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Biomedical subjects

L Yu

Publications and source records attributed to L Yu.

At least 451 records · Page 25Linked to original sources

Estrogen receptor-negative breast cancer cells transfected with estrogen receptor exhibit decreased tumour progression and sensitivity to growth inhibition by estrogen.

Breast cancer containing estrogen receptors (ER) are responsive to antiestrogen treatment and have a better prognosis compared with ER-negative tumors. The loss of estrogen receptors appears to be associated with a progression to less-differentiated cells. We transfected the human ER into the ER-negative breast cancer cell line MDA-MB-231 cells. We found that expression of adequate ER is strong associated with the ability of human breast cancer cell growth inhibition and progression. Compared with nontransfected or mock-transfected cells, ER-transfected cells exhibited growth slower, forming smaller colonies in soft agar and growth inhibited by estrogen and tamoxifen. Therefore reactivation or transfection of the estrogen receptor gene can be considered as therapeutic approaches to hormone-independent breast cancer.

Breast Neoplasms↗

p53 independent G1 arrest and apoptosis induced by adriamycin.

The biological activity of adriamycin was investigated in human breast carcinoma (HBC) cells, Adriamycin inhibited the growth of a number of HBC cell lines and induced G1 arrest followed by apoptosis. In MCF-7 cells that harbor wild-type p53, adriamycin-induced G1 arrest and apoptosis was accompanied by p53-independent regulation of WAF1/CIP1 as well as bax mRNA levels. In MDA-MB-231 cells which possess a mutant p53, adriamycin-induced G1 arrest and apoptosis was also associated with a concomitant up-regulation of WAF1/CIP1 mRNA while these cells did not express bax or bcl-2 messages. Thus, adriamycin induces G1 arrest and apoptosis via a unique pathway which appears to involve activation of downstream effectors of p53-independent manner.

Antineoplastic Agents↗

Thyroxine-binding globulin and thyroid hormones after resection of hepatocellular carcinoma.

OBJECTIVES: Some human hepatocellular carcinomas (HCCs) produce thyroxine-binding globulin (TBG). High serum TBG levels in such patients may be associated with increased thyroxine (T4) levels. This study aimed to elucidate the serum TBG and thyroid hormone profile in Japanese patients with HCC, to compare the difference between TBG-producing and -nonproducing HCCs, and to investigate the changes in serum TBG level and the thyroid hormone profile after removal of the tumor. METHODS: The 40 subjects included 20 patients with HCC, 10 healthy controls, and 10 operative controls. Serum TBG, 3,5,3'-triiodothyronine (T3), T4, and free T4 were measured serially for 4 wk after resection of HCC in 16 patients and after control operations in 10 patients. Assay methods were a radioimmunoassay for TBG and enzyme immunoassays for T3, T4, and free T4. RESULTS: Values higher than the mean +/- 2 SD of controls were considered abnormally high. Of patients with HCC, 60% had abnormally high TBG values, 65% had abnormally high T3 values, 39% had abnormally high T4 values, and 6% had abnormally high free T4 values. The mean levels of TBG and T3 were significantly higher than those in healthy controls, but no difference was found for T4 and free T4 levels. There were no significant differences in various clinicopathological factors between patients with high TBG levels and those with normal TBG levels. After resection of HCC, serum TBG decreased significantly in patients with high TBG levels but not in those with normal TBG levels. CONCLUSIONS: This study shows that >50% of HCCs in Japanese patients produce TBG; removal of the tumor reduces serum TBG in such cases.

Adult↗

Tumor necrosis factor alpha in children with sickle cell disease in stable condition.

Tumor necrosis factor alpha (TNF-alpha) is known to induce wasting in humans and animals. This study was undertaken to determine TNF-alpha concentrations in children with sickle cell disease (SCD) and whether high TNF-alpha levels are more likely to be present in children with growth deficits, infection, or pain crisis. Tumor necrosis factor alpha was measured using enzyme immunoassay in 143 blood samples obtained from 101 children. Mean TNF-alpha levels were higher in patients (50 pg/mL) than in 21 control children (19 pg/mL) and in 26 laboratory employees (20 pg/mL). During the follow-up period, 35%, 38%, and 28% of children with SCD had infection, pain crisis, or a blood transfusion, respectively. Mean TNF-alpha concentrations were higher in children who had an infection than in those who did not. No significant effect of pain crisis or blood transfusion was observed. Tumor necrosis factor alpha concentrations were above normal (> 40 pg/mL) in 15% of controls, 34% of children with SCD, and 52% of children with SCD who had an infection and 33% of those who did not. A higher percentage of children who had elevated TNF-alpha levels had weight (46% versus 31%) or height (50% versus 28.6%) deficits than children who had normal TNF-alpha levels. These results indicate that most children with SCD in stable condition have normal TNF-alpha concentrations and that those with high TNF-alpha levels are more likely to have growth deficits.

Adolescent↗

Ribozyme-mediated inhibition of a Philadelphia chromosome-positive acute lymphoblastic leukemia cell line expressing the p190 bcr-abl oncogene.

The bcr-abl oncogene is the molecular counterpart of the Philadelphia chromosome (Ph), which is detected in > 95% of patients with chronic myelogenous leukemia (CML) and 20-30% of adults with acute lymphoblastic leukemia (ALL). Leukemic cells from patients with CML express the p210 form of the bcr-abl oncogene, whereas in adult Ph+ ALL approximately 50% of cases express the p190 form of the bcr-abl oncogene, and the other 50% express the same p210 gene as is found in CML. In this study, we have designed hairpin ribozymes (RZs) specific for the p190 form of the bcr-abl oncogene to inhibit the growth of a p190 Ph+ ALL cell line, Sup-B15. The RZs cleave p190 RNA substrate in a cell-free in vitro assay. In the presence of the liposome, DMRIE-C, the RZs are protected from serum mediated catalysis in vitro. Anti-p190 RZs transfected with DMRIE-C as the vector into K562 cells, which express the p210 bcr-abl oncogene, are stable intracellularly for up to 96 hours. Up to 33% of the DMRIE-C and RZ mixtures are taken up by Sup-B15 cells cultured in suspension. Expression of the p190 bcr-abl protein product is specifically inhibited as demonstrated by Western blot analysis. Cell growth of the Sup-B15 cells is completely inhibited by anti-p190 RZs over four days in culture. Anti-p210 RZs have no significant effect on bcr-abl protein expression or cell growth by Sup-B15 cells. RZs may have a role in purging stem cell populations collected from patients with Ph+ ALL in the context of autologous bone marrow transplantation.

Blotting, Western↗

Late tension pneumocephalus following frontal craniotomy.

Tension pneumocephalus is an uncommon but life-threatening complication of craniotomy which requires urgent diagnosis and treatment. It most often occurs perioperatively following subsequent anaesthesia using nitrous oxide. All previously reported postoperative cases followed posterior fossa or upper spinal cord surgery. Only two cases associated with frontal craniotomy have been reported since 1972, both occurring intraoperatively.

Aged↗

Initial study on naturally occurring products from traditional Chinese herbs and vegetables for chemoprevention.

A number of naturally occurring products from vegetables and herbs exert chemopreventive properties against carcinogenesis. In this paper, two such compounds, isolated from garlic and from a traditional Chinese medicinal herb, are described for review. Elemene, isolated from the Chinese medicinal herb Rhizoma zedoariae, was shown to exhibit antitumor activity in human and murine tumor cells in vitro and in vivo. This novel antineoplastic agent has substantial clinical activity against various tumors. The in vitro effect of elemene on the growth of leukemia cells was evaluated by MTT assay. The IC50 values of elemene for promyelocytic leukemia HL-60 cells and erythroleukemia K562 cells were 27.5 micrograms/mL and 81 micrograms/mL, respectively, while IC50 for peripheral blood leukocytes (PBL) was 254.3 micrograms/mL. The inhibitory effect of elemene on proliferation of HL-60 cells was associated with cell cycle arrest from S to G2M phase transition and with induction of apoptosis. The apoptosis of tumor cells was confirmed by DNA ladder formation on gel electrophoresis and characteristic ultrastructural alterations. The results also demonstrated that inhibitory effects of allicin, a natural organosulfide from garlic, on proliferation of tumor cells were associated with the cell cycle blockage of S/G2M boundary phase and induction of apoptosis. These findings suggest that induction of apoptosis may contribute to the mechanisms of antitumor activity of elemene and allicin, which merit investigation as potential chemoprevention agents in humans.

Anticarcinogenic Agents↗

Immunofluorescence study of type IV collagen alpha chains in epidermal basement membrane: application in diagnosis of X-linked Alport syndrome.

OBJECTIVE: To detect the distribution of alpha 5 (IV) chain of collagen on the glomerular basement membrane (GBM) and epidermal basement membrane (EBM) in the Chinese Alport syndrome (AS) kindreds and to develop a simple diagnostic alternative method to electronic microscopy for diagnosis of AS. METHODS: Four male patients from 4 unrelated families manifested with hematuria, sensorineural hearing loss and had distinct family history. All patients had the characteristic AS pathologic changes by electron microscopy on their renal biopsy tissues. Three normal skin samples and 2 normal kidney samples were used as normal controls. Monoclonal antibody-based IF test was performed to examine the alpha 5 (IV) NC1 domain in EBM of normal controls, X-linked AS patients and their parents, and in GBM of normal controls and AS patients. RESULTS: In normal controls as well as the patients' fathers, all the monoclonal antibodies used in EBM and GBM staining showed positive reactions along basement membranes in a linear pattern. Characteristically, in AS patients there were negative reactions to monoclonal antibodies anti-alpha 5 (IV) NC1 domain in EBM and anti-alpha 3-5 (IV) NC1 domains in GBM. In patients' mothers, alpha 5 (IV) chain was distributed segmentally in EBM. CONCLUSION: The staining of alpha 5 (IV) NC1 domain in EBM by IF can be used to diagnose patients and screen defect-gene carriers of X-linked AS.

Adult↗

Identification of a novel missense mutation in Wilson's disease gene.

OBJECTIVE: To investigate the allelic heterogeneity of the ATP7B gene in Chinese patients with Wilson's disease (WD). METHODS: Exons of the ATP7B gene from 141 WD patients' DNA were amplified with polymerase chain reaction (PCR) 887-890. Mutations were then screened by single strand conformation polymorphism (SSCP) analysis and further identified by sequencing. RESULTS: The molecular structure of exon 7 of the ATP7B gene from 141 WD patients was analyzed. The same band shift in electrophoretic pattern of 4 cerebral type patients was identified with SSCP and subsequently sequenced. The results showed missense mutation at the second base of the codon as Ser 662 Cys, which is caused by a C to G transversion. CONCLUSIONS: Mutations of the ATP7B gene were investigated for the first time in China and a novel missense mutation was identified in four cases.

Adolescent↗

[Identification of a novel missense mutation in Wilson disease gene].

OBJECTIVE: To investigate the allelic heterogeneity of ATP 7 B gene in Chinese patients. METHODS: Exons of ATP7B gene from patient's DNA were amplified with PCR technique. Mutations were screened by single strand conformation polymorphism (SSCP) analysis and further confirmed by sequencing. RESULTS: The molecular structure of exon 7 of the ATP7B gene from 141 WD patients was preliminarily analyzed. A similar band shift of 4 encephalopathy type patients was identified with SSCP and sequencing. There was a missense mutation, Ser 662 Cys, which was caused by a C to G transversion at the second base of the codon. CONCLUSIONS: The mutations of Chinese ATP7B gene were investigated for the first time in China and a novel missense mutation was identified.

Adolescent↗

[Abrogated or decreased tumorigenicity and metastasis induced by retroviral-mediated B7.1 gene transfer on murine tumors with different immunogenicity].

OBJECTIVE: To investigate the differences of tumorigenicity and metastasis of marine tumors with different immunogenicity by B7.1 gene transfer. METHOD: Using retroviral-mediated gene transfer, we transduced B7.1 cDNA into a panel of murine tumor lines with different immunogenicity to study the effect of B7.1 costimulation on antitumor immunity. RESULTS: After transduced with B7.1 cDNA, the immunogenic T lymphoma EL4 regressed completely, and tumorgenicity of three nonimmunogenic tumors melanoma B16, mastocytoma P815 and mammary adenocarcinoma MA891 were significantly reduced in syngeneic mice. The experimental metastasis of B16 and spontaneous pulmonary metastasis of MA891 were profoundly suppressed. Moreover, immunization with B7.1 cDNA transduced B16 induced systemic immunity against subsequently inoculated parental B16 tumor, while this immunization method did not provide protective immunity against established parental B16 tumor. CONCLUSION: Our results show that varied extent of antitumor immunity can be induced to abrogate or decrease tumorigenecity and metastasis through B7.1 gene transduction, depending on the immunogenic potential of tumors.

Animals↗

[Analysis of sensorineural hearing loss in 77 children].

The causes and cochlear-vestibular functions were analysed in 77 deaf children. The results showed that: the occurrence of hearing impairment beyond a moderately severe degree of deafness was 109 ears. The abnormalties of electronystagmus and posturography were 88.9% (44/45). 19 cases (38 ears) were large vestibular aquaduet syndromes, which were embryo development malformations. The average age of onset was 7.1 years. 15 cases have suffered from deafness of aminoglycoside ototoxicity. The average age of onset was 2.8 years. 13 of them appear to suffer deaf-mutism because of the early onset in their lives. The deaf mechanisms of the large vestibular aqueduct syndrome and the ototoxicity were discussed.

Adolescent↗