Genetic mapping of mouse centromere protein (Incenp and Cenpe) genes.

Inner centromere protein (INCENP) and centromere protein E (CENPE) are two functionally important proteins of the higher eukaryotic centromere. Using a mouse Incenp genomic DNA and a mouse Cenpe cDNA to analyze recombinant inbred mouse sets, as well as interspecific backcross panels, we have mapped these genes to the proximal regions of mouse Chromosomes 19 and 6, respectively. Comparison of Cenpe and human CENPE, which maps to chromosome region 4q24-->q25, has further identified a new region of homology between the two species.

Centromere protein B null mice are mitotically and meiotically normal but have lower body and testis weights.

CENP-B is a constitutive centromere DNA-binding protein that is conserved in a number of mammalian species and in yeast. Despite this conservation, earlier cytological and indirect experimental studies have provided conflicting evidence concerning the role of this protein in mitosis. The requirement of this protein in meiosis has also not previously been described. To resolve these uncertainties, we used targeted disruption of the Cenpb gene in mouse to study the functional significance of this protein in mitosis and meiosis. Male and female Cenpb null mice have normal body weights at birth and at weaning, but these subsequently lag behind those of the heterozygous and wild-type animals. The weight and sperm content of the testes of Cenpb null mice are also significantly decreased. Otherwise, the animals appear developmentally and reproductively normal. Cytogenetic fluorescence-activated cell sorting and histological analyses of somatic and germline tissues revealed no abnormality. These results indicate that Cenpb is not essential for mitosis or meiosis, although the observed weight reduction raises the possibility that Cenpb deficiency may subtly affect some aspects of centromere assembly and function, and result in reduced rate of cell cycle progression, efficiency of microtubule capture, and/or chromosome movement. A model for a functional redundancy of this protein is presented.

Long-range analyses of the centromeric regions of human chromosomes 13, 14 and 21: identification of a narrow domain containing two key centromeric DNA elements.

Alpha-satellite, satellite 3 and satellite 1 DNA have been proposed as candidate components of a functional human centromere. Multiple subfamilies of these three DNA have recently been identified at the pericentric regions of the human acrocentric chromosomes. Using pulsed field gel electrophoresis, we have constructed long-range maps of the various centromeric markers for chromosomes 13, 14 and 21. These maps cover approximately 2.3 megabases of sequence for each chromosome, and the results demonstrate that within this centromeric region, chromosomes 13 and 21 have a similar organization that is partially shared by chromosome 14. A discrete satellite 3 domain was identified on each chromosome within the boundaries of the alpha-satellite DNA. No satellite 1 was detected within the defined centromeric regions suggesting that satellite 1 is not essential for centromere function.

Benign human papillomavirus infection in renal transplant recipients.

Warts and cutaneous squamous cell carcinomas are common complications of immunosuppression. We studied a total of 189 renal transplant recipients clinically for such lesions. The incidence of warts increased steadily after transplant, such that of patients transplanted for more than 5 years, 92% were found to have warts and 65% had more than five warts each. DNA extracted from scrapings of their warts showed they carried the same human papillomavirus types as the general population, and not the unique set found on patients with epidermodysplasia verruciformis (who share with transplant recipients an increased incidence of warts and squamous cell carcinomas).

Cutaneous squamous cell carcinomas and papillomaviruses in renal transplant recipients: a clinical and molecular biological study.

Papillomaviruses are strongly implicated in squamous cell carcinomas arising on mucosal surfaces of normal individuals, and in the skin carcinomas of epidermodysplasia verruciformis suffers. Renal transplant recipients often have numerous skin warts and, in Australia particularly, a very high risk of developing cutaneous squamous cell carcinoma. To determine the magnitude of this risk, and to test whether papillomaviruses are specifically associated with these cancers, we examined 188 renal transplant recipients for skin cancers and tested 235 biopsy specimens of (histologically proven) squamous cell carcinomas for the presence of viral DNA. The risk of developing squamous cell carcinoma increased with duration of transplant: the probability being 25% after 9.5 years (standard error = 1.3 years) rising to 50% at 20.6 years (standard error 6.8 years). Factors which did not appear to affect the risk of tumour development included the patients sex and their skin type. However the age at transplant significantly altered the risk with patients transplanted at greater than 35 years developing tumours about four times more rapidly than patients less than or equal to 35 years. Extensive hybridisation tests for the presence of papillomavirus DNA in squamous cell carcinomas were negative, as was the polymerase chain reaction amplification method using general L1 gene oligonucleotide primers. Our data do not support a role for papillomavirus in the maintenance of cutaneous squamous cell carcinoma.

Physiological role of dietary fiber: a ten-year review.

It is accepted nowadays that dietary fiber is an important constituent of the diet. There is growing evidence that the low fiber Western diets and the low consumption of whole grain products are important factors in several common diseases of the large bowel. Cereal fiber differs from that present in vegetables and fruit. A low intake of cereal fiber has been implicated in cancer of the large bowel, diverticular disease of the colon and coronary heart disease. High fiber diets are often prescribed for diabetes. Although fiber consumption by British and American consumers has decreased over the past century, consumption of whole wheat breads and fiber-rich breakfast cereals has received new attention during the past ten years.