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A Han

Publications and source records attributed to A Han.

At least 37 records · Page 2Linked to original sources
PubMed1996

CD2 signaling in T cells involves tyrosine phosphorylation and activation of the Tec family kinase, EMT/ITK/TSK.

Ligation of the CD2 cell surface glycoprotein expressed on T lymphocytes and NK cells induces protein tyrosine phosphorylation and activation of the Src kinases, LCK and FYN. We show here that in Jurkat T leukemia cells and in peripheral blood T cells, CD2 stimulation also leads to tyrosine phosphorylation and activation of the Tec family kinase, EMT/ITK/TSK. Activation of EMT by CD2 was induced by mitogenic pairs of CD2 mAb, certain single CD2 mAb followed by secondary antibody cross-linking, and CD58-bearing sheep red blood cells. With the use of different Jurkat cell mutants it was demonstrated that CD2-mediated activation of EMT required expression of LCK, but not require surface expression of the CD3 zeta chain. Receptor-mediated activation of LCK does not in itself lead to activation of this Tec kinase since induction of LCK by ligation of CD4 or CD5 did not result in activation of EMT. The activation of EMT during CD2 signaling suggests an important role for this kinase in CD2 co-stimulation of T cell responses.

CD2 Antigens↗
PubMed1996

Phosphorylation of each of the distal three tyrosines of the CD28 cytoplasmic tail is required for CD28-induced T cell IL-2 secretion.

Signaling by the CD28 T cell costimulatory receptor is known to involve recruitment and activation of phosphatidylinositol 3-kinase (PI3-kinase) which is dependent upon phosphorylation of tyrosine 173 of the CD28 cytoplasmic tail, present in a YMNM motif. However, whether this phosphorylation is required for CD28 costimulation and whether or not phosphorylation of any of the other three tyrosines of the CD28 cytoplasmic tail (tyrosines 188, 191 and 200) is also important for CD28 induced responses is unclear. To address this we examined the ability of chimeric receptors, consisting of the extracellular plus transmembrane membrane domain of human CD8 alpha linked to different mutated human CD28 cytoplasmic tails, to induce IL-2 secretion in Jurkat T leukemia cells in the presence of PMA and ionomycin. A receptor in which tyrosine 173 of the CD28 tail was mutated to phenylalanine was able to induce IL-2. By contrast, receptors which contained single tyrosine 188, 191 or 200 to phenylalanine substitutions were unable to induce IL-2. These results imply that in this system phosphorylation of tyrosine 173 and hence activation of PI3-kinase is not required for CD28 induced IL-2 secretion. Further, they imply that phosphorylation of each of tyrosines 188, 191 and 200 is necessary for this response. Despite an apparent requirement for phosphorylation of all three of these tyrosines, however, receptors which contain tyrosine only at positions 191 or 200 and a truncated receptor which does not contain tyrosine 200 induce normal IL-2. These last findings, therefore, illustrate the complexity of CD28 mediated activation signals.

CD28 Antigens↗
PubMed1991

Malignant CD5 B cells--biased immunoglobulin variable gene usage and autoantibody production.

Malignant CD5 B cells obtained from patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) were analyzed for immunoglobulin variable gene usage, CD5 gene expression and autoantibody production. A statistically significant biased usage of the VH5, VH6 and VKIII immunoglobulin variable gene families was observed. It is important to point out that both VH5 and VH6 are extremely small families which are located at the 3' extremity of the immunoglobulin variable gene locus. We determined that the transcription of the CD5 gene in T cell malignancies, CLL, SLL and a selected group of EBV transformed lines was identical. Autoantibody production was studied in a panel of heterohybridomas obtained by the fusion of CLL cells with mouse myeloma line SP2/0. A large fraction of these heterohybridomas secrete autoantibodies; some were monospecific, some bispecific and some polyspecific.

Antigens, CD↗
PubMed1990

Multiple small exposures of filtered mid-UV radiation increase the resistance of Chinese hamster cells to far-UV, mid-UV and filtered mid-UV radiation.

The response of Chinese hamster cells (V79-MI2G) to multiple, low doses of filtered mid-UV radiation (wavelengths longer than 300 nm) were examined over an exposure period of 30 days. Cell survival and the induction of mutation at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus using resistance to 6-thioguanine (TG) were the endpoints in this study. With increasing total accumulated dose given at 500 J/m2/day as a single short exposure, an increased resistance to cell killing was observed. This increase in resistance to cell killing was accompanied by a gradual decrease in sensitivity to the induction of mutants resistant to 6-TG. Above total accumulated doses of 5000 J/m2 the frequency of 6-TG resistance did not increase. After multiple doses of filtered mid-UV radiation the cells became more resistant to subsequent challenges with acute doses of far-UV, mid-UV or filtered mid-UV. The increased resistance to the cell killing action and to the mutation induction by UV suggests that during exposure to low, multiple doses of filtered mid-UV radiation the cells become adapted to the damaging effects of filtered mid-UV radiation.

Adaptation, Physiological↗
PubMed1990

[Identification and typing of Actinobacillus actinomycetemcomitans by restriction endonuclease analysis].

The aim of the present study was to investigate the potential of restriction endonuclease analysis (REA) for the identifying and typing of Actinobacillus actinomycetemcomitans (Aa). Bacterial chromosomal DNA was extracted and digested with BamHI, HindIII, Sal I and Xho I respectively and separated by agarose gel electrophoresis. DNA fragment patterns of Aa and Haemophilus aphrophilus differed strikingly from each ether. The patterns of Aa FDC Y4 and Aa ATCC 29523, belonging to two different serotypes, also differed notably. Among the 4 enzymes used, Sal I and Xho I gave the most satisfactory results. The results of our work suggested that REA could be used to identify and type Aa. REA is stable, sensitive, accurate and reproducible. The method might be valuable in molecular epidemiologic studies on periodontopathic organisms.

Actinobacillus↗
PubMed1989

Nutritional and hormonal regulation of the activity state of hepatic branched-chain alpha-keto acid dehydrogenase complex.

The hepatic branched-chain alpha-keto acid dehydrogenase complex plays an important role in regulating branched-chain amino acid levels. These compounds are essential for protein synthesis but are toxic if present in excess. When dietary protein is deficient, the hepatic enzyme is present in the inactive, phosphorylated state to allow conservation of branched-chain amino acids for protein synthesis. When dietary protein is excessive, the enzyme is in the active, dephosphorylated state to commit the excess branched-chain amino acids to degradation. Inhibition of protein synthesis by cycloheximide, even when the animal is starving for protein, results in activation of the hepatic branched-chain alpha-keto acid dehydrogenase complex to prevent accumulation of branched-chain amino acids. Likewise, the increase in branched-chain amino acids caused by body wasting during starvation and uncontrolled diabetes is blunted by activation of the hepatic branched-chain alpha-keto acid dehydrogenase complex. The activity state of the hepatic branched-chain alpha-keto acid dehydrogenase complex is regulated in the short term by the concentration of branched-chain alpha-keto acids (inhibitors of branched-chain alpha-keto acid dehydrogenase kinase) and in the long term by alteration in the total branched chain alpha-keto acid dehydrogenase kinase activity.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1989

Promoter-enhanced neoplastic transformation after gamma-ray exposure at 10 cGy/day.

We have measured gamma-ray-induced neoplastic transformation in C3H10T1/2 mouse embryo cells irradiated at an average 10 cGy/day throughout the useful life span of these cells for transformation studies. At cumulative total doses of 50, 150, 300, and 450 cGy, samples of cells were assayed for cell survival and neoplastic transformation with or without the administration of 0.1 micrograms/ml of 12-O-tetradecanoylphorbol-13-acetate (TPA) starting 24 h after the irradiation. The results indicate that, at a dose rate of 10 cGy/day, the rate of induction of neoplastic transformation is reduced by a factor of thirteen compared to that at 100 cGy/min. Still, frequencies above the background level are observed. These results are consistent with previous data which, at 144 cGy/day (0.1 cGy/min), showed that radiation-induced initiation events could be repaired during exposure, thus reducing the frequency of transformation from that observed at 100 cGy/min [A. Han et al., Cancer Res. 40, 3328-3332 (1980)]. Although the addition of TPA after the delivery of a particular dose at 10 cGy/day produced a significant increase in the frequency of neoplastic transformation, the degree of enhancement was less than after higher-dose-rate exposures [C.K. Hill et al., Radiat. Res. 109, 347-351 (1987)]. These results indicate that during 7 weeks of exposure, the repair of radiation-induced initiation was extensive but not complete, and suggest that a significant part of the damage persists which can be promoted by TPA. These observations support the inference that initiation and promotion are not tightly coupled and are probably independent processes.

Animals↗
PubMed1988

Multiple, small exposures of far-ultraviolet or mid-ultraviolet light change the sensitivity to acute ultraviolet exposures measured by cell lethality and mutagenesis in V79 Chinese hamster cells.

Chinese hamster V79 cells (subline MI2G) were exposed repeatedly to fractionated doses of germicidal 254 nm light (far-uv) at 6 J.m-2/fraction/day or sunlight-simulating 290-330 nm (mid-uv) at 150 J.m-2/fraction/day and sensitivities to cell killing action and mutation of far-uv and mid-uv were examined. As the number of exposure fractions increased, the cell cultures became resistant to cell killing induced by both far-uv and mid-uv. Increases in both Do and Dq were observed. Treatment with exposures of 6 J.m-2 far-uv is more efficient in yielding cell cultures that are resistant than exposures of 150 J.m-2 mid-uv. In contrast to the cells exposed to repeated far-uv, the cells exposed to repeated mid-uv were relatively more resistant to cell killing effects of mid-uv than far-uv, suggesting a possible role of photolesions other than pyrimidine dimers. When mutants resistant to 6-thioguanine were assayed during repeated exposure to far- or mid-uv light, the yield was initially linear with accumulating dose. At high total accumulated doses, the frequency decreased gradually (6 J.m-2 mid-uv) or reached a plateau (150 J.m-2 mid-uv). The sensitivity of N80 cells (exposed to 80 fractions of mid-uv) to mutation induction by uv light is higher than that of the original MI2G cells, whereas U81 cells (exposed to 81 fractions of far-uv) have a sensitivity similar to that of the original cells. Although an initial decrease in resistance to cell killing was observed, resistant cells retained their characteristics after 100 days in culture without further exposure. Cross-resistance to X rays was not shown. The data in this paper suggest that the capacity for repair of photolesions in DNA by repair processes was enhanced in cell cultures by repeated exposure to far-uv or mid-uv and that this altered the cells' ability to cope with lethal and mutagenic lesions. It remains to be seen if these changes in cell sensitivity were brought about by selective or inductive processes or a combination of both.

Animals↗
PubMed1987

Promotion, dose rate, and repair processes in radiation-induced neoplastic transformation.

C3H10T1/2 cells were exposed to low doses of 60Co gamma rays at 100 or 0.10 cGy/min and the incidence of neoplastic transformation was assayed with or without the addition of tetradecanoylphorbol-13-acetate (TPA). As we reported earlier [A. Han, C. K. Hill, and M. M. Elkind, Cancer Res. 40, 3328-3332 (1980); C. K. Hill, A. Han, F. Buonaguro, and M. M. Elkind, Carcinogenesis 5, 193-197 (1984)], the frequency of neoplastic transformation per unit dose following low doses appears to be linear and is reduced 2.3-fold at 0.10 cGy/min compared to 100 cGy/min. We report now that the addition of TPA 24 h after irradiation appreciably enhances the frequency after both low- and high-dose-rate exposures. The enhancement indicates that TPA leads to the expression of potentially effective, preneoplastic damage due to gamma rays. Our data suggest that the enhancement of transformation by TPA is essentially independent of dose rate. Also, our results suggest that the sector of preneoplastic damage which is repaired during protracted exposures becomes unavailable to enhancement by TPA.

Animals↗
PubMed1986

Central metabolism of beta-endorphin in different species of temperature acclimated rodents.

The purpose of this study was to characterize the central metabolism/processing of beta-endorphin in wild, desert rodents and to study the effect of heat and cold acclimation on central metabolism/processing and beta-endorphin half-life. This report suggests that a shift occurs in the processing of beta-endorphin in desert rodents acclimated to heat and cold leading to an accumulation of gamma-type endorphins. The data support a significant difference in beta-endorphin half-life between the rodents and the laboratory white rat.

Acclimatization↗
PubMed1985

Differences in sensitivity between human, mouse and Chinese hamster cells to killing by monochromatic ultraviolet light.

Irradiation of human (IMR-91), mouse (10T1/2) and Chinese hamster (V79) fibroblasts with monochromatic ultraviolet light (u.v.) in the far-, mid-, and near-u.v. regions resulted in cell-strain-specific changes in sensitivity as a function of the wavelength used. The data suggested cell-strain-specific action spectra for cell killing by ultraviolet light that did not correlate with the ability of examined cells to excise pyrimidine dimers.

Animals↗
PubMed1985

Neoplastic transformation is enhanced by multiple low doses of fission-spectrum neutrons.

The neoplastic transformation of C3H mouse 10T1/2 cells was measured induced by fission-spectrum neutrons delivered at a high dose rate in five fractions over 4 days. The transformation frequency was significantly enhanced over that due to single equivalent total doses. These new data, in the low dose region, demonstrate an increased transformation frequency by fractionated versus single exposures of high-dose-rate fission-spectrum neutrons; an increase equal to that observed with low-dose-rate fission-spectrum neutrons (i.e., 0.086 rad/min). Estimates of the dose modifying factor (DMF), based upon the ratio of the initial linear portions of the induction curves for high and for low dose rates, suggest the same DMF (approximately 7.8) for both five daily fractions of high-dose-rate neutrons and for low-dose-rate neutrons. However, when these results are compared to those following high-dose-rate 60Co gamma rays (100 rad/min), the relative biological effectiveness (RBE) for low-dose-rate fission-spectrum neutrons based upon slope ratios is 19.6; similarly, the RBE relative to five daily fractions of 60Co gamma rays is 78.8.

Animals↗
PubMed1984

Action spectra for killing and mutation of Chinese hamster cells exposed to mid- and near-ultraviolet monochromatic light.

We have examined the response of Chinese hamster V79 cells to monochromatic light of selected wavelengths in the mid- to near-UV region, using cell survival and induction of mutants resistant to 6-thioguanine (6-TG) or ouabain (OUA) as end points. As the wavelength increased from 313 to 405 nm, the induction of mutants resistant to 6-TG and to OUA decreased to a greater degree than did cell survival. Cells resistant to OUA were induced with considerably lesser efficiency at wavelengths of 313 and 334 nm than cells resistant to 6-TG. No mutants resistant to either 6-TG or OUA were induced by 405-nm light, and no mutants resistant to OUA were induced by 365-nm light. Thus, cell killing and mutation induction have different action spectra, and furthermore, action spectra for mutation induction at the HGPRT and Na+/K+-ATPase loci are different from each other. These observations imply important differences in the cellular mechanisms, and/or lesions, for cell inactivation, induction of 6-TG and OUA resistance for V79 cells exposed to near-UV monochromatic light.

Animals↗
PubMed1984

Fission-spectrum neutrons at a low dose rate enhance neoplastic transformation in the linear, low dose region (0-10 cGy).

The neoplastic transformation of C3H 10T1/2 cells induced by fission-spectrum neutrons delivered at a high dose rate is linear up to 40 cGy. Reducing the dose rate increases the frequency of transformation in the low dose region. At a dose rate of 0.086 cGy min-1, the initial part of the induction curve remains linear but it has a slope 9-fold greater than the initial part of the curve at a high dose rate.

Animals↗