Loss of Apc and the entire chromosome 18 but absence of mutations at the Ras and Tp53 genes in intestinal tumors from Apc1638N, a mouse model for Apc-driven carcinogenesis

The Apc1638N mouse carries a targeted mutant allele at the endogenous adenomatous polyposis coli (Apc) gene and represents a unique in vivo model to study intestinal tumor formation and progression. Heterozygous Apc+/Apc1638N mice progressively develop 5-6 adenomas and adenocarcinomas of the small intestine within the first 6 months of life following a histologic sequence similar to that observed in human intestinal tumors. Here, we present the somatic mutation analysis of a total of 57 tumors. The results indicate that in > or = 75% of the lesions tested the wild type copy of the Apc gene is lost and that this LOH event extends to the entire mouse chromosome 18. Unexpectedly, mutations at the K-, N- and H-ras genes have not been found in these tumors. Immunohistochemical analysis of the Apc1638N tumors failed to detect accumulation of the Tp53 protein. Also, no mutations have been found in exons 7 and 8 of the Tp53 gene. These results indicate that, although the genetic inactivation of Apc is involved in the initiating event of the human as well as murine intestinal tumorigenesis, tumor growth and progression follow different mutational pathways in these two species.      

Multiple polymorphic sites in factor X locus

The structure of factor X (FX) gene was analyzed in five FX deficient pedigrees with four different variants of the disease, as well as in 50 normal subjects. Genomic DNA from the deficient patients and the normal controls was digested with 12 restriction endonucleases and hybridized with a FX cDNA probe. The results seemingly exclude gross gene deletions or rearrangements in the deficient patients. A variety of polymorphic sites (ie, EcoRI, HindIII, PstI, PvuII, TaqI) was observed within the FX locus and their relative frequency was established. Intriguingly, a highly polymorphic region for the PvuII endonuclease was identified and located approximately 3 kilobases (kb) from the last 3' exon. These polymorphisms allowed us to analyze the allelic segregation in a FX deficient family and to identify a homozygous subject.     

Imaging of the Kock continent ileal urinary reservoir

The Kock continent ileal urinary reservoir (Kock pouch) is a new urinary bypass system that can overcome some of the principal complications associated with other forms of urinary diversion. It is important to understand the anatomy and radiology of this new technique since radiologists play an important role in evaluating the function of the Kock pouch as well as assessing its complications. The authors review the clinical and radiographic findings in 193 patients who had undergone Kock pouch urinary diversion. Patients are evaluated radiographically in the immediate postoperative period and at regular postoperative intervals for as long as 3 years. Routine evaluation consists of Kock pouch cystography followed by intravenous urography. When indicated, computed tomography, ultrasound, and interventional radiologic procedures are used. The normal anatomy as well as the radiographic appearance of the Kock pouch is presented. In addition, the radiographic appearance of pouch complications and their frequency are reviewed.     

Extracellular deposition of eosinophil granule major basic protein in lymph nodes of patients with Hodgkin's disease

Lymph nodes from each of the four histologic types of Hodgkin's disease were examined for the presence of eosinophils and for eosinophil degranulation by immunofluorescent localization of eosinophil granule major basic protein (MBP). Eosinophil degranulation shown by MBP deposition outside of eosinophils was found in six of eight nodes from patients with nodular sclerosing disease and in two of eight nodes from patients with lymphocyte depletion-type disease. Three nodes of the mixed cellularity type, one node of the lymphocyte predominance type, and one lymph node of the lymphocyte depletion type showed one or two small foci of extracellular MBP deposition. Lymph nodes from patients without Hodgkin's disease showed no extracellular deposition of MBP. Large numbers of eosinophils were found in seven of eight nodes of the nodular sclerosing variant, but were less frequently seen among the other types of Hodgkin's disease. The presence of extracellular MBP in lymph nodes of patients with Hodgkin's disease indicates that eosinophil degranulation commonly occurs and suggests that the released eosinophil granule proteins may participate in the inflammatory reaction in this disorder more extensively than is presently appreciated.     

Intrauterine growth retardation: predictive value of US criteria for antenatal diagnosis

We critically analyzed published data on proposed sonographic criteria for intrauterine growth retardation (IUGR) to determine the positive and negative predictive values of the criteria. The data were drawn from 21 studies and encompassed nine distinct criteria for which the sensitivity and specificity could be determined. Predictive values were computed using Bayes theorem, based on an IUGR prevalence rate of 10%. Seven of the nine criteria had positive predictive values of less than 50%, indicating that a fetus with an abnormal test result according to any of these criteria is more likely to be normal than growth retarded. The best criterion involves the ratio of head circumference to abdominal circumference, but even with this criterion, fully 38% of fetuses with abnormal test result will not be growth retarded. We conclude that none of the proposed criteria allows a confident antenatal diagnosis of IUGR to be made. Future prospective studies may reveal new criteria, or combinations of existing ones, that are highly predictive for this condition.     

PARATHYROID HORMONE-RELATED PROTEIN IN LOWER VERTEBRATES

1. Parathyroid hormone-related protein (PTHrP) is an important mediator of humoral hypercalcaemia of malignancy in humans. Normal human subjects have very low levels of PTHrP in their circulation. 2. Parathyroid hormone-related protein has recently been demonstrated in high levels in the circulation and tissues of the sea bream and the dogfish, leading to the hypothesis that PTHrP may be a ‘classical’ hormone in fish. 3. Immunohistochemistry and in situ hybridization were performed to investigate the evolutionary history of PTHrP. Tissues were examined from a number of lower vertebrates, including lungfish, lamprey and several species of bony and cartilaginous fish. Parathyroid hormone-related protein was localized to the skin and to kidney tubules in all animals studied. In the developing lungfish, PTHrP was observed in the notochord, developing brain and skeletal muscle layers. These results suggest that PTHrP is of ancient origin and has a basic and fundamental function in vertebrates.