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Biomedical subjects

C Gamallo

Publications and source records attributed to C Gamallo.

At least 19 recordsLinked to original sources
PubMed1998

Mutations in the beta-catenin gene (CTNNB1) in endometrioid ovarian carcinomas.

Mutations of the beta-catenin gene (CTNNB1) have recently been implicated in the initiation of some colon carcinomas and melanomas. In these tumors, beta-catenin abnormally accumulates in the cell nuclei. In an ongoing immunohistochemical study of the cadherin-catenin complex protein expression in ovarian carcinomas, we observed beta-catenin in tumor cell nuclei in some cases; this prompted us to study whether or not this abnormal immunostaining pattern was due to mutation in the beta-catenin gene itself. This study examines beta-catenin immunohistochemical expression in 40 stage I and II ovarian borderline tumors and carcinomas of the most common histological types. Membrane expression was heterogeneous in all 40 cases. However, the cytoplasm and nucleus of five (one borderline tumor and four carcinomas) of the six endometrioid lesions contained beta-catenin expression. PCR and sequencing analyses of a 200-bp fragment of exon 3 of the CTNNB1 gene, encompassing the sequence for glycogen synthetase kinase-3beta phosphorylation, were performed in 11 tumors. Heterozygous substitution mutations at codon 37 in two cases (S37F and S37C) and at codon 41 in one case (T41A) were found in three endometrioid lesions (one borderline tumor and two carcinomas) with abnormal beta-catenin expression. Three endometrioid carcinomas and five tumors of other histological types analyzed showed normal DNA sequences. These results implicate beta-catenin gene mutations in ovarian malignant transformation with a characteristic phenotype: endometrioid ovarian carcinoma.

Carcinoma, Endometrioid↗
PubMed1998

Cytologic features of synovial sarcoma with emphasis on the monophasic fibrous variant: a morphologic and immunocytochemical analysis of bcl-2 protein expression.

BACKGROUND: Monophasic fibrous synovial sarcoma (SS) is the most common variant of SS but few cytologic studies concerning this entity are available. bcl-2 protein immunoexpression has been described as a characteristic marker of SS and is useful for its differentiation from other sarcomas. METHODS: Twelve cytologic specimens from 11 patients with histologically proven SS were reexamined. Ten samples were obtained by fine-needle aspiration and in two cases fluid from cystic tumoral areas was obtained at surgery. Nine cases corresponded to monophasic fibrous tumors and two to biphasic tumors. Immunoexpression of bcl-2 was evaluated in all histologic specimens and in six cytologic samples. bcl-2 protein also was evaluated in 13 soft tissue tumors. RESULTS: All cytologic specimens had a similar appearance. Most smears were highly cellular and were comprised of densely packed, tridimensional groups and numerous isolated, round to oval cells. Remarkable findings included cellular monomorphism and vascular structures within the cell groups. Only one case showed cytologic evidence of epithelial differentiation. Immunoexpression of bcl-2 protein was present in 10 of the 11 histologic specimens (90.9%) and in 5 of the 6 cytologic samples (83.3%). A positive result also was observed in malignant fibrous histiocytoma, dermatofibrosarcoma protuberans, infantile hemangiopericytoma, pleomorphic liposarcoma, and malignant solitary fibrous tumor. CONCLUSIONS: Although cytomorphologic features of SS are characteristic enough to permit its recognition, clinical correlation is necessary for its correct diagnosis. The immunoexpression of bcl-2 protein is not specific of SS and other soft tissue tumors can show a similar positive reaction.

Adolescent↗
PubMed1998

Are genotypes of Trypanosoma cruzi involved in the challenge of chagasic cardiomyopathy?

Myocardial damage in Chagas' disease differs, depending on the particular Trypanosoma cruzi stock. It is reasonable to expect that the extent of phylogenetic divergence between lineages will have an impact on the biological properties of the parasite. The aim of the present work was to evaluate this impact on the cardiac damage produced by this protozoan. Heart histopathologic lesions were studied in mice infected with 15 cloned stocks of T. cruzi of various origins pertaining to 3 major clones or genotypes (19, 20, and 39) that share 3 different profiles for a given set of genetic markers. Sets of mice were infected intraperitoneally with 10(6) blood trypomastigotes of each of the T. cruzi clones. The macroscopy study showed a cardiac index (CI) higher than 0.6 (cardiomegaly) in 5 of the 15 stocks studied (33.33%). Inflammatory infiltrates appeared in stocks pertaining to the three genotypes studied without relation to the genetic pattern. Pseudocysts were present at higher levels (83%) in stocks pertaining to genotype 39. A lower rate could be seen in stocks pertaining to genotype 19 (50%). Only one stock pertaining to genotype 20 presented myocardial parasites (20%). Hearts were also studied for lesions in the different cardiac chambers. Inflammatory foci as well as pseudocysts appeared mainly in ventricles, with the left ventricle sharing the highest percentage of pathologic findings. In summary, in spite of the similar inflammatory pattern demonstrated for all stocks studied, the parasite's presence seemed to be related to the genotype of reference, but no relation could be demonstrated with the genetic distances.

Animals↗
PubMed1998

Relationships between histopathological findings and phylogenetic divergence in Trypanosoma cruzi.

Problems have been raised by natural genetic diversity of Trypanosoma cruzi, the causal agent of Chagas' disease, and other protozoa in terms of both basic and applied science. T. cruzi manifests a great diversity of medical and biological properties which could be the origin of clinical variability in the disease. We propose possible correlations between genetic distances, or phylogenetic divergence, and histopathological data. To ascertain this aspect, 15 cloned stocks pertaining to three major clones or genotypes (19, 20 and 39) were compared. Sets of 24 mice infected with each stock were studied for histopathological lesions. Brain, heart, lung, liver, spleen, urinary bladder, bone marrow, colon, kidney and skeletal muscle were extracted from each mouse. Qualitative and quantitative differences showed at histopathological examination. An important encephalic softening was found in brains of most mice infected by genotype 20, corresponding to areas of inflammation and liquified necrosis. Other inflammatory tissue lesions in the histological sections of the three genotypes were similar. Skeletal muscle tropism was higher than cardiac tropism in all the studied genotypes. All three genotypes shared parasite presence in skeletal muscle. Differences related to cardiac tropism were important: in genotype 19, 50% of studied stocks presented pseudocysts; 20% in genotype 20 and 83% in genotype 39. Parasite presence in other tissues was scanty: in brain only in genotype 20 and in spleen and liver only in genotype 39. We found important histopathogenicity differences among the three studied genotypes, but they do not support the hypothesis of zymodeme pathogenic specificity due to the great diversity among stocks within each genotype.

Animals↗
PubMed1997

Linomide administration to mice attenuates the induction of nitric oxide synthase elicited by lipopolysaccharide-activated macrophages and prevents nephritis in MRL/Mp-lpr/lpr mice.

Nitric oxide is involved as a messenger molecule in a large number of physiologic and pathologic responses. Local generation of high nitric oxide output through the expression of the calcium-independent, cytokine-inducible form of nitric oxide synthase (iNOS) can result in either protective or damaging effects. The development of drugs that specifically suppress iNOS expression or inhibit its activity may therefore provide an excellent therapeutic tool for treatment of a diverse set of dysfunctions, including asthma, inflammatory processes, and autoimmune disease. We show compelling evidence that linomide, an immunomodulator known to ameliorate autoimmune diseases, prevents accumulation in the macrophages of mRNA encoding iNOS in mice injected with LPS. This effect is partially mediated by the blocking of TNF-alpha and IL-beta production by activated macrophages. Here, we also present evidence that kidneys from MRL/Mp-lpr/lpr mice express high iNOS levels when the mice develop glomerulonephritis. The administration of linomide to MRL/Mp-lpr/lpr mice significantly decreases iNOS mRNA levels and prevents the development of glomerulonephritis, extending the half-life of mice of this strain. This linomide effect is compatible with its role in preventing the development of autoimmune disease and extends its possible use to other pathologic manifestations associated with iNOS expression, such as the systemic lupus erythematosus-associated glomerulonephritis present in MRL/Mp-lpr/lpr mice.

Adjuvants, Immunologic↗
PubMed1997

Induction of PA2.26, a cell-surface antigen expressed by active fibroblasts, in mouse epidermal keratinocytes during carcinogenesis.

The monoclonal antibody PA2.26, produced against mouse epidermal keratinocytes transformed with 7,12-dimethylbenz[a]anthracene (DMBA), recognizes a 43- to 47-kDa cell-surface protein that was absent from non-tumorigenic epidermal keratinocytes but present in transformed epidermal cell lines as well as cultured normal fibroblasts. In vivo, the antigen was absent from normal epidermis but induced in basal-like epidermal keratinocytes and dermal fibroblasts during tissue regeneration after wounding and treatment with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). The PA2.26 protein was also expressed in basal-like cells of differentiated papillomas and carcinomas generated in mice treated with DMBA and TPA. In addition, the antigen was abundantly synthesized by stromal cells of the tumors. These results suggest that PA2.26 antigen is involved in reactive processes during skin remodeling and carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

Trypanosoma rangeli: increase in virulence with inocula of different origins in the experimental infection in mice.

We compared two murine models of Trypanosoma rangeli infection. The same inoculum dose and age-matched hosts were used in both cases. One group was infected with trypomastigotes obtained from passages in mice and the other, with trypomastigotes obtained from cell culture after a passage in mice. We observed that trypomastigotes obtained from the in vitro cellular infection showed increased virulence in experimental animals, with a 70% rate of death being noted in experimental mice instead of the lack of mortality seen when in vivo-derived parasites were used. The greatest levels of parasitemia and tissual lesions in the presence of the parasite also occurred when in vitro-derived parasites were used.

Animals↗
PubMed1997

[Nonbacterial thrombotic endocarditis: a review of a necropsy series].

Nonbacterial thrombotic endocarditis (NBTE) is characterized by the deposition of thrombi on undamaged heart valves and by the increased frequency of associated arterial embolic events in patients with chronic debilitating diseases. Fifteen subjects diagnosed by necropsy of nonbacterial thrombotic endocarditis (NBTE) were studied to evaluate the general features, associated diseases, arterial embolic events, distribution and characteristics of histologic lesions. The most common underlying disease was neoplasm, which was present in 10 cases. Of these, 6 were adenocarcinomas, 3 hematological, and the remaining case was a bladder carcinoma. Other associated diseases included amyloidosis, MELAS syndrome, and sepsis. In most cases peripheral arterial embolic events were detected (9 cases). The central nervous system and the lung were involved in 7 cases (78%), heart and kidneys in 5 cases (56%), and spleen in 4 cases (44%). Other involved organs included pancreas, thyroid gland, testicles, meninges, liver and adrenal glands. The left valves were predominantly involved. The mitral valve in eight cases and the aortic valve in six cases. All cases with right involvement had the antecedent of central venous catheterization. Subendothelial fibrosis was a common histological finding which revealed the chronicity of the disease.

Adolescent↗
PubMed1997

Protective effect of Trypanosoma rangeli against infections with a highly virulent strain of Trypanosoma cruzi.

We investigated the protective effect of Trypanosoma rangeli against infection with Trypanosoma cruzi in animal models of various ages and with different doses of inoculum. The age of the mice and the dose of parasites determined the course of the infection. When T. cruzi was inoculated into mice after challenge with T. rangeli, parasitaemia was more controlled, mortality decreased and histopathology showed lower inflammatory infiltration and pseudocysts. This study proposes a new murine model of the protective effect of recombinant proteins of T. rangeli for possible application in the vaccines field.

Age Factors↗
PubMed1996

Expression pattern of the cell adhesion molecules. E-cadherin, P-cadherin and alpha 6 beta 4 intergrin is altered in pre-malignant skin tumors of p53-deficient mice.

Expression of the cell adhesion molecules E-cadherin, P-cadherin and alpha 6 beta 4 integrin and of the keratin K13 has been analyzed in chemically induced benign skin papillomas with genetically pre-determined risks for malignant conversion. It has been previously shown that papillomas induced in mice lacking both alleles of the p53 gene have a much higher rate of malignant conversion than those induced in wild-type and heterozygous p53 mice. Alterations in the expression pattern of the E-cadherin molecule, including focal loss at cell-cell contacts and heterogeneous distribution in the differentiated layers, were found in about 70% of the p53 null papillomas. In contrast, all of the wild-type and over 85% of the heterozygous p53 papillomas exhibited an expression pattern of E-cadherin indistinguishable from that of normal epidermis. Alterations in P-cadherin expression were also detected in the p53 null papillomas: aberrant suprabasal localization and heterogeneous distribution were observed more frequently than in heterozygous and wild-type p53 papillomas. The alpha 6 beta 4 integrin showed suprabasal expression in more than 70% of the papillomas derived from either wild-type, heterozygous or homozygous p53 null mice. Surprisingly, the extent of the suprabasal localization of alpha 6 beta 4 decreased in the p53 null papillomas. Aberrant keratin K13 expression was also detected in the majority of cases of all p53 genotypes, but again there was a clear decrease in expression levels in the p53 null papillomas. These alterations were also associated with keratinocytic atypia, which increased significantly in the p53 null papillomas. Changes in these parameters were particularly evident during malignant conversion in invasive regions of one progressing p53 null papilloma. Our results indicate the existence of dynamic changes in the expression pattern of the 3 cell adhesion molecules analyzed and identify down-regulation of E-cadherin as an early step in malignant conversion.

Animals↗
PubMed1996

Suppression of the metastatic phenotype of a mouse skin carcinoma cell line independent of E-cadherin expression and correlated with reduced Ha-ras oncogene products.

The HaCa4 cell line, derived from a mouse skin carcinoma induced by Harvey murine sarcoma virus, is highly tumorigenic when injected into nude mice and produces multiple metastases in the lungs. HaCa4 cells express high levels of viral Ha-ras oncogene products, anomalously synthesize the embryonic/simple epithelial keratin K8, and have lost the expression of the cell-cell adhesion receptor E-cadherin (E-CD). E-CD(+) cell clones (E62 and E24), obtained by transfection of an exogenous E-CD cDNA into HaCa4 cells, had a decreased ability to migrate through type IV collagen matrices. However, the E-CD (+) E62 clone remained as metastatic as the parental cell line, whereas the E24 clone, which does not take up the exogenous cDNA but spontaneously switches on the endogenous E-CD gene, suppressed the metastatic phenotype although it maintained its tumorigenicity. E24 cells had fivefold to sixfold lower levels of viral Ha-ras mRNA and p21 protein than the other cell lines. In addition, they did not synthesize K8 but rather switched on keratin K19. The comparison of E-CD proteins synthesized by E62 and E24 cell lines revealed no structural or functional differences because both localized at cell-cell contacts and associated with alpha-catenin, beta-catenin, and plakoglobin. Furthermore, E-CD was still expressed in metastatic lung nodules produced by E62 cells. These results suggest that suppression of the metastatic phenotype in E24 cells occurs independently of E-CD expression and correlates with decreased levels of the oncogenic ras p21 protein.

Animals↗
PubMed1996

Primary cranial vault lymphoma mimicking meningioma.

Primary lymphomas of the cranial vault are rare; only six patients have been described in the literature. We report a 75-year-old woman who was admitted to our hospital after a focal seizure. CT showed a homogeneous mass which, on contrast enhancement, was similar to a meningioma. The tumour was excised and found to be a centroblastic, centrocytic non-Hodgkin's lymphoma. Treatment was completed with radiotherapy and chemotherapy.

Aged↗
PubMed1995

Cell surface molecules related to factor J in human lymphoid cells and cell lines.

Factor J (FJ) is a cationic glycoprotein that is able to inhibit in vitro both the classical and alternative pathways of complement. FJ was purified to homogeneity from human urine by sequential chromatographic steps. To examine the expression of FJ in human cells we obtained mAbs against urine-purified FJ. Preliminary studies by immunocytochemistry revealed that one of the anti-FJ mAbs recognized cell surface components of certain cell lines, such as K562 and U937 cells, so we have focused subsequently on the detection of these homologue membrane-bound FJ Ags (FJ-h Ags) in cell lines of lymphoid (Ramos and Jurkat) and mieloyd (U937 and K562) origin, as well as in peripheral blood cells. The flow cytometry analysis of the examined cell lines revealed partial staining ranging from 10% (U937) to 29% (K562) positive cells. Flow cytometry of peripheral blood cells showed a positive staining in a small but consistent population of lymphocytes (mean = 11%, n = 17) but none at all on monocytes, granulocytes, erythrocytes, or platelets. Double Ab immunostaining of lymphocytes showed that the FJ-h positive population included mainly B lymphocytes (a mean of 63% CD19+ were FJ-h positive). When we analyzed peripheral blood lymphocytes from a patient with chronic lymphocytic leukemia B (95% CD19+/CD5+), the majority of these (55%) bore FJ-h on their surface. Acid strip of these cells did not abrogate the surface staining, which supports the finding that the Ag is tightly bound to the membrane. Immunoprecipitation from U937 cell lysates showed a single 65 kDa band under reducing conditions. FJ-h Ags purified from K562 and U937 cells displayed inhibitory activity in the functional EAC14 assay for the classical complement pathway, as did urine FJ, and they were recognized immunochemically by five different (one polyclonal and four monoclonal) anti-FJ Abs. In conclusion, FJ-homologues are present in the membranes of several human cell lines that show functional and antigenic characteristics similar to soluble urine FJ. They are also found in a small subset of peripheral blood lymphocytes, mainly B cells. The structural relationship between both soluble urine FJ and these membrane-bound FJ-h remains to be established.

Animals↗
PubMed1995

Relationship between ERBB2 and E-cadherin expression in human breast cancer.

A recent in vitro study has suggested that overexpression of ERBB2 may mediate breast tumour progression and metastasis by inhibiting the transcription of the E-cadherin (E-CD) gene. To test this hypothesis in human breast cancer in vivo, we studied the relationship between the expression of both molecules in 247 breast carcinomas immunohistochemically. Five ductal carcinomas in situ overexpressed ERBB2 and showed preserved E-CD expression. Forty-four of 226 infiltrating ductal carcinomas (19.47%) showed ERBB2 overexpression, and a statistically significant relationship was found between ERBB2 overexpression and high histological grade. E-CD expression was preserved in 111 cases (49.1%) and correlated with the histological grade. However, no significant relationship was found between ERBB2 and E-CD expression. None of the 16 infiltrating lobular carcinomas expressed ERBB2 or E-CD. These observations in different histological types of breast carcinoma strongly argue against a role for ERBB2 as a transcriptional regulator of E-CD expression in most human breast carcinomas in vivo.

Breast Neoplasms↗
PubMed1995

Fluorescence of mast cell granules in paraffin sections and cell smears induced by an N-quaternary oxazole scintillator.

The N-quaternized derivative of dimethyl-POPOP (termed Q4) induces a bluish-green fluorescent reaction in mast cell granules from paraffin sections and cell smears, in addition to a previously described bluish-white fluorescent reaction in chromatin DNA. The chromatin reaction was abolished by staining the samples either with Mayer's Haematoxylin before Q4 treatment or by Q4 treatment at pH 1.5. The reaction in mast cell granules was absent after substrate methylation. The staining sequence Haematoxylin-Eosin-Q4 also worked well in paraffin sections, allowing the observation of the current histological image under bright-field illumination as well as double-colour emission under fluorescence microscopy. The sequence is proposed as a new diagnostic procedure for demonstrating mast cell granules.

Animals↗
PubMed1995

Ethanol intake, plasma catecholamine levels, and ST-segment changes without myocardial injury in rats with short-term ethanol consumption.

The authors studied the effect of short-term ethanol consumption on the ST-segment and the association between ST-segment changes and the amount of daily ethanol intake and levels of plasma catecholamines. The study used 63 rats (control group n = 20, study group n = 43). The rats in the study group were exposed for 6 days to progressively larger doses of ethanol followed by 15 days of continuous exposure to ethanol. At baseline an electrocardiogram (ECG) was recorded, and on day 25 the ECG was repeated and plasma catecholamine levels were measured. The animals' hearts were removed and processed for histologic study. Repolarization abnormalities were observed in 68% of the ethanol-consuming rats. Two factors differentiated the subgroup of ethanol-consuming rats with ST-segment changes from the subgroup without ST-segment changes: amount of daily ethanol intake (0.0077 +/- 0.02 mL/g/d vs 0.0058 +/- 0.019 mL/g/d) and plasma epinephrine levels (3,881 +/- 733 pg/mL vs 1,478 +/- 406 pg/mL). No myocardial damage was detected. Our results suggest that in ethanol-consuming rats, high-volume daily ethanol intake and increased plasma catecholamines may mediate changes in the ST-segment.

Animals↗
PubMed1995

Prenatal growth of the human mandibular condylar cartilage.

The question of whether the condylar cartilage possesses a growth potential like that of the long bone growth plates has been the subject of contrasting viewpoints. We have recently established that the thickness of the human tibial growth plate progressively decreases during the second half of the fetal period, but that the changes in the total human condylar thickness do not correlate with fetal age or weight. The present study examined the change in the thickness of the human mandibular condyle layers during the fetal growth of the mandible. Mandibles were obtained from autopsy of 19 human fetuses ranging in fetal age from 18 to 41 weeks. The total length of the mandible, the lengths of the mandibular body and of the ramus were measured, as well as the gonial angles. The total thickness of the condyle, and the thickness of the articular, progenitor, cartilage, chondroblast, and hypertrophic chondrocyte layers were measured on the central segment of central sagittal sections of the mandibular condylar cartilage. The total mandible, the corpus and the ramus lengths increased linearly with the age of the fetus and they all correlated strongly with fetal weight. However, changes in the total condylar thickness and in the thickness of the cartilage layer (chondroblast plus hypertrophic chondrocytes) did not correlate with fetal weight or mandibular length. The thickness of the articular layer increased with weight, but changes in the progenitor layer were independent of corporal and mandibular growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Cartilage, Articular↗