Mucin profiles and potential for malignancy of human colorectal adenomatous polyps

The mucin histochemical and histologic features of 166 colorectal adenomatous polyps from 124 patients were studied. A majority of the polyps (62%) had a tubular growth pattern whereas 38% showed villous growth. Severe dysplasia was more frequently found in the latter group. A significant correlation (r = 0.27, P less than 0.001) was found between the severity of dysplasia and the size of the polyps. Moreover, the ratio between goblet and columnar cells was also found to decrease (P less than 0.0001) with the severity of dysplasia. Independent of the mucin stain used (periodic acid-Schiff, alcian blue, and high-iron diamine stains), mucin reactive cells were found to be negatively correlated (-0.17 less than r less than -0.44, P less than 0.01) with severity of dysplasia, especially in the tubular adenomas. These findings suggest that evaluation of mucin stain, related to dysplasia, may contribute to the assessment of premalignant and early malignant changes in adenomas of the colon.     

Cytomegalovirus infection induces vascular injury in the rat.

The role of cytomegalovirus (CMV) in the early development of atherosclerosis was studied in a rat model. Arterial samples derived from virus-infected normo- and hypercholesterolaemic animals were investigated by light microscopy at 1, 4, 8 and 16 weeks post infection. Early atherogenic lesions comparable to those seen in non-infected hypercholesterolaemic rats were found in CMV-infected normocholesterolaemic and hypercholesterolaemic animals, starting at 1 week post infection. The changes consisted of minimal endothelial cell damage, as shown by the en face technique, and a more than 10-fold increase in the number of leukocytes adhering to the aortic intima. The increased adhesion of leukocytes was observed in infected normocholesterolaemic rats but only in the non-infected rats which were hypercholesterolaemic. The infection of hypercholesterolaemic rats did not enhance this effect although it resulted in increased migration of the leukocytes into the subendothelial space. CMV infection of normocholesterolaemic rats induced lipid accumulation in the endothelium. In these animals approximately 1% of the endothelial cells contained lipid at 1 week post infection. In the non-infected hypercholesterol-fed animals 10% of the cells contained lipid. CMV infection in these rats induced an extra increase of the lipid-containing endothelial area. The changes in the CMV infected animals largely corresponded with the intimal injury observed in the hypercholesterolaemic rats. These results support the hypothesis that CMV may be one of the factors involved in atherogenesis.     

Recurrence of nephrocalcinosis after renal transplantation in an adult patient with primary hyperoxaluria type I

The medical history of a 42-year-old patient with primary hyperoxaluria type I is presented. Primary hyperoxaluria was suspected after renal transplantation, when oxalate deposits were found in a biopsy of the kidney graft. Diagnosis of type I hyperoxaluria was confirmed by the finding that significantly increased amounts of glycolic acid and oxalic acid were excreted. Treatment of the patient with 500 mg pyridoxine daily resulted in a decrease of the excretion of oxalate to normal values.     

Stress distribution around dental implants: influence of superstructure, length of implants, and height of mandible.

The stress distribution around dental implants was investigated by use of a two-dimensional model of the mandible with two implants. A vertical load of 100 N was imposed on abutments or the bar connection. The stress was calculated for a number of superstructures under different loading conditions with the help of the finite element method. The length of the implants and the height of the mandible were also varied. A model with solitary abutments showed a more uniform distribution of the stress when compared with a model with connected abutments. The largest compressive stress was also less in the model without the bar. Using shorter implants did not have a large influence on the stress around the implants. When the height of the mandible was reduced, a substantially larger stress was found in the bone around the implants because of a larger overall deformation of the lower jaw.     

Multiple mutations in mouse Chd7 provide models for CHARGE syndrome

Mouse ENU mutagenesis programmes have yielded a series of independent mutations on proximal chromosome 4 leading to dominant head-bobbing and circling behaviour due to truncations of the lateral semicircular canal of the inner ear. Here, we report the identification of mutations in the Chd7 gene in nine of these mutant alleles including six nonsense and three splice site mutations. The human CHD7 gene is known to be involved in CHARGE syndrome, which also shows inner ear malformations and a variety of other features with varying penetrance and appears to be due to frequent de novo mutation. We found widespread expression of Chd7 in early development of the mouse in organs affected in CHARGE syndrome including eye, olfactory epithelium, inner ear and vascular system. Closer inspection of heterozygous mutant mice revealed a range of defects with reduced penetrance, such as cleft palate, choanal atresia, septal defects of the heart, haemorrhages, prenatal death, vulva and clitoral defects and keratoconjunctivitis sicca. Many of these defects mimic the features of CHARGE syndrome. There were no obvious features of the gene that might make it more mutable than other genes. We conclude that the large number of mouse mutants and human de novo mutations may be due to the combination of the Chd7 gene being a large target and the fact that many heterozygous carriers of the mutations are viable individuals with a readily detectable phenotype.     

Are thrombocyte membranes altered in Alzheimer''s disease? A morphometric and biochemical study

Morphometric analysis of thrombocytes from patients with Alzheimer's disease, from patients with multi-infarct dementia, and from young and agematched healthy control donors, did not reveal any Alzheimer-related increase in internal membranes. Biochemical analysis showed a reduced cholesterol content of thrombocyte membrane preparations from Alzheimer patients relative to age-matched controls, but not relative to multi-infarct dementia patients. Overall distribution of protein kinase C activity (PKC) between cytosol and membrane, in resting as well as in activated thrombocytes from Alzheimer patients, was similar to that in the control groups. However, both Alzheimer and multi-infarct dementia patients had lower cytosolic levels of basal kinase and PKC activities than age-matched controls, while only Alzheimer patients had lower cytoskeletal PKC activity than controls.     

Ultrastructural aspects of chondrodystrophia calcificans congenita (syndrome of Conradi-Hünermann)

Summary An ultrastructural study of chondrodystrophia calcificans congenita is reported. Foci of initial calcification of cartilage are characterized by coexistence of three different types of crystals, probably due to abnormal proteoglycan composition of cartilage matrix. The calcification process in chondrodystrophia calcificans congenita is apparently not related to matrix vesicles as it is in normal cartilage.     

Pitfalls in TRAP assay in routine detection of malignancy in effusions

Telomerase has been found to be reactivated in a majority of cancers but is inactive in most somatic cells. Our principal goal was to determine the potential use of the telomeric repeat amplification protocol (TRAP) assay as marker for malignancy in cytological effusions. The simple selection criterion was the cytological diagnosis, and routine samples were classified into malignant (58 samples) and nonmalignant (233 samples). Of the malignant samples, 44/58 (76%) were positive by TRAP assay. Of the 14 telomerase-negative cytology-positive samples, RNA integrity was poor in 9, indicating suboptimal sample conservation for molecular analysis. In 3 of the remaining 5 samples with a negative TRAP assay, a high number of malignant cells was observed, and these cells might have been telomerase-negative. Thus, the sensitivity of TRAP assay for the presence of malignant cells was about 76%. In the cytologically nonmalignant effusions, the presence of telomerase activity was observed in 24% (55/233). Of these, 6% were highly suspicious for malignancy, 9% were doubtful, and 9% were cytologically nonmalignant effusions confirmed by a follow-up of 12 mo or more. According to these data, the specificity of the TRAP assay to detect tumor cells in effusions ranged only between 82-91%. Our results indicate that, although the TRAP assay is positive in 6-15% of putative malignant effusions, the relatively high number of TRAP false-negative and false-positive cases renders this test unsuitable for routine diagnostic purposes.