Extracellular matrix survival signals transduced by focal adhesion kinase suppress p53-mediated apoptosis

In many malignant cells, both the anchorage requirement for survival and the function of the p53 tumor suppressor gene are subverted. These effects are consistent with the hypothesis that survival signals from extracellular matrix (ECM) suppress a p53-regulated cell death pathway. We report that survival signals from fibronectin are transduced by the focal adhesion kinase (FAK). If FAK or the correct ECM is absent, cells enter apoptosis through a p53-dependent pathway activated by protein kinase C lambda/iota and cytosolic phospholipase A2. This pathway is suppressible by dominant-negative p53 and Bcl2 but not CrmA. Upon inactivation of p53, cells survive even if they lack matrix signals or FAK. This is the first report that p53 monitors survival signals from ECM/FAK in anchorage- dependent cells.     

Hematocrit values in weight-selected and relaxed lines of White Rock chickens

Hematocrits (PCV) were measured at 29 and 106 d of age (PCV1 and PCV2, respectively) in male and female White Plymouth Rocks. Four lines were used, two of which had undergone 40 generations of divergent selection for 8-wk BW (HWS, LWS), and two respective sublines (HWR, LWR), in which selection had been relaxed for five generations. At both ages, males and females did not differ for PCV in lines HWR, LWR, and LWS. For line HWS there was an age by sex interaction that resulted from an age effect for males but not for females, and from a sex effect at each age. At both ages, PCV was higher for the HW than the LW lines. Initially, there was no difference between the selected and their respective relaxed lines, but by 106 d, HWR chickens had a higher PCV than HWS chickens. In lines HWR and LWR, PCV increased with age. There was a negative correlation in HWS males for PCV1 with 28 and 56 d BW. The HWR males also had a negative correlation for PCV1 with BW at 28 d, but not between PCV2 and BW. The correlation for PCV1 with PCV2 was high and positive for HWR males and females.     

Retinal changes mimicking diabetic retinopathy in two nondiabetic, growth hormone-treated patients

A role for GH in the pathogenesis of diabetic retinopathy has long been postulated. Previous clinical studies, however, have been confounded by hyperglycemia. We have identified 2 cases of retinopathy associated with exogenous GH therapy in nondiabetic patients. Cases were identified through the MedWatch drug surveillance system of the U.S. Food and Drug Administration. Causality by concomitant medications was excluded by a search of the literature and the FDA data base. The first patient, an obese, 31-yr-old male with traumatic hypothalamic injury, presented with nonproliferative retinopathy and macular edema, resulting in decreased visual acuity (OD 20/40-1; OS count fingers), which required laser surgery. Human GH had been initiated at 0.009 mg/ kg.day, 14 months earlier, and titrated to 0.017 mg/kg.day. The second patient, a nonobese, 11-yr-old girl receiving GH for the management of short stature in Turner's Syndrome, presented with neovascularization. GH doses were 0.033 mg/kg.day for the first 17 months and 0.043 mg/ kg.day for the following 5 months. Cumulative laboratory and clinical observations suggest that GH and related peptides have a role in retinal pathology independent of the degree of glucose tolerance.     

A DIAGNOSTIC TEST FOR NONLINEAR SERIAL DEPENDENCE IN TIME SERIES FITTING ERRORS

Abstract. Time series analysts have begun to consider the applicability of nonlinear models. In order for nonlinear models to be accepted by practitioners, practicai tests must be avilable to test for the presence of nonlinearity in both raw time series and in the residuals from fitted models. A diagnostic test, based on the bispectrum, for the presence of nonlinear serial dependence in these time series is investigated here using artificial data. Detection of such nonlinear dependence is taken to indicate that nonlinear modelling methods are necessary. The theory behind the test is reviewed and simulations driven by pseudorandom numbers are presented for a variety of models and sample sizes. The simulations indicate that the test has substantial power for many models. In addition, theoretical and empirical results are presented which show that the bispectral diagnostic test is equally powerful for both the source series and for the fitting errors from a line& model. Thus, while the test is suitable for use as a diagnostic test on the fitting errors of linear time series models, prior linear modeling of the time series is not required.     

Glycogen levels in human term placental disks, umbilical cords, and membranes

Glycogen in the placenta and its appendages is important for fetal well-being. The precise location of the glycogen stores, however, is unknown. This study was initiated to quantitate glycogen levels at well-defined sampling sites in more than 641 samples from 10 uncomplicated pregnancies and to correlate these glycogen levels with clinical and morphological variables. By biochemical assay, glycogen levels were greatest in the midumbilical cord section (29.08 +/- 1.18 mg/g dry wt) and lowest in the amnionic membrane (2.31 +/- 0.08 mg/g dry wt). Within the placental disk, parenchymal glycogen levels were greatest near the cord insertion (9.31 +/- 2.68 mg/g dry wt) and lowest at the periphery (5.71 +/- 1.14 mg/g dry wt). The midumbilical cord glycogen level showed strong direct correlations (P < .001) with birth weight, umbilical cord weight, and total calculated umbilical cord glycogen and somewhat lower but significant (P < .037) direct correlations with the calculated mean umbilical cord glycogen level, total calculated placental glycogen content, and placental weight. The glycogen level in the middisk parenchymal section from the fetal surface correlated directly with gestational age. Periodic acid-Schiff stains showed that magenta glycogen granules were most abundant in the cytoplasm of the vascular smooth muscle cells. These data show significant variations in glycogen levels among sampling sites. Definition of the precise sampling site is important for clinicopathologic studies of placental glycogen and for interstudy correlations.     

Escherichia coli O157:H7 requires intimin for enteropathogenicity in calves

Enterohemorrhagic Escherichia coli (EHEC) strains require intimin to induce attaching and effacing (A/E) lesions in newborn piglets. Infection of newborn calves with intimin-positive or intimin-negative EHEC O157:H7 demonstrated that intimin is needed for colonization, A/E lesions, and disease in cattle. These results suggest that experiments to determine if intimin-based vaccines reduce O157:H7 levels in cattle are warranted.     

Analysis of the structure of cardiac rhythm during treatment of auricular fibrillation with digitalis

The structure of cardiac rhythm was studied with the help of specialized computers during digitalization in 60 patients with atrial fibrillation of different etiology. The reduction of the heart contractions rate under digitalization is accompanied by certain changes in the structure of cardiac rhythm: the arrhythmic pattern of the ventricular contractions increases with a predominant growth of the number of long R--R intervals, the transitions from short intervals to longer ones become sharper, and portions of a relatively stable ventricular rhythm appear. Three main types of dynamics of the rhythm structure were distinguished on the basis of the changes in the interval R--R histogram. The described changes in the structure of cardiac rhythm are not specific, but when Digitalis drugs are used alone they can be used as additional criteria for digitalization.     

Can phenformin-induced lactic acidosis be prevented?

Although patients taking phenformin are more likely to develop lactic acidosis in the presence of renal, cardiovascular, or hepatic disease, criteria for safe use of the drug are not well established. Eight diabetics died of lactic acidosis in Nottingham in 1972-5 and all were taking phenformin in therapeutic doses. Six had attended the diabetic clinic within a month of their terminal illness. Two patients had appreciable renal impairment and should not have been given phenformin. Four had hypertension and minimal evidence of renal disease, while in two no predisposing factor was identified. There are so many contraindications to the use of phenformin that it is doubtful whether patients on the drug can be monitored adequately. We suggest that phenformin should be withdrawn from general use.