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L J Chang

Publications and source records attributed to L J Chang.

65 records · Page 4Linked to original sources
PubMed1984

Avian sarcoma virus gag and env gene structural protein precursors contain a common amino-terminal sequence.

The initiation site for translation of the avian sarcoma virus glycoprotein precursor, Pr63env, has been determined by analyzing the amino-terminal peptides of Pr63env and the polyprotein precursor Pr76gag encoded by the viral gag gene. The acceptor splice junction used to form the env gene mRNA has also been identified. Hybrid-selected virus-specific mRNAs were translated in vitro in the presence of either L-[35S]methionine to label at every methionine residue or L-[35S]methionine-tRNAMeti to label specifically at the amino-terminal methionine residues. Tryptic peptide maps of Pr63env labeled at every methionine residue contain all of the peptides, plus one additional peptide, present in the map of Pr57env, a nonglycosylated env-encoded polypeptide of molecular weight 57,000 immunoprecipitated from tunicamycin-treated cells. Specific amino-terminal labeling of the in vitro-synthesized polypeptides showed that the peptide missing from Pr57env corresponds to the amino-terminal tryptic peptide of Pr63env, which is removed in vivo as part of the amino-terminal signal peptide. Comparison of the amino-terminal tryptic peptides of Pr63env and Pr76gag showed that they are identical. In contrast, the chymotryptic amino-terminal peptides of Pr76gag and Pr63env are not identical. The location of the acceptor-splice junction in the env mRNA of the Prague A strain of avian sarcoma virus was determined by mung bean nuclease mapping to be at nucleotide 5,078. Fusion of the gag and env gene sequences during splicing results in use of the same AUG codon to initiate synthesis of Pr76gag and Pr63env. This sequence is contained within the 397-nucleotide 5' terminal leader that is spliced to the body of the env mRNA. The possible significance of these results for the regulation of avian sarcoma virus synthesis and translation is discussed.

Amino Acid Sequence↗
PubMed1982

Detection of genes coding for human differentiation markers by their transient expression after DNA transfer.

We have developed an assay for specific genes in DNA based on transient expression. DNA prepared from patients with acute myeloblastic or acute lymphoblastic leukemia or from the continuous leukemic cell line HL60 was transferred to LTA cells; 48-72 hr later, these recipients expressed hemopoietic differentiation markers as detected by monoclonal antibodies against My-1 (granulocyte specific) and OK-T3 (T-cell specific) using immunofluorescence. The efficiency of transfer was dose and time dependent. We found that genes not expressed in the original cells were expressed after transfer by using this assay. Restriction enzyme analysis showed that My-1 was not expressed with DNA that had been incubated before transfer with either HindIII or Sal I but was present after digestion with either EcoRI or BamHI; after digestion of DNA with the same enzymes, OK-T3 expression was observed only in the HindIII-treated DNA. These studies indicate that DNA was transferred; this approach may provide an efficient method for detecting the activity of specific genes in the absence of selection.

Animals↗
PubMed1982

Relationship of pretreatment lymphoblast proliferative activity and prognosis in 97 children with acute lymphoblastic leukemia.

We have analyzed the pretreatment 3H-thymidine labeling indices in blood and marrow blast cells from 97 children with acute lymphoblastic leukemia (ALL) and circulating blasts. The median marrow labeling index (LI) was 6.2% (range 0.8%--32.7%) and the median blood LI, 3.2% (range 0.3%--20%). Blood LI was significantly correlated with leukocyte count and rosette-forming (E+) lymphoblasts but not with central nervous system leukemia or thymic mass at diagnosis. Marrow LI was related to E+ blasts only. In children with E+ leukemia, both blood and marrow LIs were significantly higher than values for other ALL subtypes (p less than 0.01) excluding undifferentiated ALL, which was characterized by an increased blood LI. Eighteen patients had a blood LI that either equaled or exceeded the marrow LI; apart from age, the clinical features, blast phenotypes, and treatment responses of this group were similar to those of patients with blood LI less than marrow LI. Among 51 patients assessed for treatment response, the estimated median length of remission was significantly shorter for those with a blood LI greater than 4% (p = 0.002) or a marrow LI greater than 6% (p = 0.011). By Cox-regression analysis, the pretreatment proliferative activity of blood and marrow blasts, unlike other initial features studied, added significant prognostic information to leukocyte count in these patients with circulating blasts. The findings provide a cogent explanation for the differential clinical responsiveness of commonly recognized ALL subclasses.

Adolescent↗
PubMed1981

Dose-dependent effects of a tumor promotor on blast cell progenitors in human myeloblastic leukemia.

AML blast cell progenitors form colonies in culture when stimulated by a media conditioned by leukocytes in th presence of PHA. Two cellular processes occur during colony formation: self renewal generates new progenitors, while others undergo a change that leads to decreased proliferative potential. We tested the effect of the potent tumor promotor, 12-0-tetradecanoyl phorbol acetate (TPA) on these events. TPA was found to be toxic to blast cell colony formation; doses in excess of 1 ng per ml usually abolished it. At doses lower than this, self renewal, as determined by replating either individual or pooled colonies, was increased. At proliferation inhibiting TPA doses, surviving cells showed a spindle morphology, and had increased ANA esterase activity. We interpret the data to mean that TPA decreases blast cell maturation at low doses and may increase it at high doses.

Cells, Cultured↗
PubMed1981

Self-renewal capacity of leukemic blast progenitor cells.

A review is presented of experimental information pertaining to the characteristics of a procedure designed to quantitate the capacity for self-renewal in clonogenic cells of human acute myeloblastic leukemia. In a series of 44 previously untreated patients, a significant correlation (p less than 0.01) was seen between low capacity for self-renewal and successful remission induction. Three cytotoxic drugs (Adriamycin, 1-beta-D-arabinofuranosylcytosine, and N-[4-(19-acridinylamino)-3-methoxyphenyl]-methanesulfonamide) were tested for preferential effect against self-renewal events. Surviving clonogenic cells to these agents had, respectively, unchanged, lower, and higher capacity for self-renewal. The implications of such drug properties are discussed.

Aminoacridines↗
PubMed1980

The cellular basis of self renewal in culture by human acute myeloblastic leukemia blast cell progenitors.

Blast cells from patients with Acute Myeloblastic Leukemia (AML) were separated according to cell size using velocity sedimentation under unit gravity. Fractions obtained in this way were plated in methyl cellulose with a growth stimulator present in media conditioned by leukocytes in the presence of phytohemagglutinin (PHA-LCM). Colonies of blast cells form under these conditions. Pooled cell suspensions from such colonies were plated in microwells; the plating efficiency of such suspensions is a measure of blast progenitor self-renewal occurring in the original blast colonies. Self-renewal assays on each fraction indicated that self renewal among blast progenitors is heterogeneously distributed with subpopulations differing in renewal capacities. The results are consistent with the view that blast cell subpopulations in AML undergo a series of transitions associated with decreasing self renewal capacity, analogous to that observed in normal hemopoiesis, where proliferative capacity decreases with increasing differentiation.

Cell Count↗
PubMedDate not supplied

Differential apoptosis effects of primate lentiviral Vpr and Vpx in mammalian cells.

The growth inhibitory effects of Vpr and Vpx are species- and cell type-dependent. HIV-1, HIV-2 and SIV Vpr are primarily cytostatic in mammalian cells and HIV-1 Vpr has been reported to induce apoptosis in human cells. Our previous studies have shown that HIV-1, HIV-2 and SIV Vpr and Vpx have differential cytostatic and cytotoxic effects in the yeast cells [Zhang et al.: Virology, 230:103-112; 1997]. Here, we further examined the apoptosis function of HIV-1 Vpr in different species of mammalian cells and investigated if other primate lentiviral Vpr and Vpx exert similar functions. Our results show that none of the primate lentiviral Vpr or Vpx we tested induces apoptosis in nonhuman species of mammalian cells. However, HIV-1 Vpr, but not HIV-2 or SIV Vpr and/or Vpx, induced apoptosis in different types of human cell lines. Further, the apoptotic effect of HIV-1 Vpr can be distinguished from that of the human interferon-gamma, a known proapoptotic protein, that HIV-1 Vpr shows little to no paracrine and/or bystander effect. When coexpressed with Bcl-2 or Bcl-X(L), the apoptotic effect of HIV-1 Vpr became markedly attenuated. These results indicate that the apoptotic effect of HIV-1 Vpr is species-dependent and is intracellularly modulated by the Bcl-2 family of proteins. Our study also suggests that the proapoptotic function of HIV-1 Vpr is developmentally associated with human but not nonhuman primate species.

Animals↗
PubMedDate not supplied

Predictors of long-term smoking cessation in head and neck cancer patients.

Cigarette smoking is a major risk factor for head and neck cancer, and individuals who continue to smoke past diagnosis and treatment are at elevated risk for further disease. In a randomized controlled trial, a state of the art provider-delivered smoking cessation intervention was compared to a usual care advice control condition. The intervention consisted of surgeon- or dentist-delivered advice to stop smoking, a contracted quit date, tailored written materials, and booster advice sessions. Subjects were 186 patients with newly diagnosed first primary squamous cell carcinomas of the upper aerodigestive tract who had smoked cigarettes within the past year. At randomization, 88.2% of subjects were current smokers. At 12-month follow-up, 70.2% of subjects completing the trial (n = 114) were continuous abstainers; among baseline smokers alone the continuous abstinence (CA) rate was 64.6%. The cotinine validation rate at 12 months was 89.6%. Modeling techniques were utilized in order to derive expected CA rates, which included noncompleter subjects (n = 72). The CA rate expected at 1 year for the entire patient population was 64.2%, and for smokers alone the expected CA rate was 59.4%. Logistic regression analysis carried out on baseline smokers identified predictors of 12-month CA status. These included medical treatment, stage of change, age, nicotine dependence, and race. The intervention effect was not significant, although the sign of the effect was positive. Based on these findings, we recommend systematic brief advice to stop smoking for head and neck cancer patients, with a stepped care approach for patients less able to quit.

Carcinoma, Squamous Cell↗