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J B Nousbaum

Publications and source records attributed to J B Nousbaum.

At least 37 records · Page 2Linked to original sources
PubMed1995

p53 protein accumulation in oesophageal squamous cell carcinomas and precancerous lesions.

AIMS: To investigate the immunohistochemical expression of p53 protein in oesophageal squamous cell carcinomas and in dysplastic areas of the oesophageal mucosa surrounding the tumours. METHODS: Biopsy samples were obtained from 20 patients with an oesophageal squamous cell carcinoma. Blocks of the tumours and of the surrounding mucosa were immunostained with the monoclonal antibody DO-7. RESULTS: Fourteen of the 20 carcinomas were positive for p53 (70%). The frequency of p53 overexpression increased with the differentiation of the tumour. Nine out of 13 dysplastic specimens were positive for p53 (69%): eight cases with severe dysplasia and one case with moderate dysplasia. No p53 immunostaining was detected in normal oesophageal epithelium. All p53 positive dysplastic specimens were taken from the mucosa adjacent to tumours that were also immunostained. In moderate dysplastic mucosa the p53 positive cells were located in the proliferative basal zone, whereas in severe dysplasia the immunostained cells increased in number and spread to upper cell layers of the epithelium. CONCLUSION: This study supports the hypothesis that TP53 gene is frequently involved in the development of oesophageal squamous cell carcinoma and that p53 protein accumulation is an early event in human oesophageal carcinogenesis.

Adult↗
PubMed1995

Prevalence, severity, and risk factors of liver disease in blood donors positive in a second-generation anti-hepatitis C virus screening test.

In a cohort of 483 blood donors positive for antibody to hepatitis C virus on second-generation enzyme-linked immunosorbent, the confirmatory second-generation recombinant immunoblot assay (Ortho Diagnostic Systems) was positive in 172 cases (36%), indeterminate in 113 (23%), and negative in 198 (41%). We further studied 94 of the donors (recombinant immunoblot assay positive in 85, indeterminate in 6, and negative in 3). Alanine transaminase (ALT) activity, assayed on three occasions, was elevated in at least one assay in 85% of the 85 recombinant immunoblot assay-positive donors. Liver disease was present in 95% of these patients (chronic persistent hepatitis, 35%; chronic active hepatitis, 53%; cirrhosis, 7%). Ten of the 13 recombinant immunoblot assay-positive donors with normal ALT activity had liver disease; polymerase chain reaction testing for viral RNA was predictive of liver disease in most cases. Donors with cirrhosis differed significantly from cirrhosis-free donors in terms of age, sex ratio, ALT activity, and excessive alcohol consumption. Three of the 6 recombinant immunoblot assay-indeterminate donors (isolated C 22) who underwent histological examination had elevated ALT activity and liver disease. The 3 recombinant immunoblot assay-negative donors evaluated were free of liver disease. This study shows that anti-HCV second-generation enzyme-linked immunosorbent positivity is confirmed in fewer than 40% of blood donors by the second-generation recombinant immunoblot assay, and that liver disease is present in 95% of recombinant immunoblot assay-positive donors. Recombinant immunoblot assay positivity combined with viremia is frequently associated with the existence of liver disease, regardless of transaminase activity. Excessive alcohol consumption may be an important factor in the onset of cirrhosis in anti-HCV-positive blood donors.

Adult↗
PubMed1995

Comparative analysis of two assays for genotyping hepatitis C virus based on genotype-specific primers or probes.

BACKGROUND/AIMS: The importance of determining the hepatitis C virus genotype has increased since several authors have described a good correlation between hepatitis C virus genotype and response to interferon treatment or to disease severity. It is thus of particular importance to develop reliable assays for hepatitis C virus genotyping. METHODS: We have comparatively analyzed hepatitis C virus genotypes of 208 French and Italian chronically infected patients using genotype-specific primers polymerase chain reaction in the capsid region and a genotype-specific probe-based assay in the 5' untranslated region (LiPA). RESULTS: We found a good concordance between the two assays for the prevalent genotypes in our regions (145/174). The nucleotide sequences in the 5'UTR and capsid domain were investigated to determine the molecular basis of some discordant results. This analysis showed that the genotype-specific probe-based assay gave more consistent results, probably because this technique is based on several probes distributed along the 5'UTR to reveal each genotype. In contrast, the low variability of 5'UTR did not always permit classification of the hepatitis C virus genotype 1 subtypes. We also found some problems, using genotype-specific primers polymerase chain reaction, for less represented genotypes; in particular, in the presence of type 2a/III we obtained more discordant results. This observation is of importance in view of the potential association of this genotype with mild liver disease and a good response to interferon-a treatment.

Base Sequence↗
PubMed1995

[Therapeutic management and survival of gastric adenocarcinoma in the province of Finistère between 1984 and 1989].

OBJECTIVES: The aim of this study was to analyze the evolution of treatment regimens and survival rates of stomach adenocarcinoma recorded in the Finistère cancer registry from 1984 to 1989. METHODS: In a population of 838,627 inhabitants, 1,280 patients with a gastric cancer were registered; 1,164 patients (693 males and 471 females) had an adenocarcinoma. Survival rates were estimated by the actuarial method, and compared using the logrank test and the Cox model. RESULTS: Surgical resection was the main treatment for 661 patients (57%). The frequency of curative resection increased from 25% between 1984 and 1986 to 35% after 1986. Among the other patients, 39 (3%) were treated by chemotherapy and/or radiotherapy, and 53 patients (4%) by endoscopy alone; 253 patients had only symptomatic treatment. The survival rates of all patients were 43% at 1 year and 20% at 5 years. The median survival was 9.2 +/- 0.6 months. In patients with cancer managed surgically, the factors associated with a better prognosis were young age, long duration of symptoms before diagnosis, ulcerated macroscopic aspect, limited tumour extension and curative surgical resection. In other patients, 2 factors were associated a with better prognosis: the absence of metastases and an endoscopic palliative treatment. CONCLUSIONS: Surgical resection is the main treatment of gastric adenocarcinoma. Although the frequency of surgery increased, the prognosis of gastric adenocarcinoma did not improve within this 6-year period.

Adenocarcinoma↗
PubMed1994

[Flow cytometry and digestive pathologies].

Flow cytometry provides rapid evaluation of nuclear DNA content and cell cycle analysis. The major applications of flow cytometry in gastroenterology are the evaluation of DNA content and proliferative indices as prognostic indicators of gastrointestinal malignancies, and the screening of premalignant conditions of the digestive tract.

Digestive System Diseases↗
PubMed1994

Four-week treatment with omeprazole increases the metabolism of caffeine.

OBJECTIVES: It has been suggested that omeprazole is an inducer of the cytochrome P450 1A, both in vitro and in vivo. To evaluate whether omeprazole treatment might affect the activity of P450 1A2, we performed a study of caffeine metabolism, which is mainly via P450 1A. METHODS: Thirteen subjects (one healthy volunteer and 12 patients) who were treated with omeprazole, 20 mg each morning for 4 wk, and a control group of 13 healthy volunteers, participated in the study. A test of caffeine metabolism was performed before treatment, 28 days after beginning treatment and, whenever possible, 28 days after treatment. Blood samples were analyzed for theobromine, paraxanthine, and theophylline, by high performance liquid chromatography. RESULTS: P4501A2 activity was determined as the ratio of (paraxanthine + theobromine + theophylline)/(metabolites + caffeine) which represents the total caffeine N-oxidative demethylations; this ratio was expressed as a percentage. For patients, on day 0, the percentage of total metabolism was 34.3% +/- 8.3; on day 28, it was 42.7% +/- 10.8; the difference was statistically significant (p < 0.01). No intra-individual variation of P450 1A2 activity was observed in the control group. CONCLUSIONS: These results demonstrate that omeprazole increases the metabolism of caffeine, especially N-1 and N-3 demethylation pathways, after 28 days of treatment with omeprazole, and suggest that omeprazole, when used for this period, is an inducer of hepatic cytochrome P4501A2.

Caffeine↗
PubMed1993

TP53 gene mutation profile in esophageal squamous cell carcinomas.

Esophageal squamous cell carcinoma is a form of cancer occurring most commonly in males, particularly those living in some areas of Asia, Africa, and western Europe. In some of these tumors, a sequence alteration has been identified in the coding region of the TP53 gene which is known to inactivate the tumor suppressor function of its product. Using a GC clamp (i.e., a GC rich domain) denaturing gradient gel electrophoresis assay we have been able to identify sequence modifications in 27 of the 32 tumor samples analyzed (84%). Most of the mutations occur in exon 6, a region of the gene which has not previously been reported as being a hot spot for the mutations of other cancers. Twelve of the mutations reported here have not been described in other types of tumors and these consist mostly of frameshift or splice mutations. The distribution of mutations [transitions (45%), transversions (34%), and frameshift (21%)] suggests that the etiological contribution of genotoxic factors might be complex and might associate different exogenous and endogenous mutagen exposures.

Adult↗
PubMed1993

[Treatment of and survival after epidermoid cancer of the esophagus in the department of Finistère between 1984 and 1988 (716 cases)].

The incidence of esophageal cancer in the French county of Finistère is among the highest in France (26.7/10(5) for males). The authors analyzed the survival rates for squamous cell carcinomas from data of the Finistère tumor registry in order to describe different prognostic groups of patients using the multivariate Cox model. From 1984 to 1988, 716 patients with esophageal squamous cell carcinomas were registered in an overall population of 828,000 residents: 675 males and 41 females. Survival was calculated using the actuarial method. Six hundred and seventy five patients died before the point date (31 Dec 1989). Only one patient was lost to follow-up. The actuarial survival rates of all patients were 89 +/- 1% at 3 months, 68 +/- 2% at 6 months, 37 +/- 2% at one year, 12 +/- 1% at 3 years and 6 +/- 1% at 5 years; median survival was 9.1 +/- 0.4 months. Survival was significantly related to cancer size, tumor extension and surgical contraindications. In the Cox model, age, cancer size, surgical contraindications, year of diagnosis were independent prognostic predictors. There was a significant increase in survival rates after 1986: median survival was 8.1 +/- 0.4 months between 1984 and 1986 and 10.1 +/- 0.5 months between 1987 and 1988. Patients treated by curative resection had higher actuarial survival rates (median survival 22.5 +/- 4.1 months) than patients who underwent palliative resection (median survival 11.3 +/- 1.2 months). In patients with cancer managed surgically, the prognostic predictors were tumor size, curative vs palliative surgical resection and association with chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

[Isolated portal vein thrombosis: a rare complication of chronic pancreatitis].

In chronic pancreatitis (CP) portal vein thrombosis (PT) is a less well known complication than splenic vein thrombosis (ST). In the literature up until 1990, 26 cases with PT, have been reported and only 10 cases presented a isolated PT, without ST. We report a new case of isolated PT without ST in a non alcoholic man, who presented with gastroesophageal CP and a cavernomatous transformation of the portal vein. No varices ere detected by endoscopy; because the risk of bleeding was very small, a prophylactic treatment was unnecessary. The pancreas was resected preserving the spleen and cavernomatous transformation or the periportal veins and the patient was cured from his pains. The surgical tactic is an original treatment, particularly when curable pancreatic cancer is suspected.

Adult↗
PubMed1992

Endosonography can detect residual tumour infiltration after medical treatment of oesophageal cancer in the absence of endoscopic lesions.

Endoscopic ultrasound (endosonography) is useful in the preoperative staging of oesophageal tumours. It may also have a role in evaluation and surveillance of patients with inoperable carcinomas. Thirty four patients with inoperable oesophageal cancer were investigated by endosonography and computed tomography before medical treatment. In 10 patients receiving combined chemotherapy and radiotherapy, the endoscopic lesions resolved and biopsy specimens were negative. When endosonography suggested the persistence of tumour infiltration in these patients, a local recurrence or distant metastases appeared within a few months. In contrast, when no infiltration was detected, no tumoral recurrence or progression was observed within eight months. These results suggest that endosonography is better than endoscopic biopsy specimens and computed tomography in assessing the response of oesophageal carcinoma to non-surgical treatment.

Combined Modality Therapy↗
PubMed1992

[Demonstration of clonal heterogeneity in adenocarcinomas on Barrett's esophagus by flow cytometric study of cellular DNA content].

Flow cytometry was used to examine the spatial distribution of nuclear DNA content in Barrett's mucosa, in one patient with high grade dysplasia and in 6 patients with Barrett's adenocarcinoma. All tumors were aneuploid. Each adenocarcinoma but the most advanced seemed to arise from a single clone of aneuploid or near-tetraploid cells which was found in all biopsy specimens taken from the tumor. Multiple aneuploid populations of cells were seen in the larger tumors. Eight clones were individualized in the most advanced case of cancer. In all patients with carcinoma, the mucosa surrounding the tumor was aneuploid. Some areas were characterized by the same DNA index as in the tumor, others contained distinct aneuploid cell populations. The spatial distributions of aneuploid clones and dysplastic areas were not perfectly superimposed. These data suggest that neoplastic progression in Barrett's esophagus is associated with genomic instability preceding the development of malignancy. Clonal heterogeneity in Barrett's adenocarcinoma is more marked when compared to other tumors and suggests a majoration of genomic instability during tumor progression.

Adenocarcinoma↗
PubMed1991

[Flow cytometric analysis of cellular DNA content in Barret's esophagus. A study of 66 cases].

Dysplasia is the only marker for malignant potential in Barrett's esophagus. The histologic interpretation of dysplasia is sometimes difficult, particularly when attempting to distinguish dysplastic changes from those of a regenerating and inflammatory mucosa. In order to find an objective marker to identify patients with high risk of malignant transformation, the authors evaluated 497 biopsies from 66 patients with Barrett's esophagus with flow cytometry. The aim of the study was to correlate DNA content and proliferative abnormalities with histology. All biopsies classified histologically as negative for dysplasia had a diploid DNA content. The percentage of biopsies with an aneuploid DNA content increased with the histologic grade of dysplasia: 2 percent of indefinite dysplasia, 11 percent of low grade dysplasia, 44 percent of high grade dysplasia and 78 percent of biopsy specimens with cancer biopsies were aneuploid. Mean S and G2M fractions of diploid biopsy specimens increased with the severity of histologic changes. The S and G2M fraction threshold values that could differentiate patients that were negative for dysplasia from those with high grade dysplasia or cancer were 9 percent and 6 percent, respectively. Aneuploidy or G2M fraction greater than 6 percent was the best discriminating criteria between those two distinct groups of patients. All 6 patients with high grade dysplasia or cancer had aneuploid cell populations or increased G2M fraction, whereas none of the 35 patients whose biopsies were histologically negative for dysplasia had evidence of genomic instability or increased G2M fraction. Flow cytometric abnormalities were found in 10 out of 25 patients whose biopsies were classified as indefinite for dysplasia or low grade dysplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗