Simulation of deep submicron SOI N-MOSFET considering the velocityovershoot effect

A set of numerical simulations were performed on 0.22 μm SOI MOSFET's with relatively uniform channel field and charge using the hydrodynamic model, the energy transport model, and the drift-diffusion model. The simulation results based on the advanced models (hydrodynamic and energy transport) show nearly identical results for the I-V characteristics and they agreed quite well with the experimental results, while the results from drift-diffusion model do not. Also the simulation results show that both the hydrodynamic and energy transport models handle the effect of velocity overshoot on the I-V characteristic of the 0.12 μm device well     

Back pain in patients with ductal pancreatic cancer. Its impact on resectability and prognosis after resection

BACKGROUND: Back pain is a frequent and often ominous clinical sign in patients with ductal pancreatic cancer. METHODS: From 1971 to 1993 a pancreatic carcinoma could be resected in 192 patients, whereas 261 patients underwent either probatory laparotomy alone or palliative bypass procedures. In a retrospective study including uni- and multi-variate survival analysis we have determined the impact of preoperative back pain on both resectability and long-term prognosis after resection. RESULTS: Among the presenting symptoms of patients with ductal pancreatic cancer back pain was a predictive sign of irresectability. In the presence of preoperative back pain the long-term prognosis after resection of the tumour was also significantly impaired. In a multivariate analysis it could be demonstrated that the prognostic impact of back pain was as strong as the influence of residual tumour, tumour grading, and tumour size. CONCLUSIONS: Back pain often indicates irresectability of ductal pancreatic carcinoma and also impairs the long-term prognosis even after curative resection.     

Construction of a mouse blastocyst cDNA library by PCR amplification from total RNA

Prostaglandin E2 (PGE2) and beta-adrenergic agonists can suppress lipopolysaccharide-induced tumor necrosis factor-alpha (TNF) production from elicited macrophages. We assessed the responsiveness of rat peritoneal macrophages to PGE2 and the beta-adrenergic agonist isoproterenol during immunologically-mediated arthritis. We assessed macrophage sensitivity to these mediators from resident macrophages and macrophages elicited with either streptococcal cell wall or complete Freund's adjuvant. Peritoneal macrophages were obtained from female Lewis rats that were (1) injected with complete Freund's adjuvant and non-arthritic (CFA); (2) injected with streptococcal cell wall and arthritic (ART); (3) injected with streptococcal cell wall and non-reactive (NON) and (4) non-elicited resident macrophages (RES). When challenged with graded concentrations of lipopolysaccharide (0.1 to 10,000 ng/ml), macrophages obtained from each group of rats released TNF in a concentration-dependent manner, with macrophages from arthritic rats (ART) producing the greatest amount of TNF (p < 0.001). While PGE2 suppressed lipopolysaccharide (100 ng/ml) stimulated TNF production in a concentration-dependent manner in all groups, the greatest sensitivity to PGE2 was observed with macrophages obtained from rats which received streptococcal cell wall when compared to both complete Freund's adjuvant-elicited and resident macrophages (p < 0.05). The beta-adrenergic agonist isoproterenol also inhibited lipopolysaccharide-stimulated TNF production from macrophages in all groups. In addition, the specific beta 2-adrenergic antagonist, ICI 118.551, shifted isoproterenol concentration-effect curves to the right (p < 0.01). Minimal responsiveness to isoproterenol was observed with resident peritoneal macrophages. Maximum isoproterenol-induced inhibition of TNF production was observed with complete Freund's adjuvant-elicited macrophages, and significantly less in macrophages of streptococcal cell wall-injected rats. Of particular interest, macrophages obtained from streptococcal cell wall-injected rats, which became arthritic, were significantly less sensitive to isoproterenol than those which did not develop arthritis (p < 0.02). In addition, these changes in sensitivity were not reflected by changes in the sensitivity of both CFA and ART groups to dibutyryl cAMP. The present study demonstrates a shift in the balance between inhibitory mediator responses in rats inoculated with one of two different adjuvants. These investigations support the role of PGE2 and a neurotransmitter as immunomodulating compounds which may effectively maintain an inflammatory lesion such as arthritis.     

Expression of the multidrug resistance-associated protein (MRP) gene in human cancers

We determined the expression of a newly recognized drug resistance gene, the multidrug resistance-associated protein (MRP) gene, [Cole et al., Science (Washington DC), 258: 1650-1654, 1992], in normal human tissues and in >370 human tumor biopsies using a quantitative RNase protection assay and immunohistochemistry. MRP mRNA appeared to be ubiquitously expressed at low levels in all normal tissues, including peripheral blood, the endocrine glands (adrenal and thyroid), striated muscle, the lymphoreticular system (spleen and tonsil), the digestive tract (salivary gland, esophagus, liver, gall bladder, pancreas, and colon), the respiratory tract (lung), and the urogenital tract (kidney, bladder, testis, and ovary). The human cancers analyzed could be divided into three groups with regard to MRP expression. Group 1 consists of tumors that often exhibit high to very high MRP mRNA levels (e.g., chronic lymphocytic leukemia). Group 2 comprises the tumors that often exhibit low, but occasionally exhibit high MRP mRNA expression (e.g., esophagus squamous cell carcinoma, non-small cell lung cancer, and acute myelocytic leukemia). Group 3 comprises the tumors with predominantly low levels of MRP mRNA, comparable to the levels found in normal tissues (e.g., other hematological malignancies, soft tissue sarcomas, melanoma, and cancers of the prostate, breast, kidney, bladder, testis, ovary, and colon). Using the MRP-specific mAbs MRPr1 and MRPm6, we confirmed the elevated MRP mRNA levels in tumor tissues by immunohistochemistry. We conclude that hyperexpression of MRP is observed in several human cancers, and that additional studies are needed to assess the clinical relevance of MRP.     

Transcytosis of the polymeric Ig receptor requires phosphorylation of serine 664 in the absence but not the presence of dimeric IgA

MDCK cells expressing the polymeric immunoglobulin (poly-Ig) receptor, cocultured with IgA-producing hybridoma cells, transported dimeric IgA (dIgA) from the basolateral into the lumenal compartment, where it was recovered as secretory component-dIgA complexes. The tail of the receptor was phosphorylated on serines 664 and 726. Each serine was mutated to alanine. Appearance of A726 receptor at the basolateral surface was reduced approximately 5-fold. This was accompanied by a approximately 5-fold reduction in dIgA transcytosis. Basolateral delivery of receptor was not affected by mutation A664, and in the absence of dIgA, the receptor accumulated in recycling basolateral endosomes. In coculture, however, dIgA transcytosis by A664 receptor was normal. Thus, entry of receptor into the transcytotic pathway requires Ser-664 phosphorylation only in the absence of dIgA.     

Persistent inhibition of neutrophil function by glucose based dialysis solutions

Local defense mechanisms play an important role in prevention of peritonitis, a major complication of continuous ambulatory peritoneal dialysis (CAPD) therapy. The authors have shown that hypertonic, lactate containing glucose based dialysis solutions (GBDS) used in CAPD lead to an immediate and complete pH-dependent inhibition of actin polymerization and phagocytosis in polymorphonuclear neutrophils (PMN) in vitro. Earlier studies have shown that the pH of the fluid equilibrates from 5.2 to approximately 6.4 during the first 30 min of intraperitoneal dwell time. Thus, the authors designed the current study to determine whether the inhibition of cytoskeletal function and intracellular acidosis induced by acidic solutions are reversed by this pH adjustment. To this end, actin polymerization, phagocytosis, and intracellular pH were studied in PMN isolated from healthy human donors during a 10 min incubation in commercially available GBDS at pH 5.2 and again after pH adjustment to 6.4. Actin polymerization was assessed by measuring F-actin content using NBD phallacidin staining and fluorescence activated cell scanner analysis. Phagocytosis was assessed using zymosan particles, and intracellular pH was monitored by spectrofluorometry. The impairment of cytoskeletal alterations in cells exposed to GBDS at pH 5.2 was persistent and not fully reversed by adjusting the pH. Likewise, phagocytosis remained markedly inhibited and intracellular pH did not rise after adjustment of pH. Thus, the results demonstrate a persistent cytotoxic effect of CAPD solutions on human phagocytes. The authors think that CAPD solutions must be modified to provide a more physiologic pH environment for proper phagocyte function.     

Gunshot wounds: 10-year experience of a rural, referral trauma center

The 10-year experience of a Level II trauma center with 122 gunshot wounds referred from a large rural area was analyzed to illustrate differences from the experience of urban centers. Most frequent causes of injury were attempted suicide in 38 (31%) patients, hunting mishaps in 32 (26%), unintentional accidents in 29 (24%), and intentional assault in 18 (15%). Of weapons specified, rifles were documented in 48 (39%) instances, shotguns in 25 (21%), and handguns in 24 (20%). Body regions injured were the trunk in 47 (39%) patients, head in 35 (29%), lower extremity in 31 (25%), and upper extremity in 29 (24%). Twenty-five patients (20%) died as a result of their injuries. The cause of death was brain injury in 18 (72%), exsanguination from truncal wounds in 5 (20%), myocardial infarction in 1 (4%), and multiple organ failure in 1 (4%). We conclude that the distributions of cause and type of gunshot wounds are unique in a rural setting. These differences have profound consequences in designing effective prevention programs for our area and support the design of more efficient trauma systems for rural North America.     

Atrial natriuretic peptide inhibits evoked catecholamine release by altering sensitivity to calcium

Natriuretic peptides are cyclized peptides produced by cardiovascular and neural tissues. These peptides inhibit various secretory responses such as the release of renin, aldosterone and autonomic neurotransmitters. This report tests the hypothesis that atrial natriuretic peptide reduces dopamine efflux from an adrenergic cell line, rat pheochromocytoma cells, by suppressing intracellular calcium concentrations. The L-type calcium channel inhibitor, nifedipine, markedly suppressed dopamine release from depolarized PC12 cells, suggesting that calcium entering through this channel was the predominant stimulus for dopamine efflux. Atrial natriuretic peptide maximally reduced depolarization-evoked dopamine release 20 +/- 3% at a concentration of 100 nM and this effect was abolished by nifedipine, but not by pretreatment with the N-type calcium channel inhibitor, omega-conotoxin, or an inhibitor of calcium-induced calcium release, ryanodine. In cells loaded with Fura-2, atrial natriuretic peptide both augmented depolarization-induced increases of intracellular free calcium concentrations and accelerated the depolarization-induced quenching of the Fura-2 signal by manganese, findings consistent with enhanced conductivity of calcium channels. Dopamine efflux induced by either the calcium ionophore, A23187, or staphylococcal alpha toxin was attenuated by atrial natriuretic peptide. Additionally, a natriuretic peptide interacting solely with the natriuretic peptide C receptor in these cells, C-type natriuretic peptide, also suppressed calcium-induced dopamine efflux in permeabilized cells. These data are consistent with natriuretic peptides attenuating catecholamine exocytosis in response to calcium but inconsistent with the neuromodulatory effect resulting from a reduction in intracellular calcium concentrations within pheochromocytoma cells.