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Biomedical subjects

J Piris

Publications and source records attributed to J Piris.

At least 19 recordsLinked to original sources
PubMed1991

Linked DNA markers for presymptomatic diagnosis of familial adenomatous polyposis.

41 symptom-free individuals aged 0-39 years who were at risk of familial adenomatous polyposis (FAP) were genotyped with six linked DNA probes. 28 individuals were informative for probes flanking the gene and 14 people assigned a probe-derived risk of over 0.93 were subsequently shown to be affected by clinical screening. 4 individuals who had been discharged from follow-up were designated high risk by this method. In those screened negative, risk was calculated from genotypic, colonic, and CHRPE findings and 89% of subjects had a risk below 0.003. An integrated risk analysis may have an important place in screening programmes for FAP.

Adenomatous Polyposis Coli↗
PubMed1991

MCC, a candidate familial polyposis gene in 5q.21, shows frequent allele loss in colorectal and lung cancer.

MCC is a gene located within human chromosome band 5q.21 that shows somatically acquired mutations in colorectal cancer, and may be identical to the gene responsible for inheritance of familial adenomatous polyposis. Here we demonstrate that alleles contiguous with or within MCC are deleted in a high proportion of sporadic colorectal carcinomas. Of 106 carcinomas that were informative concurrently at close-flanking sites both centromeric and telomeric to MCC, 41.5% showed acquired allele loss contiguous with MCC. Evidence is presented to show that the true frequency of loss of MCC alleles is higher still. In contrast, allele losses in chromosome 5 that were incompatible with involvement of MCC were very rare (2% of a total series of 201 informative tumours). Interstitial deletion was the commonest mechanism of allele loss, and L5.71-3, a probe known to include coding sequences of MCC, marks the most consistently deleted site. Moreover mapping of chromosome breakpoints with six probes within 5q.21 sited the common critical deletion in a 2.5 Mb region which included L5.71-3. However use of L5.71-3 itself suggested that critical deleted regions may lie on either side of the probed sequence. The simplest explanation for this unexpected finding is that MCC itself is the essential deleted gene, the lost exons lying sometimes centromeric to, sometimes telomeric to and occasionally within the region detected by L5.71-3. Tumours in which MCC-related alleles were lost by interstitial deletion were in general larger than those with other mechanisms of acquired homozygosity (e.g. mitotic recombination), but there were no other obvious associations with clinicopathological features. Between 20% and 25% of lung cancers also showed acquired allele losses contiguous with MCC. The significance of this observation is still to be determined, as lung tumours show allele losses at many other sites, but the specificity of the probes used in this study does establish that the 5q.21 losses in these tumours are compatible with involvement of MCC.

Adenomatous Polyposis Coli↗
PubMed1991

p53 expression in colorectal tumors.

The expression of the nuclear phosphoprotein p53 was studied immunohistochemically in a series of 150 benign and malignant colorectal tumors. Using monoclonal antibody PAb1801, tumors divided unequivocally into two groups on the basis of immunohistochemistry. Forty of the carcinomas (46.5%) showed positive staining but only 4 of the adenomas (8.7%) were positive (P less than 0.001). The few positive adenomas always showed moderate or severe dysplasia. Metaplastic polyps (n = 9) and small familial adenomatous polyposis-related adenomas (n = 9) were uniformly negative. Carcinomas with p53 expression did not differ from those without in terms of site, differentiation or the prognostic indicators of Dukes' stage, DNA ploidy, or tumor histology. The improved morphologic resolution available in periodate lysine paraformaldehyde dichromate (PLPD)-fixed, paraffin-embedded tissue permitted several conclusions to be made: p53 is confined to neoplastic nuclei; staining in positive tumors is heterogeneous and often more marked at the infiltrative margins; and staining intensity is dramatically reduced in mitotic cells. It is concluded that expression of immunohistochemically detectable p53 (probably representing mutated forms of the protein) occurs in some adenomas around the time of transition to carcinoma. Therefore there is an association with the appearance of infiltrative behavior but not with degree of tumor progression (including metastasis) at the time of resection.

Adenomatous Polyposis Coli↗
PubMed1990

Immunohistochemical demonstration of altered intracellular localization of the C-Myc oncogene product in human colorectal neoplasms.

The distribution of the c-myc oncogene product p62 was examined by immunohistochemistry using the monoclonal antibody Mycl-9E10 in a series of 50 colorectal resections for carcinoma. The specimens were specially handled to ensure rapid fixation in formalin, and a significant improvement was shown in the quality and localization of staining compared with routinely handled specimens. Non-neoplastic mucosa showed the presence of nuclear staining of epithelial cells in 93 per cent of the samples, whilst all carcinomas showed cytoplasmic staining and infrequent nuclear staining. Adenomas showed an intermediate pattern, with significantly more frequent cytoplasmic distribution than non-neoplastic mucosa, but less than carcinomas. The results show that whilst fixation conditions are important in the immunolocalization of the c-myc protein product, there may be a consistent difference between non-neoplastic mucosa and carcinoma in the manner of association of p62 with the nucleus.

Carcinoma↗
PubMed1989

Pharyngoesophageal dysmotility in globus sensation.

Ambulatory esophageal pH monitoring, radiologic examination, endoscopy, and manometry were undertaken in 142 patients with globus. The results demonstrate that abnormal gastroesophageal reflux occurred in 23% of patients, implying that, while reflux may be responsible for globus in some patients, it is not the cause of globus sensation in the majority of individuals with this symptom. Comparing patients with globus and control subjects, there were no differences in lower esophageal sphincter pressures, esophageal body motility, or tonic upper esophageal sphincter pressures, but patients with globus exhibited higher pharyngeal and upper esophageal sphincter after-contraction pressures during deglutition. The physiological significance of this pharyngeal and upper esophageal dysmotility is not clear and it may be no more than a secondary phenomenon. Alternatively, it may contribute to the generation of globus, perhaps in combination with other physical and psychological triggers.

Diagnosis, Differential↗
PubMed1989

Gastroesophageal reflux and posterior laryngitis.

Esophageal acid exposure was assessed by 23-hour ambulatory pH monitoring and compared with a biopsy of the posterior larynx and proximal esophagus in 97 patients with hoarseness, burning pharyngeal discomfort, or globus sensation. Patient results were compared with normal acid exposure times obtained in 54 control subjects. In 24 patients there were laryngeal abnormalities but both esophageal biopsy results and acid exposure times were normal. Laryngeal disease was found in association with prolonged acid exposure time or esophagitis in only 17 of the 97 patients (17.5%) studied. Recent reports appear to have overestimated the importance of acid reflux as a cause of posterior laryngitis.

Adult↗
PubMed1988

Optimal preservation of p21 ras immunoreactivity and morphology in paraffin-embedded tissue.

Specific immunostaining of p21 ras protein by the well-characterized pan-ras antibody Y13-259 is achieved in paraffin sections of human and animal tissues fixed in periodate-lysine-paraformaldehyde-dichromate (PLPD). Intensity of staining is as good as in cryostat sections, with superior histological detail. Localization to plasma membrane is demonstrated in rodent cells genetically manipulated to express abundant p21 ras (the FHO5T1 cell line), both in preparations suspended in agar after culture in vitro and in those growing as tumour in vivo. Strong positive staining is observed in neoplasms of human breast and colon, tissues in which there is independent evidence of elevated ras gene expression. The superior morphology afforded by this technique allows clear characterization of p21 ras expression in small premalignant lesions for which other methods of detection of oncogene expression are not appropriate.

Animals↗
PubMed1987

Globus sensation is not due to gastro-oesophageal reflux.

Oesophageal manometry and prolonged ambulatory pH monitoring were performed in 47 patients with the globus sensation, 48 control subjects and 28 patients with documented oesophagitis. Globus patients also underwent video-recorded barium examination and rigid endoscopy. Manometry was normal in 38 of the globus group (94%). The mean percentage time below pH 4 was 4.16 in controls, 5.11 in globus patients (NS) and 18.54 in oesophagitis patients (P less than 0.0005). Oesophageal acid exposure did not correlate with sex, smoking or heartburn and correlated with age only in oesophagitis patients (P less than 0.001). Biopsy showed mild laryngitis in 2 globus patients and distal oesophagitis in 6 (13%). Abnormal oesophageal acid exposure and distal oesophageal dysmotility are not aetiological factors in the majority of patients with globus pharyngis.

Adult↗
PubMed1986

Pepsinogens in gastric carcinomas.

Polyclonal rabbit antisera raised against the two major groups of human pepsinogens (PG I and PG II) were used in an immunohistochemical study of human gastric carcinomas. Thirty-two carcinomas, classified histologically according to the Lauren classification as diffuse or intestinal, were studied; and the staining patterns of the tumor and adjacent gastric mucosa were assessed. In some of the tumors of both types, PG I and/or PG II staining of the neoplastic cells was seen, with PG I being found significantly more frequently than PG II. No characteristic staining pattern was associated with either Lauren type. (The presence of pepsinogens in gastric carcinoma cells therefore appears unlikely to be of relevance to the Lauren type of the tumor.) These findings do not support the notion of a separate histogenesis for diffuse and intestinal types of gastric carcinoma.

Carcinoma↗
PubMed1986

Evaluation of a monoclonal antibody to ras peptide, RAP-5, claimed to bind preferentially to cells of infiltrating carcinomas.

RAP-5, a monoclonal antibody raised against a p21ras peptide, has been claimed to show immunohistochemical localisation of cells with infiltrative properties in human tumours. We confirmed that this antibody reveals pronounced cellular heterogeneity in human colonic neoplasms but could find no obvious relationship to infiltrative activity. RAP-5 bound to many different cell types, neoplastic and normal. In order to clarify the specificities of RAP-5 we applied it to two cell lines: nontumorigenic hamster fibroblasts in which ras expression is barely detectable, and a vigorously tumorigenic line derived from these fibroblasts by insertion of the human mutated Ha-ras oncogene in a high expression vector. Another antibody to p21ras, Y13-259, clearly distinguished between these cell lines both on immunoblots and immunocytochemically, but RAP-5 did not. Rather, it bound to proteins of a variety of molecular weights in both cell lines. The results show that RAP-5 is unlikely to be a useful reagent for detection of ras associated proteins in human tissues.

Adenocarcinoma↗
PubMed1985

Immunohistochemical detection of the ras oncogene p21 product in an experimental tumour and in human colorectal neoplasms.

The monoclonal antibody Y13 259 to the ras oncogene protein product p21 was used in an immunohistochemical study of ras expression in human colorectal neoplasms. The ability of the antibody to detect enhanced levels of ras expression was confirmed by its use with an experimental neoplasm known to express ras at high levels. Human colonic adenocarcinomas in general showed a similar staining intensity to that seen in normal mucosa. Adenomas however showed consistently high p21 expression as indicated by staining intensity. This suggests that elevated ras expression may be important in the development of adenomas, but that high levels need not be sustained in the conversion to invasive carcinoma.

Adenocarcinoma↗
PubMed1984

Ketoconazole and fungal sinusitis.

A case of a young man with chronic sinusitis. After many years and multiple surgical procedures, fungal hyphae were noted. The patient made a complete recovery with oral ketoconazole.

Adolescent↗
PubMed1983

Carcinoid tumour of the larynx. A report of two cases.

Two cases of carcinoid tumours of the larynx are described. One was histologically a typical carcinoid whilst the other showed cellular atypia, numerous mitoses and invasion of the surrounding tissues. Both were argyrophilic but not argentaffin positive whilst electron microscopy demonstrated the presence of neurosecretory granules and amyloid. The previous literature on these rare tumours of the larynx is reviewed.

Aged↗
PubMed1980

Optimum dose of sulphasalazine for maintenance treatment in ulcerative colitis.

Sulphasalazine is widely used in the maintenance treatment of ulcerative colitis but the optimum dose is not known. In the present study, 170 patients were allotted at random to three treatment groups, in which the daily dose was 1, 2 and 4 g respectively, and the trial period of treatment lasted for six months. A daily dose of 2 g was found to be much more efficacious than 1 g. A daily dose of 4 g was more efficacious than 2 g but at the price of fairly frequent symptomatic side-effects. Haematological abnormalities were observed at all dosage levels, but they occurred chiefly among the patients on 4 g daily. Both symptomatic and the haematological side-effects were usually associated with high concentrations of serum sulphapyridine and these high levels occurred chiefly among the slow acetylators. It is concluded that, for general use, a daily dose of 2 g sulphasalazine is satisfactory for the maintenance treatment of ulcerative colitis. If a patient does not do well on 2 g daily, it is worth trying a larger dose but in this case the patient's condition should be monitored by blood film, haemoglobin, MCV, and reticulocyte count.

Clinical Trials as Topic↗