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M Giralt

Publications and source records attributed to M Giralt.

At least 91 records · Page 5Linked to original sources

ETS transcription factors regulate the expression of the gene for the human mitochondrial ATP synthase beta-subunit.

Elements responsible for the transcriptional activity of the human ATP synthase beta-subunit (ATPsyn beta) gene promoter have been studied through transient expression in HepG2 hepatoma cells of a CAT gene connected with various 5'-deletion mutants of the 5'-flanking region. Promoter activity was mostly dependent upon a single CCAAT motif as well as a nearby Ets domain binding region. This last region contains two sites that bind Ets-related proteins present in liver nuclear extracts as well as recombinant purified Ets-1 protein. The ATPsyn beta promoter was trans-activated by Ets-1 and Ets-2 expression vectors, and this effect was lost when the Ets binding region was deleted. The Ets binding region of the ATPsyn beta promoter increased basal expression and conferred Ets-1- and Ets-2-dependent trans-activation to the herpes symplex thymidine kinase minimal promoter. A double-point mutation of the main Ets-binding site, which suppresses Ets binding, blocks Ets-dependent trans-activation. It is concluded that the gene for the mitochondrial ATPsyn beta is a target of transcriptional activation by members of the Ets family of transcription factors. It is suggested that Ets transcription factors may be involved in the enhanced expression of the ATPsyn beta gene in highly proliferating cells and in the coordinate transcription of nuclear genes for mitochondrial proteins.

Base Sequence↗

Identification of tissue-specific protein binding domains in the 5'-proximal regulatory region of the rat mitochondrial brown fat uncoupling protein gene.

The 5' proximal region of the rat uncoupling protein gene, extending from -611 to +110, contains cis-acting elements involved in cell-specificity and cAMP regulation of transcription. DNAse I footprinting of this region was performed using protein extracts from brown adipose tissue and liver nuclei. Nine protein binding domains were observed using nuclear proteins from both tissues. They include the elements for basal promoter activity (TATA and CCAAT elements), a cAMP-responsive element, two C/EBP binding sites and three unidentified DNA-protein binding domains sharing a common GCCCCT sequence. A purine rich region at -402/-362 was observed to bind proteins abundant in liver but scarce in brown adipose tissue nuclei. A single region at -512/-487 was identified as the only element that binds nuclear proteins present in brown adipose tissue but absent in liver. This putative tissue-specific element in the uncoupling protein gene contains a sequence identical to mammalian or viral gene elements that bind members of the ETS family of transcription factors.

Animals↗

CCAAT/enhancer-binding proteins alpha and beta in brown adipose tissue: evidence for a tissue-specific pattern of expression during development.

CCAAT/enhancer-binding protein (C/EBP) alpha mRNA and its protein products C/EBP alpha and 30 kDa C/EBP alpha are expressed in rat brown-adipose tissue. Results also demonstrate the expression of C/EBP beta mRNA and its protein products C/EBP beta and liver inhibitory protein (LIP) in the tissue. The abundance of C/EBP alpha and C/EBP beta proteins in adult brown fat is similar to that found in adult liver. However, the expression of C/EBP alpha and C/EBP beta is specifically regulated in brown fat during development. C/EBP alpha, 30 kDa C/EBP alpha, C/EBP beta and LIP content is several-fold higher in fetal brown fat than in the adult tissue, or liver at any stage of development. Peak values are attained in late fetal life, in concurrence with the onset of transcription of the uncoupling protein (UCP) gene, the molecular marker of terminal brown-adipocyte differentiation. When adult rats are exposed to a cold environment, which is a physiological stimulus of brown-adipose tissue hyperplasia and UCP gene expression, a specific rise in C/EBP beta expression with respect to C/EBP alpha, 30 kDa C/EBP alpha and LIP is observed. Present data suggest that the C/EBP family of transcription factors has an important role in the development and terminal differentiation of brown-adipose tissue.

Adipose Tissue, Brown↗

CCAAT/enhancer binding proteins alpha and beta are transcriptional activators of the brown fat uncoupling protein gene promoter.

Primary brown adipocytes differentiated in culture were transiently transfected with plasmids containing different extensions of the 5'-flanking region of the rat uncoupling protein gene placed upstream of the bacterial chloramphenicol acetyltransferase reporter gene. Co-transfection of expression vectors for CCAAT/enhancer binding protein (C/EBP) alpha and C/EBP beta trans-activated the rat uncoupling protein gene promoter due to sequences in the 5' proximal region. DNAse I footprint analysis showed the presence of two C/EBP binding sites at positions -457/-440 and -335/-318, which interact with purified C/EBP beta as well as with C/EBP proteins present in brown fat or liver nuclear extracts. Two copies of each site placed upstream of the enhancerless SV40 promoter confer C/EBP alpha and C/EBP beta responsiveness to this heterologous promoter when co-transfected into HepG2 cells. It is concluded that the UCP gene is a target for C/EBP-dependent transcriptional regulation. This suggests that the C/EBP family of transcription factors is involved in the establishment of the characteristic phenotype of the brown adipocyte.

Adipocytes↗

Regulation of metallothionein-I+II levels in specific brain areas and liver in the rat: role of catecholamines.

The role of the catecholamines noradrenaline, adrenaline and dopamine on metallothionein (MT) levels of specific areas of the rat brain has been studied. MT-I or MT-I + II levels were measured by radioimmunoassay using specific antibodies that cross-react only slightly with human MT-III (growth inhibitory factor, GIF). The inhibition of tyrosine hydroxylase with alpha-methyl-p-tyrosine (MPT), which depletes brain dopamine, noradrenaline, and adrenaline, increased MT levels in all brain areas studied (frontal cortex, cortex, medulla oblongata plus pons, midbrain, striatum, hippocampus, hypothalamus, and cerebellum) when considering the results of two separate experiments. The alpha- and beta-receptor blockers, phentolamine, and propranolol, alone or together, did not increase brain MT levels in any area of the brain, suggesting that the effect of MPT in vivo is related to inhibition of the synthesis of dopamine rather than of noradrenaline and adrenaline. Dopamine, noradrenaline, and serotonin increased MT-I levels in primary cultures of neurons, whereas decreased them in astrocyte-enriched primary cultures. Since MT-I levels are about ten times higher in astrocytes than in neurons, the increased brain MT levels induced by MPT may reflect the suppression of the normal inhibitory effect of dopamine on astrocyte MT levels. The increase in MT concentrations induced in most parts of the brain by immobilization stress was not prevented by MPT, phentolamine, or propranolol, suggesting that it was not mediated by the central monoamines.

Animals↗

Effect of zinc, copper and glucocorticoids on metallothionein levels of cultured neurons and astrocytes from rat brain.

The knowledge of brain metallothionein (MT) regulation and especially of MT presence in specific cell types is scarce. Therefore, the effect of several well-known MT inducers, measured by radioimmunoassays using antibodies that cross-react with MT-I and MT-II or specific for MT-I and which do not cross-react with human growth inhibitory factor (GIF or MT-III), has been studied in primary cultures of neurons or astrocytes obtained from rat cerebrum. MT-I levels in glial cells were about ten times higher than those in neuronal cells (538 +/- 194 vs. 49 +/- 16 pg MT-I/micrograms protein, mean +/- S.D. from three separate cell preparations). Increasing the concentration of Zn in the bovine serum albumin (BSA)-containing culture medium up to 50 microM significantly increased MT-I levels by up to 3.5-fold in neurons and 2.5-fold in astrocytes. In contrast, Cu up to 50 microM increased MT-I levels in a saturable manner in both neurons (up to 5-fold) and astrocytes (up to 1.5-fold), the maximum effect occurring at 5 microM Cu. In general, the combination of Zn and Cu further increased MT-I levels. The effect of the metals on MT-I appeared to reflect metal uptake, since MT-I induction was less marked when the BSA concentration in the medium was increased from 2 to 10 mg/ml. Dexamethasone increased MT-I levels in both neurons and astrocytes in vitro in a concentration-dependent manner. Endotoxin, IL-1 and IL-6 did not have a significant effect on glial MT levels at the concentrations studied. The administration of dexamethasone to rats increased MT-I levels in non-frontal cortex, cerebellum, pons+medulla, midbrain and hippocampus, but not in hypothalamus, frontal cortex and striatum. Endotoxin increased liver but not brain MT-I levels. Immunocytochemical studies in adult rat brain preparations with a polyclonal antibody that cross-reacts with MT-I and MT-II indicated that immunostaining was always nuclear in glial cells, whereas in neurons it was nuclear in the cerebral cortex, hippocampus and the granular layer of the cerebellum, and nuclear plus cytoplasmic in Purkinje cells in the cerebellum, hypothalamic nuclei and gigantocellular reticular nucleus in the brain stem. Meninges, choroidal plexus, ependymal and endothelial cells were also MT-immunoreactive.

Analysis of Variance↗

Modifications of glutathione S-transferase (GST) activity in the last period of pregnancy in rats treated with benzo(a)pyrene (BP).

Pregnant rats were treated with benzo(a)pyrene (BP) (50 mg/kg every 2 days) from day 7 of pregnancy and killed at day 16 or day 19. Km of erythrocyte glutathione S-transferase (GST) decreased during pregnancy in control rats (1.29 x 10(-3) M at day 16; 1.02 x 10(-3) M at day 19) and even more in treated rats at day 19 (0.71 x 10(-3) M). Vmax was lower in treated rats at day 19 (0.56 mumol/min/g haemoglobin) than in control rats (0.88 mumol/min/g haemoglobin) suggesting inhibition of the enzyme. Placental weight diminished in treated rats at day 19 but was not affected at day 16. Chromatofocusing of placental GST showed a single peak (pH 8.3-8.6) in control and treated rats on day 16 and an additional peak (pH 7.0-7.4) in treated rats on day 19. An increase in Km (2.84 x 10(-3) M) and Vmax (69 nmol/min/mg protein) in placental GST was observed in treated rats at day 16 (Km = 1.61 x 10(-3) M; Vmax = 43.3 nmol/min/mg protein, in control rats) followed by a decrease in these parameters in rats treated until day 19 (Km = 1.63 x 10(-3) M; Vmax = 48.7 nmol/min/mg protein). These results suggest that BP, initially, stimulates GST synthesis in placenta, followed by an inhibition of the enzyme at day 19. Fetal weight was also affected by BP treatment, especially at day 16. Km and Vmax values of fetal GST were higher in treated rats at day 16 than in control rats but these differences were not detectable at day 19. This may be explained by the more protective role of the placenta at day 19 than at day 16. Glutathione content in erythrocytes, placenta and fetus was not affected by BP.

Animals↗

Metabolic regulation of gene transcription.

The impact of nutrients on gene expression has become an area of considerable interest as the number of genes coding for key regulatory proteins in metabolic pathways are studied in detail. This has been greatly aided by a number of new techniques developed to study gene transcription in animals. We will use as an example studies on the regulation of transcription of the gene coding for P-enolpyruvate carboxykinase, a key enzyme in hepatic and renal gluconeogenesis. The promoter for P-enolpyruvate carboxykinase contains a number of regulatory elements within 500 bp of the start-site of gene transcription that are required for the response of the gene to metabolic signals. These elements bind tissue-specific transcription factors in complex patterns of interactions, which result in the coordinate control of P-enolpyruvate carboxykinase gene expression. An analysis of the regulation of transcription of this gene involves the use of a number of techniques ranging from gene transfection into cells in culture to the introduction of chimeric genes containing the P-enolpyruvate carboxykinase promoter into transgenic mice. This review presents a progress report on the current status of research on the nutritional and hormonal regulation of transcription of the P-enolpyruvate carboxykinase gene.

Activating Transcription Factor 2↗

Regulation of metallothionein concentrations in rat brain: effect of glucocorticoids, zinc, copper, and endotoxin.

The effects of known inducers of liver metallothionein (MT) synthesis on MT concentrations in the rat brain have been determined using antibodies that are specific for MT I and II and do not cross-react with MT III. There were substantial differences in the MT concentrations in different areas of the brain. Dexamethasone increased MT levels after 24 h in the frontal cortex, cortex, medulla oblongata plus pons, midbrain, striatum, hippocampus, and cerebellum but not in the hypothalamus. Corticosterone produced similar results except in the hippocampus. Long-lasting adrenocorticotropic hormone increased MT concentrations after 12 h in midbrain and striatum but not in the liver. Adrenalectomy decreased MT concentrations after 6 days in the medulla oblongata plus pons, striatum, hippocampus, and hypothalamus but increased concentrations in the liver and kidneys; these effects were reversed by corticosterone. The role of glucocorticoids in the regulation of MT levels therefore differs between tissues and within specific areas of the brain. Injection of zinc or copper intracerebroventricularly and the use of a zinc-deficient diet increased and decreased MT levels, respectively, in some but not all brain areas. Endotoxin increased liver MT but not brain MT I levels after 8 h.

Adrenalectomy↗

Inhibition of iodothyronine 5'-deiodinase by iopanoic acid does not block nuclear T3 accumulation during rat fetal development.

We studied the effect of iopanoic acid (IOP), an iodinated contrast medium, on iodothyronine 5'-deiodinase (5'D) and nuclear T3 content (nT3) in fetal tissues. In 18- and 20 day-old fetuses from control dams, nT3 was higher in interscapular brown adipose tissue (IBAT, 69 +/- 5 and 281 +/- 8 fmol/mg of DNA) than in brain (16 +/- 2 and 42 +/- 3 fmol/mg of DNA) or liver (5.6 +/- 1 and 27 +/- 2 fmol/mg of DNA). IOP administration (10 mg, twice daily) to pregnant rats on days 18 and 19 postconception significantly blocked 5'D activity in fetal IBAT and brain at day 20. Liver 5'D was not affected. The rise in nT3 was not modified by IOP treatment in IBAT, but it was enhanced in brain and liver of IOP-treated fetuses on day 20. In contrast, in adult rats, IOP treatment reduced IBAT nT3. Prolongation of IOP treatment until day 21 decreased fetal body weight on day 22 and inhibited IBAT 5'D. No change was produced in mitochondrial oxidative capacity, the subunit II of cytochrome oxidase, or uncoupling protein mRNA expression in IBAT from IOP-treated fetuses. Thus, the finding that IOP does not decrease the nT3 of fetal IBAT explains the lack of effect of IOP on uncoupling protein expression in fetuses, in contrast with the known decrease in adults. Present results also show that IOP increases nT3 in brain and liver, indicating a general incapacity of IOP to decrease nT3 in fetal tissues. It is concluded that the effects of IOP during fetal life differ from those in adults.

Adipose Tissue, Brown↗

The effect of acute and chronic ACTH administration on pituitary-adrenal response to acute immobilization stress. Relationship to changes in corticosteroid-binding globulin.

The effect of single and chronic ACTH administration on serum levels of the corticosteroid-binding globulin (CBG) and pituitary-adrenal (PA) responsiveness to acute immobilization (IMO) stress was studied in adult Sprague-Dawley rats. Single ACTH administration significantly reduced CBG levels but did not alter PA response to acute IMO. Chronic ACTH administration caused a greater fall in CBG than single ACTH administration and blunted PA response to IMO. The effect of chronic ACTH administration on CGB levels recovered 2 days after the last administration, but the ACTH response to IMO was normal only by day 7 after the last ACTH injection. The present data indicate that ACTH administration to rats reduced CBG levels and impaired PA response to acute stress, but impaired PA responsiveness cannot be solely attributed to changes in CBG.

Adrenocorticotropic Hormone↗

[Importance of the pre-donation epidemiological survey to detect donors with a risk of transmitting HCV].

PURPOSE: To determine if the investigation of previous clinical features through an inquiry could be useful to predict HCV infection in blood donors as assessed by recombinant immunoblot assay. MATERIAL AND METHODS: From january 1990 to august 1991, 79 HCV seropositive blood donors by recombinant immunoblot assays (58 RIBA 1 and 21 RIBA II) were selected to be inquired and to perform a clinical examination. The inquiry included the following parameters: age, sex, social environment, history of liver disease, presence or absence for parenteral risk factors (surgery, blood transfusion, odontological procedures, acupuncture, tattoos, etc...). RESULTS: 1) General data: mean age, 43 years (range 20-65); male/female 54/25 (ratio 2.16); urban/rural environment 50/29 (ratio 1.72); new/regular blood donors 17/62 (ratio 0.27). 2) Inquiry results: In seven cases (8.9%) previous symptoms were detected. Hepatic stigmata were present in 12 donors (15.2%). A 67.0 showed previous surgical procedures; 48.1% had odontological history; 24.0% were recipients for blood transfusion; parenteral treatment using nondisposable material were detected in 19 cases (24.0%); acupuncture in 4 donors (5.0%); tattoos in only one case. Social habits were: alcoholic consumption in 44.3% and regular medicine ingestion in 19.0%; a 81.0% had a unique partner and a 8.9% preferred multiple heterosexual contacts. A 29.1% inhabit in unfamiliar house and the remaining 70.9% lived in apartments buildings; the mean of family members was 3.7 persons (range 2-8). REMARKS: a) It is pointed out the scarce and physical expression of the HCV infection. So in many aspects the inquiry is useless and time consuming. b) Nevertheless, we have detected some parenteral risk factors in seropositive cases. Regarding this particular aspect the inquiry is useful. Taken into account the previous we suggest to add an item with the parenteral risk factors to the ordinary self-answering inquire, addressed to all blood donors in each donation.

Adult↗

[Incidence, clinico-biological characteristics, and clinical course of 1,203 monoclonal gammopathies (1971-1992)].

PURPOSE: To evaluate the incidence of monoclonal gammopathies (MG) in our sanitary district, to determine the associated diseases, and to analyse their clinical course along a period of over 20 years. PATIENTS AND METHODS: The study comprised 1,203 patients with MG, of whom 397 had multiple myeloma (MM) and 806 had non-myelomatous monoclonal gammopathies (NMMG). All patients were diagnosed and followed in the Department of Haematology of the Miguel Servet Hospital, in Zaragoza, between january 1971 and december 1992. The SWOG criteria for MM and those proposed by Kyle for NMMG were followed in all cases. The explorations performed in every patient included physical examination, x-ray skeletal survey, peripheral blood study, bone-marrow aspiration or biopsy, study of liver and kidney function. The protein study carried out in blood and urine included agarose gel electrophoresis and electroimmunofixation. Descriptive statistics and determination of actuarial accumulated risk for the transformation of MG undetermined significance (MGUS) into malignant MG (MMG) were also carried out. RESULTS: Incidence: The yearly incidence of MG remained stable up to 1985 as 25 new cases; from that time on, a 30-40% yearly increase was noticed, this increase being mainly related with NMMG. Distribution: MM included 397 patients (33.0%), while 806 cases (67.0%) had NMMG. In these last were included those MG associated to haematologic malignancies, 139 cases (11.5%) or to other diseases, 286 cases (23.8%), as well as MGUS, 347 cases (28.9%), and in 34 cases the MG acquired a transient character. The mean age in the series was 62.1 years, ranging between 2 and 92, and the M/F ratio was 1.13. IgG was the commonest immunochemical type, 762 cases (63.3%), followed by IgA, 214 cases (17.8%) and IgM, 114 cases (9.5%) Multiple MG appeared in 3.8% of the cases, 64 instances, with monoclonal component present only in urine. Of the MG associated to blood diseases, the highest frequency corresponded to lymphoproliferative disorders (74.8%), and of those MG associated to other disease, neoplasms and liver diseases were the commonest. The second place in frequency corresponded to MGUS, in which a periodical follow-up with median duration of 37.8 months was kept in 93.6% of the cases. Ten patients evolved into MMG within a median of 60 months, having an actuarial accumulated risk of 4.5%, 15% and 26% at 5, 10 and 15 years, respectively. CONCLUSIONS: (1) MG are relatively frequent disorders, representing an important number of interventions for a general haematology department each year. (2) MM is the commonest of all MG, followed by MGUS. (3) The clinical importance of MM lies upon the possibility of evolving into MMG. In this series, ten patients developed MMG within a median of 60 months and having an actuarial risk of 4.5%, 15% and 26%, respectively, at 5, 10 and 15 years.

Female↗

[Transient monoclonal gammopathies. Study of 34 cases].

PURPOSE: To evaluate the incidence of transitory monoclonal gammopathies (MG) defined as a narrow spike in serum electrophoresis disappearing after a variable period of time. MATERIAL AND METHODS: A follow up (1986-1992) in all the cases with "minimal" MG (< 10 g/L) to evaluate the transitory or permanent nature of the patients sera was performed along a 7-year period. Serum protein electrophoresis along with immunofixation electrophoresis were performed in order to identify and characterize the monoclonal components in all the cases. RESULTS: Thirty four out of 592 monoclonal gammopathies (5.7% of the total and 8.6% of the non-myelomatous monoclonal components) fulfilled the criteria of transitory monoclonal gammopathies. There was predominance of adult patients (88.2%), females (64.7%) and subjects over 40 years of age (67.6%). The monoclonal component was small in all the cases (mean 4.5 g/L). After immunochemical characterization, IgG was found in 23 cases and IgM in 9; the light chain was Kappa in 25 and lambda in 7; two patients had 2 or 3 monoclonal components. In 31 of the 34 cases the associated pathology was infectious; this being neoplastic in 2 and hypersensitivity to drugs in the remaining patient. The infectious agents could be identified in 24 instances as mainly gram-negative bacteria. CONCLUSIONS: 1) The appearance of a transitory monoclonal gammopathy is not an unusual finding. 2) This alteration does not have any prognostic significance. 3) The appearance of a small monoclonal component, especially in infectious diseases, should not elicit deeper studies.

Adolescent↗

Glutathione S-transferase in normal human anagen hair follicles.

Glutathione S-transferase (GST) has been quantified and characterized in healthy human anagen hair follicles obtained from 36 men and 36 women (26 +/- 7 years of age). GST activity was determined using 1-chloro-2,4-dinitrobenzene as a substrate, and the values in men were: 0.5 +/- 0.2 mU/follicle, significantly different from women (0.36 +/- 0.2 mU/follicle); 196 +/- 98 mU/mg protein and 309 +/- 158 mU/mg DNA without significant differences from women. Enzyme activity showed a high degree of inter-individual variability (23.5-fold when expressed per follicle, 18.29-fold expressed per mg of protein and 22.75-fold per mg of DNA) in the whole population and this variability was higher in women. Ion-exchange chromatography by KCl and enzyme immunoassay suggest that the GST present in hair follicles corresponds with the acidic form. The percentage of anagen hairs in each subject showed a positive correlation with the following parameters: GST/hair, GST/DNA and DNA/hair. It is concluded that GST may contribute to the maintenance of the hair growth cycle.

Adult↗

[Retrospective analysis of hemotherapy support in 226 cases of myelodysplastic syndromes].

PURPOSE: To evaluate the transfusion requirements (red cells and platelets) in 226 patients with myelodysplastic syndromes (MDS). PATIENTS AND METHODS: The number of patients under study was 226: 59 with refractory anaemia (RA), 49 with sideroblastic anaemia (RSA), 56 with refractory anaemia with excess of blast cells (RAEB), 48 with RAEB in transformation (RAEBT), and 14 with chronic myelomonocytic leukaemia (CMML). The period of the study was from January 1975 to December 1992. The mean age of the series was 67.4 years (ranging between 28 and 92) and the male/female ratio was 1.8. Transfusion frequency (TF) was defined as the time elapsed between two consecutive transfusions of two units of packed red cells. A platelet transfusion (PT) was comprised of 6 units of platelets or 1 unit obtained by thrombopheresis. The statistical analysis was performed with the chi 2 and Student's tests. RESULTS: Anaemia was present in 96.9% of the patients, regardless of the cytologic classification. Haemorrhages appeared in 41.6% of the cases with maximal frequency in CMML (78.6%) and minimal in RSA (10.2%). TF: Transfusion was required by 90.2% of the patients (86% of the RA, 79.6% of the RSA, 48.4% of RAEB, 97.9% of the RAEB-T, and 100% of the CMML). The mean TF was 1.5 months (1.9 for RA, 1.7 for RSA, 1.3 for RAEB, 0.9 for RAEB-T, 2.2. for CMML). PT: Platelet support was needed by 38.1% of the patients (30.5% of RA, 8.1% of RSA, 48.2% of RAEB, 58.3% of RAEB-T and 64.3% of CMML). The mean number of PT per patient was 7.2 (5.2 for RA, 3.8 for RSA, 9.7 for RAEB, 10.2 for RAEB-T, 7.1 for CMML). STATISTICAL ANALYSIS: The differences appreciated in TF were significant for the good prognostic groups (RA + RSA) as compared with the poor-risk ones (AREB + AREB-T + CMML) (p < 0.01), although significance is lost when these groups were taken one by one. For PT, significant differences appeared when comparing RA + RSA with RAEB + RAEB-T + CMML (p < 0.001); when the groups were compared one by one, significant differences were found only for RA versus RSA (p < 0.01). CONCLUSIONS: 1) Red cell support was required by 90.2% of the patients with MDS, while platelet support was needed in 38.1% of the cases. 2) The cytologic poor-risk groups (RAEB, RAEB-T and CMML) required greater transfusion support as a whole than did the good prognostic ones (RA + RSA). 3) However, only RA showed significant differences with respect to RSA regarding PT, the remaining groups showing no such differences. 4) An irregular pattern was seen in RA and CMML with respect to PT in the former and to both TF and PT in the latter.

Adult↗

Effect of superoxide dismutase, allopurinol and glucocorticoids on liver and lung metallothionein induction by endotoxin in the rat.

Liver and lung metallothionein (MT) levels were increased by endotoxin. The administration of superoxide dismutase (SOD) or allopurinol (ALLO) before (30-60 min) or after (24-32 h) the endotoxin treatment either increased or did not affect the effect of endotoxin on MT levels, depending on the particular treatment and tissue. SOD and ALLO also increased liver and lung MT levels in control rats. In contrast, liver MT levels tended to be decreased by the glucocorticoid prednisolone (PRED) when administered before the endotoxin and were significantly decreased when it was administered after endotoxin. The effect of PRED on lung MT levels was completely different, since it decreased the effect of endotoxin when injected before the lipopolysaccharide, but increased it when injected after the endotoxin. Liver lipid peroxidation, as measured by thiobarbituric acid reactants (TBARs), increased after endotoxin in the liver but not in the lung, an effect even potentiated in some cases by the antioxidants studied. As expected, tissue MT and TBARs could not be correlated.

Allopurinol↗