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Biomedical subjects

M Giralt

Publications and source records attributed to M Giralt.

At least 109 records · Page 6Linked to original sources
PubMed1993

Effect of stress, adrenalectomy and changes in glutathione metabolism on rat kidney metallothionein content: comparison with liver metallothionein.

Eighteen hours of immobilization stress, accompanied by food and water deprivation, increased liver metallothionein (MT) but decreased kidney MT levels. Food and water deprivation alone had a significant effect only on liver MT levels. In contrast, stress and food and water deprivation increased both liver and kidney lipid peroxidation levels, indicating that the relationship between MT and lipid peroxidation levels (an index of free radical production) is unclear. Adrenalectomy increased both liver and kidney MT levels in basal conditions, whereas the administration of corticosterone in the drinking water completely reversed the effect of adrenalectomy, indicating an inhibitory role of glucocorticoids on MT regulation in both tissues. Changes in glutathione (GSH) metabolism produced significant effects on kidney MT levels. Thus, the administration of buthionine sulfoximine, an inhibitor of GSH synthesis, decreased kidney GSH and increased kidney MT content, suggesting that increased cysteine pools because of decreased GSH synthesis might increase kidney MT levels through an undetermined mechanism as it appears to be the case in the liver. However, attempts to increase kidney MT levels by the administration of cysteine or GSH were unsuccessful, in contrast to what is known for the liver. The present results suggest that there are similarities but also substantial differences between liver and kidney MT regulation in these experimental conditions.

Adrenal Glands↗
PubMed1993

Chronic stress reduces serum but not liver metallothionein response to acute stress.

Rats subjected to chronic immobilization stress showed a reduced serum metallothionein (MT) response to acute immobilization stress compared to nonchronically stressed rats. In contrast, liver MT response to acute immobilization stress was not influenced by previous chronic immobilization stress. These results suggest that serum MT levels are likely under endocrine regulation and that they do not reflect directly liver MT levels. Instead it appears that both MT pools are regulated differently. The fact that liver MT is resistant to adaptation to chronic stress may be related to its physiological function.

Acute Disease↗
PubMed1993

Chronic stress induced changes in LH secretion: the contribution of anorexia associated to stress.

The effects of chronic intermittent immobilization (IMO) on serum LH levels of adult male rats were studied. Chronic IMO (2 h daily for 13 days) did not alter basal LH levels, but abolished the LH response to acute stressors (IMO and tailshock). The inhibition of LH caused by acute exposure to IMO for 4 or 18 h was similar in control and chronic IMO rats. Also the LH response to exogenous LHRH administration was normal in chronically stressed rats. When a group of rats eating the same amount of food as that eaten by immobilized rats was introduced (pair-fed), an inhibition of LH response to acute stressors quite similar to that found in chronic IMO rats was observed. These data indicate that chronic stress-induced inhibition of LH release caused by short-term exposure to acute stressors was located above the pituitary and was mainly due to anorexia accompanying daily exposure to the stressor.

Analysis of Variance↗
PubMed1993

Effects of chronic immobilization stress on GH and TSH secretion in the rat: response to hypothalamic regulatory factors.

The effect of chronic immobilization (2 h/day) for 13 days on basal and stress levels of GH and TSH, and their response to various hypothalamic regulatory factors was studied in male Sprague-Dawley rats. Chronic immobilization (IMO) resulted in reduced serum TSH levels in stress situations but not in resting conditions. GH secretion was inhibited both in resting and stress situations. Chronic IMO impaired both GH and TSH responses to GRH and TRH, respectively, but also to another peptide (VIP) stimulatory for the two hormones. Whereas somatostatin administration inhibited GH secretion in control but not in chronic IMO rats, its inhibitory effect on TSH was slight and similar in the two experimental groups. The present results suggest that chronic exposure to a severe stressor such as IMO alters GH and TSH secretion, at least in part by changes in the response of the pituitary to the hypothalamic regulatory factors. The actual influence of chronic IMO on the release of these peptides into the median eminence remains to be studied.

Animals↗
PubMed1993

Enhanced glutathione S-transferase activity and glutathione content in human bladder cancer. Followup study: influence of smoking.

Glutathione content and glutathione S-transferase activity have been studied in human bladder specimens obtained from controls and from patients with superficial transitional cell carcinoma (tumor samples and peri-tumor normal tissues from the same patient). After combining an earlier study from our laboratory with the additional material presented (9 healthy controls and 25 transitional cell carcinoma patients), it can be observed that glutathione S-transferase activity was significantly greater in tumor than in peri-tumor normal tissue (34 patients, p < 1 x 10(-7)) or in normal mucosa (17 controls, p < 1 x 10(-3)). Glutathione content was significantly greater in tumor than in peri-tumor normal tissue (p < 5 x 10(-3)) or in normal mucosa (p < 2 x 10(-2)), with this increase being evident only in smokers. When comparing normal mucosa and peri-tumor samples no significant differences were found either for glutathione S-transferase activity or for glutathione content. Results demonstrate the relationship between the glutathione S-transferase/glutathione system and development of transitional cell carcinoma, as well as its role in cellular resistance to chemotherapy.

Aged↗
PubMed1993

Ontogeny of thyroid hormone receptors and c-erbA expression during brown adipose tissue development: evidence of fetal acquisition of the mature thyroid status.

We have determined the developmental changes in thyroid hormone receptor expression and thyroid hormone status in rat brown adipose tissue (BAT). The present study demonstrates that c-erbA alpha and -beta genes are expressed in the developing BAT. The 6.5-kilobase (kb) beta 1, 2.6-kb alpha 2, 5.5-kb alpha 1, and 6.6-kb alpha transcripts showed peak values on day 20 of fetal life. High affinity T3-binding sites were found in fetal BAT. Binding capacity was similar (18-day-old fetuses) or higher (20-day-old fetuses) than in postnatal or adult brown fat. In contrast, T3 receptors were scarce in fetal liver, and values in adult liver were similar to those in fetal BAT on day 20. The profiles of iodothyronine 5'-deiodinase, nuclear T3 content, and receptor occupancy also showed peak values in fetal BAT on day 20, but they were very low in fetal liver. Thus, BAT has already achieved complete maturation of its thyroid status on day 20 of gestational age. This highly tissue-specific developmental pattern is unique among other mammalian thyroid-sensitive tissues studied to date. Between days 18 and 20 of rat fetal development, there is a specific induction of the uncoupling protein gene expression, the main marker of differentiated adipocytes. The results suggest that thyroid hormones may be involved in the establishment of the differentiated phenotype of the brown fat cell in fetal life.

Adipose Tissue, Brown↗
PubMed1993

Effect of endotoxin on rat serum, lung and liver lipid peroxidation and on tissue metallothionein levels.

The effect of endotoxin on serum and lung and liver lipid peroxidation, as measured by thiobarbituric acid reactants (TBARs), as well as on lung and liver metallothionein (MT) has been studied in the rat. Endotoxin consistently increased serum and liver TBARs in a time-response manner. The increase in the serum preceded that in the liver, with peaks 3-6 h and 24 h after endotoxin administration, respectively. In contrast, lung TBARs levels did not increase regardless of the experimental approaches studied, suggesting that the rat is not a good model for the adult respiratory distress syndrome. Endotoxin increased both lung and liver MT levels in a time-response manner, although to a lesser degree in the former than in the latter tissue, indicating that this protein may have a significant role in the response of the organism to a septic insult.

Animals↗
PubMed1992

Opposing actions of Fos and Jun on transcription of the phosphoenolpyruvate carboxykinase (GTP) gene. Dominant negative regulation by Fos.

Jun homodimers and Fos/Jun heterodimers bind to the gene for phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK) at three sites within the first 350 base pairs of the promoter. These include CRE-1 (-82 to -90), and P3(II) and P4 (-252 to -258 and -268 to -285, respectively). Over-expression of Jun in HepG2 cells resulted in a 10-15-fold increase in the level of transcription of a chimeric PEPCK (-490 to +73)-CAT gene, while expression of Fos decreased transcription and blocked the induction of transcription from the PEPCK promoter by Jun. The action of Fos and Jun on PEPCK gene transcription involved each of the Fos/Jun-binding sites and was modulated by additional transcriptional regulatory elements within the PEPCK promoter. The ability of Fos to inhibit PEPCK transcription was dependent upon P3(I), a region of the promoter which does not bind Fos/Jun heterodimers, but does bind members of the C/EBP family of transcription factors. Stimulation of PEPCK transcription by 8-Br-cAMP or by overexpression of the catalytic subunit of protein kinase A was inhibited by Fos expression. The inhibitory effects of phorbol esters and protein kinase C on PEPCK gene expression may be mediated through the action of Fos and Jun.

Binding Sites↗
PubMed1992

[Non-Hodgkin's lymphomas. I. Clinico-biological features of 307 cases].

PURPOSE: To assess the clinico-biological features appearing in 307 patients with non-Hodgkin's lymphomas (NHL). PATIENTS AND METHODS: The clinical records of 338 patients diagnosed of NHL between January 1975 and December 1988 were revised in retrospect. All cases with histologic diagnosis of NHL aged over 14 years were included, and classified in accordance with the Working Formulation criteria. The following data were analysed: age, sex, first complaints, time elapsed since onset, histologic type, number of sites involved, bulky disease, anaemia, thrombocytopenia, LDH, stage, type of treatment and initial response, survival, and cause of death. The statistical evaluation was performed by actuarial analysis (Kaplan and Meier) and comparison (log-rank test) of survival. RESULTS: According to the three categories of the malignancies, the NHL were distributed into low-grade (37.8%), intermediate (36.1%) and high-grade (26.9%). The mean age of the series was 56.6 years and the M/F ratio was 1.3. Lymph node enlargement was the commonest finding; 36.4% of the patients had symptoms related with the disease, and 26.7% had bulky disease. Anaemia was present in 37.7% of the cases and thrombocytopenia in 14.3%, with similar distribution among the three grades. High LDH levels were found in 44% of the patients. At diagnosis, 85% of the patients were in advanced stages (III+IV) already. Complete response was attained in 51.1% of the cases, with median survival of 48 months. CONCLUSIONS: The clinico-evolutive data found here are similar to other reports in the literature. In one-half of the patients the cause of the first visit is lymph node enlargement. Complete remission is achieved by one out of two patients, this figure being similar for each of the histologic groups. The Working Formulation is useful in determining the different prognostic groups with respect to survival.

Adolescent↗
PubMed1992

[Non-Hodgkin's lymphomas. II. Analysis of the prognostic factors in a series of 307 patients].

PURPOSE: To analyse different clinico-biologic data in order to assess their prognostic value in non-Hodgkin's lymphoma (NHL) patients. MATERIAL AND METHODS: The series comprises 307 patients with NHL diagnosed and treated between 1975 and 1988. The histopathologic diagnosis was revised in accordance with the working formulation system, three prognostic groups being thus considered: low-grade (LGL), intermediate-grade (IGL) and high-grade (HGL) lymphomas. Age, sex, clinical course prior to diagnosis, presence of B symptoms, histologic type, number of lymph-node areas involved, bulky disease, anaemia, thrombocytopenia, LDH, stage and response to therapy were all evaluated for the study. Survival curves were drawn with the Kaplan-Meier method, and the log-rank test was used for comparison of median survival. Whenever the univariate analysis achieved statistical significance, a multivariate analysis was performed by means of a multiple correlation and regression study in accordance with the Cox's model, in which the variables were expressed in a binary model. RESULTS: The following 8 values were found significant in the univariate study of low-grade lymphomas: age, number of involved areas, bulky disease anaemia, thrombocytopenia, LDH, stage, and initial response to treatment. In intermediate-grade lymphomas, the significant findings were age, number of affected areas, bulky disease, thrombocytopenia, LDH, stage, and initial response. For high-grade lymphomas, number of affected areas, thrombocytopenia, LDH, stage and initial response were found statistically significant. Although no significant differences were found for survival within each of the three grades, such differences were significant between them. In the multivariate analysis, age was significant only in the LGL (p < 0.0001) in IGL, age (p < 0.07) and initial response to therapy (p < 0.0001) achieved significant value, and in HGL, stage (p < 0.02) and initial response to treatment (p < 0.0001) attained significance. CONCLUSIONS: The univariate analysis provides various prognostic factors of statistically significance, as reported in the literature, but these after the multivariate analysis was applied, were reduced to age, stage and initial response to treatment.

Adolescent↗
PubMed1991

Identification of a thyroid hormone response element in the phosphoenolpyruvate carboxykinase (GTP) gene. Evidence for synergistic interaction between thyroid hormone and cAMP cis-regulatory elements.

Transcription of the gene for the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK) in the liver is regulated by many hormones including thyroid hormone (T3). In order to identify the elements in the promoter which are required for transcriptional induction by T3, we cotransfected a T3 receptor expression vector with a PEPCK-CAT reporter gene into HepG2 cells. Using vectors with deletions in the PEPCK promoter, we identified a single T3 response element (TRE) between positions -332 and -308. This element binds [125I]T3-labeled T3 receptor contained in nuclear extracts prepared from rat liver. Furthermore, the P3(I) element (-250 to -234), a previously described cis-sequence involved in mediating the induction of PEPCK gene transcription by cAMP, is also required for the T3 responsiveness of the promoter. In the absence of either the TRE or the P3(I) binding sites, no stimulation of transcription from the PEPCK promoter by T3 was observed, indicating that both elements are required for the T3 transcriptional regulation. Finally, a synergistic induction of PEPCK gene transcription by T3 and cAMP is described. This interaction requires both T3- and cAMP-responsive cis-acting elements.

Base Sequence↗
PubMed1991

Life expectancy of patients with chronic nonleukemic myeloproliferative disorders.

This study determines, within the frame of current therapeutic possibilities, the impact of chronic nonleukemic myeloproliferative disorders on expected survival. The survival data for 1067 patients (454 with polycythemia vera, 247 with essential thrombocythemia, and 366 with idiopathic myelofibrosis) were collected from 38 Spanish institutions. The actuarial survival probability of each group of patients was compared with that of the age-matched and sex-matched control population. The survival of the patients with polycythemia vera and essential thrombocythemia did not differ from that of the control population (P = 0.92 and, 0.22, respectively), whereas the survival of the patients with idiopathic myelofibrosis was strikingly reduced with respect to the control population (P = 0.0000000007). Thus, in terms of survival, current therapeutic procedures may be considered as quite satisfactory in patients with polycythemia vera and essential thrombocythemia. On the other hand, due to poor survival of patients with idiopathic myelofibrosis, new therapeutic approaches for this condition are clearly needed.

Aged↗
PubMed1991

alpha Interferon in the management of essential thrombocythaemia.

Thirteen patients (mean age 60.7 years; female:male ratio 10:3) with essential thrombocythaemia were treated with 3 million units (MU)/day interferon alfa-2b subcutaneously (s.c.) for 12 weeks, with all patients requiring a dose reduction after 4 weeks. The mean pretreatment platelet count was 1,400 x 10(9)/L and megakaryocytes were increased in all cases. Splenomegaly was present in six patients and haemorrhagic phenomena were observed in two. Nine patients (69.2%) had objective responses, including two (15.4%) complete responses (platelets less than 450 x 10(9)/L) which were then maintained with 5 MU interferon twice a week. Acute toxicity consisted of flu-like symptoms in 12 patients. Chronic toxicity (mainly leucopenia) was observed in nine patients. In conclusion, initial therapy and then requiring maintenance therapy at a reduced dose. However, the frequent side effects observed make it advisable to use a low dose of interferon alfa-2b, and to treat only those patients with significant symptoms and signs of thrombocytosis.

Adult↗
PubMed1991

[Analysis of 4 prognostic scoring systems in 197 myelodysplastic syndrome patients].

PURPOSE: To evaluate the prognostic significance of four scoring systems applied with predictive trends to myelodysplastic syndromes (MDS). MATERIAL AND METHODS: This study is comprised of 197 patients with MDS diagnosed in accordance with the FAB criteria and followed-up in our Department between Jan '75 and Dec '89. The following MDS subtypes were found: refractory anaemia (RA), 58 cases; sideroblastic refractory anaemia (SRA), 42 cases; refractory anaemia with excess of blasts (RAEB), 46 cases; RAEB in transformation (RAEB-T), 39 cases; and chronic myelomonocytic leukaemia (CMML), 12 cases. The following scoring systems were applied: Mufti's 1985, Varela's 1985, Sanz's 1989 and our own of 1991. The statistical analysis was performed according to Kaplan-Meier actuarial system and the log-Rank test of actuarial survival. RESULTS: (1) Three groups (A, B and C) can be defined by the Bournemouth system, with median survivals of 57.6, 17 and 7.6 months, respectively. The majority of cases (118) were included in group B. Group A has not reached 25% of actuarial survival probability, whereas groups B and C did at 32 and 10 months, respectively. With regard to the morphologic subtypes, RA and SRA were included in groups A and B, and RAEB, RAEB-T and CMML pertained mostly of group C. Sixty cases (90.9%) evolving into acute leukaemia (AL) corresponded to those last groups. (2) The three groups defined by Varela's system (0-1, 2-5 and 6 or more) have median survival of 85.6, 24 and 14 months, respectively. Like in the former system, group 0-1 has not reached 25% actuarial probability, this appearing at 70 and 20 months, respectively, in groups 2-5 and greater than 6. The distribution of the cytological varieties, RA and SRA amongst the groups is heterogeneous although there are more common within the cases included in groups 0-1. All the cases evolving into AL were included in the groups 2-5 and greater than 6. (3) The 3 groups of the system proposed by Sanz (0-1, 2-3 and 4-5) had median survival of, respectively, 58, 15 and 14 months. Like in the preceding cases, group 0-1 has not reached the 25% actuarial probability, while this figure appears at 28 months for group 2-3 and at 20 months for group 4-5. RA and SRA varieties are included chiefly in group 0-1, while RAEB and RAEB-T appear mostly in groups 2-3 and 4-5. The distribution of the cases and evolving into AL in heterogeneous according to this system, although they predominate in groups 2-3 and 4-5. (4) The prognostic groups are defined by the system proposed by us (namely 0-2, 3-5, 5 greater than or equal to 6) with median survivals of 89.3, 17 and greater than 11 months, respectively. Striking difference was seen when studying the cumulated survivals observed, on each of the three percentages considered, between the groups. The different cytological varieties distributed reasonably with higher incidence of RA and SRA in group I and RAEB, RAEB-T and CMML in group III. This system offers statistical significance when comparing RA with SRA, RAEB with RAEB-T and, obviously. RA+SRA with RAEB+RAEB-T+CMML. The evolution into AL showed also statistical significance with respect to the three groups. CONCLUSIONS: 1. Three prognostic groups regarding the patient's survival could be established in our series with all the scoring systems analyzed, except that of Sanz. 2. Low risk (RA and SRA) and high risk (RAEB, RAEB-T and CMML) cytological varieties can be identified with all the scoring systems; that of Sanz is also capable of discriminating RA from SRA. 3. Some prediction on the possibility of evolution into AL can be attained of with each system. 4. The scoring system proposed by us shows higher discriminating capability on the cytologic varieties as well as higher predictive value on the possibility of evolution into AL. Nevertheless, it must be evaluated in other series in order to reach general acceptance.

Actuarial Analysis↗