Biomedical subjects

H Zhu

Publications and source records attributed to H Zhu.

At least 19 recordsLinked to original sources

PubMed2003

Role and regulation of CXC-chemokines in acute experimental keratitis.

The aim of this study was to elucidate the expression of chemokines, their role and regulation in bacterial corneal infection using three bacterial strains (Pseudomonas. aeruginosa- invasive, cytotoxic and contact lens induced acute red eye strains) which have been shown to produce three distinct patterns of corneal disease in the mouse. The predominant chemokine expressed in response to all three strains was MIP-2. Prolonged expression of high levels of MIP-2 was associated with increased severity of corneal inflammation. Significantly reduced disease severity upon administration of anti-MIP-2 antibodies suggested that MIP-2 may play an important role in the pathogenesis of Pseudomonas keratitis at least in part by being a major chemoattractant for polymorphonuclear leukocytes (PMN) recruitment. Interestingly, the numbers of bacteria in eyes with neutralized MIP-2 activity did not decrease even though the severity of the disease was decreased. This implies PMNs as the major destructive factor in microbial keratitis. Further, neutralization of IL-1beta activity alone using monoclonal antibodies resulted in significant reduction of both MIP-2 and KC activity indicating that chemokine levels were regulated by IL-1beta. These studies demonstrate that the regulation of MIP-2 activity may be beneficial in reducing corneal damage during microbial keratitis in rodents and perhaps that regulation of the human homologue of MIP-2, IL-8, may be useful for controlling keratitis in humans.

Acute Disease↗

PubMed2003

Superinfection of Laodelphax striatellus with Wolbachia from Drosophila simulans.

Wolbachia are maternally inherited, intracellular alpha-proteobacteria that infect a wide range of arthropods. They manipulate the reproduction of hosts to facilitate their spread into host populations, through ways such as cytoplasmic incompatibility (CI), parthenogenesis, feminization and male killing. The influence of Wolbachia infection on host populations has attracted considerable interest in their possible role in speciation and as a potential agent of biological control. In this study, we used both microinjection and nested PCR to show that the Wolbachia naturally infecting Drosophila simulans can be transferred into a naturally Wolbachia-infected strain of the small brown planthopper Laodelphax striatellus, with up to 30% superinfection frequency in the F(12) generation. The superinfected males of L. striatellus showed unidirectional CI when mated with the original single-infected females, while superinfected females of L. striatellus were compatible with superinfected or single-infected males. These results are, to our knowledge, the first to establish a superinfected horizontal transfer route for Wolbachia between phylogenetically distant insects. The segregation of Wolbachia from superinfected L. striatellus was observed during the spreading process, which suggests that Wolbachia could adapt to a phylogenetically distant host with increased infection frequency in the new host population; however, it would take a long time to establish a high-frequency superinfection line. This study implies a novel way to generate insect lines capable of driving desired genes into Wolbachia-infected populations to start population replacement.

Animals↗

PubMed2003

Active control of acoustic reflection, absorption, and transmission using thin panel speakers.

This paper explores the development of thin panels that can be controlled electronically so as to provide surfaces with desired reflection coefficients. Such panels can be used as either perfect reflectors or absorbers. They can also be designed to be transmission blockers that block the propagation of sound. The development of the control system is based on the use of wave separation algorithms that separate incident sound from reflected sound. In order to obtain a desired reflection coefficient, the reflected sound is controlled to appropriate levels. The incident sound is used as an acoustic reference for feedforward control and has the important property of being isolated from the action of the control system speaker. In order to use a panel as a transmission blocker, the acoustic pressure behind the panel is driven to zero. The use of the incident signal as a reference again plays a key role in successfully reducing broadband transmission of sound. The panels themselves are constructed using poster board and small rare-earth actuators. Detailed experimental results are presented showing the efficacy of the algorithms in achieving real-time control of reflection or transmission. The panels are able to effectively block transmission of broadband sound. Practical applications for these panels include enclosures for noisy machinery, noise-absorbing wallpaper, the development of sound walls, and the development of noise-blocking glass windows.

Journal Article↗

PubMed2002

Binding affinities and geometries of various metal ligands in peptide deformylase inhibitors.

Removal of the N-terminal formyl group from newly synthesized proteins by the enzyme peptide deformylase (PDF) is essential for normal growth of bacteria but not higher organisms. Recently, PDF has been explored as a target for novel antibiotics. Screening a collection of natural products for antimicrobial activity identified actinonin and two matlystatin analogs as potent PDF inhibitors. A number of synthetic analogs of these natural products were prepared and their inhibitory potency determined. Previous work has shown that PDF is an iron metalloproteinase also containing a catalytic glutamic acid residue. Ligation of the ferrous cation is an essential feature of potent inhibitors. The structures of actinonin, a matlystatin analog and a synthetic inhibitor complexed with PDF were determined by crystallography. A quantum mechanics/molecular mechanics (QM/MM) method was used to reproduce the geometry of known complexes, to predict the protonation state in the active site and to predict the geometry of additional complexes. The requirement for protonation of the active site glutamate anion is an important factor in understanding the potency of inhibitors with acidic iron-ligating groups such as hydroxamate and carboxylate. Even though potent inhibitors of PDF have been discovered, their bacteriostatic mechanism of action and the rapid development of resistance in vitro may limit their potential as antibacterial drugs.

Amidohydrolases↗

PubMed2002

Different Mg to Fe ratios in the mixed metal MgFe hydroxy-carbonate compounds and the effect on phosphate binding compared with established phosphate binders.

Due to the side effects of the current oral phosphate binders, there is a need for effective alternatives. A number of mixed metal hydroxy-carbonate compounds (MMHCs) based on Mg and Fe have recently been established as effective phosphate binders. We have now carried out further studies on the MMHCs with different ratios of Mg(2+):Fe(3+) in different forms to assess for phosphate binding efficacy and ionic release in aqueous solution and food slurries. The compounds that provide the most promise are those with Mg(2+):Fe(3+) ratios of 2:1 and 4:1 in the unaged/dry form. Their phosphate binding efficacy was compared with a wide range of established phosphate binders, such as aluminum hydroxide [Al(OH)(3)], calcium carbonate (CaCO(3)), calcium acetate (CaAc(2)), magnesium hydroxide [Mg(OH)(2)], and lanthanum carbonate [La(2)(CO(3))(3)] in various food slurries. The results showed that the MgFe compounds were much more effective (on a weight for weight basis) than the established binders, and their properties were relatively pH independent. Calcium compounds (CaCO(3) and CaAc(2)) were ineffective under the experimental conditions. Mg(OH)(2) was effective at low pH but not at pHs greater than 5.0, and also released two- to threefold more magnesium than the MgFe compounds. Al(OH)(3) showed some degree of efficacy, but the binding capacity was, at best, less than 50% of the MMHCs. La(2)(CO(3))(3) required at least a 10-fold increase in weight to give comparable binding to the MMHCs. In conclusion, MgFe hydroxy-carbonate compounds are effective phosphate binders and may provide a better alternative to both existing and emerging binders for combating hyperphosphataemia.

Binding Sites↗

PubMed2002

Investigation of a novel preparation of testosterone decanoate in men: pharmacokinetics and spermatogenic suppression with etonogestrel implants.

We have investigated the pharmacokinetics and effects on the male reproductive axis of a novel preparation of testosterone decanoate (TD) with a progestogen implant. Twenty healthy Chinese men were administered TD (400 mg intramuscular 4 weekly) with two subcutaneous (SC) etonogestrel implants. Trough testosterone concentrations rose with repeated administration. Peak concentrations 1 week after the fourth injection were 31 +/- 2 nmol/liter. Both LH and FSH were rapidly suppressed and continued to fall during treatment. Spermatogenesis was also suppressed, to <or=1 x 10(6)/mL in all men with 16 (80%) azoospermic at 12 weeks. Treatment was associated with an increase in weight, and also increases in hemoglobin concentration (9%) and hematocrit (15%). No subjects withdrew from the study, although the study was terminated after subjects had completed 12 to 18 weeks as some men were found to have elevated liver enzyme tests. These data demonstrate that the pharmacokinetics of TD are improved compared to previous injectable testosterone preparations, although peak testosterone concentrations rise briefly into the supraphysiological range. The speed and degree of spermatogenic suppression suggest that this combination has promise as an effective male contraceptive.

Adult↗

PubMed2002

Analysis of HCV-immunoglobulin isotype complexes provide new insights into antibody response to HCV.

Hepatitis C virus (HCV) is known for its ability to establish persistent infection and cause chronic hepatitis in most infected individuals. The antibody response to HCV in HCV-circulating immune complexes (CIC) is unknown. In the present study, we have characterized distinct changes in patterns of HCV-immunoglobulin (Ig) constituents with disease category, viral mutation and clinical markers. The number of samples positive for single HCV-Ig, HCV-IgG and HCV-IgA, HCV-IgM and HCV-IgA, HCV-IgM and HCV-IgG, HCV-IgM, HCV-IgG and HCV-IgA in 47 samples tested were 8 (17%), 1 (2.1%), 9 (19.1%), 4 (8.5%) and 17 (36.2%), respectively. The occurrence of HCV-IgM and HCV-IgA in combination of two isotypes of HCV-Ig became predominant. These results show that defective IgG in HCV-CIC may contribute to long-term viremia. Further analysis indicated that the frequency of HCV RNA/IgA-CIC in the abnormal aspartic aminotransferase (AST) group was significantly higher than that of the normal AST group, and HCV RNA/IgA-CIC frequency in the abnormal alanine aminotransferase (ALT) group was slightly higher than that in the normal ALT group. IgA complexes may reflect the damage degree of liver function during the course of HCV infection. We also found that there were more mutations in supernatant than in other constituents from single-strand conformation polymorphism (SSCP) analysis. Our results suggest that Ig-complexed virions and free virions may have different biological consequences, with the latter being elusive to immunological elimination. The findings in this study may provide some new insights into antibody response to HCV.

Adolescent↗

PubMed2002

Analysis of complement-bound HCV complexes using a novel immuno-capture RT-PCR method.

Recently, more and more evidence has supported the hypothesis that liver cell injury was immune-mediated in patients with hepatitis C virus (HCV) infection, and that circulating immune complexes (CICs) might play a role in the pathogenesis of chronic hepatitis C (HC). In the present study, we have combined immuno-capture and reverse transcriptase-polymerase chain reaction (RT-PCR), and developed a quick method of high specificity for the detection of complement-bound HCV-CIC. We found that there were higher frequencies of HCV-C1q CIC than that of HCV-factor B, and there was a deviation of complement from immunoglobulin (Ig) in HCV-CIC. These findings suggest that immuno-capture RT-PCR (iRT-PCR) for the detection of HCV-bound CIC is a valuable method for the analysis of the composition of the immune complexes, and for the understanding of host immune response and immune pathogenesis in HCV-infected individuals.

Adolescent↗

PubMed2002

Oral desogestrel with testosterone pellets induces consistent suppression of spermatogenesis to azoospermia in both Caucasian and Chinese men.

BACKGROUND: Effective hormonal male contraception requires a high prevalence of spermatogenic suppression, which has proved particularly difficult in Caucasian populations. We have investigated the combination of oral desogestrel with depot testosterone in Caucasian and Chinese men. METHOD: Thirty men in Edinburgh and 36 men in Shanghai received 150 or 300 microg desogestrel p.o. daily for 24 weeks with 400 mg testosterone pellets s.c. on day 1 and at 12 weeks. RESULTS: Eight men withdrew before completing 24 weeks treatment. Testosterone concentrations remained within the normal range. Spermatogenesis was profoundly suppressed in all men. Azoospermia was achieved by a higher proportion of men in the 300 microg desogestrel group: 28/28 men versus 22/31 men (P < 0.05). All Caucasian men in the 150 microg group achieved sperm concentrations of < 1 x 10(6)/ml whereas three men in the Shanghai group maintained sperm concentrations of > 3 x 10(6)/ml. Fifteen men continued on this regimen for a subsequent 24 weeks: all remained azoospermic for the duration of treatment. High-density lipoprotein cholesterol fell by 15% in Caucasian men, but was unchanged in the Chinese men; both groups showed some weight gain. CONCLUSION: This combination of oral desogestrel with depot testosterone maintains physiological testosterone concentrations with consistent suppression of spermatogenesis to azoospermia in both Caucasian and Chinese men and therefore has many of the properties necessary for a contraceptive preparation for men.

Administration, Oral↗

PubMed2002

A new high sensitivity thermoluminescent phosphor with low residual signal and good stability to heat treatment: LiF:Mg,Cu,Na,Si.

The preliminary investigations are reported on the characteristics of a new, high-sensitivity thermoluminescence phosphor material (LiF:Mg,Cu,Na,Si) prepared in this laboratory. The main dosimetric peak of this phosphor occurs at 197 degrees C at a heating rate of 1 degrees C.s(-1). The glow curve shape shows minimal differences and sensitivity remains stable when annealed in the range from 250 to 280 degrees C for 10 min. Its TL sensitivity to gamma radiation is about 30 times higher than that of TLD-100 with a residual signal 0.2% following a 260 degrees C readout at a heating rate of 15 degrees C.s(-1). This negligible residual signal renders LiF:Mg,Cu,Na,Si usable in unannealed form. Its TL response at both 260 degrees C and 280 degrees C are reproducible within a coefficient of variation of 2% over ten re-use cycles without systematic decrease. It retains the main advantages of LiF:Mg,Cu,P phosphor, and has a lower residual signal and a better stability to heat treatment.

Copper↗

PubMed2002

Comparative study of trapping parameters and repeatability of LiF:Mg,Cu,P (GR-200A) from different production batches.

Distinct differences in repeatability between two different production batches had been observed. The results are presented of an investigation into the change of sensitivity of LiF:Mg,Cu,P originating from 7 different production batches prepared during 1994 to 2000 after repeated usage. Computerised glow curve analysis has been used to determine the trapping parameters of these thermoluminescent materials. The sensitivity in LiF:Mg,Cu,P for all investigated batches remains stable after repeated usage. The maxima of glow peaks 2 to 4 are found at the same temperature within very small limits. The activation energy and frequency of glow peaks 2 to 4 vary little from batch to batch. For all investigated peaks, no correlation has been found between glow sensitivity and trapping parameters. The peak areas of glow peaks 3 and 4 originating from 4 batches prepared during 1996 to 2000 are significantly larger than that of the other three batches. The GR-200A LiF:Mg,Cu,P has been improved dramatically in recent years.

Copper↗

PubMed2002

Influence of readout parameters on TL response, re-usability and residual signal in LiF:Mg,Cu,P.

It has recently been recommended that heating rates do not exceed 10 K.s(-1) and that the maximum temperature of readout should not exceed 265 degrees C for LiF:Mg,Cu,P. In some cases, a decrease of sensitivity in this material in the first of several re-use cycles had been reported. Influence of heating rates up to 30 K.s(-1), duration time up to 40s and maximum readout temperatures up to 270 degrees C on TL response, re-usability and residual signal was investigated. It was found that the maximum readout temperatures above 240 degrees C may lead to the thermoluminscent response decrease in the first several re-use cycles. The readout parameters can be optimised to minimise the residual signal (less than 0.4%) and to retain a constant sensitivity at the same time at high heating rates up to 30 K.s(-1) in a short time (less than 1 min per TL chip) without the necessity of heating above 240 degrees C. A concept of 'efficient residual signal' was put forward to quantify more accurately the real residual signal which affects the precision of the next measurement.

Copper↗

PubMed2002

New advances in LiF:Mg,Cu,P TLDs (GR-200A).

In order to volume-produce LiF:Mg,Cu,P TLDs, increase the repeatability of preparation technology and further improve the features of TLDs, especially the moisture resistant property and the accuracy in ultra-low dose, the prescription and preparation techniques have been investigated further in recent years. The main features of GR-200A have been improved dramatically by adding a chemical additive and adopting a particular preparation technology. Recent improvements are presented including prescription, preparation technology, TL sensitivity, signal-to-noise rate, detection threshold, residual signal, the moisture resistant property and the uncertainty in low dose measurements. The sensitivity of GR-200A has been increased to 65 times as high as TLD-100 from the original 29 times. The residual signal has been decreased to less than 1% from the original of about 2.5% following 240 degrees C readout. The detection threshold decreases and the signal-to-noise ratio increases. The uncertainty in low dose measurements is reduced significantly. The resistance to humidity has been improved remarkably. The preparation technology to volume-produce GR-200A is stable.

Copper↗

PubMed2002

Spatial distribution of indoor aerosol deposition under accidental release conditions.

Indoor aerosol dispersion and particle deposition was investigated using a series of puff releases of nonspecific activatable tracers simulating an accidental source. Initial particle size distribution included the respirable range, with most of the particles between 0.5 to 5.0 microm. Tracers were released in a nuclear laboratory/work environment and were collected via passive collector foils to obtain the spatial distribution of deposition. The observed distribution characteristics did not always correspond to the measured air flow patterns, and they showed a non-negligible dependence on aerosol dynamics such as thermophoretic effects. The collected data represent integrated deposition flux, which can serve for validation of aerosol dynamics models that aim to predict the deposition fluence of particles and may also be used for planning surface contamination surveys following accidental releases.

Accidents, Occupational↗

PubMed2002

Mutations of the UMOD gene are responsible for medullary cystic kidney disease 2 and familial juvenile hyperuricaemic nephropathy.

INTRODUCTION: Medullary cystic kidney disease 2 (MCKD2) and familial juvenile hyperuricaemic nephropathy (FJHN) are both autosomal dominant renal diseases characterised by juvenile onset of hyperuricaemia, gout, and progressive renal failure. Clinical features of both conditions vary in presence and severity. Often definitive diagnosis is possible only after significant pathology has occurred. Genetic linkage studies have localised genes for both conditions to overlapping regions of chromosome 16p11-p13. These clinical and genetic findings suggest that these conditions may be allelic. AIM: To identify the gene and associated mutation(s) responsible for FJHN and MCKD2. METHODS: Two large, multigenerational families segregating FJHN were studied by genetic linkage and haplotype analyses to sublocalise the chromosome 16p FJHN gene locus. To permit refinement of the candidate interval and localisation of candidate genes, an integrated physical and genetic map of the candidate region was developed. DNA sequencing of candidate genes was performed to detect mutations in subjects affected with FJHN (three unrelated families) and MCKD2 (one family). RESULTS: We identified four novel uromodulin (UMOD) gene mutations that segregate with the disease phenotype in three families with FJHN and in one family with MCKD2. CONCLUSION: These data provide the first direct evidence that MCKD2 and FJHN arise from mutation of the UMOD gene and are allelic disorders. UMOD is a GPI anchored glycoprotein and the most abundant protein in normal urine. We postulate that mutation of UMOD disrupts the tertiary structure of UMOD and is responsible for the clinical changes of interstitial renal disease, polyuria, and hyperuricaemia found in MCKD2 and FJHN.

Alleles↗

PubMed2002

Expression of a novel reticulon-like gene in human testis.

Identification of genes that are specifically expressed in the adult testis or the fetal testis is important for the study of genes related to the development of the testis. In this study, a human testis cDNA microarray was established. PCR products of 9216 clones from a human testis cDNA library were dotted on a nylon membrane; mRNA from adult and fetal testes were purified and probes were prepared by a reverse transcription reaction with testis mRNA as template. The microarray was hybridized with probes of adult and fetal testes, and 96.8 and 95.4% of clones were positive, respectively. In total, 731 clones were differentially expressed: 592 were highly expressed in adult testis and 139 were highly expressed in fetal testis. Among these genes, a new reticulon (Rtn)-like gene was detected and named Rtn-T. Rtn-T was highly expressed in adult human testis. The cDNA of Rtn-T contains 3491 bp and the putative protein had 968 amino acids. This protein is homologous to the six known members of the Rtn family (KIAA0886, Rtn xL, reticulon 4a, Nogo-A, Nogo-A short form, and brain my043) but was different at the 5' end. All homologues originate from one gene, and result from both different promotor regions and different splicing. Rtn-T lacks the first exon and contains a second exon that is lacking in the other homologues. Rtn-T is shorter than KIAA0886, Rtn xL, reticulon 4a and Nogo-A, but longer than the Nogo-A short form and brain my043. Sequence analysis showed that Rtn-T protein has two hydrophobic regions that may be membrane-spanning domains. Expression profiles showed that Rtn-T is specifically and strongly expressed in testis. The results of the present study indicate that the Rtn-T gene is differentially expressed in adult and fetal testes and encodes a membrane protein that may have a function in testis development.

Adult↗

PubMed2001

A putative flavin electron transport pathway is differentially utilized in Xenopus CRY1 and CRY2.

Xenopus laevis cryptochromes (xCRYs) can suppress xCLOCK/xBMAL1-mediated activation of a period E box-containing promoter. This suppression is a crucial part of the vertebrate circadian oscillator. Similar to CRYs in other species, as well as to the closely related photolyases, xCRYs have a conserved flavin binding domain. We show here that an intact flavin binding domain is required for normal function. However, it appears that each xCRY may utilize the bound flavin differently. Mutation in any of the three conserved tryptophan residues in the putative electron transport chain inhibits xCRY2b function, while only the mutation in the last of the three tryptophans significantly affects xCRY1 function. Although knockout studies in mice have suggested that CRY1 and CRY2 are not totally redundant, this is the first time that molecular/biochemical differences between CRY1 and CRY2 have been demonstrated. Both CRYs seem to require an intact flavin binding domain, suggesting that electron transport is important in their ability to suppress CLOCK/BMAL1 activation. However, only xCRY2b appears to depend on electron transport through the conserved tryptophan pathway.

Animals↗

PubMed2001

[Implantation of skeletal muscle stem cells in inhibition of fibroatrophy of ischemic myocardium: an experimental study].

OBJECTIVE: To investigate the effect of stem cells derived from autogenous skeletal muscle, namely satellite cells, and implanted into ischemic myocardium on inhibition of myocardium fibroatrophy. METHODS: The left anterodecendant arteries (LAD) of 12 adult dogs were ligated so as to establish animal model of acute myocardiac infarction. Satellite cells isolated from the greatest gluteal muscle of dogs were labeled with 4' 6-dimidino-2-phenylindone (DAPI), and then infused into the ventricular myocardium of the isogenic dogs through LAD. Specimens of ischemic myocardium were taken 2, 4, and 8 weeks after myoblast implantation. Histologic sections are examined under common light microscope and fluorescent microscope. Twelve dogs were used as controls. RESULTS: In the ischemic myocardium where satellite cells had been implanted, fibroaastrophy was efeectively inhibited. The implanted satellite cells had differentiated into fully developed striated muscle cells. Vitreous degeneration and disorder of basic structure could be observed in the ischemic myocardium in the control group. CONCLUSION: The satellite cells from autologous skeletal muscle differentiate into cardiac muscle cell-like cells in the ischemic area and inhibit fibroatrophy of the ischemic myocardium after implantation, thus bringing a hope of a new cure for myocardial damage.

Animals↗