The lack of a role for p53 in astrocytomas in pediatric patients

Mutations in the p53 gene, which codes for a cell division regulatory protein, have been identified in approximately one-third of adult astrocytomas. We evaluated 35 astrocytic tumors (17 pilocytic, 4 diffuse low grade, 12 anaplastic, and 2 glioblastoma) in pediatric patients for p53 mutations, using polymerase chain reaction-single-stranded conformation polymorphism analysis as a screening technique. Additionally, those tumors identified with homozygosity in the area of the p53 gene on chromosome 17 by Southern blotting were sequenced to look for p53 mutations. No tumors were identified with polymerase chain reaction-single-stranded conformation polymorphism analysis shifts indicative of mutations in the p53 gene. Five of 21 tumors were homozygous in the region of the p53 gene on chromosome 17; no mutations in exons 5 to 8 were found in any of these tumors. The frequency of p53 mutation in pediatric astrocytomas is significantly less than the frequency for adult tumors, regardless of tumor grade. Furthermore, the frequency of p53 mutations in high-grade astrocytomas is significantly lower in pediatric tumors than in adult tumors. These results suggest that p53 is not important in the oncogenesis of pediatric astrocytomas. Oncogenesis in pediatric astrocytomas may occur by different mechanisms than those of similar tumors in adults.     

Interstitial iridium-192 implantation combined with external radiotherapy in anal cancer: ten years experience

BACKGROUND: The Quebec Neuroblastoma Screening (QNS) Project completed a 5-year program for measuring urinary vanillylmandelic acid (VMA)/homovanillic acid (HVA) levels at age 3 weeks and/or 6 months in 89% of 476,603 Quebec-born infants from 1989-1994; 45 screening positive preclinical cases (S-positive cases) and 20 congenital/neonatal (C/N) cases were identified. As of April 1997, an additional 59 cases in the same birth cohort were diagnosed clinically; these neuroblastomas developed after screening verified normal VMA/HVA levels (S-negative cases). METHODS: Pathology specimens from 45 of 59 S-negative cases were reviewed centrally and classified according to the Shimada system. Results were compared with clinical data and also with S-positive and C/N cases. RESULTS: Of 45 S-negative cases, 27 tumors had favorable histology (FH) and 18 had unfavorable histology (UH). Approximately 52% of FH tumors were diagnosed before age 1 year, whereas UH tumors were nearly exclusively (94%) diagnosed after age 1 year (P < 0.01). Approximately 89% of FH tumors were Stage I, II, or IV-S, whereas 72% UH tumors were Stage III or IV (P < 0.001). All children with FH tumors were alive at last follow-up (range of follow-up period: 9-79 months; median, 35 months), whereas 8 children with UH tumors died of disease even after limited follow-up (range of follow-up period: 0-60 months; median, 20 months). By contrast, S-positive and C/N cases were predominantly (97%) FH tumors, often (76%) Stage I, II, or IV-S, with excellent clinical outcome (survival rate of 98%). CONCLUSIONS: The majority of the UH neuroblastomas that developed in the birth cohort of the QNS Project were included in the group of S-negative cases and could not be detected by the screening at age 3 weeks and/or 6 months.     

Detection of polyomaviral DNA in clinical samples from immunocompromised patients: correlation with clinical disease

Characterization of the region between HLA-B and the TNF loci in the human MHC revealed the presence of duplicated loci, named CL1 and CL2, that included repeat sequences. Development and use of a PCR typing methodology that amplified both CL microsatellites simultaneously indicated that PCR product patterns analysed on native agarose gels were allelic (Abraham et al., 1992). The purpose of the current study was to determine the molecular explanation for the unique patterns achieved. Sequence analysis of the CL1 locus from 32 chromosomes representing 10 ancestral haplotypes indicated that six alleles were present. The CL microsatellites also provided an opportunity to study the evolutionary relationships between MHC haplotypes from different racial groups. Sequence comparison of closely related ancestral haplotypes from different racial groups suggested that the CL1 microsatellite has not changed in the period since divergence.     

Degradation of annexin I in bronchoalveolar lavage fluid from patients with cystic fibrosis

BACKGROUND/AIMS: The number of perisinusoidal myofibroblasts has been shown to be increased in hepatocellular carcinoma, as compared to cirrhosis. This increase might suggest a cooperative relationship between tumour cells and myofibroblasts. To assess this relationship, we undertook: (a) an immunohistochemical study to confirm the existence of an increased number of perisinusoidal myofibroblasts in human hepatocellular carcinoma, as compared to cirrhosis with or without liver cell dysplasia, (b) an in vitro study testing the role of normal or tumoral human hepatocytes in myofibroblast proliferation. METHODS: Forty explanted cirrhotic livers, including 14 with hepatocellular carcinoma and 24 with liver cell dysplasia, were studied. Myofibroblasts were detected by immunohistochemistry using an antibody directed against alpha-smooth muscle actin. Hepatic myofibroblasts in culture were obtained by outgrowth from human liver explants. RESULTS: There was a progressive increase in the number of perisinusoidal myofibroblasts, from cirrhotic nodules without dysplasia to liver cell dysplasia and hepatocellular carcinoma. Conditioned medium from isolated normal human hepatocytes had only minor mitogenic effects on myofibroblasts, as assessed by measuring DNA synthesis and cell growth. In contrast, conditioned medium from a human hepatoma cell line (HepG2 cells) markedly stimulated the proliferation of human myofibroblasts. This mitogenic activity was stored in HepG2 cells and secreted in the extracellular medium rather than being simply released following cell lysis. CONCLUSIONS: These results suggest that the increased number of myofibroblasts in hepatocellular carcinoma might be due to a paracrine mechanism involving soluble mitogenic factor(s) secreted by tumour cells.     

Large intestine obstruction complicated with perforation: a rare manifestation of Schistosoma mansoni infection

The authors report a case of a 25 year old Brazilian man with a history of crampy abdominal pain in the left iliac fossa for 2 weeks, abdominal distention, mucous diarrhea and anorexia. The patient presented signs of hemodynamic instability and a hard mass palpated in the left iliac fossa presented peritoneal irritation. At laparotomy, fecal peritonitis and a punched-out perforation of the midsigmoid colon were found. A left hemicolectomy was performed with terminal colostomy. Specimen examination revealed a thickened rectosigmoid wall, narrow lumen and multiple mucosal polyps. Microscopically, chronic granulomatous colitis with Schistosoma mansoni eggs confirmed the etiology. To the authors' knowledge, this is the first case of obstruction complicated with perforation due to mansoni schistosomiasis reported in the literature.