Induction of surface tumor necrosis factor (TNF) expression and possible facilitation of surface TNF release from human monocytic cells by granulocyte-macrophage colony-stimulating factor or gamma interferon in combination with 1,25-dihydroxyvitamin D3

1,25-dihydroxyvitamin D3 (1,25(OH)2D3), gamma interferon (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) can regulate monocyte maturation and activation. Using the human monocytoid cell line U937, we have shown that these agents increase surface tumor necrosis factor (TNF) expression without directly affecting TNF release. GM-CSF and IFN-gamma combined with 1,25(OH)2D3 increased cellular TNF secretion to levels not seen with these agents alone. Ability to express and secrete TNF in part depended on degree of monocytic maturation. The combination of 1,25(OH)2D3 and GM-CSF, however, facilitated lipopolysaccharide (LPS)-mediated release of surface TNF from U937 cells, an effect that was temporally independent of maximal maturation. 1,25(OH)2D3 plus IFN-gamma was less effective than 1,25(OH)2D3 plus GM-CSF at facilitating TNF secretion. We postulate that 1,25(OH)2D3 and GM-CSF are required together to prime a specific mechanism, probably a protease, which cleaves TNF from the surface of monocytic cells. This protease, once primed, can be activated by a secondary stimulus such as LPS.     

Assessment of the effects of release variables on the consequences of LNG spillage onto water using FERC models

Liquefied natural gas (LNG) release, spread, evaporation, and dispersion processes are illustrated using the Federal Energy Regulatory Commission models in this paper. The spillage consequences are dependent upon the tank conditions, release scenarios, and the environmental conditions. The effects of the contributing variables, including the tank configuration, breach hole size, ullage pressure, wind speed and stability class, and surface roughness, on the consequence of LNG spillage onto water are evaluated using the models. The sensitivities of the consequences to those variables are discussed.     

血浆的粘度特性

蒸馏水、盐水、血浆、血清等均被用作生物摩擦磨损研究中的润滑剂。由于血浆在成分上与人体组织液相近，作为生物摩擦磨损的润滑剂，更接近于真实情况，但对其粘度特性并未认真考察。本文采用生理盐水稀释，对不同浓度的抗凝新鲜血浆的粘度特性进行了研究。并对其影响因素进行了讨论。结果表明：在我们的实验条件下，血浆表现出非牛顿性，影响因素中以切变率的影响作用较大。     

Physician's working diagnosis compared to the Euricterus Real Life Data Diagnostic Tool Trial in three jaundice databases: Euricterus Dutch, independent prospective and independent retrospective

BACKGROUND/AIMS: In the European Union Euricterus Project on (sub)Icterus proforma, the history and physical examination items were to be used for the physician's working diagnosis (PWD) and 'among others, for the development of the real life data electronic diagnostic tool, Trial. Trial delivers diagnosis probabilities based on Bayes' Theorem (B), completed by Trial Algorithm (TA). We wanted to compare the diagnostic accuracies (PWD and Trial probabilities as a percentage of the final diagnosis (FD) in a patient population) in 3 Dutch databases. METHODOLOGY: The inclusion criteria for both Euricterus and Trial were age > or = 16 and bilirubin > or = 20 mmol/l. Euricterus data gathering took place at the bedside on a proforma with (among other questions) 79 questions on history and physical examination as well as the diagnosis levels for the PWD (1 alternative possible) and FD (17 disease categories, dc). Trial was developed on the data of 7,104 Euricterus patients and its data-entry Demo has the same questions. It calculates the probability of each diagnosis of the 17 dc as a percentage, as each significant finding is encountered (BO, Bayesian Overall). It can simultaneously calculate the resemblance of the patient's signs and symptoms to each disease concomitantly (BV, Bayesian Vertical), and to any subset of a disease. Any probability is further tested for compatibility using TA, a subset of BV, delivering TA-PWD, TA-BO and TA-BV. The Trial test patients came from 3 databases: a Euricterus Dutch Patients Random Sample EDRS (n = 184, internal database) and 2 independent databases: prospective P (n = 80) and retrospective R (n = 152), totalling 416 patients. RESULTS: The accuracies of PWD and Trial showed no differences between the databases, and the results are therefore pooled (n = 416). With testing on the highest probability found, the PWD accuracy was 78%, TA-PWD 81%, TA-BO 74% and TA-BV 72%. The true FD's were mentioned (at any probability) in the PWD in 86%, TA-PWD in 92%, TA-BO in 94% and TA-BV in 91% of the patients. Testing only patients whose FD was "certain" or whose data were without omissions did not improve accuracy. Testing on probability > 95% improved BO and BV accuracy, but not TA-BO or TA-BV. CONCLUSIONS: The Physician's Working Diagnosis accuracy was approximately 80% and did not greatly improve after TA. The Trial TA-BO and TA-BV accuracies were only slightly less than the PWD. For well-trained physicians, Trial strengthens the physician's judgment, and for those less trained (or those to be trained), it delivers a (sub)icterus diagnostic disease probability at nearly consultant level.     

Modification of IgH PCR clonal analysis by the addition of sucrose and cresol red directly to PCR reaction mixes

We present the findings of a "new" sublethal MCA syndrome in three siblings, one female and two boys, the only children of healthy, non-consanguineous parents. In addition to prenatal growth retardation and early demise, they presented the same pattern of multiple malformations: relative microcephaly with bird-headed face, microphthalmos/coloboma iris/cloudy corneae, genital anomalies with hypospadias and cryptorchidism in the two males. Associated anomalies included: cardiac defects (2/3), unilateral cleft lip/cleft palate (1/3), anal stenosis (2/3) and unilateral renal agenesis (1/3).     

Transgenic mice expressing human ApoB95 and ApoB97. Evidence that sequences within the carboxyl-terminal portion of human apoB100 are important for the assembly of lipoprotein

The structural features of apolipoprotein (apo) B that are important for its covalent linkage to apo(a) to form lipoprotein(a) (Lp(a)) are incompletely understood. Although apoB100 cysteine 4326 is required for the disulfide linkage with apo(a), other structural features, aside from a single free cysteine residue, must be important for apoB's initial interaction with apo(a) and for facilitating the formation of the disulfide bond. To determine if sequences carboxyl-terminal to cysteine 4326 affect the efficiency of Lp(a) formation, we used "pop-in, pop-out" gene targeting in a human apoB yeast artificial chromosome to introduce nonsense mutations into exon 29 of the apoB gene. The mutant yeast artificial chromosomes, which coded for the truncated versions of human apoB, apoB95, and apoB97, were then used to express these mutant forms of apoB in transgenic mice. As judged by in vitro assays of Lp(a) formation, apoB95 (4330 amino acids) formed a small amount of Lp(a) but did so slowly. In contrast, apoB97 (4397 amino acids) formed Lp(a) rapidly, although not quite as rapidly as the full-length apoB100 (4536 amino acids). These results were supported by an analysis of double-transgenic mice expressing both human apo(a) and either apoB95 or apoB97. In mice expressing both apoB95 and apo(a), there was only a trace amount of Lp(a) in the plasma, and most of the apo(a) was free, whereas in mice expressing both apoB97 and apo(a), virtually all of the apo(a) was bound to apoB97 in the form of Lp(a). These results show that sequences carboxyl-terminal to apoB95 (amino acids 4331-4536) are not absolutely required for Lp(a) formation, but this segment of the apoB molecule, particularly residues 4331-4397, is necessary for the efficient assembly of Lp(a).     

Psychosocial, behavioral, and health factors related to menopause symptomatology

California Proposition 65 (Prop65) provides a mechanism by which the manufacturer may perform a quantitative risk assessment to be used in determining the need for cancer warning labels. This paper presents a risk assessment under this regulation for professional and do-it-yourself insulation installers. It determines the level of insulation glass fiber exposure (specifically Owens Corning's R-25 PinkPlus with Miraflex) that, assuming a working lifetime exposure, poses no significant cancer risk under Prop65's regulations. "No significant risk" is defined under Prop65 as a lifetime risk of no more than one additional cancer case per 100,000 exposed persons, and nonsignificant exposure is defined as a working lifetime exposure associated with "no significant risk." This determination can be carried out despite the fact that the relevant underlying studies (i.e., chronic inhalation bioassays) of comparable glass wool fibers do not show tumorigenic activity. Nonsignificant exposures are estimated from (1) the most recent RCC chronic inhalation bioassay of nondurable fiberglass in rats; (2) intraperitoneal fiberglass injection studies in rats; (3) a distributional, decision analysis approach applied to four chronic inhalation rat bioassays of conventional fiberglass; (4) an extrapolation from the RCC chronic rat inhalation bioassay of durable refractory ceramic fibers; and (5) an extrapolation from the IOM chronic rat inhalation bioassay of durable E glass microfibers. When the EPA linear nonthreshold model is used, central estimates of nonsignificant exposure range from 0.36 fibers/cc (for the RCC chronic inhalation bioassay of fiberglass) through 21 fibers/cc (for the i.p. fiberglass injection studies). Lower 95% confidence bounds on these estimates vary from 0.17 fibers/cc through 13 fibers/cc. Estimates derived from the distributional approach or from applying the EPA linear nonthreshold model to chronic bioassays of durable fibers such as refractory ceramic fiber or E glass microfibers are intermediate to the other approaches. Estimates based on the Weibull 1.5-hit nonthreshold and 2-hit threshold models exceed by at least a factor of 10 the corresponding EPA linear nonthreshold estimates. The lowest nonsignificant exposures derived in this assessment are at least a factor of two higher than field exposures measured for professionals installing the R-25 fiberglass insulation product and are orders of magnitude higher than the estimated lifetime exposures for do-it-yourselfers.