Mutation frequencies in murine keratinocytes as a function of carcinogenic status

A link between genetic abnormalities and carcinogenesis is well established. It follows that a correlation exists between mutation frequency and malignant progression. We have determined the spontaneous and DNA damage-induced mutation frequencies for a series of cell lines derived from SENCAR mouse keratinocytes at various stages of malignant progression. Nontumorigenic mouse keratinocytes (3PC), papillomas (MT1/2), squamous-cell carcinomas (CH72), and spindle-cell carcinomas (CH72T4) were transfected with damaged or undamaged shuttle vectors containing a supF mutation reporter gene. The plasmid mutation frequencies were determined by blue/white screening. The spontaneous plasmid mutation frequency of the squamous-cell carcinoma line was slightly higher than the mutation frequencies of the other cell lines tested. The DNA damage induced by triplex-directed psoralen crosslinks increased the mutation frequencies sixfold to eighteenfold in all cell lines tested, with no significant differences among the cell lines. Sequence analyses revealed that the spindle-cell carcinoma line had a different spontaneous mutation spectrum from the other cell lines. DNA damage-induced mutations were predominantly point mutations at the triplex-duplex junction in all of the cell lines tested, as expected. These data suggested that a strong mutator phenotype was not required for progression to an advanced malignant phenotype in our model system.     

Advances in molecular carcinogenesis: current and future use of mouse models to screen and validate molecularly targeted anticancer drugs

Survival of patients with advanced solid tumors has not significantly improved over the past 30 years. Although molecularly targeted anticancer drugs offer promise, few drugs make it through the end of the Food and Drug Administration approval process. Animal models that more closely resemble human carcinogenesis may bridge the gap between preclinical success and benefits for patients. We discuss pros and cons of several mouse models, including genetically engineered mice that each represent different aspects of human cancer, and the screening of targeted drugs in these models.     

The epidemiology of fatty liver

There are insufficient data available on the epidemiology of fatty liver to design a complete and correct view of the prevalence, incidence and natural history of this disorder. This article, mainly based on the revision of recently published papers in this field, attempts to give an overview of the current findings on the epidemiology of fatty liver worldwide. The possible factors involved in the development of fat accumulation in the liver, and their potential role in the progression of the disorder will be also addressed.     

Cytomegalovirus pneumonitis in a patient with Hodgkin disease and ataxia-telangiectasia

We describe a child with with Hodgkin disease and ataxia-telangiectasia who also developed an unusual pneumonitis caused by a cytomegalovirus which was fatal.     

Evidence for both reaching and grasping activity in the medial parieto-occipital cortex of the macaque

In humans, the caudal pole of the superior parietal lobule is involved in the control of both reaching and grasping movements, whereas in monkey it is reported to be involved only in the control of reaching. Using single-unit recordings from trained macaque monkeys, we investigated whether area V6A, a visuomotor area located in the caudal part of the posterior parietal cortex, is involved in both components of prehension, the hand transport towards the visual target and the grip formation to secure the grasp. In Experiment 1, neural activity was recorded in V6A while two monkeys performed two instructed-delay reaching tasks (reach-to-point and reach-to-grasp) under controlled conditions in darkness. Fourty-five of 93 tested neurons (48%) were modulated during reach-to-point and 62% (52/84) during reach-to-grasp. In 63% of cells (51/81) neural activity was significantly different between reach-to-point and reach-to-grasp tasks, suggesting that grip formation could influence neural activity. In Experiment 2, two monkeys performed natural reach-to-grasp movements in fully lit environment; V6A neural activity and arm-hand movements were recorded by a digital camcorder and analysed frame-by-frame using a digital video technique. Thirty of the 58 tested neurons (52%) were modulated during natural prehension; about 30% of these neurons (8/30) were modulated only during the last phase of prehension, i.e. during finger flexion around the object to be grasped. This is the first direct demonstration that both reaching and grasping modulate neural activity in the caudal part of the posterior parietal cortex of the macaque. Our work suggests a strict functional homology between human and monkey superior parietal lobule.