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.     

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.     

Stevens-Johnson syndrome during anti-tuberculosis chemotherapy in HIV-seropositive patients: report on six cases

Hypersensitivity reactions may occur during antituberculous chemotherapy. Severe reactions are rare, and in the three years 1983-86 during which we have both worked in Africa managing large numbers of patients with tuberculosis we only saw one or two cases with severe and generalised cutaneous hypersensitivity. In the last 12 months, however, there have been a number of cases with severe Stevens-Johnson syndrome which developed during antituberculous chemotherapy and has invariably been associated with seropositivity to HIV (human immunodeficiency virus).     

Hemorrhage following mandibular osteotomies: a report of 21 cases

Hemorrhage associated with mandibular osteotomies, especially to the extent that it becomes life threatening, is a rare occurrence and its risk is less than that following maxillary orthognathic surgery. Twenty-one cases of significant bleeding following mandibular sagittal split ramus osteotomies, vertical and oblique ramus osteotomies, and genioplasties are presented. Life-threatening hemorrhage associated with mandibular osteotomies is primarily an intraoperative problem and the incidence of major postoperative and recurrent hemorrhage is not as great as following maxillary osteotomies. Suggestions for the avoidance and treatment of these bleeding complications are 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.     

Calcium-activated proteolysis of intracellular domains in the cell adhesion molecules NCAM and N-cadherin.

One of the consequences of increased intracellular calcium in response to a variety of physiological stimuli is the calcium activation of cytosolic proteases. Unlike lysosomal proteases with broad specificity, these calcium-activated neutral proteases show limited proteolysis of a restricted set of substrate proteins suggesting they may play a regulatory role in cellular physiology. In this study we show that the neural cell adhesion molecules NCAM-180 and N-cadherin are substrates for such endogenous calcium-activated neutral proteases. In contrast, a third neural cell adhesion molecule G4/L1 was not susceptible to calcium-activated proteolysis. The threshold for activation of NCAM and N-cadherin proteolysis is in the micromolar range of calcium suggesting that NCAM and N-cadherin are substrates for a mu-type calpain (calpain I). The site recognized by this protease is within intracellular domains of NCAM-180 and N-cadherin which are important for their interaction with cytoskeletal components. These results suggest that calcium-activated proteolysis at these sites in vivo could disrupt the linkage between extracellular ligand binding to these adhesion molecules and the normal intracellular effectors of such extracellular binding events.