Biomedical subjects
Publications and source records attributed to C C Lin.
Two further cases of variant Philadelphia chromosome are presented. The possible presence of a specific oncogene on the long arm of chromosome #22 is discussed.
Two cell lines (COLO 201 and COLO 205) derived independently from a single adenocarcinoma of the human colon each harbored an approximately 10-fold amplification of the cellular oncogene c-myb and a proportional abundance of the 4-kilobase mRNA derived from c-myb. By contrast, expression of c-myb could not be detected in cells from a variety of other solid tumors, including other colon carcinomas. Analysis of the amplified DNA with restriction endonucleases failed to reveal any topographical abnormalities within c-myb. Neither COLO 201 nor COLO 205 carry the double minute chromosomes and homogeneously staining regions of chromosomes that frequently serve as karyotypic signatures of amplified DNA. Instead, amplified c-myb is carried on what appear to be disomic or trisomic copies of the same anomalous marker chromosome that is characteristic of both COLO 201 and COLO 205. The karyological origin of this abnormal chromosome is not presently apparent. Our findings show c-myb expression by cells outside of the hemopoietic lineage, raise the possibility that amplification and/or ectopic expression of c-myb may have contributed to the genesis of the tumor from which the cells of COLO 201 and COLO 205 arose, and suggest that amplification of cellular oncogenes may be a more common factor in tumorigenesis than might have been suspected from available karyological data.
The pharmacokinetics of rosaramicin was studied in subjects receiving 500 mg of the drug (i) by 1-h intravenous infusion, (ii) in solution orally, or (iii) as tablets orally. After intravenous administration, the rosaramicin levels in serum declined rapidly with t1/2S of 0.27 h for the distribution phase and 3.28 h for the elimination phase. The apparent volume of distribution was 3.78 liter/kg, and the total body clearance was 13.41 ml/min per kg, indicating extensive tissue distribution or metabolism or both. Similar pharmacokinetic data were obtained after oral administration of the drug in solution or tablets and after intravenous dosing. The absolute bioavailability of the drug administered orally, in either tablets or solution, was 32 to 39%. The metabolism and excretion of [14C]rosaramicin administered orally were also evaluated in volunteers. The serum area under the curve (infinity) of unchanged rosaramicin was 19% of that of total radioactivity, indicating extensive metabolism of the drug. About 7.0% of the radioactivity was recovered in the urine, and 86.7% was recovered in the feces. Only a small amount of unchanged rosaramicin was present in the urine (7 to 9% of urinary radioactivity), but none was present in the feces. The major metabolite, 20-bis-ureidorosaramicin, represented 17 to 38% of the radioactivity in the urine and 26 to 29% of the radioactivity in the feces.
GELRITE, a new gelling agent with good thermal stability and clarity, was evaluated in media for culturing selected thermophilic microorganisms. It was also evaluated for performing counts of thermophilic bacteria from soil samples. In most cases, GELRITE was shown to be superior to agar for these applications.
We studied the effects of gene amplification on human globin gene expression in Chinese hamster ovary cells. The normal human alpha-globin gene (N alpha 2) and a hybrid gene (M alpha G) containing the 5' promoter-regulator region of the mouse metallothionein gene and the human structural alpha 2-globin gene were linked to a modular SV2-cDNA dihydrofolate reductase (DHFR) gene. The recombinant DNA molecules were introduced into Chinese hamster ovary cells by calcium phosphate precipitation. After initial selection to retain the DHFR and linked sequences, the cells were cultured in increasing concentrations of methotrexate up to 0.2 mM. Southern blot analysis of total cellular DNA showed an approximately 500- to 1,000-fold increase in the number of copies of DHFR and human alpha-globin genes. The transcription of the alpha-globin and DHFR genes increased as their copy number within the cells increased. The transcription of the amplified hybrid M alpha G gene was also inducible with cadmium treatments. Both mature mRNA and "read-through" transcripts were observed. DHFR constituted approximately 10% of pulse-labeled cellular proteins in these cells, but no human alpha-globin was detected. In vitro translation of polyadenylated RNA from these cells showed that alpha-globin mRNA transcribed from the amplified alpha-globin genes was functional and directed alpha-globin chain synthesis. In situ hybridization of 3H-labeled alpha-globin and DHFR DNA probes in chromosome preparations from the two cell lines indicated that both genes were coamplified in the same chromosomal locations in each cell type. These results indicate that gene amplification enhances human globin gene expression in cultured Chinese hamster ovary cells.
The ultrastructural organization of double minute chromosomes (DMs) and marker chromosomes displaying homogeneously staining regions (HSRs) have been investigated in two cell lines, COLO-320 DM and COLO-320 HSR, derived from a human colon carcinoma. Double minute chromosomes in the COLO-320 DM cell line vary in number from several to several hundred and in diameter from 0.5 to 2 micron. These chromosomes lack kinetochore structures which appear as discrete electron dense plates on the centromeric chromosomes. The DMs are composed of regularly arranged nucleosome-containing fibers. These are folded to form 30 nm fibers which extend as loops from the central portion of the chromosome. In COLO-320 HSR, a majority of cells contain a single submetacentric HSR marker chromosome with HSR regions in both chromosome arms. The HSR chromosome appears structurally analogous in EM preparations to the other centromeric chromosomes of the karyotype.
Adenovirus type 8 (Ad 8) has been the major and important causative agent of epidemic keratoconjunctivitis (EKC). By enzymatic cleavage analysis with five endonucleases, PstI, HindIII, BamHI, SalI and SstI, 27 out of 149 Ad 8 isolates recovered from patients with EKC during the period from July, 1980 to July, 1981 in Kaohsiung, Taiwan, were studied. By cleavage patterns, 27 Ad 8 isolates in Kaohsiung were classified into four subtypes which were found to be different from the subtypes (Ad 8A, Ad 8B) prevalent in Sapporo (1).
The immune response to beef insulin in mice is controlled by genes in the IA subregion. We have previously shown that B6.C-H-2bm12 (bm12) mice, an A beta gene mutation of B6, have a selective loss of responsiveness to beef insulin, whereas other IAb controlled responses such as (TG)AL and collagen are unchanged. F1 hybrid mice between two nonresponder genotypes Ik and Ibm12 were found to be good responders to beef insulin suggesting functional complementation. In this report, we define the cellular and molecular basis of this complementation by investigating the determinants on Ia molecules and nominal antigen that are recognized by (B10.A X bm12)F1 proliferating T cells. Genetic analyses demonstrated that the Ik region was the only nonresponder genotype that complemented Ibm12, thus restoring responsiveness to beef insulin. More precisely an IAk and not an IEk gene product was found to be responsible for this complementation. Antibody blocking studies furthermore showed that the A alpha b:A beta k hybrid Ia mediated the response to beef insulin in (B10.A X bm12)F1 mice. Clonal analyses of the response to beef insulin in these F1 mice confirmed these conclusions, because the insulin-specific response in all 21 F1-T cell clones studied thus far was found to be dependent upon presentation via the A alpha b:A beta k hybrid Ia molecule. Dissection of the antigenic specificity of the F1-T cell clones demonstrated recognition of at least two insulin determinants, one A-loop (A8-A10) associated and the other non-loop (A4 or B chain) associated. Therefore these studies identify the molecular and antigenic basis of the Ir gene complementation seen in the response to beef insulin of (B10.A X bm12)F1 hybrids.
An attempt was made to prepare enzyme immunoassay (EIA) kit for the detection of hepatitis B surface antigen (HBsAg). The diagnostic reagents were prepared by the 'sandwich" principle in which polystyrene microtiter plates were used. Two-step glutaraldehyde coupling procedure was used for the preparation of antibody-peroxidase (horseradish) conjugate. Purified anti-HBs IgG fraction of guinea pig antisera was used for coating plates and for antibody-enzyme conjugate preparation. This method had been compared with Ausria II-125 (RIA, Abbott Lab.) in 423 government employees. Among 80 (18.9%) positive results six were inconsistent reactions by Ausria II-125. Only one of the six positive specimens was repeatedly positive and was confirmed by Auszyme II (EIA, Abbott Lab.). 14 out of the 343 (81.1%) negative results were positive reactions detected by Ausria II-125. A half of them was still negative detected by Auszyme II. The lowest detectable dose of our EIA, in which the Hepatitis Sensitivity Panel-5 (Abbott Lab.) was used and incubation period was set for 2 hr., was 3.2 ng/ml for ad subtype of HBsAg. While that of Auszyme II was 0.93 ng/ml.
Latex agglutination inhibition test was developed for the detection of staphylococcal enterotoxin. Water soluble carbodiimide was used for coupling enterotoxin to latex particles. Test samples were added to the anti-enterotoxin serum at first. Then, enterotoxin-linked latex particles were added to the mixture. When enterotoxin was present in the test sample, it reacted with anti-enterotoxin antibodies and inhibited antitoxin to agglutinate enterotoxin-linked latex particles. The inhibition of latex agglutination resulted in tho formation of sedimentation in the button of the well of microtiter or microcentrifuge tube. The test was read after 8 hours or overnight incubation at room temperature and the concentration of staphylococcal enterotoxin B as low as 0.5 micrograms/ml could be detected.
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In order to determine whether the epidemiological characteristics of lung cancer have changed within a certain period of time in Taiwan and to propose some causative factors for its rapid rate of increase we performed chronological and epidemiological studies based on the analysis of: (1) available vital statistics and demographic data for Taiwan after 1932; (2) data reported by WHO for international comparison; (3) prevalence surveys carried out in 1972-73 and 1977-78; and (4) 7,307 clinical cases collected from major hospitals since 1952. Some possible factors, i.e., the smoking history of patients, yearly tobacco consumption, geographical distribution of patients, and the number of motor vehicles were studied in correlation with epidemiological characteristics. We have found that the mortality of lung cancer in Taiwan has been increasing rapidly for both sexes. The rate of increase is probably the highest in the world. The prevalence rate increased from 15.26 per 100,000 population in 1972-73 to 22.35 in 1977-78. The male to female ratio has remained unchanged, roughly at 2:1, over the past 50 years. Adenocarcinoma contributed to about 60% of lung cancer in women and 35% in men. This proportion has not changed during the past 30 years. The cancer showed a striking urban predominance. The causes of the rapid increase in lung cancer in Taiwan cannot be explained solely by tobacco smoking, particularly for women, although it certainly plays an important role.
A detailed electronmicroscopic study on glycogen-rich tumor is presented. The neoplasm originated from the minor salivary glands on the ventral surface of the tongue. The role of myoepithelial cells in the histogenesis of this lesion is not supported. It is proposed that the tumor arises from "undifferentiated" stem cells analogous to cells in the "end bud" stage of salivary gland morphogenesis. The presence of a large amount of glycogen is secondary to defective carbohydrate metabolism within the tumor cells.
Three cases of monomorphic basal cell adenoma of the parotid glands were studied with light microscopy. In one patient, fresh tissue was available for electron microscopic observations. On the basis of ultrastructural findings it was concluded that myoepithelial cells play little, if any, role in the histogenesis of this lesion. The tumor originates from the undifferentiated stem cells analogous to the cells seen at the "end bud" stage of salivary gland morphogenesis prior to their further cytodifferentiation and functional maturation into secretory and myoepithelial cells. In fully developed salivary glands such undifferentiated stem cells reside as "reserve" cells in the intercalated ductal system.