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Biomedical subjects

M Rodrigues

Publications and source records attributed to M Rodrigues.

At least 73 records · Page 4Linked to original sources
PubMed1994

Synergistic antiplatelet action of nitric oxide (NO) with PGD2 and its metabolite PGJ2--relevance for cerebral circulation?

The PGI2/NO axis is well accepted for its central regulatory role in maintaining haemostatic balance in large arteries. Earlier findings suggest that PGD2 may also play a role in haemostatic regulation of human cerebral circulation. We therefore wondered whether PGD2 and its metabolite PGJ2 synergise in-vitro with NO. We approached this question using platelets of ten healthy donors and ADP as aggregation-inducing stimulus. Both PGD2 and PGJ2 do inhibit ADP-induced platelet aggregation in a dose-dependent manner. Platelet aggregation findings demonstrate that PGD2 and NO synergise, as does the metabolite PGJ2. Our data are indicative that the PGD2/NO and, in less extent, PGJ2/NO synergism might be of special importance for the cerebrovascular haemostatic control.

Adenosine Diphosphate↗
PubMed1994

[Instruments in nuclear cardiology].

The instrumentation required for performing nuclear cardiology can be schematically separated in three classes: 1) The usual material of nuclear medicine necessary for the reception, maintenance, preparation, administration and elimination of radionuclides and radiopharmaceuticals, 2) The instruments necessary for the detection of radiations and for the register and analysis of data, 3) The cardiologic material required for performing the stress and for monitoring coronary patients. There are well defined and sinalized areas. In the daily routine, protection of radiations and quality control of the radiopharmaceuticals and the equipment are fundamental. Gamma camera is the most used detector. Collimators and computers are other equipments essential for performing scintigraphy.

Cardiology↗
PubMed1993

Priming with recombinant influenza virus followed by administration of recombinant vaccinia virus induces CD8+ T-cell-mediated protective immunity against malaria.

Live vectors expressing foreign antigens have been used to induce immunity against several pathogens. However, for the virulent rodent malaria parasite Plasmodium yoelii, the use of recombinant vaccinia virus, pseudorabies virus, or Salmonella, expressing the circumsporozoite protein of this parasite, failed to induce protection. We generated a recombinant influenza virus expressing an epitope from the circumsporozoite protein of P. yoelii known to be recognized by CD8+ T cells and demonstrated that this vector induced class I major histocompatibility complex-restricted cytotoxic T cells against this foreign epitope. Immunization of mice with this recombinant influenza virus, followed by a recombinant vaccinia virus expressing the entire circumsporozoite protein, induced protective immunity against sporozoite-induced malaria. The sequence of immunization appears to be crucial, since a primer injection with recombinant vaccinia virus, followed by a booster injection with recombinant influenza virus, failed to induce protection. The protection induced by immunization with these recombinant viruses is mostly mediated by CD8+ T cells, as treatment of mice with anti-CD8 monoclonal antibody abolishes the anti-malarial immunity. The use of different live vectors for primer and booster injections has a synergistic effect on the immune response and might represent an effective general strategy for eliciting protective immune responses to key antigens of microbial pathogens.

Amino Acid Sequence↗
PubMed1993

99Tcm-HMPAO brain SPECT in the evaluation of prognosis after surgical resection of astrocytoma. Comparison with other noninvasive imaging techniques (CT, MRI and 201Tl SPECT).

High-grade astrocytoma represents the most common primary malignant brain tumour in the adult, and is associated with high morbidity and mortality rates. The aim of this study was to investigate the prognostic value of 99Tcm-hexamethylpropyleneamine oxime (HMPAO) brain single photon emission computed tomography (SPECT) in predicting neurological function and tumour therapy response after surgical resection of astrocytoma. The correlation between 99Tcm-HMPAO studies and other noninvasive methods [computed tomography (CT), magnetic resonance imaging (MRI) and 201Tl (SPECT)] was evaluated. The clinical population included 21 patients with previous surgical debulking of astrocytoma. All patients were evaluated with 99Tcm-HMPAO brain SPECT. Seven patients, who suffered progressive clinical deterioration after radiotherapy, underwent dual-isotope SPECT imaging with 201Tl and 99Tcm-HMPAO. Neurological examinations and CT were performed in all patients. Magnetic resonance imaging was performed in seven patients. Prior to radiotherapy and/or chemotherapy, the patients with neurological improvement during the follow-up evaluation commonly showed less intense abnormal 99Tcm-HMPAO uptake than the patients without neurological improvement. In addition, after therapy none of the former patients had increased 99Tcm-HMPAO uptake. Most patients without neurological improvement had evidence of high focal uptake. Computed tomography and MRI usually demonstrated pathological contrast enhancement regardless of the presence or absence of improvement of neurological function. Foci of high 201Tl accumulation were observed on SPECT images in five patients. In four of these patients, the 99Tcm-HMPAO was greater than in normal brain, and in two patients the 99Tcm-HMPAO uptake was lower than in normal brain. One patient with decreased 99Tcm-HMPAO uptake in a medium-sized lesion had a normal 201Tl study. Our hypothesis that 99Tcm-HMPAO SPECT may be useful for providing prognostic information after surgical debulking of astrocytoma seems to be promising. Further studies are needed to document this new important role of 99Tcm-HMPAO SPECT.

Adolescent↗
PubMed1993

Modulation of retinoblastoma cell characteristics by hexamethylene bis-acetamide and other differentiating agents in culture.

The undifferentiated Y-79 retinoblastoma cell line can be induced by specific agents to express characteristics of mature retinal cells. In the present study, attached Y-79 cell cultures were treated with hexamethylene bis-acetamide (HMBA) and other differentiating agents and examined for "neuronal" and other properties. Immunocytochemical staining was performed with antibodies against neuron- and retina-specific antigens, [synaptophysin, interphotoreceptor retinoid-binding protein (IRBP), neural cell adhesion molecule (N-CAM), and rod- and cone-specific transducin (TR alpha and TC alpha)] and microtubule-associated protein (MAP-1) and tubulin. Enhanced expression of tubulin was observed with cAMP treatment in FBS media. Expression of N-CAM was observed in all groups. Morphological differentiation was pronounced with HMBA and butyrate treatment, with HMBA inducing increased tubulin expression after 2 weeks of treatment. Expression of TR alpha was minimal under all culture conditions, whereas TC alpha was ubiquitously expressed. This supports the concept that Y-79 retinoblastoma is predominantly of cone neuronal origin and that, surprisingly, immunocytochemical differentiation is not correlated with the marked morphological changes induced by the major differentiating agents used.

Acetamides↗
PubMed1993

The relative contribution of antibodies, CD4+ and CD8+ T cells to sporozoite-induced protection against malaria.

Protective immunity against Plasmodium yoelii, induced by sporozoite immunization, was investigated using a quantitative method based on the measurement of plasmodial ribosomal RNA in the liver of sporozoite-challenged mice. The relative importance of the different immune mechanisms induced by sporozoite immunization was determined by evaluating quantitatively the anti-parasite activity of antibodies, CD4+ and CD8+ T cells. The role of antibodies was determined by passive transfer of immune sera to naive mice. The transfer to mice of sera obtained after a single immunizing dose reduced the liver stages by 47%. The respective contribution of CD4+ and CD8+ T-cell subsets was determined in B10 (H-2b) mice, treated with a monoclonal antibody (mAb) which inhibits B-cell maturation, and subsequently immunized once with irradiated sporozoites. These mice produced low levels of anti-sporozoite antibodies, but were capable of inhibiting the development of liver stages as efficiently as non-manipulated immunized mice. Administration of either anti-CD4 or anti-CD8 mAb to these mice, did not significantly decrease their capacity to inhibit the development of liver stages. We only observed a significant loss of immunity when the mice were depleted in vivo of both CD4+ and CD8+ T cells. In contrast to earlier studies, we found that the induction of protective immunity is not a phenomenon restricted to a few strains of mice having a particular genetic make-up. The apparent non-responsiveness observed in some strains of mice can be overcome by using larger immunizing doses.

Animals↗
PubMed1993

Immunoscintigraphy with 99mTc-labelled anti-CEA monoclonal antibody in colorectal carcinoma.

With the introduction of immunoscintigraphy (IS) with 99mTc-labelled anti-CEA monoclonal antibodies (MoAb), a clinical relevant method in nuclear medicine can be expected in the diagnosis and follow up of colorectal cancers. We performed IS (whole body, planar and SPECT) with a 99mTc-labelled intact anti-CEA MoAb (BW 431/26) in 18 patients with primary colorectal carcinoma, metastases or suspicious recurrences from colorectal carcinoma. The results of anti-CEA IS, serum CEA and Ca 19-9 levels were evaluated. Immunoscintigraphy yielded an overall sensitivity of 70.0%, 37.5% for primary tumors, 75.0% for recurrences and 100% for distant metastases. Serum CEA levels were elevated in 10 out of 18 patients (sensitivity 55.5%) and Ca 19-9 were elevated in eight out of 18 patients (sensitivity 44.4%). In the group of patients with metastases, CEA had a sensitivity of 100% and Ca 19-9, of 83.3%. From this prospective study, we can conclude that IS with 99mTC-BW 431/26 is a reliable tool in the post-operative follow-up study of patients with colorectal carcinoma, namely in the detection of distant metastases.

Aged↗
PubMed1992

Clinical and histopathologic changes in the host cornea after epikeratoplasty for keratoconus.

Five consecutive patients underwent epikeratoplasty for keratoconus. Postoperatively, four patients had poor visual acuity (average, 20/200) secondary to folds in Descemet's membrane and interface scarring. Two underwent penetrating keratoplasty eight months later. Histopathologic examination of the host corneas and the overlying lenticules disclosed epithelial irregularity and subepithelial fibrosis. The host corneas showed folds in Descemet's membrane and focal posterior stromal fibrosis. Electron microscopy disclosed breaks in Bowman's membrane with irregular collagen, posterior aggregates of amorphous material, and focal endothelial degeneration. The fifth patient had graft ulceration and vascularization that required removal of the lenticule. She underwent a penetrating keratoplasty five months later and histopathologic examination demonstrated persistent folds in Descemet's membrane. Immunostaining of specimens from three cases disclosed a reduced expression of sulfated epitopes of keratan sulfate and an increase in sulfated dermatan sulfate in the lenticule and host corneal tissues. These alterations in stromal proteoglycans are characteristic of stromal scars and keratoconus and provide evidence of pathologic processes in the graft tissue. Because of potential complications, epikeratoplasty should be considered only for those patients who are unsuitable candidates for contact lenses or penetrating keratoplasty.

Adult↗
PubMed1992

The in vivo cytotoxic activity of CD8+ T cell clones correlates with their levels of expression of adhesion molecules.

CD8+ T cell clones specific for a defined epitope present in the circumsporozoite protein of Plasmodium yoelii display striking differences in their in vivo antiplasmodial activity. The adoptive transfer of certain clones (YA23 and YA26) into naive mice inhibits by 90% or more the development of liver stages of malaria parasites and protects against malaria infection. The adoptive transfer of two other T cell clones (YB8 and YA15) results, respectively, in partial or no inhibitory activity on parasite development. We found that "protective" and "nonprotective" cytotoxic T lymphocyte (CTL) clones do not differ in their fine epitope specificity and display similar levels of lysis and DNA degradation of target cells in vitro. Their pattern of production of lymphokines and granule-associated proteins also failed to correlate with their in vivo antiplasmodial activity. Histological studies combined with autoradiography showed that, upon adoptive transfer, only T cells from the protective CTL clones are capable of "associating" with a significant percentage of parasitized hepatocytes. Fluorescence-activated cell sorter analysis of surface molecules revealed pronounced differences in the levels of CD44 and VLA-4 expression by the different clones, correlating closely with their in vivo protective activity. The correlation between in vivo antiparasite activity and the expression of CD44 was further corroborated by the results of sorting, from the partially protective YB8 clone, two sub-populations expressing high and low levels of CD44. These were protective and nonprotective, respectively. The clones also differed in their adhesive properties. Cross-linking of CD44, using specific antibodies, induced LFA-1-mediated homotypic aggregation of protective clones, while nonprotective cells failed to aggregate.

Amino Acid Sequence↗
PubMed1992

Mosaic expression of brush-border enzymes in infants with chronic diarrhea and malnutrition.

The chronic diarrhea observed in young malnourished infants that is sensitive to dietary glucose and other carbohydrates is associated with variable degrees of patchy mucosal villous atrophy. To explore intrinsic mucosal function in the pathogenesis of this alimentary intolerance, we have conducted an immunohistologic investigation of brush-border enzyme proteins of clinically obtained, mucosal biopsy samples. We used a group of monoclonal antibodies against human brush-border aminopeptidase, sucrase/isomaltase (SI), maltase, and lactase enzyme proteins. SI was strongly and uniformly expressed in crypts and villi of 11 of the 14 subjects; in 3 subjects, however, SI was expressed in a mosaic pattern. Maltase and lactase were occasionally absent, but more commonly were expressed in a mosaic distribution. The mosaic expression of brush-border enzyme proteins has been reported in congenital enzyme deficiencies associated with normal intestinal histology. We report the mosaic expression of brush-border enzyme proteins as a functional alteration associated with a pathological lesion of the mucosa in infants with chronic diarrhea. Our observation challenges the existing concept of ontogenic regulation of brush-border enzyme activity.

Aminopeptidases↗
PubMed1991

The interaction between CD8+ cytotoxic T cells and Leishmania-infected macrophages.

Leishmania is resident within the macrophages of its vertebrate host. In any intramacrophage infection, where the pathogen is present in a form capable of mediating cell to cell transmission, the contribution of a cytotoxic T cell response to protective immunity is questionable. This study presents data from an in vitro model designed to elucidate the outcome of an interaction between CD8+, cytotoxic T cells and infected macrophages. Experiments were conducted with an H-2d-restricted, cytotoxic CD8+ T cell clone and Leishmania parasites present in mixed macrophage cultures, with the parasites confined to either histocompatible BALB/c macrophages, or incompatible CBA macrophages. Initial experiments indicated that the viability of Leishmania was unaffected by the lysis of its host macrophage by cytotoxic T cells. However, extended experiments showed that the parasites were killed between 24 and 72 h. The same results were obtained regardless of whether the parasites were resident in the target, BALB/c, macrophages or the bystander, CBA, macrophages. Addition of neutralizing, anti-IFN-g antibody to the cultures ablated most of the leishmanicidal behavior, indicating that parasite death was attributable to macrophage activation, resulting from cytokine secretion from the T cells following the initial recognition event.

Animals↗
PubMed1991

Dominant suppression of adenovirus mediated transformation and insufficiency of p105Rb binding as a condition for oncogenic transformation.

An adenovirus-specific transformation resistant cell line (G2) expressing biologically active E1a proteins and originally isolated as a revertant from Ad2-transformed rat cells (F4), was shown to form stable Rb-E1a and 300K-E1a complexes in immunoprecipitation experiments. Consistent with the transformation resistant phenotype, cell hybrids between G2 and F4 were all nontumorigenic. Retrovirus insertion mutagenesis resulted in tumorigenic cell lines and identified a common locus responsible for the E1a-specific dominant tumor suppressor phenotype of G2 cells.

Adenoviruses, Human↗
PubMed1991

Role of parathyroid hormone in rat remnant kidney ammonium metabolism.

The role of parathyroid hormone (PTH) in ammonium metabolism in the rat remnant kidney was studied by examining the effects of parathyroidectomy (PTx) in rats with intact kidneys and with 5/6 nephrectomy (Nx). PTx in rats with intact kidneys caused a rise in urine pH and a decrease in urinary ammonium excretion without affecting in vitro ammonium production rate or the ammonium content in the cortex. Unexpectedly, the ammonium content in the medulla was markedly reduced by PTx so that the corticomedullary ammonium gradient was inverted. As compared to control rats, rats with 5/6 Nx had a lower urinary ammonium excretion rate, a higher in vitro ammonium production rate, and an increase in ammonium content in both cortex and medulla with reduced corticomedullary ammonium gradient. PTx in rats with 5/6 Nx led to a further decrease in urinary ammonium excretion, attenuated the increase in the in vitro ammonium production rate, and lowered the ammonium content in both cortex and medulla with inverted corticomedullary ammonium gradient. These effects of PTx in Nx rats were corrected by continuous PTH infusion with Alzet minipump. In summary, results from these studies indicate that PTH plays an important role in maintaining the urinary ammonium excretion. In rats with intact kidneys, PTH contributes to urinary ammonium excretion by increasing urinary acidification and medullary ammonium accumulation. In rats with reduced nephron mass, PTH enhances urinary ammonium excretion by stimulating ammonium production and retaining medullary ammonium in the remnant kidney.

Ammonia↗
PubMed1991

Juvenile ceroid lipofuscinosis. Evidence for methylated lysine in neural storage body protein.

Juvenile ceroid lipofuscinosis, or Batten disease, is a hereditary disorder characterized by progressive visual loss, seizures, cognitive and psychomotor deterioration, and early death, usually between 15 and 35 years of age. Individuals with this disease have massive deposits of autofluorescent inclusion bodies in cells of most tissues. The accumulation of these intracellular deposits suggests that juvenile ceroid-lipofuscinosis is a storage disease resulting from the inability of cells to metabolize some normal cellular constituent. It has been reported that the storage material is largely protein, much of which is a specific mitochondrial protein that apparently is not properly metabolized in subjects with Batten disease. The storage bodies were partially purified from the retinas of two siblings who died as a result of juvenile ceroid lipofuscinosis, as well as from the cerebral cortex of an unrelated individual with this disorder. Chromatographic analysis of storage body protein acid hydrolysates indicated that they contained a large amount of the modified amino acid epsilon-N-trimethyllysine. The abundance of this amino acid in the storage protein suggests that the disease may result from excessive methylation or from a failure to demethylate intermediate forms of the stored proteins. Acid hydrolysis also solubilized a fluorescent component from the retinal storage material, suggesting that the stored protein has a bound fluorescent adduct.

Adult↗
PubMed1990

Tumor necrosis factor mediated cytolysis requires the adenovirus E1a protein but not the transformed phenotype.

Adenovirus transformed cells are susceptible to lysis by human recombinant tumor necrosis factor (TNF). This susceptibility correlates with the presence of E1a in these cells. A flat revertant cell line which expresses a biologically functional E1a but not the transformed phenotype was nevertheless susceptible to TNF. However, flat revertants retransformed by 5-azacytidine, without concomitant reactivation of E1a, were resistant to TNF-alpha. This result suggests TNF susceptibility is not transformation but E1a dependent. To study the mechanism of cytolysis in these cell lines, we examined the possibility that changes in the transcription of E1a were brought about by TNF, as it was reported in the case of a c-myc transformed cell line. The results showed that TNF did not affect either E1a or c-myc transcription in our cells during the development of the cytotoxic response.

Adenoviridae↗
PubMed1990

Thyroid carcinoma metastatic to the medial rectus muscle.

Isolated extraocular muscle metastasis is rare and is unreported for thyroid carcinoma. The authors describe a 72-year old man who presented with pain, redness, and proptosis of the right eye. Orbital computed tomography showed a large fusiform soft tissue mass along the medial aspect of the right orbit, involving the medial rectus. Orbital exploration disclosed a mass within the medial rectus muscle sheath involving the muscle belly. Histopathologic examination including electron microscopy, revealed metastatic thyroid carcinoma. Systemic treatment with radioactive iodine was recommended and refused by the patient. One year later, he died of complications from his metastatic disease.

Adenocarcinoma↗
PubMed1990

Synergism between distinct enhanson domains in viral induction of the human beta interferon gene.

This study demonstrates distinct virus-inducible enhanson properties for three regions of the human beta interferon (IFN-beta) promoter; maximum virus inducibility required syngerism among all three enhansons. Expression of the IRF-1 transcription factor differentially increased the expression of plasmids containing (AAGTGA)4 or PRDIII (-94 to -78) motifs but was inefficient in the induction of the intact IFN-beta promoter. The human T-cell lymphotropic virus type I Tax protein was a strong positive activator of PRDII (-64 to -55)-containing plasmids but was also unable to stimulate the IFN-beta promoter. Induction of the intact IFN-beta promoter linked to a reporter plasmid was achieved in lymphoid and epithelioid cellular backgrounds by a triple transfection with IRF-1 and Tax expression plasmids or a combination of IRF-1 and phorbol ester, indicating that at least two trans-activating events and the association of two proteins on the promoter template are required for IFN-beta activation.

Acetylation↗