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Biomedical subjects

H C Zhang

Publications and source records attributed to H C Zhang.

At least 19 recordsLinked to original sources
PubMed2006

A modified electrocardiographic algorithm for differentiating typical atrioventricular node re-entrant tachycardia from atrioventricular reciprocating tachycardia mediated by concealed accessory pathway.

Non-invasive prediction of tachycardia mechanism is becoming clinically important in the era of catheter ablation for curing supraventricular tachycardia. Twelve-lead electrocardiograms (ECGs) during sinus rhythm and atrioventricular node re-entrant tachycardia (AVNRT) or atrioventricular reciprocating tachycardia (AVRT) with a narrow QRS complex were obtained from 154 consecutive adult patients who had received successful radiofrequency catheter ablation. The ECGs of initial 104 patients were analysed by three observers without knowledge of the electrophysiological diagnosis. The two arrhythmias were accurately diagnosed in 68% of cases. Three criteria were found to be discriminators of tachycardia mechanism by univariable analysis. Pseudo r/Q/S waves predicated AVNRT in 92% of cases (sensitivity 71%; specificity 95%). Retrograde P wave predicated AVRT in 86% of cases (sensitivity 75%; specificity 85%), RP interval > or =100 ms in 93% (sensitivity 71%; specificity 94%) and ST-segment elevation in lead aVR in 83% (sensitivity 71%; specficity 83%). According to the initial results, we proposed a modified stepwise ECG algorithm which used pseudo r/S/Q waves, RP interval and ST-segment elevation in lead aVR during tachycardia. Two observers assessed the modified algorithm in the remaining 50 patients. The algorithm was able to correctly diagnose the tachycardia mechanism in 84% and 87%, respectively. Using the modified algorithm can improve the accuracy and simplify the differential diagnosis between typical AVNRT and AVRT via concealed accessory pathway in adult patients.

Adult↗
PubMed2006

Origin and phylogeographical structure of Chinese cattle.

Complete mitochondrial D-loop sequences of 231 samples were used to explore the origin and genetic diversity of Chinese cattle. Phylogenetical analysis of these sequences revealed both Bos taurus and Bos indicus mitochondrial types in Chinese cattle. Four of the previously identified mitochondrial DNA lineages (T1-T4) were identified in the Bos taurus type, including lineage T1, which was found for the first time in Chinese cattle. Two lineages (I1 and I2) were identified in the Bos indicus type. Our results support the suggestion that the Yunnan-Guizhou Plateau is the domestication site of Chinese zebu. We also found evidence that Tibetan cattle originated from taurine and zebu cattle. The distribution pattern of Chinese cattle breeds was closely related to the geographical and climatic background. It was possible to divide Chinese cattle in this study into two major groups: northern and southern cattle.

Animals↗
PubMed2003

Effect of phosphate fertilizer application on phosphorus (P) losses from paddy soils in Taihu Lake Region. I. Effect of phosphate fertilizer rate on P losses from paddy soil.

A field plot study was conducted on two types of paddy soils in the Taihu Lake Region, during the rice season of year 2000 in order to assess phosphorus (P) losses by runoff and vertical leaching, which are considered the two main pathways of P movement from paddy soil into its surrounding water course. Commercial NPK compound fertilizer and single superphosphate fertilizer were applied to furnish 0, 30, 150, and 300 kg applied P ha m(-2). The experiments consisted of three replicates of each treatment in Changshu site and four replicates in Anzhen site, with a plot size of 5 x 6 m2 in a randomized block. Results revealed that the average concentration range for total P (TP) in runoff was 1.857-7.883, 1.038-5.209, 0.783-1.255 and 0.572-0.691 mg P l(-1) respectively for P300, P150, P30 and P0 in Anzhen, while it was 2.431-2.449, 1.578-1.890, 1.050-1.315 and 0.749-0.941 mg P l(-1) respectively in Changshu. In all treatments, particulate P (PP) represented a major portion of the TP lost in runoff, it was 80% in Anzhen, and it was even more (>90%) in Changshu. Phosphate fertilizer treatments significantly affected P concentrations and P loads in the runoff. The mean concentration and average seasonal TP load from the P150 plots were 1.809 mg P l(-1) and 395 g P ha m(-2) season(-1) respectively, and lower than that from the P300 plots (2.957 mg P l(-1) and 652 g P ha m(-2) season(-1)). These were obviously higher than from the P30 (0.761 mg P l(-1) and 221 g P ha m(-2) season(-1)) and P0 (0.484 mg P l(-1) and 146 g P ha m(-2) season(-1)) respectively. There was no significant difference found between the P30 and the P0 in both sites. Under usual P application rate, there were total 31.7 and 20.6 tones P removed by runoff from permeable (Anzhen site) and waterlogged (Changshu site) paddy soils in the southern Jiangsu region (major part of the TLR) in the rice season of the year 2000. But if the P application rate is unusual high, or the Olsen P in soil accumulates to above a certain level, then this could sharply increase in the future. The average concentration of molybdate reactive phosphorus (MRP) in the vertical leachate from the four different P treatments ranged from 0.058 to 0.304 mg P l(-1) in Anzhen and from 0.048 to 0.394 mg P l(-1) in Changshu. P application rate significantly affected the MRP concentration at each depth in both sites, except for the 90 cm in Anzhen. The average MRP loads during the rice season moved by vertical leaching from the four treatments ranged from 163 to 855 g P ha m(-2) season(-1) in Anzhen and 208-1,825 g P ha m(-2) season(-1) in Changshu. Vertical leachate movement does not necessarily mean that it moves towards surface water and contaminate the watercourses in this flat plain paddy soil region, it does, however, imply that P can move down from surface layers of soil to deeper levels.

Crops, Agricultural↗
PubMed2002

Effects of age and menopause on spinal bone mineral density in Japanese women: a ten-year prospective study.

In order to determine the age and menopause-related changes in spinal bone mineral density (BMD) in healthy Japanese women, the spinal BMD at L(2-4) was measured by dual X-ray absorptiometry (DXA) in 172 healthy Japanese women aged 31-69 years (mean age 53.1+/-6.7 years) in 1990 and 2000. This prospective study showed that there was no significant decrease of BMD in premenopausal women, but there was a significant decrease of BMD (-1.59%/year) in the early post menopausal women when compared with the premenopausal and late postmenopausal women (P <0.0001). The rate of decrease in BMD slowed down with the prolongation of the years since menopause (YSM). In postmenopausal women the annual rate of decrease in BMD for obese women was significantly lower than that for slim ones (P <0.01), suggesting that fat tissue may be effective for preventing bone loss. A multiple regression analysis of variables contributing to the annual rate of decrease in spinal BMD showed that YSM and physiological age were the most influential factors, considering other factors such as weight, height and bone mass index. In conclusion, an accelerated bone loss was seen in the early postmenopausal stage. The YSM and physiological age were the most important factors that affect the rate of bone loss in healthy postmenopausal Japanese women.

Absorptiometry, Photon↗
PubMed2001

Thrombin receptor (PAR-1) antagonists. Solid-phase synthesis of indole-based peptide mimetics by anchoring to a secondary amide.

A novel, 10-step, solid-phase method, based on a secondary amide linker, was developed to construct a diverse library of indole-based SFLLR peptide mimetics as thrombin receptor (protease-activated receptor 1, PAR-1) antagonists. The key steps include stepwise reductive alkylation, urea formation, and Mannich reaction. Screening of the library led to a quick development of the SAR and the significant improvement of PAR-1 activity.

Amides↗
PubMed2001

Biaryl-based macrocyclic and polymeric chiral (salophen)Ni(II) complexes: synthesis and spectroscopic study.

Polymeric/oligomeric and macrocyclic (salophen)Ni(II) complexes have been synthesized starting from both an achiral biphenol dialdehyde and an optically active BINOL dialdehyde. It was found that these polysalophens contain nonplanar coordination of Ni(II) units that are paramagnetic. This is different from the previously reported (salophen)Ni(II) complexes which are square planar and diamagnetic. The nonplanar (salophen)Ni(II) units make the new polymeric Ni(II) complexes different from the helical structure proposed for chiral biaryl-based polymers containing square-planar (salophen)Ni(II) units. The copolymerization of the chiral binaphthyl monomer with the achiral biphenyl monomer demonstrates that the chirality of the binaphthyl unit is not propagated along the biphenyl polymer chain.

Journal Article↗
PubMed2001

Administration of a potent antagonist of protease-activated receptor-1 (PAR-1) attenuates vascular restenosis following balloon angioplasty in rats.

Human platelets possess two distinct thrombin-activated receptors, PAR-1 (protease-activated receptor-1) and PAR-4, whereas human vascular smooth muscle cells possess only PAR-1. Although such thrombin receptors have been studied extensively in vitro, their physiological roles are still rather ill-defined. We have now employed a potent, selective PAR-1 antagonist, RWJ-58259, to probe the in vivo significance of PAR-1 in thrombosis and vascular injury. RWJ-58259 was examined in two thrombosis models in guinea pigs: the arteriovenous (A-V) shunt assay (monitoring thrombus weight) and the Rose Bengal intravascular photoactivation assay (monitoring time to occlusion). Administration of RWJ-58259 (10 mg/kg, total i.v. dose) did not inhibit thrombus formation in either thrombosis model, although local, intrashunt delivery in the A-V shunt model did elicit a modest antithrombotic effect (thrombus weight reduction from 35 +/- 2 to 24 +/- 4 mg). These results are consistent with the presence of more than one thrombin-sensitive receptor on guinea pig platelets, in analogy with human platelets. Indeed, we were able to establish that guinea pig platelets express three thrombin receptors, PAR-1, PAR-3, and PAR-4. We also examined RWJ-58259 in a vascular restenosis model involving balloon angioplasty in rats. Perivascular administration of RWJ-58259 (10 mg) significantly reduced neointimal thickness (77 +/- 5 microm to 45 +/- 5 microm, P < 0.05), clearly demonstrating an important role for PAR-1 in vascular injury. From these results, it is evident that a PAR-1 antagonist is not especially effective for treating platelet-dependent thrombosis; however, it could well be beneficial for treating restenosis attendant to arterial injury.

Angioplasty, Balloon↗
PubMed2001

Enhancement of protease activity involved in modulation of cell mutability by microgravity stress in UVC-irradiated human cells.

It is an intriguing question whether gravity-changing stress modulates human cell mutability. To resolve this problem, it is necessary to determine the cellular events leading to modulation. We previously detected protease activation just after UV (UVC, principally 254 nm wavelength) irradiation followed by hypomutability in cultured human cells. We here investigated whether UV-activated protease activity is affected in human UVAP-1 cells exposed to gravity-changing stress prior to UV irradiation.

Cell Line↗
PubMed2000

Inhibition of farnesyltransferase with A-176120, a novel and potent farnesyl pyrophosphate analogue.

Farnesylation of Ras is required for its transforming activity in human cancer and the reaction is catalysed by the enzyme farnesyltransferase. Recently, we discovered a novel chemical series of potent farnesyl pyrophosphate (FPP) analogues which selectively inhibited farnesyltransferase. Our most potent compound to date in this series, A-176120, selectively inhibited farnesyltransferase activity (IC(50) 1.2+/-0.3 nM) over the closely related enzymes geranylgeranyltransferase I (GGTaseI) (IC(50) 423+/-1.8 nM), geranylgeranyltransferase II (GGTaseII) (IC(50) 3000 nM) and squalene synthase (SSase) (IC(50)>10000 nM). A-176120 inhibited ras processing in H-ras-transformed NIH3T3 cells and HCT116 K-ras-mutated cells (ED(50) 1.6 and 0.5 microM, respectively). The anti-angiogenic potential of A-176120 was demonstrated by a decrease in Ras processing, cell proliferation and capillary structure formation of human umbilical vein endothelial cells (HUVEC), and a decrease in the secretion of vascular endothelial growth factor (VEGF) from HCT116 cells. In vivo, A-176120 reduced H-ras NIH3T3 tumour growth and extended the lifespan of nude mice inoculated with H- or K-ras-transformed NIH3T3 cells. A-176120 also had an additive effect in combination with cyclophosphamide in nude mice inoculated with K-ras NIH3T3 transformed cells. Overall, our results demonstrate that A-176120 is a potent FPP mimetic with both antitumour and anti-angiogenic properties.

Alkyl and Aryl Transferases↗
PubMed2000

Hepatitis C virus core protein induces apoptosis and impairs cell-cycle regulation in stably transformed Chinese hamster ovary cells.

Hepatitis C virus (HCV) infection is associated with the development of hepatocellular carcinoma. Several lines of evidence suggest that the core protein of HCV may play a role in the development of this cancer. The authors examined regulation of the cell cycle in stable cell lines derived from Chinese hamster ovary (CHO-K1) cells that constitutively expressed one or more of the structural proteins of HCV. In media containing low concentrations of serum (serum starvation), cell lines expressing the core protein showed a significantly lower population of viable cells than noncore-expressing cells. The low viability of the core-expressing cells was a result of the increased population of cells undergoing apoptosis. Interestingly, the cell cycle analysis revealed that the arresting function at G(0) was impaired, and the cell cycle was accelerated in core-expressing cell lines even under serum starvation. Thus, the HCV core protein sensitizes the apoptosis to serum starvation, although it promotes the cell cycle in CHO-K1 cells. To explain these findings, the authors examined the expression of revival apoptosis and cell-cycle-related genes. Expression of the c-myc genes was significantly induced in core-expressing cells in response to serum starvation. Other apoptosis-inducing genes downstream of c-myc, p53, p21WAF1/CIP1 and Bax were significantly highly induced, although there was no induction of Bcl-2, which prevents apoptosis in core-expressing cells. Thus, the HCV core protein induced apoptosis and impaired the regulation of the cell cycle by activating c-myc expression, whereas the p53 and Bax pathways play a role in the induction of apoptosis.

Animals↗
PubMed1999

Design, synthesis, and biological characterization of a peptide-mimetic antagonist for a tethered-ligand receptor.

Protease-activated receptors (PARs) represent a unique family of seven-transmembrane G protein-coupled receptors, which are enzymatically cleaved to expose a truncated extracellular N terminus that acts as a tethered activating ligand. PAR-1 is cleaved and activated by the serine protease alpha-thrombin, is expressed in various tissues (e.g., platelets and vascular cells), and is involved in cellular responses associated with hemostasis, proliferation, and tissue injury. We have discovered a series of potent peptide-mimetic antagonists of PAR-1, exemplified by RWJ-56110. Spatial relationships between important functional groups of the PAR-1 agonist peptide epitope SFLLRN were employed to design and synthesize candidate ligands with appropriate groups attached to a rigid molecular scaffold. Prototype RWJ-53052 was identified and optimized via solid-phase parallel synthesis of chemical libraries. RWJ-56110 emerged as a potent, selective PAR-1 antagonist, devoid of PAR-1 agonist and thrombin inhibitory activity. It binds to PAR-1, interferes with PAR-1 calcium mobilization and cellular function (platelet aggregation; cell proliferation), and has no effect on PAR-2, PAR-3, or PAR-4. By flow cytometry, RWJ-56110 was confirmed as a direct inhibitor of PAR-1 activation and internalization, without affecting N-terminal cleavage. At high concentrations of alpha-thrombin, RWJ-56110 fully blocked activation responses in human vascular cells, albeit not in human platelets; whereas, at high concentrations of SFLLRN-NH(2), RWJ-56110 blocked activation responses in both cell types. Thus, thrombin activates human platelets independently of PAR-1, i.e., through PAR-4, which we confirmed by PCR analysis. Selective PAR-1 antagonists, such as RWJ-56110, should serve as useful tools to study PARs and may have therapeutic potential for treating thrombosis and restenosis.

Base Sequence↗
PubMed1999

Effect of novel CAAX peptidomimetic farnesyltransferase inhibitor on angiogenesis in vitro and in vivo.

Ras oncogenes can contribute to tumour development by stimulating vascular endothelial growth factor (VEGF)-dependent angiogenesis. The effect of Ras on angiogenesis may be affected by farnesyltransferase inhibitors (FTI) since farnesylation of Ras is required for its biological activity. In this paper we evaluated the effect of A-170634, a novel and potent CAAX FTI on angiogenesis. Human umbilical vein endothelial cell (HUVEC) tube formation and VEGF secretion were used to assess the effect of A-170634 on angiogenesis in vitro. In vivo, nude mice were injected with the K-ras mutant colon carcinoma cell line HCT116 and treated subcutaneously with A-170634 using osmotic minipump infusion for 10 days. The effect of A-170634 on corneal angiogenesis in vivo was assessed using pellets containing hydron, VEGF, A-170634 or vehicle. In vitro, A-170634 selectively inhibited farnesyltransferase activity over the closely related geranylgeranyltransferase I, inhibited Ras processing, blocked anchorage-dependent and -independent growth of HCT116 K-ras mutated cells, decreased HUVEC capillary structure formation, decreased VEGF secretion from tumour cells and HUVEC growth stimulating activity in a dose-dependent manner. In vivo, tumour growth was decreased by 30% and vascularisation in and around the tumours was reduced by 41% following drug-treatment with no apparent toxicity to the animals. VEGF-induced corneal neovascularisation was reduced by 80% following A-170634 treatment for 7 days. The data presented here demonstrated that A-170634 was a potent and selective peptidomimetic CAAX FTI with anti-angiogenic properties. These results implied that A-170634 may affect tumour growth in vivo by one or more antitumour pathways.

Alkyl and Aryl Transferases↗
PubMed1995

Cyclotheonamide derivatives: synthesis and thrombin inhibition. Exploration of specific structure-function issues.

Macrocyclic pentapeptide analogues (5-9) of the sponge natural product cyclotheonamide A (CtA, 3) were prepared by means of our convergent [3 + 2] synthetic protocol, in which a late-stage primary amine group is available for substitution (Maryanoff et al. Proc. Natl Acad. Sci. U.S.A. 1993, 90, 8048). These analogues, as well as CtA and cyclotheonamide B (CtB, 4), were examined for their ability to inhibit the serine protease alpha-thrombin, in comparison with suitable reference standards. We characterized Michaelis-Menten and slow-binding kinetics for the cyclotheonamide derivatives. An attempt was made to utilize the unoccupied hydrophobic S3 subsite of thrombin via analogues 5 and 6. Also, removal of the hydroxyphenyl group, which is thought to be involved in an aromatic stacking interaction with Trp60D of thrombin, was explored via analogue 9. The importance of the alpha-keto and olefin groups was examined via 7 and 8, respectively. The relationship of structure and function with the analogues proved to be less predictable than anticipated.

Amino Acid Sequence↗
PubMed1994

[The operative treatment of hip fracture in patient over 80 years old: report of 81 cases].

The treatment of hip fracture in 81 cases of elderly (age ranged from 80 to 95) were reviewed. 13 of them were over 90 years old and 42 (52%) were accompanied with more than three preexistent diseases, mainly cardiovascular and cerebrovascular diseases. The femoral neck fracture (31 cases) were treated by Smith-Petersen nail or femoral head prosthesis replacement, the intertrochanteric fracture of femur (50 cases) were treated by McLaughlin or Richard nail. 24 cases (29.6%) had post-operative complications, e.g. pneumonia in 9 cases, cerebrovascular disease in 7 cases, cardio-vascular disease in 5 cases. Most of them recovered promptly after appropriate treatment. 5 patients died of pneumonia, the mortality is 6%. Internal fixation of hip fractures in elderly is one of very important methods of relieving pain, lowering morbidity and mortality, and early recovery of motion and normal daily life. It is believed that the proper evaluation of patient's general condition, appropriate treatment of preexistent disease, smooth anesthesia, skillful technique and intensive nursing care are needed for getting good results. The large majority of them will tolerate the operation nicely, even in high risk.

Aged↗
PubMed1993

Effects of three kinds of topical eye-drops on the experimental rabbit dry eye.

We studied the ultrastructural changes of the corneal epithelium of the experimental rabbit dry eye and the effects of three topically applied eye-drops. Fourty rabbits were divided into experimental rabbit dry eye group, 0.1% bromhexine-treated group, 50% Chinese medicinal herb-treated group and 0.01% retinoic acid-treated group. Ten days after surgical removal of lacrimal gland, nictitating membrane and Harder's gland of the rabbit eyes, and corroding the conjunctiva with 50% trichloroacetic acid, the rabbit eyes showed typical dry eye signs. A lot of pathologic ultrastructural changes of the corneal epithelium were observed. Fourteen days after topically applying the three eye-drops, no significant effect was found on the ultrastructural changes of the dry eye corneal epithelium in the 0.1% bromhexine-treated and 50% Chinese medicinal herb-treated groups. However, in the 0.01% retinoic acid-treated eyes, normal microvilli and microplicae reappeared, denuded corneal epithelium was covered by new epithelial cells, no cell swelled, degenerated mitochondria recovered, basement membrane returned completely, and the completely recovered corneal epithelial cell count showed a significant difference compared with the control (P < 0.01). We conclude that removing the lacrimal gland, nictitating membrane and Harder's gland of rabbit eye, and corroding the conjunctiva with 50% trichloroacetic acid can result in rabbit dry eye and topically applying 0.01% retinoic acid can promote the recovery of the dry corneal epithelium.

Animals↗