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A Ariza

Publications and source records attributed to A Ariza.

At least 55 records · Page 3Linked to original sources
PubMed1998

[The head-thrust test (HTT): physiopathological considerations and its clinical use in daily practice].

The basis of the head-thrust test is that when a head thrust is made in the horizontal plane, the ipsilateral semicircular channel (SCC) shows gaze stabilization because the homolateral SCC is completely inhibited. This test was studied by electronystagmography and the main parameters, the amplitude and latency of the compensatory ocular movements, were analyzed. The sensitivity, specificity, and positive and negative predictive value of this test were estimated in a series of 22 patients. The values were, respectively, 54, 100, 100 and 68%.

Electronystagmography↗
PubMed1997

[Significance of heterozygosity loss in the long arm of chromosome 5 (5q21) in small cell carcinoma of the lung].

BACKGROUND: Loss of heterozygosity (LOH) at 5q21, where the APC/MCC genes reside, is one of the genetic alterations that characterizes lung cancer. The aim of this study was to analyse LOH frequency on chromosome 5q21 in patients with non-small cell lung cancer and its relationship with TNM staging and histological subtypes. PATIENTS AND METHODS: Tumor and corresponding normal DNA were isolated from 60 patients with non-small cell lung cancer and a subsequent polymerase chain reaction (PCR) with microsatellite markets within the APC/MCC region was performed. The PCR products were resolved by electrophoresis. The comparison between the normal and tumor DNA patterns allowed us to detect the samples harboring LOH. RESULTS: LOH at 5q21 was detected in 20% of the patients. LOH at 5q21 was found in 16% of stage I patients, 8% in stage II patients and 40% in stage IIIA patients. A trend towards worse survival was detected in stage IIIA patients with LOH at 5q21 (9 months median time survival) in comparison with patients with LOH (21 months), although the difference was not statistically significant (p = 0.11). No significant differences in LOH were observed among histological types. In addition, we found no correlation between LOH and higher frequency of mutations rate affecting K-ras and p53 genes. CONCLUSIONS: LOH at 5q21 is a frequent genetic alteration in non-small cell lung cancer and correlates with locally advanced disease (stage IIIA). Our results suggest that LOH at the 5q21 region could be a prognostic factor in non-small cell lung cancer.

Carcinoma, Non-Small-Cell Lung↗
PubMed1997

Prognostic value of replication errors on chromosomes 2p and 3p in non-small-cell lung cancer.

As chromosomes 2p and 3p are frequent targets for genomic instability in lung cancer, we have addressed whether alterations of simple (CA)n DNA repeats occur in non-small-cell lung cancer (NSCLC) at early stages. We have analysed by polymerase chain reaction (PCR) assay replication errors (RER) and loss of heterozygosity (LOH) at microsatellites mapped on chromosomes 2p and 3p in 64 paired tumour-normal DNA samples from consecutively resected stage I, II or IIIA NSCLC. DNA samples were also examined for K-ras and p53 gene mutations by PCR-single-stranded conformational polymorphism (PCR-SSCP) analysis and cyclic sequencing, as well as their relationship with clinical outcome. Forty-two of the 64 (66%) NSCLC patients showed RER at single or multiple loci. LOH was detected in 23 tumours (36%). Among patients with stage I disease, the 5-year survival rate was 80% in those whose tumours had no evidence of RER and 26% in those with RER (P = 0.005). No correlation was established between RER phenotype and LOH, K-ras or p53 mutations. RER remained a strong predictive factor (hazard ratio for death, 2.89; 95% confidence interval, 2.23-3.79; P = 0.002) after adjustment for all other evaluated factors, including p53, K-ras, LOH, histological type, tumour differentiation and TNM stage, suggesting that microsatellite instability on chromosomes 2p and 3p may play a role in NSCLC progression through a different pathway from the traditional tumour mechanisms of oncogene activation and/or tumour-suppressor gene inactivation.

Adult↗
PubMed1997

Liver cell atypias: a comparative study in cirrhosis with and without hepatocellular carcinoma.

Various criteria have been proposed for the identification of early neoplastic changes in the setting of both small hepatocellular carcinomas and macroregenerative nodules. In this study we have applied those criteria to cases of liver cirrhosis without tumour (group I) and hepatocellular-carcinoma-associated cirrhosis (group II) to assess their discriminatory value in these two situations. Group I included 50 liver biopsies with uncomplicated cirrhosis while group II encompassed 48 liver biopsies of cirrhotic nodules adjacent to hepatocellular carcinomas. The histological changes sought were large cell dysplasia, small cell dysplasia, cytoplasmic basophilia, small microacinar structures, peripheral distribution of nuclei, nuclear irregularities and thickened liver cell plates. These changes were also assessed in macroregenerative nodules (nine in group I and seven in group II). None of these changes was useful to discriminate between group I and group II cirrhotic nodules when assessed separately. On the other hand, cirrhotic nodules showing three or fewer changes were never associated with malignancy, whereas those exhibiting four or more alterations were often located in the vicinity of a tumour. Acinar structures, thickened cell trabeculae, peripheral distribution of nuclei and nuclear irregularities seem to be the most specific indicators of proximity to a hepatocellular carcinoma. Similar results were obtained for macroregenerative nodules. These results may be helpful as guidelines to the probability of having a hepatocellular carcinoma elsewhere in livers containing atypical cirrhotic nodules, and may also prove valuable in the selection of appropriate material for investigating early molecular events in hepatic carcinogenesis.

Biopsy↗
PubMed1997

Beta-cell function abnormalities in islets from an adult subject with nesidioblastosis and autoantibodies against the islet cells.

Human islets from an adult subject with nesidioblastosis were isolated and used to perform in vitro studies. Isolated nesidioblastotic islets showed an increased basal rate of insulin secretion (nesidioblastotic islets, 81.3 +/- 6.4 vs. control islets, from cadaveric organ normal donors, 10.2 +/- 0.9 microU/islet/90 min) without any further release with increasing glucose concentration. In addition, islets isolated from the pancreas with nesidioblastosis contained more insulin than control islets, 1,547.0 +/- 128.7 vs. 935.0 +/- 51.7 microU/islet, and the levels of insulin mRNA were also higher than those measured in controls. Interestingly, the serum of the subject with nesidioblastosis contained autoantibodies that stained brightly and selectively a population of islet cells whose distribution coincided with that expected of alpha cells. In summary, pancreatic islets in nesidioblastosis display beta-cell functional abnormalities. Moreover, the finding of antibodies against islet cells is a common feature in the serum of nesidioblastotic subjects; nevertheless, their pathological significance warrants further investigation.

Adolescent↗
PubMed1996

Cyclin D1 overexpression in non-small cell lung carcinoma: correlation with Ki67 labelling index and poor cytoplasmic differentiation.

Cyclin D1 is part of the molecular system regulating the cell cycle G1 to S transition point. Its overexpression, a common finding in carcinomas of the breast, oesophagus, and head and neck, has also been demonstrated in a high percentage of non-small cell lung carcinomas (NSCLCs). The role of cyclin D1 in NSCLC has been studied by correlating its immunoreactivity with the Ki67 labelling index in paraffin-embedded, autoclaved surgical samples of 56 NSCLC cases. In addition, flow cytometric determination of ploidy and cell cycle status was carried out on 172 fresh tumour samples from the same cases. Twenty-four (42.8 per cent) NSCLCs showed positive cyclin D1 immunostaining, a finding which showed no relationship to ploidy pattern, cell cycle phase, histological subtype, or lymph node metastasis, but was significantly associated with the Ki67 labelling index (P = 0.03) and with poor cytoplasmic differentiation (P = 0.01). Cyclin D1-positive nuclei were abundant in poorly differentiated zones and absent in the best differentiated areas, particularly in heavily keratinized fields. These data indicate that in NSCLC, cyclin D1 overexpression is not only associated with a high cell proliferation rate, but also seems to play a role in the process of tumour differentiation.

Adult↗
PubMed1996

Differential expression of CD44v6 in adenocarcinoma of the pancreas: an immunohistochemical study.

Alternative splicing gives rise to numerous CD44 isoforms, some of which seem to have a role in tumour metastasis. Specifically, a variant form of CD44 with sequences encoded by exon v6 (CD44v6) confers metastatic potential when transfected into a nonmetastasizing cell line of rat pancreatic adenocarcinoma. This study has investigated standard CD44 (CD44s) and CD44v6 expression immunohistochemically in 6 samples of normal pancreatic tissue, 4 of tissue affected by chronic pancreatitis, and 24 of tissue from metastasizing and nonmetastasizing pancreatic adenocarcinomas. In addition, 18 samples from lymph node or visceral metastases were included in the study. CD44s was expressed in nonneoplastic tissue and in tissue from pancreatic adenocarcinomas. In contrast, CD44v6 was not detected in any of the normal tissue or chronic pancreatitis specimens, whereas 54% of pancreatic adenocarcinomas and 55% of metastases expressed this variant exon. Although it is not clear whether CD44 isoforms containing exon v6 play a part in malignant progression in the human exocrine pancreas, it seems plausible that the expression of multiple isoforms containing this and other variant exon confers a selective advantage on pancreatic adenocarcinoma.

Adenocarcinoma↗
PubMed1996

Gastrointestinal autonomic nerve tumor: further observations regarding an ultrastructural and immunohistochemical analysis of six cases.

Gastrointestinal autonomic nerve tumor (GANT) is a specialized form of stromal neoplasm whose ultrastructural features support a myenteric plexus derivation and provide the basis for its diagnosis. GANT actual frequency, relationship to skeinoid fibers, and CD34 expression status are some of the controversial aspects of this entity. Out of 14 gastrointestinal stromal tumors gathered during a 1-year period, six (42%) instances were diagnosed as GANT by electron microscopic study of at least five ultrathin sections per case. Additionally, GANTs were immunohistochemically investigated with a panel of nine antibodies including CD34. Ultrastructurally, every GANT case showed diagnostic findings and evidence of skeinoid fibers, whereas immunohistochemically all except one were CD34 positive. Immunoreactivity for neuron-specific enolase, synaptophysin, and vimentin was a common occurrence as well. In conclusion, GANT seems to be more frequent than hitherto recognized, skenoid fibers are a regular feature of GANT, and a positive CD34 immunoreaction does not discriminate between GANT and other non-smooth muscle, non-schwannian neoplasms.

Aged↗
PubMed1996

CD44 distribution in sweat gland tumors suggests it has different functional roles in the various cell types.

CD44 is a polymorphic group of membrane glycoproteins with multiple functions that include cell adhesion. Since on normal sweat glands CD44 is expressed only in eccrine coil secretory cells, it has been considered as a possible marker of this type of differentiation. We have immunohistochemically investigated the distribution of CD44 in paraffin-embedded samples of 41 benign and malignant sweat gland tumors by using a monoclonal antibody directed against the standard isoform of CD44. CD44 was strongly expressed in epithelial cells at the peripheral row of syringomas and in cuticular areas of eccrine poromas. Apocrine tumors such as apocrine hidrocystoma, syringocystadenoma papilliferum, or hidradenoma papilliferum showed intense CD44 positivity in the portion of cells in contact with the neighboring stroma and focally on the luminal side of cells with apocrine secretion. Cylindromas and spiradenomas presented focal CD44 positivity, virtually limited to clear cells. Malignant neoplasms exhibited irregular CD44 staining, which was more intense in the less differentiated zones and tumors. Our results indicate that CD44 is not a useful marker for a specific form of sweat gland differentiation. Nevertheless, its characteristic patterns of distribution might reflect the variety of functional roles assumed by the different CD44 isoforms in each epithelial cell.

Adenoma, Sweat Gland↗
PubMed1996

Accumulation of wild-type p53 protein in progressive multifocal leukoencephalopathy: a flow of cytometry and DNA sequencing study.

p52 protein accumulation in JC virus (JCV)-infected cells of progressive multifocal leukoencephalopathy (PML) has been previously shown. Since many viral proteins are known to bind and stabilize p53, we are addressing the question of whether p53 protein accumulation in PML is the result of its sequestration by JCV and not the outcome of a p53 gene mutation which would prolong its half-life. We have investigated the status of the p53 gene in frozen autopsy brain samples from five PML patients. After isolating genomic DNA, p53 gene exons 2 through 9 were amplified and sequenced. No discrepancies were found in the DNA sequences of exons 2 through 9 and their intron/exon barriers when compared to those published for wild-type p53. On the other hand, dual (p53/DNA) flow cytometry analysis revealed p53 expression above that of the isotypic controls for each case. No aneuploid populations could be identified, however, which seems at odds with the aneuploid status normally associated with mutation-induced p53 dysfunction. These results indicate that the p53 gene harbors no mutations in PML and provide further evidence of p53 protein accumulation in this condition. Since p53 protein buildup in JCV-infected cells is not the consequence of a mutagenic interaction between JCV and the cell genome, we propose instead that p53 accumulation results from its binding and stabilization by JCV T protein.

Base Sequence↗
PubMed1996

DNA amplification in glial cells of progressive multifocal leukoencephalopathy: an image analysis study.

JC virus (JCV), the agent of progressive multifocal leukoencephalopathy (PML), has been shown by both immunohistochemistry and flow cytometry to be associated with p53 protein stabilization. Since stabilization/inactivation of p53 is associated with the development of genomic instability, abnormal cell DNA contents are to be expected in JCV-infected cells of PML. This work explores that possibility by image analysis evaluation of DNA content in PML-infected oligodendrocytes and bizarre astrocytes. Brain paraffin sections of PML lesions from five adult male patients with the acquired immune deficiency syndrome (AIDS) were treated with the Feulgen technique to obtain a stochiometric staining of DNA and analyzed with a microscope image processor. Inclusion-bearing oligodendrocytes exhibited near tetraploid DNA indices in each of the five cases, whereas atypical astrocytes were in the hypertetraploid range in all cases and were polyploid in four instances. This evidence of DNA amplification in PML glial cells is congruent with the functional abolition of p53 protein in association with JCV infection and lends further support to the role of p53 as a keeper of diploid status and guardian of genomic stability.

Adult↗
PubMed1996

CD44 and melanocytic tumors: a possible role for standard CD44 in the epidermotropic spread of melanoma.

CD44 is a polymorphic family of cell membrane glycoproteins that mediate cell-matrix and cell-cell interactions involved in the mechanisms of tumor invasion and metastasis, and are subject to differential regulation during normal and malignant cell growth. We have investigated immunohistochemically the expression of CD44S and the variant isoforms CD44v3 and CD44v6 in paraffin-embedded tissue from 5 Spitz nevi, 3 compound melanocytic nevi, 2 blue nevi, 6 primary melanomas, 15 cutaneous metastases (three epidermotropic, nine dermal and three ulcerated) and 10 lymph node metastases of melanoma. Melanocytes were extensively positive for CD44S in primary melanomas and benign melanocytic proliferations. Among 15 cases of cutaneous metastases of melanoma, the three epidermotropic metastases, as well as one of the three ulcerated ones were positive for CD44S. CD44S expression was diminished or totally absent in six of the nine dermal metastases, in two of the ulcerated metastases and in seven of the ten lymph node metastases. CD44v3 and CD44v6 melanocytic expression was absent in all the lesions studied. According to our results, selective retention of CD44S expression by melanocytes in epidermotropic metastases of melanoma seems to indicate that preservation of CD44S may contribute to the intraepidermal spread of melanoma.

Antibodies, Monoclonal↗
PubMed1996

Expression of CD15 in normal and metaplastic Paneth cells of the digestive tract.

AIMS: To substantiate that incubation with monoclonal antibody CD15 (C3D-1) elicits a distinctive immunoreaction in normal small intestinal Paneth cells, normal and metaplastic Paneth cells along the digestive tract were assessed to determine whether they are also immunoreactive to CD15. METHODS: Paneth cells in paraffin wax embedded specimens of normal small intestine, appendix and proximal ascending colon, and from cases of chronic gastritis and ulcerative colitis were investigated immunohistochemically for lysozyme and CD15 antigen expression by means of the avidin-biotin peroxidase complex method. RESULTS: CD15 antibody reacted with a high proportion of both normal and metaplastic Paneth cells. Paneth cell immunoreactivity to CD15, however, was less intense and less extensive than to antilysozyme antibody, though the latter also stained many other cell types and was more commonly associated with nonspecific background staining. CONCLUSIONS: CD15 seems to be a valuable adjuvant for the study of Paneth cells in the normal and diseased digestive tract. Furthermore, as CD15 has been shown to be involved in activation of phagocytes, its expression in Paneth cells reinforces their proposed role as antimicrobial agents and regulators of the intestinal flora.

Appendix↗
PubMed1996

Expression of CD44H and CD44v3 in normal oesophagus, Barrett mucosa and oesophageal carcinoma.

AIMS: To examine CD44H and CD44v3 expression in normal gastric and small bowel mucosa, normal and Barrett oesophagus, and oesophageal epithelial malignancies (squamous cell carcinoma and adenocarcinoma). METHODS: Ninety five specimens, comprised of 40 of normal oesophageal, gastric and small bowel mucosa, 22 of Barrett oesophagus (two with dysplastic changes), 20 of resected adenocarcinomas, and 13 of squamous cell carcinoma, were evaluated. The samples were fixed in formalin and subsequently stained with anti-CD44H and anti-CD44v3 monoclonal antibodies using the avidin-biotin peroxidase technique. RESULTS: In contrast to normal oesophagus, which showed positivity for both CD44 epitopes (CD44H and CD44v3) in the basal third of the epithelium, antral and intestinal subtypes of Barrett oesophagus expressed CD44H only, the distribution being focal in non-dysplastic and diffuse in dysplastic Barrett mucosa. Similarly, normal antral glands and small bowel epithelium were focally immunopositive for CD44H at the base of the crypts. All squamous cell carcinomas were diffusely positive for both isoforms, whereas 75% (15/20) of the adenocarcinomas expressed CD44H and 60% (12/20) expressed CD44v3. CONCLUSIONS: CD44H is expressed in the proliferating areas of both normal squamous epithelium and Barrett mucosa. CD44H expression seems to increase progressively in dysplasia and infiltrating carcinoma, similar to the process described in the stomach. CD44v3 expression, usually not observed in normal or neoplastic gastric mucosa, was present in normal squamous epithelium and oesophageal squamous cell carcinoma. CD44v3 immunoreactivity was also identified in 60% of adenocarcinomas. These findings suggest that CD44v3 may play a role in the development of oesophageal carcinoma of both squamous and glandular types.

Adenocarcinoma↗
PubMed1996

Molecular staging of non-small cell lung cancer according to K-ras genotypes.

We have previously demonstrated a strong association between K-ras gene mutations, as determined by PCR followed by allele-specific oligonucleotide hybridization (ASO-h), and survival in non-small cell lung cancer patients. The purpose of this study was to determine the relationship between tumor aggressiveness and specific-type K-ras point mutations in non-small cell lung cancer. We developed procedures to examine the status of the K-ras gene by ASO-h and by single-strand conformation polymorphism assay of DNA obtained from formalin-fixed paraffin-embedded tumors. K-ras point mutations at codons 12 and 61 were assessed in 275 consecutively treated stage I-IV non-small cell lung cancers. Among patients with stage I disease, median survival time was 41.5 months in those whose tumors had no evidence of K-ras mutations and 27 months in those with K-ras 12 mutations; among patients with stage IIIA disease, median survival time was 7 months in those with K-ras codon 12 aspartic and serine mutations and 15 months for those with other K-ras mutations (P = 0.01). In a multivariate analysis, specific-type K-ras codon 12 point mutation remained a strong predictive factor (hazard ratio for death, 2.06; 95% confidence interval, 1.11-3.81; P = 0.02) after adjustment for other evaluated factors, including TNM stage and histology. Thus, we concluded that in patients with non-small cell lung cancer, specific K-ras 12 point mutations detected by DNA amplification and either ASO-h or single-strand conformation polymorphism methods predicted a significantly increased risk of recurrence and death, independently of stage and histology.

Adult↗
PubMed1995

Standard and variant CD44 isoforms are commonly expressed in lung cancer of the non-small cell type but not of the small cell type.

Cluster of differentiation 44 (CD44) encompasses a polymorphic family of cell membrane glycoproteins involved in the mechanism of tumour invasion and metastasis. Since non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) display very different rates of progression, a significant discrepancy in their CD44 expression profiles is to be expected. An immunohistochemical study was undertaken on the expression of standard CD44 (CD44s) and the variant isoforms containing the domains encoded by variant exon 3 (CD44v3) or variant exon 6 (CD44v6) in paraffin-embedded bronchial biopsy specimens from 32 NSCLC cases and 11 SCLC cases. An absolute lack of immunoreactivity for CD44s, CD44v3, and CD44v6 was obtained in every case of SCLC, whereas 28 of the 32 NSCLC cases showed a positive immunoreaction for at least one of the three epitopes investigated. In conclusion, the occurrence of standard and variant CD44 isoforms in NSCLC and their absence in SCLC suggest the possibility that CD44 is in some way instrumental in conditioning the biological behaviour of NSCLC, but not of SCLC, whose metastatic cascade would be set in motion by the activation of hitherto unidentified, CD44-independent pathways.

Adult↗
PubMed1995

Desmin myopathy: a multisystem disorder involving skeletal, cardiac, and smooth muscle.

Myopathy associated with desmin-type intermediate filaments is an uncommon disorder of skeletal and/or cardiac muscle. The present study focuses on a 28-year-old man with generalized muscular atrophy, cardiomyopathy, and intestinal malabsorption and pseudo-obstruction. Abundant sarcoplasmic granular and filamentous aggregates that were ultrastructurally continuous with Z lines or dense bodies and exhibited intense immunostaining for desmin were present throughout the skeletal musculature, myocardium, and smooth muscle of the intestine. Moreover, neurofilament-immunoreactive axonal spheroids were identified in the spinal cord and roots. These widely distributed findings illustrate the multisystemic character of desmin myopathy, which in this instance first adds intestinal smooth muscle involvement to its already known skeletal and cardiac muscle manifestations. The additional presence of neurofilament aggregates in the spinal cord and roots constitutes an extremely rare conjunction of intermediate filament pathology of the neuromuscular system.

Adult↗