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Biomedical subjects

J Soler

Publications and source records attributed to J Soler.

At least 19 recordsLinked to original sources
PubMed1992

Inactivation of Phycomyces isocitrate lyase by thiol-reactive reagents. Evidence for an essential thiol group.

Isocitrate lyase from the mycelium of Phycomyces blakesleeanus was inactivated with thiol-reactive reagents, 5,5'-dithiobis-(2-nitrobenzoic)acid, p-hydroxymercuribenzoic acid, N-ethylmaleimide or iodoacetate, at pH 6.8 and 25 degrees C. In all cases the inactivation is characterized by a biphasic kinetic profile. The rapid initial phase of inactivation does not increase linearly with increasing reagent concentration, but exhibits an apparent saturation effect, suggesting the formation of a reversible complex between the enzyme and the reagent prior to the inactivation step. Re-activation of the enzyme was observed under thiol excess treatment. The pH dependence of the initial phase of inactivation suggests that a group on the enzyme with pKa = 6.8 is being modified. The effect of ligands was tested on the inactivation reaction. Mg(2+)-Ds-isocitrate and Ds-isocitrate provided total protection, whereas Mg2+ ions, succinate and oxalate provided only partial protection of the enzyme against inactivation. On the basis of these results, we would suggest that the thiol-reactive reagents modify at least one thiol group crucial for the enzymatic activity and probably located in the interface between succinate and glyoxylate subsite.

Hydrogen-Ion Concentration↗
PubMed1992

Growth hormone response to thyrotropin-releasing hormone in acromegalic patients: reproducibility and dose-response study.

The aim of the study was to analyze 14 consecutive patients with active acromegaly who had not undergone any therapy, the dose response of growth hormone (GH) to thyrotropin-releasing hormone (TRH), the existence of reproducibility of such response as well as to rule out the possibility of spontaneous fluctuations of GH which would mimic this response. On several nonconsecutive days, we investigated the GH response to saline serum, 100, 200 (twice) and 400 micrograms of TRH administration. We also studied both basal serum prolactin, serum prolactin after TRH administration and thyrotropin values. Our results show an absence of GH response after saline serum infusion, whereas after TRH doses, 36.3 42.8 and 45.4% positive responses were obtained, respectively. All GH responders were concordant to the different doses administered. The mean of GH concentrations of the different doses at different times did not reach significant differences. The response to the administration of the same dose brought about a significative increase, although it was not identical. It demonstrated a progressive increase of the area under the response curve, as did the means of increments after each TRH administration, albeit without reaching statistical significance. Between the GH-responding and GH-nonresponding groups there were no differences in either basal serum prolactin or serum prolactin and thyroid-stimulating hormone levels after TRH stimulation. The present study clearly shows that TRH elicits serum GH release from GH-secreting pituitary tumors. The response was reproducible in qualitative terms rather than quantitative, and no dose-response relationship was found between the TRH concentrations and the amounts of GH secreted.

Acromegaly↗
PubMed1992

High-dose chemotherapy with bone marrow rescue for treatment of Hodgkin's disease.

Between December 1st 1984 and July 1st 1991, 20 patients, 11 males and 9 females, median age 36 years (range 14-54) with Hodgkin's disease were treated with high dose chemo-radiotherapy followed by autologous bone marrow rescue. At the time of autologous bone marrow transplantation, 8 patients were in complete remission, 9 in sensitive relapse and 3 were resistant to conventional treatments. There were 3 early procedure-related deaths: 1 cardiac failure due to cyclophosphamide treatment, 1 veno-occlusive disease, and 1 patient died from CMV interstitial pneumonitis, 4 months after ABMT. Of the 17 other patients, 15 are alive, 12 in complete remission, 2 in relapse and 1 patient is not evaluable due to short-follow-up follow-up. Disease free survival is 65% at 20 months with a follow-up of 60 months. There is a trend for a better disease-free survival in patients in complete remission at the time of autologous bone marrow transplantation vs patients in sensitive relapse, although it does not reach statistical significance (80% vs 37%).

Adolescent↗
PubMed1992

Oxidative modification of lactate dehydrogenase by a non-enzymatic metal ion-catalyzed oxidation system.

Exposure of lactate dehydrogenase from rabbit muscle to the Fe(III)/EDTA/ascorbate oxidation system leads to a time-dependent enzymatic inactivation (rate of inactivation of 7.35 x 10(-3) min-1), as well as to a spontaneous fragmentation of the protein. Fe(III) is the most important compound in this system, having the highest inactivating effects at concentrations above 10 microM. The substrate pyruvate and the products of the enzymatic reaction, when added at high concentration to the full mixture of the system, have a partial protective effect on the catalytic activity.

Animals↗
PubMed1992

Salivary testosterone as an index of antiandrogen therapy in hirsutism.

The purpose of this study is to examine whether salivary testosterone (ST) in hirsute women treated with antiandrogen therapy can be considered a good parameter for the evaluation of clinical response. Twenty-three hirsute women, four with polycystic ovarian disease and 19 with idiopathic hirsutism were treated with cyproterone acetate and ethynyl-oestradiol with levonorgestrel in a reverse sequential regime for three months. Basal ST from hirsute women was 0.18 +/- 0.11 nmol/L (normal values 0.03-0.17) and a decrease to 0.11 +/- 0.06 was observed in the first month of treatment, to 0.1 +/- 0.059 after two months and to 0.11 +/- 0.06 after three months, all of them significantly different from basal values (p < 0.05). We found a relationship between ST decrease and the clinical response to antiandrogen therapy. On the basis of these results we suggest that ST values could be a good index for the follow-up of antiandrogen therapy in hirsute women.

Adolescent↗
PubMed1991

Presenting features and prognosis of chronic lymphocytic leukemia in younger adults.

We have analyzed 117 younger patients with chronic lymphocytic leukemia (CLL) (mean age, 44.5 years; SD, 4.8; range, 19 to 49; male/female ratio, 2.08) with three main objectives: (1) to see whether these patients have distinctive presenting clinical features; (2) to investigate the impact of the disease on survival; and (3) to analyze whether already well-known prognostic factors are also useful when applied to these patients. As compared with an older age population (greater than or equal to 50 years), there were no major differences in presenting features except for an increased proportion of males (2.08 v 1.21; P less than .025) and a higher hemoglobin level (13.47 +/- 2.70 g/dL v 12.84 +/- 2.77 g/dL; P less than .05) in the younger group. Median survival is 12.3 years (expected median from a control group, 31.2 years). Clinical stages, bone marrow patterns, blood lymphocyte counts, and its doubling time are all useful to separate different risk groups of patients. Whereas patients with favorable prognostic factors have a survival probability of about 80% 14 years after diagnosis, those with poor prognostic features have a median survival of less than 3 years. It is concluded that CLL in younger adults has no major distinctive presenting features and that known prognostic factors are useful to separate different risk groups of patients. These results should be of help in planning therapy for younger persons with CLL.

Adult↗
PubMed1991

[Pituitary apoplexy: analysis of endocrine function in 17 cases].

BACKGROUND: From a neurological standpoint, pituitary apoplexy (PA) is a well defined syndrome. There are few systematic studies addressing pituitary hormone secretion after a PA episode. The aim of the present study was to assess the frequency and degree of endocrine dysfunction due to PA. METHODS: In 17 consecutive patients, the secretion of growth hormone (GH), the pituitary-adrenal axis status, thyrotropin (TSH), prolactin and gonadotropins (LH, FSH) were evaluated after the administration of insulin, thyrotropin releasing hormone (TRH) and gonadotropin-releasing hormone (LHRH) after an episode of PA. 20-90 days after surgery the measurements were repeated. Antidiuretic hormone (ADH) was measured by plasma/urine osmolality after water deprivation and, in some cases, by administration of hypertonic saline. RESULTS: The most commonly found deficiency was that of GH (84%), which in two cases resulted in cure of acromegaly, followed by that of LH (78%). Pituitary-adrenal dysfunction was improved in two patients after surgery. In all cases except one there was a reduced secretion of at least two hormones. If serum prolactin was reduced, the rest of pituitary function was usually impaired. In one case, permanent diabetes insipidus developed after PA. The prevalence of PA in pituitary adenomas was 9%. CONCLUSIONS: Pituitary hormone secretion after a PA episode is almost invariably impaired. This impairment may be reversed after surgery. Hypoprolactinemia is an indicator of pituitary hypofunction.

Adenoma↗
PubMed1991

[Limitations of joint mobility in patients with type 1 diabetes mellitus].

BACKGROUND: To assess limitation of joint mobility in patients with type I diabetes mellitus and to evaluate its relation with retinopathy, joint mobility was prospectively assessed in 96 diabetic patients and 68 healthy controls. METHODS: Joint mobility was explored with the praying maneuver and the measurement in mobility degrees of the third and fifth metacarpophalangeal joints, wrists and elbows. The degree of metabolic control was assessed with the mean glycosylated hemoglobin in the last two years. Retinopathy was investigated with direct funduscopy. The results were statistically evaluated with chi-square and Student's t tests and the linear coefficient. RESULTS: A reduced joint mobility was found in 41 diabetics and 5 controls (p less than 0.0001). The reduction in joint mobility was related with the patients' age but not with the degree of metabolic control. 85% of diabetics with joint involvement had retinopathy of some degree. CONCLUSIONS: A limited joint mobility is a common complication of type I diabetes mellitus. The demonstration of this abnormality in diabetic patients might represent a first and simple marker of microangiopathy.

Adolescent↗
PubMed1991

Mitochondrial F1-ATPase moiety from Phycomyces blakesleeanus: purification, characterization, and kinetic studies.

Mitochondrial F1-ATPase was purified from the mycelium of Phycomyces blakesleeanus NRRL 1555(-) and its kinetic characteristics were studied. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the enzyme reveals five bands (alpha, beta, gamma, delta, and epsilon) characteristic of the F1 portion with apparent molecular weights of 60,000, 53,000, 31,000, 25,000, and 21,000, respectively. The molecular weight of the native F1-ATPase from Phycomyces blakesleeanus was in agreement with the stoichiometry alpha 3 beta 3 gamma delta epsilon. The MgATP complex is the true substrate for ATPase activity which has a Km value of 0.15 mM. High concentrations of free ATP or free Mg2+ ions inhibit the ATPase activity. ADP appears to act as a negative allosteric effector with regard to MgATP hydrolysis, with the apparent Vmax remaining unchanged.

Adenosine Diphosphate↗
PubMed1991

Hysteretic behaviour and GSSG substrate inhibition shown by glutathione reductase from Phycomyces blakesleeanus.

Phycomyces blakesleeanus glutathione reductase shows hysteretic behaviour under experimental conditions, when GSSG substrate inhibition is observed. The progress curves for the reaction show an acceleration phase. The degree of hysteresis varied inversely as the enzyme concentration. It increased when GSSG or NADPH concentration increased, whereas the addition of GSH or NADP+ to the initial reaction mixture prevented it from occurring. In addition, hysteresis was dependent on pH, ionic strength and temperature, decreasing as any of these parameters increased. The parallel effects of pH and ionic strength on the GSSG substrate inhibition and hysteretic behaviour suggest a relationship between these two mechanisms. From the overall results reported in this paper, we propose that the hysteretic behaviour shown by Phycomyces glutathione reductase could be due to a process of time-dependent accumulation of reaction products rather than to a slow conformational change.

Glutathione↗
PubMed1991

Thyroid stimulating antibodies in patients with Graves' ophthalmopathy.

The possible pathogenetic role of thyroid stimulating antibodies (TSAb) was studied in 24 patients. The TSAb were measured by their ability to stimulate concentration of cAMP in human thyroid slices incubated in vitro with the immunoglobulins of these patients. The patients were divided in two groups: Group I, 16 patients with eye disease and hyperthyroidism and Group II, eight patients with eye disease but without hyperthyroidism. TSAb, were found to be high in 15 patients of the Group I (3.22 +/- 1.74 pmol cAMP/mg of wet tissue, mean +/- S.E.M.) whilst were normal in six patients of the Group II (0.98 +/- 0.53 pmol cAMP/mg of wet tissue, mean S.E.M.) (p < 0.001). These findings indicate that TSAb is not a marker of the Graves' ophthalmopathy and support the concept that hyperthyroidism and exophthalmos are two separate disorders.

Adolescent↗
PubMed1991

[Thyroid dysfunction induced by amiodarone in Catalonia. Prevalence and characteristics].

The purpose of this study was to review the epidemiological aspects and the characteristics of the thyroid disfunction produced by amiodarone in Catalonia, an area with type I endemic goiter. For this purpose, three groups of patients have been studied: 1) 102 patients with prolonged amiodarone treatment, out of whom 6 (5.9%) presented hyperthyroidism, and 2 (1.9%) hypothyroidism. 2) 909 patients with hyperthyroidism of any origin out of which 42 (4.6%) were produced by amiodarone. 3) 203 patients presenting primary hypothyroidism of any origin out of which 11 (3.8%) were induced by amiodarone. Out of the 48 patients with amiodarone induced hyperthyroidism, 16 presented multinodular goiter, 2 toxic thyroid goiter and 7 Graves Basedow disease. Thyroid uptake of 131I was studied in 10 cases being normal or increased in six of them, all with a underlaying thyroid pathology. Out of the 13 patients with amiodarone induced hypothyroidism, 3 presented diffuse goiter; thyroid uptake of 131I was studied in 5 patients, being normal or increased in 4 cases, 2 of which with thyroid pathology. Amiodarone administration very often produces thyroid disfunction, specially hyperthyroidism. These patients with hyperfunctional thyroids usually present underlying thyroid pathologies in which thyroid uptake of 131I are frequently not suppressed as well as in those patients in whide amiodarone induced hypothyroidism.

Adolescent↗
PubMed1991

Inhibition by excess of free ATP, and free Mg2+ ions of the mitochondrial F1-ATPase moiety from Phycomyces blakesleeanus.

High concentrations of either Mg-ATP complex, free ATP, or free Mg2+ ions were inhibitors of the mitochondrial F1-ATPase moiety from Phycomyces blakesleeanus. Free Mg2+ acts as a linear competitive inhibitor with regard to Mg-ATP hydrolysis with a Ki value of 2.8 mM. The inhibition by free ATP was markedly biphasic and thus simple competitive inhibition alone is not sufficient to explain the inhibitory effect. From these results conclusions were drawn about the binding of the substrate, Mg-ATP complex, to the enzyme.

Adenosine Triphosphate↗
PubMed1991

Allogeneic bone marrow transplantation in chronic lymphocytic leukemia: 17 cases. Report from the EBMTG.

Allogeneic bone marrow transplantation (BMT) was performed in 17 patients with chronic lymphocytic leukemia (CLL): 15 resistant and two untreated forms. There were 12 males and five females with a mean age of 40 years (32-49). The conditioning regimens and graft-versus-host disease (GVHD) prophylaxis varied. Successful engraftment was obtained in 15 evaluable cases. Lymphocytosis and clinical symptoms subsided in all but one case. All 15 evaluable patients developed acute GVHD. Among the 17 patients grafted, one early death was observed at the 15th day post-BMT, and one refractory patient died 2 months after BMT. Of the remaining 15 patients in complete remission (CR), four died from GVHD, hemorrhage and graft failure, and two relapsed at 7 and 54 months after BMT and died. Nine patients are alive in CR with a mean follow-up of 25.6 months (4-48). Chimerism was complete in eight patients and partial in the two T cell-depleted cases. In one case, an immunoglobulin gene rearrangement study showed no residual disease. These results suggest that allogenic BMT might be an alternative and possible curative therapy for refractory CLL in young patients when performed relatively early in the disease.

Adult↗
PubMed1990

Isocitrate lyase from Phycomyces blakesleeanus. The role of Mg2+ ions, kinetics and evidence for two classes of modifiable thiol groups.

Isocitrate lyase was purified from Phycomyces blakesleeanus N.R.R.L. 1555(-). The native enzyme has an Mr of 240,000. The enzyme appeared to be a tetramer with apparently identical subunits of Mr 62,000. The enzyme requires Mg2+ for activity, and the data suggest that the Mg2(+)-isocitrate complex is the true substrate and that Mg2+ ions act as a non-essential activator. The kinetic mechanism of the enzyme was investigated by using product and dead-end inhibitors of the cleavage and condensation reactions. The data indicated an ordered Uni Bi mechanism and the kinetic constants of the model were calculated. The spectrophotometric titration of thiol groups in Phycomyces isocitrate lyase with 5.5'-dithiobis-(2-nitrobenzoic acid) gave two free thiol groups per subunit of enzyme in the native state and three in the denatured state. The isocitrate lyase was completely inactivated by iodoacetate, with non-linear kinetics. The inactivation data suggest that the enzyme has two classes of modifiable thiol groups. The results are also in accord with the formation of a non-covalent enzyme-inhibitor complex before irreversible modification of the enzyme. Both the equilibrium constants for formation of the complex and the first-order rate constants for the irreversible modification step were determined. The partial protective effect of isocitrate and Mg2+ against iodoacetate inactivation was investigated in a preliminary form.

Ammonium Sulfate↗