[Contamination by Serratia marcescens of a unit of packed red blood cells].
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Bacteremia↗
Biomedical subjects
M Giralt
Publications and source records attributed to M Giralt.
[Which are the true incidence rates of primary hematological disorders acquired in our population?].
PURPOSE: To define demographic and epidemiological characteristics of primary haematological disorders (PMHD) in patients referred to a haematology department in 1,240 beds general hospital. PATIENTS AND METHODS PERIOD OF STUDY: 01/94-12/94. We have performed a study in patients older than 14, to determine the age adjusted incidence rates of PHD in the assigned population: 439,279 inh (M: 210,139; F: 229,140), with a negative-vegetative growth (-1.39/10(3) inh/y). A total of 1,242 new cases was received, 302 of them were diagnosed of PHD. Epidemiological method: incidence rates (IR), age and sex adjusted incidence rates (AIR), truncated standardized incidence rates (TSIR) and confidence interval (CI) were calculated. STATISTICAL METHOD: Normal distribution, descriptive and frequency distribution analysis were performed along with chi 2 test. RESULTS: Demographic data: mean age (+/- SD): 63.54 y +/- 15.81; range 19-92. M/F: 177/125, males mean age 62.85 +/- 16.29, females: 64.52 +/- 15.11. The PHD distribution was: MGUS 84 cases; NHL 57; MDS 33; CLL 26; CMPD 26; MM 21; HD 14; AL 11; ITP 10; CML 9; AIHA 5; hypoplastic anaemia 3; and cryoglobulinaemia 3. AIR (cases/10(5) inhab/y): Consulting rate 261.79. The PHD incidence rate was 31.00 (M: 38.01; F: 25.51). In patients under 60 y the AIR of PMDH was 31.31 (M: 36.42, F: 26.25), and in those older than 60 y the AIR was increasing, with 178.86 (M: 247.21, F: 128.52). The AIR for subtypes was: MGUS, 8.01 (M: 3.56, F: 1.93); CLL 2.28 (M: 2.69, F: 1.95); CMPD 3.17 (M: 2.83, F: 3.51); MM 1.92 (M: 2.43, F: 1.49); HD 2.27 (M: 3.54, F: 1.04); AL 1.41 (M: 1.54, F: 1.30); ITP 1.15 (M: 1.20, F: 1.12); CML 1.09 (M: 1.19, F: 1.01); AIHA 0.61 (M: 0.55, F: 0.69); hypoplastic anaemia 0.24 (M: 0.19, F: 0.30); cryoglobulinaemia 0.34 (M: 0.55, F: 0.14). REMARKS: The elderly have increased incidence of PHD. The AIR is higher in males and in older than 60 y, unless for CMPD. Most frequent PHD were MGUS and NHL.
Adult↗
[Clinical characteristics of type I Gaucher's disease in Spain. Preliminary results of national survey. Spanish Group on Gaucher's Disease].
BACKGROUND: To know the incidence and distribution of Gauchers's disease (GD) in Spain, a national inquiry was carried out in order to analyze the clinical, genetic and evolutive features of these patients. PATIENTS AND METHODS: A questionnaire including demographic, clinical, diagnostic, biological, radiological and evolutive data was sent to the hospitals. Each case with a presumptive diagnosis was considered a "censored patient". The cases without enzymatic or genetic diagnosis were studied in a reference laboratory (the same for all the samples). The Zimran's Severity index was employed to evaluate the clinical status. The enzymatic activity of acid beta-glucosidase was studied in cellular extracts of peripheral blood granulocytes by a fluorescent method using an artificial substrate (methyl-umbeliferyl-beta-deglycoside). The characterization of the mutations of the glucosidase gene was determined by PCR molecular analysis in the samples of DNA studying the mutations: N370S, L444P, 84GG and IVS2+1. RESULTS: Seventy five patients were censored; in 48 the inquiry was completed. These patients belonged to 54 families. The mean age at diagnosis was 24.7 years, being the M/F distribution 16/32. The illness was asymptomatic in 13.3%, visceral disease was present in 83.3% of patients and bone disease in 70.8%. The 45.8% of patients had hemoglobin levels < 110 g/l, 35.4% low leucocyte count < 4,0 x 10(9)/l and 77.0% low platelet count < 150 x 10(9)/l. High acid phosphatase levels were observed in 100% of cases and in 34.7% biochemical hepatic dysfunction was observed. The test for acid glucosidase showed a marked decrease in enzymatic activity. In 71% of the patients morphologic documentation (splenic or hepatic tissue, bone marrow biopsy or aspirates) was performed. The most frequent mutations observed were N370S (47.7% of the alleles detected), and L444P (24.4%). In 18.7% of the cases the disease was stable or slightly progressive, in 27.0% the spleen was removed between 1-14 years of the being made and 45.8% were put onto an alglucerase trial. CONCLUSIONS: The incidence of GD in Spain is at present lower that the previously reported for other european countries. The clinical features are not different except in the case of bone disease, less frequent in our cases, probably limited by the absence of MR. The pattern of distribution of mutation is also similar.
Adult↗
Inhibition of corticosteroid-binding globulin caused by a severe stressor is apparently mediated by the adrenal but not by glucocorticoid receptors.
The effect of stress on serum corticosteroid-binding globulin (CBG) was studied in adult male Sprague-Dawley rats. CBG was measured either by a homologous radioimmunoassay (RIA) or by a binding assay (BA) using 3H-corticosterone. Exposure of adult male rats to a severe stressor such as immobilization (IMO) for 1 h did not alter serum CBG levels, but a significant decrease was found after 6 and especially 24 h IMO. This decrease was not observed after 24 h exposure to a milder treatment such as food and water deprivation. The effect of different periods of exposure to two stressors, IMO or restraint, was also studied. The following results were obtained:serum CBG levels were reduced by IMO, but only by restraint; IMO-induced reduction of CBG levels was always observed 24 h after starting exposure to IMO, independently of the actual period of exposure to the stressor; and IMO-induced inhibition of CBG was proportional to the hours of exposure to the stressor. Although IMO-induced inhibition of CBG was prevented by adrenalectomy, a role for glucocorticoid acting through their classical type II receptors is unclear as far as treatment of rats with the glucocorticoid receptor antagonist RU486 (100 mg/kg) did not prevent the inhibition caused by IMO. The present data clearly indicate that acute exposure to a stressor is able to decrease CBG levels provided that duration of exposure to the stressor and its intensity are high and that the effect is tested at least 6 h after the onset of stress. The effect appears to be mediated by some adrenal factor(s) other than glucocorticoids.
Adrenal Glands↗
Transition-metal saccharide chemistry and biology: saccharide complexes of Cu(II) and their effect on in vivo metallothionein synthesis in mice.
Monosaccharide (D-Glc, D-Fru, D-Gal, D-Xyl, D-Rib) and disaccharide (Mal) complexes of Cu(II) were synthesized from two different precursors, viz. [NEt4]2 [CuCl2Br2] and CuCl2.2H2O, in nonaqueous media, and isolated in the solid state. The complexes were found to be primarily dimeric and trimeric and water soluble. These were characterized by diffuse reflectance, aqueous solution absorption, CD, FTIR, magnetic susceptibility, EPR, EXAFS, XANES, and elemental analysis. Aqueous solution stability in the pH range 4-8 was studied by cyclic voltammetry and absorption spectroscopy. The effect of subcutaneously injected Cu-Fru, Cu-Xyl, and Cu-Rib complexes on the in vivo metallothionein synthesis in mice was found to be significant in liver, but not in brain, in accordance with the observed copper accumulation in these tissues.
Animals↗
[9th Antonio Raichs memorial lecture. Myelodysplastic syndromes].
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Antineoplastic Agents↗
[Magnetic resonance in the diagnosis of extent and osseous complications of Gaucher's disease type 1].
OBJECTIVE: To evaluate the usefulness of magnetic resonance (MR) for investigating bone involvement in Gaucher disease type 1 (GD). METHODS: Ten adult patients with the diagnosis of GD type 1 were studied. Weighted sequences were performed in spin-echo (SE) T1 and T2 of 4 body areas: spine, pelvis, hips, and femurs. The patterns of bone infiltration proposed for the study were: homogeneous infiltration (H), non-homogeneous infiltration (NH), and normality (N). Four patients were receiving enzyme replacement therapy. RESULTS: All patients (100%) showed changes associated with infiltration with Gaucher cells. The distribution of patterns was as follows: the homogeneous pattern predominated (60 and 50%, respectively) in spine (6H/2NH/2N) and pelvis (5H/3NH/2N), whereas the non-homogeneous pattern predominated (60% and 80%, respectively) in hips (1H/6NH/3N) and femurs (1H/8NH/1N). As bone complications two cases of hip avascular necrosis were noted, one of them with bilateral involvement, one case with infarcts in femur diaphysis and other case with medullar edema in a bone crisis. CONCLUSION: MR is an excellent technique for detecting medullar bone infiltration and complications in GD type 1.
Adolescent↗
[Hematologists, the administration, and the future].
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Forecasting↗
[Alglucerase treatment of type I Gaucher's disease. Preliminary results in Spain. Spanish Group on Gaucher's Disease].
AIM: To evaluate the efficacy of the treatment with alglucerase (Ceredase) in spanish patients diagnosed of Gaucher disease type 1 (GD). PATIENTS AND METHODS: A national inquiry has been performed among the hospitals with GD's patients on therapy. A form including pretherapy haemoglobin, platelet levels, liver and spleen size and bone lesions was submitted to the participating centers. A quarterly follow-up was requested. Descriptive statistics and frequency distribution analysis were performed through a Statview 4.02 database. RESULTS: Participating centers 22; evaluable patients 34. The mean age at diagnosis was 18.9 +/- 12.7 years, being the M/F ratio 0.47. Organomegaly was present in 88.2% and 70.5% had bone disease. Low haemoglobin levels (< 110 g/L) had detected in 48.6%, leucopenia (< 4.0 x 10(9)) were in 36.6% and low platelet level (< 15.0 x 10(9)) in 73.2%. The most frequent mutations observed were N370S (39.7% of the alleles detected), and L444P(20.4%). Time on therapy: between 6-12 months, 18 patients, > 1 year 16 patients, > 2 years 11 (5 reaching 3 years). Dosage schedulle:a) 10-20 U/Kg/week, 8 cases, b) 30-60 U/Kg/ two weeks, 26 cases. Eight patients were splenectomized before therapy. After one year on therapy haemoglobin and platelet levels become normal in 82.3% and 47.0% of patients respectively and the liver and spleen size were reduced 66 and 42%. There are not significant differences among weekly (8 patients) or forthnightly (26 patients) dosages except in the spleen size more reduced in the later group (43% vs 65%). Haemoglobin and platelet levels were similar among splenectomized or non-splenectomized patients, but the reduction of the liver size (80 vs 17%) was significatively greater in the former. One patient developed an asymptomatic antialglucerase antibody during the first month on therapy. CONCLUSIONS: The infusion of alglucerase is effective in the treatment of the GD type 1, with a significant reduction of organomegalies and a definite improvement in haemoglobin and platelet levels. The efficacy seems to be unrelated with the schedule employed or the splenic removal; nevertheless liver enlargement was more reduced in the splenectomized cases and the spleen size among the patients with the regimen of "high dose/low frequence". Bone healing requires a very long time therapy. The treatment is safe and the antibody production low.
Adolescent↗
[The kinetic characteristics of the erythrocyte glutathione S-transferase system as a function of sex and the tobacco habit].
BACKGROUND: Erythrocytic glutathion S-transferase (GST) plays an important role as a protective mechanism against oxidative stress. The present study was conducted to evaluate the influence of both smoking habit and sex upon the kinetic characteristics of the enzyme. SUBJECTS AND METHODS: 176 healthy subjects (100 men and 76 women), smokers and nonsmokers, were included. Enzyme parameters were calculated in erythrocytic haemolysates using 1-chloro-2,4-dinitrobenzene (CDNB) and glutathion (GSH) as substrates. Haemoglobin (Hb) was removed by affinity chromatography. In samples coming from 51 men and 42 women the native haemolysate was subjected to thermal shock (52 degrees C) and the enzyme parameters were compared with those obtained in the non-denatured samples. RESULTS: In non-denatured samples, Km (mM) and Vmax (mumol/min/g Hb) values for CDNB were significantly higher (p < 0.001) in smokers than in non smokers, especially in women. Thus, respectively for Km and Vmax (mean +/- standard deviation): for men non smokers, 1.43 +/- 0.54, 1.63 +/- 0.42 and smokers, 1.74 +/- 0.5, 1.8 +/- 0.69; for women, non smokers 1.42 +/- 0.56, 1.57 +/- 0.46 and smokers, 2.05 +/- 0.59, 2.51 +/- 0.6. Thermal denaturation diminished the enzyme activity in all cases and modified the Km values, these results were opposite to those obtained in the non-denatured samples. Thus, for Km and Vmax respectively: for men, smokers, 1.6 +/- 0.71 and 0.9 +/- 0.32 and non smokers, 1.4 +/- 0.66 and 0.53 +/- 0.29; for women, non smokers, 2.00 +/- 0.58, 1.13 +/- 0.29 and smokers 1.22 +/- 0.77, 0.52 +/- 0.23. The GSt content was similar in the four groups studied (3.75 +/- 1.15 mumol SH/g Hb). CONCLUSIONS: The greater thermolability of GST activity and the increase in the Km values observed in smokers, especially in women, should be considered as indicative of an increased risk for the erythrocytes against oxidative stress.
Adult↗
Metal-saccharide chemistry and biology: saccharide complexes of zinc and their effect on metallothionein synthesis in mice.
Monosaccharide (D-Fru, D-Gal, D-Glc, D-Xyl, and D-Rib) and disaccharide (Mal) complexes of Zn2+ were synthesized using different precursors and isolated in the solid state. These were found to be anionic with a Zn-to-saccharide ratio of 1:1 and 2:1 for monosaccharide and disaccharide complexes, respectively. Electrochemical behaviour in aqueous solution was studied by extensive cyclic voltammetric studies in the pH range 3.7-10.3. The effect of subcutaneously injected Zn-D-Fru, Zn-D-Gal and Zn-D-Glc complexes on the metallothionein synthesis in mice was found to be significant in the liver, but not in the brain.
Animals↗
Interactions between metallothionein inducers in rat liver and primary cultures of rat hepatocytes.
The interaction of Zn, stress and endotoxin on liver metallothionein (MT) regulation has been studied in the rat. Zn, stress and endotoxin increased liver MT levels significantly, by 12-, 5- and 8-fold, respectively. The previous administration of Zn to stress or endotoxin treatments increased MT levels by 35- and 42-fold, respectively, indicating a synergistic effect in both cases. In contrast, when liver MT was preinduced by stress, MT levels were further increased by endotoxin only in an additive manner. In another experiment where liver MT induction by stress was studied in control rats and in rats with preinduced MT by Zn, endotoxin or stress, it was found that Zn pretreated animals had higher MT-I mRNA levels than endotoxin- or stress-pretreated ones. No synergisms between dexamethasone, Zn, TNF and IFN were observed in primary culture of hepatocytes. These results suggest that the observed synergisms between Zn and other MT inducers in vivo in the liver is a consequence of increased Zn levels in the body and mobilization capacity, with concomitant MT synthesis.
Animals↗
Influence of thyroid hormones on the human ATP synthase beta-subunit gene promoter.
The action of thyroid hormones on the expression of the mitochondrial ATP synthase beta-subunit gene (ATPsyn beta) is controversial. We detected a binding site for the thyroid hormone receptor between -366 and -380 in the human ATPsyn beta gene by DNase I footprint analysis and band-shift assays. However, expression vectors in which the chloramphenicol acetyl transferase (CAT) reporter gene is driven by the 5' upstream region of ATPsyn beta gene were unresponsive to T3 when transiently transfected to HepG2 or GH4C1 cells. CAT constructs driven by the rat phosphoenolpyruvate carboxykinase (PEPCK) or the growth hormone (GH) promoters were stimulated several fold by T3 in parallel experiments. It is proposed that the biological effects of thyroid hormones on the ATPsyn beta expression occur through indirect mechanisms.
Animals↗
Glutathione, glutathione S-transferase and reactive oxygen species of human scalp sebaceous glands in male pattern baldness.
We investigated the contribution of reactive oxygen species to the development of sebaceous gland hyperplasia and the characteristics of the glutathione S-transferase/glutathione system in male pattern baldness. Glutathione S-transferase, glutathione, and thiobarbituric acid-reactive substances were determined in sebaceous gland-enriched scalp skin of men affected by male pattern baldness and were subjected to hair autotransplantation. In comparison with the hairy occipital-donor areas, the following results were obtained in alopecic frontoparietal samples: glutathione S-transferase-specific activity increased 7-fold (p < 0.001); enzyme affinity towards 1-chloro-2,4-dinitrobenzene decreased 2-fold (p = 0.009); glutathione content decreased 2.5-fold (p = 0.017); and thiobarbituric acid reactive substances increased 2-fold (p = 0.006). Chromatofocusing analysis, bromosulfophthalein IC50 values, enzyme-linked immunosorbent assay, and immunohistochemistry with polyclonal antibodies raised against glutathione S-transferases alpha, mu, and pi demonstrated the presence of alpha, pi, and probably the 5.8 alpha isoenzymes in the sebaceous gland. These results support the hypothesis that reactive oxygen species are involved in the pathogenesis of sebaceous gland hyperplasia in male pattern baldness.
Adult↗
Effect of stress on mouse and rat brain metallothionein I and III mRNA levels.
The effect of immobilization stress on brain and liver metallothionein (MT) mRNA levels has been studied in mice and rats. Stress increased brain and liver MT-I mRNA levels in mice in a time-dependent manner, in agreement with the MT-I+II protein levels, suggesting an increased gene transcription during stress. In contrast, the brain-specific isoform, MT-III, tended to decrease during stress. In selected brain areas of rats, the overall tendency for both MT-I and MT-III mRNA levels was to be transiently decreased by stress in hippocampus, and increased in hypothalamus, cerebellum and the remaining brain tissues; adrenalectomy significantly affected MT mRNA levels either in basal conditions or during stress, with very different temporal patterns of response depending on the brain area studied. These results suggest that glucocorticoids could be involved in MT-I but also MT-III regulation. In both rats and mice, the subtle response to stress observed in the brain contrasts with the robust response in the liver, suggesting that the factors involved in MT regulation in both tissues differ substantially. In primary cultures enriched in astrocytes or neurons, MT-III mRNA was clearly detected by Northern blotting in both cases, suggesting that it is expressed in both types of cells. Dexamethasone appeared to decrease MT-III mRNA levels in cultured neurons and to increase them in astrocytes, which indicates that glucocorticoids have a different role in MT-III regulation in both cell types.
Animals↗
Co-ordinate decrease in the expression of the mitochondrial genome and nuclear genes for mitochondrial proteins in the lactation-induced mitochondrial hypotrophy of rat brown fat.
The relative abundance of the mitochondrial-encoded mRNAs for cytochrome c oxidase subunit II and NADH dehydrogenase subunit I was lower in brown adipose tissue (BAT) from lactating rats than in virgin controls. This decrease was in parallel with a significant decrease in mitochondrial 16 S rRNA levels and in the relative content of mitochondrial DNA in the tissue. BAT from lactating rats showed lowered mRNA expression of the nuclear-encoded genes for the mitochondrial uncoupling protein, subunit IV of cytochrome c oxidase and the adenine nucleotide translocase isoforms ANT1 and ANT2, whereas mRNA levels for the ATP synthase beta-subunit were unchanged. However, the relative content of this last protein was lower in BAT mitochondria from lactating rats than in virgin controls. It is concluded that lactation-induced mitochondrial hypotrophy in BAT is associated with a co-ordinate decrease in the expression of the mitochondrial genome and nuclear genes for mitochondrial proteins. This decrease is caused by regulatory events acting at different levels, including pre- and post-transcriptional regulation. BAT appears to be a useful model with which to investigate the molecular mechanisms involved in the co-ordination of the expression of the mitochondrial and nuclear genomes during mitochondrial biogenesis.
Adipose Tissue, Brown↗
A novel regulatory pathway of brown fat thermogenesis. Retinoic acid is a transcriptional activator of the mitochondrial uncoupling protein gene.
The mitochondrial uncoupling protein (UCP) is responsible for the thermogenic function of brown fat, and it is a molecular marker of the brown adipocyte cell type. Retinoic acid (RA) increased UCP mRNA levels severalfold in brown adipocytes differentiated in culture. This induction was independent of adrenergic pathways or protein synthesis. RA stimulated ucp gene expression regardless of the stage of brown adipocyte differentiation. In transient transfection experiments RA induced the expression of chloramphenicol acetyltransferase vectors driven by 4.5 kilobases of the 5'-noncoding region of the rat ucp gene, and co-transfection of expression vectors for RA receptors enhanced the action of RA. Retinoic acid receptor alpha was more effective than retinoid X receptor in promoting RA action, whereas a mixture of the two was the most effective. The RA-responsive region in the ucp gene was located at -2469/-2318 and contains three motifs (between -2357 and -2330) of the consensus half-sites characteristic of retinoic acid response elements. This 27-base pair sequence specifically binds purified retinoic acid receptor alpha as well as related proteins from brown fat nuclei. In conclusion, a novel potential regulatory pathway of brown fat development and thermogenic function has been recognized by identifying RA as a transcriptional activator of the ucp gene.
Adipocytes↗
[Hematology: a specialty in crisis?].
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Hematology↗