No impact of repeated endoscopic screens on gastric cancer mortality in a prospectively followed Chinese population at high risk.

BACKGROUND: Gastric cancer (GC) is the leading cause of cancer deaths in China. Our study prospectively evaluated the impact of repeated endoscopic screens on GC mortality in a high-risk population in China. METHODS: Between 1989 and 1999, a population-based gastroscopic screening was conducted in 4,394 residents of Linqu County, China, a region with the highest rates of GC worldwide. Residents ages 35 to 64 years received initial gastroscopies with biopsies in 1989. Repeated endoscopies were performed in 1994 and 1999. Cancer occurrences and deaths were actively monitored throughout the entire period until July 2000. Mortality from GC was compared with expected values based on mortality rates obtained for Linqu in the 1990-1992 Chinese Cancer Mortality Survey. RESULTS: Between March 1989 and July 2000, 39,303 person-years were accumulated; 85 new GCs occurred, 29 (34.5%) were in early stage. Fifty-eight cases (68%) were identified at one of the screens. The number of observed deaths from GC (37) was close to the expected (36.8). The standardized mortality ratio was 1.01 (95% CI 0.72-1.37) for the entire cohort, 1.13 (95% CI 0.77-1.57) for males, and 0.65 (95% CI 0.26-1.32) for females. CONCLUSIONS: Despite high population coverage with repeated screens, no reduction in GC mortality was observed in this high-risk population in China.     

Postprandial induction of chaperone gene expression is rapid in mice.

Molecular chaperones assist in the biosynthesis and processing of proteins. Most chaperones are induced by physiological stresses. We have shown that dietary energy restriction decreases the mRNA and protein levels of many endoplasmic reticulum chaperones in the livers of mice. Here, we have investigated the response of chaperone mRNA to feeding. Control and 50% energy-restricted C3B10RF1 mice were deprived of food for 24 h, fed, and killed 0, 1.5, 5 or 12 h after feeding. Chaperone mRNAs were strongly induced as early as 1.5 h after feeding in control and energy-restricted mice. The integrated levels of these mRNA over 24 h were significantly lower in energy-restricted mice. The mRNA response to energy intake was mirrored over the course of days in the level of chaperone protein. A similar but smaller response to feeding was found in kidney and muscle. Puromycin and cycloheximide failed to inhibit the feeding response, suggesting that feeding releases chaperone expression from an unstable inhibitor. Studies with dibutyryl-cAMP- and glucagon-supplemented, normal and streptozotocin-diabetic mice suggest that glucagon and insulin may be mediators of the feeding response. Adrenalectomy enhanced the feeding induction, but dexamethasone administration had no effect. Thus, postprandial changes in insulin and glucagon may link chaperone gene expression to feeding, possibly in several tissues including liver.     

Enhancement of spontaneous killer cytotoxicity by soluble factor

Two-stage stimulation of SK activity of normal human peripheral blood lymphocytes by soluble factors was demonstrated. The first stage was initiated by factors present in supernatant derived from normal B-LCL cultures. Only cell lines which could induce SK activity in culture in an MLR-type reaction had the capacity to produce the active factor. Supernatant factor required adherent cells to cause SK augmentation. The interaction of adherent cells plus supernatant factor resulted in the production of a second soluble factor which stimulated an increase in SK activity in responding lymphocyte populations. This second stage involved a different soluble factor which acted directly on the non-SK, Fc-negative lymphocyte population, and within 3 hr. Data obtained using antisera to interferon (IF) indicated that IF is a component of the second soluble factor, and not of the supernatant factor derived from the B-LCL.     

Changes in outcome with sphincter preserving surgery for rectal cancer in Korea, 1991-2000.

AIM: To report the clinical and oncological data of patients operated on for rectal cancers 3-5 cm from the AV over a 10 year period, including the Sphincter preservation (SP) rate. METHODS: We reviewed medical records of 304 patients with rectal cancers 3-5 cm from the AV who underwent surgical resection from January 1991 through December 2000. The 10 years were divided into three periods based on the introduction of new surgical techniques, specifically, ultralow anterior resection (ULAR) with double stapling in March 1994 and ULAR with coloanal anastomosis in April 1997. The rates of SP, complications and patient survival during these periods were compared. RESULTS: The SP rate increased significantly over the 10 years, from 16.4% in period I (January 1991-February 1994), to 53.0% in period II (March 1994-March 1997), to 86.5% in period III (April 1997-December 2000) (p<0.001). Over time, the age of the patients increased (p=0.004), the length of the distal resection margin became shorter (p=0.005), and the rate of lymph node metastasis increased (p=0.016). The factors significantly influencing SP were the period (p<0.001) and the distance from the AV (p<0.001). Over time, morbidity did not increase, and overall and disease free survival rates did not decrease. In contrast, the overall survival of N2 cases significantly increased over time (p=0.0492). CONCLUSION: Over 10 years, the SP rate in rectal cancers 3-5 cm from the AV was significantly increased by the introduction of the double stapling and coloanal anastomosis techniques. These surgical methods, however, had no effect on morbidity, disease free survival and overall survival rates.     

CD44 ligation induces apoptosis via caspase- and serine protease-dependent pathways in acute promyelocytic leukemia cells.

We have recently reported that ligation of the CD44 cell surface antigen with A3D8 monoclonal antibody (mAb) triggers incomplete differentiation and apoptosis of the acute promyelocytic leukemia (APL)-derived NB4 cells. The present study characterizes the mechanisms underlying the apoptotic effect of A3D8 in NB4 cells. We show that A3D8 induces activation of both initiator caspase-8 and -9 and effector caspase-3 and -7 but only inhibition of caspase-3/7 and caspase-8 reduces A3D8-induced apoptosis. Moreover, A3D8 induces mitochondrial alterations (decrease in mitochondrial membrane potential DeltaPsi m and cytochrome c release), which are reduced by caspase-8 inhibitor, suggesting that caspase-8 is primarily involved in A3D8-induced apoptosis of NB4 cells. However, the apoptotic process is independent of TNF-family death receptor signalling. Interestingly, the general serine protease inhibitor 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF) decreases A3D8-induced apoptosis and when combined with general caspase inhibitor displays an additive effect resulting in complete prevention of apoptosis. These results suggest that both caspase-dependent and serine protease-dependent pathways contribute to A3D8-induced apoptosis. Finally, A3D8 induces apoptosis in all-trans-retinoic acid-resistant NB4-derived cells and in APL primary blasts, characterizing the A3D8 anti-CD44 mAb as a novel class of apoptosis-inducing agent in APL.     

Neuroleptic drugs in the management of behavioral symptoms of Alzheimer's disease.

Physicians have long been wary of chronically administering neuroleptic drugs to the demented elderly for fear of significant side effects. In this article, the authors present evidence to support these fears. A discussion of the early and late emerging side effects of neuroleptic drugs is presented.     

Spontaneous regression of a temporal arachnoid cyst

Surgery is considered to be the standard therapy for arachnoid cysts (ACs). We report the case of a 13-year-old boy in whom a right temporal AC disappeared spontaneously over a period of 10 years. Bulging of the right temporal skull led to the detection of the cyst by computed tomography (CT) scan at the age of 3 years. There were no other clinical symptoms. Subsequent CT scans showed spontaneous regression of the cyst without surgical intervention. The question as to how ACs should be treated is discussed.     

Regulation of NGF gene expression in CNS glia by cell-cell contact.

Nerve growth factor (NGF) gene expression in central nervous system (CNS) glia appears to be associated with active glial growth. To study the underlying molecular mechanisms, we examined the effects of a number of growth-related factors on NGF mRNA expression in glial cultures. Our results suggest that glial membrane interaction, as a consequence of growth, actively inhibits NGF gene expression in CNS glia.     

Critical illness polyneuromyopathy after artificial respiration.

Up to now, 71 critically ill patients have been reported with neuromuscular complications after artificial respiration. The authors review the literature and present data of a personal series of 22 patients all suffering from severe flaccid tetraparesis and muscle atrophy, which developed after an average of two weeks artificial respiration. The prognosis was relatively good in those surviving the primary disease. The multiconditional causes are discussed with emphasis on the combination of polyneuropathy and myopathy. Tumor necrosis factor (TNF), a key mediator of sepsis, which also has an influence on muscle and nerves, is mentioned as a possible cause of this illness.