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Biomedical subjects

L Zhuang

Publications and source records attributed to L Zhuang.

At least 37 records · Page 2Linked to original sources
PubMed2000

Role of lipophilicity in determining cellular uptake and antitumour activity of gold phosphine complexes.

PURPOSE: The lipophilic cation [Au(I)(dppe)2]+ [where dppe is 1,2-bis(diphenylphosphino)ethane] has previously demonstrated potent in vitro antitumour activity. We wished to determine the physicochemical basis for the cellular uptake of this drug, as well as of analogues including the 1:2 adducts of Au(I) with 1,2-bis(di-n-pyridylphosphino)ethane (dnpype; n = 2, 3 and 4), and to compare in vitro and in vivo antitumour activity. METHODS AND RESULTS: Logarithmic IC50 values for the CH-1 cell line bore a parabolic dependence on drug lipophilicity, as measured either by high-performance liquid chromatography or by n-octanol-water partition. Cellular uptake of drug, as measured by inductively coupled plasma mass spectrometry, varied by over three orders of magnitude over the series. Logarithmic uptake had a parabolic dependence on drug lipophilicity but a linear relationship to logarithmic IC50 values. Free drug concentrations were determined under the culture conditions and logarithmic free drug IC50 values and uptake rates were linearly related to lipophilicity. Uptake of drug in vivo in tissue from murine colon 38 tumours was approximately proportional to the dose administered. Host toxicity varied according to lipophilicity with the most selective compound having an intermediate value. This compound was also the most active of those tested in vivo, giving a growth delay of 9 days following daily intraperitoneal dosing (10 days) at 4 micromol kg(-1) day(-1). It was also significantly more active than another lipophilic cation, MKT-077. CONCLUSIONS: Alteration of lipophilicity of aromatic cationic antitumour drugs greatly affects cellular uptake and binding to plasma proteins. Changes in lipophilicity also affect host toxicity, and optimal lipophilicity may be a critical factor in the design of analogues with high antitumour activity.

Animals↗
PubMed2000

Molecular mechanism of ultraviolet-induced keratinocyte apoptosis.

This article reviews advances in the study of the molecular mechanisms for ultraviolet (UV)-induced keratinocyte apoptosis, with particular reference to the cytokines tumor necrosis factor-alpha (TNF-alpha) and Fas ligand (FasL). TNF-alpha and FasL induce their respective receptors and then activate caspase enzymes that are critically involved in the apoptotic process. This activation is further amplified by intracellular mitochondria-associated mechanisms. Using gene-targeted knockout mice lacking either the TNF-Rp55 or the TNF-Rp75, we have shown that TNF-alpha plays an important role in UV-induced keratinocyte apoptosis via TNF-Rp55. TNF-Rp55 shares homology with Fas and contains an intracellular death domain. UV seems to directly stimulate cross-linking of Fas, resulting in the engagement of the death machinery. Fas-associated death domain protein (FADD) acts as an adapter protein in both the TNF-Rp55 and Fas death-inducing cascades and is responsible for downstream signal transduction by recruiting caspases. Moreover, signaling of p53 contributes to the induction of apoptosis by regulating Bcl-2 family expression and increasing surface Fas expression. In addition to induction mechanisms of apoptosis, there are numerous inhibitory molecules that play a role in restricting the apoptotic pathway. Thus, the ultimate determination of whether or not a cell undergoes apoptosis after UV radiation is based on the balance between agonist and antagonist pathways.

Animals↗
PubMed2000

Association analysis of variants in the core promoter region of angiotensinogen gene with essential hypertension in Tibetan population.

OBJECTIVE: To detect the variants in the core promoter region of angiotensinogen(AGT) gene, and to analyse the relationship between the AGT gene polymorphisms and essential hypertension in Tibetan population. METHODS: This is a case-control study consisting of 103 essential hypertensive subjects and 82 normotensive controls matched by age and sex. The variants in the AGT gene core promoter region were screened by polymerase chain reaction/single strand conformation polymorphism(PCR/SSCP) and further identified by automated sequencing. The A(-6)G polymorphism was determined in DNA extracted from leucocytes by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP). RESULTS: (1) There were two different electrophoresis band patterns in PCR/SSCP analysis. PCR product direct sequencing showed that the two band patterns represented the AA, AC genotypes in the (-20) site of AGT gene respectively. The distribution of A(-20)C genotype was almost identical in essential hypertensive and normotensive groups (P>0.8). The A allele frequency was very high in both groups (control: 0.9175, hypertensive: 0.9124). (2)Distribution of genotype in the (-6) site of AGT gene was much different between the patient group and control group (P<0.005). The frequency of G allele was statistically higher in the patient group than in controls (0.374 vs 0.220, P<0.025). CONCLUSION: Both Tibetan hypertensives and normotensives have higher frequency of A allele in AGT gene (-20) site. The higher frequency of G allele in the AGT gene (-6) site in Tibetan hypertension patients suggests that this allele may be the genetic susceptibility factor in the proceeding of essential hypertension in the Tibetan population.

Angiotensinogen↗
PubMed2000

[Effect of anti-endotoxin therapy on vaso-active substances in decompensated liver cirrhosis].

OBJECTIVE: To study the anti-endotoxin therapy on the plasma levels of nitric oxide, prostacyclin, tumor necrosis factor-alpha in patients with liver cirrhosis after hepatitis. METHODS: Thirty patients with decompensated liver cirrhosis accepted anti-endotoxin therapy with oral Amoxycillin and Smedta for 2 weeks. Plasma levels of endotoxin, nitric oxide, prostacyclin and tumor necrosis factor-alpha were detected before and after therapy in study group and control group, respectively. The relationship between endotoxin and vasoactive substances and between the four substances and the status of patients were analyzed. RESULTS: The four substances were all increased significantly (P<0.01) in patients with liver cirrhosis compared with control group and decreased obviously after treatment for 2 weeks (endotoxin from 0.546X10(21) U/L to 0. 347X10(21) U/L, no from 56.498 mumol/L to 31.256 mumol/L, 6-keto-PGF1 alpha from 716.964 ng/L to 539.867ng/L, and TNF-alpha from 3.090 mug/L to 1.750 mug/L (P<0.01). CONCLUSION: The plasma levels of nitric oxide, prostacyclin and tumor necrosis factor-alpha increased because of endotoxemia. Amoxycillin and Smecta can clear endotoxin out effectively.

Adult↗
PubMed2000

[Analyses on the association of CA-repeat polymorphism and A1166-->C variant in the 3'-flanking region of AT(1)R gene with essential hypertension in Tibetans].

OBJECTIVE: To investigate whether CA-repeat polymorphism and A1166 --> C variant in the 3n-flanking region of AT(1)R gene are in association with the genetic susceptibily to essential hypertension (EH) in Tibetans. METHODS: A case-control study was carried out. Sibpair analysis and family linkage analysis were conducted. The CA-repeat polymorphism of AT &(1) R gene was identified by polymerase chain reaction(PCR) with fluorescence labeled dCTP as substrate and by semi-automatic sequence technology. The A1166 -->C variant was detected by PCR-RFLP. RESULTS: Association of AT&(1)R gene locus with EH was confirmed through the case-control study in well-characterized group of 113 Tibetan EH patients and 131 normotensives(chi(2)=26.44, P<0.001). A closer examination of this gene locus found 11 alleles from Tibetan population; allele A7 (138 bp) was more frequent in both the patients and the controls. Allele A8(140 bp) was in strong positive association with genetic susceptibility to EH in Tibetans. Frequency of allele A8 was 20.5% in EH and 7.3% in normotensives. The difference of allele frequencies between the groups was significant (chi(2)=9.64, P=0.002, OR=3.46, 95% CI 1.44-8.51). Affected sibpair analysis showed chi(2)=3.85, P=0.025; family linkage analysis gave Lod score of 0.80. No association between A1166 --> C variant in AT(1)R gene and EH in Tibetans was observed (P>0.05). CONCLUSION: The result suggests that CA-repeat polymorphism of AT(1)R gene be in association with EH in Tibetans, which implicates that AT(1)R gene may be in linkage disequilibrium with the causative genes of EH.

Adult↗
PubMed2000

Different Wnt-5A gene expressions in the renal cell carcinoma GRC-1 cell line during the cell cycle.

OBJECTIVE: To investigate the gene expression at transcription level of growth factor Wnt-5A in different phase during the cell cycle. METHODS: We synchronized the renal cell carcinoma GRC-1 cell line by double thymidine blocks and high-pressure N2O gae methods and amplified Wnt-5A cDNAs from different phase using Semi-quantitative RT-PCR (reverse transcriptase polymerase chain reaction). The PCR products were electrophoresized on the agrose gel and detected by Gel Doc 1000 computer controlled system integrating the volumes of each band, representing the intensities of all pixels in a defined band. RESULTS: The different mRNA expressions of growth factor Wnt-5A was detected in RCC GRC-1 cell line. In S phase, the highest level of Wnt-5A transcript was observed, and in G1 and M phase, medial and lowest, respectively. The differences between S and M stages were statistically significant (P < 0.05). CONCLUSION: Growth factor Wnt-5A has the potential effect on tumorigenesis. It contributes to all phases during cell cycle but in S phase especially.

Carcinoma, Renal Cell↗
PubMed2000

[Beta-catenin and its mRNA in renal cell carcinoma].

OBJECTIVES: To investigate the role of beta-catenin in renal cell carcinoma. METHODS: The expression of beta-catenin in 26 cases of renal cell carcinoma was studied by LSAB immunohistochemistry, Western blotting and RT-PCR. RESULTS: The expression of beta-catenin was higher in cancer tissues than in normal kidney tissues in 25 cases and the level of beta-catenin was associated with tumor stage. The expression was obviously higher in pT3 and pT4 than in pT1 and pT2 (P < 0.01). The expression of its mRNA was not higher in tumor cells than in normal cells. Beta-catenin was expressed mainly in cytoplasm. CONCLUSIONS: Beta-catenin might be related to the occurrence and development of kidney tumor.

Adult↗
PubMed2000

[Using multiplex PCR for the detection of virulence genes in Escherichia coli O157:H7].

OBJECTIVE: To detect and characterize the virulence genes in E. coli O157:H7 isolated from various reservoir in six areas of Jiangsu province. METHOD: The virulence genes of Shiga-like toxin (SLT(1) and SLT(2)), intimin (eaeA) and hemolysin (hlyA) were chosen as the target genes and amplified in multiplex PCR assays. RESULTS: Of the eighty-five E. coli O157:H7 strains, the overall virulence gene prevalence was found to be 56.5% (48/85). The prevalence rates virulence genes of isolates from various areas were different from 0% up to 90.5%. It seemed to exist a relationship between the virulence gene prevalence and the level of incidence. In the areas where rates of incidence were divided into high, low, sporadic or zero, the prevalence rates were 85.7% (36/42), 52.6% (10/19) and 8.3% (2/24), respectively. The prevalence rates of isolates were also different from various reservoirs, decreasing by sheep, cattle, pig and poultry. One isolate from a rabbit was positive for SLT(2), eaeA and hly genes. Of forty-eight isolates carrying virulence genes, 38 (79.2%) had SLT(2), eaeA and hly genes, taking the dominate virulence gene pattern, 8 (16.6%) had all of the four virulence genes 2 (4.2%) had both SLT(2) and hly genes respectively. In addition, SLT(1) gene showed a lower prevalence, which was different from some findings abroad. CONCLUSION: Since virulence gene pattern of E. coli O157:H7 is an important molecular epidemiological marker, it can provide an useful information for epidemiologic studies, and helpful to the design of prevention and control strategies. For virulence gene detection, multiplex PCR seems to be a simple, rapid, specific and sensitive method.

Adhesins, Bacterial↗
PubMed1999

TNF receptor p55 plays a pivotal role in murine keratinocyte apoptosis induced by ultraviolet B irradiation.

Excess exposure of skin to ultraviolet B (UVB) results in the appearance of so-called sunburn cells. Although it has been demonstrated that sunburn cells represent apoptotic keratinocytes, the molecular mechanisms for UVB-induced apoptosis in keratinocytes have not been fully elucidated. The cytokine, TNF-alpha, has been shown to induce apoptosis in a variety of cell types. Since UVB induces keratinocytes to release TNF-alpha, we hypothesized that TNF-alpha is involved in UVB-induced apoptosis in keratinocytes. In order to confirm this hypothesis and to further delineate which type of TNF receptor signaling mediates the apoptosis pathway, we performed both in vivo and in vitro experiments using gene-targeted knockout mice lacking either the TNF p55 receptor or the TNF p75 receptor. In the in vivo study, wild-type and mutant mice were exposed to UVB, and apoptotic keratinocytes were detected by examining DNA fragmentation using in situ nick-end labeling. For the in vitro experiments, keratinocytes derived from the wild-type and mutant mice were irradiated with UVB, and the degree of apoptosis was determined by flow cytometry, nick-end labeling of DNA, and a DNA ladder assay. Both in vivo and in vitro studies demonstrated that the deletion of TNF receptor p55 could suppress UVB-induced apoptosis in keratinocytes. Our observations support the notion that TNF-alpha is involved in UVB-induced keratinocyte apoptosis, and demonstrate that p55 receptor signaling plays a pivotal role in this event.

Animals↗
PubMed1999

Enhanced epidermal Langerhans cell migration in IL-10 knockout mice.

The migration of epidermal Langerhans cells (LC) to lymph nodes (LN) is critical in the initiation of contact hypersensitivity (CHS) responses. Studies suggest that contact allergen-induced epidermal proinflammatory cytokines, including IL-1 and TNF-alpha, play important roles in promoting LC migration. Contact allergens also induce epidermal anti-inflammatory cytokines such as IL-10. Since IL-10 down-regulates proinflammatory cytokine production and inhibits CHS, we hypothesized that IL-10 might inhibit LC migration. To test this hypothesis, IL-10 knockout (KO) mice were epicutaneously sensitized with the hapten, FITC, and 24 h later hapten-bearing cells in the draining LN were examined. The number of hapten-bearing cells in the LN was significantly greater in IL-10 KO mice than in wild-type mice. The mutant mice also had an exaggerated CHS to FITC. Pretreatment with anti-TNF-alpha Ab or IL-1R antagonist significantly reduced the number of hapten-bearing cells in the LN, suggesting that IL-10 modulation of LC migration involves IL-1 and TNF-alpha. Moreover, IL-10 KO mice demonstrated a greater increase in TNF-alpha, IL-1alpha, and IL-1beta mRNAs in the allergen-exposed epidermis, and keratinocytes derived from the mutant mice were able to produce higher amounts of TNF-alpha and IL-1alpha protein. These data suggest that IL-10 plays an inhibitory role in LC migration and that this effect may occur via the down-regulation of TNF-alpha and IL-1 production.

Animals↗
PubMed1999

The human prolactin receptor gene structure and alternative promoter utilization: the generic promoter hPIII and a novel human promoter hP(N).

The 5'-untranslated region of the human prolactin receptor (hPRLR) gene contains two alternative first exons, hE1(3), the human counterpart of the rat and mouse E1(3) and a novel human type of alternative first exon termed hE1N, also a common non-coding exon 2 and a third exon containing the translation initiation codon. hE1(3) was localized approximately 800 bp 5' from the hE1N in the genome. The two distinct first exons hE1(3) and hE1N are expressed in human breast tissue, breast cancer cells, gonads and liver. Overall, the transcript containing hE1(3) is prevalent in most tissues. The coding region of the gene comprises eight exons (exon 3-10), in which exon 10 encodes most of the intracellular domain. hE1(3) and hE1N are transcribed from alternative promoters hPIII and hP(N), respectively. The hPIII, containing identical Sp1 and C/EBP elements as in the rodent promoters, shares 81% similarity in the region -480/-106 to both the rat and mouse. The novel promoter hP(N) contains putative binding sites for ETS-family proteins and a half-site for nuclear receptors. Therefore, both promoters likely utilize distinct mechanisms in controlling the hPRLR gene transcription. The different promoter utilization of the hPRLR gene in diverse tissues may confer differential prolactin response through activation of different promoters.

Base Sequence↗
PubMed1999

Neuroprotective interactions in rats between paclitaxel and cisplatin.

Paclitaxel and cisplatin are associated with dose-limiting neurotoxicity that may result from their differing effects on microtubule stability in peripheral nerves. We hypothesized that such different actions of paclitaxel and cisplatin could be exploited to minimize their neurotoxicity by giving them in combination. Paclitaxel (9-18 micromol/kg/week or 7.7-15.4 mg/kg/week) and cisplatin (5-10 micromol/kg/week or 1.5-3 mg/kg/week) were given alone and in combination to female Wistar rats. Treatment was given once per week for a total of 7-10 weeks. Paclitaxel and cisplatin were given 24 h apart when they were given in combination. Changes in sensory nerve conduction velocity (SNCV) and dorsal root ganglia (DRG) morphology were measured. The nature of their interaction was analyzed using an isobologram. Their antitumor activity alone or in combination was also determined in C57B1/6 mice bearing colon 38 tumors. Reductions in SNCV occurred with paclitaxel alone (P = 0.009), cisplatin alone (P = 0.012), and cisplatin given 24 h before paclitaxel (P < 0.0001). In contrast, there was no significant change in SNCV with paclitaxel given 24 h before cisplatin (P = 0.11). An isobologram showed that the SNCV effects of the drug combinations were less than additive or antagonistic. Cisplatin-induced morphometric changes in DRG neurons were less marked when cisplatin was given with paclitaxel (P = 0.004). Concentrations of platinum in dorsal root ganglia, sural nerves, and sciatic nerves were not altered by giving paclitaxel before cisplatin. Tumor growth delays (TGD) were greater after treatment with paclitaxel (23.4 micromol/kg or 20 mg/kg) given 24 h before cisplatin (23.3 micromol/kg or 7 mg/kg) (TGD = 7.5 days) than after paclitaxel (23.4 micromol/kg or 20 mg/kg) (TGD = 2.0 days) or cisplatin (23.3 micromol/kg or 7 mg/kg) (TGD = 3.5 days) alone. Paclitaxel and cisplatin antagonized each other's neurotoxicity in Wistar rats. Combining cytotoxic agents with opposing effects on peripheral nerves has potential for minimizing neurotoxicity in patients.

Animals↗
PubMed1999

[Study on the safety after cesarean section].

OBJECTIVE: In order to assess the safety after cesarean section, the complications and morbidity rate within 2 years after delivery between cesarean section and spontaneous delivery were compared. METHODS: A retrospective cohort study was used in this study. RESULTS: The prevalence of anemia, mobility restriction of uterus, chronic pelvic pain and wound ache during the 2 years postpartum in cesarean section group were 11.1%, 9.6%, 4.3% and 5.1% respectively, which were significantly higher than those in women with spontaneous delivery. CONCLUSION: In order to protect women's health, the indications for cesarean section must be mastered strictly.

Adult↗
PubMed1999

Aberrant expression of growth factor Wnt-5A in six urinary malignant cell lines.

OBJECTIVE: To investigate the expression of growth factor Wnt-5A in urinary tumor cell lines. METHODS: By semi-quantitative RT-PCR (reverse transcriptase polymerase chain reaction), the expression of Wnt-5A in six urinary malignant cell lines, one primary cultured renal fibroblast and one case of normal human renal tissue was detected using Gel Doc 1000 computer controlled molecular analysis system. RESULTS: The expression of Wnt-5A in-urinary tumor cell lines was much higher than that in primary cultured renal fibroblasts (PRF) and normal human renal tissue (NRT). The levels of Wnt-5A mRNA were different between six malignant cell lines. CONCLUSION: The overexpression of growth factor Wnt-5A has a potential effect on the oncogenesis of urinary malignancies.

Carcinoma, Renal Cell↗
PubMed1999

Carpal tunnel syndrome: a retrospective analysis of 262 cases and a one to one matched case-control study of 61 women pairs in relationship between manual housework and carpal tunnel syndrome.

OBJECTIVES: To get a more comprehensive recognition about carpal tunnel syndrome (CTS), especially the manual housework as its risk factor, and to facilitate early diagnosis and proper treatment. METHODS: 262 CTS patients (396 CTS hands) were analyzed retrospectively. A 1:1 matched case-control study of 61 woman pairs in relationship between manual housework and the occurrence of CTS was carried out. RESULTS: In 262 CTS patients, 84% were female, and the dominant hand was more frequently affected; repetitive and forceful movement of the hand and wrist might be associated with CTS. Typical clinical manifestations include pain and paresthesia in the median nerve territory, but 75.3% of our 396 CTS hands had all five digits involved. Conduction abnormalities appeared selectively in the median nerve distal to the wrist. In the case-control study, for manual washing, rolling or kneading dough, and knitting woolen sweater, the odds ratios (OR) of CTS between high and low intensities were 3.86 (95% confidence interval 1.79-8.33, chi 2 = 11.76, P < 0.01), 6.25 (95% confidence interval 2.50-15.63, chi 2 = 15.21, P < 0.01) and 1.13 (95% confidence interval 0.57-2.22, chi 2 = 0.125, P > 0.05) respectively; and those between long and short duration (i.e. the number of years engaging in these manual housework) were 2.33 (95% confidence interval 0.63-8.64, chi 2 = 1.6, P > 0.05), 1.88 (95% confidence interval 0.81-4.38, chi 2 = 2.13, P > 0.05) and 1 (chi 2 = 0, P > 0.05). CONCLUSIONS: The diagnosis of CTS requires confirmation of illness history, symptoms and signs with objective electrodiagnostic tests. Manual washing and rolling or kneading dough might be associated with the onset of CTS.

Adult↗
PubMed1998

Transcriptional regulation of the generic promoter III of the rat prolactin receptor gene by C/EBPbeta and Sp1.

Three promoters are operative in the rat prolactin receptor gene as follows: promoter I (PI) and II (PII) are specific for the gonads and liver, respectively, and promoter III (PIII) is common to several tissues. To investigate the mechanisms controlling the activity of promoter III, its regulatory elements and transcription factors were characterized in gonadal and non-gonadal cells. The TATA-less PIII domain was localized to the region -437 to -179 (ATG +1) containing the 5'-flanking region and part of the non-coding first exon. Within the promoter domain, a functional CAAT-box/enhancer binding protein (C/EBP) (-398) and an Sp1 element (-386), which bind C/EBPbeta and Sp1/Sp3, respectively, contribute individually to promoter activation in gonadal and non-gonadal cells. However, significant redundancy was demonstrated between these elements in non-gonadal cells. Additionally, an element within the non-coding exon 1 (-338) is also required for promoter activity. Activation of PIII by the widely expressed Sp1 and C/EBPbeta factors explains its common utilization in multiple tissues. Moreover, whereas the rat and mouse PIII share similar structure and function, the mouse PI lacks the functional SF-1 element and hence is inactive. These findings indicate that promoter III is of central importance in prolactin receptor gene transcription across species.

Animals↗