Nuclear transfer and cloning

Ultraviolet-induced erythema is now recognized as an important clinical marker for skin cancer risk. People with a history of repeated erythematous exposures to sunlight are more likely to develop both melanoma and nonmelanoma skin cancers. Is erythema the most important thing we need to be concerned about in terms of protecting the public from the harmful effects of sunlight? What do we know about UV-induced erythema, and why is it a powerful influence on skin cancer risk?     

Maintenance of recombinant type A gamma-aminobutyric acid receptor function: role of protein tyrosine phosphorylation and calcineurin

In the present study, rundown of gamma-aminobutyric acid (GABA)-activated Cl- channels was studied in recombinant GABAA receptors stably expressed in human embryonic kidney cells (HEK 293), with conventional whole-cell and amphotericin B-perforated patch recording. When [ATP]i was lowered to 1 mM and resting [Ca++]i was buffered to a relatively high level, the response of alpha 3 beta 2 gamma 2 GABAA receptors to relatively low [GABA] (up to 50 microM) did not show rundown in the whole-cell configuration. However, high [GABA] (greater than 200 microM) induced significant rundown, which was observed by decreases in both the maximum GABA-induced current and GABA EC50. Rundown was prevented completely with a solution containing 4 mM Mg(++)-ATP and low resting [Ca++]i, or during perforated patch recording. The magnitude of rundown was comparable in alpha 1 beta 2 gamma 2 and beta 2 gamma 2 receptors. Neither stimulation nor inhibition of protein kinase A or protein kinase C had a significant effect on rundown. However, sodium metavanadate, an inhibitor of protein tyrosine phosphatase, significantly reduced rundown. In addition, inhibition of protein tyrosine kinase activity by either genistein or lavendustin A induced rundown of the GABA response. Inhibition of the Ca++/calmodulin-dependent phosphatase calcineurin with fenvalerate also prevented rundown of the response to GABA. Our results demonstrate that rundown of GABAA receptor function is concentration-dependent, due to depletion of ATP and/or unbuffered [Ca++]i, and does not depend on the presence or subtype of the alpha subunit. We propose that protein phosphorylation at a tyrosine kinase-dependent site, and a distinct unidentified site, which is dephosphorylated by calcineurin, maintains the function of GABAA receptors.     

Continuous active T-gate travelling-wave transistor

In the letter experimental results are presented which show that a continuous active gate travelling-wave transistor (TWT) can be used for medium power applications in a wide bandwidth. To reduce the gate resistance, a T-gate configuration has been chosen. This allows one to extend the frequency bandwidth of such a device. Simulations have been performed using small- and large-signal models taking in addition the parasitic capacitances into account. A distributed Schottky diode has been used to adjust the phase synchronisation and therefore to achieve flat gain.<>     

Influence of GMPLS on network providers' operational expenditures: a quantitative study

GMPLS is promoted as a major technology for the automation of network operations. It is often claimed to allow the reduction of operational expenses. However, detailed analysis and quantitative evaluation of the changes induced by such technologies is very rare. In this article we quantify the cost reduction potential of GMPLS. We present a detailed analysis and modeling of traditional operator processes. We also develop a model for the expected changed processes when using GMPLS and identify the differences quantitatively. A survey with major telecom operators has been done, and the process models have been verified and parameterized. This allowed quantitative evaluations of the OPEX changes with GMPLS. The results show that, depending on the network operator's processes, different impacts can be expected. As an overall result we could verify that a reduction on the order of 50 percent of OPEX can be expected for most operational models.     

Acute Meckel's diverticulum in a senior patient

Meckel's diverticulum is the most common congenital abnormality of the intestinal tract, occurring in 2% of autoptic studies. The case of an 85-year-old man referred to the Emergency Surgery Unit for intestinal obstruction and lower gastrointestinal tract bleeding is reported. Surgical exploration revealed a complicated Meckel's diverticulum full of coproliths, immersed in pus and blood. Examination of the resected diverticulum showed necrotic diverticulitis in the absence of ectopic gastric or pancreatic tissues.     

Creativity of undergraduates with and without family history of alcohol and other drug problems

BACKGROUND: Colonoscopic surveillance is a standard procedure in many patients with long standing, extensive ulcerative colitis (UC), in order to avoid death from colorectal cancer. No conclusive proof of its benefits has been presented however. AIMS: To evaluate the association between colonoscopic surveillance and colorectal cancer mortality in patients with UC. PATIENTS: A population based, nested case control study comprising 142 patients with a definite UC diagnosis, derived from a study population of 4664 patients with UC, was conducted. METHODS: Colonoscopic surveillance in all patients with UC who had died from colorectal cancer after 1975 was compared with that in controls matched for age, sex, extent, and duration of the disease. Information on colonoscopic surveillance was obtained from the medical records. RESULTS: Two of 40 patients with UC and 18 of 102 controls had undergone at least one surveillance colonoscopy (relative risk (RR) 0.29, 95% confidence interval 0.06 to 1.31). Twelve controls but only one patient with UC had undergone two or more surveillance colonoscopies (RR 0.22, 95% confidence interval 0.03 to 1.74), indicating a protective dose response relation. CONCLUSION: Colonoscopic surveillance may be associated with a decreased risk of death from colorectal cancer in patients with long standing UC.     

Clearance of technetium 99m N-NOET in normal, ischemic-reperfused, and membrane-disrupted myocardium

BACKGROUND: Technetium 99m-labeled bis(N-ethoxy, N-ethyl dithiocarbamato) nitrido technetium(v) (99mTcN-NOET) is a new neutral cardiac perfusion imaging agent that has been shown to have very high uptake and retention in vitro. The purpose of this study was to determine the clearance kinetics of 99mTcN-NOET in control, ischemic-reperfused, and membrane-disrupted myocardium. METHODS AND RESULTS: After a 100 microCi (3.7 x 10(6) Bq) bolus of 99mTcN-NOET was injected, myocardial clearance was monitored for 1 hour by the use of a sodium iodide detector in 30 isolated, Krebs-Henseleit (KH) perfused rat hearts. Seven hearts were used as controls (group 1). In seven ischemic-reperfused hearts, tracer administration and uptake was followed by 30 minutes of no flow and 1 hour of reflow (group 2). In six additional ischemic-reperfused hearts, tracer administration was followed by deprivation of flow for 1 hour followed by 1 hour of reflow (group 3). Six hearts were perfused with a 0.5% Triton X-100 KH perfusate for 1 hour (group 4). Four hearts were perfused with KH for 10 minutes, followed by cyanide for 10 minutes (group 5). This cycle was repeated three times. Activities remaining in each heart at the end of each experiment were quantitated, and activity at peak uptake was calculated. The 99mTcN-NOET myocardial clearance was near linear in the control (0.6 +/- 0.4) and both ischemic-reperfused groups with virtually no fractional clearance (1.2% +/- 0.6% and 2.1% +/- 0.6%, respectively; p = NS). In the Triton X-100 membrane-disrupted hearts, clearance was substantial (94.2% +/- 4.0%; p < 0.0001 compared with the control and ischemic-reperfused groups). Cyanide treatment produced rapid clearance, which was arrested by a return to the standard KH perfusate. Peak uptake as a percentage of injected dose was 74.9% +/- 1.4% for all groups combined. CONCLUSION: Thus 99mTcN-NOET has extremely high myocardial retention after 1 hour in normal myocardium and is not significantly affected by ongoing myocardial ischemia or reperfusion injury in this model. Clearance is increased markedly in extreme conditions of membrane disruption. These data are consistent with the concept that 99mTc-NOET is localized predominantly in or on cell membranes. 99mTcN-NOET is a promising, new myocardial perfusion imaging agent that exhibits a stable myocardial distribution in the setting of acute developing injury.     

Regulation of BRCA1 and BRCA2 expression in human breast cancer cells by DNA-damaging agents

Germline mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 have been linked to the development of breast cancer, ovarian cancer, and other malignancies. Recent studies suggest that the BRCA1 and BRCA2 gene products may function in the sensing and/or repair of DNA damage. To investigate this possibility, we determined the effects of various DNA-damaging agents and other cytotoxic agents on the mRNA levels of BRCA1 and BRCA2 in the MCF-7 and other human breast cancer cell lines. We found that several agents, including adriamycin (a DNA intercalator and inhibitor of topoisomerase II), camptothecin (a topoisomerase I inhibitor), and ultraviolet radiation induced significant decreases in BRCA1 and BRCA2 mRNA levels. Decreased levels of BRCA1 and BRCA2 mRNAs were observed within 6-12 h after treatment with adriamycin and persisted for at least 72 h. Adriamycin also induced decreases in BRCA1 protein levels; but these decreases required several days. U.V. radiation induced dose-dependent down-regulation of BRCA1 and BRCA2 mRNAs, with significant decreases in both mRNAs at doses as low as 2.5 J/m2, a dose that yielded very little cytotoxicity. Adriamycin-induced down-regulation of BRCA1 and BRCA2 mRNAs was first observed at doses that yielded relatively little cytotoxicity and little or no apoptotic DNA fragmentation. Adriamycin and U.V. radiation induced distinct dose- and time-dependent alterations in the cell cycle distribution; but these alterations did not correlate well with corresponding changes in BRCA1 and BRCA2 mRNA levels. However, the adriamycin-induced reduction in BRCA1 and BRCA2 mRNA levels was correlated with p53 functional status. MCF-7 cells transfected with a dominant negative mutant p53 (143 val-->ala) required at least tenfold higher doses of adriamycin to down-regulate BRCA1 and BRCA2 mRNAs than did parental MCF-7 cells or control-transfected MCF-7 clones. These results suggest that BRCA1 and BRCA2 may play roles in the cellular response to DNA-damaging agents and that there may be a p53-sensitive component to the regulation of BRCA1 and BRCA2 mRNA expression.