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Biomedical subjects

L Cui

Publications and source records attributed to L Cui.

At least 91 records · Page 5Linked to original sources

Modification of sample size in group sequential clinical trials.

In group sequential clinical trials, sample size reestimation can be a complicated issue when it allows for change of sample size to be influenced by an observed sample path. Our simulation studies show that increasing sample size based on an interim estimate of the treatment difference can substantially inflate the probability of type I error in most practical situations. A new group sequential test procedure is developed by modifying the weights used in the traditional repeated significance two-sample mean test. The new test has the type I error probability preserved at the target level and can provide a substantial gain in power with the increase of sample size. Generalization of the new procedure is discussed.

Biometry↗

In vivo gene transfer of a suicide gene under the transcriptional control of the carcinoembryonic antigen promoter results in bone marrow transduction but can avoid bone marrow suppression.

We constructed the CEA419/CD retrovirus vector carrying the cytosine deaminase (CD) gene directed by the carcinoembryonic antigen (CEA) promoter. pCD2 retrovirus vector carrying the CD gene directed by the retrovirus long terminal repeat promoter was also used. When mice bearing intraperitoneally disseminated colorectal carcinomas (CRCs) were infused intraperitoneally with pCD2 or CEA419/CD retrovirus-producing cells, a CD fragment was detected in CRCs and bone marrow cells. It was shown that the CD gene was expressed both in CRCs and in the bone marrow of animals infused with pCD2 retrovirus-producing cells, while the CD gene was expressed solely in CRCs of animals infused with CEA419/CD retrovirus-producing cells. These results indicate that the use of a tumor-selective promoter may warrant the safety of in vivo gene therapy using suicide genes.

Adenocarcinoma↗

Regulation of aquaporin-2 expression by the alpha(2)-adrenoceptor agonist clonidine in the rat.

Aquaporin-2 (AQP-2), the major water channel responsible for water balance, has been shown to be regulated by the binding of vasopressin to V(2) vasopressin receptors in the medullary collecting duct. alpha(2)-Adrenoceptor agonists such as clonidine have been associated with an increase in free water clearance that was secondary to an inhibition of the ability of vasopressin to increase cAMP levels in the collecting ducts. This investigation focused on the possibility that this increase in free water clearance following administration of an alpha(2)-adrenoceptor agonist was associated with a reduction in medullary AQP-2 expression. In the anesthetized rat, clonidine increased urine flow rate (32+/-5 versus 137+/-16 microl/min, p<.05) and free water clearance (-58+/-6 versus 3+/-8 microl/min, p<.05) compared with the group receiving the saline vehicle infusion. The increase in free water clearance with clonidine administration was associated with a reduction in whole kidney AQP-2 mRNA levels (282+/-25 versus 216+/-11 A units, p<.05). This decrease in water reabsorption was associated with a redistribution of AQP-2 away from the luminal membrane of the medullary collecting duct to the cytosol. These effects were not secondary to changes in serum vasopressin levels, as these were similar in the vehicle control and clonidine groups (59+/-5 pg/ml versus 64+/-7 pg/ml, p = NS). The rapid redistribution of AQP-2 and the reduction in AQP-2 mRNA following clonidine administration are consistent with the hypothesis that the alpha(2) adrenoceptor regulates water excretion at least in part by effects on AQP-2.

Adrenergic alpha-Agonists↗

[Clinical observation of the effect of shuxinsu capsule in treating angina pectoris].

OBJECTIVE: To observe the therapeutic effect of Shuxinsu capsule (SXSC) in treating angina pectoris patients. METHODS: One hundred and fifty angina pectoris patients were divided into two groups. Group A (80 cases), randomly divided into two subgroups, SXSC treated and Yixin oral liquid (YXOL) control group, each group consisted of 40 cases. Group B (70 cases) was an openly treated group (OTG). RESULTS: 17 cases were markedly effective in the SXSC treated group in relieving the symptoms, effective were 16, the total effective rate was 82.50%, while in the control group, the markedly effective cases, the effective cases and the total effective rate were 13, 16 and 72.50% respectively; there was significant difference between these two groups (u = 1.99, P < 0.05). In the treated group (SXSC and OTG) of 110 cases, the markedly effective, effective cases on ECG were 34 and 30 respectively. The total effective rate was 58.18%, higher than that of the control group, which was 55.00%, but the difference was insignificant. The activity of SOD in RBC and the amount of plasma LPO were significantly different after treatment in the SXSC group. Both of the medications had effect to reduce serum total cholesterol (TC) and triglyceride (TG), the TC was lower and high density lipoprotein-cholesterol (HDL-C) higher significantly after treatment in the SXSC group. CONCLUSION: SXSC has significant effect on angina pectoris.

Aged↗

[Clinical study on jinmaitong composita on diabetic peripheral neuropathy].

OBJECTIVE: To verify the effect of Jinmaitong composita (JMTC) on red blood cell aldolase reductase activity (RBC-AR), RBC sorbitol (RBC-S) and nerve conductive velocity in diabetic peripheral neuropathy (DN). METHODS: Sixty-six patients with DN were divided randomly into two groups, 33 patients in treated group treated with JMTC and 33 cases in the control group treated with Jinkui Shenqi (JKSQ), RBC-AR, RBC-S and nerve transmission speed were observed before and after three months treatment. RESULTS: Level of RBC-AR, RBC-S apparently decreased and nerve conductive velocity increased (P < 0.05, P < 0.01) after TMTC treatment. CONCLUSION: JMTC was able to improve the nerve conduction significantly with a lowering of RBC-AR and RBC-S and has good result in treating Diabetic peripheral neurophathy.

Aged↗

[Remote effects of local injection of botulinum toxin type A].

OBJECTIVE: To assess the severity and temporal profile of remote effects of botulinum toxin type A, BTX-A (Botox from Allergan Inc, USA and CBTX-A made by Lanzhou Biological Products Institute, China) injected locally on neuromuscular junction. METHODS: Patients had enrolled in a prospective study for their movement disorders, 18 cases with Botox and 22 cases with CBTX-A were studied. Single fiber electromyography (SFEMG) in the extensor digitorum communis muscle or tibialis anterior muscle was performed before and 2-3 weeks, 5-8 weeks, 4-5 months after injection of Botox or CBTX-A. RESULTS: It was measured totally 119 times. Significant increase of jitter was demonstrated 2-3 weeks after injections in both groups and MCD was in direct proportion to dose of injections. Fiber density value increased at the same time or later and lasted until 4-5 months after injections. CONCLUSIONS: Subclinical effects on neuromuscular transmission of remote uninjected muscles after injections of Botox and CBTX-A are demonstrated, which indicates that the toxin spread distantly from the site of injection. SFEMG is valuable for studying the pathogenesis of the remote effects of BTX-A and for avoiding reinjection too frequently.

Adolescent↗

[Construction of eukaryotic vector for human interleukin-15 cDNA and its expression in lung carcinoma cell lines].

OBJECTIVE: Human interleukin(hIL)-15 expression of lung cancer cell lines transfected by rhIL-15 cDNA in vitro was observed. METHODS: The recombinant plasmid pL-IL-15-SN was established by inserting IL-15 cDNA into vector pLXSN at sites of EcoR I and BamH I. The pL-IL-15-SN was transfected into human lung squmosuse carcinoma (PG) cell line and murine lung adenocarcinoma (LA795) cell line, respectively. Positive clones were obtained by the selection in G418 conditioned culture. Bioactivity on rIL-15 was detected by dependant-proliferation of CTLL-2 cells in vitro. RESULTS: Three positive PG and four positive LA795 cell clones were obtained respectively. The results of the assays for hIL-15 bioactivity showed that the expression levels of rhIL-15 ranged from 142 to 201 or from 138 to 178U/(ml.10(6)) for positive PG cells or LA795 cells, respectively. CONCLUSIONS: Human and murine lung carcinoma cells transfected with IL-15 cDNA can express hIL-15 with bioactivity.

Adenocarcinoma↗

[Efficient, stable expression of human interleukin-15 cDNA in Chinese hamster oval cells].

OBJECTIVE: To express the human interleukin 15(IL-15) cDNA in Chinese hamster oval (CHO) cells, which would benefit to the further research in the biological activities and the clinical applications of IL-15. METHODS: The entire human interleukin-15(IL-15) coding region, deleted of all the uncoding fragments, was amplified by PCR. The amplified products were subcloned into the EcoR I and Xba I sites of the pcDNA3 plasmid, forming the recombinant eukaryotic expressing vector, pcDNA3-IL-15, which was then identified by the Bg1 II enzymatic digestion, PCR amplification and the sequence analysis. The construct was transfected into CHO cells by means of lipofectamine, followed by a series of determinations to screen the positive cell colonies, such as RT-PCR, SDS-PAGE, ELISA and CTLL-2 proliferation assay. RESULTS: 8 positive cell colonies highly expressed human IL-15 were obtained after G418 selection. The bioassay showed that the mean activities of the supernatants from the CHO-IL-15 cells were (318.54 +/- 32.76) U/(10(6) cells.d) and maintained stable after 6 months culture. CONCLUSIONS: Human IL-15 cDNA was expressed efficiently and persistently in CHO cells.

Animals↗

[Synthesis and distribution of type IV collagen in mice testes].

OBJECTIVE: The variations of the synthesis and distribution type IV collagen in the testes of young, adult, and old mice were studied. METHODS: Biotin-avidin DCS system indirect immunofluorescence technique and in situ hybridization method were used. RESULTS: Sertoli cell could synthesize type IV collagen. Type IV collagen was present in the basement membrane of seminiferous tubules in mouse testis. Type IV collagen mRNA signal was seen in the Sertoli cells. The content of type IV collagen and type IV collagen mRNA peaked at day 15, and then declined successively to adult value and the aged value. CONCLUSIONS: The results suggest that the extracellular matrix of testis might play an important role in the process of spermatogenesis.

Age Factors↗

Use of polyclonal antibodies against carcinogen-DNA adducts in analysis of carcinogenesis.

Polyclonal antibodies against 3,2'-dimethyl-4-aminobiphenyl (DMAB)- and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-DNA adducts were raised for their immunohistochemical demonstration in paraffin-embedded sections. Both carcinogens target multiorgans in rats with colon, mammary glands and prostate as common tumor sites. PhIP is particularly important because it is a cooked food-derived carcinogen to which man is exposed on a daily bases. Dose-related nuclear staining in various tissue of rats was observed 24 h after single applications of both carcinogens but no observable decrease in staining intensity was evident in most organs by 168 h. Staining specificity in terms of sites of tumor development was lacking. However, in target organs, semiquantitative data on adduct formation correlated with alteration in tumor response by modifying factor(s). Furthermore, human prostate tissue implanted into nude mice showed positive staining. Thus, the antibodies can be applied as tools to clarify tissue or cell-specific carcinogenesis, carcinogen-exposure levels and metabolic activation in various species, including man after tissue transplantation.

Aminobiphenyl Compounds↗

Insulin secretagogues activate the secretory granule receptor-like protein-tyrosine phosphatase IAR.

To investigate the potential role of protein-tyrosine phosphatases (PTPs) in regulated secretion, cellular PTP activity was measured in pancreatic beta cell lines after exposure to insulin secretagogues. A peak of elevated PTP activity was detected in whole cell lysates after 15-20 min of treatment of the cells with high KCl, glucose, or TPA, which did not appear upon treatment with control compounds. Neither was it detected in cells that do not undergo regulated secretion. The PTP activation was transient, SDS-resistant, and localized to the cytoskeleton fraction of cells. The cytoskeletal localization of IAR, a receptor-like PTP associated with secretory granules of neuroendocrine cells, suggested the possibility that IAR is the secretagogue-activated PTP. The transient expression of human IAR in betaTC3 and HIT-T15 beta cells, followed by treatment with secretagogues or control compounds and immunoprecipitation of human IAR, showed that immunoprecipitates from the secretagogue-treated cells contained an elevated PTP activity. The secretagogue-induced activation of IAR had identical kinetics to that of the endogenous PTP. Although ectopic IAR was present in membrane and cytoskeletal fractions from the cells, only the cytoskeleton-associated IAR could be activated. Thus IAR represents the endogenous secretagogue-responsive PTP, or at least a component of it, and is one of the few receptor-like PTPs for which enzymatic activation has been demonstrated. Insulin secretion is detected prior to IAR activation, suggesting that IAR is not required for immediate secretion but likely plays a role in events downstream of insulin secretion or in another pathway related to the specialized function of secretory cells.

3T3 Cells↗

Perturbation of Hsp90 interaction with nascent CFTR prevents its maturation and accelerates its degradation by the proteasome.

Maturation of wild-type CFTR nascent chains at the endoplasmic reticulum (ER) occurs inefficiently; many disease-associated mutant forms do not mature but instead are eliminated by proteolysis involving the cytosolic proteasome. Although calnexin binds nascent CFTR via its oligosaccharide chains in the ER lumen and Hsp70 binds CFTR cytoplasmic domains, perturbation of these interactions alone is without major influence on maturation or degradation. We show that the ansamysin drugs, geldanamycin and herbimycin A, which inhibit the assembly of some signaling molecules by binding to specific sites on Hsp90 in the cytosol or Grp94 in the ER lumen, block the maturation of nascent CFTR and accelerate its degradation. The immature CFTR molecule was detected in association with Hsp90 but not with Grp94, and geldanamycin prevented the Hsp90 association. The drug-enhanced degradation was decreased by lactacystin and other proteasome inhibitors. Therefore, consistent with other examples of countervailing effects of Hsp90 and the proteasome, it would seem that this chaperone may normally contribute to CFTR folding and, when this function is interfered with by an ansamycin, there is a further shift to proteolytic degradation. This is the first direct evidence of a role for Hsp90 in the maturation of a newly synthesized integral membrane protein by interaction with its cytoplasmic domains on the ER surface.

ATP Binding Cassette Transporter, Subfamily B↗

Comparison of carcinoembryonic antigen promoter regions isolated from human colorectal carcinoma and normal adjacent mucosa to induce strong tumor-selective gene expression.

To establish in vivo gene therapy against cancer, it is requisite to induce strong, cancer cell-selective expression of a therapeutic gene. Comparison of the promoter activity of 5' flanking regions of the carcinoembryonic antigen (CEA) gene isolated from various origins is therefore of considerable interest. The 5' flanking region of the CEA gene between -135 and +69 bp upstream from the transcriptional start site, which is recognized as the core promoter region, was isolated from CEA-producing human colorectal carcinoma (CRC), normal adjacent mucosa, CEA-producing cell lines and CEA-non-producing cell lines. No mutations were observed by single-strand conformation polymorphism in the CEA promoter regions. Subsequent sequence analysis revealed that there were no mutations in the CEA promoter regions isolated from CEA-producing CRC and normal adjacent mucosa. Furthermore, nuclear extracts prepared from CEA-producing human CRC cells could equally bind to both the CEA promoter fragments isolated from CEA-producing CRC and normal mucosa. Both CEA promoter regions could direct 5- to 20-fold higher expression of a luciferase reporter gene in CEA-producing cells than in CEA-non-producing cells. Therefore, we suggest that the use of either CEA promoter region isolated from CRC or normal mucosa is equally effective to induce strong, CEA-producing cancer-selective expression of a therapeutic gene.

Base Sequence↗

Characteristics of nonneoplastic human prostate tissue transplanted into nude mice.

BACKGROUND: Prostate tumors are characterized by sex hormone-associated growth and mesenchymal-epithelial interactions. This study was conducted to establish an ex vivo system where human prostate tissue could be maintained for a certain period under conditions resembling the in vivo situation in man to provide an experimental tool for investigation of prostate disease. METHODS: Human prostate tissues (peripheral zone and transition zone) obtained by total cystectomy were transplanted into the subcutis of male KSN nude mice for up to 24 weeks without exogenous hormonal manipulation. RESULTS: Transplants could be maintained, and although they showed several histological alterations, such as cystic dilation, basal-cell hyperplasia, and squamous-cell metaplasia, many retained a nearly normal appearance for the entire 24-week duration. Immunohistochemically, androgen receptors were strongly positive in the nuclei of glandular epithelial cells. Prostate-specific antigen (PSA) and prostatic acid phosphate (PAP) (both from DAKO, Glostrup, Denmark), were also expressed in the cytoplasm. The proportion of cells expressing proliferating cell nuclear antigen (PCNA) was not related to the period of transplantation and did not differ between the peripheral and transition zones. CONCLUSIONS: The results clearly demonstrate that human prostate tissues transplanted into nude mice can maintain their morphological and biological characteristics for up to 24 weeks. This provides a simple and useful tool for basic research into human prostate neoplasia.

Animals↗

Relationship between CD44 expression and differentiation of human prostate adenocarcinomas.

It is well documented that CD44 plays an important role in tumor metastasis. We investigated whether there is a correlation between the expression of its isoforms in prostate cancer cells and patient prognosis using 72 cases with biopsy specimens. Immunohistochemistry demonstrated expression of CD44H (68.1%), v6 (36.1%) and v9 (68.1%) to be relatively more frequent than that of other isoforms. A positive correlation between CD44H expression and tumor differentiation was found but this did not extend to clinical staging or prognosis. Likewise, results for CD44v6 or v9 expression suggest that they may be useful markers for prostate adenocarcinoma differentiation but not prognosis.

Adenocarcinoma↗

The mosquito Anopheles stephensi limits malaria parasite development with inducible synthesis of nitric oxide.

We have discovered that the mosquito Anopheles stephensi, a natural vector of human malaria, limits parasite development with inducible synthesis of nitric oxide (NO). Elevated expression of A. stephensi NO synthase (NOS), which is highly homologous to characterized NOS genes, was detected in the midgut and carcass soon after invasion of the midgut by Plasmodium. Early induction is likely primed by bacterial growth in the blood meal. Later increases in A. stephensi NOS expression and enzyme activity occurred at the beginning of sporozoite release. Circulating levels of nitrite/nitrate, end-products of NO synthesis, were significantly higher in Plasmodium-infected mosquitoes. Dietary provision of the NOS substrate L-arginine reduced Plasmodium infections in A. stephensi. In contrast, dietary provision of a NOS inhibitor significantly increased parasite numbers in infected mosquitoes, confirming that A. stephensi limits Plasmodium development with NO.

Amino Acid Sequence↗

Slight promotion effects of intermittent administration of testosterone propionate and/or diethylstilbestrol on 3,2'-dimethyl-4-aminobiphenyl-initiated rat prostate carcinogenesis.

In order to determine the effects of intermittent hormonal manipulation on the promotion stage of rat prostate carcinogenesis, testosterone and/or estrogen were administered to F344 rats for 40 weeks after 20-weeks treatment with the prostate carcinogen, 3,2'-dimethyl-4-aminobiphenyl. For this purpose testosterone propionate (TP) and diethylstilbestrol (DES) were introduced into silastic tubes, 2- and 0.5-cm long, respectively, and implanted into the subcutis for seven repeated cycles of 30 days treatment and 10 days withdrawal. Intermittent administration of TP resulted in suppression of ventral prostate adenocarcinoma development and slight but non-significant increases in the incidences of invasive carcinomas of the lateral prostate and seminal vesicles. Intermittent administration of DES completely suppressed tumorigenesis in all sites and the combination of TP and DES generally inhibited prostate tumor development. Thus, under the present experimental conditions, no strong enhancing effects of cyclic hormonal manipulation were observed on rat prostate carcinogenesis. Indeed, the opposite appeared to be the case.

Aminobiphenyl Compounds↗