[Hepatic epithelioid hemangioendothelioma: presentation of a case].
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Biomedical subjects
Publications and source records attributed to J Palacios.
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This study was carried out to evaluate the frequencies of alleles of four polymorphic markers in the 17q21 region in breast cancer patients, and their relation to seven pathological parameters. One hundred and sixty-four patients with breast cancer and 102 controls were analyzed. D17S856, D17S855, D17S1323 and D17S1327 polymorphic markers were studied, and used to investigate loss of heterozygosity in this region. The frequencies of alleles at marker D17S856 differed significantly in breast cancer patients and controls, and were related to histologic features considered to indicate a poor prognosis. When present, the pathophenotype of tumors associated with LOH in the 17q21 region is modified.
The immunohistochemical expression pattern of beta-catenin has been correlated with beta-catenin gene mutations, clinicopathological features, and disease outcome in 69 stage I and II ovarian carcinomas. beta-Catenin expression was localized in the nuclei, in addition to the cytoplasm and membrane, in 11 tumors (16%): nine endometrioid carcinomas with widespread nuclear expression and two serous carcinomas with focal nuclear expression. The remaining 58 carcinomas (84%) only had membranous beta-catenin expression. All but one of the endometrioid carcinomas with nuclear beta-catenin expression had considerable squamous metaplasia, and five of these cases had large areas of endometrioid tumor of low malignant potential. In addition, beta-catenin nuclear expression was observed in atypical epithelial cells in endometriotic glands adjacent to an endometrioid carcinoma. Sequencing was performed on 25 tumors and corresponding normal tissue: all 13 endometrioid tumors as well as 12 carcinomas of other histological types (four serous, two clear cell, two mucinous, and two mixed). There were oncogenic mutations in the phosphorylation sequence for GSK-3beta in exon 3 of the beta-catenin gene in seven endometrioid carcinomas with beta-catenin nuclear expression. Three mutations affected codon 32 (D32G, D32Y, and D32Y), one affected codon 33 (S33C), two affected codon 37 (S37C and S37F), and one affected codon 41 (T41A). No mutations were observed in the other 18 carcinomas analyzed, comprising two endometrioid and two serous carcinomas with beta-catenin nuclear expression, and 14 carcinomas of different histological types with only membranous expression. In the univariate and multivariate survival analyses, beta-catenin nuclear expression was selected as an indicator of good prognosis, because no patient whose tumor expressed beta-catenin in the nuclei showed relapses or died, in contrast to the 19 relapses and deaths among patients with tumors that only had beta-catenin membranous expression, including three of the four patients with endometrioid carcinomas. Oncogenic beta-catenin mutation is characteristic of a group of endometrioid carcinomas with a good prognosis, most of which originate from previous benign or borderline lesions. Endometrioid carcinomas with exclusively membranous expression of beta-catenin seem to represent a different subgroup of carcinomas that probably have a worse prognosis. In early-stage ovarian cancer, determination of the beta-catenin expression pattern could prove to be a useful marker for selecting low-risk patients.
Lactobacillus casei CRL 705, isolated from a dry fermented sausage, produces an antibacterial peptide which is active against Listeria monocytogenes. Previous studies have shown that this compound is potentially useful to control food-borne pathogens in ground meat. In view of the potential application of this antimicrobial substance in food fermentation, a detailed biochemical analysis of this peptide is required. In this work, the purification and amino acid sequence of this bacteriocin is presented. The adsorption-desorption pH-dependent property of lactocin 705 was exploited for purification. The active extract was further subjected to RP-HPLC and SDS-PAGE. The active antimicrobial band was electroeluted from an SDS-PAGE gel and its amino acid sequence determined. Lactocin 705 had an estimated molecular weight of 3357.80 and an isoelectric point of 10.03. The peptide contains a high ratio of glycine residues and does not show any modified amino acids, like lanthionine or beta-methyllanthionine. The sequence was unique when compared to several databases.
Loss of heterozygosity (LOH) in loci of the 17q21 and 13q12-13 regions can collaborate in the inactivation of BRCA1, BRCA2, and possibly other genes implicated in the pathogenesis of breast carcinomas. We investigate allelic losses in microsatellites of the BRCA1 and BRCA2 regions, and their correlations with seven pathologic parameters in 140 breast carcinomas. Those cases showing LOH in the region of the RB gene, 13q14, were excluded from the study. The LOH analysis was performed by amplifying DNA by PCR, using four markers of the 17q21 region (D17S856, D17S855, D17S1323, and D17S1327) and four markers of the 13q12-13 region (D13S290, D13S260, D13S310, and D13S267). LOH in the BRCA1 region was found in 47% of tumors, correlating significantly with estrogen receptor content (p = 0.025), progesterone receptors (p = 0.004), higher grade (p = 0.0008), peritumoral vessel invasion (p = 0.001), and lymph node metastases (p = 0.002). When we excluded the cases with LOH in the BRCA2 region and those not informative for it, the significance disappeared. In the BRCA2 region, a rate of LOH of 51% was found; it correlated significantly with estrogen receptor content (p = 0.002), progesterone receptors (p = 0.03), peritumoral vessel invasion (p = 0.005), higher grade (p = 0.002), and lymph node metastases (p = 0.001). When cases with BRCA1 losses and those not informative were excluded, again the significance disappeared. Concomitant losses in the BRCA1 and BRCA2 regions were found in 32% of cases, correlating significantly with lymph node metastases (p = 0.0002), estrogen receptor content (p = 0.003), progesterone receptors (p = 0.001), histologic grade (p = 0.01), and peritumoral vessel invasion (p = 0.0004). These results suggest that concomitant losses in both regions could have a functional effect, influencing the presence of a poor tumor pathophenotype in breast carcinomas.
Agglutination of fifty bacterial strains isolated from gastric-intestinal tract of chickens with yeasts treated with glutaraldehyde and glycine was assayed to study possible adhesion mechanisms to epithelia. It was found that Lactobacillus fermentum, Lactobacillus fermentum subsp. cellobiosus and Lactobacillus animalis agglutinated yeasts massively and this agglutination was inhibited in each strain by different representative sugars: agglutination was inhibited in three selected strains with 0.2 M mannose. The three strains agglutinated chicken red blood cells, but did not agglutinate human red blood cells, whereas the agglutinating capacity for other animal erythrocytes was variable. The lectins were partially purified on a Sephadex G-75 column and affinity chromatography. The molecular weight of each of the protein subunits was estimated as about 50-67 kDa using electrophoretic techniques. After treatment with lipase and metaperiodate modifications bacterial superficies and/or liberation of some structures produced an unspecific interaction with increase in the yeast agglutination and hemagglutination. The optimal conditions of work were: pH 6-7, Ca2+ 1 mM, Mg2+ 2 mM and 37-42 degrees C.
Rhizobium leguminosarum bv. viciae strain UPM791 induces in symbiosis with peas the synthesis of a nickel-containing hydrogenase which recycles the hydrogen evolved by nitrogenase. The genes required for synthesis of this hydrogenase, hupSLCDEFGHIJKhypABFCDEX, are clustered in the symbiotic plasmid. Analysis of a hypA-deficient mutant showed that HypA is essential for symbiotic hydrogenase activity and required for correct processing of the hydrogenase large subunit. Unlike other microoxically induced hyp genes, the hypA gene was only expressed in pea bacteroids from its own promoter. The hypA mRNA 5' end was mapped 109 bp upstream of the translational start codon. This distinct pattern of expression suggests a different role for HypA and the remaining Hyp proteins in hydrogenase synthesis.
Cs-137 and K-40 have been determined in soil samples and in wild edible mushrooms from a forest ecosystem located at the Nuclear Centre of Mexico (NCM) and in several surrounding localities. The transfer factors for Cs-137 were studied in 21 mushroom species from 1993 to 1997. The Cs-137 and K-40 determinations were performed using a gamma spectrometer system of low level counting with a high purity germanium (HPGe) detector. The local mushroom species that were found to show higher Cs-137 transfer factors were Clavariadelphus truncatus, Cortinarius caerulescens, Gomphus floccosus and Lyophyllum decastes. The Cs-137 levels obtained at the NCM in some mushroom samples were slightly lower than those from surrounding localities indicating that the nuclear facility has not emitted Cs-137 to the atmosphere.
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.
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.
Endocardial mapping has led to a detailed knowledge of reentry mechanisms in atrial flutter. Multipolar and deflecting tip catheters allow recording local electrograms from multiple areas of the right atrium, and from the coronary sinus. In common flutter, with the typical "sawtooth" pattern, there is circular activation of the right atrium in a "counterclockwise" direction, descending in the anterior and lateral walls, and ascending in the septum and posterior wall. Superior and inferior vena cava, linked by a "line" of functional block in the posterolateral wall, make the central obstacle for circular activation. The cranial and caudal turning points are the atrial "roof," and the isthmus between the inferior vena cava and the tricuspid valve. Complex conduction patterns, probably including slow conduction are detectable in the low septal area, around the coronary sinus. Atypical flutter, without the sharp negative deflections of common flutter, sometimes shows circular activation in the right atrium, rotating in the opposite direction of common flutter (clockwise). Other atypical flutters show no circular right atrial activation, and only partial data from coronary sinus activation, combined with the response to atrial stimulation (entrainment) allow the diagnosis of left atrial reentry, without a precise delimitation of the circuits. In patients having undergone cardiac surgery, atypical flutter may be based on reentry around surgical scars. To our knowledge, the mechanism of type II flutter has not been disclosed in humans.
Common atrial flutter is due to reentrant activation of the right atrium, rotating around anatomic structures and areas of functional block, in counterclockwise direction in the frontal plane. The myocardium between the inferior vena cava and the tricuspid valve is critical to close the activation circuit, and ablation of this isthmus by catheter-delivered radiofrequency can interrupt flutter, and eventually destroy the circuit, preventing recurrence of the arrhythmia. Flutter interruption does not mean complete isthmus ablation, and the procedure endpoint is to attain flutter non-inducibility, and isthmus block. Despite non-inducibility, flutter may recur, and new procedures may be needed for complete ablation. Atrial fibrillation can occur in up to 35% of the cases during follow-up but is generally well controlled with drugs that were ineffective against flutter before ablation. Some atypical atrial flutters show circular right atrial activation, using the same circuit in a clockwise direction, and these can also be interrupted by ablation of the inferior vena cava-tricuspid valve isthmus. Other atypical flutters can have different anatomic substrates in the right or left atrium, and mapping has to define specific isthmuses as ablation targets in each case. Left atrial flutter remains inaccessible to ablation.
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.
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)
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.
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.
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.
The mutation of the p53 gene is a common phenomenon in numerous human tumors, leading to the accumulation of nonfunctioning p53 protein in the cell nucleus, which can be detected by immunohistochemistry. In breast cancer, it has been suggested that the overexpression of p53 protein in the nucleus is an indicator of poor prognosis, which must be borne in mind in selecting coadjuvant treatment for each patient. This study is an immunohistochemical analysis of p53 expression in 153 cases of mammary carcinoma, correlating it with histological grade, axillary node status, hormone receptors, cell-proliferation fraction and expression of the c-erbB-2 oncoprotein. Of all the breast-cancer tissue analyzed, 43.79% was positive for p53. The overexpression of this protein bears a direct statistically significant relationship to histological grade, cell-proliferation fraction and c-erbB-2, and an inverse relationship to estrogen and progesterone receptors. No statistically significant relationship was found with axillary node status. The expression of p53 in poorly differentiated tumors-commonly receptor negative and with a high proliferation fraction-may indicate greater tumor aggressiveness and a high risk of relapse.