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Biomedical subjects

H Zhu

Publications and source records attributed to H Zhu.

At least 73 records · Page 4Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

[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↗

[The effect of estrogen receptor gene Px haplotype on bone mineral density in Chinese postmenopausal women].

OBJECTIVE: To investigate the relationship among the PvuII and XbaI polymorphism of estrogen receptor (ER) gene and bone mineral density (BMD, z-score) and bone biochemical markers in Chinese postmenopausal women. METHODS: The BMD of lumbar vertebrae (L2-4) and femoral neck (FN) of 186 postmenopausal women (aged 65.0 +/- 0.6 yr) were measured by DEXA. The polymorphism of ER gene (PvuII and XbaI) was detected by PCR-RFLP method. Serum AKP, BGP and urinary Pyd were measured by ELISA. Results The polymorphism of ER receptor can be divided into two sets: PP (14.5%), Pp (50.0%), and pp (35.5%); and 3 PvulI RFLPs and XX (7.0% ), Xx (27.4%), and xx (65.6%) 3 XbaI RFLPs. The bone markers were not significantly different among the 3 groups in each of the two sets of polymorphism. The FN BMD of women of pp genotype was higher than that of Pp genotype (P = 0.02). The BMD of 12-4 was higher in women of XX genotype than those in women of Xx and xx genotypes (P = 0.0003 and 0.0002 respectively). Women without Px haplotype (PPXX, PpXX, ppxx, n=79) had higher L2-4 BMD (P = 0.02) and FN BMD (P = 0.03) and lower serum AKP (P = 0.04) than those with Px genotype (PPxx and PPXx, Ppxx, PpXx, n=107). CONCLUSION: pp and XX genotype of ER gene may play a certain role in maintaining FN and L2-4 BMD. The genotypes without Px haplotype might exert some favorable effect on BMD, while those with Px haplotype may be harmful to bone

Aged↗

Morphine induces synchronous oscillatory discharges in the rat locus coeruleus.

The noradrenergic locus coeruleus (LC) plays a role in opioid dependence and withdrawal. In the present study, using a multiple-electrode recording technique that allowed several LC neurons to be recorded simultaneously over long time periods, LC neuronal activities were recorded before and after intracerebroventricular injection of morphine (26 nmol) under halothane anesthesia. We found that morphine did not simply decrease firing rates of LC neurons, as reported in earlier studies, but that it induced persistent oscillatory discharges in 49% (87 of 178) of the LC neurons recorded. Cross-correlation analysis revealed that almost all LC neurons (86 of 87) that exhibited oscillatory discharges were synchronized with at least one other neuron. When stated in terms of simultaneously recorded neuron pairs, 59% (292 of 492) of the oscillatory neuron pairs discharged synchronously. The morphine-induced synchronous oscillation began at approximately 10 min after morphine injection, reached its peak in approximately 20-30 min, persisted throughout the recording periods (up to 110 min after morphine injection, the longest recording time), and were reversed by an opioid receptor antagonist naltrexone. These data suggest that although the overall firing rate of LC neurons was reduced by morphine, the morphine-induced synchronous oscillatory activity may summate temporally and spatially at LC axon terminals and facilitate release of noradrenaline. Noradrenaline is an important neuromodulator and has been shown to induce and facilitate synaptic plasticity at LC target sites. We propose that the morphine-induced long-lasting synchronous oscillatory activity in the LC may be a neuronal signal that could induce synaptic plasticity leading to opioid addiction.

Action Potentials↗

Hyaluronan promotes CD44v3-Vav2 interaction with Grb2-p185(HER2) and induces Rac1 and Ras signaling during ovarian tumor cell migration and growth.

In this study we initially examined the interaction between CD44v3 (a hyaluronan (HA) receptor) and Vav2 (a guanine nucleotide exchange factor) in human ovarian tumor cells (SK-OV-3.ipl cell line). Immunological data indicate that both CD44v3 and Vav2 are expressed in SK-OV-3.ipl cells and that these two proteins are physically linked as a complex in vivo. By using recombinant fragments of Vav2 and in vitro binding assays, we have detected a specific binding interaction between the SH3-SH2-SH3 domain of Vav2 and the cytoplasmic domain of CD44. In addition, we have observed that the binding of HA to CD44v3 activates Vav2-mediated Rac1 signaling leading to ovarian tumor cell migration. Further analyses indicate that the adaptor molecule, growth factor receptor-bound protein 2 (Grb2) that is bound to p185(HER2) (an oncogene product), is also associated with the CD44v3-Vav2 complex. HA binding to SK-OV-3.ipl cells promotes recruitment of both Grb2 and p185(HER2) to the CD44v3-Vav2 complex leading to Ras activation and ovarian tumor cell growth. In order to determine the role of Grb2 in CD44v3 signaling, we have transfected SK-OV-3.ipl cells with Grb2 mutant cDNAs (e.g. Delta N-Grb2 that has a deletion in the amino-terminal SH3 domain or Delta C-Grb2 that has a deletion in the carboxyl-terminal SH3 domain). Our results clearly indicate that the SH3 domain deletion mutants of Grb2 (i.e. the Delta N-Grb2 (and to a lesser extent the Delta C-Grb2) mutant) not only block their association with p185(HER2) but also significantly impair their binding to the CD44v3-Vav2 complex and inhibit HA/CD44v3-induced ovarian tumor cell behaviors. Taken together, these findings strongly suggest that the interaction of CD44v3-Vav2 with Grb2-p185(HER2) plays an important role in the co-activation of both Rac1 and Ras signaling that is required for HA-mediated human ovarian tumor progression.

Adaptor Proteins, Signal Transducing↗

Peptide mass mapping constrained with stable isotope-tagged peptides for identification of protein mixtures.

Through proteolysis and peptide mass determination using mass spectrometry, a peptide mass map (PMM) can be generated for protein identification. However, insufficient peptide mass accuracy and protein sequence coverage limit the potential of the PMM approach for high-throughput, large-scale analysis of proteins. In our novel approach, nonlabile protons in particular amino acid residues were replaced with deuteriums to mass-tag proteins of the S. cerevisiae proteome in a sequence-specific manner. The resulting mass-tagged proteolytic peptides with characteristic mass-split patterns can be identified in the data search using constraints of both amino acid composition and mass-to-charge ratio. More importantly, the mass-tagged peptides can further act as internal calibrants with high confidence in a PMM to identify the parent proteins at modest mass accuracy and low sequence coverage. As a result, the specificity and accuracy of a PMM was greatly enhanced without the need for peptide sequencing or instrumental improvements to obtain increased mass accuracy. The power of PMM has been extended to the unambiguous identification of multiple proteins in a 1D SDS gel band including the identification of a membrane protein.

Amino Acid Sequence↗