Biomedical subjects
Publications and source records attributed to C C Lin.
We report a patient with non-B non-T acute lymphoblastic leukemia (ALL) who has translocation t(10;19)(q26;q13), which has not been reported previously. A brief review of the translocations involving chromosome #19 in ALL is also presented.
Tritium-labeled dihydroalprenolol was used to quantify beta-adrenergic-receptor sites in day 28 fetal rabbit lung tissue. Each of the amniotic sacs of pregnant New Zealand White rabbits on day 26 of gestation was injected in vivo with estrogen (estradiol phosphate, 1.6 micrograms) in one horn and normal saline solution in the contralateral one. The animals were put to death 48 hours later and the fetal lung tissues were assayed. Estrogen increased the number of beta-adrenergic-receptor sites in the treatment group compared to the control group (216 versus 163 fmol/mg of protein, p less than 0.02 by paired t test). In the presence of estrogen, beta-adrenergic-receptor activity is enhanced in the preterm fetal rabbit. This effect may be implicated in the beta-adrenergic mediation of phospholipid synthesis and release in fetal alveolar cells.
The steady-state bioavailabilities of dexbrompheniramine and pseudoephedrine were evaluated following multiple-dose administrations of a repeat-action combination tablet containing 6 mg of dexbrompheniramine maleate with 120 mg of pseudoephedrine sulfate every 12 h for 7 d compared with reference standards. The reference standards used in this study were concomitant administration of conventional 2-mg dexbrompheniramine maleate tablets every 4 h and 120-mg pseudoephedrine sulfate repeat-action tablets every 12 h, each for 7 d. Twelve healthy adult male volunteers completed this randomized two-way crossover study. Blood samples for subsequent assay were obtained at frequent time intervals throughout each 7-d dosing phase. Sensitive and specific gas-liquid chromatographic methods were used for the determination of dexbrompheniramine and pseudoephedrine in plasma. Based on the plasma levels, the times to reach steady state were determined. In addition, the major bioavailability parameters (Cmin, Cmax, tmax, and AUC) for days 6 and 7 of dosing were determined and statistically evaluated. The results of this study demonstrate that, at steady state, the repeat-action combination tablet and concomitant administration of the reference standards are bioequivalent.
We retracted information from a computerized databank which contains the cytogenetic findings of 17,000 patients with leukemia and lymphoma. Cytogenetic data from patients with solid tumors were compiled from Dr. Mitelman's catalogue on "Chromosome aberrations in cancer". We compared the observed distribution of breaks in chromosome bands involved in structural rearrangements with the random distribution of breaks generated by Monte Carlo simulation and showed that a majority but not all of the bands known to contain a fragile site are involved in structural aberrations in cancer and that some of them are associated with specific chromosome structural changes in specific types of cancer.
Cell lines (COLO 320 DM and COLO 320 HSR), established from a human neuroendocrine tumor, contain an amplified cellular oncogene (c-myc). We have previously shown that the homogeneously staining regions (HSRs) of a marker chromosome in the COLO 320 HSR cells that evolved in culture from COLO 320 DM cells contain amplified c-myc. Molecular hybridization in situ has now been used to demonstrate that the HSRs are on both arms of what was once an X chromosome. We also show that amplified c-myc copies are present in the isolated double minute chromosomes (DMs) of the COLO 320 DM cells that were characteristic of the tumor cells initially established from the patient. The results suggest that the amplified c-myc appeared first as DMs and was subsequently transposed to engender HSRs on an X chromosome. The initial COLO 320 tumor cell may have acquired two "early replicating" (i.e., active) X chromosomes and lost the "late replicating" (i.e., inactive) X.
The ultrastructure of the centromere region of chromosomes from mouse L929 cells treated with agents that affect centromere condensation have been examined using light, transmission electron, and scanning electron microscopic techniques. Micrographs of expanded centromeres from treated chromosomes illustrate that both the biarmed chromosomes that were generated by Robertsonian fusion during the past history of the strain and the functional centromere of the multicentromeric marker chromosomes display a prominent gap. This gap probably represents the original site of association of the acrocentric chromosomes and is also the site of the kinetochore. Despite the multicentromeric nature of the marker chromosome a single pair of kinetochores were found only at the central heterochromatic region. The functional implications of these structural findings are discussed.
Histone-depleted chromosomes have revealed a scaffold and loop architecture of metaphase chromosomes. In its simplest form this arrangement contradicts many classical observations suggesting chromosomes have a helical substructure. We have obtained preparations that allow the visualization of several levels of chromosome structure. These images suggest that metaphase packing is achieved by the compaction through helical coiling of a 200-300 nm fiber that is in turn composed of radial loops. These observations imply that any scaffold elements associated with radial loops are not distributed as previously proposed but must follow a complex and more extensive path within the metaphase chromatid.
Sch 34343 showed a linear dose response (with respect to AUCs) in mice following both intravenous and subcutaneous administration. It was 100% bioavailable following subcutaneous administration. Peak serum levels, AUCs, beta-phase half-life and recovery of Sch 34343 from the urine of mice indicated that it was similar to cephalothin and cefamandole. In experimental mouse infections, against Gram-negative strains, Sch 34343 was more active than cephalothin, equal to or more active than cefamandole and cefoxitin, but less active than latamoxef (moxalactam) and cefotaxime following single or multiple dose therapy. It was the most active compound against Staphylococcus. Sch 34343 was equally active against strains sensitive to beta-lactams and strains producing beta-lactamases. In an anaerobic abscess model in mice, Sch 34343 was more active than cefoxitin and clindamycin against Bacteroides fragilis. In Escherichia coli meningitis in rabbits, it cured rabbits with a single intravenous dose of 50 mg/kg.
Pharmacokinetic parameters of Sch 34343 have been determined for mice, rats, rabbits, monkeys, dogs and humans and correlated among species as an exponential function of body weight. The pertinent pharmacokinetic parameters tested are apparent and steady-state volumes of distribution, total body clearance, elimination phase half-life, and mean residence time. This study showed that the extrapolation of animal data to humans on a new investigational drug, Sch 34343, can be potentially useful.
Two sisters with similar clinical features are described. Their clinical manifestations include mental retardation, delayed speech development, low percentiles for height, weight and head circumference, dysmorphic ears, cubitus valgus, pseudoclubbing of fingers, flexion deformity of toes, small kidneys, elevated serum creatinine and blood urea nitrogen (BUN). High resolution chromosome analysis revealed a complete deletion of 16qh with a concurrent small deletion of the adjacent euchromatic segment 16q12.1 in one of the no. 16 chromosomes of both sisters, whereas the parents had normal no. 16 chromosomes. Length polymorphism of the 16qh regions appeared to indicate a maternal origin of the deleted no. 16 chromosome in both sisters. The clinical features of both sisters were attributed to the 16q12.1 deletion. Since both parents were cytogenetically normal, the two sisters were considered as a recurrence of a similar de novo interstitial deletion. Possible mechanisms which could lead to recurrence of a seemingly de novo event are discussed.
In a series of 493 apparently consecutive products of spontaneous abortions obtained for cytogenetic studies, tissue culture was attempted in 428 cases; chromosome analysis using the Q-banding technique was completed in 215 cases (50.2%). Abnormal karyotypes were identified in 80 cases (37.2%). Maternal tissue contamination was apparent and the actual frequency of karyotypic abnormal abortuses could be as high as 50%. Comparison of the frequency of a specific type of chromosome abnormalities with nine other series of studies showed the lowest frequency of autosomal trisomies and the highest frequency of triploidies and structural aberrations in the Calgary series. In addition, a significantly lower gestational age was observed for triploidies 69, XXX as compared to the 69, XXY.
A simple technique for synchronization of human lymphocyte cultures with fluorodeoxyuridine (FudR) is presented. The S-phase block induced by the FudR is released by simultaneous exposure to 5-bromodeoxyuridine (BrdU) and Hoechst 33258 or by thymidine and Hoechst 33258. This method provides a high mitotic index with high percentage of prometaphase chromosomes. This simple method is highly advantageous and easy to utilize in clinical cytogenetics.
A 4.4-kb PstI fragment containing the entire beta-gene of the human beta-globin gene cluster plus both 5'- and 3'-flanking sequences was used as a probe to study the chromosomal localization of the beta-gene by in situ hybridization. Using random oligonucleotides as primers, the beta-gene DNA was 3H-labeled with the large fragment of DNA polymerase I (Klenow fragment) to a specific activity of 1.2 X 10(8) cpm/micrograms. Almost 80% of hybridization grains observed were located on the distal short arm of chromosome 11. High-resolution chromosome analysis suggests a more precise location of the beta-gene to region 11p15.4----p15.5.
Antioxidants belong to a class of compounds used to retard oxidation of chemicals in foods. These compounds, such as BHA, BHT, TBHQ, PG, etc. are approved to be used in foods by government agencies. In the past 10 years considerable interest has been directed to the antimicrobial properties of these compounds due to the observations by various scientists that many of these compounds can suppress the growth of viruses, protozoa, bacteria, yeast, and molds and their subsequent production of toxic materials in foods. Thus, the dual purpose usage of these compounds (i.e., antioxidation and antimicrobial) has been the subject of many research papers. This review is designed to summarize major publications on this subject as well as present some detailed studies on the effect of major antioxidants on bacteria and mold generated in the laboratory of the author in recent years.
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