Possibility of selection against mtDNA mutations in tumors

Several studies of tumors have revealed substantial numbers of clonally expanded somatic mutations in mitochondrial DNA (mtDNA), not observed in adjacent intact tissues. These findings were interpreted as indicating the involvement of mtDNA mutations in tumorigenesis. Such comparisons, however, ignore an important confounding factor: the monoclonal origin of tumors as opposed to the highly polyclonal nature of normal tissues. Analysis of recently published data on the incidence of somatic mutations in nontumor monoclonal cells suggests that, contrary to the prevailing view, the process of tumorigenesis may be accompanied by active selection against detrimental mtDNA mutations.     

Neurologic aspects of traumatic brain injury

Traumatic brain injury is a common neurologic condition that can have a significant emotional and financial burden. Neurologic injury is classified on the basis of initial clinical status by the Glasgow Coma Scale, and also by the type and location of head injury. Complications in the management of these patients are reviewed, ranging from intracranial pressure management and stroke to post-traumatic epilepsy. In addition, predictive prognostic variables that can be used to predict outcome based on a patient's presentation at the time of a head trauma are discussed. Finally, interventions such as induced hypothermia that can be undertaken to try to optimize outcome, are discussed along with current data in support of or against such techniques.     

RENAL FUNCTION IN CHRONICALLY CATHETERIZED CONSCIOUS DIABETIC RATS USING CONSTANT AND SERVO-CONTROLLED INFUSION

1. Infusion experiments were performed on chronically catheterized conscious rats to assess kidney function before and after the induction of diabetes mellitus with streptozotocin. 2. Two infusion regimens were used, a conventional constant-infusion protocol and a novel computer-driven, servo-controlled fluid replacement technique. The latter enables body fluid status to be maintained throughout a study occasion by servo-controlled replacement of spontaneous urinary fluid losses. 3. The chronically catheterized conscious rat infused using a servo-controlled system appears to be the optimum model for a study of diabetic renal function. The conscious preparation circumvents problems associated with anaesthesia and acute surgery. The servo-controlled infusion protocol maintains the altered fluid status of the diabetic condition. Both hyperfiltration and polyuria, characteristics of human diabetes often absent in anaesthetized and/or constantly infused diabetic rats, were seen in all conscious servo-controlled diabetic animals. 4. The new regimen enables a more accurate assessment of renal function in experimental diabetes than with previous protocols. It should prove useful in future studies, particularly those assessing the role of anti-diabetic drugs on the kidney.     

Unexplained diarrhoea and failure to thrive in 2 siblings with unusual facies and abnormal scalp hair shafts: a new syndrome

A family is described in which 2 siblings born to healthy parents presented with abnormal facies, persistent diarrhoea, and early death. Exhaustive pathological and biochemical investigations failed to find a cause. The scalp hair of both babies had an abnormal amino-acid composition, and presented an appearance that was unique on scanning electron microscopical examination; this fact and the clinical picture probably represents a new syndrome.     

Modulation of implantation-associated integrin expression but not uteroglobin by steroid hormones in an endometrial cell line

In order to test the hypothesis that integrin and uteroglobin (UG) expression in cultured endometrial cells are affected by hormone treatment, Ishikawa-CH endometrial cancer cells were cultured and exposed to oestradiol or oestradiol and progesterone regimens and assayed using immunohistochemistry. We evaluated the intensity of immunohistochemical staining for the integrin monomers alpha(v) and beta1, the dimers alpha(v)beta3 and alpha(v)beta6, and for the secretory protein uteroglobin under various experimental conditions. Cells grown in control media stained positively for the integrin monomers alpha(v) and beta1, the dimer alpha(v)beta3, and for UG. Oestradiol and sequential oestradiol/progesterone reversibly suppressed staining for the dimer alpha(v)beta3. Hormone treatment had no effect on the staining of the beta1 and alpha(v) monomers or UG. The alpha(v)beta6 dimer antibody did not stain under any experimental treatment conditions. These data indicate that expression of the integrin complex alpha(v)beta3 is reversibly suppressed by oestradiol in Ishikawa cells and that these cells may be a good model for studying hormone-driven molecular changes in endometrium.