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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

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

IRBP: preparation and characterization of site-specific monoclonal antibodies.

Interstitial retinoid binding protein (IRBP) is a 136,000 molecular weight photoreceptor cell protein which is a highly pathogenic autoantigen for the induction of experimental autoimmune uveitis (EAU). In this study we produced a series of monoclonal antibodies (MAbs) which define different epitopes in the native molecule. These MAbs were further subdivided into three distinct groups based on a radioimmunoassay, and by ELISA assay using native IRBP and synthetic peptides corresponding to its entire amino acid sequence. Group I MAbs (MAbD7-B1 and MAbC6-B4) bound to native IRBP but not to any synthetic peptides, suggesting that their antigenic epitopes are strictly conformation dependent. Group II MAbs (MAbC7-D3 and MAbG8-H4) bound weakly to multiple peptides which shared amino acid sequence similarity located within each of four homology domains indicating that these epitopes are also conformation dependent. In group III (MAbH3-B5, MAbH7-A5, and MAbB6-D12) MAb binding was localized to a specific peptide. The MAbH3-B5 binding site was further refined to amino acid positions 361 to 367 in the native molecule. MAbH3-B5 was also useful in localizing IRBP in the mouse retina by immunohistochemical techniques. The application of these MAbs in the study of EAU and interphotoreceptor transport mechanisms is discussed.

Amino Acid Sequence↗

[Electrocardiographic symptom-signal correspondence in Holter records].

STUDY OBJECTIVE: To determine the correspondence symptom-sign in 24-hours ambulatory electrocardiography records. DESIGN: Retrospective study. SETTING: Pulido Valente Hospital (Lisbon). Serviço de Cardiologia. Department of Ambulatory Electrocardiography. PATIENTS: 80 patients, who made 24-hours ambulatory electrocardiography and wrote correctly the diary. Two observators analysed the correspondence symptom-sign of 269 symptomatic moments, 10 minutes before and after the symptom by reviewing the compressed print. RESULTS: We found correspondence symptom-sign in 50% of the symptomatic moments. The correspondence change with the symptom type (increased for palpitations and dyspnea), the presence of Cardiopathy (increased for chest pain and dyspnea in patients with cardiopathy) type of cardiopathy (increased in patients with Mitral Valve Prolapse and Valvular disease) and expression used by the patient.

Adolescent↗

[Rhythm profile in patients with psoriatic arthritis].

OBJECTIVE: To analyze the rhythmic profile in patients with psoriatic arthritis (PA). DESIGN: In order to evaluate the rhythmic profile of patients with PA, we have carried out ambulatory 24 hour ECG recordings in 22 patients presented consecutively to the Holter ECG laboratory. SETTING: Patients followed in a specialised rheumatology consultation, in Santa Maria Hospital. PATIENTS: We have studied 22 patients (pts), 10 male and 12 female, aged 49.8 +/- 8.4 years, presenting PA diagnosed in average 12.9 years before. A group of 36 individuals, 25 male and 11 female, aged 37 +/- 8 years and without disease, were used as control. RESULTS: All patients were in sinus rhythm with a mean heart rate of 71 +/- 6 (min - 51.5 +/- 7.0 and max - 130.3 +/- 15.0). In 8 (36.6%) there were sinus bradycardia less than 50/min and sinus tachycardia (greater than 120/min) in 15 patients (68.1%). Two patients (9%) presented supraventricular tachycardia and one had AV block. There were premature atrial systoles in 14 pts (63.6%), and ventricular arrhythmias in 9 (40.9%). In control group, there were sinus bradycardia in 16.6%, sinus tachycardia in 33.3%, premature atrial systoles in 33.3% and ventricular arrhythmias in 25% of them; in 11% there were conduction disturbances. CONCLUSIONS: a) Premature atrial systoles were the rhythm disturbance more prevalent. b) Patients with PA presented a significant higher incidence of sinus bradycardia and sinus tachycardia. c) Cardiac conduction disturbances were not frequent. d) Our results may suggest the presence of a subtle autonomic dysfunction in patients with psoriatic arthritis.

Adult↗

[Anthracycline cardiotoxicity. Review of the literature and presentation of a study protocol].

Anthracyclines are drugs with widespread applications on the chemotherapy of cancer. Cardiotoxicity is an important side effect of these drugs, well known for doxorubicin, the most representative of this group of drugs. Dysrhythmias and heart failure are the most important among the toxic effects of anthracyclines and are dependent on cumulative doses reason why WHO established maximal doses for the different anthracyclines. Pathogenic hypothesis about the mechanism of the myocardial lesion induced by anthracyclines include the production of free oxygen radicals, alterations of energetic metabolism and disturbances of calcium and sodium exchange at membrane level. Early detection of the toxicity of these drugs is of utmost importance. Electrocardiography has low sensitivity and specificity. Echocardiography gives specific information about previous cardiac pathology and enables the detection of complication of the basic neoplastic disease. However, detection of early changes of left ventricular function is not accomplished so well, as it is with equilibrium radionuclide angiography. Left ventricular ejection fraction is the method of choice in the early detection of cardiotoxicity of these drugs, and its frequent evaluation enables to individualize the doses in each patient, and so, a most accurate use of the therapeutic potential of the anthracyclines. Radionuclide angiography has some important indications on the selection of patients for treatment with anthracyclines, namely: to identify patients that must be excluded from the treatment; select patients at risk of congestive heart failure; to decide the appropriate moment to stop the drugs; change the therapeutic schema, etc.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Pleomorphic adenocarcinoma of ciliary epithelium simulating an epibulbar tumor.

A 72-year-old woman had epibulbar nodules and a blind eye following trauma in childhood. Histologic examination disclosed a pleomorphic adenocarcinoma of ciliary epithelium with invasion of the epibulbar region, retina, retinal pigment epithelium, and optic nerve. The diagnosis was confirmed by histochemical stains and electron microscopy. The pigmented and nonpigmented neoplastic cells of the ciliary epithelium had a patchy basement membrane around the cell membrane and produced hyaluronic acid in the stroma.

Adenocarcinoma↗

Coexpression of neuronal, glial, and major histocompatibility complex class II antigens on retinoblastoma cells.

This study identifies the presence of major histocompatibility complex class II antigens on retinoblastoma cells. In addition, the modulation of HLA-DR by interferon-gamma as well as the preferential expression of this major histocompatibility complex molecule over HLA-DQ is described. Double labeling experiments revealed that HLA-DR antigen is shared concomitantly with cells of glial and neuronal character. Investigations such as these underscore the possibility that expression of major histocompatibility complex class II antigens may function as immunological components in the host or play a role in the cellular differentiation of these tumor cells.

Antigens↗

Retinal insulin receptors: localization using a polyclonal anti-insulin receptor antibody.

Although retinal insulin receptors have recently been described biochemically, the location of these receptors within the retina is unknown. The study presented here used a polyclonal anti-insulin receptor antibody (B10), immunofluorescence and immunoelectron microscopy to determine the location of insulin receptors in bovine, monkey and human retina. It was found that antibody immunofluorescence formed discrete bands localized predominantly to photoreceptor and neuronal cell bodies. In addition to the strong association with neuronal perikarya, a lower level of antibody binding was observed in photoreceptor outer segments. In human retina, some of the antibody immunofluorescence also had a pattern that suggested B10 binding to glial-like cells.

Animals↗

Meibomian gland changes in the rhino (hrrhhrrh) mouse.

The rhino mouse, a single gene recessive mutation, is characterized by abnormal epidermal differentiation and maturation leading to the loss of hair at 1 month of age as well as follicular and epidermal hyperkeratoses. We evaluated the lids and corneas of nine rhino mice and their normal litter mates at various ages from 3 months to 1 year. Tissue specimens were studied by light microscopy, scanning and transmission electron microscopy as well as immunoperoxidase using a polyclonal rabbit anti-keratin antibody. At 3 months of age there was a thickening and hyperkeratinization of the palpebral epidermis which extended into and included the meibomian gland central duct. Whereas in the skin, hyperkeratinization is followed by follicular hyperkeratosis and dermal cyst formation, in the meibomian gland, ductal hyperkeratinization appeared to lead to loss of well developed acini followed by atrophy of the gland at 1 year as confirmed by immunostaining for keratin proteins. Scanning electron microscopy revealed marked plugging of the meibomian gland orifice with keratinized cells or debris in contrast to the patent orifice of the normal lid. Ocular surface changes included the presence of a whitish exudate covering the surface of the eye and increased numbers of preexfoliative corneal epithelial cells. These findings suggest that the rhino mouse may represents the first naturally occurring disorder of the meibomian gland.

Animals↗