Biomedical subjects

H Zhou

Publications and source records attributed to H Zhou.

At least 73 records · Page 4Linked to original sources

PubMed2004

Grafts of immortalized chromaffin cells bio-engineered to improve met-enkephalin release also reduce formalin-evoked c-fos expression in rat spinal cord.

Transplantation of adrenal medullary tissue for terminal cancer pain has been tested clinically, but this approach is not practical for routine use because of the shortage of organ donors and lack of tissue homogeneity. As a first alternative step, we have generated immortalized chromaffin cells over-expressing opioid peptides, namely met-enkephalin. Rat chromaffin cells have been genetically modified with vectors containing expression cassettes with either synthetic met-enkephalin or pro-enkephalin gene coding regions, fused with the nerve growth factor signal peptide for secretion. After stable transfection and differentiation in vitro, met-enkephalin and pro-enkephalin cells had higher met-enkephalin immunoreactivity and secreted met-enkephalin levels, compared to control cells containing the expression vector only. In the formalin hindpaw-injection model, 15 days after subarachnoid transplant of cells, grafts of met-enkephalin and pro-enkephalin cells significantly reduced the number of formalin-evoked c-fos immunoreactive spinal neurons in the spinal cord, compared to grafts of vector-alone chromaffin cells. The use of such expandable cell lines, for chronic spinal delivery of opiates, could offer an attractive and safe alternative strategy based on ex vivo gene therapy for the control of opioid-sensitive chronic pain.

Analysis of Variance↗

PubMed2004

Contribution of anal scent gland and urinary odorants to mate recognition in the ferret.

Previous research [J. Neurosci. 21 (2001) 5832-5840] showed that ferrets of both sexes require olfactory signals to identify opposite-sex mating partners at a distance. The present experiments assessed the contributions of anal scent gland and urinary odorants to these preferences. Sexually experienced, ovohysterectomized female and castrated male ferrets were injected daily with estradiol benzoate and testosterone propionate, respectively. When tested in an airtight Y-maze, subjects of both sexes preferred to approach volatile odors emitted from opposite- versus same-sex stimulus ferrets that were anesthetized and placed in the goal boxes, regardless of whether the anal scent glands of stimulus ferrets had been surgically removed or left intact. Subjects of each sex showed an equal preference to approach volatile odors emitted from anesthetized opposite-sex ferrets that were scent-gland intact as opposed to descented. Female subjects preferred to approach volatile anal scent gland odorants, as well as urinary odorants from male, as opposed to female conspecifics. Male subjects preferred to approach volatile anal scents from females versus males; however, males showed no preference for female over male urinary odorants. Our results suggest that anal scent gland odorants are sufficient, but not required, for mate recognition in the ferret. Instead, a combination of body odorants including, but not restricted to, those derived from anal scent gland secretions apparently underlie olfactory sex discrimination and partner preference in this carnivore.

Animals↗

PubMed2004

In vivo mammary tumourigenesis in the Sprague-Dawley rat and microdosimetric correlates.

Standard methods for risk assessments resulting from human exposures to mixed radiation fields in Space consisting of different particle types and energies rely upon quality factors. These are generally defined as a function of linear energy transfer (LET) and are assumed to be proportional to the risk. In this approach, it is further assumed that the risks for single exposures from each of the radiation types add linearly. Although risks of cancer from acute exposures to photon radiations have been measured in humans, quality factors for protons and ions of heavier atomic mass are generally inferred from animal and/or cellular data. Because only a small amount of data exists for such particles, this group has been examining tumourigenesis initiated by energetic protons and iron ions. In this study, 741 female Sprague-Dawley rats were irradiated or sham irradiated at approximately 60 days of age with 250 MeV protons, 1 GeV/nucleon iron ions or both protons and iron ions. The results suggest that the risk of mammary tumours in the rats sequentially irradiated with 1 GeV/nucleon 56Fe ions and 250 MeV protons is less than additive. These data in conjunction with earlier results further suggest that risk assessments in terms of only mean LETs of the primary cosmic rays may be insufficient to accurately evaluate the relative risks of each type of particle in a radiation field of mixed radiation qualities.

Animals↗

PubMed2004

Onset and rate of striatal atrophy in preclinical Huntington disease.

BACKGROUND: Huntington disease (HD) is characterized by striatal atrophy that begins long before the onset of motor symptoms. OBJECTIVE: To determine when striatal atrophy begins, the extent and rate of atrophy before diagnosis of motor symptoms, and whether striatal atrophy can predict when symptom onset will occur. METHODS: Caudate and putamen volumes were measured on MRI scans of 19 preclinical subjects with the HD gene expansion who were very far (9 to 20 years) from estimated onset, and on serial scans from 17 preclinical subjects, six of whom were diagnosed with HD within 5 years after the initial scan. RESULTS: Striatal volumes were significantly smaller for the subjects who were very far from estimated onset than for age-matched control subjects. Statistical models fit to the longitudinal data suggest that rate of caudate atrophy becomes significant when subjects are approximately 11 years from estimated onset and rate of putamen atrophy becomes significant approximately 9 years prior to onset. In the six incident cases, caudate and putamen were approximately one-third to one-half of normal volume at diagnosis, and caudate volume alone was able to predict with 100% accuracy those subjects who would be diagnosed within 2 years of imaging. CONCLUSIONS: Striatal atrophy begins many years prior to diagnosable HD, and assessment of atrophy on MRI may be very useful in both predicting HD onset and in tracking progression in future therapeutic trials in preclinical subjects.

Adult↗

PubMed2004

MoViES: molecular vibrations evaluation server for analysis of fluctuational dynamics of proteins and nucleic acids.

Analysis of vibrational motions and thermal fluctuational dynamics is a widely used approach for studying structural, dynamic and functional properties of proteins and nucleic acids. Development of a freely accessible web server for computation of vibrational and thermal fluctuational dynamics of biomolecules is thus useful for facilitating the relevant studies. We have developed a computer program for computing vibrational normal modes and thermal fluctuational properties of proteins and nucleic acids and applied it in several studies. In our program, vibrational normal modes are computed by using modified AMBER molecular mechanics force fields, and thermal fluctuational properties are computed by means of a self-consistent harmonic approximation method. A web version of our program, MoViES (Molecular Vibrations Evaluation Server), was set up to facilitate the use of our program to study vibrational dynamics of proteins and nucleic acids. This software was tested on selected proteins, which show that the computed normal modes and thermal fluctuational bond disruption probabilities are consistent with experimental findings and other normal mode computations. MoViES can be accessed at http://ang.cz3.nus.edu.sg/cgi-bin/prog/norm.pl.

Computational Biology↗

PubMed2004

TRMP: a database of therapeutically relevant multiple pathways.

UNLABELLED: Disease processes often involve crosstalks between proteins in different pathways. Different proteins have been used as separate therapeutic targets for the same disease. Synergetic targeting of multiple targets has been explored in combination therapy of a number of diseases. Potential harmful interactions of multiple targeting have also been closely studied. To facilitate mechanistic study of drug actions and a more comprehensive understanding the relationship between different targets of the same disease, it is useful to develop a database of known therapeutically relevant multiple pathways (TRMPs). Information about non-target proteins and natural small molecules involved in these pathways also provides useful hint for searching new therapeutic targets and facilitate the understanding of how therapeutic targets interact with other molecules in performing specific tasks. The TRMPs database is designed to provide information about such multiple pathways along with related therapeutic targets, corresponding drugs/ligands, targeted disease conditions, constituent individual pathways, structural and functional information about each protein in the pathways. Cross links to other databases are also introduced to facilitate the access of information about individual pathways and proteins. AVAILABILITY: This database can be accessed at http://bidd.nus.edu.sg/group/trmp/trmp.asp and it currently contains 11 entries of multiple pathways, 97 entries of individual pathways, 120 targets covering 72 disease conditions together with 120 sets of drugs directed at each of these targets. Each entry can be retrieved through multiple methods including multiple pathway name, individual pathway name and disease name. SUPPLEMENTARY INFORMATION: http://bidd.nus.edu.sg/group/trmp/sm.pdf

Biomarkers↗

PubMed2004

Ultrasound organometry: the importance of body height adjusted normal ranges in assessing liver and spleen parameters among Chinese subjects with Schistosoma japonicum infection.

Hepatosplenic measurements among 550 Chinese subjects, aged 3-59 years from Yueyang city--a nonendemic area for schistosomiasis in Hunan province, China--were performed to define normal ranges of ultrasound organometry for assessing hepatosplenic morbidity in Schistosoma japonicum infection. Measurements included the size of the liver (left lobe and right lobe), the main portal vein stem, the peripheral periportal vein branches, and spleen length and thickness. The results document the significant relationship between body height and organometric parameters. The reference values stratified by body height improve the accuracy of assessment. Thus, height-based normal ranges established in this study can be applied in hospital routine and in field studies of patients infected with S. japonicum in Hunan province and in other endemic areas of China.

Adolescent↗

PubMed2004

Radiation-induced bystander effect and adaptive response in mammalian cells.

Two conflicting phenomena, bystander effect and adaptive response, are important in determining the biological responses at low doses of radiation and have the potential to impact the shape of the dose-response relationship. Using the Columbia University charged-particle microbeam and the highly sensitive AL cell mutagenic assay, we show here that non-irradiated cells acquire mutagenesis through direct contact with cells whose nuclei have been traversed with a single alpha particle each. Pretreatment of cells with a low dose of X-rays four hours before alpha particle irradiation significantly decreased this bystander mutagenic response. Results from the present study address some of the fundamental issues regarding both the actual target and radiation dose effect and can contribute to our current understanding in radiation risk assessment.

Acetylcysteine↗

PubMed2004

Kinase- and rapsyn-independent activities of the muscle-specific kinase (MuSK).

The muscle-specific receptor tyrosine kinase (MuSK) is co-localized with nicotinic acetylcholine receptors (AChRs) in the postsynaptic membrane of the skeletal neuromuscular junction, and is required for all known aspects of postsynaptic differentiation. Studies in vitro have shown that Z(+)-agrin, a nerve-derived proteoglycan, activates MuSK's kinase activity to promote clustering of AChRs and MuSK itself with a cytoplasmic, receptor-associated protein, rapsyn. These studies, however, have used soluble forms of agrin, whereas agrin is cell- or matrix-attached in vivo. We show here that immobilized (particle- or cell-attached) agrin but not soluble agrin is able to aggregate MuSK in the absence of rapsyn and that this aggregation does not require MuSK's kinase activity but does require MuSK's cytoplasmic domain. Moreover, immobilized agrin can promote clustering of AChRs by a mechanism that requires MuSK and rapsyn but does not require MuSK's kinase activity. These results imply that rapsyn and signaling components activated by MuSK kinase may be dispensable for some early aspects of postsynaptic differentiation.

Agrin↗

PubMed2004

Effect of age on the incidence of venous thromboembolism after major surgery.

BACKGROUND: Most guidelines for administration of thromboprophylaxis after major surgery use age as a major predictor of postoperative venous thromboembolism (VTE). We sought to quantify the effect of age on the risk of symptomatic VTE after a spectrum of surgical procedures. METHODS: Using the California Patient Discharge Data Set and specific ICD-9-CM surgical procedure codes, we retrospectively determined the incidence of VTE diagnosed within 91 days after 40 different urgent or elective surgeries performed in the hospital between 1992 and 1996. Logistic regression was used to quantify the effect of age on the incidence of postoperative VTE and to adjust for other risk factors. RESULTS: 1,464,452 cases underwent one of 40 different procedures (mean cases per procedure = 35,718, range 4500-145 500). There was a significant interaction between age and the type of surgery performed (P<0.0001). Qualitative analysis of the effect of age on the incidence of VTE stratified by the presence or absence of malignancy revealed three general patterns: a steady increase in the incidence of VTE with age, exemplified by appendectomy or cholecystectomy; an increase in VTE up to approximately age 65 with no increase thereafter, exemplified by total hip arthroplasty; and no effect of age on the incidence of VTE, exemplified by vascular surgery. CONCLUSIONS: The relationship between age and the risk of VTE after surgery is complex and depends on the nature of the surgery and the underlying pathologic process. Advancing age was a significant predictor for VTE following surgeries performed for conditions not inherently associated with significant comorbidity. Conversely, advancing age was not associated with a higher incidence of VTE after surgeries performed for conditions strongly associated with serious underlying comorbidity, such as a malignancy or severe peripheral vascular disease.

Adult↗

PubMed2004

[Diagnostic imaging of vascular leiomyosarcomas].

Primary vascular leiomyosarcomas are very rare tumors, with the venous variety most often arising from the inferior caval vein and the arterial variety from the pulmonary artery. The tumors show either an exclusive intra- or extravascular pattern or a mixed growth pattern. The clinical symptoms depend on tumor location, with intraluminal tumors of the inferior caval vein causing edema or a Budd-Chiari syndrome. Leiomyosarcomas of the pulmonary artery can mimic chronic central or recurrent peripheral pulmonary embolism. Contrast enhanced spiral CT with multiplanar reconstruction is the diagnostic method of choice when a vascular leiomyosarcoma is suspected. MRI with MR-angiography can be added. If a tumor of undetermined origin shows a broad contact with a vessel and/or an intraluminal component, possible primary vascular leiomyosarcoma should be included in the differential diagnosis.

Budd-Chiari Syndrome↗

PubMed2004

Wound infection due to Absidia corymbifera and Candida albicans with fatal outcome.

A case of a mixed infection due to Candida albicans and the zygomycete Absidia corymbifera in a 38-year-old, previously healthy, Caucasian male is presented. The infection developed following serial rib fractures, and ruptures of kidney, liver and biliary tract as well as a pancreatic contusion resulting from a traffic accident. During intensive care treatment the patient underwent several surgical procedures but subsequently experienced multi-organ failure and sepsis. Some weeks later, fungal growth was observed macroscopically on the patient's skin and wounds. From wound swabs C. albicans and A. corymbifera were grown. Histopathology of abdominal tissue yielded pseudohyphae and coenocytic hyphae. Although surgical debridement and antifungal treatment with amphotericin B and 5-flucytosine were started immediately, the patient died in therapy-refractory septic multi-organ failure.

Absidia↗

PubMed2004

Polymer-carbon black composite sensors in an electronic nose for air-quality monitoring.

An electronic nose that uses an array of 32 polymer-carbon black composite sensors has been developed, trained, and tested. By selecting a variety of chemical functionalities in the polymers used to make sensors, it is possible to construct an array capable of identifying and quantifying a broad range of target compounds, such as alcohols and aromatics, and distinguishing isomers and enantiomers (mirror-image isomers). A model of the interaction between target molecules and the polymer-carbon black composite sensors is under development to aid in selecting the array members and to enable identification of compounds with responses not stored in the analysis library.

Air Conditioning↗

PubMed2004

Allelic polymorphism in the ovine DQA1 gene.

Variation in the ovine DQA1 gene was investigated by amplification of exon 2 using PCR, followed by single-strand conformational polymorphism (SSCP) analysis, cloning, and DNA sequencing. Fourteen novel SSCP patterns, representing 14 different sequences, were identified. Eight of these 14 sequences were identical to published DQA1 sequences from sheep, whereas the remaining six were novel but similar to the published DQA1 sequences from sheep and cattle. These six new sequences exhibited conserved region and variable region patterns similar to the published sheep DQA1 sequences, but were different than the published DQA2 sequences from sheep. All of these 14 putative sheep DQA1 sequences fulfilled the criteria used by the established bovine leukocyte antigens major histocompatibility complex nomenclature committee for assignment as new alleles. Comparison of the available DQA1 sequences from sheep and cattle revealed several clusters of ovine DQA1 sequences, and some sheep alleles were more similar to cattle alleles than other sheep alleles. The occurrence of trans-species polymorphism suggests the action of balancing selection at the DQA1 locus. Twenty-four percent of the nucleotide positions showed variation within exon 2, and this variation seems to have arisen largely by point mutation and gene conversion. The nonsynonymous and synonymous substitution rates were similar in both the putative antigen-binding site codons and the putative nonantigen-binding site codons. The extensive polymorphism reported in this article is consistent with polymorphism reported at the bovine DQA1 locus.

Alleles↗

PubMed2004

Diversity of the ovine DQA2 gene.

Variation in the ovine DQA2 gene was investigated in approximately 2,000 sheep from six breeds. Fragments of DNA containing the ovine DQA2 exon 2 were amplified using PCR. Single-strand conformational polymorphism analysis and DNA sequence analysis were employed to detect genetic variation. Twenty-three nucleic acid sequences, encoding 22 DQA2 amino acid sequences, were identified. This increases the number of alleles identified from 10 to 23. In some cases, three or four unique sequences were isolated from individual sheep, suggesting that these DQA2 sequences may represent two loci. Phylogenetic tree analysis revealed that 5 of these 23 sequences were more closely related to cattle DQA3 or DQA4 sequences than to other sheep DQA2 sequences. These sequences clustered together and were called DQA2-like to differentiate them from other DQA2 sequences. There was no evidence of DQA5-like sequences in sheep. Information theory-based analysis indicated that some of the DQA2-like sequences had low information content at splice sites, suggesting that these alleles may have low functional activity. Allelic lineages were observed not only at the DQA2 locus, but also at the DQA2-like locus, supporting the trans-species mode of evolution of MHC genes. Comparison of the allelic sequences suggests that polymorphism seems to have arisen largely by point mutation and gene conversion, and a recent gene conversion event seems to have occurred between the DQA2 and DQA2-like loci. The high level of sequence polymorphism detected and varied number of loci demonstrate the extensive diversity of the ovine DQA2 gene.

Alleles↗

PubMed2004

Population-based pharmacokinetics of the soluble TNFr etanercept: a clinical study in 43 patients with ankylosing spondylitis compared with post hoc data from patients with rheumatoid arthritis.

OBJECTIVE: The purpose of this study was to evaluate the pharmacokinetics of etanercept in patients with ankylosing spondylitis (AS) in a phase 3 study. METHODS: Serum etanercept concentrations were analyzed from samples obtained at weeks 4 and 12 from 43 patients with AS (median age: 45 years; median body weight: 75 kg; white/non-white: 40/3; male/female: 34/9) receiving 25 mg subcutaneously twice weekly for 12 weeks. A population pharmacokinetics analysis using NONMEM was conducted to estimate individual etanercept pharmacokinetic parameters. Initially, appropriate base and covariate population pharmacokinetic models were built based on data from 10 prior clinical studies of etanercept administered subcutaneously or intravenously to healthy subjects (n = 53) and to patients with rheumatoid arthritis (RA) (n = 212). The influence of demographic characteristics on the pharmacokinetics of etanercept was thoroughly evaluated. The stability of the final model was evaluated using both internal (bootstrapping) and external (data splitting) validation approaches. Finally, the selected final population covariate model was used to estimate the Bayesian pharmacokinetic parameters for the patients with AS. RESULTS: The data from the 10 prior clinical studies were optimally fitted to a 2-compartment linear population covariate model. Both age (< 17 years) and body weight (< 60 kg) were found to be important covariates on clearance. Both bootstrapping and data splitting validated the population model. The mean Bayesian-predicted etanercept clearance and steady-state trough concentration were 0.072 l/h and 2,004 ng/ml, respectively. The pharmacokinetic parameters of etanercept in the patients with AS were similar to those observed in the patients with RA. CONCLUSIONS: The pharmacokinetics of etanercept in patients with AS were similar to those in patients with RA. The AS disease state does not appear to alter the disposition of etanercept.

Adult↗

PubMed2003

Molecular modeling of polymer composite-analyte interactions in electronic nose sensors.

We report a molecular modeling study to investigate the polymer-carbon black (CB) composite-analyte interactions in resistive sensors. These sensors comprise the JPL electronic nose (ENose) sensing array developed for monitoring breathing air in human habitats. The polymer in the composite is modeled based on its stereoisomerism and sequence isomerism, while the CB is modeled as uncharged naphthalene rings with no hydrogens. The Dreiding 2.21 force field is used for the polymer, solvent molecules and graphite parameters are assigned to the carbon black atoms. A combination of molecular mechanics (MM) and molecular dynamics (NPT-MD and NVT-MD) techniques are used to obtain the equilibrium composite structure by inserting naphthalene rings in the polymer matrix. Polymers considered for this work include poly(4-vinylphenol), polyethylene oxide, and ethyl cellulose. Analytes studied are representative of both inorganic and organic compounds. The results are analyzed for the composite microstructure by calculating the radial distribution profiles as well as for the sensor response by predicting the interaction energies of the analytes with the composites.

Air Conditioning↗

PubMed2003

Fabrication and performance of a medium-dependent SiO2/Si photonic heterostructure device.

An optical device based on a photonic bandgap heterostructure is designed, fabricated, and characterized. The sample contains two sets of Si/SiO2 photonic crystals with different periods. When the device is working in air, it reflects omnidirectionally both TE and TM mode lights at the wavelength near 1.3 microm. The reflectivity measured in the bandgap is higher than 98% in an incident angle range 0 degrees-70 degrees. When the device is surrounded with silica (n > 1.33), it permits the total transmission for the TM mode but prevents the TE mode from propagating, thus behaving as a polarization splitter. The experimental extinction ratio of the reflected TE/TM is approximately 31 dB. The uniformity of the device performance over a large sample area is demonstrated.

Journal Article↗