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.

Definition of dietary fiber and hypotheses that it is a protective factor in certain diseases.

Crude fiber (CF) is the residue of plant food left after extraction by dilute acid followed by dilute alkali. Dietary fiber (DF), a new term, is the residue of plant food resistant to hydrolysis by human alimentary enzymes. DF is composed of cellulose, hemicellulose, and lignin; these constituents are not reported in food tables. For instance, whole wheatmeal has DF about 11%, CF about 2%. It is suggested that a new term, dietary fiber complex (DFC), should include all substances of DF plus all chemical compounds naturally associated with, and concentrated around, these structural polymers. CF supplies from starchy staples, wheat and potato, in England and Wales were probably stationary from 1770 to 1860, fell greatly from 1860 to 1910, rose during food controls in 1942 to 1953, and declined slightly from 1954 to 1970. It is postulated that fiber is a protective factor against certain colonic disorders, such as diverticular disease, and certain metabolic diseases, such as ischemic heart disease, diabetes mellitus, and obesity. These three diseases had changing trends of mortality rates in England during the food control years. Westernization of African diets is accompanied by a large fall in CF from starchy foods and vegetables and an increased prevalence of the same three diseases.

The development of the concept of dietary fiber in human nutrition.

Fundamental studies of the laxative action of wheat bran were undertaken in the United States in the early decades of the 20th century. Walker in South Africa extended these studies among African blacks and later suggested that cereal fiber protected them against certain metabolic disorders. Trowell in Uganda elaborated this concept with regard to the rarity of common noninfective diseases of the colon. Another stream of inquiry stemmed from the hypothesis of Cleave who postulated that the presence of refined sugar, and to a lesser extent white flour, caused many metabolic diseases, while the loss of fiber caused certain colonic disorders. Meanwhile Burkitt had collected massive evidence of the rarity of appendicitis and many venous disorders in rural Africa and parts of Asia. In 1972 Trowell proposed a new physiological definition of fiber in terms of the residue of plant foods that resisted digestion by alimentary enzymes of man. Southgate has proposed chemical methods to analyze the components of dietary fiber: cellulose, hemicellulose, and lignin.

Diabetes mellitus and dietary fiber of starchy foods.

The rarity of diabetes mellitus in rural Africans and the increased incidence in urban Africans suggested that high-fiber, high-carbohydrate diets might protect against diabetes. Conversely it has been suggested that low-fiber starchy food is a diabetogenic factor in susceptible human phenotypes. Many years ago experimental studies demonstrated that carbohydrate tolerance was increased in healthy adults if they ate high-carbohydrate diets but was decreased if they ate high-fat diets. From 1940 in England and Wales, diabetes death rates reported only those who died directly from diabetes mellitus; all cardiovascular complication deaths were excluded. Standardized diabetes mellitus death rates in England and Wales fell from 1941 until 1954 to 1957 by 55% in men and 54% in women. These years coincided with the production of high-fiber National flour. These data suggested the dietary fiber hypothesis of the etiology of diabetes mellitus, namely that fiber-depleted starchy foods were diabetogenic and conversely that high-fiber starchy foods were protective. Recent experimental studies of diabetic hyperglycemic men have shown that high-fiber, high-carbohydrate diets cause remission of diabetes mellitus in many men who had been treated previously by oral agents of moderate doses of insulin, but not those who had previously received large amounts of insulin.

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.

From normotension to hypertension in Kenyans and Ugandans 1928-1978.

PIP: From at least 1928 until about 1940 essential hypertension was reported to be a rare disease among the population in Kenya and Uganda. Currently, it is 1 of the common causes of heart failure and a major cause of cerebrovascular disease in many hospitals in these 2 nations. Field data in these countries suggest that blood pressure rises during adult life, and essential hypertension occurs in salt-sensitive individuals, when sodium chloride daily intake is excessive. If the intake of potassium chloride is less than that of sodium chloride, and the intake of dietary fiber decreases much, as happens when diets are westernized, these may act as subsidiary risk factors. The East African diets are becoming more and more westernized. The 1st major dietary change involves the addition of much salt to low-salt unprocessed foods. With progressive westernization of diets the foods processed by manufacturers replace homegrown staples. These processed foods contain considerably more sodium, rather less potassium, and much less dietary fiber. While this multiple dietary change takes place, blood pressure levels, previously low and not rising with age, begin to rise during adult life. Essential hypertension, once rare, becomes common in sodium sensitive persons. Diets comparable in many respects to the 1930 Kikuyu diet are suggested to reverse essential hypertension. The therapeutic diet should be of low sodium chloride and should contain much unrefined high fiber high starch foods.^ieng