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J Palacios

Publications and source records attributed to J Palacios.

At least 19 recordsLinked to original sources

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

Atrial flutter mapping and ablation. I. Studying atrial flutter mechanisms by mapping and entrainment.

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.

Atrial Flutter

Radiofrequency catheter ablation of atrial flutter circuits.

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.

Atrial Flutter

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

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

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

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

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

p53 in breast cancer. Its relation to histological grade, lymph-node status, hormone receptors, cell-proliferation fraction (ki-67) and c-erbB-2. Immunohistochemical study of 153 cases.

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.

Adult

[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

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

Lethal Pallister-Killian syndrome: phenotypic similarity with Fryns syndrome.

The Pallister-Killian syndrome is a sporadic multiple congenital anomaly syndrome characterized by "coarse" face, profound mental retardation, and epilepsy. Chromosomes of peripheral lymphocytes are usually normal, but tissue cultures show varying degrees of mosaicism for isochromosome 12p. In babies who die neonatally of severe malformations, including diaphragmatic hernia, and who also have a "coarse" face, acral hypoplasia, and other internal anomalies, Fryns syndrome is more likely to be suspected than Pallister-Killian syndrome, especially if karyotyping is unavailable or if peripheral lymphocytes have a normal chromosome constitution. An initial diagnosis of Fryns syndrome had to be modified in 3 successive newborn infants since chromosome analysis or in situ hybridization with a chromosome 12 probe on kidney tissue demonstrated the mosaic aneuploidy characteristic of Pallister-Killian syndrome. These 3 patients confirm that a similar pattern of malformations can be present in both conditions at birth. It consists of "coarse" face, acral hypoplasia, diaphragmatic hernia, and other defects. Newborn infants who present this phenotype, but lack a conclusively normal chromosome test, may not have Fryns syndrome. A diagnosis of Fryns syndrome should be made carefully to avoid the risk of inappropriate genetic counseling.

Abnormalities, Multiple

E-cadherin expression in basal cell carcinoma.

E-cadherin (E-CD) is a calcium-dependent cell-cell adhesion molecule which is expressed in almost all epithelial tissues. E-CD expression is involved in epidermal morphogenesis and is reduced during tumour progression of mouse epidermal carcinogenesis. It has been suggested that E-CD could play a role as an invasion-suppressor molecule. In the present work we have studied the E-CD expression in 31 patients with basal cell carcinoma (BCC) using an immunohistochemical technique with a monoclonal antibody (HECD-1) specific for human E-CD. E-CD expression was preserved in all specimens of superficial and nodular BCC, and was reduced in 10 of 15 infiltrative BCCs. A heterogeneous distribution of cells with different immunostaining intensity was more frequently observed in specimens of infiltrative BCC. These results suggest that E-CD might be related to the growth pattern and the local aggressive behaviour of BCC, and support the idea that E-CD might play a role as an invasion-suppressor molecule in vivo.

Adult

Mechanisms of entrainment of human common flutter studied with multiple endocardial recordings.

BACKGROUND: The mechanisms of common atrial flutter entrainment have not been directly studied in humans. METHODS AND RESULTS: Endocardial mapping in six cases of common flutter showed large right atrial (RA) reentry circuits. Activation was craniocaudal in the anterolateral right atrium and caudocranial in the septum. The inferior vena cava-tricuspid isthmus (IVC-TV) closed the circuit. The high right atrium was paced at progressively shorter cycle lengths (CLs) in all, and the IVC-TV was paced in three cases. We recorded six to eight simultaneous RA electrograms from septum and anterior wall. Transient entrainment was recognized from all sites by capture of all electrograms at two or more paced CLs, with total or partial preservation of baseline flutter sequence and return to baseline after pacing. Antidromic circuit penetration was documented in five cases during high RA pacing and in one with IVC-TV pacing. Short CLs induced orthodromic conduction delays that resulted in a postpacing pause longer than basal flutter CL. ECG fusion with high RA pacing correlated poorly with antidromic septal penetration. This was related to overlap of orthodromic septal activation with anterior wall activation of the following cycle. Pacing disorganized flutter into a brief irregular rapid rhythm in two cases and atrial fibrillation in one case. In two cases, complete antidromic septal penetration led to sudden flutter interruption, and in another case it led to circuit inversion. CONCLUSIONS: Direct recordings confirm orthodromic and antidromic penetration of flutter circuits by high and low RA pacing. Short CLs modify the circuit. Disorganization is the most common mode of flutter interruption.

Aged

Hormonal receptors, cell proliferation fraction (Ki-67) and c-erbB-2 amplification in breast cancer. Relationship between differentiation degree and axillary lymph node metastases.

In view of the limitations of conventional prognostic factors such as differentiation degree, metastatic lymph nodes, hormonal receptors and others, especially when early lesions are found, additional new markers have been studied, such as gene amplification and cell proliferation index, in order to choose the appropriate treatment. Primary breast carcinoma tumors from 97 patients were examined for differentiation degree, metastatic lymph nodes, hormonal receptors, c-erbB-2 amplification and cell proliferation index (Ki-67). A negative relationship with hormonal receptors and c-erbB-2 amplification, Ki-67 and differentiation degree was found, whereas the relationship between c-erbB-2, Ki-67 and differentiation degree was positive. No relationship was found between these factors and metastatic lymph nodes. The concurrence of high cell proliferation index, c-erbB-2 amplification and negative hormonal receptor presence would indicate a subpopulation with a high risk of recurrence. But a larger survival study is necessary to correlate these factors with clinical outcome.

Adult

Detection of delta F508 cystic fibrosis mutation by polymerase chain reaction from old paraffin-embedded tissues: a retrospective autopsy study.

This study analyzes the usefulness of the polymerase chain reaction technique in the detection of delta F508 mutation in 11- to 25-yr-old formalin-fixed paraffin-embedded tissues obtained from the autopsy of 38 cystic fibrosis patients (nine with meconium ileus). Two different pairs of oligonucleotide primers were used: C16 B/C16 D that amplify 98 and/or 95 bp and FQ1/FQ2 that amplify 50 and/or 47 bp. After two independent rounds of polymerase chain reactions with the two sets of primers, amplification products were obtained in 67.5% of the cases when using C16 B/C16 D primers and in all cases when using FQ1/FQ2 primers. Fifty percent of the chromosomes analyzed in the 29 patients without meconium ileus had the delta F508 mutation, which was present in 13 heterozygous and 8 homozygous patients. The remaining eight cystic fibrosis patients did not carry that mutation. These results are similar to those reported in cystic fibrosis patients from Spain. In the meconium ileus group, we found a higher than expected proportion of delta F508 mutation; all patients showed the delta F508 mutation in at least one chromosome, seven patients (77.8%) being homozygous and two (22.2%) heterozygous. Present results indicate that delta F508 mutation can be detected by polymerase chain reaction in old paraffin-embedded tissues when appropriate primers are used.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence

Severe axial anomalies in the oculo-auriculo-vertebral (Goldenhar) complex.

We have studied 4 infants with oculo-auriculo-vertebral (OAV) complex or Goldenhar "syndrome" who also had severe axial anomalies, including multiple vertebral segmentation errors affecting the thoracic and the lumbar spine. One of them presented a previously unreported pattern of vertebral and rib anomalies similar to spondylocostal dysostosis. Three patients had twins, and all 4 patients had other associated non-skeletal malformations which affected the midline, i.e., cleft lip and palate, esophageal atresia with tracheoesophageal fistula, and ventricular septal defect. The broad extent of the axial anomalies, the association with midline defects and twinning, and the combination in the same patient of two distinct conditions support the concept that OAV complex is a polytopic developmental field defect arising during blastogenesis.

Abnormalities, Multiple