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Biomedical subjects

D Pinto

Publications and source records attributed to D Pinto.

At least 37 records · Page 2Linked to original sources
PubMed1997

Analysis of the allelic diversity of a (CA)n repeat polymorphism among alpha 1-antitrypsin gene products from northern Portugal.

The level of molecular heterogeneity associated with alpha 1-antitrypsin gene products was assessed in the population of northern Portugal using three restriction fragment length polymorphisms (RFLPs) corresponding to specific amino acid substitutions and a highly variable (CA)n repeat polymorphism located at the 5' end of the PI gene. The allelic affinities inferred from the analysis of the DNA polymorphisms essentially agree with the evolutionary pattern proposed for the PI gene products on the basis of their amino acid sequences. PI*Z can be considered the most recent common PI allele and was found to be associated with the same predominant haplotype previously reported in northern European populations, thus confirming the hypothesis that most European Z alleles are derived from a single mutation. However, a rare deficient variant that is the likely result of a recurrent Z mutation on an M2 or M4 background was additionally observed. PIS was also found to be associated with a strongly predominant haplotype and seems to be the second most recent PI common allele, while M2 and M3 show weaker associations, suggesting more ancient origins of their corresponding mutations. M1Ala213 and M1Vat213 display more homogeneous (CA)n allele frequency distributions, M1Ala213 representing the most ancient PI allele as inferred from its highest variance in (CA)n allele length.

Alleles↗
PubMed1997

Long-term follow-up and post-relapse survival in patients with non-metastatic osteosarcoma of the extremity treated with neoadjuvant chemotherapy.

BACKGROUND: Most of the studies of the treatment of non-metastatic osteosarcoma of the extremity have reported results in terms of probability of survival up to five years with a minimum follow-up of less than two to three years. Definition of reliable indicators of prognosis and predictive factors for survival require mature data derived from a long-term survival analysis. PATIENTS AND METHODS: A review of 127 patients with non-metastatic osteosarcoma of the extremity, treated between March 1983 and June 1986, was performed. The treatment protocol consisted of primary chemotherapy with MTX (randomization to high vs. moderate dosages) and CDP followed by surgery. Postoperatively, patients with < 60% tumor necrosis received ADM and BCD; those with tumor necrosis > or = 60% < 90% (Fair Responders FR) were given MTX, CDP and ADM. Up to January 1984, patients with tumor necrosis > 90% received MTX and CDP only, and after then they were given the same treatment as for FR. A multivariate analysis to test predictive factors for survival was performed. RESULTS: With a median follow-up of 134 months (range 114-153), the 12-year DFS was 46%. A good histologic response, an LDH baseline value within the normal range, and the use of high-dose MTX were positive predictive factors for DFS. With a median time of observation for survivors of 130 months, the 12-year overall survival was 53%. None of the patients who relapsed with local or distant recurrences other than lung metastasis are now alive. Patients with a relapse-free interval longer than 24 months had a significantly better post-relapse survival than those with a shorter relapse-free interval (40% vs. 7%; P = 0.0159). All of the patients who were not surgically treated had disease progression and died within 40 months after the first recurrence. The surgically-treated patients had a 30% post-relapse survival probability. CONCLUSIONS: In non-metastatic osteosarcoma of the extremity, chemotherapy-induced tumor necrosis, the baseline LDH serum value and the use of HDMTX are significant predictive factors for DFS. The relapse-free interval and the possibility of metastasectomy are significant factors conditioning the post-relapse survival.

Adolescent↗
PubMed1997

Reactions to managed care among psychologists and social workers.

Although the delivery system for mental health care is undergoing unprecedented changes with managed care, few empirical assessments of practitioners' responses exist. Directories of managed care providers were used to contact 139 providers of managed mental health care for an anonymous survey of experiences with case management and short-term therapy. The differential effects of managed care on the practices of doctoral-level psychologists, master's-level psychologists, and social workers were examined.

Adult↗
PubMed1997

[Magnetic resonance angiography in the study of pulmonary veins: TOF 3D versus 2D].

The aim of this work was to optimize the magnetic resonance angiography (MRA) technique for the selective study of the pulmonary veins. Twenty consecutive patients (13 men and 7 women; mean age: 30.5 years) were examined. MRA was performed with a 1 T superconductive magnet and the 3D time of flight (TOF) technique. Fast sequences (3D FISP: TR 58 ms, TE 6 ms, FA 20 degrees, matrix 192 x 256; and 2D FLASH: TR 44 ms, TE 10 ms, FA 30 degrees, matrix 192 x 256) were used. Coronal and sagittal images were submitted to MIP processing; presaturation pulses for the pulmonary arteries were located in the mediastinal region. In the right lung, 3D TOF on the coronal plane well showed 124 veins, while sagittal images showed 106 veins. In the left lung, 3D TOF on the coronal plane well showed 96 vessels, while sagittal images showed 44 vessels. In the right lung, 2D TOF on the coronal plane well showed 54 veins, while sagittal images showed 36 vessels. In the left lung, 2D TOF on the coronal plane well showed 22 vessels, while sagittal images showed 21 vessels. Therefore, 3D TOF yielded better results than 2D TOF (p < 0.05). To conclude, 3D TOF with contrast agent administration is a useful tool to study the pulmonary veins; those with a larger caliber are better depicted and the integration of coronal and sagittal images depicts more veins.

Adult↗
PubMed1996

Comparative effects of selective cyclooxygenase 1 and cyclooxygenase 2 inhibitors on myeloperoxidase and 3 alpha-hydroxysteroid dehydrogenase.

The clinical efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) is believed to result from the ability of these compounds to inhibit the inducible isoform of the enzyme cyclooxygenase, COX2. The gastrointestinal and renal side effects of these drugs, in contrast, are thought to relate to their ability to inhibit the constitutive isozyme, COX1. There is structural and pharmacological evidence that suggests that NSAIDs may also inhibit two unrelated enzymes, myeloperoxidase (MP) and 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD), potentially with untoward consequences for the patient. Our laboratories have been investigating a new structural class of potential COX inhibitors, the tri-cyclic aromatics. In this study we have examined the inhibitory potency of selected compounds for the enzymes human COX1, human COX2, human MP, and rat liver 3 alpha-HSD. The compounds selected span a range of COX isoform selectivities, from specific for COX2 to selective for COX1 only, and include three representative tri-cyclic aromatics. We found that compounds within the tri-cyclic aromatic class do not act as potent inhibitors of either myeloperoxidase or 3 alpha-HSD. These results demonstrate the unique inhibitor selectivity that can be achieved with the tri-cyclic aromatics. Examples of COX1 selective, and COX2 selective inhibitors within this structural class are presented.

3-Hydroxysteroid Dehydrogenases↗
PubMed1996

[Magnetic resonance angiography of the origin of the supraaortic trunks: the tridimensional time-of-flight with single volume technique].

This work was aimed at studying the origin of the epiaortic vessels with Magnetic Resonance Angiography (MRA). Twenty normal volunteers (mean age: 21.5 years) were examined with MRA with a superconductive magnet at 1 T (Impact). All volunteers were examined with a body coil and the time of flight (TOF) technique. The FISP 3D TONE sequence was used, with the following parameters: TR 46 ms, TE 10 ms, FA 20 degrees, ST 2.2 mm, matrix 192 x 256. The images, acquired on the axial plane with three presaturation pulses, were rotated according to the maximum intensity projection on the Z axis. To classify the images, a multiple choice card was used by a reader, with three diagnostic judgements for the different segments of the vessels (i.e., good, poor and not visualized). 3D TOF MRA permitted good visualization of the right and left common carotid in 80% and 77% of cases, of the right and left vertebral arteries in 55% and 50% of cases, of the left and right subclavian arteries in 47% and 62% of cases, and of the anonymous artery in 100% of cases. To conclude, our preliminary results indicate FISP 3D TOF MRA as the best noninvasive technique to study the origin of the epiaortic vessels.

Adult↗
PubMed1996

[The innervation of the digestive tract: its morphofunctional and neurochemical aspects].

The innervation of the alimentary tract (or enteric nervous system, ENS) represents the third division of the autonomic nervous system and it appears to be unique for its intrinsic ability to mediate reflex activity even when disconnected from the central nervous system. Enteric nerve cells can be classified in subclasses according to combined classic morphological criteria (Dogiel type I, II and III) and electrophysiological properties (type S and AH). A further major feature of the ENS lies in the variety of chemical messengers expressed in its neuronal elements. These substances can act either as neurotransmitters or neuromodulators. A common finding of enteric neurons is to synthetize and store several chemical messengers, a phenomenon known as neurochemical coding. As a consequence, neurotransmission involves the release and action of more than one messenger, an event referred to as plurichemical transmission. Recently, the use of combination of methods (such as immunohistochemical, pharmacological and electrophysiological techniques) has led to the identification of specific functionally distinct categories of enteric neurons. Thus, inhibitory and excitatory motor neurons, interneurons, vasomotor and sensory neurons are now recognized to constitute the complex network of the ENS. These neuronal elements are synaptically connected to form microcircuits which play a pivotal role to control digestive functions, including motility, blood flow, secretion and absorbtion.

Animals↗
PubMed1994

Mechanism of selective inhibition of the inducible isoform of prostaglandin G/H synthase.

Selective inhibition of the inducible isoform of prostaglandin G/H synthase (cyclooxygenase-2; COX2; EC 1.14.99.1) can be achieved with compounds of the general form of aryl methyl sulfonyls and aryl methyl sulfonamides. DuP 697 and NS-398 are representative examples of these compounds. Both inhibit the constitute (COX1) and inducible (COX2) isoforms of the enzyme with equal potency shortly after mixing, but their potencies increase with time for COX2 selectively. This time-dependent inhibition follows first-order kinetics, and the rate constant for inactivation of COX2 is dose dependent for both compounds. Kinetic analysis allows us to determine KI and kinact (the maximal rate of inactivation) for each inhibitor. The potency of both compounds is substrate concentration dependent, as expected for time-dependent competitive inhibitors. COX2 that has been incubated with these inhibitors, and then extensively dialyzed against buffer, shows no recovery of enzyme activity, while complete recovery of activity is seen for COX1. Thus, these inhibitors irreversibly inactivate COX2 with time, while showing minimal reversible inhibition of COX1. We isolated these inhibitors after long incubation with excess enzyme and subsequent denaturation of the enzyme. Both inhibitors showed no loss of potency resulting from interactions with COX2, suggesting that inhibition is not mediated by covalent modification of the enzyme. These data suggest that binding of these inhibitors to COX2 induces a slow structural transition of the enzyme that results in its selective inactivation.

Animals↗
PubMed1986

Lack of isotype exclusion and expression of aberrant lambda light chain on secreted MOPC-315 myeloma proteins.

The presence of aberrant lambda 1 light (L) chain fragment (lambda 1 F) on the secreted myeloma protein of MOPC-315 has been demonstrated by serological and immunochemical methods. We developed a highly sensitive radioimmunoassay that utilizes exquisitely specific xenogeneic anti-lambda 1 antibodies to detect the minute amounts of lambda 1 F on lambda 2-bearing MOPC-315 myeloma proteins. In addition, structural evidence that lambda 1 F is present on MOPC-315 myeloma protein was demonstrated by subjecting 125I-labeled MOPC-315 myeloma protein to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions followed by autoradiography. The relative amounts of lambda 1 F and lambda 2-chain on MOPC-315 myeloma were measured by two independent methods. The molar ratio of lambda 1 F to lambda 2 was calculated to be 1:68 by radioimmunoassay and 1:80 by analytical SDS-PAGE. This represents the first demonstration that an aberrant L-chain fragment combines with a heavy chain and is secreted in association with antigen-binding myeloma proteins. The implications of these results on L-chain isotype exclusion are discussed.

Animals↗
PubMed1983

Prognostic value of tumour thickness in cutaneous malignant melanoma.

The relation between survival and histological features in 91 patients with malignant melanoma was studied and the results were analysed by Clayton's method for interpretation of censored survival data. There was a significant correlation between tumour thickness and survival. The risk of dying from malignant melanoma after 10 years of follow up was less than 15% if the primary tumour was less than 1.5 mm thick but more than 80% if the lesion was thicker than 8 mm. The type of melanoma, level of invasion, mitotic rate, and presence of ulceration also correlated with survival, but these variables are related to tumour thickness.

Adult↗
PubMed1979

Contrast computed tomography in the diagnosis of acute cholecystitis.

Computed tomography (CT) has the ability to detect small variations in tissue density. Meglumine diatrizoate was given intravenously to four patients with clinical acute cholecystitis as part of the CT scanning procedure. The enhancement of the thick gallbladder wall, together with an enlarged gallbladder and the presence of stones, confirmed the diagnosis of acute cholecystitis. Our present experience indicates that, after contrast medium administration, CT has a distinct place in the assessment of acute inflammation of the gallbladder.

Acute Disease↗