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Biomedical subjects

L Y Li

Publications and source records attributed to L Y Li.

At least 55 records · Page 3Linked to original sources
PubMed1998

Morphology and function of human benign tumors and normal thyroid tissues maintained in severe combined immunodeficient mice.

In the improved SCID (severe combined immunodeficient) mice, various human benign tumors of the head and neck region were well maintained morphologically and functionally for 3 years until the experiments were terminated, e.g. transplanted parathyroid adenoma secreted parathyroid hormone (PTH) in the SCID mice for more than 1 year. Normal human thyroid tissue was also well maintained in the SCID mice for 3 years. Rapid and high uptake of radioiodine into the transplanted human thyroid tissue was observed. Furthermore, transplanted human thyroid tissue secreted thyroid hormone (T3) and T3 secretion was stimulated by the injection of human thyroid stimulating hormone (TSH). These findings suggest that the improved SCID mice will provide an invaluable experimental system for investigating the function of normal human tissues and the influence of endogenous and exogenous factors on human tissues.

Adenoma↗
PubMed1998

Induction of apoptosis in proliferating human endothelial cells by the tumor-specific antiangiogenesis agent combretastatin A-4.

The antiangiogenic, tubulin-binding drug combretastatin A-4 exhibits a selective toxicity for proliferating endothelial cells in vitro and induces vascular shutdown in tumor models in vivo. The mechanism of combretastatin A-4 cytotoxicity has now been investigated with cultured proliferating human umbilical vein endothelial cells by examining various markers of apoptosis. Incubation of cells with 0.1 mM combretastatin A-4 induced the conversion (first detected after 6 h) of the CPP32 proenzyme to active caspase-3, a cysteine protease that plays an important role in apoptosis in many cell types; the drug also increased caspase-3 activity. Another early event observed was the binding of annexin V to 50% of the cells 8 h after drug treatment. Internucleosomal DNA fragmentation, another hallmark of apoptosis, was detected in cells incubated with 0.1 mM combretastatin A-4 for 24 h. Staining with Hoechst 33258 revealed that about 75% of cells exhibited a nuclear morphology characteristic of apoptosis after incubation with drug for 24 h. Incubation of cells for up to 8 h with combretastatin A-4 did not induce the release of lactate dehydrogenase or increase the uptake of propidium iodide, both indicators of membrane integrity. These results indicate that the selective cytotoxic effect of combretastatin A-4 is mediated by the induction of apoptosis rather than by necrosis and may provide an enhanced clinical strategy in cancer chemotherapy with this new agent.

Animals↗
PubMed1998

High incidence of esophageal cancer in esophageal achalasia by the oral administration of N-amyl-N-methylnitrosamine and its prevention by nicardipine hydrochloride in mice.

Esophageal achalasia (EA) is a rare disease in man and animals and there are many discussions on its higher risk of esophageal cancer. N-Amyl-N-methylnitrosamine (AMN) which specifically induces esophageal tumors in mice and rats was given to three mutant mouse strains, i.e. 101/N, STX/Le and BXH-8, which develop a high incidence of EA. The incidence of EA in 101/N, STX/Le, BXH-8 and normal C57BL/6J mice was 38.5% (110/286), 30.1% (43/143), 91.8% (190/207) and 0% (0/167), respectively. The average numbers of AMN-induced esophageal tumors in EA(+) were significantly higher than those of EA(-) in all of the 101/N, STX/Le and BXH-8 mice. Furthermore, significantly larger size tumors and invasive squamous cell carcinomas were found in EA(+) mice than in EA(-) mice. These results indicate the higher sensitivity of EA for both tumor induction and promotion, possibly due to the longer retention of AMN. In fact, relaxation of the lower esophagus by a smooth muscle relaxing calcium-channel blocker, nicardipine hydrochloride, significantly prevented the induction of esophageal tumors.

Administration, Oral↗
PubMed1998

Dose rate effectiveness and potentially lethal damage repair in normal and double-strand break repair deficient murine cells by gamma-rays and 5-fluorouracil.

SCID (severe combined immunodeficiency) fibroblasts established from C.B 17-scid/scid embryos showed higher sensitivity to high (1.105 Gy/min) and low (0.00069 Gy/min) dose rate gamma-rays and also to 5-fluorouracil, a cancer sedative producing double-strand breaks, than wildtype cells from C.B17- +/+ embryos. Furthermore, SCID cells were deficient in repairing DNA damage induced by high dose rate gamma-rays even after dose fractionation and after 24 h recovery periods, while wildtype cells showed an apparent repair ability on DNA damage after these gamma-ray exposures. This is the first report to prove that SCID cells lack the repair of gamma-ray-induced potentially lethal damage and also of 5-fluorouracil-induced double-strand breaks. However, SCID cells showed a significantly higher survival rate by low dose rate exposure than by high dose rate exposure as in the case of wildtype cells, indicating that SCID cells have a deficiency in DNA repair for high dose rate gamma-rays, but not for low dose rate exposure. This suggests an important finding that the dose rate effect (diminution of cell killing by low dose rate exposure) is caused not only by the repair of double-strand breaks induced by gamma-rays but in most parts by less yields of double-strand breaks due to dispersed or low intensity ionization in the cell.

Animals↗
PubMed1998

CP/MAS 13C spectral editing of dried pine leaves.

The recently developed CP/MAS 13C spectral editing technique is applied to the study of the structure of the dried Australian pine leaves. Subspectra of quaternary carbon C, methenyl CH, methylene CH2 and methyl CH3 for Australian pine leaves have been obtained. Simple formulae for spectral editing are proposed.

Carbon Isotopes↗
PubMed1997

Induction of cancer, actinic keratosis, and specific p53 mutations by UVB light in human skin maintained in severe combined immunodeficient mice.

To study the mechanism and risk of human skin cancer from solar light, we exposed human skin transplanted to severe combined immunodeficient mice to daily doses of UVB for periods of approximately 2 years. We have succeeded for the first time in inducing cancer and solar (actinic) keratosis in human skin by UVB. Of 18 normal skins exposed to doses of 7.3 x 10(5) to 1.8 x 10(6) J/m2, 14 actinic keratoses (77.8%) and 3 squamous cell carcinomas (16.7%) developed, whereas neither actinic keratosis nor cancer was observed in 15 human skins not exposed to UVB. Each human skin showed a different susceptibility, and skins sensitive for actinic keratosis were also sensitive for cancer induction. Among p53 mutations at various sites, mutation at codon 242 (C TGC --> C CGC; Cys --> Arg) was specifically observed in both skin cancers and actinic keratoses. Furthermore, double or triple mutations were induced in all UVB-induced skin cancers and in three of eight actinic keratoses. Most of the mutations (17 of 20) occurred at dipyrimidine sites.

Animals↗
PubMed1997

A novel case of unilateral blepharophimosis syndrome and mental retardation associated with de novo trisomy for chromosome 3q.

We have evaluated a 3 2/12 year old girl who presented with unilateral blepharophimosis, ptosis of the eyelid, and mental retardation. Additional dysmorphic features include microcephaly, high, narrow forehead, short stubby fingers, and adduction of the right first toe. Cytogenetic analysis showed an unbalanced karyotype consisting of 46,XX,add(7)(q+) that was de novo in origin. Fluorescence in situ hybridisation (FISH) using microdissected library probe pools from chromosomes 1,2,3,7, and 3q26-qter showed that the additional material on 7q was derived from the distal end of the long arm of chromosome 3. Our results indicate that the patient had an unbalanced translocation, 46,XX,der(7)t(3;7)(q26-qter;q+) which resulted in trisomy for distal 3q. All currently reported cases of BPES (blepharophimosis-ptosis-epicanthus inversus syndrome) with associated cytogenetic abnormalities show interstitial deletions or balanced translocations involving 3q22-q23 or 3p25.3. Our patient shares similar features to BPES, except for the unilateral ptosis and absence of epicanthus inversus. It is possible that our patient has a contiguous gene defect including at least one locus for a type of blepharophimosis, further suggesting that multiple loci exist for eyelid development.

Adult↗
PubMed1997

Consecutive maintenance of human solitary and hereditary colorectal polyps in SCID mice.

Recently, the sequential changes from adenoma to adenocarcinoma have been well studied in human colorectal carcinogenesis. To study the precise clonal changes from colorectal polyps to cancer, we have established an experimental system to maintain human colorectal polyps in severe combined immunodeficient (SCID) mice that have been improved by the selective inbreeding of C.B17-scid/scid homozygous male and female showing undetectable serum IgG and IgM (< 1 microgram/ml). Two of two solitary polyps from two nonhereditary colon polyp patients, four of five colon polyps from two Peutz-Jeghers' syndrome patients and one polypoid lesion from a familial polyposis coli (FAP) patient grew very slowly but steadily, at approximately one-tenth the rate of their malignant form, (i.e., adenocarcinoma), in the improved SCID mice and were maintained for a long period (more than 2 years), over several mouse generations. However, two polyps from FAP and Peutz-Jeghers' syndrome patients could not be transplanted further because of microinfection at the transplanted site due to incomplete sterilization of original human tumors prior to surgical operation (endoscopic polypectomy). Transplanted colon polyps had a semitransparent, soft and sticky appearance, with cells containing large amounts of mucin. Malignant transformation of human colon polyp to adenocarcinoma has not been observed during the maintenance period (about 2 years) in SCID mice. In the consecutively maintained human colon polyps, however, K-ras mutations were detected at codon 12, while these mutations were not found in their original polyps in the patients.

Adenomatous Polyposis Coli↗
PubMed1997

[An epidemiological investigation of eperythrozoon infection in human and animals (III)].

This paper reported an epidemiological investigation on human and animal infection to Eperythrozoon in 5 provinces. The results showed that Eperythrozoon infection existed in human as well an in animals in those provinces. Due to geographical variation, the infection rates were different. The infection rate was not associated with sex and age in human. The overall infection rate of different Eperythrozoonoses was higher than in healthy humans. The cases of Eperythrozoonoses among human and pig-herd were reported in this paper.

Adolescent↗
PubMed1996

Fluorometric study of the isoform difference of mammalian metallothionein.

A fluorometric method for studying the isoform difference of mammalian metallothionein (MT), which lacks aromatic amino-acid residues, is reported. Cadmium-induced rabbit and hedgehog liver MT exhibited a strong luminescence signal in the range of 335 to 340 nm when excited at 285 nm in aqueous solution. The differences in emission intensity of the two major isoforms of MTs are significant. When titrated with chloride acid, which is believed to proton the metal-thiolate coordination bound to the -SH group in MT, a 10-nm red-shift property of the emission spectrum was observed, and the red-shift properties of the isoforms varied with the species. The observed fluorescence property of MT was considered to be the result of its polypeptide chains, which was confirmed by comparing the luminescence and absorption spectra during the titration of MT with diethylenetriaminepentaacetic acid. The new luminescence property of MT should be useful in studying the isoform and function difference of MT.

Animals↗
PubMed1996

Alternative splicing of the FMR1 gene in human fetal brain neurons.

The alternative splicing expression of the FMR1 gene was reported in several human and mouse tissues. Five regions of FMR1 gene can be alternatively spliced, but the combination of them has not been investigated fully. We reported here the analysis of alternative splicing pattern of the FMR1 gene in cultured fetal human neurons, using a RT-PCR and cloning strategy. Eleven splicing types were cloned and different isoforms were not equally represented. The dominant isoform represents nearly 40%, and the other isoforms were relatively rare. One isoform has a different carboxylterminus. Most of the alternative spliced regions appear hydrophilic; thus, they may locate on the surface of the FMR1 protein.

Alternative Splicing↗
PubMed1996

Determination of LTE4 in human urine by liquid chromatography coupled with ionspray tandem mass spectrometry.

A sensitive and specific high-performance liquid chromatographic/ionspray tandem mass spectrometric (LC/ionspray MS/MS) method was developed and validated to quantitate leukotriene E4 (LTE4) in human urine. This method involves solid-phase extraction with Empore membrane disks to isolate LTE4 and its internal standard, LTE4-d3, from the urine stabilized with antioxidant and metal ion chelating agent. The reconstituted extracts were analyzed by LC/ionspray MS/MS in the selected reaction monitoring (SRM) mode. The assay has a lower level of quantitation (LOQ) of 50 pg ml-1 for LTE4 based on 5 ml aliquots of urine. The calibration graphs were linear from 50 pg ml-1 to 10 ng ml-1 for LTE4 extracted from urine. The inter- and intra-assay precision (RSD) and accuracy (DEV) did not exceed 11% and 8% at any level of the calibration standards and quality control (QC) samples, respectively. The recovery of LTE4 using the Empore disk solid-phase extraction technology was independent of LTE4 concentration in human urine. The overall extraction recovery for LTE4 was 72% (RSD = 2.14%).

Antioxidants↗
PubMed1996

NMR microscopy of polyacrylamide hydrogel.

Polyacrylamide Hydrogel (PAMG) is a kind of water-absorbing functional material. It has the ability of absorbing large amounts of water and releasing water under different conditions. So PAMG has an extensive background of applications in many fields. It is an interesting problem to clarify the distribution and status of water in PAMG1. This paper reports experiments in which the proton distribution and structures of networks in gamma-irradiation crosslinked PAMG samples have been shown by using spin-echo single-slice imaging of nuclear magnetic resonance microscopy.

Acrylic Resins↗
PubMed1996

Human papillomavirus type 11 and 16 E5 represses p21(WafI/SdiI/CipI) gene expression in fibroblasts and keratinocytes.

Here we report that the E5 proteins of human papillomavirus type 11 (HPV-11) and HPV-16 suppressed the expression of the p21(WafI/SdiI/CipI) tumor suppressor gene in NIH 3T3 cells and immortalized human keratinocytes. The promoter activity of p21 was repressed by E5 of HPV-11 and -16, suggesting that p21 gene suppression by E5 was at the transcriptional level. Using an inducible system, we demonstrated that increased induction of HPV-11 E5 in NIH 3T3 cells and keratinocytes led to increased repression of p21 promoter activity. The repression of p21 promoter activity by a series of E5 mutants was somewhat correlated with their respective transforming activities. Previously, we and other investigators showed that the E5 proteins of HPV-11 and -16 can activate the expression of c-jun. The repression of p21 gene expression might be a mechanism of oncogene-mediated growth promotion, since the expression of c-jun also led to a reduction of the levels of p21 RNA and protein in keratinocytes. This is the first demonstration that E5 proteins of HPV-11 and -16 repress p21 gene expression, and this might be one of the mechanisms by which E5 stimulates cell proliferation. In addition, this is also the first report of c-jun repression of p21.

3T3 Cells↗
PubMed1996

E5 proteins of human papillomavirus types 11 and 16 transactivate the c-fos promoter through the NF1 binding element.

Human papillomavirus type 11 (HPV-11) and HPV-16 contain an E5 gene that can induce c-fos gene expression in mouse fibroblasts. This study investigated the human c-fos promoter characteristics by mapping the c-fos promoter sequence with several deletion and point mutants that confer responsiveness to E5 of HPV-11 or HPV-16. The mutant studies show that NF1 binding sequences within the c-fos promoter were crucial for the induction of the c-fos gene by E5, and the gel shift assay study suggested that E5 of both HPV-11 and HPV-16 is associated, perhaps indirectly, with this NF1 element in the transactivation of the human c-fos promoter. Using an inducible system, we demonstrate that increased induction of the HPV-11 E5 gene in cells led to increased transactivation of the NF1 element. In addition, the transactivating activity of a series of HPV-11 E5 mutants on the NF1 element had a strong correlation with their respective transforming activities.

3T3 Cells↗
PubMed1996

The stimulatory effect of opioids on mitogen-activated protein kinase in Chinese hamster ovary cells transfected to express mu-opioid receptors.

The mitogen-activated protein (MAP) kinase of Chinese hamster ovary cells (CHO mu66 cell line) transfected to express mu-opioid receptors was markedly activated by mu agonists. The rank order of effectiveness of agonists was approximately the same as the rank order of their binding affinities to the mu receptor. The delta and kappa receptor-specific agonists cyclic[D-Pen2, D-Pen5]enkephalin and U69,593 showed a very weak stimulatory effect. The mu agonist-stimulated MAP kinase activity peaked at approximately 4-8 min and lasted almost 1 hr. The stimulatory effect of mu agonists was antagonized by the opioid receptor antagonist naltrexone and inhibited by pretreatment of cells with pertussis toxin. This opioid-induced activation of MAP kinase activity may have a role in the long term effects of opioids.

Animals↗
PubMed1996

[An epidemiological investigation of eperythrozoon infection in human and animals (II)].

This paper reported an epidemiological investigation on human and animals infection of eperythrozoon in 1 provinces. The results showed that eperythrozoon infection appeared in human as well as in swines, sheep, cats, donkeis and chickens. Due to geographical variations, the infection rates showed a significant difference, both in human and animals. The infection rate was not associated with sex, age or occupation in human, but was associated with seasons in animals. High peak of infection rates in animals was in May, June, July and August.

Adolescent↗