Temperature dependence of the EL2 metastability in semi-insulating GaAs: Thermal hysteresis between the metastable and reverse transitions.
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Biomedical subjects
Publications and source records attributed to A Alvarez.
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The peroxisomal membrane appears to play a crucial role in transporting proteins into the organelle. Some human genetic disorders involving peroxisome biogenesis, such as Zellweger syndrome, may be caused by genetic defects of the import machinery located in the peroxisomal membrane. In order to characterize the proteins of the human peroxisomal membrane, we isolated peroxisomes from human liver. We obtained their membranes using various procedures and analyzed their proteins by SDS-polyacrylamide gel electrophoresis and silver staining. We compared the protein composition of peroxisomal membranes with membranes derived from mitochondria and microsomes. The main peroxisomal membrane proteins (PMPs) have apparent molecular masses of 147, 112, 95, 87, 81, 79, 74, 69(70), 53-52 (double band), 47, 45, 43, 37, 31, 28, 22, and 17 kDa. The following PMPs of 147, 112, 79, 69(70), 53-52 (double band), 47, 43, 31, 28, 22, and 17 kDa fit the criteria for integral membrane proteins. We then produced rabbit polyclonal and mouse monoclonal antibodies that recognized some human PMPs. One of these antibodies detected mainly PMP43. We used this antiserum to evaluate the presence and subcellular distribution of the PMP43 in fibroblasts derived from patients affected by Zellweger syndrome. These results represent new information about the protein composition of the human peroxisomal membrane and provide biological tools for further characterization of the human PMPs and their genes in normal and pathological conditions.
Liver injury was induced by a single dose (60 mg/kg) of cocaine in male albino Swiss mice untreated or pretreated with phenobarbital (in drinking water 1 gm/L), for 5 days before cocaine administration. One parameter of liver injury, serum isocitrate dehydrogenase activity, showed sharp increases at 24 hr of cocaine treatment; we also noted decrease hepatic levels of ATP, GSH, cytochrome P-450 and NADPH/NADP+ ratio and increases in malondialdehyde concentration. Histopathological study of liver slices showed perivenous and periportal necrosis induced by cocaine in untreated mice and mice pretreated with phenobarbital, respectively. A regenerative postnecrotic response, which peaked at 48 hr, was demonstrated by the appearance of mitotic cells. Mitotic index analysis showed that proliferative cells appear to be unevenly distributed in the hepatic acinus and were mainly located in the vicinity of the damaged acinar region. Genomic DNA ploidy and the distribution of DNA in the phases of the cell cycle were studied in nuclei of isolated hepatocytes. At 12 hr of cocaine administration, both in untreated and phenobarbital-pretreated mice, the following changes were observed: a sharp decrease in tetraploid (4N) cells (40% to 17% and 25% to 6%, respectively) and octoploid (8N) cells (5% to 2% and 2% to 1%, respectively), together with the appearance of a hypodiploid population (13% and 31%, respectively). Hypodiploid population was characterized as apoptotic cells by detection of DNA fragmentation in agarose gel. These results suggest that a significant percentage of cell death induced by cocaine occurs by means of the apoptosis death program. Comparison of the initial values of DNA ploidy with those obtained at 7 days of cocaine administration showed remarkable increases in polyploid populations (4N and 8N) and a decrease in diploid cells (2N), indicating that the process of differentiation occurs when liver restores its functionality.
1. Kinetic and physico-chemical studies on human placental microsomal fraction confirmed that the ATPase and ADPase activities detected in this fraction correspond to the enzyme ATP-diphosphohydrolase or apyrase (EC 3.6.1.5). These include substrate specificity, and coincident M(r) and pI values of both ATPase-ADPase activities. 2. This enzyme hydrolyses both the free unprotonated and cation-nucleotide complex, the catalytic efficiency for the latter being considerably higher. 3. Microsomal apyrase is insensitive to ouabain and Ap5A. The highly purified enzyme was only inhibited by o-vanadate, DES and slightly by DCCD. 4. Apyrase seems to be a glycoprotein from its interaction with Concanavalin-A. 5. Preliminary studies on the essential amino acid residues suggest the participation of Arg, Lys and His residues, and discard the requirement of -SH, COO-, -OH, and probably also Tyr and Trp. 6. Two kinetic modulatory proteins of apyrase were detected in placental tissue. An activating protein was found in the soluble fraction and an inhibitory protein was loosely bound to the membranes. 7. The proposed in vivo function for apyrase is related to the inhibition of platelet aggregation due to its ADPase activity, which is supported by the direct effect on washed platelets and by its plasma membrane localization.
OBJECTIVE: To ascertain the etiology and outcome of episodes of bacteremia and fungemia over a three-year period (1990-1992) in patients with hematological malignancies. DESIGN: Retrospective study. SETTING: Hematology service of a 1,500-bed Spanish university hospital. RESULTS: Of a total of 178 episodes of significant bacteremia or fungemia in 101 patients, 53% affected patients with acute leukemia. Gram-positive microorganisms were found to be the cause in 70% of the monomicrobial episodes. The most frequently isolated microorganism was coagulase-negative Staphylococcus (35%), followed by Staphylococcus aureus (11%). Most blood-stream infections occurred during an episode of neutropenia (59%). A total of 34 patients died during hospitalization; in 14, infection was the cause of death. CONCLUSIONS: A marked increase in the incidence of bacteremias caused by gram-positive microorganisms has been observed in our hospital over the last 10 years, especially in patients with hematological malignancies. The mortality due to bacteremia is similar to that found by other authors in series of bacteremia in hematological patients, and we have not found significant differences in the mortality due to bacteremia between neutropenic and non-neutropenic patients (Infect Control Hosp Epidemiol 1994;15:101-104).
Maintaining B16F10 tumor cells in stirring culture for 48 h leads to an increase in lung and liver colonizing capacity in comparison with cells in adherent culture. Parallel to the increased metastatic capacity, we have observed a decrease in the proliferative rate of tumor cells (as the percentage of proliferating cell nuclear antigen-positive cells) and an increase in the population of tumor cells expressing Ia antigen. These results are not exclusive to B16F10 cells, since the same results were obtained when we analyzed 3LL cells maintained in identical culture conditions. In all the tumor lines tested, we found an association between the nonproliferating and the Ia-positive cell populations. We induced Ia expression by treating B16F10 cells in adherent culture with the lectin concanavalin A and again, coincident with an increase in metastatic capacity, we found the same association between the two parameters analyzed--nonproliferating state and Ia antigen expression. In addition, it was found that B16F10 cells induce lymphocytic proliferation, and a direct relationship was established between the number of Ia+ cells and lymphocytic proliferation.
The present study was performed in vivo in rabbits to evaluate the functional and morphologic effects of verapamil in a model of ischemic acute renal failure (ARF). Particularly impressive was the ultrastructural integrity of renal tubules in the animals exposed to both ischemia and verapamil. Three groups were studied: Group A: no ischemia; Group B: renal ischemia alone; and Group C: renal ischemia with verapamil. Creatinine clearance was higher in Group C (0.77 mL/min/kg) compared to Group B (0.13 mL/min/kg) at 24 h of reperfusion (p < .005) as well as at 48 and 72 h (0.73 mL/min/kg) vs. 0.35 mL/min/kg; p < .05 and 0.90 mL/min/kg vs. 0.46 mL/min/kg; p < 0.05, respectively). Light microscopic evaluation of Group C rabbits revealed significantly better preservation of proximal tubule (PT) brush border (p < .0005) and less desquamation of PT (p < .05) compared to Group B. Ultrastructural examination of in vivo perfused kidneys also demonstrated decreased loss of microvilli of PT (p < .0005) as well as less cellular edema (p < .005), fewer cells with apical PT membrane rupture (p < .01), better preservation of mitochondria (p < .005), less flattening of the PT basolateral labyrinth (p < .05), and fewer hypertrophic actin bands at the basal surface of PT epithelial cells (p < .05). These results suggest that verapamil markedly attenuates PT morphologic injury in a rabbit model of reversible ischemic ARF. The functional protection observed in these studies may be related, in part, to the improved structural integrity of the renal tubules. Renal transplantation and anticipated renal ischemia (i.e., surgical interventions) are two important situations where treatment with verapamil or other calcium channel blockers may prove to be clinically beneficial.
Five cases of duodenal obstruction due to biliary stones (Bouveret's syndrome) are reported. Presenting symptoms were gastric outlet obstruction, upper gastrointestinal bleeding or jaundice. Diagnosis was achieved either by endoscopy, upper gastrointestinal X-Ray series or at the operating room. Surgical procedures to remove obstruction were needed in every case: cholecystectomy was simultaneously performed on two occasions. After reviewing the literature, previous biliary symptoms were found in 65% of the cases; diagnosis was achieved preoperatively in 85%, mainly by endoscopy procedures; simultaneous cholecystectomy was carried out in 56% of cases; postoperative mortality was 24%, rising when simultaneous cholecystectomy was performed.
We report a case of a 25-year-old women admitted to the emergency room of Santa Maria Hospital with pancytopenia and fever. We describe the diagnostic work-up, laboratory findings, therapy, outcome and follow-up after discharge Lastly, we discuss aplastic anemia as a rare systemic lupus erythematosus complication, with only ten cases reported to date.
BACKGROUND: The rearrangement of the bcr/abl gene constitutes the molecular substrate of the Philadelphia chromosome (Ph'). The aim of this study was to analyze the usefulness of bcr/abl rearrangement in the diagnosis and evolution of chronic myeloid leukemia (CML). METHODS: The rearrangement of the bcr/abl gene was studied in 81 cases of which 34 corresponded to patients with CML (29 Ph' positive chromosome, 2 Ph' negative chromosome and 3 without karyotype), 2 patients with Ph' positive acute lymphoblastic leukemia, 15 patients with chronic myeloproliferative syndromes different from CML and 30 controls. Of the patients with CML, 6 were reevaluated when a blastic crisis was developed, 2 after receiving interferon treatment and 1 following allogeneic bone marrow transplantation. The technique used was that of Southern blotting using the restriction enzymes Bgl II and BamHI and the transprobe. RESULTS: Rearrangement of the bcr/abl gene was observed in all the patients with CML except in one with Ph' negative chromosome. In the remaining cases bcr/abl rearrangement was not observed. CONCLUSIONS: The Southern blotting technique for the study of the bcr/abl gene rearrangement is a sensitive and specific method in the diagnosis of chronic myeloid leukemia constituting a valid alternative to chromosomic study when this cannot be carried out or is not conclusive. It may also be used for the control of treatment in chronic myeloid leukemia.
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Thioacetamide proved to be a potent necrogenic agent when a single dose of 6.6 mmol/kg was administered intraperitoneally to rats. Its necrogenic ability was assessed on the basis of morphological and biochemical changes. The injury of centrilobular hepatocytes showed a peak of cell death 24 hr after thioacetamide administration; it was followed immediately by the regenerative response. Parallel increases of serum aminotransferases, isocitrate dehydrogenase and gamma-glutamyl transferase activities were observed. Severe liver damage was also evident at 24 hr on the basis of glutathione depletion (29% of control), malondialdehyde production (169%), cytochrome P-450 level decrease (26%) and increased activity of glutathione S-transferase (160%). We checked the regenerative response by determining nuclear DNA content in isolated hepatocytes 0, 6, 12, 18, 24, 36, 48 and 72 hr after thioacetamide administration. Changes in DNA cell distribution between G0-G1, S and G2 + M phases of the cell cycle were observed. The sharp decrease in the percentage of the tetraploid cell population (G2 + M phases) and the abrupt increase of the S-phase cells at 36 and 48 hr suggest transition from adult to fetal in hepatocyte populations obtained 24 and 36 hr after thioacetamide treatment. At 72 hr of treatment, hepatocyte populations showed recovery to adult state. In the shift from the adult to fetal, registered at 24, 36 and 48 hr after thioacetamide administration, mitosis seemed to precede the synthesis of DNA.
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Membrane-bound and soluble forms of erythrocyte sorbitol dehydrogenase (SORD) activity are compared in normal individuals. Both isoenzymes showed similar properties. In a family with red cell SORD deficiency and congenital cataracts, Km values for sorbitol and NAD+ as well as the effect of the enzymatic deficiency on sorbitol accumulation in red cells incubated in high-glucose or high-fructose media were determined. In SORD-deficient patients, the enzymatic deficiency was observed in both crude haemolysate and SORD-M preparations with sorbitol, galactitol, xylitol or ribitol as substrates. The mutation responsible for SORD deficiency did not modify the Km for sorbitol and NAD+. Finally, SORD deficiency produced a significant increase of sorbitol accumulation in red cells incubated in high-concentration glucose media and a significant decrease when the cells were incubated in high-concentration fructose media.
A rare association of sebaceous naevus of Jadassohn and primary mediastinal lipomatosis is presented. These are two benign conditions that can have serious complications.
Rat thymic dendritic cells (DC) have been analyzed by flow cytometry in order to study the variations on the cell surface marker expression upon culture at 37 degrees C. Our results demonstrate that whereas expression of major histocompatibility complex (MHC) molecules, CD45, Mac-1, LFA-1, B-cell markers, macrophage markers and some T-cell markers (as CD2, CD4 and CD8) did not undergo changes in culture, the level of expression of the adhesion molecules VLA-4 and ICAM-1, and the T-cell markers CD5, CD25 and Thy-1 increased after 14 h incubation at 37 degrees C. VLA-4, ICAM-1 and Thy-1 expression was up-regulated from intermediate to high levels, the percentage of CD5+ cells increased from 20% to 50%, and the interleukin-2 (IL-2) receptor alpha chain (CD25) was induced in 50% of DC after the culture period. These results are discussed with regard to the functional significance of DC phenotypic variations, and their implications concerning the development of in vitro systems designed for T-cell differentiation studies involving purified DC.
A patient with multilobated B-cell malignant lymphoma with lesions limited to the skin is described. The light, electron microscopic, and immunohistochemical features of this unusual morphologic variant of non-Hodgkin's lymphoma are described. The nosologic position of this histologic subtype is discussed. The clinical course, with lesions confined to the skin, and the response to treatment suggest a favorable prognosis.
This report describes the results of six antimicrobial regimens used for the treatment of brucellosis in an open, randomized study performed over two periods (1980-1983 and 1984-1987). In the first period, rifampicin and doxycycline were used for 4 weeks, trimethoprim-sulfamethoxazole for 6 months, and doxycycline for 6 weeks. During the second period, we used streptomycin for 2 or 3 weeks together with doxycycline for 6 weeks and rifampicin with doxycycline for 6 weeks. Comparison of the results showed the following: (1) no statistically significant findings were revealed when the different regimens were compared and (2) the regimens containing streptomycin yielded statistically more favorable results than those consisting of rifampicin and monotherapy when the patients treated with rifampicin were compared with those taking streptomycin and those receiving single-agent therapy. No significant differences were observed between monotherapeutic regimens and those including rifampicin.