Ultraviolet-B-induced G1 arrest is mediated by downregulation of cyclin-dependent kinase 4 in transformed keratinocytes lacking functional p53.

In order to identify potential novel targets for ultraviolet-B-induced skin tumorigenesis, we assessed the effect of ultraviolet-B exposure on cell cycle progression of transformed keratinocytes with mutant p53. We show that ultraviolet-B exposure of human epidermoid carcinoma A431 cells results in G1 cell cycle arrest in both asynchronously growing and synchronized cells. A significant increase in G1 cell population was observed following exposure to doses of ultraviolet-B as low as 10 mJ per cm2.

Diabetes in Africans. Part 2: Ketosis-prone atypical diabetes mellitus.

Diabetes is increasing with ageing and changes in lifestyle in populations of African ancestry as described in the first part of this review. Apart from classical type 1 and Type 2 diabetes, atypical presentations are observed in these populations, especially "tropical" and "ketosis-prone" atypical diabetes. Ketosis-prone atypical diabetes that has been classified by ADA as idiopathic Type 1 diabetes or Type 1b is the most common atypical form.

Diabetes in Africans. Part 1: epidemiology and clinical specificities.

The prevalence of diabetes in African communities is increasing with ageing of the population and lifestyle changes associated with rapid urbanisation and westernisation. Traditional rural communities still have very low prevalence, at most 1-2%, except in some specific high-risk groups, whereas 1-13% or more adults in urban communities have diabetes. Type 2 diabetes is the predominant form (70-90%), the rest being represented by typical type 1 patients and patients with atypical presentations that require more pathophysiological insight.

Stage-specific alterations of cyclin expression during UVB-induced murine skin tumor development.

We have evaluated the in vivo correlation between the expression of cell cycle markers and skin tumor development in SKH-1 hairless mice in a complete photocarcinogenesis protocol. Irradiated mice developed an average of 16 tumors per animal by week 23 with the average number of carcinomas per mouse being 2.1.

Effect of satiation on brain activity in obese and lean women.

Objective: To investigate the response of the brains of women to the ingestion of a meal.

Research Methods And Procedures: We used measures of regional cerebral blood flow (rCBF), a marker of neuronal activity, by positron emission tomography to describe the functional anatomy of satiation, i.e.

Group I projections from intrinsic foot muscles to motoneurones of leg and thigh muscles in humans.

1. Group I projections from intrinsic plantar muscles to motoneurones (MNs) of human leg and thigh muscles were investigated. Changes in firing probability of single motor units (MUs) in the tibialis anterior (TA), peroneus brevis (Per brev), soleus (Sol), gastrocnemius medialis (GM), vastus lateralis (VL), semitendinosus (ST) and biceps (Bi) were studied after electrical stimuli applied to: (i) the tibial nerve (TN) at ankle level, (ii) the corresponding homonymous nerve, and (iii) the skin of the heel, to mimic the TN-induced cutaneous sensation.

Role for cyclin-dependent kinase 2 in mitosis exit.

Mitosis requires cyclin-dependent kinase (cdk) 1-cyclin B activity [1]. Exit from mitosis depends on the inactivation of the complex by the degradation of cyclin B [2]. Cdk2 is also active during mitosis [3, 4].

Mre11 protein complex prevents double-strand break accumulation during chromosomal DNA replication.

Mre11 complex promotes repair of DNA double-strand breaks (DSBs). Xenopus Mre11 (X-Mre11) has been cloned, and its role in DNA replication and DNA damage checkpoint studied in cell-free extracts. DSBs stimulate the phosphorylation and 3'-5' exonuclease activity of X-Mre11 complex.

Exercise training-induced triglyceride lowering negatively correlates with DHEA levels in men with type 2 diabetes.

Objective: To investigate the effect of an exercise training program on lipid profile in correlation with DHEA level and body weight and body composition in type 2 diabetic men.

Design: Longitudinal, controlled clinical intervention study with exercise training consisting of an 8 week supervised program of aerobic exercise (75% VO(2) peak, 45 min), twice a week and intermittent exercise, once a week, on a bicycle ergometer.

Subjects: Sixteen men (age 45.

Low acute insulin secretory responses in adult offspring of people with early onset type 2 diabetes.

The offspring of Pima Indians with early onset type 2 diabetes are at high risk for developing diabetes at an early age. This risk is greater among those whose mothers were diabetic during pregnancy. To define the metabolic abnormalities predisposing individuals in these high-risk groups to diabetes, we conducted a series of studies to measure insulin secretion and insulin action in healthy adult Pima Indians.

[Physical exercise and insulin sensitivity].

Physical exercise is known to be essential in the treatment of type 2 diabetes. An increased glucose uptake is evidenced during acute muscular exercise, over the post-exercise period, and following physical training. In this paper, we review metabolic and molecular aspects of physical exercise.

Responses to DNA damage in Xenopus: cell death or cell cycle arrest.

Xenopus embryos divide rapidly following fertilization. During this rapid period of cleavage, cell divisions are not sensitive to DNA replication or spindle assembly inhibition. Here, we have investigated the consequences of eliciting DNA damage in these embryos.

Oxidative damage and stress response from ochratoxin a exposure in rats.

Ochratoxin A (OTA) is a mycotoxin found in some cereal and grain products. It is a potent renal carcinogen in male rats, although its mode of carcinogenic action is not known. Oxidative stress may play a role in OTA-induced toxicity and carcinogenicity.

Genotoxicity testing of extracts from aflatoxin-contaminated peanut meal, following chemical decontamination.

One of the most important concerns in the decontamination of aflatoxin-containing feed commodities is the safety of the products for food-producing animals and for human consumption of products derived from these animals. A new method, based on the use of florisil and C18 solid phase extraction columns, was developed for the preparation of extracts from decontaminated peanut meal, which allowed testing with in vitro genotoxicity assays without interference of the residual aflatoxin B1. Recovery of degradation products in the extracts was evaluated by the use of radiolabelled [14C]-aflatoxin B1 (AFB1) added to naturally-contaminated peanut meal (3.

Absorption, distribution and excretion of aflatoxin-derived ammoniation products in lactating cows.

Peanut meal naturally contaminated with 3.5 mg/kg aflatoxin B1 (AFB1) was spiked with radiolabelled AFB1 (meal 14C-I0) and decontaminated by a small-scale copy of an industrial ammoniation process (meal 14C-I1). During the process 15% of the radioactivity was lost, whereas 90% of the remaining radiolabel could not be extracted from the meal.

Expression and subcellular localization of X-ATM during early Xenopus development.

ATM, the gene mutated in ataxia telangiectasia, is a protein essential for handling DNA strand breaks. We recently isolated the Xenopus homologue of ATM, X-ATM and we report here the detailed expression pattern of the protein and the mRNA during early Xenopus development. During the cleavage stages, ATM protein was concentrated in and around the nuclei of all cells with low levels of expression also detected in the cytoplasm.

Effects of a single bout of exercise and exercise training on steroid levels in middle-aged type 2 diabetic men: relationship to abdominal adipose tissue distribution and metabolic status.

Lower androgen levels have been suggested to be associated with type 2 diabetes and central obesity and are probably involved into the development of atherosclerosis. The present study investigates the effect of acute and chronic exercise on Dehydroepiandrosterone (DHEA) levels in relation to abdominal fat distribution and metabolic status in type 2 diabetes. Twenty weight-stable, middle-aged males with type 2 diabetes were enrolled in the study and participated in a submaximal (VO(2) peak) and moderate (50% VO(2) peak) exercise bout.

Interfacial properties of amiodarone: the stabilizing effect of phosphate anions.

Amiodarone, a drug used in heart therapy, is poorly soluble in water at room temperature, but forms transparent phases much more concentrated than the critical micellar concentration (CMC), when crystals are heated (above 60 degrees C) in presence of water and cooled down to room temperature. These pseudosolutions were supposed to be made of a complex system of micelles. In order to better understand the effects of pH and ion species on the supramolecular organization of amiodarone, interfacial pressure measurements were performed at the air/water interface on a Langmuir trough.

Metabolism of ochratoxin A: absence of formation of genotoxic derivatives by human and rat enzymes.

Ochratoxin A (OTA) is a potent renal carcinogen in male rats, although its mode of carcinogenicity is not known. The metabolism and covalent binding of OTA to DNA were investigated in vitro with cytochromes P450, glutathione S-transferases, prostaglandin H-synthase, and horseradish peroxidase. Incubation of OTA with rat or human liver microsomes fortified with NADPH resulted in formation of 4-(R)-hydroxyochratoxin A at low rates [10-25 pmol min(-1) (mg of protein)(-1)].

Reconstitution of an ATM-dependent checkpoint that inhibits chromosomal DNA replication following DNA damage.

Cell cycle checkpoints lead to the inhibition of cell cycle progression following DNA damage. A cell-free system derived from Xenopus eggs has been established that reconstitutes the checkpoint pathway inhibiting DNA replication initiation. DNA containing double-strand breaks inhibits replication initiation in a dose-dependent manner.