PubMed Health⌕ Search

Biomedical subjects

M Rodrigues

Publications and source records attributed to M Rodrigues.

At least 91 records · Page 5Linked to original sources

[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↗

Resistance to retransformation by adenovirus but not by heterologous oncogenes in an E1-positive transformation revertant cell line may be mediated by a cellular function.

Using an indirect selection method based on drug-resistance, we have previously reported the isolation of flat revertants from adenovirus 2 transformed rat cells. Here, we demonstrate that one of these revertants has suffered a mutation in a cellular effector gene specifically required for the adenovirus-mediated expression of the transformed phenotype. Evidence for this conclusion includes the following: (1) the cells contain a 16-times amplified copy of the E1 region, thus reducing the chances of viral mutations, (2) the cells synthesized E1a and E1b proteins indistinguishable from those of the transformed parent, (3) the mutation has been stable for over 2 years, and most importantly (4) the revertant was resistant to re-transformation by E1 but not by c-myc, N-ras or polyoma middle t oncogenes.

3T3 Cells↗

Development of the anchoring structures of the epithelium in rabbit and human fetal corneas.

The sequence of development of the components of the corneal adhesion complex (hemidesmosomes, basal lamina and anchoring fibrils) was studied in rabbit and human fetal corneas using electron microscopy and histochemical localization of type VII (anchoring fibril) collagen. In the rabbit, basal lamina was present at 15 days gestation, followed by hemidesmosomes (HDs) and anchoring fibrils (AFs) at 20 days gestation. Type VII collagen was first localized at 20 days. At 25 days, HDs remained low compared to the adult value. During human corneal development, basal lamina was present at 8 weeks gestation. Through 12 weeks of gestation, no HDs or AFs were discernible nor was there any type VII localization. At 13-19 weeks, HDs and cross-banded AFs were seen, and localization of type VII collagen was first noted. A palisade of filaments extending perpendicularly from the basal lamina into the underlying stroma was discernible from 13 to 27 weeks. A distinct Bowman's layer was present at 19 weeks. By 27 weeks, HDs/micron membrane were greater than or equal to the adult value, and AF penetration into the underlying stroma was also greater than or equal to the adult value. Bowman's layer had not reached adult values by term. These data indicate that after basal lamina deposition, HDs and AFs develop synchronously in both species. In humans the palisade of filaments may be the precursor of Bowman's layer, and the AF network develops within Bowman's layer.

Animals↗

Immunopathology and electron microscopy of Acanthamoeba keratitis.

In order to evaluate the local cellular immune response to Acanthamoeba infection we performed immunohistochemical examinations of the corneal buttons of two patients with Acanthamoeba keratitis. We found that the corneal stroma was infiltrated with polymorphonuclear leukocytes and HLA-DR positive macrophages that appeared to be stromal keratocytes by light microscopy. Despite the presence of chronic inflammation in both patients, no stromal lymphocytes were seen in one patient and a sparse lymphocytic infiltrate was seen in the other patient. Electron microscopy confirmed the presence of macrophages, neutrophils, and Acanthamoeba organisms in these two patients.

Adult↗

Isolation of variants resistant to methylglyoxal bis(guanylhydrazone) from adenovirus-transformed rat cells.

It is presumed that proteins encoded by viral oncogenes interact with proteins encoded by cellular genes to bring about the transformed phenotype. To demonstrate the existence of such cellular genes we attempted to isolate mutants with a nontransformed phenotype from an adenovirus-transformed rat cell line (F4) which contains multiple copies of the transforming E1 region. F4 cells were mutagenized with ethyl methanesulfonate and variants resistant to the anticancer drug methylglyoxal bis(guanylhydrazone) were selected. The proportion of such variants was about one in 10(6) and increased 5-fold after mutagenesis. Two variant clones (G1 and G2) were isolated and characterized: they were 5-fold more resistant to methylglyoxal bis(guanylhydrazone); they had a stable phenotype; they showed decreased drug uptake; they had a reduced ability to grow in soft agar, low serum, and nude mice; there was no detectable change in the restriction pattern of integrated viral genes or in the expression of the E1a and E1b proteins. These properties suggest that selection for methylglyoxal bis(guanylhydrazone) resistance may result in the isolation of variants with phenotypic characteristics of nontransformed cells. It was likely that these variants were altered in a cellular function required for the maintenance of the transformed phenotype.

Adenoviridae↗

Lectin receptors of amyloid in corneas with lattice dystrophy.

We analyzed lectin binding patterns of amyloid glycoconjugates in patients with lattice dystrophy of the cornea. Results of paraffin and frozen sections differed in some instances. With paraffin sections, three lectins--wheat germ agglutinin (WGA), Ricinus communis agglutinin I (RCA-I), and concanavalin A (Con A)--stained the abnormal deposits. In frozen sections, the abnormal deposits were stained by five lectins--WGA, RCA-I, Con A, peanut agglutinin (PNA), and soybean agglutinin (SBA). In paraffin sections, PNA and SBA did not stain amyloid deposits. In both paraffin and frozen sections, some lectin-positive deposits corresponded to the Congo red-positive material, whereas others were present surrounding and encroaching on the Congo red-reactive material. This study demonstrates that WGA-, RCA-I-, Con A-, PNA-, and SBA-positive abnormal deposits are present in corneas with lattice dystrophy. Since lectins bind to specific sugar residues, we conclude that the abnormal deposits consist, at least in part, of glycoconjugates and that these glycoconjugates contain oligosaccharides with N-acetylglucosamine/sialic acid, mannose/glucose and terminal beta-galactose residues and chains with terminal beta-galactose-N-acetylgalactosamine disaccharides.

Adult↗

Retinal insulin receptors. 1. Structural heterogeneity and functional characterization.

Neural cells of the bovine retina contain specific, high-affinity receptors for insulin. When solubilized and wheat-germ purified, these receptors exhibit a kinase activity that is capable of phosphorylating the receptor's beta-subunit (autophosphorylation) and a tyrosine-containing exogenous substrate, poly (Glu, Tyr) 4:1. Studies of the structure of retinal insulin receptors revealed the existence of two insulin receptor subpopulations. For these populations, the apparent molecular weights of the alpha-subunit were 120- and 133 kDa. This structural heterogeneity does not appear to be related to the presence of vascular contamination and stands in contrast to the brain and liver where a single alpha-subunit type was found (120 kDa for brain and 133 kDa for liver). In addition to being distinguishable by their molecular weights, the two populations of retinal insulin receptors could be distinguished in terms of (a) their solubility in Triton X-100, (b) glycosylation, and (c) recognition by anti-insulin receptor antibody. Despite these structural differences, the two populations of retinal insulin receptors appear to have similar insulin binding affinities.

Animals↗

Retinal insulin receptors. 2. Characterization and insulin-induced tyrosine kinase activity in bovine retinal rod outer segments.

Bovine retinal rod outer segments (ROS) possess specific, high-affinity receptors for insulin. These receptors exhibit an insulin-stimulatable tyrosine-specific activity that is capable of phosphorylating the receptor's own beta-subunit and exogenous substrate. ROS insulin receptors exhibit heterogeneity in the apparent molecular weight of the receptor's alpha-subunit. In this regard, insulin receptors from this single cell type resemble insulin receptors obtained from whole retina, but are unlike receptors from brain and liver.

Animals↗

Suprabasal expression of a 64-kilodalton keratin (no. 3) in developing human corneal epithelium.

We have previously shown that a basic 64-kilodalton (no. 3 in the catalog of Moll et al.) and an acidic 55-kilodalton (no. 12) keratin are characteristic of suprabasal cell layers in cultured rabbit corneal epithelial colonies, and therefore may be regarded as markers for an advanced stage of corneal epithelial differentiation. Moreover, using an AE5 mouse monoclonal antibody, we showed that the 64-kilodalton keratin marker is expressed suprabasally in limbal epithelium but uniformly (basal layer included) in central corneal epithelium, suggesting that corneal basal cells are in a more differentiated state than limbal basal cells. In conjunction with previous data implicating the centripetal migration of corneal epithelial cells, our data support a model of corneal epithelial maturation in which corneal epithelial stem cells are located in the limbus, the transitional zone between the cornea and conjunctiva. In the present study, we analyzed the expression of the 64-kilodalton keratin in developing human corneal epithelium by immunohistochemical staining. At 8 weeks of gestation, the presumptive corneal epithelium is composed of a single layer of cuboidal cells with an overlying periderm; neither of these cell layers is AE5 positive. At 12-13 weeks of gestation, some superficial cells of the three- to four-layered epithelium become AE5 positive, providing the earliest sign of overt corneal epithelial differentiation. At 36 weeks, although the epithelium is morphologically mature (four to six layers), AE5 produces a suprabasal staining pattern, this being in contrast to the adult epithelium which exhibits uniform staining.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Immunoelectron microscopic localization of photoreceptor-specific markers in the monkey retina.

Antibodies for several molecules that function in the visual process were used to localize these molecules in primate rod and cone cells. These antibodies (monoclonal or polyclonal) were prepared against Interphotoreceptor Retinoid-binding Protein (IRBP), S-antigen (S-Ag), opsin, alpha-transducin and also against cyclic GMP (cGMP). Lowicryl-embedded tissues were labeled with secondary antibodies linked to colloidal gold. Although IRBP is predominantly an extracellular protein, the relatively small amount found intracellularly was localized mainly in rods, with little in cones. Opsin, S-Ag and cGMP were found mainly in rod cell outer segments. A polyclonal antiserum raised against transducin-alpha purified from rod outer segments predominantly labeled rod cells, but an antiserum against the carboxyterminal decapeptide of transducin-alpha labeled both rod and cone cells. Thus, most of these specialized molecules are present predominantly in rod cells, confirming major differences in components of the visual cycle in rods and cones.

Animals↗

Nephropathic cystinosis: immunohistochemical and histopathologic studies of cornea, conjunctiva and iris.

Specimens of a cornea, conjunctiva and iris were removed at the time of penetrating keratoplasty in a case of nephropathic cystinosis. Immunohistochemical studies revealed the presence of class II antigens on the stromal keratocytes of the cornea and the vascular endothelial cells, pericytes and fibroblasts of the conjunctiva. In addition, there were thinning and focal breaks in Bowman's membrane. Both of these findings may have contributed to the severe photophobia and blepharospasm seen in patients with longstanding cystinosis.

Child↗

Expression of HLA-DR antigen on retinal pigment epithelial cells in retinitis pigmentosa.

Class II (HLA-DR) antigens are cell surface molecules that play a major role in the initiation and perpetuation of immune responses. Although most cells do not constitutively express class II antigens, selected cells can be stimulated to do so in some immunologically mediated disorders. When retinal pigment epithelial cells were evaluated by either immunoperoxidase or immunofluorescent staining of frozen eye sections from normal individuals, HLA-DR antigens were not detected. In contrast, retinal pigment epithelial cells from two patients with retinitis pigmentosa did express HLA-DR antigens. These findings demonstrated that at some time during the course of retinitis pigmentosa, the retinal pigment epithelial cell is activated to express HLA-DR.

Aged↗

Immunochemical distribution of interphotoreceptor retinoid-binding protein in selected species.

An enzyme-linked immunosorbent assay (ELISA) was used to quantitate interphotoreceptor retinoid-binding protein (IRBP) in tissues of monkey and other species using rabbit antiserum against monkey IRBP. A 1:7500 antiserum dilution was found optimal with the linear range extending to 250 micrograms IRBP/ml. The highest IRBP concentration was found in cannulation fluid of the monkey interphotoreceptor space, although vitreous and aqueous humors also contained IRBP. The presence of IRBP in the vitreous was confirmed by Western blot and 3H-retinol binding studies. The pineal gland of monkey and rat also was found to contain IRBP, as assessed by ELISA and immunocytochemistry; IRBP was below the limits of detection in turtle and chicken retina. IRBP levels were uniformly low in retinas of human cases with hereditary retinal degeneration, including retinitis pigmentosa (three cases) and choroideremia (two cases). The presence of IRBP in pineal as well as in the vitreous and aqueous humors may indicate a broader role for this putative retinoid-transport protein than previously suspected.

Animals↗