metabolism in cultured human fetal fibroblasts.

Testosterone metabolism and dihydrotestosterone (DHT) receptor activity were studied in fibroblasts cultured from genital and non-genital tissues of 8- to 22-week old human fetuses. As early as the eighth week of gestation, DHT receptor activity was detected in non-genital skin. The binding capacity (Bmax) was greater in genital skin fibroblasts (mean +/- SD = 474 +/- 32 moles x 10--18/micrograms DNA) than non-genital skin (mean +/- SD = 124 +/- 42 moles x 10(-18)/micrograms DNA). DHT receptor binding (Bmax) was found in fibroblasts derived from testes (112 moles x 10(-18)/micrograms DNA), but not intestine (less than 10 moles x 10(-18)/micrograms DNA). The DHT receptor activity of fetal skin fibroblasts of genital origin was similar to that of fibroblasts derived from the foreskin of normal newborns. DHT receptors from fetal and newborn fibroblast cultures had similar sedimentation coefficients in sucrose density gradient centrifugation, but there were small differences in their relative affinities for 17 beta-estradiol and cyproterone. Low, but detectable 5 alpha-reductase activity was observed at 8 weeks gestation in non-genital skin fibroblasts and was present in fibroblasts from a variety of tissues of older fetuses, including testes, kidneys and lungs. The highest 5 alpha-reductase activity of 210 pg/hour/micrograms DNA was found in fibroblasts cultured from clitoral tissue from a 10-week old fetus. In all but one specimen, the 5 alpha-reduced products were either DHT or 5 alpha-androstanedione. The demonstration of 5 alpha-reductase activity and specific DHT receptors in fetal tissues suggests that the intracellular mechanism for androgen action is present in the fetus, similar to that after birth.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1979

Selective inhibition by secosteroids of 5 alpha-reductase activity in human sex skin fibroblasts.

The effects of 5,10-secoestra-4,5-diene-3,10,17-trione (Compound I) and 5,10-seco-19-norpregna-4,5-diene,3,10,20-trione (Compound II) on the 5 alpha-reductase activity and on the androgen receptors of normal human sex skin fibroblasts were investigated. The Vmax and Km of the transformation of testosterone to 5 alpha-reduced products was 387 pg/microgram DNA/30 min and 234 X 10(-9)M, respectively. When the inhibitors were introduced in the assay, the 5 alpha-reductase activity was markedly reduced, Compound I being a less potent inhibitor than Compound II. At 15 min, the inhibition was greater than at 30 and 60 min. The Ki for Compound I was 1.60 x 10(-6)M with a Vmax of 83 to 553 pg/microgram DNA/30 min. For Compound II, the Ki was 0.53 x 10(-6)M with a Vmax of 70 to 340 pg/microgram DNA/30 min. The inhibition was of the noncompetitive type. Studies with androgen receptors showed that Compound I had a lower affinity for the receptors than Compound II. The ID50 for 3H-DHT and 3H-T for Compound I were 42.9 x 10(-7)M and 8.6 x 10(-7)M, respectively, whereas for Compound II, they were 10.6 x 10(-7)M and 4.8 x 10(-7)M.

5-alpha Reductase Inhibitors↗
PubMed1979

Antibody method for measurement of dihydrotestosterone receptors in cultured human skin fibroblasts.

We have adapted the method of Castañeda and Liao to the assay of DHT receptors in cultured fibroblasts arising from human skin. An antitestosterone antibody (100% crossreactivity for DHT) was coupled to CNBr-activated Sepharose. Confluent monolayers of fibroblasts were incubated with 3H-DHT (2 nM) at 37 degrees C for 30 min. Fibroblasts were then collected, sonicated, and centrifuged at 1200 x g for 15 min. The receptor assay was carried out on the supernatant; the antibody-sepharose was used to remove both unbound and nonspecifically bound DHT. Experience showed that the antibody did not entirely remove the nonspecifically bound and free DHT. A blank (sample heated at 60 degrees C for 3 min) was therefore subtracted to obtain an accurate value of specifically bound DHT. In spite of this, the antibody method, when compared to the gel filtration method, was more rapid and more convenient. Its reproducibility was similar to that of the gel filtration method, and its sensitivity was somewhat greater in patients with low levels of DHT-receptor complex. Improved sensitivity could be particularly useful when dealing with partial AIS.

Cells, Cultured↗
PubMedDate not supplied

Pituitary and adrenal hormone responsiveness to Synacthen in melancholic subjects versus subjects with minor depression.

Increased adrenal cortex responsiveness to adrenocorticotropic hormone (ACTH) has been suggested to contribute to increased cortisol secretion in dexamethasone nonsuppression and melancholia. To further examine this hypothesis, the following variables were examined in 68 patients with unipolar depression (minor, n = 24; simple major, n = 25; melancholic, n = 19): basal or post-Synacthen [ACTH(1-24), 250 micrograms IV] intact ACTH(1-39), beta-endorphin/beta-lipotropin, cortisol, and androstenedione concentrations, as well as the postdexamethasone (DST) plasma ACTH(1-39) and cortisol values. Melancholic subjects showed significantly higher baseline ACTH(1-39), beta-endorphin/beta-lipotropin, and androstenedione values compared with subjects with minor depression. No significant differences in post-Synacthen cortisol or androstenedione secretion between any of the groups or between [ACTH(1-39) or cortisol] DST nonsuppressors and suppressors were found. No significant relationships between DST and ACTH test results were observed. Abnormally increased post-DST cortisol values in melancholic subjects were highly predicted (> 68% of the variance) by post-DST intact ACTH levels. ACTH(1-39) values were significantly lower after Synacthen administration in melancholic subjects than in subjects with minor depression. These results are not consistent with the hypothesis that melancholia is characterized by an increased adrenocortical responsivity to exogenous ACTH compared with minor depression or that DST nonsuppression is due to adrenal hyperresponsiveness.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Interleukin-2 and interleukin-6 in schizophrenia and mania: effects of neuroleptics and mood stabilizers.

There is some evidence that schizophrenia may be accompanied by alterations in cell-mediated immunity (CMI) and that antipsychotic agents may modulate CMI. The purpose of this study was to investigate the plasma levels of interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), sIL-2R, and transferrin-receptor (TfR) in schizophrenia and mania, and the effects of treatment with neuroleptics or mood stabilizers on these variables. The subjects were 14 schizophrenic patients, 10 manic patients and 21 healthy volunteers. The above immune variables were measured in baseline conditions and after treatment with neuroleptics in schizophrenic patients and valproate in manic patients. Plasma concentrations of IL-6, sIL-6R, sIL-2R and TfR were significantly higher in the combined group of psychotic patients than in healthy volunteers. Plasma IL-6 was significantly higher in schizophrenic patients, while plasma sIL-6R and sIL-2R were significantly higher in mania than in normal controls. In schizophrenic patients, plasma levels of IL-6, sIL-6R and TfR were significantly lower after treatment with neuroleptics than before treatment. No significant effects of valproate on the immune-inflammatory markers could be found in the manic patients. It is suggested that activation of CMI may occur in both schizophrenia and mania and that neuroleptics may have immunosuppressive effects through suppression of IL-6 or IL-6R-related mechanisms.

Adult↗
PubMedDate not supplied

Relationships between basal hypothalamic-pituitary-thyroid-axis activity and plasma haptoglobin levels in depression.

The present study was carried out in investigate the relationship between basal hypothalamic-pituitary-thyroid (HPT)-axis function and the acute phase (AP) response in depression. Toward this end, the authors measured serum concentrations of basal thyroid-stimulating-hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3), and plasma levels of an AP protein, i.e. haptoglobin (Hp) in 38 depressed in-patients and in 11 normal controls. In depression, basal TSH was significantly and negatively related to Hp values, whereas in normal controls a trend toward a positive correlation between both factors was found. Depressed patients with increased Hp levels (> or = 250 mg/dl) showed significantly lower basal TSH levels than patients with normal Hp levels. No significant correlations were found between Hp plasma levels and either FT4 or FT3 serum concentrations. The results support the hypothesis that lower TSH secretion in major depression may be related to the AP response in that illness, and may constitute an expression of a coordinated neuroendocrine-immune response to nonthyroidal illness.

Acute-Phase Reaction↗
PubMedDate not supplied

The dexamethasone suppression test, the Hamilton Depression Rating Scale and the DSM-III depression categories.

The Hamilton Depression Rating Scale (HDRS) score and plasma cortisol values were measured in 100 depressed patients at 8 a.m., 4 p.m. and 11 p.m. after oral administration of 1 mg dexamethasone the previous night. The patients were categorized according to DSM-III as suffering from either minor depression (including dysthymic disorder, 300.40; adjustment disorder with depressed mood, 309.00; atypical depression, 296.82) or major depression (without melancholia, 296.X2; with melancholia, 296.X3; with psychotic features, 296.X4). Plasma cortisol levels of greater than or equal to 3.5 micrograms/dl at 8 a.m. were found to be the most sensitive (56.9%) and specific (94.3%) discriminator between minor and major depression. Plasma cortisol levels at 4 p.m. and 11 p.m. or the combination of several cortisol values also differentiated between minor and major depression; however, the results were not so conclusive. According to the ratings on the Hamilton Depression Scale the patients with major depression were more severely depressed (P less than 0.001) than patients suffering from minor depression. Cortisol values at 8 a.m., 4 p.m., 11 p.m. and the highest levels were significantly (P less than 0.001) correlated with the HDRS score. A maximum of 20.2% of the score variance could be explained by the correlation with the highest cortisol value observed. Severity of illness does not exclusively account for the biological differences between minor and major depression.

Adjustment Disorders↗
PubMedDate not supplied

The importance of creatinine flow, age and 24 h urinary output in the interpretation of the MHPG flow.

The 3-methoxy-4-hydroxyphenylglycol (MHPG) flow, the creatinine flow in 24 h urine and the plasma creatinine level were determined in 42 psychiatric control patients. The creatinine clearance was calculated. The relationship between MHPG flow in 24 h urine and creatinine clearance, creatinine flow, 24 h urinary output, age, sex and weight of the patient were studied by means of single and multiple regression methods. The MHPG flow was significantly correlated with creatinine clearance (r = 0.597), creatinine flow (r = 0.646) and sex of the patient (rpb = 0.434). The variance of the MHPG flow can be explained by the regression with creatinine flow, age and urinary output for a maximum 51.5%. These variables have to be taken into account for the interpretation of data concerning the MHPG flow in subsequent experimental designs. The results of the measurements of the MHPG flow can best be expressed as the residual values obtained after partialling out the predictable component calculated by multiple regression with creatinine flow, age and 24 h urine output.

Adult↗
PubMedDate not supplied

Repeated dexamethasone suppression test in depressed patients.

In 17 depressed patients with initially abnormal results on the dexamethasone suppression test (DST), serial plasma samples for the determination of cortisol concentrations were taken every 10 days, following overnight dexamethasone administration at 11 p.m. Severity ratings were repeated on the days of blood sampling. There was a gradual normalization of the DST and progressive clinical improvement during selective antidepressant therapy. The DST was closely related (r = 0.573, P less than 0.005) to the patients' clinical mood level during the depressive episode. At the point where normalization of the DST occurred, the patients were still moderately severely ill. DST conversion occurred early in the treatment, i.e. after 23.9 (+/- 15.1) days, and preceded symptomatic improvement by 24.5 (+/- 18.1) days. Normalization of the DST was a predictor (r = 0.691, P less than 0.005) of the time of clinical improvement, but not of clinical recovery. The test was a biological discriminator between severe and less severe depressions. The time of symptomatic improvement (r = 0.505, P less than 0.05), but not of biological remission, depended on age; severe depressions lasted longer in the elderly patients.

Depressive Disorder↗
PubMedDate not supplied

The cortisol responses to 5-hydroxytryptophan, orally, in depressive inpatients.

Baseline cortisol levels at 8:00 a.m. and the cortisol responses at 90 and 120 min after oral administration of 200 mg 5-hydroxytryptophan (5-HTP) (L-isomer, non-enteric-coated) were assessed in 65 depressed inpatients. Patients were categorized according to DSM-III as major (296.22; 296.32; 296.23; 296.33; 296.24; 296.34) and minor (300.40; 309.00; 296.82) depressives. We observed a significant rise of plasma cortisol in patients with major depression at 90 (P = 0.0001) and 120 (P = 0.002) min, but not in patients with minor depression. Patients with major depression showed significantly higher cortisol responses than those with minor depression (P = 0.016). This significant rise of plasma cortisol after 5-HTP could be attributed to sex-linked differences: we observed significant (P = 0.0065) rises in cortisol responses in women with major depression compared to depressed men and women with minor depression. These differences could not be attributed to age, concomitant benzodiazepine use or pre/postmenopausal status. Baseline cortisol correlated negatively with the cortisol response to 5-HTP. The increased cortisol responses in women with major depression remained significant even after the effects of baseline cortisol were partialled out. This rise in cortisol response can be explained by an increased responsiveness of the hypothalamic-pituitary-adrenal axis to 5-HTP.

5-Hydroxytryptophan↗
PubMedDate not supplied

Sex-related differences in the relationships between self-rated depression and biological markers.

Gender-related differences in self-reported depression, in biological factors putatively related to depression and in the associations between severity of illness and biological factors were investigated. To this end the Zung Self-Rating Depression Scale (SDS), the ratio L-tryptophan/valine + leucine (L-TRP/CAA) and basal cortisol in serum at 8 a.m. were determined in 51 depressed inpatients undergoing a dexamethasone suppression test (DST). In the total study group no significant relationships were established between severity of illness and either of the biological markers. In women, SDS correlated significantly (P less than 0.01) negatively with the ratio L-TRP/CAA and positively with post-dexamethasone cortisol (P less than 0.01). In men these relationships tended to be inverted. The differences in the two sexes between these correlation coefficients were significant (P less than 0.01). These gender-related differences in the relationships between self-reported depression and the biological variables could be explained by differential psychoneuroendocrine and psychobiochemical responses. Future work on the severity of illnesses in terms of biological factors must take into account these differential responses between depressed males and females.

Adult↗