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R Zhang

Publications and source records attributed to R Zhang.

At least 91 records · Page 5Linked to original sources
PubMed2001

Vaccination with calpain induces a Th1-biased protective immune response against Schistosoma japonicum.

A large subunit of calpain, a calcium-activated neutral proteinase, from Schistosoma japonicum was cloned and expressed in Escherichia coli. When BALB/c mice were immunized with purified recombinant calpain (r-calpain) emulsified in complete Freund's adjuvant, a significant reduction in the number of recovered worms and also in egg production per female worm was observed (P<0.01). Spleen cells of the immunized mice showed enhanced production of gamma interferon (IFN-gamma) by activated CD4(+) T cells. Considering our observation of elevated expression of inducible nitric oxide synthase mRNA in immunized mice, r-calpain-induced IFN-gamma seemed to upregulate the production of nitric oxide by macrophages and subsequently mediated the killing of schistosomulae in the lung. On the other hand, spleen cells of immunized mice showed only faint interleukin-4 production in response to r-calpain in vitro, suggesting that immunization with r-calpain alters the Th1-Th2 balance in murine hosts even during a Th2-promoting S. japonicum infection. Furthermore, histopathological study of the livers of immunized mice showed that granulomas formed around eggs were diminished in both size and number. Egg production by female worms was clearly decreased in immunized mice, suggesting that r-calpain also has antifecundity effects. Taken together, these results point to S. japonicum calpain as a potential vaccine candidate for both worm killing and disease prevention, possibly through the induction of a strong Th1-dominant environment in immunized mice.

Animals↗
PubMed2001

Dynamic regulation of heart rate during acute hypotension: new insight into baroreflex function.

UNLABELLED: To examine the dynamic properties of baroreflex function, we measured beat-to-beat changes in arterial blood pressure (ABP) and heart rate (HR) during acute hypotension induced by thigh cuff deflation in 10 healthy subjects under supine resting conditions and during progressive lower body negative pressure (LBNP). The quantitative, temporal relationship between ABP and HR was fitted by a second-order autoregressive (AR) model. The frequency response was evaluated by transfer function analysis. RESULTS: HR changes during acute hypotension appear to be controlled by an ABP error signal between baseline and induced hypotension. The quantitative relationship between changes in ABP and HR is characterized by a second-order AR model with a pure time delay of 0.75 s containing low-pass filter properties. During LBNP, the change in HR/change in ABP during induced hypotension significantly decreased, as did the numerator coefficients of the AR model and transfer function gain. CONCLUSIONS: 1) Beat-to-beat HR responses to dynamic changes in ABP may be controlled by an error signal rather than directional changes in pressure, suggesting a "set point" mechanism in short-term ABP control. 2) The quantitative relationship between dynamic changes in ABP and HR can be described by a second-order AR model with a pure time delay. 3) The ability of the baroreflex to evoke a HR response to transient changes in pressure was reduced during LBNP, which was due primarily to a reduction of the static gain of the baroreflex.

Acute Disease↗
PubMed2001

Vagal cardiac function and arterial blood pressure stability.

This study was designed to investigate the importance of vagal cardiac modulation in arterial blood pressure (ABP) stability before and after glycopyrrolate or atropine treatment. Changes in R-R interval (RRI) and ABP were assessed in 10 healthy young (age, 22 +/- 1.8 yr) volunteers during graded lower body negative pressure (LBNP) before and after muscarinic cholinergic (MC) blockade. Transient hypertension was induced by phenylephrine (1 microg/kg body wt), whereas systemic hypotension was induced by bilateral thigh cuff deflation after a 3-min suprasystolic occlusion. Power spectral densities of systolic [systolic blood pressure (SBP)] and diastolic ABP variability were examined. Both antimuscarinic agents elicited tachycardia similarly without significantly affecting baseline ABP. The increase in SBP after phenylephrine injection (+14 +/- 2 mmHg) was significantly augmented with atropine (+26 +/- 2 mmHg) or glycopyrrolate (+27 +/- 3 mmHg) and associated with a diminished reflex bradycardia. The decrease in SBP after cuff deflation (-9.2 +/- 1.2 mmHg) was significantly greater after atropine (-15 +/- 1 mmHg) or glycopyrrolate (-14 +/- 1 mmHg), with abolished reflex tachycardia. LBNP significantly decreased both SBP and RRI. However, after antimuscarinic agents, the reduction in SBP was greater (P < 0.05) and was associated with less tachycardia. Antimuscarinic agents reduced (P < 0.05) the low-frequency (LF; 0.04-0.12 Hz) power of ABP variability at rest. The LF SBP oscillation was significantly augmented during LBNP, which was accentuated (P < 0.05) after antimuscarinic agents and was correlated (r = -0.79) with the decrease in SBP. We conclude that antimuscarinic agents compromised ABP stability by diminishing baroreflex sensitivity, reflecting the importance of vagal cardiac function in hemodynamic homeostasis. The difference between atropine and glycopyrrolate was not significant.

Adrenergic alpha-Agonists↗
PubMed2001

[Mercury concentration of fish in Tokyo Bay and the surrounding sea area].

Total mercury in the muscles of three fish species was analyzed in fish caught in Tokyo Bay and the surrounding sea areas, Sagami Bay and Choshi. Tokyo Bay is a semi-closed sea area surrounded by Tokyo, Kanagawa and Chiba prefectures. Sagami Bay and Choshi are open to the Pacific Ocean. A total of 412 fish consisting of northern whiting (Sillago japonica), flatfish (Limanda yokohamae) and sardine (Sardinops melanosticta) were caught in these areas over a 6 months period from November 1998 to April 1999. Total mercury concentration ranged from 0.008-0.092 microgram/g (wet wt.) in northern whiting, 0.006-0.065 microgram/g in flatfish and 0.001-0.045 microgram/g in sardine. All concentrations were below the restriction limit of fish mercury in Japan, 0.4 microgram/g of total mercury concentration. A significant correlation was found between mercury concentrations and body length or body weight in northern whiting and flatfish, irrespective of the sea area. A correlation was also found between mercury concentration in fish and their feeding habits: among the 3 species caught in the same area, crustacean feeding northern whiting had the highest, polychaete feeding flatfish moderate, and plankton feeding sardine had the lowest mercury concentration. In a comparison of mercury concentration in the same species caught in different sea areas, a higher concentration was noted in fish caught in the semi-closed sea area of Tokyo Bay, than in fish caught in the open sea areas of Sagami Bay and Choshi. This difference was most marked in fish caught at the bottom of Tokyo Bay and we considered that the mercury concentration of seawater and sediment in these areas was the cause of mercury accumulation in fish. These findings suggest that improved water quality control and environmental monitoring is necessary in semi-closed sea areas such as Tokyo Bay.

Animals↗
PubMed2001

An adenoviral vector expressing functional heterogeneous proteins herpes simplex viral thymidine kinase and human interleukin-2 has enhanced in vivo antitumor activity against medullary thyroid carcinoma.

To explore a more efficient multi-gene antitumor treatment, we developed an adenoviral vector expressing both herpes simplex virus thymidine kinase (HSVtk) and human interleukin-2 (hIL-2) (AdCMVTKhIL2). Production of hIL-2 is expected to augment antitumor T cell and natural killer cell activity. Two separate cassettes expressing HSVtk and hIL-2, each under the control of the human cytomegalovirus (CMV) immediate early gene promoter, were inserted into the early 1 region of adenovirus type 5. This vector showed similar direct cytotoxicity towards infected rat medullary thyroid carcinoma (rMTC) cells as did the single gene vector, AdCMVtk. rMTC cells infected with the virus in vitro showed high sensitivity to ganciclovir. After infection with AdCMVTKhIL2 at 100 m.o.i. for 1 h, more than 20 000 U hIL-2 were produced during 24 h by 1 &times 10(6) rMTC cells on day 2 and day 3. hIL-2 was also detected in the supernatants of primary cultures from tumors treated in vivo by the AdCMVTKhIL2 vector. Infected cells lost their tumorigenicity when transplanted subcutaneously into syngeneic rats, whereas all control animals developed tumors. More than 63% of tumors (19 out of 30 treated tumors) were destroyed when AdCMVTKhIL2 was injected intratumorally, compared with 38% when tumors were treated with AdCMVIL2, and 12% when treated with AdCMVtk, indicating an antitumor effect superior to that of each single vector given alone at the same dosage. These results indicate that the AdCMVTKhIL2 vector efficiently produces both HSVtk and hIL-2, and provides an enhanced antitumor activity.

Adenoviruses, Human↗
PubMed2001

Antisense anticancer oligonucleotide therapeutics.

Recent progress made in molecular biology, biotechnology, and genetics, especially in identifying, cloning, sequencing and characterization of normal and pathogenic genes, has led to the development of genetic therapy. Major efforts in the field can be summarized in two general approaches: gene therapy and antisense therapy. The second is to deliver to the target cells antisense molecules that target to mRNA with which they can hybridize and specifically inhibit the expression of pathogenic genes. Antisense oligonucleotides offer the possibility of specific, rational, genetic-based therapeutics. With encouraging results from preclinical and clinical studies of antisense oligonucleotides in the past decade, significant progress has been made in developing antisense therapy, with the first antisense drug now being approved for clinical use. In this article, we will discuss approaches to developing these drugs from preclinical to clinical settings. Of particular interest for the area of human cancer therapy, several cancer targets, including bcl-2, BCR-ABL, C-raf-1, Ha-ras, c-myc, PKC, PKA, p53 and MDM2, are reviewed as examples to illustrate the progress in this field and emphasize the importance of target selection and advanced antisense chemistry in the development of antisense therapy.

Antineoplastic Agents↗
PubMed2001

Relationship between plasma D(-)-lactate and intestinal damage after severe injuries in rats.

AIM: To explore the kinetic changes in plasma D(-)-lactate and lipopolysaccharide (LPS) levels, and investigate whether D(-)-lactate could be used as a marker of intestinal injury in rats following gut ischemia/reperfusion, burn, and acute necrotizing pancreatitis (ANP). METHODS: Three models were developed in rats: (1)gut ischemia/reperfusion obtained by one hour of superior mesenteric artery occlusion followed by reperfusion; (2)severe burn injury created by 30% of total body surface area (TBSA) full-thickness scald burn; and (3)ANP induced by continuous inverse infusion of sodium taurocholate and trypsin into main pancreatic duct. Plasma levels of D(-)-lactate in systemic circulation and LPS in portal circulation were measured by enzymatic-spectrophotometric method and limulus amebocyte lysate (LAL) test kit, respectively. Tissue samples of intestine were taken for histological analysis. RESULTS: One hour gut ischemia followed by reperfusion injuries resulted in a significant elevation in plasma D(-)-lactate and LPS levels, and there was a significant correlation between the plasma D(-)-lactate and LPS (r = 0.719, P<0.05). The plasma concentrations of D(-)-lactate and LPS increased significantly at 6h postburn, and there was also a remarkable correlation between them (r=0.877 P<0.01). D(-)-lactate and LPS levels elevated significantly at 2h after ANP, with a similar significant correlation between the two levels (r = 0.798, P < 0.01). The desquamation of intestine villi and infiltration of inflammatory cells in the lamina propria were observed in all groups. CONCLUSION: The changes of plasma D(-)-lactate levels in systemic blood paralleled with LPS levels in the portal vein blood. The measurement of plasma D(-)-lactate level may be a useful marker to assess the intestinal injury and to monitor an increase of intestinal permeability and endotoxemia following severe injuries in early stage.

Animals↗
PubMed2001

[Studies on association between lipoprotein lipase gene polymorphisms of Pvu II site and hypertriglyceridemics in Chinese].

OBJECTIVE: To explore whether Pvu II restriction fragment length polymorphisms (RFLP) in the lipoprotein lipase(LPL) gene are associated with hypertriglyceridemics (HTG). METHODS: Pvu II restriction fragment length polymorphisms in the lipoprotein lipase gene on a sample of 135 HTG patients and 193 age-matched healthy individuals in Chengdu area were detected with the method of PCR-RFLP. RESULTS: The P+ P+ genotype frequency and P+ allelic frequency of LPL gene for HTG cases are higher than those for control groups (0.460 vs 0.337,P<0.05; 0.689 vs 0.565,P<0.01). The serum levels of TGapoCII, apoCIII, apoE and TG/HDL-C in P+P+ genotype are higher than those in P-P- genotype(P<0.05). CONCLUSION: The results suggest that P+P+ genotype in the lipoprotein lipase gene is associated with susceptibility to hypertriglyceridemics in Chinese population.

Adult↗
PubMed2001

Antisense anti-MDM2 oligonucleotides as a novel therapeutic approach to human breast cancer: in vitro and in vivo activities and mechanisms.

The mouse double minute 2 (MDM2) oncogene has been suggested as a target for cancer therapy. It is amplified or overexpressed in many human cancers, including breast cancer, and MDM2 levels are associated with poor prognosis of several human cancers, including breast cancer, ovarian cancer, osteosarcoma, and lymphoma. In the present study, we investigated the functions of MDM2 oncogene in the growth of breast cancer and the potential value of MDM2 as a drug target for cancer therapy by inhibiting MDM2 expression with a specific antisense antihuman-MDM2 oligonucleotide (oligo). The selected antisense mixed-backbone oligo was evaluated for its in vitro and in vivo antitumor activity in human breast cancer models: MCF-7 cell line containing wild-type p53 and MDA-MB-468 cell line containing mutant p53. In MCF-7 cells, p53 and p21 levels were elevated, resulting from specific inhibition of MDM2 expression by the antisense oligo (AS). In MDA-MB-468 cells, after inhibition of MDM2 expression, p21 levels were elevated, although p53 levels remained unchanged. After i.p. administration of the antisense anti-MDM2 oligo, in vivo antitumor activity occurred in a dose-dependent manner in nude mice bearing MCF-7 or MDA-MB-468 xenografts. In both models, in vivo synergistically or additive therapeutic effects of MDM2 inhibition and the clinically used cancer chemotherapeutic agents irinotecan, 5-fluorouracil, and paclitaxel (Taxol) were observed. These results suggest that MDM2 have a role in tumor growth through both p53-dependent and p53-independent mechanisms. We speculate that MDM2 inhibitors, such as ASs, have a broad spectrum of antitumor activities in human breast cancers, regardless of p53 status. This study should provide a basis for future development of anti-MDM2 ASs as cancer therapeutic agents used alone or in combination with conventional chemotherapeutics.

Animals↗
PubMed2001

Metabolism and biliary excretion of the novel anticancer agent 10-hydroxycamptothecin in the isolated perfused rat liver.

10-hydroxycamptothecin (HCPT), a natural analog of the alkaloid camptothecin (CPT), is a promising anticancer agent currently undergoing preclinical trials. Though HCPT is less toxic and more active in various human cancer cell lines and in animal tumor models than the clinically approved CPT-analog topotecan, little is known about its biotransformation products and their route of elimination. To investigate the metabolism and biliary excretion, livers of male Wistar rats were perfused with HCPT (5 microM). Bile and perfusate samples were collected for 60 min and quantified by reversed-phase high-performance liquid chromatography (HPLC). Besides HCPT, three metabolites, namely HCPT glucuronide (M1), hydroxyHCPT glucuronide (M2), and hydroxyHCPT (M3) could be identified by enzymatic hydrolysis with beta-glucuronidase and mass spectroscopy. Biliary secretion of HCPT and M1-M3 reached a peak secretion of 1532+/-124, 75+/-16, 5.8+/-1.6 and 2.1+/-0.5 pmoles/g liver.min, respectively, after 25 min. The total amount of HCPT and M1-M3 excreted into bile during the time of perfusion (60 min) was low and represented a mean of 9.9+/-3.2%, 0.44+/-0.17%, 0.041+/-0.010%, and 0.022+/-0.004% of the initial HCPT dose, respectively. In the perfusate, besides HCPT M1 and M2 but not M3 could be detected (maximum concentrations after about 20 min: 3248+/-210, 16.8+/-2.8 and 1.0+/-0.4 pmoles/g liver.min, respectively). The cumulative efflux of HCPT and M1 and M2 into the perfusate was 21.1+/-3.9%, 0.145+/-0.036% and 0.018+/-0.004% of the initial dose, respectively, indicating a preferable non-biliary secretion for HCPT and a predominant biliary elimination for conjugated HCPT biotransformation products. In conclusion, HCPT is biotransformed in a rat liver model to three metabolites, mainly excreted into bile, which may be of clinical relevance during cancer therapy.

Animals↗
PubMed2001

Percutaneous transluminal stenting in patients with carotid artery stenosis.

OBJECTIVE: To assess the efficacy and safety of percutaneous transluminal stenting for patients with carotid artery stenosis. METHODS: Selective percutaneous transluminal stenting was performed for patients with symptomatic carotid artery stenosis (luminal narrowing > or = 70%). Success rates and complications associated with the procedures were observed. During six months of follow-up, both recurrent symptom and restenosis rates were recorded. RESULTS: There were 17 bifurcating lesions among 27 stenoses in 26 patients, of whom 18 had concomitant coronary artery diseases. The acute procedural success rate was 96.3% (26/27), and the degree of stenosis was reduced from 88.6% +/- 8.9% (range 70-100) to 0.4% +/- 2.0% (range 0-10). Six patients developed severe bradycardia and hypotension, and 3 experienced transient loss of consciousness during balloon dilatation. During hospitalization, 2 patients experienced loss of consciousness and convulsion, respectively, due to hyperperfusion, and both recovered 12 hours later. There were 2 minor stroke cases (7.4%) but no cases of major stroke or death. At the 6-month follow-up, there were no cases of TIA or new onset of stroke. There was no restenosis detected in 16 cases using angiography and in 10 cases using MRI in 6 to 16 months of follow-up. CONCLUSIONS: Percutaneous transluminal stenting for patients with carotid artery stenosis has a high procedural success rate with few and acceptable complications. Few patients suffered from recurrent symptoms or showed restenosis in long-term follow-up.

Aged↗
PubMed2001

[Spatial structure and pattern of Nilaparvata lugens population in large-scale].

Brown planthopper(BPH), Nilaparvata lugens, is a major pest of rice. Its spatial distribution of different generations in Guangdong Province was studied by using variograms. The results showed that this population distributed in a clump pattern in rice fields during the 1st rice season. 3 generations of this population had different spatial structures, with the clump range of 400 km, 200 km and 205 km respectively in the 1st rice season. The simulation distribution maps of BPH, which was interpolated by Ordinary Kriging, showed that the density of BPH populations in west Guangdong province were higher than that in the east. The effect of sampling size on the spatial structure of BPH was not significant.

Animals↗
PubMed2001

[The impact of calpain-10 gene combined-SNP variation on type 2 diabetes mellitus and its related metabolic traits].

OBJECTIVE: To investigate the impact of calpain-10 gene (CAPN-10) combined single nucleotide polymorphism (SNP) variation on type 2 diabetes mellitus (T2DM) and its related clinical metabolic traits in Chinese. METHODS: The study population consisted of 268 Chinese residents in Shanghai. Among them, 144 were subjects with normal glucose tolerance (NGT) and 124, with T2DM. Plasma glucose (PG), insulin (INS), c-peptide (CP) and free fatty acids (FFA) levels were measured at fasting and 30, 60, 120, and 180 minutes after oral 75 g glucose challenge. The islet beta-cell insulin secretion and tissue insulin sensitivity were assessed. CAPN-10 UCSNP44,-43,-19 and -63 were genotyped. RESULTS: (1) In Chinese NGT subjects, the major allele of UCSNP-44 was allele T (frequency=91%), of UCSNP43 was G(89%), of UCSNP-19 was I (3 repeats of a 32 bp sequence) (67%) and of UCSNP-63 was C allele (79%). Significant differences were observed in comparison of these allele frequencies in Chinese to those in other ethnic groups reported in the literature. (2) 14 genotype combinations of these four SNPs were observed in Chinese NGT subjects. 69% of the NGT population was composed of four genotype combinations, in the order of UCSNP44,-43,-19 and -63, i.e., combination A:TT-GG-DI-CC(haplotype combination was 1121/1111) (frequency=10%), combination B:TT-GA-II-CC(1121/1221)(10%), combination C:TT-GG-II-CC(1121/1121)(26%) and combination D:TT-GG-DI-CT(1121/1112)(22%).(3) The frequencies of the above mentioned SNP in single or in combinations were not different significantly between NGT and T2DM groups. (4) The variation of clinical metabolic parameter levels shifted from completely normal towards abnormal glucose intolerance among genotype combination subgroups. In comparison between combination A and combination D, subjects in the former subgroups had: higher PG levels with delayed peak after glucose challenge; less and lower decrement of FFA levels after challenge with no rising in late stage; higher insulin levels with delayed peak after challenge; and the tendency of decreased insulin sensitivity. More than half of the comparisons remained statistically significant after adjusted with age, gender, body mass index and waist circumference. CONCLUSION: The variation of calpain-10 gene has impact on the variation of clinical metabolic parameter levels related to type 2 diabetes mellitus. Such impact depends upon the haplotypes as well as the haplotype combination of calpain-10 gene variations.

Alleles↗
PubMed2001

Optimal timing of coronary stenting in unstable angina patients.

OBJECTIVE: To assess the efficacy and safety of intracoronary stenting in the acute phase of unstable angina pectoris (UAP). METHODS: Fifty-five patients with UAP were randomized to early (Group I, n = 29) and delayed interventional treatment (Group II, n = 26). Coronary angiography and stenting were performed within 48 hours in Group I and 7-10 days later in Group II. Procedural success rate, time interval from admission to angina relief and duration of hospitalization were recorded. Cardiac events within 30 days were observed as well. RESULTS: Clinical characteristics and angiographic features were similar between the two groups. There was no significant difference in the procedural success rate (93% versus 96%), but the cardiac event rate within 30 days was significantly lower in Group I than in Group II (0% versus 9.2%, P < 0.05). The time interval from admission to angina relief (4.4 +/- 3.1 days versus 5.7 +/- 2.9 days) and the duration of hospitalization (8.8 +/- 3.2 days versus 13.5 +/- 3.1 days) were significantly reduced in Group I (both P < 0.05). CONCLUSIONS: Intracoronary stent implantation is effective and safe in the acute phase of UAP. Early percutaneous coronary intervention results in rapid improvement in symptomatology and a shorter hospitalization. Its long-term effect has to be confirmed in a future randomized study.

Aged↗
PubMed2001

[Expression of glutathione S-transferase-pi in human esophageal squamous cell carcinoma].

OBJECTIVE: To evaluate the expression of glutathione S-transferase-pi (GST-pi) in human esophageal squamous cell carcinoma (ESCC) and its correlation with the clinicopathological data. METHODS: Immunohistochemical method (labeled avidin biotin method) and ELISA were used to detect the expression of glutathione S-transferase-pi (GST-pi) in 143 cases of formalin fixed, paraffin embedded ESCC tissue sections. Serum GST-pi was determined before and after operation in 43 patients with ESCC. RESULTS: GST-pi was positively stained immunohistochemically in 58.7%(84/143) of ESCC and 79.6%(109/139) of surrounding noncancerous esophageal tissues (P < 0.05). The expression level of GST-pi was significantly higher in well differentiated than poorly differentiated carcinomas(P < 0.05). No significant correlation was observed between GST-pi levels and lymph node metastasis, pathological staging or long term survival. The preoperative and postoperative mean serum GST-pi levels in ESCC patients were significantly higher than those in 34 normal subjects (P < 0.05, P < 0.025); the mean serum GST-pi level in postoperative patients was lower than that in preoperative patients, but the difference was not significant. CONCLUSION: GST-pi is a useful tumor marker for human ESCC.

Adult↗
PubMed2001

[An analysis of clinicopathologic features affecting prognosis of thymoma].

OBJECTIVE: To discuss the relationship between the clinicopathologic characteristics and prognosis of thymoma. METHODS: One hundred and thirty cases of thymoma were analyzed in terms of myasthenia gravis(MG), tumor size, necrosis, mitosis, capsule, histologic type according to the Lattes-Bernatz(L-B) classification and Muller-Hermelink(M-H) classification, staging according to Masaoka. RESULTS: Association with MG, size of tumor, necrosis, mitosis and L-B classification were of no prognostic significance. The survival rate was higher in patients with a well encapsulated tumor. According to the M-H subtypes, the prognosis was better in patients in medullary type than in patients with cortical type thymoma. In patients with well-differentiated thymic carcinoma(WDTC), their 5-year survival rate was 43.4%, and none survived at 10 years. The survival of patients decreased with the increase in clinical stage of the disease. Cell atypia and invasion of neighboring organs were of prognostic impact on survival. CONCLUSION: Histologic typing according to M-H classification and clinical staging according to Masaoka, cell atypia and invasion to neighboring organs are of prognostic value in patients with thymoma.

Adolescent↗