Search PubMed⌕ Search

Biomedical subjects

Z Zhu

Publications and source records attributed to Z Zhu.

At least 253 records · Page 14Linked to original sources
PubMed1998

An efficient route to human bispecific IgG.

Production of bispecific IgG (BsIgG) by coexpressing two different antibodies is inefficient due to unwanted pairings of the component heavy and light chains. To overcome this problem, heavy chains were remodeled for heterodimerization using engineered disulfide bonds in combination with previously identified "knobs-into-holes" mutations. One of the variants, S354C:T366W/Y349'C:T366'S:L368'A:Y407++ +'V, gave near quantitative (approximately 95%) heterodimerization. Light chain mispairing was circumvented by using an identical light chain for each arm of the BsIgG. Antibodies with identical light chains that bind to different antigens were identified from an scFv phage library with a very restricted light chain repertoire for the majority (50/55) of antigen pairs tested. A BsIgG capable of simultaneously binding to the human receptors HER3 and cMpI was prepared by coexpressing the common light chain and corresponding remodeled heavy chains followed by protein A chromatography. The engineered heavy chains retain their ability to support antibody-dependent cell-mediated cytotoxicity as demonstrated with an anti-HER2 antibody.

Antibody Specificity↗
PubMed1998

Intracellular transport of varicella-zoster glycoproteins.

Previous observations have established that varicella-zoster virus (VZV) is enveloped in the trans-Golgi network (TGN) in cultures infected with VZV and that the glycoprotein gE is targeted to the TGN by a signal sequence (AYRV) and an acidic TGN signal patch in its cytosolic domain. Neither sequence is present in other VZV glycoproteins. Like gE, gI was targeted to the TGN when it was expressed in transfected cells, suggesting that gI also contains TGN targeting information (colocalized with gE and the AP-1 adaptin complex). In contrast, gB, gC, gH, and gL immunoreactivities were not detected in the TGN when they were expressed individually in transfected cells. In VZV-infected cells, gE, gI, gH, and gL were all concentrated in the TGN. Since VZV glycoproteins that lack targeting sequences (gB, gC, gH, and gL) concentrated in the TGN of infected cells, it is proposed that gE and gI, which have such sequences, serve as navigator glycoproteins, forming complexes that direct the signal-deficient glycoproteins to the TGN.

Amino Acid Sequence↗
PubMed1998

Effect of corticosterone administration on mammary gland development and p27 expression and their relationship to the effects of energy restriction on mammary carcinogenesis.

The inhibitory activity against mammary carcinogenesis mediated by energy restriction is accompanied by a reduction in the degree of mammary ductal branching, and an increase in adrenal cortical activity. Levels of p27/kip1 protein, a gene product associated with cell cycle growth arrest, have also been shown to be elevated in mammary epithelium and in mammary lesions of energy-restricted animals. Based on these data we have proposed that increased secretion of adrenal cortical steroids accounts, in part, for the effects of energy restriction. In this experiment the hypothesis tested was that corticosterone administration would mimic the effects of energy restriction, both on mammary gland development and on levels of p27 protein in mammary ductal epithelium. To test this hypothesis corticosterone was fed to female rats for 4 weeks. Dietary corticosterone increased serum and urinary corticosterone levels in a dose-dependent manner (P < 0.01). The effects of corticosterone treatment on mammary gland development were analyzed digitally; p27 protein was detected immunohistochemically. The ductal extension and branching of the mammary gland were reduced in a dose-dependent manner by corticosterone treatment (P < 0.05); however, the magnitude of the effect was greater on ductal branching. Overall, increasing dietary corticosterone reduced the total volume of mammary epithelium in a dose-dependent manner, an effect that remained even after adjustments for differences among animals in body mass. Consistent with this effect, the amount of p27 protein present in ductal mammary epithelial cells increased dose-dependently in response to increasing corticosterone administration (P < 0.01). The hypothesis is proposed that dietary administration of corticosterone may imitate the effects of energy restriction on mammary carcinogenesis by regulation of mammary tissue size homeostasis via p27/kip1 mediated arrest of cell cycle progression.

Adrenal Cortex Hormones↗
PubMed1998

Aryl phosphate derivatives of bromo-methoxy-azidothymidine are dual-function spermicides with potent anti-human immunodeficiency virus.

Detergent-based vaginal microbicides, in addition to their high contraceptive failure rates, cause mucosal erosion and local inflammation that might increase the risk of heterosexual human immunodeficiency virus (HIV) transmission. In a systematic effort to identify a microbicide contraceptive potentially capable of preventing the sexual transmission of HIV as well as providing fertility control, a series of novel aryl phosphate derivatives of 5-bromo-6-methoxy-3'-azido-3'-deoxythymidine (AZT; zidovudine) were synthesized and examined for dual anti-HIV and sperm-immobilizing activity (SIA). Whereas AZT displayed potent anti-HIV activity (IC50 = 0.006 microM) but lacked SIA (EC50 > 300 microM), two 5-bromo-6-methoxy-aryl phosphate derivatives of AZT, compounds WHI-05 and WHI-07, exhibited potent anti-HIV activity as well as SIA. The IC50 (HIV) and EC50 (SIA) values for WHI-07 were 439-fold and 13.5-fold lower, respectively, than those for the detergent-based virucidal spermicide, nonoxynol-9 (N-9). Sperm motion kinematics using computer-assisted sperm motion analysis combined with confocal laser scanning microscopy, high-resolution low-voltage scanning, and transmission electron microscopy demonstrated that both WHI-05 and WHI-07 cause a complete and irreversible loss of sperm motility in a concentration- and time-dependent fashion without concomitantly affecting the sperm acrosomal membrane integrity. In experiments designed to assess the fertilizing capacity of treated sperm, preincubation of sperm with either compound resulted in a concentration-dependent loss of the ability to adhere to and penetrate zona-free hamster eggs as well as inhibition of binding to human zona. WHI-07 applied intravaginally prior to artificial insemination of epididymal sperm drastically reduced fertility in hormonally primed CD-1 mice. Unlike the intravaginal application of N-9, repetitive intravaginal application of WHI-07 did not damage the vaginal epithelium or cause local inflammation. Structure-function relationship analyses showed that the addition of bromo-methoxy functional groups to AZT was essential for, and the aryl phosphate derivatization contributory to, the SIA of both compounds. Compounds WHI-05 and WHI-07 may be useful as dual-function vaginal contraceptives for women who are at high risk for acquiring HIV/acquired immunodeficiency virus syndrome by heterosexual vaginal transmission.

Animals↗
PubMed1998

Penetration kinetics of 5-fluorouracil into pancreatic fluid in post-pancreatoduodenectomy patients.

Our aim was to investigate the pharmacokinetic behavior of 5-fluorouracil (5-FU) in pancreatic fluid and to evaluate its penetration characteristics in post-pancreatoduodenectomy patients. After completing the external drainage of the pancreatic duct during pancreatoduodenectomy surgery, eight patients were administered 1.0 g 5-FU i.v. by a 5 min infusion after the eighth day post-surgery on average. Blood and pancreatic fluid were collected, and the 5-FU concentrations were determined by HPLC assay. Their pharmacokinetic parameters were obtained by PCNONLIN and statistical analysis was performed. The Cmax was 20.03 +/- 18.25 mg/l in pancreatic fluid with a Tmax of 15.6 +/- 9.5 min following i.v. administration and 49.69 +/- 20.75 mg/l in plasma. 5-FU in plasma and pancreatic fluid were all in conformity with a non-linear model with a K(m) of 1098.08 +/- 1426.57 and 11.08 +/- 6.38 mg/l, respectively. The concentrations in pancreatic fluid were similar to that observed in plasma with an average penetration index up to 1.01 +/- 0.49. It is suggested therefore that 5-FU is capable of penetrating from blood into the pancreas as evidenced by the observed pancreatic concentrations.

Body Fluids↗
PubMed1998

Effects of ciprofloxacin, streptomycin, and gentamicin on rabbit corneal transendothelial electrical potential difference.

PURPOSE: A previous report suggested that high concentrations of ciprofloxacin in the anterior chamber may cause dose-dependent acute corneal decompensation. Therefore we evaluated the effect of varying concentrations of ciprofloxacin in the anterior chamber on the corneal endothelium and compared these effects with those of gentamicin and streptomycin. METHODS: We assessed endothelial transport function by determining transendothelial electrical potential differences (TEPDs) of rabbit corneas. Our control solution was bicarbonate-buffered balanced saline with glucose (BSG), to which we added ciprofloxacin (50, 100, 125, and 150 microg/ml), gentamicin (1,000 and 2,000 microg/ml), and streptomycin (196, 437, and 696 microg/ml). RESULTS: At high concentrations exceeding minimal inhibitory concentrations against 90% of common ocular isolates (MIC90), accelerated decay of TEPDs was seen with all three antibiotics. Adverse effects on TEPDs were noted at concentrations corresponding to >50 times MICs with ciprofloxacin and 40 x MICs with gentamicin, but only 2 times MICs with streptomycin. CONCLUSION: Our study shows that concentrations of ciprofloxacin, gentamicin, and streptomycin below or equal to their MIC90 levels do not adversely affect endothelial transport function in a rabbit model.

Animals↗
PubMed1998

Inhibitory effect of enalapril on neurally mediated syncope in elderly patients.

A dramatic increase in catecholamine (CA) concentration is believed to be a primary trigger of the neurally mediated syncope (NMS) in elderly subjects. The hypercontractile state of the heart might be alleviated by angiotensin-converting enzyme (ACE) inhibitor through depression of CA release from the sympathetic nerve ending. Thus ACE inhibitor might have positive effect on the prevention of NMS. In this study, 24 elderly subjects who had reproducible NMS induced with head-up tilt test (HUT) were randomized and double-blind divided into placebo and ACE-inhibitor groups. The plasma CA concentration [norepinephrine (NE) and epinephrine (E)] were measured during HUT, and the effects of enalapril on NMS were observed in the two groups. Before administration of enalapril, plasma CA concentrations were significantly increased during HUT compared with those in the supine position; In contrast, administration of the enalapril (10 mg/day) for >1 year inhibited the concentration of plasma CA increase and prevented syncope in all 12 patients (p < 0.05); however, placebo had no effect on plasma CA concentrations and syncope disappeared in only two of 12 patients after administration of placebo. From this study, we conclude that enalapril can prevent NMS in patients, presumably because of its part in the inhibition of CA release from sympathetic nerve endings.

Aged↗
PubMed1998

Determination of concentration of cytosolic NADH-cytochrome b5 reductase in erythrocytes from normal Chinese adults, neonates and patients with hereditary methemoglobinemia by double-antibody sandwich ELISA.

NADH-cytochrome b5 reductase (b5R), present in various tissues of the body, is a redox enzyme of multiple functions. The deficiency of the enzyme leads to hereditary methemoglobinemia. With rabbit anti-b5R antibody for plate coating and enzyme-labeled anti-b5R monoclonal antibody as reporter, we have developed a sandwich ELISA procedure for the determination of b5R concentration. This procedure is sensitive to a wide range of linearity, and convenient in coping with large numbers of samples. Using this novel method, cytosolic b5R concentration in the erythrocytes of 30 normal Chinese adults was estimated to be 25.63+/-8.54 ng/mg Hb. It was found that the concentration of red cell soluble b5R of five newborns was significantly lower than that of normal adults and soluble b5R was undetectable in the erythrocytes of 4 patients with type I hereditary methemoglobinemia. Our results demonstrated that the reduced b5R activity in red cell cytosol of both neonates and type I hereditary methemoglobinemic patients results largely or mainly from the lowered b5R concentration. Our novel method might be further exploited for in-depth investigation of the relationship between the qualitative and quantitative changes of b5R with regard to physiological and pathological conditions.

Adult↗
PubMed1998

Angiotensin AT1B receptor mediates calcium signaling in vascular smooth muscle cells of AT1A receptor-deficient mice.

Our studies on angiotensin II receptor subtype 1A (AT1A) knockout mice define how endogenous receptors other than AT1A receptors stimulate changes in cytosolic calcium concentration ([Ca2+]i) in cultured aortic vascular smooth muscle cells (VSMCs). Wild-type cells have a 1.7 ratio of AT1A/AT1B receptor mRNA as determined by semiquantitative reverse transcriptase-polymerase chain reaction. Mutant cells express AT1B receptor mRNA but not that for the AT1A receptor. In wild-type cells with AT1A present, Ang II (10(-7) mol/L) produces a characteristic rapid peak increase in [Ca2+]i of 150 to 180 nmol/L, followed by a plateau phase characterized by a sustained 70 to 80 nmol/L increase in [Ca2+]i. An unexpected finding was that the magnitude and time-dependent pattern of [Ca2+]i changes produced by Ang II were similar in cells that lacked AT1A receptors but possessed AT1B receptors. The response in mutant cells indicates effective coupling of an Ang II receptor to one or more second messenger systems. The similarity of response patterns between cells with and without AT1A receptors suggests that non-AT1A receptors are functionally linked to similar signal transduction pathways in mutant cells. The fact that mutant and wild-type cells exhibit similar patterns of calcium mobilization and entry supports the notion that AT1A and non-AT1A receptors share common signal transduction pathways. The AT2 receptor ligands PD-123319 and CGP-42112 do not alter Ang II effects in either VSMC type, suggesting a paucity of AT2 receptors and/or an absence of their linkage to [Ca2+]i pathways. The nonpeptide AT1 receptor blocker losartan antagonizes Ang II-induced [Ca2+]i increases in both cell groups, supporting mediation by native AT1B receptors and effective coupling of this subtype to second messenger systems leading to calcium entry and mobilization. Our results demonstrate that Ang II causes calcium signaling in AT1A-deficient VSMCs that is mediated by an endogenous losartan-sensitive AT1B receptor.

Angiotensin II↗
PubMed1998

Sulfonylurea receptor mRNA expression in pituitary macroadenomas.

ATP-sensitive K+ (KATP) channels modulated by sulfonylurea compounds have been previously identified in the anterior pituitary of the rat and have been demonstrated to influence GH release. Recently, a sulfonylurea receptor (SUR) has been cloned from an islet cell tumor and identified as a member of the ATP binding cassette superfamily capable to coupling with inwardly rectifying potassium channels. To determine if the same receptor is expressed in pituitary tumors, SUR mRNA levels were measured in 28 human macroadenoma specimens using an RNase protection assay. All immunonegative, corticotrophin (ACTH), growth hormone (GH), and GH/prolactin (GH/Prl) immunostaining tumors expressed detectable amounts of SUR message. Among these tumors, only the GH and GH/ Prl adenomas were functional. Of the tumors immunostaining for luteinizing hormone (LH), follicle-stimulating hormone (FSH), or both, SUR mRNA was present in small amounts in 5/11. Only 1/3 Prl immunostaining tumors contained SUR mRNA. In summary, we have demonstrated that SUR mRNA expression is common in several types of silent pituitary adenomas and in functional tumors that secrete GH. Lower levels are seen in some gonadotrophin immunostaining tumors.

ATP-Binding Cassette Transporters↗
PubMed1998

Microsatellite instability in an animal model of mammary carcinogenesis.

Alterations in the length of simple repetitive genomic sequences (microsatellite instability, MSI) may characterize a distinct mechanism of mammary carcinogenesis. In order to investigate whether MSI is associated with chemically-induced mammary carcinogenesis in the rat, 30 microdissected mammary carcinomas were analyzed using 27 different microsatellite markers from chromosomes 1, 3, 5, 7 and 8. DNA was extracted from rat mammary cancer and adjoining microscopically normal tissues from the same slide, amplified by PCR, using different polymorphic DNA markers and the reaction products were analyzed for microsatellite instability. The results of this study indicate that 30% of cases (9 out of 30) showed microsatellite instability at a minimum of 1 locus. Three cases (out of 30) showed microsatellite instability at only three loci or less, called MSI-L (low frequency MSI). Six cases (out of 30) showed MSI at four loci or more, called MSI-H (high frequency MSI). Six cases showed MSI at D5Mit11 and D5Mgh3 loci, five cases showed MSI at D1Mit14, D1Mgh6, D5Mgh5 and D8Mgh10 loci, four cases had MSI at D1Mgh2, and D3Mgh7 loci, three cases had MSI at D3Mit3, D3Mgh5, D7Mgh1 loci, two cases had MSI at D7Mit11 locus and one case had MSI at D3Mgh9 locus. The results of these experiments suggest that MSI may be an important etiological event in the pathophysiology of mammary carcinogenesis.

Animals↗
PubMed1998

[A study on the relationship of primary hypertension in elderly and their quality of life in Changsha City].

To study the relationship between hypertension and their quality of life in Changsha City, in the elderly primary questionnaire concerning quality of life developed by the Chinese Geriatric Association was used to investigate 555 aged workers. A community-based control programme on hypertension and it's impact was analysed. The results of stepwise regression suggested that physical status and function of daily activities were both subjective and objective determinants of importance. Morbidity of hypertension was the highest among all chronic diseases influecing aged worker's health status. The total score of quality of life and activities in aged people with hypertension was obviously low. There were many problems in the community-based control program on hypertension in urban districts. The treatment on systolic hypertension has positive effect. Strenthening community-based control of hypertension has important impact on improving the quality of life among aged people.

Aged↗
PubMed1998

Pharmacokinetics of 5-fluorouracil and its penetration into pancreatic juice in dogs.

AIM: To study the pharmacokinetic behavior of 5-fluorouracil (5-FU) in pancreatic juice in dogs and its correlation with 5-FU in plasma, and to evaluate its penetration characteristics. METHODS: After placing a pancreatico-drainage tube, 8 dogs were injected 5-FU 250 mg i.v. Blood and pancreatic samples were collected and the 5-FU concentrations were determined by HPLC. The pharmacokinetic parameters were obtained with statistical analysis. RESULTS: The mean slopes of the terminal phase (K10) in plasma and pancreatic juice were 9.4 h-1 and 10.2 h-1, respectively (P > 0.05). The pharmacokinetic behaviors of 5-FU in plasma and pancreatic juice fitted a nonlinear model. Its penetration index was 3.39 +/- 2.84. The penetration of 5-FU from blood to pancreatic juice was relatively rapid, demonstrating a consistently higher concentration in pancreatic juice than in plasma. CONCLUSIONS: The elimination phase of 5-FU in plasma was similar to that in pancreatic juice, indicating that they were in the same kinetic compartment.

Animals↗
PubMed1998

[Internal fixation with mini-titanium plate for midface fractures].

Thirty four patients with midface bone fractures were fixed by rigid internal fixation (RIF) with min-titanium plate. An optimum exposure is provided for the fracture sites of zygomatic, zygomatic arch, orbital floor and maxilla with the coronal incision and adjuvant incisions. The approach was of benefit to accurate anatomic reduction and fixation of the fracture segments. RIF with min-titanium plate provided three-dimensional stability. The fixation of zygomatic-frontal crevice and zygomatic maxillary crevice were the key for obtaining sufficient stability, and at least two fixation screws were required above zygomatic-frontal crevice.

Adult↗
PubMed1998

[The effect of removable partial denture on the composition of bacteria on the apt-to-decay site of abutment teeth].

This study was aimed at the composition of plaques which were on the base teeth's carious sensitive sites, just after the insertion of the removable partial denture (RPD). The results showed that the ratios of bacterial detection in different teeth at the same period and those on the different sites of same teeth at different periods were not significantly different. There was a tendency that the detection ratio of the stomatococcus at the early period was higher than that of other bacteria, but at the middle period the ratios declined, and at the late period it was higher again. The detection ratio of the bacillus was on the contrary in the study. At the same time, the composition of the plaques changed significantly after the dentures had been used for 7, 14, and 21 days and 3 months. After 3 months, the ratios of the stomatococcus and the bacillas returned to their normal levels. The 3 main cariogenic bacteria were all detected in this study. The Streptococcus mutant was the dominant bacterium in the plaques and its ratio went up with the time duration. The ratio for the lower second molar was higher than that for the mandibular second premolar (P < 0.05). The detection ratios of the Actinomyces viscosus and lactobacillus were lower. In conclusion, after the insertion of RPD, the oral microbial ecosystem would be changed and the cariogenic bacteria began to implant on the surface of the base teeth. So RPD is a potential factor to cause the caries.

Actinomyces viscosus↗
PubMed1998

[Effects of surface roughness of two restorative materials on early Streptococcus sanguis adhesion in vitro].

This was an in vitro study aimed at the surface roughness of two kinds of commonly used restorative materials resin and alloy necessary to affect the adhesive behavior of Streptococcus sanguis(S. s) on them after 24 h. The surface roughness(SR) of each tested sample was evaluated with a profilometer quantitatively and observed with scanning electron microscope (SEM) morphologically. Then the adhesive microbial amount was determined by the clone forming unit counting method, and adhesion morphology was analyzed with SEM. The result showed a positive linear relation between the adhesion amount of S. s and the SR. The relative coefficients were rresin = 0.46(P < 0.01) and ralloy = 0.25(P < 0.01) respectively. These suggest the SR of the restorative material is important for the early adhesion of oral microbes in vitro. Therefore, before the prothesis is inserted in the patient's oral cavity, its surface should be polished as smoothly as possible so that the bacterial adhesive amount on its surface can be decreased, and hence the patient may keep in good oral health and have a prolonged use of the prothesis.

Bacterial Adhesion↗
PubMed1998

[Community investigation of the activities of daily living (ADL) and medical conditions of the elderly in Shanghai].

OBJECTIVE: To study the ADL status and prevalence of medical conditions in aged population in Shanghai, and to analyze the impact of dementia syndrome and other illnesses to ADL performance. METHODS: Both the Chinese version of ADL scale (five items) and the list of self-reported illnesses questionnaire (32 conditions) were used in the survey. After screening and case-identification, 3745 noninstitutionalized aged residents, who were 65 years and older, were included in the analysis sample. A separate multiple logistic regression model was used in both groups (65-74 years and over-75), observing the effect of age, gender, education and medical conditions (as control variables) on ADL dependence. RESULTS: The prevalence rate of functional dependence in ADL was 8.28%, and the prevalence curve was doubled steeply along with each ten years. The most prevalent medical conditions (> 20%) were hypertention, heart disease, cataract/glaucoma and artheritis/rheumatism, whereas, dementing disorder was 4.61%. Of all illnesses, stroke, Parkinson's disease, dementia, diabetes and emphysema were the most important predictors of ADL dependence in both aged groups. In the group more than 75 years old, cancer, arteriosclerosis and hypertension seemed to be strongly related to ADL dependence, dementia syndrome was one of the remarkable risk factors. CONCLUSION: Dementing disorders such as Alzheimer's disease may lead to severe disturbance of ADL performance in the aged, therefore, the community rehabilitative measures and health care services should be stressed by the society to improve the quality of life of the elderly.

Activities of Daily Living↗