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Biomedical subjects

X R Lin

Publications and source records attributed to X R Lin.

12 recordsLinked to original sources

Pharmacokinetic study of intralesional cisplatin for the treatment of hepatocellular carcinoma.

BACKGROUND: In the current study the authors examined the pharmacokinetics of direct intralesional injection of cisplatin/epinephrine/bovine collagen gel in patients with hepatocellular carcinoma and cirrhosis. METHODS: Six patients with cirrhosis and unresectable hepatocellular carcinoma received a direct intralesional injection (range, 6.7-26.7 mg) into their tumors under ultrasonographic guidance. The authors determined the total cisplatin (Pt) concentration in the plasma and urine and nonprotein-bound free Pt in plasma ultrafiltrate using flameless atomic absorption spectrometry. Data from individual patients were analyzed to calculate the pharmacokinetic parameters via a noncompartmental method for constant infusion. To demonstrate that the changes in pharmacokinetics are not related to the underlying cirrhosis, a similar methodology was applied to measure the pharmacokinetic parameters of four similar patients who were treated with cisplatin, 75 mg/m(2), as a 1-hour intravenous infusion. RESULTS: The time to attain maximum concentration of total Pt after intralesional injection was dose-dependent and ranged from 2-13 hours. The concentration-time curve was biphasic in nature. The initial half-life of total Pt in patients who received an intralesional injection varied with the cisplatin dose. The initial half-life for cisplatin doses < 15 mg was approximately 9 hours and the initial half-life at higher cisplatin doses (> 15 mg) was approximately 25 hours. The area under the curve (AUC) was dose-dependent with values ranging from 38-150 microm/mL x hour. Pharmacokinetic parameters for free Pt (ultrafiltrate) were significantly different. The time to attain maximum concentration (t-max) and terminal half-life were shorter and the average AUC was approximately 100-fold lower than total Pt. After the intravenous infusion of cisplatin, the t-max for total and free Pt was 1.3 hours and 1.1 hours, respectively. The terminal half-life and average AUC for total Pt was 194 hours and 247 microg/mL per hour, respectively, and its corresponding parameters for free Pt after intravenous infusion were much lower, similar to the findings for the intralesional injection. CONCLUSIONS: The prolonged t-max and initial half-life noted with the intralesional injection of cisplatin/epinephrine/collagen gel are consistent with its proclaimed ability to retain cisplatin at the tumor and delay its release in systemic circulation. The kinetics of intralesional cisplatin injection also suggest local sequestration of the drug in the injected site. Parameters of intravenous cisplatin infusion in cirrhotic patients are similar to those of patients from the historic control group.

Aged↗

Quantitative and genotypic analysis of TT virus infection in Chinese blood donors.

BACKGROUND: The TT virus (TTV) is a member of a newly described family of human viruses related to the C ircoviridae viruses. Its association with specific diseases has not been established, and screening of blood donors has not been implemented. To date, 16 genotypes have been identified. STUDY DESIGN AND METHODS: Sera from 471 healthy blood donors (aged 11-58 years) were randomly selected and tested for TTV by the use of two sets of primers: NG59d/NG61d/NG63d primers and T801/T935 primers. Quantitative competitive PCR (QC-PCR) was developed to measure the TTV DNA concentration among the blood donors. Sequencing of a part of the genome was performed to identify the various genotypes. Several samples showed a mixed genotype infection. RESULTS: TTV was detected in 251 (53.3%) of 471 healthy Hong Kong blood donors by the use of NG59d/NG61d/NG63d primers. The prevalence of the virus increased steadily with age (p = 0.03). TTV DNA was detected in 90 percent (90 of a randomly selected 100) of samples by the use of T801/T935 primers. TTV DNA concentration was also measured by QC-PCR in the blood donors who were positive for TTV DNA in the first round of the heminested PCR. TTV titers ranged from 4.8 x 10(2) copies per mL to 6 x 10(4) copies per mL, with a median value of 1.2 x 10(4) copies per mL. Sequencing and phylogenetic analysis of a 223-bp fragment from open reading frame 1 showed three main genotypes (G1 [60.7%], G2 [24.3%], and G3 [14%]) and a new genotype 17 (G17), with the latter bearing 60-percent nucleotide homology with other genotypes deposited at GenBank. In addition, a new TTV subtype, G2f, was found. CONCLUSION: The prevalence of TTV is high in healthy Chinese blood donors. Three main genotypes (G1, G2, and G3) were detected. In addition, a new TTV genotype, tentatively designated as G17, and a new subtype, G2f, were identified.

Adolescent↗

Gross elevation of TT virus genome load in the peripheral blood mononuclear cells of cancer patients.

TT virus (TTV) is a recently described circular DNA virus of about 3.8 kb, which is related to the circoviridae viruses. It is commonly detected in healthy subjects and no association with any specific disease has been established. TTV was initially thought to be hepatotropic, but subsequent reports have shown that it is detectable in other tissues, including kidney, prostate, mammary gland, brain, bone marrow, and peripheral blood mononuclear cells. Plasma samples from cancer patients and healthy subjects were tested for the presence or absence of TTV by heminested polymerase chain reaction (PCR). We also developed a quantitative competitive PCR (QC-PCR) assay for TTV that permits accurate measurement of TTV DNA load. Using this assay, the TTV genome load in peripheral blood mononuclear cells (PBMCs) of healthy control subjects (n = 50) and patients with various types of cancer (n = 148), including breast cancer, non-Hodgkin's lymphoma, colon cancer, hepatocellular carcinoma, nasopharyngeal carcinoma, and other cancers, was measured. TTV DNA was detected in 69 of 100 plasma samples (69%) of cancer patients tested and in 39 of 100 plasma samples (39%) randomly selected from 1000 plasma samples of blood donors (p < 0.05). TTV DNA was detectable in the PBMCs of 99% of the cancer patients and 86% of the controls. However, the median virus load was more than 100-fold higher in the cancer patients (3599 copies/100,000 cells) than among the controls (30 copies/100,000 cells; p < 0.0001). There was no significant difference in TTV load among the different cancer types. Using a cutoff value of >250 copies per 100,000 PBMCs, 93.2% of cancer patients were "positive" compared to only 4% of healthy control subjects. Almost all the cancer patients have TTV infection and their TTV genome load in PBMCs is significantly higher than that in control subjects. It remains to be elucidated whether such findings are specific to cancer patients or occur in all seriously ill subjects.

Adult↗

Camptothecin induces differentiation, tissue transglutaminase and apoptosis in cultured keratinocytes.

Cultured normal human adult keratinocytes were exposed to (S)-(+)- camptothecin over the concentration range 10(-5) to 10(-10) M. The dose-dependent inhibition of growth was recorded using cell counting. The induction of terminal differentiation was demonstrated by the relative increase in squamous and cornified cells, and the concomitant decrease in small, proliferative cells, with an overall decrease in total cell numbers on going from 10(-10) to 10(-6) M concentration of the drug. The induction of apoptosis was studied by assay of two types of transglutaminase, "tissue" and "keratinocyte", and by assay of histone-linked mono- and oligonucleosomes. Induction of apoptosis was accompanied with increase in "tissue" transglutaminase and in the amount of nucleosomes, the latter being indicative of endonuclease activity. This activity was sharply increased at a camptothecin concentration of 10(-5) M, and may have been facilitated by "tissue" transglutaminase at lower concentrations. The data suggest that camptothecin restricts keratinocyte growth by several mechanisms including apoptosis and emphasize its possible use in topical therapy for psoriasis.

Adult↗

Psoriasis in China.

This paper presents a review of the epidemiology, the frequency of HLA antigen, the special clinical forms, the associations, and the treatment of psoriasis in China. Special attention is paid to the practice of treating psoriasis with traditional Chinese medicine and combinations of traditional Chinese and Western medicine.

China↗

Lectin histochemistry in psoriasis, lichen planus and seborrheic keratosis.

Lectin binding patterns in psoriasis, lichen planus and seborrheic keratosis lesions were studied using 14 different biotinyl lectins and avidin-horseradish peroxidase. Compared with normal epidermis, there were significant quantitative and qualitative differences, some of which were characteristic.

Epidermis↗

The exuperantia gene is required for Drosophila spermatogenesis as well as anteroposterior polarity of the developing oocyte, and encodes overlapping sex-specific transcripts.

The Drosophila gene exuperantia (exu) is a maternal effect gene which is needed for proper localization of the bcd RNA during the formation of oocytes. We have extended the characterization of the exu phenotype and find that the gene functions in the male as well as the female germline. Six of seven exu alleles are male-sterile; mutant defects in spermatogenesis first appear during meiosis. A genetic analysis presented here shows that the exu gene does not encode a zygotic vital function. The isolation of two overlapping deficiencies that delete exu function localizes the gene cytologically to polytene bands 57A4-B1. We describe the molecular cloning and identification of the gene, and show that it encodes overlapping sex-specific transcripts of 2.9 kb in the male and 2.1 kb in the female. We also show that these two transcripts are limited in expression to the germline. We demonstrate that one allele, exuVL57, is a deletion of about 700 bp which results in a loss of both transcripts.

Alleles↗