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Biomedical subjects

S L Li

Publications and source records attributed to S L Li.

At least 73 records · Page 4Linked to original sources
PubMed1992

Low p53 level in immortal, non-tumorigenic oral keratinocytes harboring HPV-16 DNA.

The p53 protein level was determined in normal oral keratinocytes and two non-tumorigenic, immortal oral keratinocyte lines harboring human papillomavirus-16 (HPV-16)DNA. The p53 mRNA level in the immortal cells was higher than the normal counterpart, but the p53 protein level was notably lower in the immortalised cells. The half-life of p53 protein in the normal and immortal cells was < 1 h, and the p53 cDNA sequence of these cells showed no mutation. The immortal cells transcribed a high amount of E6/E7 mRNA encoded by HPV-16, but normal cells did not. These observations suggest that the immortal keratinocytes may translate normal level of wild-type p53 protein, and the low p53 level in these cells may be due to the enhanced degradation of the protein by HPV-16 E6 protein.

Blotting, Northern↗
PubMed1992

In vitro and animal studies of the role of viruses in oral carcinogenesis.

The linkage of herpes simplex virus (HSV) and human papillomavirus (HPV) to the development of oral cancer has been studied. In spite of the presence of viral nucleic acids in some human oral cancer specimens, HSV alone is not carcinogenic in animals: repeated viral inoculation to mouse or hamster oral mucosa fails to produce tumours or histopathological evidence of malignancy. However, HSV demonstrates co-carcinogenicity in vivo: viral inoculation significantly enhances the oncogenic capacity of chemical carcinogens in the oral cavity of mice and hamsters. Though the detailed mechanisms of HSV cocarcinogenicity are unknown, HSV promotes the chemical carcinogen-induced activation of certain cellular proto-oncogenes and inactivation of p53 tumour suppressor gene. Human papillomaviruses type 16 (HPV-16) and 18 (HPV-18) demonstrate oncogenicity by transforming normal human oral keratinocytes in vitro. While normal cells exhibit a limited life-span, cells transformed by these viruses show immortality and altered morphology in comparison with their normal counterparts. The HPV-immortalised cells contain multiple copies of intact viral genome integrated into cellular chromosomes. These cells also express several viral-specific mRNAs including viral E6/E7 mRNAs. Notably, these cells contain low levels of p53 protein and overexpressed cellular myc proto-oncogene compared to their normal counterpart; however, the immortilised cell lines are non-tumorigenic in nude mice.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1992

Malignant lymphoma associated with human AIDS and with SIV-induced immunodeficiency in macaques.

Malignant lymphomas associated with human (HIV) and simian (SIV) immunodeficiency virus infections are reviewed and compared. Recent observation of a high frequency of lymphomas in a series of cynomolgus macaques, highly immunodeficient after infection with SIVsm(smm3) are described. In addition to the increased frequency in human and monkey AIDS, SIV and HIV lymphomas share several important features. Clinically and by histology they present as aggressive high-grade malignant tumors with a predilection for extranodal growth in viscera, skin, central nervous system, testis, and retroorbitally. Most malignant lymphomas are of B-cell origin. AIDS lymphomas in humans are heterogeneous with regard to Epstein-Barr virus (EBV) association. Similarly, most lymphomas in monkeys experimentally infected with SIV tested to date were shown to be associated with an EBV-like simian herpes virus. These observations point to the possibility of using SIV-immunodeficient macaques for study of EBV and other oncogenic and immunosuppressive factors in AIDS-associated lymphomagenesis.

AIDS-Related Complex↗
PubMed1992

Sequential combined tumorigenic effect of HPV-16 and chemical carcinogens.

We immortalized oral keratinocytes by transfection with recombinant human papillomavirus type 16 (HPV-16) DNA and established two cell lines, human oral keratinocytes-16A (HOK-16A) and -16B (HOK-16B). These cell lines were morphologically different from the normal counterpart, contained HPV-16 DNA as integrated form and expressed numerous viral genes. However, these cells proliferated only in culture medium containing low calcium (0.15 mM) and are not tumorigenic in nude mice. To test the hypothesis that tumors can be developed by sequential combined effect of human papillomavirus and chemical carcinogens in the oral cavity, these immortalized cell lines were chemically transformed by exposure to either benzo[a]pyrene or methanesulfonic acid ethyl ester. Such transformants proliferated in medium containing physiological calcium levels (1.5 mM) and demonstrated enhanced growth potential in nude mice, whereas primary human oral keratinocytes treated with these chemical carcinogens failed to show any evidence of transformation. Chemically transformed cells contained integrated, intact HPV-16 sequences and transcribed significantly higher amount of HPV-16 E6/E7 messages and transforming growth factor-alpha (TGF-alpha) compared with the immortalized oral keratinocytes. Like the HPV-immortalized cell lines, the chemically transformed oral keratinocytes contained lower levels of newly synthesized, wild-type p53 proteins compared to normal cells, and expressed wild-type c-Ha-ras. These results indicate that this in vitro system is useful for investigating the mechanisms of multistep oral carcinogenesis.

Base Sequence↗
PubMed1992

Clinical features and predictive markers of disease progression in cynomolgus monkeys experimentally infected with simian immunodeficiency virus.

OBJECTIVE: To study the pathogenicity of simian immunodeficiency virus (SIVsm) in cynomolgus monkeys in order to establish an animal model for human AIDS. METHODS: Thirty-three cynomolgus monkeys were monitored for more than 2 years following experimental infection with SIVsm. RESULTS: All the macaques became SIV-infected, as demonstrated by virus recovery from peripheral blood lymphocytes and by the appearance of viral antibodies. SIVsm was found to be pathogenic, killing 29 out of the 33 monkeys (88%) within 26 months. Clinically, infected monkeys developed lymphadenopathy, splenomegaly, diarrhoea, weight loss, neurological symptoms and a remarkably high incidence (39%) of malignant lymphomas. All lymphomas were high-grade malignant and of B-cell origin. Disease progression was associated with low CD4+ lymphocyte count, involution of initially hyperplastic follicular B-cell areas in lymph nodes, reappearance of viral antigen in serum, loss of anti-Gag antibodies and development of systemic giant cell disease in 55% of the monkeys. CONCLUSIONS: There are many similarities between SIVsm-induced AIDS in cynomolgus monkeys and human AIDS with regard to clinical, virological, immunological and pathological manifestations.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Long-term tolerance and efficacy of 3'-azidothymidine and 3'-fluorothymidine treatment of asymptomatic monkeys infected with simian immunodeficiency virus.

Macaques chronically infected with simian immunodeficiency virus were treated with zidovudine (20 mg/kg of body weight per day for 9 weeks) or 3'-fluorothymidine (5 mg/kg of body weight per day for 9 weeks or three doses of 2 mg/kg per day for 24 days). Hematological changes in the treated animals included macrocytic anemia and leukopenia. Determination of antiviral effects in this model requires improved assay methods.

Anemia↗
PubMed1992

[Opportunistic malignant lymphomas in SIV infected primates--a model for Epstein-Barr virus associated lymphomas in AIDS].

In a series of 33 cynomolgus monkeys (Macaca fascicularis) experimentally infected with Simian Immunodeficiency virus (SIV), strain smm3, 13 animals developed malignant Non-Hodgkin lymphomas. These lymphomas presented with unusual primary manifestations like in the orbita, testes, and brain. The morphological features and immunophenotyping identified the tumors as high malignant B-cell lymphomas. In all tumors as well as in tumor-derived cell lines a cynomolgus B-lymphotropic herpes virus (CBLV) with structural homogeneity to the Epstein-Barr virus (EBV) could be demonstrated by Southern blotting with EBV-specific probes. The lymphoma cells also expressed CBLV-associated nuclear antigens involved in B-cell transformation crossreacting with EBNA-specific human sera and monoclonal antibodies. Ig-gene rearrangement studies revealed clonal populations, however, no translocations of the c-myc oncogene could be detected. The lymphomas developing with high frequency in SIV-induced immunodeficiency resemble a major subtype of human EBV-associated AIDS lymphomas. This animal model can therefore be used to further elucidate interactions of HIV and EBV in AIDS-related lymphomagenesis.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Role of thiol-disulfide exchange in insulin binding to its receptor.

The effects of reduction by DTT, oxidation by DTNB and treatment with NEM on the thiol contents and insulin binding to its receptor in mice liver membranes were studied. Reduction with DTT leads to a parallel increase in the thiol content and the specific binding of insulin to the membrane. Scatchard analysis of the results shows little change in the number of binding sites but a twofold increase of the binding constant. Washing the membrane with bound insulin by a DTT containing buffer results in a more marked increase in the release of bound insulin than washing with buffer alone, suggesting that part of the insulin is bound to its receptor by covalent disulfide linkages through a thiol-disulfide exchange reaction and reduction with DTT leads to a marked increase in this "disulfide-linked" insulin. Treatment with DTNB or NEM of the DTT-reduced membrane seems to reverse the effect of DTT reduction, although the reaction of the untreated membrane with DTNB or NEM had little or no effect on the specific binding of insulin. It is suggested that initially, part of the thiols responsible for the exchange reaction may not be available for reaction with DTNB and reduction with DTT generates further thiols leading to increased specific binding in general and increased insulin binding to the receptor through covalent disulfide linkages in particular.

Animals↗
PubMed1991

Aggregation of IGF-I receptors or insulin receptors and activation of their kinase activity are simultaneously caused by the presence of polycations or K-ras basic peptides.

Several groups including us reported that basic proteins and polycations activate the insulin receptor tyrosine-specific protein kinase (TPK) in vitro. However, some inconsistency has become obvious in the observations. The most intriguing was the brief description by Morrison et al. [(1989) J. Biol. Chem. 264, 9994-10001] that polylysine had no effect on the IGF-I receptor TPK despite its 84% identity to the insulin receptor TPK. In the present study, we used highly purified IGF-I and insulin receptor TPKs in an effort to solve the discrepancies noted in the recent publications and to reveal the mechanism by which polycations stimulate the receptor TPKs. We report that the IGF-I receptor TPK is stimulated by polycations and basic proteins in a manner similar to their effects on the insulin receptor TPK. When effects of polylysine and polyarginine on both receptor TPKs were closely compared, subtle qualitative differences were found: Polylysine stimulated autophosphorylation and exogenous substrate phosphorylation activities of both insulin receptor TPK and IGF-I receptor TPK similarly. In contrast, another polycation, polyarginine, affected both TPKs in a manner quite different from polylysine: Polyarginine stimulated insulin receptor autophosphorylation to a greater extent than polylysine did while it had a very small effect on the IGF-I receptor autophosphorylation as well as the exogenous substrate phosphorylation activities of the two receptor TPKs. We have further extended the studies to include the domains of natural proteins which contain a polylysine-like sequence.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

Patients treated with a monoclonal antibody (ab1) to the colorectal carcinoma antigen 17-1A develop a cellular response (DTH) to the "internal image of the antigen" (ab2).

The anti-tumor effector functions of unconjugated MAb in cancer therapy are not fully understood. Direct cytotoxic mechanisms have been demonstrated as well as induction of anti-idiotypic (ab2) and anti-anti-idiotypic (ab3) antibodies. If such a humoral response is induced, then an idiotypic cellular response would also be anticipated. Human monoclonal ab2s which mimic a tumor-associated antigen (TAA) (CO17-1A) of colorectal carcinoma (CRC) cells ("the internal image of the antigen") were produced. These ab2s were injected intradermally to patients with metastatic CRC who had been treated with the anti-colon carcinoma MAb 17-1A (ab1). Five out of 12 patients had a specific DTH (delayed-type hypersensitivity) reaction of the tuberculin type, which was proven by immunohistochemical analysis of skin biopsies. Serum ab3 was demonstrated in 4/4 tested DTH+ patients and also in 4 DTH patients. Control patients did not show any skin reactivity. Generation of an idiotypic response induced by the infused antibody (ab1) might be regarded as an active anti-tumor "vaccination". Induction of an idiotypic cellular and humoral cascade might be an important anti-tumor effector function of MAb and should be considered in future strategies for such therapy in cancer patients.

Antibodies, Anti-Idiotypic↗
PubMed1991

Expression of MHC-class-I antigens in human carcinomas and sarcomas analyzed by isoelectric focusing.

We analyzed the expression of class-I antigens in ex vivo human tumor cells by isoelectric focusing (IEF) the anti-class-I mAb W6/32 immunoprecipitates prepared from cell lysates. Out of 42 experiments, 27 were technically successful. The patient's blood lymphocytes were used as controls. In vitro exposure of the tumor cells to IFN gamma and TNF alpha elevated class-I antigen expression. In 11 cases, defects in MHC-class-I-antigen expression were observed. In 2 cases the antigens were detected only in the cytokine-treated tumor samples, probably due to a defect in the association between beta 2m and class-I heavy chains. Selective changes in the expression of alleles were seen in 10 cases and might involve HLA A, B and C antigens. Alterations in class-I expression as compared with the lymphocytes were observed in 9 of 13 cases in which the tumor cells were collected from metastases, and only in 2 of 14 primary tumors.

Adenocarcinoma↗
PubMed1991

Changes in the level of IL-2, T cell subsets and the function of T suppressor cells in patients with schistosomiasis japonica.

The level of interleukin-2 (IL-2) produced by peripheral blood mononuclear cells in vitro, T cell subsets and the function of T suppressor cells (Ts) in patients with schistosomiasis japonica were investigated. It was found that the level of IL-2 induced by schistosomal antigens was significantly high and positively related to the percentage of CD4+ cells. In the groups of chronic and advanced schistosomiasis japonica, the level of IL-2 induced by schistosomal antigens was markedly lower than that in the group of acute schistosomiasis japonica, but significantly higher than that in the group of normal controls. The IL-2 level was negatively related to the percentage of CD8+ T cells and the ratio of CD4+/CD8+. The level of IL-2 induced by PHA was greatly reduced in the group of advanced schistosomiasis japonica. The changes in the level of IL-2 and its relationship with T cell subsets and the function of Ts are also discussed.

CD4-CD8 Ratio↗
PubMed1991

Synergism of herpes simplex virus and tobacco-specific N'-nitrosamines in cell transformation.

Previous studies indicate that herpes simplex virus (HSV) enhances the carcinogenic activity of smokeless tobacco and tobacco-related chemical carcinogens in animals. Since tobacco-specific N'-nitrosamines (TSNAs) such as N'-nitrosonornicotine (NNN) and 4-(N-methyl-N'-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are major chemical carcinogens of smokeless tobacco and are known to be responsible for the development of oral cancers in smokeless tobacco users, the combined effects of TSNAs and HSV in cell transformation were investigated. Exposure of cells to NNN or NNK followed by virus infection resulted in a significant enhancement of transformation frequency when compared with that observed with chemical carcinogens or virus alone. This study suggests that TSNAs and HSV can interact together and show synergism in cell transformation.

Animals↗
PubMed1991

Immortalization of normal human oral keratinocytes with type 16 human papillomavirus.

Primary human oral keratinocytes were transformed by transfection with recombinant human papillomavirus type 16 (HPV-16) DNA, and two transformed cell lines named human oral keratinocytes-16A and -16B (HOK-16A and HOK-16B) were established. While normal cells and cells transfected with vector only exhibited a limited lifespan, the HOK-16A and HOK-16B lines demonstrated immortality and altered morphology from their normal counterpart. The HOK-16A and HOK-16B lines contained approximately 40 and approximately 25 copies of intact HPV-16 DNA as integrated form per cell respectively, and both cell lines expressed several viral specific poly(A+) RNAs. Notably these cell lines also overexpressed cellular myc proto-oncogene in comparison with the normal counterpart. However, the immortalized cell lines were not able to produce tumors in nude mice, indicating that the cells are partially transformed. The HOK-16A and HOK-16B lines are, therefore, useful for investigating the multistep molecular events of oral carcinogenesis.

Blotting, Northern↗
PubMed1991

Studies on the mutagenicity of hair dyes made in China.

A total of 13 commercial hair dye products made in China were tested for mutagenicity in 2 short-term bioassays, the histidine-requiring mutants of Salmonella typhimurium (strains TA98 and TA100) and the micronucleus test with mouse bone-marrow polychromatic erythrocyte cells in vivo. The results showed that the 13 hair dyes were not mutagenic in strains TA98 and TA100 with and without S-9. In the micronucleus test, no mutagenic effect was observed.

Animals↗
PubMed1990

Marfan syndrome in China: a collective review of 564 cases among 98 families.

This is a collective review of 564 patients with Marfan syndrome among 98 pedigrees reported from 18 provinces and cities in China over a 37-year period from 1951 to 1987. A positive family history of Marfan syndrome was found in 74.3% of the patients: the mode of inheritance was dominant in 73.8% and recessive in 0.5%. Sporadic cases occurred in 25.7%. A screening of 29,067 children found five children with Marfan syndrome, giving a prevalence of 17.2 per 100,000 of the population, a gene frequency of 8.61 per 100,000 genes, and a penetrance of 71.69%. Pleiotropy was clear in these cases: arachnodactyly in 77%, ectopia lentis in 86.8%, and dilated aortic root in 80.1%. Chromosome examination showed no regular aberrations except in a family of five in whom a giant-satellited chromosome 14 was found in three afflicted members but not in the two unaffected relatives. The high prevalence of aortic root dilation in Marfan syndrome makes echocardiography the most useful and practical means of diagnosis. Close follow-up and regular echocardiographic evaluation are indicated not only in patients with Marfan syndrome but also in their families, for both diagnostic and therapeutic purposes.

Adolescent↗