PubMed HealthSearch

Biomedical subjects

M Pinto

Publications and source records attributed to M Pinto.

At least 19 recordsLinked to original sources

Accuracy of SPECT scanning in diagnosing pseudoarthrosis: a prospective study.

The present study attempted to analyze the efficacy of single photon emission computed tomography (SPECT) in diagnosing pseudoarthrosis after fusion using surgical exploration as the gold standard. This study examined the SPECT scans of 38 patients before they underwent surgical exploration of their fusion mass for suspected pseudoarthrosis or in conjunction with instrumentation removal. Surgical findings were compared with the radiologists' findings to determine the efficacy of SPECT in diagnosing pseudoarthrosis. Radiographic determination of pseudoarthrosis has been difficult after attempted fusion of the spine. Multiple radiographic modalities have been touted as accurate depicters of the failure of spinal fusion. However, no method has been found to be highly accurate in the clinical setting. Thirty-eight patients (mean age = 42.8, 21 males/17 females, 35 of 38 with instrumentation) underwent SPECT scans before surgical exploration of their fusion mass for suspected pseudoarthrosis or in conjunction with instrumentation removal as part of this prospective study. The average interval from their fusion procedure until their SPECT scan was 23.9 months (range, 9-120 months). All surgical findings were recorded with regard to solidity of the fusion and the level of the possible pseudoarthrosis. All SPECT scans were read at a time after surgery by an independent nuclear radiologist who had not read their SPECT scans before surgery and who did not know the results of exploration. Results of the radiologist's reading were then compared with surgical exploration findings, and sensitivity and specificity was calculated. There were 24 solid fusions and 14 pseudoarthroses. SPECT scans correctly identified 7 of the 14 pseudoarthroses and 14 of the 24 solid fusions. This represents a sensitivity of 0.50 and a specificity of 0.58. SPECT scanning correctly diagnosed the one solid fusion and two pseudoarthrosis patients in the three patients who had no instrumentation. This study demonstrates that SPECT scanning alone is inaccurate in diagnosing pseudoarthrosis when using surgical exploration as the gold standard. Given recent pressures for cost containment, we cannot recommend SPECT scanning as a routine modality for use in the diagnosis of pseudoarthrosis. We cannot define the accuracy of SPECT scanning used together with computed tomography scans, plain films, or other radiographic modalities in the diagnosis of pseudoarthrosis.

Adult

Effect of an aerobic training on magnesium, trace elements and antioxidant systems in a Down syndrome population.

The aim of the present study was to determine the effect of an aerobic training on plasma and red blood cells' levels of magnesium, copper, selenium and zinc and on some oxidative stress parameters in a Down syndrome (DS) sample population. Sixteen young male adults with DS participated in the protocol. Among them, eight were randomly assigned to the control group and the remaining eight participated in a 16 week training programme consisting of 10 min warm-up followed by an aerobic session at a work intensity of 60 to 75 per cent of VO2 peak lasting from 15 to 25 min, increasing 5 min every 5 weeks and by a 5 min cool-down period, 3 days/week. Blood was withdrawn by butterfly from antecubital vein of each subject at fast, 2 days before the beginning of the programme and 2 days after its ending. Before the training period, when comparing the two groups, no significant differences were observed in the evaluated parameters. However, when comparing with a healthy population, red blood cells magnesium and plasma and red blood cells selenium mean values were low in both groups and mean SOD activity was 1.4 times higher. After the protocol the mean values of the minerals studied did not show significant differences between groups except for plasma zinc that was lower (p = 0.029) in the trained group. Plasma TBARS increase was significant in the trained group (p = 0.034) but not in the control group and plasma GSH of the trained group had a significantly higher increase than the control group (p = 0.003). The levels of plasma TBARS after the training programme that were inversely correlated with red blood cells GSSG levels (p = 0.023) and the higher increase of plasma GSH mean values observed, may be explained by the effect of the exercise period on the peroxidation and reduction of glutathione and also on the synthesis and efflux of GSH. Red blood cells magnesium levels remained low after the training programme which is in accordance with other studies. Plasma zinc decreased during the programme could be related to the activated expression of antioxidant mechanisms after the training.

Adolescent

[Classic strategies for diagnosis of cryptosporidiosis in patients with AIDS and chronic diarrhea].

Cryptosporidium sp., a protozoa organism, has been increasingly recognized in association with severe enteritis in patients with the Acquired Immunodeficiency Syndrome. The studied subjects included 84 adult patients with AIDS and chronic diarrhea. We describe 14 patients with intestinal infection caused by Cryptosporidium sp. The mean CD4 count in these patients was < or = 300 cells/mm3 (7 out of 14). Examination of duodenal aspirates and feces included dimethylsulfoxide, auramine and acid-fast preparation of concentrated samples. We carried out videoesophagogastroduodenoscopy (VEDA) to visually inspect the mucosa and obtain biopsy specimens. VEDA revealed granular duodenum in ten patients and jasper duodenum in one of them. Duodenal biopsy specimens were stained with hematoxylin-eosin, Giemsa and Azure II. Histologic changes included atrophy (3/14), duodenitis (2/14) or both (3/14). Transmission electron microscopy was used for the identification of developmental stages of Cryptosporidium sp.

AIDS-Related Opportunistic Infections

[Why and how should we teach molecular biology at medical and pharmacy schools].

Molecular biology becomes an increasingly important topic in the medical and pharmaceutical academic education. For many reasons the basic education in molecular biology is necessary irrespective of a future orientation of physicians and pharmacists. The article seeks to define the limits of molecular biology in terms of both the scientific discipline and the teaching topic, and pinpoints the main factors and aspects, as well as pitfalls of molecular biological education as an integral part of medical and pharmaceutical study.

Education, Medical

Products of the grg (Groucho-related gene) family can dimerize through the amino-terminal Q domain.

The murine grg (Groucho-related gene) products are believed to interact with transcription factors and repress transcription, thereby regulating cell proliferation and differentiation. Most proteins in the grg family contain all of the domains found in the Drosophila Groucho protein, including the S/P (Ser-Pro-rich) domain required for interaction with transcription factors and the WD40 domain, which is thought to interact with other proteins. However, at least two Grg proteins contain only the amino-terminal Q (glutamine-rich) domain. We examined whether the Q domain is used for dimerization between Grg proteins, using the yeast two-hybrid system and binding assays with glutathione S-transferase fusion proteins. We found that Grg proteins are able to dimerize through the Q domain and that dimerization requires a core of 50 amino acids. Surprisingly, the dimerization does not require the leucine zipper located within the Q domain.

Amino Acid Sequence

Low temperature enhancement of reporter genes expression directed by human immunodeficiency virus type 1 long terminal repeat.

Bacteria and eukaryotic cells respond to cold stress by inducing and enhancing the synthesis of specific arrays of proteins. We describe here cold-induced enhancement of expression for two reporter genes; luciferase and beta-galactosidase, both under the control of HIV-1 LTR sequences, observed in mouse fibroblasts and human HeLa cells respectively. Increased expression of luciferase in fibroblasts when shifted to 25 degrees C was detectable at 30 degrees C but was not observed following cold shock at 4 degrees C. To sustain the cold-induced effect, cells had to be kept at subphysiological temperature. The observed enhancement of luciferase activity did not result from a particular site of integration of the reporter gene and was evident whether cold-stressed cells were stationary or growing. Cold-induced expression of luciferase was evidenced at the protein level, enzymatic activity and RNA level, furthermore, active transcription and translation were required for overexpression. The cold effect which has been generalized with the reporter gene beta-galactosidase appears to be a process involving, at least in part, the HIV-1 LTR sequences and might correspond to an increase in the half-life of mRNA. The cold-dependent enhanced expression of luciferase and beta-galactosidase reported here, together with data describing the activation of HIV-1 LTR by hyperthermia, point out the particular temperature sensitivity of these regulatory sequences. This potential thermal modulation may be useful in the comprehension of regulatory processes in latency and reactivation of viral expression during HIV-1 infection.

3T3 Cells

[Idiopathic pulmonary hemosiderosis].

We report a case of a 23 year-old man admitted to hospital with cough, fever and recurrent episodes of haemoptysis. Laboratory findings, which included a pulmonary biopsy, established the diagnosis of Idiophatic Pulmonary Hemosiderosis (IPH). Despite a number of morphologic, immunologic and ultrastructural studies, the etiology and pathogenesis of this disease remain indetermined. To diagnose an IPH all the other causes of pulmonary hemorrhage must be excluded. This is a rare disease, even more rare in adults. Based on these facts the authors publish this article, which includes the case report and a literature review.

Adult

GRP78 induction by cyclosporin A in human HeLa cells.

Immunosuppressive drugs such as cyclosporin A (CsA) and FK506 are known to have pleiotropic effects on cells. Here we demonstrate that treatment of HeLa cells with low concentrations of CsA (but not of FK506) induces the synthesis of a stress protein, GRP78, located inside the endoplasmic reticulum. High concentrations of CsA lead to a general decrease in protein synthesis. When cells are stressed (heat-shocked) during the CsA treatment, the synthesis of heat shock proteins is reinforced. FK506 has no detectable effects at any concentration. The mechanism of induction of GRP78 by CsA remains presently unknown. Whatever the mechanism involved, GRP78 overexpression might be responsible for some of the physiological effects of CsA.

Carrier Proteins

Standardization of prothrombin times in newborn infants.

The prothrombin time (PT) for patients receiving warfarin varies widely, reflecting the heterogeneity of thromboplastin reagents. The International Committee on Thrombosis and Haemostasis recommends that PT values for these patients be expressed as international normalized ratios. This study showed that thromboplastin reagents also significantly influence PT values in neonatal plasma and that expressing PT values as international normalized ratios decreases this variability.

Adult

Pulmonary surfactant inhibits interleukin-2-induced proliferation and the generation of lymphokine-activated killer cells.

The generation of lymphokine-activated killer (LAK) cell activity and the proliferative response to human recombinant interleukin-2 (IL-2) were significantly reduced when either human peripheral blood lymphocytes (PBL) or purified CD56+/CD3- lymphocytes were cultured in the presence of pulmonary surfactant. Surfactant concentrations ranging between 30 and 500 micrograms/ml produced increasing levels of inhibition ranging from 20 to 95%. For any given concentration of surfactant, increasing the IL-2 concentration produced increasing levels of LAK activity but never overcame the suppressive effects of the surfactant. Time course studies demonstrated that surfactant is inhibitory only if added to PBL during the first 2 days of IL-2 culture, suggesting a preferential action during the induction phase of LAK activity. Pretreatment of PBL with surfactant for as little as 2 to 4 h inhibited their subsequent response to IL-2 culture, suggesting that inhibition is rapid, persistent, and directly due to alterations in PBL responsiveness. To determine if surfactant alters cell membrane function, we measured the effects of surfactant exposure on LAK:tumor binding. Binding of LAK cells to both K562 and M14 tumor targets was inhibited in a concentration-dependent manner. Concurrently, we observed a reduced expression of IL-2 alpha-chain receptors on surfactant-treated CD56+/CD3- cells and a dramatic reduction in the expression of adhesion molecules including CD2, LFA-1, LFA-3, and ICAM-1. We conclude that pulmonary surfactant has the potential to suppress cytotoxic and proliferative responses to IL-2, alters cell-to-cell interactions, and reduces the expression of activation and adhesion molecules on LAK cells.

Adult

Mammalian heat shock protein families. Expression and functions.

When prokaryotic or eukaryotic cells are submitted to a transient rise in temperature or to other proteotoxic treatments, the synthesis of a set of proteins called the heat shock proteins (hsp) is induced. The structure of these proteins has been highly conserved during evolution. The signal leading to the transcriptional activation of the corresponding genes is the accumulation of denatured and/or aggregated proteins inside the cells after stressful treatment. The expression of a subset of hsp is also induced during early embryogenesis and many differentiation processes. Two different functions have been ascribed to hsp: a molecular chaperone function: chaperones mediate the folding, assembly or translocation across the intracellular membranes of other polypeptides, and a role in protein degradation: some of the essential components of the cytoplasmic ubiquitin-dependent degradative pathway are hsp. These functions of hsp are essential in every living cell. They are required for repairing the damage resulting from stress.

Animals

Denaturation of proteins during heat shock. In vivo recovery of solubility and activity of reporter enzymes.

Using beta-galactosidase and luciferase as reporter enzymes, we have previously shown that enzymatic inactivation occurring during a heat shock is concomitant with protein insolubilization (Nguyen, V. T., Morange, M., and Bensaude, O. (1989) J. Biol. Chem. 264, 10487-10492). In this paper, we observe that pretreatment of cells with D2O and glycerol, compounds known to stabilize protein structure, leads to a parallel decrease of protein inactivation and insolubilization, suggesting that these two phenomena result most probably from heat-induced protein denaturation. We found that heat shock-promoted inactivation and insolubilization are not irreversible processes, since even in the absence of protein synthesis, beta-galactosidase solubility and luciferase solubility and activity are recovered in vivo after a heat treatment. Cognate heat shock proteins might be involved in this renaturation process.

Animals

In vivo protective effect of lipopolysaccharide against Pseudomonas aeruginosa exotoxin A in mice.

Lipopolysaccharide (LPS) treatment of mice 1 to 5 days prior to administration of Pseudomonas aeruginosa exotoxin A (PA) induced full or partial protection against PA intoxication. The optimal LPS dose that induced resistance was 50 to 100 micrograms per mouse. Simultaneous administration of LPS and PA to mice, however, increased their sensitivity to PA two- to fourfold. Mice pretreated with LPS demonstrated a markedly enhanced clearance rate of 125I-labeled PA from peripheral blood, livers, and kidneys. In mice exposed to LPS and PA simultaneously, the rate of elimination of labeled PA was lower than that in control mice. While protein synthesis was inhibited significantly in livers and other organs of PA-exposed mice, in LPS-pretreated mice, PA-induced inhibition of protein synthesis was either diminished or totally prevented and elongation factor 2 (EF2) levels were normal. In mice treated only with LPS, enhanced protein synthesis and increased levels of EF2 were observed, suggesting that LPS protection against PA intoxication was perhaps a consequence of excessive amounts of EF2 induced by LPS.

ADP Ribose Transferases

Cystic fibrosis in the Portuguese population: haplotype distribution and molecular pathology.

The aim of this study was to obtain an estimate of the frequency of the delta F508 mutation in the Portuguese population, and of the tightness of its association with specific haplotypes. Furthermore, the genotype/clinical phenotype relationship and the feasibility of prenatal diagnosis were also investigated. The analysis of 42 cystic fibrosis (CF) families revealed that (1) 52% of CF chromosomes carry the deletion of codon 508; (2) there seems to be a positive correlation between the occurrence of the delta F508 mutation and the severity of the disease; and (3) fully informative prenatal diagnosis can be offered in 76% of at-risk pregnancies by using both genomic and allele specific oligonucleotide probes.

Chromosome Deletion

Heterogeneity of laboratory test results for antiphospholipid antibodies in patients treated with chlorpromazine and other phenothiazines.

Ninety-seven psychiatric patients who have been treated with the antipsychotic drug chlorpromazine or another phenothiazine have been investigated for the presence of antiphospholipid antibodies. A variety of coagulation studies and specific antiphospholipid immunoassays were performed to define the spectrum of antigen specificity of these antibodies. Coagulation studies showed an increasing sensitivity for the lupus anticoagulant with reagents of differing phospholipid content. Prolonged activated partial thromboplastin times (APTTs) were found in five patients with the use of an insensitive APTT reagent and in 14 patients with a lower phospholipid content reagent. In every case, attempted correction of the clotting time with normal plasma was unsuccessful. Twenty-one patients had abnormal kaolin clotting time profiles. In seven of these patients, test results with both APTT reagents had been normal. Antibody reactivity was tested against three negatively charged phospholipids, phosphatidyl-serine, cardiolipin, and phosphatidylinositol. Only five patients demonstrated reactivity against phosphatidylinositol, whereas high antibody titers were observed in 28 patients against one or both of phosphatidylserine and cardiolipin. Twenty-three of these patients were found to have elevated anticardiolipin-specific IgM antibodies. Overall, 41 of the patients had at least one laboratory abnormality suggestive of antiphospholipid antibody activity. Seven of the 26 patients, taking phenothiazines other than chlorpromazine, had positive test results for antiphospholipid antibodies. No clinical thromboembolic events were recorded in any patient. These findings demonstrate the heterogeneity of antiphospholipid antibody specificity induced in patients treated with various phenothiazine drugs and indicate that none of these patterns of reactivity marks a predisposition for thromboembolism in this population.

Adult