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At least 1,027 records · Page 57Linked to original sources
PubMed2006

17-allylamino-17-demethoxygeldanamycin synergistically potentiates tumor necrosis factor-induced lung cancer cell death by blocking the nuclear factor-kappaB pathway.

Nuclear factor-kappaB (NF-kappaB), a survival signal induced by tumor necrosis factor (TNF), contributes substantially to the resistance to TNF-induced cell death. Previous studies suggest that heat shock protein 90 (Hsp90) regulates the stability and function of receptor-interaction proteins (RIP) and IkappaB kinase beta (IKKbeta), the key components of the TNF-induced NF-kappaB activation pathway. In this study, we showed that the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17AAG) was synergistic with TNF to induce apoptotic cell death in a panel of lung tumor-derived cell lines. Treatment with 17AAG caused degradation of RIP and IKKbeta that, in turn, blocked TNF-induced NF-kappaB activation and antiapoptotic gene expression. The synergistic cytotoxicity was detected only when TNF treatment followed 17AAG preexposure. Importantly, the potentiation of cell death was abolished in NF-kappaB-disabled cells that express a nondegradable IkappaBalpha mutant (IkappaBalphaAA). These results suggest that the cytotoxicity seen with 17AAG and TNF treatment results from blocking TNF-induced NF-kappaB activation. The other components of the TNF receptor I signaling cascade were not altered, whereas TNF-induced c-Jun NH(2)-terminal kinase activation and apoptosis were potentiated. A similar synergism for inducing apoptosis was also observed in 17AAG-treated and TNF-related apoptosis-inducing ligand (TRAIL)-treated cancer cells. Our results suggest that NF-kappaB plays a key role in the resistance of lung cancer cells to TNF and TRAIL and that disabling this survival signal with 17AAG followed by TNF or TRAIL treatment could be an effective new therapeutic strategy for lung cancer.

Apoptosis↗
PubMed1987

Distribution of blood groups in the East African Somali population.

The results of a population survey on blood group distribution in Somalia, East Africa, are presented. Over 1,000 subjects were tested for most blood groups included in the survey. The sampling covered the whole country and was well in accordance with the population density as estimated by the recorded birth places of the subjects. Altogether, 46 blood group antigens were tested, partly common antigens within 11 of the major blood group systems, but also infrequent and very frequent antigens, some not tested before in Africa, were included. The results were compared with the available data for other related peoples and for populations from the same geographical area. The standard genetic distances were also applied in the comparison. The results suggest that only a minor component in the genetic constitution of the Somali population can be ascribed to Caucasian admixture. They are markedly in contrast with some earlier findings. During the survey we observed a previously unknown Rh gene complex occurring with a polymorphic frequency in Somalis.

Adult↗
PubMed1982

Complement biosynthesis by the human hepatoma-derived cell line HepG2.

The human hepatoma-derived cell line, HepG2, synthesized and secreted functional complement proteins C1r, C1s, C2, C3, C4, C5, factor B, C1 inhibitor, C3b inactivator, a small amount of C6, and trace amounts of C8; but failed to produce detectable C1q, C7, or C9. Immunochemically, C2, C3, C4, C5, and B were isolated from culture medium as proteins with molecular sizes and subunit structures identical to the corresponding components isolated from serum. C2 and factor B from cellular lysates had slightly lower molecular weights than the corresponding proteins in culture medium. C3, C4, and C5 were detected as single chain precursor molecules in cellular lysates. These results demonstrate that human C5, like C3 and C4, is synthesized as a single chain precursor that is converted by limited proteolysis to the native two-chain molecule. It also establishes the precursor-product relationship for human pro-C4 and native C4, pro-C5, and native C5.

Carcinoma, Hepatocellular↗
PubMed1983

Demonstration that a human hepatoma cell line produces a specific insulin-like growth factor carrier protein.

Insulin-like growth factors (IGF's) circulate in blood complexed to specific carrier proteins. The BRL 3A and BRL 3A2 rat liver cell lines secrete a 30,000-50,000 mol wt IGF carrier protein. Since the liver parenchymal cell is a likely source of IGF carrier protein synthesis, we have evaluated medium conditioned by three human hepatocellular carcinoma- or hepatoblastoma-derived cell lines for the presence of IGF carrier protein. The HEP G2 and the HEP 3B, but not the PLC/PRF/5, cell lines secrete a specific IGF carrier protein(s) into serum-free medium. This carrier protein is specific for IGF molecules. Multiplication-stimulating activity, IGF I, and IGF II were equipotent in competing for the binding of [125I]multiplication-stimulating activity to HEP G2 medium. The HEP G2 IGF carrier protein is trypsin sensitive, acid stabile, and does not contain a glycoprotein moiety. It has a molecular size of 30,000-50,000, as assessed by Sephadex G-200 gel filtration. These studies suggest that the HEP G2 cell line is a useful model to study the synthesis and secretion of human IGF carrier protein.

Binding, Competitive↗
PubMed1984

Hormonal influences on the secretion of steroid-binding proteins by a human hepatoma-derived cell line.

We examined the influence of numerous substances on the secretion of corticosteroid-binding globulin (CBG) and testosterone-estradiol binding globulin (TeBG) by a human hepatoma-derived cell line. Thyroxine, at physiologic concentrations, resulted in an increased secretion of TeBG but not CBG. Estrogens, antiestrogens, and androgens were without effect on either of these binding proteins.

Animals↗
PubMed1985

Characterization of thyroxine-binding globulin secreted by a human hepatoma cell line.

T4-binding globulin (TBG) is a glycoprotein synthesized by the liver and is the principal carrier of T4 and T3 in serum. In this report, we demonstrate that the Hep G2 cell line, derived from a human hepatoblastoma, synthesizes and secretes TBG, the properties of which were characterized. Hep G2 cells secreted TBG into the medium after more than 100 transfers in tissue culture conditions. At confluency and after changing to serum-free culture conditions, TBG accumulation into the medium was linear for 3 days and constituted approximately 0.16% of the proteins synthesized over 24 h. Its abundance relative to albumin is 10-fold greater than that found in normal human serum. TBG secreted by the Hep G2 cells was indistinguishable from native normal human serum TBG, as determined immunologically, by electrophoresis on polyacrylamide gel in denaturing and nondenaturing conditions, and by isoelectric focusing. It also specifically bound T4 and T3, albeit with slightly reduced affinity, and had increased heat lability. Although slightly different from normal serum TBG in caucasians, the physical and biological properties of the Hep G2-derived TBG are similar to those of the variant TBG found in the serum of some healthy Australian Aborigines.

Carcinoma, Hepatocellular↗
PubMed1977

Periostitis of the mandible. A case report and review of the literature.

Periostitis of the mandible has not been previously discussed in the otolaryngologic literature and only infrequently in the dental literature. It is characterized by a hard, painless, fixed mass overlying the mandible in a child or young adult. The etiology is usually an endosteal infection in the molar region with periosteal inflammation. Reactive new bone is deposited beneath the elevated periosteum, external to the outer cortex of the jaw, and separated from it by a layer of suppurative fluid. Treatment consists of removal of involved teeth and infected bone, drainage of the fluid pocked and appropriate antibiotics. Patients are followed with repeat X-rays and erythrocyte sedimentation rates. A case is presented and the world literature is reviewed. The otolaryngologist should be aware of this entity and include it in the differential diagnosis of any fixed jaw mass to avoid mistaking it for a more malignant process with unfortunate consequences.

Adolescent↗
PubMed2002

Parametric dependencies of high-diffraction-order achromatized aplanatic configurations that employ circular or crossed-linear diffractive optical elements.

The parametric relationships of achromatized transmissive and reflective diffractive optical elements (DOEs) are explored for a number of configuration classes as a function of diffraction order, focal ratio, wavelength, and field angle. The necessity for blazing high-diffraction-order DOEs is elucidated. The ray image sizes are presented in dimensionless imaging space and thus are applicable to any size of optical system. Several aplanatic configurations are evaluated.

Journal Article↗
PubMed2004

Optical phased array configuration for an extremely large telescope.

Extremely large telescopes are currently under consideration by several groups in several countries. Extrapolation of current technology up to 30 m indicates a cost of over dollars 1 billion. Innovative concepts are being explored to find significant cost reductions. We explore the concept of an Optical Phased Array (OPA) telescope. Each element of the OPA is a separate Cassegrain telescope. Collimated beams from the array are sent via an associated set of delay lines to a central beam combiner. This array of small telescope elements offers the possibility of starting with a low-cost array of a few rings of elements, adding structure and additional Cass elements until the desired diameter telescope is attained. We address the salient features of such an extremely large telescope and cost elements relative to more conventional options.

Journal Article↗
PubMed2004

Conversion of distiller's grain into fuel alcohol and a higher-value animal feed by dilute-acid pretreatment.

Over the past three decades ethanol production in the United States has increased more than 10-fold, to approx 2.9 billion gal/yr (mid-2003), with ethanol production expected to reach 5 billion gal/yr by 2005. The simultaneous coproduction of 7 million t/yr of distiller's grain (DG) may potentially drive down the price of DG as a cattle feed supplement. The sale of residual DG for animal feed is an important part of corn dry-grind ethanol production economics; therefore, dry-grind ethanol producers are seeking ways to improve the quality of DG to increase market penetration and help stabilize prices. One possible improvement is to increase the protein content of DG by converting the residual starch and fiber into ethanol. We have developed methods for steam explosion, SO2, and dilute-sulfuric acid pretreatment of DG for evaluation as a feedstock for ethanol production. The highest soluble sugar yields (approximately 77% of available carbohydrate) were obtained by pretreatment of DG at 140 degrees C for 20 min with 3.27 wt% H2SO4. Fermentation protocols for pretreated DG were developed at the bench scale and scaled to a working volume of 809 L for production of hydrolyzed distiller's grain (HDG) for feeding trials. The pretreated DG was fermented with Saccharomyces cerevisiae D5A, with ethanol yields of 73% of theoretical from available glucans. The HDG was air-dried and used for turkey-feeding trials. The inclusion of HDG into turkey poult (as a model non-ruminant animal) diets at 5 and 10% levels, replacing corn and soybean meal, showed weight gains in the birds similar to controls, whereas 15 and 20% inclusion levels showed slight decreases (-6%) in weight gain. At the conclusion of the trial, no negative effects on internal organs or morphology, and no mortality among the poults, was found. The high protein levels (58-61%) available in HDG show promising economics for incorporation of this process into corn dry-grind ethanol plants.

Acids↗
PubMed2005

Industrial scale-up of pH-controlled liquid hot water pretreatment of corn fiber for fuel ethanol production.

The pretreatment of cellulose in corn fiber by liquid hot water at 160 degrees C and a pH above 4.0 dissolved 50% of the fiber in 20 min. The pretreatment also enabled the subsequent complete enzymatic hydrolysis of the remaining polysaccharides to monosaccharides. The carbohydrates dissolved by the pretreatment were 80% soluble oligosaccharides and 20% monosaccharides with <1% of the carbohydrates lost to degradation products. Only a minimal amount of protein was dissolved, thus enriching the protein content of the undissolved material. Replication of laboratory results in an industrial trial at 43 gallons per minute (163 L/min) of fiber slurry with a residence time of 20 min illustrates the utility and practicality of this approach for pretreating corn fiber. The added costs owing to pretreatment, fiber, and hydrolysis are equivalent to less than 0.84 dollars/gal of ethanol produced from the fiber. Minimizing monosaccharide formation during pretreatment minimized the formation of degradation products; hence, the resulting sugars were readily fermentable to ethanol by the recombinant hexose and by pentose-fermenting Saccharomyces cerevisiae 424A(LNH-ST) and ethanologenic Escherichia coli at yields >90% of theoretical based on the starting fiber. This cooperative effort and first successful trial opens the door for examining the robustness of the pretreatment system under extended run conditions as well as pretreatment of other cellulose-containing materials using water at controlled pH.

Biotechnology↗
PubMed2001

Continuous countercurrent extraction of hemicellulose from pretreated wood residues.

Two-stage dilute acid pretreatment followed by enzymatic cellulose hydrolysis is an effective method for obtaining high sugar yields from wood residues such as softwood forest thinnings. In the first-stage hydrolysis step, most of the hemicellulose is solubilized using relatively mild conditions. The soluble hemicellulosic sugars are recovered from the hydrolysate slurry by washing with water. The washed solids are then subjected to more severe hydrolysis conditions to hydrolyze approx 50% of the cellulose to glucose. The remaining cellulose can further be hydrolyzed with cellulase enzyme. Our process simulation indicates that the amount of water used in the hemicellulose recovery step has a significant impact on the cost of ethanol production. It is important to keep water usage as low as possible while maintaining relatively high recovery of soluble sugars. To achieve this objective, a prototype pilot-scale continuous countercurrent screw extractor was evaluated for the recovery of hemicellulose from pretreated forest thinnings. Using the 274-cm (9-ft) long extractor, solubles recoveries of 98, 91, and 77% were obtained with liquid-to-insoluble solids (L/IS) ratios of 5.6, 3.4, and 2.1, respectively. An empirical equation was developed to predict the performance of the screw extractor. This equation predicts that soluble sugar recovery above 95% can be obtained with an L/IS ratio as low as 3.0.

Biomass↗
PubMed2006

Axonal transport of human immunodeficiency virus type 1 envelope protein glycoprotein 120 is found in association with neuronal apoptosis.

Patients infected by human immunodeficiency virus type 1 (HIV-1) develop acquired immune deficiency syndrome-associated dementia complex (ADC), a disorder characterized by a broad spectrum of motor impairments and cognitive deficits. The number of cells in the brain that are productively infected by HIV-1 is relatively small and consists predominantly of macrophages and microglia, yet HIV-1 causes widespread neuronal loss. A better understanding of the pathogenic mechanisms mediating HIV-1 neurotoxicity is crucial for developing effective neuroprotective therapies against ADC. The HIV-1 envelope glycoprotein 120 (gp120), which is shed from the virus, is one of the agents causing neuronal cell death. However, the cellular mechanisms underlying its neurotoxic effect remain unclear. We report that gp120 injected into the rat striatum or hippocampus is sequestered by neurons and subsequently retrogradely transported to distal neurons that project to these brain areas. Cleaved caspase-3 and terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling, hallmarks of apoptosis, were seen in neurons internalizing and transporting gp120. The retrograde transport of gp120 and apoptosis were mediated by the chemokine receptor CXCR4 because AMD3100, a selective CXCR4 inhibitor, blocked both events. Furthermore, colchicine or nocodazole, two inhibitors of intracellular trafficking, abolished gp120-mediated apoptosis in distal areas. These results indicate that axonal transport of gp120 might play a role in HIV-1-mediated widespread neuronal cell death.

Animals↗
PubMed1993

Important role of hepatitis C virus infection as a cause of chronic liver disease in Somalia.

In a case-control study, 62 Somali patients with chronic liver disease (CLD) including primary hepatocellular carcinoma (HCC) and the same number of age and sex matched controls were investigated for serological markers of hepatitis C virus (HCV) and hepatitis B virus (HBV) infections. Antibody to HCV (anti-HCV) was detected in 40.3% and 6.5% of cases and controls, respectively. The corresponding prevalences of hepatitis B surface antigen (HBsAg) were 37.1% and 9.7%, respectively. Of the HBsAg-positive cases, 34.6% had antibodies to hepatitis D virus (anti-HD) compared with 14.3% among the HBsAg-positive controls. Anti-HCV was less prevalent in HBsAg-positive cases than among HBsAg-negative patients (p < 0.001), indicating that these agents were independent causes of CLD/HCC. The odds ratios for patients with CLD/HCC associated with the presence of anti-HCV, anti-HD, HBsAg without anti-HD and anti-HCV, were found to be 9.8, 10.4, and 3.3, respectively. When the patients were divided into tumour and non-tumour cases, using the criteria of serum alpha-fetoprotein > 100 ng/ml and/or solid hepatic lesions detected by ultrasonography, they did not differ with regard to frequencies of HBsAg and/or anti-HCV, although they did differ when these markers were taken together (43/49 versus 5/13, respectively). The mean age of the tumour patients with anti-HCV alone was significantly higher than that of tumour patients with HBsAg as the sole marker, 61.7 versus 31.4 years (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗