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Biomedical subjects

C Gamallo

Publications and source records attributed to C Gamallo.

At least 19 recordsLinked to original sources
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↗
PubMed1995

Differential patterns of placental and epithelial cadherin expression in basal cell carcinoma and in the epidermis overlying tumours.

P-cadherin (P-CD) and E-cadherin (E-CD) are expressed by keratinocytes and play an important role in skin morphogenesis. P-CD expression is restricted to the basal layer of normal epidermis, whereas E-CD is expressed in all the living layers. We have previously reported a reduced expression of E-CD in most cases of infiltrative basal cell carcinoma (BCC). In the present work we have investigated by immunohistochemistry the expression of both P-CD and E-CD in a new series of 32 patients with BCC. Most cases of superficial multicentric BCC and some nodular tumours had preserved expression of both cadherins in all tumour cells. The majority of nodular BCCs had partially reduced expression of one or both cadherins with an ordered distribution of cells showing different cadherin staining throughout the tumour mass. A severe reduction of E-CD expression with a disordered distribution of cells with different immunostaining intensity was observed in most specimens of infiltrative BCC. In contrast, P-CD expression was preserved in all cases of infiltrative BCC. These results suggest that P-CD and E-CD play different roles in the growth pattern of BCC. In addition, both anomalous P-CD expression and reduced E-CD expression were frequently observed in the spinous layer of epidermis overlying tumours. This phenomenon was significantly associated with the presence of keratinocytic atypia, which suggests that disturbed cadherin expression could be a marker of premalignant changes and/or hyperproliferative activity in human epidermis.

Aged↗
PubMed1995

A new murine model of severe acute toxoplasma encephalitis.

We have developed a new murine model of toxoplasmic encephalitis based on the intracerebral inoculation of tachyzoites of the highly virulent RH strain of Toxoplasma gondii. Intracerebral infection resulted in a mortality of 100% on day five. Large inflammatory abscessed infiltrates developed by the second day after inoculation and expanded throughout the remaining period of observation. Numerous tachyzoites were detectable in brain parenchyma by the second day of infection. The marked and precocious histopathological brain lesions produced by the RH strain are useful to detect therapeutic rather than prophylactic effects of drugs against toxoplasmic encephalitis. In this model pyrimethamine, sulphadiazine and its combination were useful in terms of mortality, histopathology and spread of infection whereas clindamycin showed no activity. This murine model of toxoplasmic encephalitis is useful to evaluate antitoxoplasma agents with high therapeutic activity.

Acute Disease↗
PubMed1995

p53 protein expression in viral warts from patients with epidermodysplasia verruciformis.

The p53 protein is the product of a tumour suppressor gene, which is implicated in many human malignancies. p53 expression was investigated by immunohistochemistry in a series of viral warts (n = 12) from five patients with epidermodysplasia verruciformis (EV), using a monoclonal anti-p53 antibody (DO7). p53 expression was also investigated in a series of common warts (n = 8), flat warts (n = 8), and penile bowenoid papulosis (n = 6) from non-EV patients. Immunostaining was positive in 11 of 12 (92%) EV warts, whereas p53 reactivity was negative in most cases of warts from non-EV patients. Exons 5-8 of the p53 gene were screened by the polymerase chain reaction-single strand conformation polymorphism technique in four EV warts, which were strongly stained for p53, and p53 mutations were not detected. These results suggest an association between p53 accumulation (probably of wild type) and EV warts.

Epidermodysplasia Verruciformis↗
PubMed1995

Anomalous expression of P-cadherin in breast carcinoma. Correlation with E-cadherin expression and pathological features.

Previous studies on the cell-cell adhesion molecules P- and E-cadherin have shown that P-cadherin is not expressed in breast cancer. In contrast, the expression of E-cadherin is a normal event in these tumors, but a reduction in the levels of this molecule in neoplastic cells is associated with the histological type, high histological grade, greater tumor size, and metastasis. The expression pattern of P- and E-cadherin were immunohistochemically studied in tissue sections from normal breast tissue, benign breast lesions, and 57 infiltrating breast carcinomas. Cadherin expression was analyzed in parallel with pathological features and the immunohistochemical expression of estrogen and progesterone receptors in breast carcinomas. P-cadherin was detected in the myoepithelial cells and E-cadherin in luminal epithelial cells from normal breast and benign breast lesions. P-cadherin expression was detected in 9 of 45 cases (20%) of infiltrating ductal carcinomas of no special type; none of the special histological types that were analyzed (7 infiltrating lobular carcinomas, 3 colloid carcinomas, and 2 infiltrating papillary carcinomas) expressed P-cadherin. In infiltrating ductal carcinomas, P-cadherin expression correlated significantly with a reduction in E-cadherin expression, histological grade (all cases were grade III tumors), and hormone receptor content (8 of 9 cases were estrogen and progesterone receptor negative). Although E-cadherin was not found in the 7 infiltrating lobular carcinomas, it was present in the remaining histological types and was preserved in 15 infiltrating ductal and 3 colloid and 2 papillary carcinomas and was reduced in 30 infiltrating ductal carcinomas. In addition, a reduction in E-cadherin expression was significantly associated with high histological grade and a lack of steroid hormone receptors in infiltrating ductal carcinomas. No apparent relationship was found between P- and E-cadherin expression and tumor size and axillary lymph node metastasis. The distinct patterns of P- and E-cadherin expression observed in this study strongly suggest a differential role for these cadherins in human breast carcinogenesis.

Actins↗
PubMed1995

[A retrospective study of delta F508 mutation in 22 patients operated on for meconium ileus].

Meconium ileus is the earliest clinical manifestation of cystic fibrosis. We report 22 neonates with meconium ileus who had clinical evidence of cystic fibrosis. Patients were categorized as simple with inspissated meconium in the ileum with dilated loops proximally or complicated with volvulus or atresia and/or a perforation resulting in meconium peritonitis. Histopathology of the surgically resected specimens of small bowel revealed lesions typical of cystic fibrosis. Genetic studies were performed on all subjects, this study analyzes the usefulness in the detection of delta F508 mutation in formalin-fixed paraffin-embedded tissues obtained from patients with meconium ileus, ten of whom had the delta F508/delta F508 mutation.

Cystic Fibrosis↗
PubMed1995

[Pulmonary granulomatosis caused by lentil aspiration].

Pulmonary nodular granulomatosis caused by aspirated lentils is a rare entity. We report the case of a healthy 8 years-old girl who suffered a choking life-threatening choking event during a meal, with cardiorespiratory arrest. After a delay of one month delay without symptoms, she developed respiratory distress with radiologic changes. Lung biopsy disclosed foreing body granulomas. Steroids were not used because of their uncertain effectiveness in these cases. One year later the patient's progress was satisfactory.

Child↗
PubMed1995

Chronic exposure of cultured transformed mouse epidermal cells to transforming growth factor-beta 1 induces an epithelial-mesenchymal transdifferentiation and a spindle tumoral phenotype.

Transformed mouse epidermal keratinocytes of the cell line PDV, when cultured under the presence of transforming growth factor-beta 1 (TGF-beta 1), escaped the block of growth exerted by this factor in normal keratinocytes and underwent marked changes in cell differentiation. TGF-beta 1 induced disruption of epithelial interactions, dispersion of cells, increased local movement, and conversion to a fibroblast-like morphology. These changes were reversible and correlated with down-regulation of epithelial protein markers such as E-cadherin and cytokeratins and upregulation of vimentin. TGF-beta 1-treated cells with a fibroblast-like phenotype induced spindle cell carcinomas upon transplantation in athymic nude mice, whereas untreated PDV cells or fusiform cells reverted to the epithelial phenotype and produced well-differentiated squamous cell carcinomas. Nontumorigenic immortalized epidermal keratinocytes, when grown under the presence of TGF-beta 1, did not transdifferentiate to a mesenchymal phenotype, their proliferation was blocked, and cells finally died. These results suggest a role of TGF-beta 1 in the progression of squamous carcinoma cells to spindle carcinomas in mouse skin carcinogenesis.

Animals↗
PubMed1995

Differential spatiotemporal expression of E- and P-cadherin during mouse tooth development.

Changes in E- and P-cadherin (E- and P-CD) expression during embryonic mouse first molar development were analyzed by immunohistochemistry. During the induction and morphogenesis stages (bud, cap and early bell stages), E-CD was expressed in the cells of the invaginating epithelial tooth bud and in the cells of the outer enamel epithelium, stellate reticulum and stratum intermedium, suggesting a role for this molecule in the maintenance of enamel organ architecture. On the other hand, P-CD was strongly expressed in the inner enamel epithelium suggesting its participation in the processes of mesenchymal induction. during the cytodifferentiation stage (late bell stage), E-CD was expressed in polarizing preameloblasts, but cadherin expression was restricted to the basal and apical poles of differentiated secretory ameloblasts, where the zonula adherens type of cell-cell junctions is located. The present study demonstrates for the first time the spatiotemporal expression of cadherins during tooth development and suggests differential and specific roles for E-CD and P-CD during the morphogenesis and cytodifferentiation processes of this organ.

Animals↗