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Biomedical subjects

H Zhou

Publications and source records attributed to H Zhou.

At least 37 records · Page 2Linked to original sources

Manipulation of the induction of adjuvant arthritis in Sprague-Dawley rats.

OBJECTIVE: To investigate the roles of various variables in the induction of adjuvant-induced arthritis (AIA) in the outbred Sprague-Dawley (SD) rats, and further characterize its arthritic features by comprehensive examinations. METHODS: The roles of different preparative techniques, inoculation routes and doses of Mycobacterium tuberculosis (MT) suspension as well as the sex preference in the induction of AIA were comparatively studied using clinical assessment. The hind paws of animals were analyzed by radiological and histological examinations. The serum levels of cytokines interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha were determined by ELISA. RESULTS: The particle size and dose of MT played a dominant role in the induction and severity of AIA. Male rats manifested markedly more severe arthritic signs than female rats. After subcutaneously inoculated with 500 microg MT, male rats developed pronounced arthritis with 100% incidence and low variable clinical signs. Even using only 62.5 microg MT, AIA was efficiently induced in male rats and characterized by upregulated expression profiles of IL-1beta, IL-6 and TNF-alpha. CONCLUSIONS: Since outbred SD rats are much cheaper and more readily available than Lewis rats, this well-developed SD rat AIA model is an efficient and cost-effective arthritis model available for screening novel anti-arthritic agents.

Animals↗

[Nodular lesions of liver parenchyma caused by pathological vascularisation/perfusion].

Nodular regenerative hyperplasia (NRH) is characterized by a non-cirrhotic micronodular transformation of the liver parenchyma. It is based on the obliteration of small portal veins. Macroregenerative nodules (MRN) develop in areas of favourable blood flow in otherwise hypoperfused liver tissue. Hypoperfusion is caused by obliteration of liver veins and/or large portal veins with the subsequent atrophy or extinction of parenchyma. The hyperperfused and sometimes rapidly growing MRN might simulate a malignant tumor in CT and MRT. Morphologically, MRN resemble FNH. In contrast to hepatocellular adenoma, they show a more or less nodular architecture with fibrous septa and ductular structures. NRH and cases of MRN without cirrhosis can indicate an extrahepatic/systemic disease causing altered liver perfusion. MRN in liver cirrhosis must be differentiated from dysplastic nodules and highly differentiated hepatocellular carcinoma by cytological and microarchitectural criteria. Focal nodular hyperplasia (FNH) can imitate liver cirrhosis, steatohepatitis, cholangitis or chronic hepatitis, if biopsy material does not include normal perilesional liver tissue. Telangiectatic FNH might resemble classic hepatocellular adenoma. Neoductular structures and septation argue for this rare subtype of FNH. Neoductular transformation of hypoperfused liver parenchyma might imitate cholangioma or cholangiocarcinoma.

Humans↗

Collection, storage, preservation, and normalization of human urinary exosomes for biomarker discovery.

Urinary exosomes containing apical membrane and intracellular fluid are normally secreted into the urine from all nephron segments, and may carry protein markers of renal dysfunction and structural injury. We studied methods for collection, storage, and preservation of urinary exosomal proteins. We collected urine from healthy volunteers, added protease inhibitors, and stored urine samples at 4, -20, and -80 degrees C for 1 week or 7 months. Samples were thawed with and without extensive vortexing, and three fractions were isolated: urinary sediment, supernatant, and exosome fraction. Protein concentration, electrophoresis patterns, and abundance of seven exosome-associated proteins were measured. Exosome-associated proteins were not detected in sediment or supernatant fractions. Protease inhibitors prevented degradation of exosome-associated proteins. Freezing at -20 degrees C caused a major loss in exosomes compared to fresh urine. In contrast, recovery after freezing at -80 degrees C was almost complete. Extensive vortexing after thawing markedly increased exosome recovery in urine frozen at -20 or -80 degrees C, even if frozen for 7 months. The recovery from first and second morning urine was similar. The abundance of cytosolic exosome-associated proteins did not decrease during long-term storage. We concluded: (1) protease inhibitors are essential for preservation; (2) storage at -80 degrees C with extensive vortexing after thawing maximizes the recovery of urinary exosomes; (3) the difference between first and second morning urine exosome-associated protein was small, suggesting minimal protein degradation in the urinary tract/bladder; (4) urinary exosomes remain intact during long-term storage. These urine collection, storage, and processing conditions may be useful for future biomarker discovery efforts.

Biomarkers↗

Simvastatin improves sepsis-induced mortality and acute kidney injury via renal vascular effects.

Acute kidney injury (AKI) occurs in about half of patients in septic shock and the mortality of AKI with sepsis is extremely high. An effective therapeutic intervention is urgently required. Statins are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors that also have pleiotropic actions. They have been reported to increase the survival of septic or infectious patients. But the effect of simvastatin, a widely used statin, on sepsis-induced AKI is unknown. The effects of simvastatin and tumor necrosis factor (TNF)-alpha neutralizing antibody were studied in a clinically relevant model of sepsis-induced AKI using cecal ligation and puncture (CLP) in elderly mice. Simvastatin significantly improved CLP-induced mortality and AKI. Simvastatin attenuated CLP-induced tubular damage and reversed CLP-induced reduction of intrarenal microvascular perfusion and renal tubular hypoxia at 24 h. Simvastatin also restored towards normal CLP-induced renal vascular protein leak and serum TNF-alpha. Neither delayed simvastatin therapy nor TNF-alpha neutralizing antibody improved CLP-induced AKI. Simvastatin improved sepsis-induced AKI by direct effects on the renal vasculature, reversal of tubular hypoxia, and had a systemic anti-inflammatory effect.

Acute Kidney Injury↗

Marek's disease virus-induced transient paralysis is associated with cytokine gene expression in the nervous system.

Marek's disease (MD)-associated transient paralysis (TP) was experimentally induced in chickens by intraperitoneal inoculation of RB1B strain of Marek's disease virus (MDV). Between 7 and 11 days post-infection (d.p.i.), neck and limb paralysis was observed in 18% of infected chickens, which was associated with various degrees of edema, vacuolation, perivascular cuffing of mononuclear cells, and glial cell infiltration mainly in the cerebrum, cerebellum, and brain stem. The chickens that were infected but did not progress to develop TP until 12 d.p.i. also had similar lesions suggestive of encephalitis in the cerebrum, cerebellum, and brain stem. Chickens infected with MDV had more interleukin (IL)-6, IL-12, and interferon (IFN)-gamma in their brain tissues compared to uninfected chickens. Moreover, IL-18 was significantly increased in brain tissues of birds showing clinical signs of TP compared to uninfected birds. Importantly, the expression of IL-6, IL-18, and IFN- gamma in brain tissues of MDV-infected chickens with signs of TP was significantly increased compared to that in asymptomatic MDV-infected birds. MDV genome load in the brain of chickens showing clinical signs of TP was higher than that in asymptomatic MDV-infected chickens but was not statistically significant. The lesions in the cervical, thoracic, and lumbar spinal cord segments in MDVinfected chickens were characterized mainly by perivascular cuffing of mononuclear cells irrespective of the group. The expression of mRNA for IL-18 and IFN-gamma genes was not significantly different in spinal cord tissues of chickens with TP compared to clinically normal, MDV-infected and noninfected chickens. These results suggest possible underlying immunologic mechanisms for MDV-induced TP.

Animals↗

Transcriptional analysis of host responses to Marek's disease viral infection.

This study was aimed at investigating the genes that control host responses to Marek's disease virus (MDV). Spleen tissues from infected and age-matched uninfected control chickens were examined 4, 7, 14, and 21 d postinfection for gene expression differences, using both microarray and quantitative real-time polymerase chain reaction (PCR) methodologies. Up to 51% of genes assayed during microarray analysis showed a significant change (p < or = 0.05) in expression after MDV infection, of which cell surface molecules, transcription and signal transduction molecules, housekeeping and metabolism mediators, and cytokines and cytokine receptors were most commonly differentially expressed. Setting a fold change threshold (> or =2), 14 of 84 genes showed differential expression over time. In addition, some genes showed differential expression at more than one time point. For example, the granzyme-A homolog gene remained upregulated in infected chickens, with fold changes of 7.98, 13.91, and 9.07 at 7, 14, and 21 d postinfection, respectively. Other genes that were differentially expressed at more than one time point were invariant chain, IgM, and CD3. Quantitative real-time PCR analysis was used to validate microarray results for a subset of genes showing a :2-fold change in expression. Expression of all but one gene (CD28) was confirmed. Identification of genetic mechanisms initiated by in vivo infection with MDV expands the current understanding of immune response to the virus in addition to host response elements associated with viral pathogenesis.

Animals↗

Genome-wide linkage analysis to identify chromosomal regions affecting phenotypic traits in the chicken. I. Growth and average daily gain.

A genome scan was used to detect chromosomal regions and QTL that control quantitative traits of economic importance in chickens. Two unique F(2) crosses generated from a commercial broiler male line and 2 genetically distinct inbred lines (Leghorn and Fayoumi) were used to identify QTL affecting BW and daily average gain traits in chickens. Body weight at 2, 4, 6, and 8 wk was measured in the 2 F(2) crosses. Birds were genotyped for 269 microsatellite markers across the entire genome. Linkage distance among microsatellite markers was estimated by the CRIMAP program. The program QTL Express was used for QTL detection. Significance levels were obtained using the permutation test. For the 8 traits, a total of 18 and 13 significant QTL were detected at a 1% chromosome-wise significance level, of which 17 and 10 were significant at the 5% genome-wise level for the broiler-Leghorn cross and broiler-Fayoumi cross, respectively. Highly correlated growth traits showed similar QTL profiles within each cross but different QTL profiles between the 2 crosses. Most QTL for growth traits in the current study were detected in Gga 1, 2, 4, 7, and 14 for the broiler-Leghorn cross and Gga 1, 2, 4, 5, 8, and 13 for the broiler-Fayoumi cross. Potential candidate genes within the QTL region for growth traits at 1% chromosome-wise significance level were discussed. The results in the current study lay the foundations for fine mapping these traits in the advanced intercross lines and provide a start point for identification causative genes responsible for growth traits in chickens.

Animals↗

Genome-wide linkage analysis to identify chromosomal regions affecting phenotypic traits in the chicken. II. Body composition.

Two informative chicken F(2) populations based on crosses between a broiler breeder male line and dams from genetically distinct, highly inbred (>99%) chicken lines, the Leghorn G-B2 and Fayoumi M15.2, have been used for genome-wide linkage and QTL analysis. Phenotypic data on 12 body composition traits (breast muscle weight, breast muscle weight percentage, abdominal fat weight, abdominal fat weight percentage, heart weight, heart weight percentage, liver weight, liver weight percentage, spleen weight, spleen weight percentage, and drumstick weight, and drumstick weight percentage) were collected. Birds were genotyped for 269 microsatellite markers across the genome. The QTL Express program was used to detect QTL for body composition traits. Significant levels were obtained using the permutation test. For the twelve traits, a total of 61 (Gga 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 15, 18, 24, and Z) and 45 (Gga 1, 2, 3, 4, 6, 7, 8, 9, 10, 12, 15, 17, and E46) significant QTL were detected at the 5% chromosome-wise significance level, of which 19 and 11 were significant at the 5% genome-wise level for the broiler-Leghorn cross and broiler-Fayoumi cross, respectively. Phenotypic variation for each trait explained by all QTL across the genome ranged from 3.22 to 33.31% in the broiler-Leghorn cross and 4.83 to 47.12% in broiler-Fayoumi cross. Distinct QTL profiles between the 2 crosses were observed for most traits. Cryptic alleles were detected for each trait. Potential candidate genes within the QTL region for body composition traits at the 1% chromosome-wise significance level were identified from databases for future association study. The results of the current study will increase the knowledge of genetic markers associated with body composition traits and aid the process of identifying causative genes. Knowledge of beneficial genetic variation can be incorporated in breeding programs to enhance genetic improvement through marker-assisted selection in chickens.

Animals↗

Diagnostic value of markers M2A, OCT3/4, AP-2gamma, PLAP and c-KIT in the detection of extragonadal seminomas.

AIMS: To compare the suitability of new seminoma markers including transcription factors AP-2gamma, OCT3/4 and M2A for detection of metastatic and extragonadal seminomas with the two well-known markers c-KIT and PLAP. MATERIALS AND METHODS: The immunohistochemical distribution of PLAP, c-KIT, M2A, AP-2gamma and OCT3/4 was examined in two pineal germinomas, 28 metastatic seminomas and 10 of their testicular primaries. Evaluation of specificity was achieved by additional tissue array studies on 75 malignancies other than germ cell tumours (GCT). Clinical data including serum PLAP were available in 18 patients. RESULTS: Compared with other markers, significantly better staining results were observed with antibodies to M2A and AP-2gamma in all seminomatous GCT. In contrast, the staining pattern with antibodies to c-KIT, PLAP and OCT3/4 was variable or absent. The lowest specificity was obtained with c-KIT, which was expressed in a variety of non-GCT. The only M2A+ mesothelioma expressed no other seminoma markers. No correlation between serum PLAP level and tissue PLAP expression was found. CONCLUSIONS: M2A and AP-2gamma are the most sensitive markers for seminoma metastases or primary extragonadal seminomas. Combination of these markers provides highly specific and clear results for detection of a seminomatous GCT.

Adult↗

Dynamic distribution of Thr3-phosphorylated histone H3 in CHO cells in mitosis.

The phosphorylation of histone H3 at Ser10, Ser28, Thr11 and Thr3 of the amino terminal has been proved related to mitosis of the mammalian cells. However, the function of the Thr3 phosphorylation of H3 remains unclear. In this study, indirect immunofluorescence labelling and laser confocal microscopy were used to examine the cellular dynamic distribution of Thr3-phosphorylated H3 at mitosis in CHO cells. The results showed that the Thr3 phosphorylation began at early prophase and spread throughout the chromosomes at late prophase. At metaphase, most of the Thr3-phosphorylated H3 was distributed along the entire chromosomal arms and maintained until early anaphase. During late anaphase and telophase, the fluorescent signal of Thr3-phosphorylated H3 disappeared from chromosomes. There was a precise spatial and temporal correlation between H3 phosphorylation of Thr3 and stages of chromatin condensation. The timing of Thr3 phosphorylation and dephosphorylation in mitosis were similar to that reported for Thr11 phosphorylation of H3. The Thr3-phosphorylated H3 localized along the arms of chromosomes during metaphase and early anaphase. It was different from the Ser10-phosphorylated H3, which localized at telomere regions, and Thr11-phosphorylated H3, which localized at centromeres. The results suggest that the Thr3 phosphorylation of histone H3 may play a specific role, which is different from Ser10 phosphorylation and Thr11 phosphorylation in mitosis.

Animals↗

Minicore myopathy with ophthalmoplegia caused by mutations in the ryanodine receptor type 1 gene.

BACKGROUND: Minicore myopathy (multi-minicore disease [MmD]) is a congenital myopathy characterized by multifocal areas with loss of oxidative activity on muscle biopsy. MmD is clinically heterogeneous and distinct phenotypes have been associated with recessive mutations in either the selenoprotein N (SEPN1) or the skeletal muscle ryanodine receptor (RYR1) gene, also implicated in central core disease and malignant hyperthermia. External ophthalmoplegia is an additional finding in a subset of patients with MmD. OBJECTIVE: To clinically and genetically examine families with MmD and external ophthalmoplegia. METHODS: The authors investigated 11 affected individuals from 5 unrelated families. Clinical, histopathologic, and imaging studies were performed and RYR1 haplotyping and mutational analysis were carried out. RESULTS: All patients had multiple cores involving the entire fiber diameter on longitudinal sections. Weakness and wasting in the shoulder girdle, scoliosis, moderate respiratory impairment, and feeding difficulties were prominent. In contrast to SEPN1-related myopathies, soleus was more severely affected than gastrocnemius on muscle MRI. Haplotyping suggested linkage to the RYR1 locus in informative families and mutational screening revealed four novel RYR1 mutations in three unrelated families; in addition, functional haploinsufficiency was found in one allele of two recessive cases. CONCLUSION: These findings expand the phenotypic spectrum associated with mutations in the skeletal muscle ryanodine receptor (RYR1) gene. Recessive mutations of domains commonly affected in malignant hyperthermia appear to be particularly prevalent in multi-minicore disease with external ophthalmoplegia and might suggest a different pathomechanism from that involved in central core disease.

Adolescent↗

Coarse-grained free-energy-functional treatment of quasistatic multiscale processes in heterogeneous materials.

A new treatment of quasistatic (reversible) multiscale processes in heterogeneous materials at nonzero temperature is presented. The system is coarse grained by means of a finite-element mesh. The coarse-grained free-energy functional (of the positions of the nodes of the mesh) appropriate to the thermodynamic-state variables controlled in the relevant process is minimized. Tests of the new procedure on a Lennard-Jonesium crystal yield thermomechanical properties in good agreement with the "exact" atomistic results.

Journal Article↗

Spatial statistical modeling of disease outbreaks with particular reference to the UK foot and mouth disease (FMD) epidemic of 2001.

In this paper we examine issues relating to the analysis of spatially-referenced disease data. Initially, we discuss the use of exploratory statistical tools such as density estimation and nonparametric regression. We then consider the need for descriptive epidemic models in space, time, and space-time models for epidemic dynamics. Implicitly space-time must be considered in any analysis of the spatial structure of epidemics. The use of Bayesian models for disease spread is discussed and applied to the recent foot and mouth outbreak in the UK.

Animals↗

Convenient anaerobic techniques, science from the supermarket shelf.

We describe the application and evaluation of a widely available commercial jar as an anaerobic container suitable for the growth of a wide variety of anaerobes. A system for generating stable anaerobiosis was developed by combining standard anaerobic environment generators with Click-Clack jars produced by Click-Clack Ltd. This system was simple, reliable, and reduced capital outlay on anaerobic jars by at least an order of magnitude.

Bacteria, Anaerobic↗

Heterogeneity in codon usages of sobemovirus genes.

When conventional phylogenetic trees were built using 14 genome sequences of 9 sobemoviruses, two main lineages were apparent: monocot-infecting viruses and dicot-infecting viruses. To investigate whether members of the genus Sobemovirus originated from monocot hosts or from dicot hosts, we constructed relationship trees based on Relative Synonymous Codon Usage (RSCU) of the viruses. The RSCU relationship trees grouped the monocot-infecting and dicot-infecting viruses even better than the genome phylogenetic trees. The RSCU approach also enabled direct comparisons among viral and host species. When host species were added into the RSCU tree, the viral species clustered with the monocot hosts, indicating codon usage homologies to monocots. The stability of the RSCU tree was improved when RSCU values were calculated for individual viral open reading frames (ORFs). Most interestingly, the codon usages of the viral ORF-2 that encodes the replicase showed affinity to that of the plants whereas codon usages of the other viral ORFs were not relevant to the host species. All ORF-2s from 3 monocot viruses and 4 out of 6 dicot viruses had greater RSCU affinities to sequences of ORFs in monocot than to dicot hosts, possibly indicating that ORF-2, and therefore the replicase module of sobemovirus has a monocot origin.

Arabidopsis↗

An investigation of valence shell orbital momentum profiles of difluoromethane by binary (e,2e) spectroscopy.

The electron binding energy spectra and momentum profiles of the valence orbitals of difluoromethane, also known as HFC32 (HFC-hydrofluorocarbon) (CH(2)F(2)), have been studied by using a high resolution (e,2e) electron momentum spectrometer, at an impact energy of 1200 eV plus the binding energy, and by using symmetric noncoplanar kinematics. The experimental momentum profiles of the outer valence orbitals and 4a(1) inner valence orbital are compared with the theoretical momentum distributions calculated using Hartree-Fock and density functional theory (DFT) methods with various basis sets. In general, the shapes of the experimental momentum distributions are well described by both the Hartree-Fock and DFT calculations when large and diffuse basis sets are used. However, the result also shows that it is hard to choose the different calculations for some orbitals, including the methods and the size of the basis sets employed. The pole strength of the ionization peak from the 4a(1) inner valence orbital is estimated.

Journal Article↗