Transforming the cell surface through proteolysis

Protein shedding, or the proteolytic cleavage of a protein from the surface of a cell, is emerging as an important mechanism in the regulation of cellular activity but it is poorly understood. Growing evidence suggesting that protein shedding and protein function are closely linked may lead to new strategies for the treatment of a wide range of diseases.     

Synthesis and pharmacological evaluation of new flosulide analogues, synthesized from natural safrole

OBJECTIVE: To study the effect of adjuvant chemotherapy after curative hepatic resection in patients with hepatocellular carcinoma. DESIGN: A randomized controlled trial. SETTING: A tertiary referral center. PATIENTS: During a 54-month period, 142 patients with hepatocellular carcinoma underwent hepatic resection at 1 institution. Sixty-six patients who survived the operation and had no demonstrable evidence of residual disease on ultrasonographic examination and hepatic angiographic testing at 1 month after surgery agreed to participate in the study. The median follow-up time was 28.3 months. INTERVENTION: Thirty patients received a combination of intravenous epirubicin hydrochloride (8 doses of 40 mg/m2 each at 6-week intervals) and transarterial chemotherapy using an emulsion of iodized oil and cisplatin (3 courses with a maximum dose of 20 mL each at 2-month intervals). Thirty-six patients had no adjuvant treatment. MAIN OUTCOME MEASURES: Recurrence rate and disease-free survival. RESULTS: A total of 138 courses of intravenous epirubicin was given to the 30 patients. Sixty-one courses of transarterial chemotherapy were given to only 29 of the 30 patients assigned to the treatment group, because the hepatic artery in 1 patient was thrombosed. Six patients (20%) had chemotherapy-related complications with no mortality. Twenty-three of 30 patients in the treatment group and 17 of 36 patients in the control group had recurrences (P=.01). Patients who received adjuvant chemotherapy had a higher incidence of extrahepatic metastases (11 patients vs 5 patients; P=.03). The respective disease-free survival rates at 1, 2, and 3 years were 50%,36%, and 18% for the treatment group and 69%, 53%, and 48% for the control group (P=.04). CONCLUSION: In a group of patients who underwent curative resection of hepatocellular carcinoma, postoperative adjuvant chemotherapy using the present regimen was associated with more frequent extrahepatic recurrences and a worse outcome.     

Microcomputer compilation and solution of crosswords

A system is described which enables crosswords to be automatically compiled or solved, or which alternatively may assist in their manual compilation or solution. Illustrative examples are quoted and the performance of the system, which has been written for an Acorn BBC model B microcomputer with disc pack and printer, is discussed.     

Time of appearance and histology of tumors induced in the dorsal skin of C3Hf mice by ultraviolet radiation from a mercury arc lamp

The time course of skin tumor induction was determined in hair-clipped inbred agouti C3Hf mice irradiated three times per week with a medium-pressure quartz-mercury lamp; 4 different UV doses were used. Although the ears were also exposed to the radiation, in the 3 groups given the highest doses no ear tumors were observed by the time each animal had developed at least 1 tumor on its back. No tumors were found in the animals receiving the lowest UV dose. In the group receiving the highest dose, males developed tumors earlier than did females; this trend continued in the lower dose groups. Many tumors that developed in the back skin were well-differentiated squamous cell carcinomas. Others were less well-differentiated squamous cell carcinomas. Others were less well defined so that the cell of origin was difficult to determine. In the group receiving the highest UV dose, the squamous cell carcinomas were few, whereas at the lower doses they predominated.     

You're Not Paranoid; They Really Are Watching You!

Ensuring both pervasive security and ease of use is a challenge for our research community. Pervasive privacy will be even more difficult to achieve.     

Sudden cardiac death: a retrospective and prospective study

Since the inception of mobile coronary care units (MCCU), patients with sudden cardiac death (SCD) saved by advanced emergency medical technicians (EMT-A) can be studied retrospectively and prospectively. Forty-eight cases of SCD found in ventricular fibrillation (VF) were successfully resuscitated. Only 32% had a myocardial infarction. Most survivors were New York Heart Association (NYHA) class I or II. All class IV survivors with severe congestive heart failure died within 45 days. All class II survivors had angina as the limiting factor. Of all patients with VF, 23% survived. Eighty percent of survivors were class I or II and have resumed previous lifestyles. No clear cut symptom complex was identified. Rescue response time was generally less than five minutes. Intracardiac medications were administered without complications. Empirical administration of sodium bicarbonate correlated poorly with arterial blood gas determinations.     

Molecular alterations in early gastric carcinomas. No apparent correlation with Helicobacter pylori status

The effect of nitric oxide (NO) donors on high-voltage-activated Ca2+ channels in insulin-secreting RINm5F cells was investigated using the patch-clamp technique in the whole-cell configuration. Sodium nitroprusside (SNP, 2-400 microM) induced a dose-dependent reduction in Ba2+ currents with maximal inhibition of 58%. The IC50 for SNP was 45 microM. A different NO donor, (+/-)S-nitroso-N-acetylpenicillamine (SNAP, 500 microM), also produced a 50% decrease in current amplitude. When 200 microM SNP was administered together with the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidozoline-1-oxyl-3-oxide (carboxy-PTIO, 300 microM), the Ba2+ current inhibition was lowered to 7%. Administration of 500 microM 8-bromoguanosine 3':5'-cyclic monophosphate sodium salt (8-Br-cGMP) mimicked the effects of SNP, causing a comparable decrease (56%) in peak-current amplitude. When soluble guanylyl cyclase was blocked by 10 microM 1H-[1,2, 4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ), the inhibitory effect of 200 microM SNP was reduced from 39% to 15%. The SNP-induced current decrease was 36% of controls after the blockade of L-type Ca2+ channels and 30% in the presence of 2.5 microM omega-conotoxin-MVIIC. These data indicate that NO inhibits both L-type and P/Q-type Ca2+ channels in RINm5F cells, probably by an increase in the intracellular levels of cGMP. NO may then significantly influence the Ca2+-dependent release of hormones from secretory cells as well as that of neurotransmitters from nerve terminals.