Characterization of charge trapping in submicrometer NMOSFET's bygate capacitance measurements

Trapping of net positive charge at low gate stress voltage, and of net negative charge at high gate stress voltage, is observed through changes in the gate-to-drain capacitance of the stressed junction. These observations can be explained in terms of electron trapping, hole trapping, and generation of acceptor-like interface states located in the upper half of the bandgap. Channel shortening is also observed and found to exhibit a logarithmic time dependence     

Formula creatinine clearance as a substitute for 24-hour creatine clearance in children with kidney transplantation

A 10-year-old German shepherd dog presented with a periodontal 10 mm interproximal defect between the left mandibular fourth premolar and first molar teeth. Bone graft removed from the caudoventral portion of the ipsilateral hemimandible was placed in the defect as a component of the periodontal treatment plan. The use of bone graft likely contributed to periodontal pocket reduction.     

Education for the nurse of tomorrow: a community-focused curriculum

A competitive enzyme-linked immunoadsorbent assay (ELISA) technique has been developed to facilitate quantitative analysis of the earliest step in the initiation of the extrinsic pathway of coagulation, i.e., complex formation of factor VII/VIIa with tissue factor. The ELISA measures the binding of biotinylated human plasma factor VII to relipidated recombinant human tissue factor. Quantitation of the relative affinity (expressed as IC50) of any factor VII molecular population or structural analogue for tissue factor can be determined by competitive binding. Subnanomolar concentrations of both wild-type recombinant human factor VII (rFVII) and rFVII(R152Q), a mutation at the FVII activation site, competed effectively with biotinylated plasma-derived factor VII in binding to tissue factor. In contrast, the affinity of rFVII(R79Q), a mutation in the first epidermal growth factor-like domain, was 12-fold lower. Following activation of rFVII(R79Q), its affinity for tissue factor and enzymatic activity increased 4-fold and 6-fold, respectively. For wild-type rFVII, enzymatic activity rose significantly following activation. However, its affinity for tissue factor was unchanged. We conclude that both the activation state of factor VII and the mutation of amino-acid residues within the first epidermal growth factor-like domain may alter the affinity of factor VII for tissue factor.     

Potentiation by specific short-chain fatty acids of differentiation and apoptosis in human colonic carcinoma cell lines

The architecture of normal colonic mucosa suggest that terminally differentiated epithelial cells near the top of the crypt are extruded into the colonic lumen. Morphological studies have identified apoptotic cells among the differentiated phenotypes near the crypt-lumen interface, suggesting a link between pathways of differentiation, apoptosis, and cellular shedding. We studied these processes in HT29 and SW620 cells and found that compared to adherent cells, those cells which were shed during standard, uninduced culture conditions exhibited nonrandom DNA fragmentation characteristic of apoptosis. Moreover, these apoptotic cells, which accumulate in the media, exhibited a more differentiated phenotype. Because short-chain fatty acids (SCFAs) are natural effectors of colonic cell differentiation in vivo, we investigated the specificity of three 4-carbon atom SCFAs on potentiating differentiation and apoptosis, and thus accumulation of shed cells in the conditioned media, in these colonic carcinoma cell lines. Whereas the unbranched SCFA butyrate induced a more differentiated phenotype and enhanced apoptosis, two derivatives of butyrate, branched isobutyric acid and a nonmetabolizable fluorine-substituted analogue, heptafluorobutyric acid, were ineffective in inducing either differentiation or apoptosis. Thus, potentiated differentiation and apoptosis in colonic carcinoma cells were linked to SCFA structure and, most likely, utilization.     

Development of a vibratory white finger prevention program for shipyard workers: an exploratory study

OBJECTIVE: To study the effects of thevetoside (TS), a cardiac glycoside, and an inhibitor of Na+, K(+)-ATPase, on tumor cells cultured in vitro. METHODS: The cytotoxic effects of TS on tumor cells were determined by trypan blue dye exclusion, neutral red vital staining and clonogenic assay. The time-effect relationship and growth inhibition of tumor cells by TS were assayed with trypan blue exclusion method. RESULTS: TS at low doses (0.005-0.1 mg.L-1), with dose dependence, was able to kill SMMC-7721, SGC-7901 and HeLa cells. IC50 values for SMMC-7721, SGC-7901 and HeLa cells were 0.007, 0.011 and 0.018 mg.L-1 by trypan blue dye exclusion test and 0.016, 0.055 and 0.078 mg.L-1 by neutral red vital staining test. TS inhibited the clonal forming rate of SMMC-7721 and SGC-7901 significantly with IC50 values of 0.021 and 0.036 mg.L-1, respectively. Only when the cells were continuously treated with TS for more than 8 hours, the drug-induced cell lethality could be displayed and strengthened quickly. The growth of tumor cells was notably inhibited after they were exposed to 0.1 microgram/ml of TS for 12 hours. All the experimental results of antitumor activity in vitro showed that SMMC-7721 was most sensitive to TS among the three kinds of tumor cells. CONCLUSIONS: TS has cytotoxic action on tumor cells cultured in vitro and this lethal effect must have an action process, in which tumor cells are not dead but suffer from deadly injury and lost the capability of unlimited proliferation.     

The use of toxicologic data in mechanistic risk assessment: 1,3-butadiene as a case study

The National Research Council (NRC) recently published a report. Science and Judgment in Risk Assessment, that critiqued the current approaches to characterizing human cancer risks from exposure to chemicals. One issue raised in the report relates to the use of default options for quantitation of cancer risks. Default options are general guidelines that can be used for risk assessment when specific information about a chemical is absent. Research on 1,3-butadiene represents an interesting case study in which existing knowledge on this chemical indicates that two default options may no longer be tenable: (1) humans are as sensitive as the most sensitive animal species, and (2) the rate of metabolism is a function of body surface area rather than inherent species differences in metabolic capacity. Butadiene, a major commodity chemical used in the production of synthetic rubber, is listed as one of 189 hazardous air pollutants under the 1990 Clean Air Act Amendments. Butadiene is a carcinogen in rats and mice, with mice being substantially more sensitive than rats. The extent to which butadiene poses a cancer risk to humans exposed to this chemical is uncertain. Butadiene requires metabolic activation to DNA-reactive epoxides to exert its mutagenic and carcinogenic effects. Research is directed toward obtaining a better understanding of the cancer risks of butadiene in humans by evaluating species-dependent differences in the formation of the toxic butadiene epoxide metabolites, epoxybutene and diepoxybutane. The data include in-vitro studies on butadiene metabolism using tissues from humans, rats, and mice as well as experimental data and physiological model predictions for butadiene in blood and butadiene epoxides in blood, lung, and liver after exposure of rats and mice to inhaled butadiene. The findings suggest that humans are more like rats and less like mice regarding the formation of butadiene epoxides. The research approach employed can be a useful strategy for developing mechanistic and toxicokinetic data to supplant default options used in carcinogen risk assessments for butadiene.     

Evidence for the involvement of protein kinase C isoforms in alpha-1 adrenergic activation of phospholipase A2 in FRTL-5 thyroid cells

BACKGROUND: FRTL-5 thyroid cells are a cell line extensively used for the investigation of thyroid functions. Activation of alpha-1 adrenergic receptors stimulates both arachidonic acid (AA) release and cytosolic Ca2+ increase in this cell line. Cytosolic Ca2+ and arachidonic acid are known to be important second messengers regulating a variety of thyroid functions. The generation of these messengers is regulated primarily by two different types of phospholipases, phospholipase C (PLC) and phospholipase A2 (PLA2). METHODS: Norepinephrine (NE, 10 mumol/L) was used as an alpha-1 adrenergic activator, and cytosolic-free Ca2+ concentration ([Ca2+]i) was determined using the fluorescent dye indo-1. Arachidonic acid release was measured as an indicator of PLA2 activation, and protein kinase C (PKC) activity determination and isoforms identification were performed using commercial kits. RESULTS: Norepinephrine increased [Ca2+]i and AA release. Prevention of NE-induced cytosolic Ca2+ influx, either by removal of extracellular Ca2+ or by use of Ca2+ channel blockers, NiCl2 or CoCl2, inhibited AA generation entirely. Inhibition of NE-induced increase in [Ca2+]i by the Ca2+ chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), also significantly suppressed NE-induced AA release. Inhibition of PKC activity by PKC inhibitors (H-7 or staurosporine) or downregulation induced by prolonged treatment with phorbol 12-myristate 13-acetate (PMA) or thyleametoxin (TX) significantly blocked the NE-induced AA release, which indicates PKC is involved in mediating NE-induced AA release. Protein kinase C activity measurement indicated that NE induced an activation of PKC in 5 minutes. To further characterize the role of PKC or Ca2+ in regulation of AA release, we identified PKC isoforms by immunoblotting with specific antibodies against 8 different Protein kinase C isoforms. PKC-alpha, -beta I, -beta II, -gamma, delta, -epsilon, -zeta, and -eta isoforms were identified. Norepinephrine induced translocation of PKC-alpha, -beta I, -beta II, -gamma, -delta, and -epsilon isoforms but not -zeta and -eta from cytosol to membrane. Chelation of intracellular Ca2+, prevention of Ca2+ influx, or prolonged treatment with thymeleatoxin (TX) completely blocked the NE-induced translocation of PKC-alpha. CONCLUSIONS: These results, taken together with data obtained from AA experiments, suggest that PKC plays a critical role in alpha-1 adrenergic receptor mediated PLA2 activation and subsequent AA release. Extracellular Ca2+ influx is a prerequisite for both PKC-alpha translocation and AA release. Whether Ca2+ acts directly upon the PLA2, or via PKC-alpha, to regulate AA generation is an intriguing question that remains to be clarified.     

Cellular roles of kinesin and related proteins

Frequency response characteristics of six popular stethoscopes are reported for the higher frequency range (to 3000 Hz) to supplement equivalent measurements for the lower frequencies (35-1000 Hz) published previously. Spectra of the sounds of swallowing from the throat, transduced with an accelerometer, demonstrate important frequency composition in this higher range. Two stethoscope models were found to have superior transmission characteristics for use in cervical auscultation of swallowing sounds.     

Respective importance of the different risk factors for osteoporosis

Among the factors which influence accumulation of bone mass, genetic factors related to race and family are preponderant: they account for approximately 80% of the variance observed in adulthood. At puberty, nutritional factors and physical activity modulate the accumulation of bone and determine whether or not optimal bone mass is achieved. In women, estrogen deprivation following menopause, and also more minor disorders of gonad function, are the main causes of decreased bone mass; their respective contributions are analyzed.