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Biomedical subjects

J Yang

Publications and source records attributed to J Yang.

At least 127 records · Page 7Linked to original sources

Total synthesis of human and rat coupling factor-6 amide and pressor effects in the rat.

Mitochondrial coupling factor-6 (CF-6) is a component of the ATP synthase complex essential for energy transduction. CF-6, which is localized to the surface of endothelial cells (ECs) and released by shear stress, has been implicated as an endogenous vasoconstrictor. Previous methods of obtaining CF-6 through purification and recombinant methods were laborious and inefficient. Here, we describe the chemical synthesis of human CF-6, (33-108)-NH(2), its C-terminal fragment (55-108)-NH(2), which is termed pCF-6; the rat CF-6, (33-108)-NH(2), its C-terminal fragment pCF-6, (55-108)-NH(2); and two N-terminal fragments of the rat pro-coupling factor-6, (24-52)-NH(2) and (33-52)-NH(2). Biological activities of each peptide were initially screened with bioassays and verified by in vivo studies. Accordingly, intravenous administration of CF-6, pCF-6, rat CF-6, and rat pCF-6 produced a modest but statistically significant increase in blood pressure and heart rate in urethane anesthetized rats, whereas the N-terminal rat pro-coupling factor-6, (24-52)-NH(2) and (33-52)-NH(2) caused no significant pressor response. Thus, the biologically active site probably resides at the C-terminal portion of CF-6 peptides.

Amino Acid Sequence↗

Oscillating laminar electrokinetic flow in infinitely extended circular microchannels.

This article addresses the problem of oscillating laminar electrokinetic liquid flow in an infinitely extended circular microchannel. Based on the Debye-Huckel approximation for low surface potential at the channel wall, a complex variable approach is used to obtain an analytical solution for the flow. The complex counterparts of the flow rate and the current are linearly dependent on the pressure gradient and the external electric field. This property is used to show that Onsager's principle of reciprocity continues to be valid (involving the complex quantities) for the stated problem. During oscillating pressure-driven flow, the electroviscous effect for a given value of the normalized reciprocal electrical double-layer (EDL) thickness is observed to attain a maximum at a certain normalized frequency. In general, an increasing normalized frequency results in a reduction of EDL effects, leading to (i). a volumetric flow rate in the case of streaming potential approaching that predicted by the theory without EDL effects, and (ii). a reduction in the volumetric flow rate in the case of electroosmosis.

Journal Article↗

Oscillating laminar electrokinetic flow in infinitely extended rectangular microchannels.

This paper has addressed analytically the problem of laminar flow in microchannels with rectangular cross-section subjected to a time-dependent sinusoidal pressure gradient and a sinusoidal electric field. The analytical solution has been determined based on the Debye-Hückel approximation of a low surface potential at the channel wall. We have demonstrated that Onsager's principle of reciprocity is valid for this problem. Parametric studies of streaming potential have shown the dependence of the electroviscous effect not only on the Debye length, but also on the oscillation frequency and the microchannel width. Parametric studies of electroosmosis demonstrate that the flow rate decreases due to an increase in frequency. The obtained solutions for both the streaming potential and electroosmotic flows become those for flow between two parallel plates in the limit of a large aspect ratio.

Journal Article↗

The effect of epidermal growth factor on the incremental Young's moduli in the rat small intestine.

Biomechanical remodelling of the rat small intestine after treatment with epidermal growth factor (EGF) subcutaneously for 2 days (n=6), 4 days (n=6), 7 days (n=6), and 14 days (n=4) was studied. The incremental circumferential, longitudinal and cross moduli close to the in vivo state were computed from bi-axial test data (combined inflation and axial stretching) by a least square method. The moduli in the circumferential direction and the longitudinal direction differed in all groups, i.e. the mechanical properties were anisotropic in both normal and EGF-treated rats. Time-dependent variation existed for the Young's moduli in all directions during EGF treatment (P<0.05). The circumferential modulus decreased during the first 7 days of EGF treatment and it almost remodelled back to that of the control group after 14 days treatment. The incremental modulus in the circumferential direction ranged between 17.4 and 24.2 kPa. The modulus in the longitudinal direction ranged between 22.9 and 32.4 kPa. The longitudinal modulus after 4 days EGF treatment was significantly larger than that of control group (P<0.02). The cross modulus decreased during the first 4 days of EGF treatment thereafter it increased to a maximum at 7 days. The values for the cross moduli were between 4.7 and 6.6 kPa. In conclusion, the mechanical properties in the intestinal wall are anisotropic and remodel during treatment with EGF.

Adaptation, Physiological↗

Elements regulating angiogenesis and correlative microvessel density in benign hyperplastic and malignant prostate tissue.

PURPOSE: To quantify the ex vivo production of proangiogenic proteins (vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (tPA)) and angiogenesis inhibitors (plasminogen activator inhibitor type-1 (PAI-1) and angiostatin) from epithelial and stromal components of primary prostate cancer (CaP) and benign prostatic hyperplasia (BPH) cultures. To perform microvessel density (MVD) counts on sections of BPH and CaP from the same prostatectomy specimens. SCOPE: Angiogenic cytokine expression was measured by immunoassays and in vitro angiostatin generating capacities assessed using immunoblotting. CaP and BPH tissue was immunostained using factor VIII antibody to determine MVD. CONCLUSIONS: Elements regulating angiogenesis are present in both primary cultures of CaP and BPH, suggesting that angiogenic ability is well established in the absence of carcinoma.

Angiogenic Proteins↗

A new glycine substitution mutation in the COL7A1 gene in a Chinese family with dominant dystrophic epidermolysis bullosa.

Dystrophic epidermolysis bullosa (DEB) is caused by mutations in the COL7A1 gene encoding type VII collagen, the major component of anchoring fibrils. The characteristic genetic lesion in dominant DEB (DDEB) is a glycine substitution in the collagenous domain of the protein. In this study, we identified a Chinese family with a four-generation pedigree of DDEB, in whom a novel glycine substitution mutation in COL7A1 was demonstrated. A heterozygous nucleotide G-->A transition at position 6208 in exon 74 of COL7A1 was detected, which resulted in a glycine to arginine substitution (G2070R) in the triple-helical domain of type VII collagen. This substitution was not found in 110 unrelated normal alleles. This report emphasizes the predominance of glycine substitution mutations in DDEB and contributes to the expanding database on COL7A1 mutations.

Adolescent↗

Correlation between periodontal status and biting ability in Chinese adult population.

This study investigated the relation between periodontal condition and biting ability in a Chinese population using the pressure-detecting sheet. A total of 142 subjects residing in Nanchang, Jiangxi province, China, participated in the study. The examination included probing pocket depth (PD), clinical attachment level (CAL), bleeding on probing and coronal caries teeth. Biting abilities per person, biting force, biting pressure and occlusal contact area were measured using the sheet. Number of teeth present showed positive correlation with biting force and occlusal contact area, but were negatively correlated with biting pressure. No significant correlation was observed between the mean PD, percentage of pocket > or = 4 mm, bleeding index and any of biting abilities. The mean CAL showed a significantly negative correlation with biting force and occlusal contact area. Multiple stepwise regression analysis selected the number of teeth present, sex and age as the significant factors affecting the biting ability. However, no periodontal indices were picked up as the significantly contributing factor. There appears to be little effect of periodontal condition on biting ability. Ageing was selected as a contributing factor to reduction in the Chinese adults, but not in the Japanese population.

Adult↗

Two subtypes of hepatitis B virus-associated glomerulonephritis are associated with different HLA-DR2 alleles in Koreans.

Hepatitis B virus (HBV)-associated glomerulonephritis (HBV-GN) is occurring at high prevalence in most Asian endemic areas. There have been some reports on human leucocyte antigen (HLA) associations with HBV infections; however, HLA association with HBV-GN has been rarely reported. Forty-six adult Korean patients with HBV-GN (42 male and four female patients, age 20-66), 100 HBsAg (-) healthy controls, and 89 individuals with chronic HBV infection were studied for HLA-DRB1 and DQB1 gene polymorphisms using high-resolution DNA typing methods. In HBV-GN patients, a strong association with HLA-DR2 was observed compared with HBsAg (-) controls (OR = 4.0). Different HLA-DR2 alleles were associated with different pathologic subtypes of HBV-GN: DRB1*1502 with membranoproliferative glomerulonephritis (MPGN, n = 35) (OR = 14.5) and DRB1*1501 with membranous nephropathy (MN, n = 11) (OR = 3.8). HLA-DQB1*0601, strongly linked to DRB1*1502, was also associated with MPGN subtype of HBV-GN (OR = 4.3). All these associations were also significant compared with chronic HBV infection group. For chronic HBV infection per se, DRB1*1302, DQB1*0402, and DQB1*0604 had some protective effect (OR = 0.4, OR = 0.3, and OR = 0.1, respectively), and DRB1*1101 was weakly associated (OR = 4.6) in Koreans. These results suggest that HLA-DR or related genetic factor is associated with disease susceptibility to HBV-GN in Koreans, and different pathologic subtypes of HBV-GN are influenced by the genetic factors of the patients.

Adult↗

Functional brain mapping in freely moving rats during treadmill walking.

A dilemma in functional neuroimaging is that immobilization of the subject, necessary to avoid movement artifact, extinguishes all but the simplest behaviors. Recently, we developed an implantable microbolus infusion pump (MIP) that allows bolus injection of radiotracers by remote activation in freely moving, nontethered animals. The MIP is examined as a tool for brain mapping in rats during a locomotor task. Cerebral blood flow-related tissue radioactivity (CBF-TR) was measured using [14C]-iodoantipyrine with an indicator-fractionation method, followed by autoradiography. Rats exposed to walking on a treadmill, compared to quiescent controls, showed increases in CBF-TR in motor circuits (primary motor cortex, dorsolateral striatum, ventrolateral thalamus, midline cerebellum, copula pyramis, paramedian lobule), in primary somatosensory cortex mapping the forelimbs, hindlimbs and trunk, as well as in secondary visual cortex. These results support the use of implantable pumps as adjunct tools for functional neuroimaging of behaviors that cannot be elicited in restrained or tethered animals.

Animals↗

Interaction of the initiator protein of an IncB plasmid with its origin of DNA replication.

The replication initiator protein RepA of the IncB plasmid pMU720 was purified and used in DNase I protection assays in vitro. RepA protected a 68-bp region of the origin of replication of pMU720. This region, which lies immediately downstream of the DnaA box, contains four copies of the sequence motif 5'AANCNGCAA3'. Mutational analyses identified this sequence as the binding site specifically recognized by RepA (the RepA box). Binding of RepA to the RepA boxes was ordered and sequential, with the box closest to the DnaA binding site (box 1) occupied first and the most distant boxes (boxes 3 and 4) occupied last. However, only boxes 1, 2, and 4 were essential for origin activity, with box 3 playing a lesser role. Changing the spacing between box 1 and the other three boxes affected binding of RepA in vitro and origin activity in vivo, indicating that the RepA molecules bound to ori(B) interact with one another.

Bacterial Proteins↗

Shear modulus of porcine coronary artery: contributions of media and adventitia.

The epicardial coronary arteries experience significant torsion in the axial direction due to changes in the shape of the heart during the cardiac cycle. The objective of this study was to determine the torsional mechanical properties of the coronary arteries under various circumferential and longitudinal loadings. The coronary artery was treated as a two-layer composite vessel consisting of intima-medial and adventitial layers, and the shear modulus of each layer was determined. Eight porcine hearts were obtained at a local abattoir, and their right coronary and left anterior descending arteries were isolated and tested in vitro with a triaxial torsion machine (inflation, longitudinal stretch, and circumferential twist). After the intact vessel was tested, the adventitia was dissected away, leaving an intact media that was then tested under identical triaxial loading conditions. We proposed a biomechanical analysis to compute the shear modulus of the adventitia from the measured shear moduli of the intact vessel and the media. To validate our predictions, we used four additional hearts in which the shear modulus of the adventitia was measured after dissection of media. Our results show that the shear modulus does not depend on the shear stress or strain but varies linearly with circumferential and longitudinal stresses and in a nonlinear way with the corresponding strains. Furthermore, we found that the shear modulus of the adventitia is larger than that of the intact vessel, which is larger than the vessel media. These results may have important implications for baroreceptor sensitivity, circulation of the vasa vasorum, and coronary dissection.

Animals↗

Effects of oestrogen deficiency on rat mandibular and tibial microarchitecture.

OBJECTIVES: To investigate the effects of oestrogen deficiency on the microarchitecture of trabecular bone in the mandible and the tibia and to test whether they are correlated. METHODS: Twenty-four age-matched Lewis-Brown-Norway female rats underwent surgical intervention either to remove ovaries (ovariectomy, n=12) or to create a complementary control group (sham-operated, n=12). Sixteen weeks later, the animals were sacrificed and the left side of the mandibles and the tibias were scanned with high resolution micro-CT (15 micro m). Multiple morphological measures including the ratio of bone volume/tissue volume, trabecular thickness, trabecular separation and structure model index were obtained from the experimental and control groups. RESULTS: Ovariectomy significantly decreased the ratio of bone volume/soft tissue volume and trabecular thickness, whilst significantly increasing trabecular separation and structure model index in the mandible (P<0.005) and the tibia (P<0.005). There were significant positive correlations between the mandible and the tibia for trabecular separation (r=0.68, P<0.01) and structure model index (r=0.60, P<0.01). CONCLUSIONS: Oestrogen deficiency results in microarchitectural alterations of trabecular bone in both the mandible and the tibia within 16 weeks. The size of marrow spaces and the shape of trabeculae in the mandible correlate with osteoporotic changes in the long bone.

Animals↗

Recent developments on the role of mitochondria in poly(ADP-ribose) polymerase inhibition.

Numerous pathophysiological disorders involve some element of oxidative stress and bioenergetic deficit. Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors have been used recently as a promising new therapeutic strategy aimed at halting the bioenergetic decline associated with oxidative brain insults and other conditions. PARP-1 uses NAD+ as a substrate and is activated during stressful circumstances, mainly in the nucleus. PARP-1 inhibitors are well known for blocking the excessive consumption of NAD+, thereby preserving energy metabolism. But what is the role of mitochondria in this process? Recent investigations have begun to focus on whether mitochondrial function can also be preserved by PARP-1 inhibitors. This review will present some of the latest mechanistic evidence documenting the potential involvement of PARP-1 inhibitors in protecting mitochondrial function and preventing necrosis, apoptosis and mitochondrial calcium cycling.

Animals↗

Metalloprotease-specific poly(ethylene glycol) methyl ether-peptide-doxorubicin conjugate for targeting anticancer drug delivery based on angiogenesis.

This article proposes a novel cancer-targeting drug-delivery system based on angiogenesis, in which the enzymatic activity of type IV collagenases is used to cleave the inactive drug conjugate, thereby activating drug fragments. In this study, the amount and distribution of metalloprotease (MMP)-2 and MMP-9 secreted from Lewis lung carcinoma (LCC) cells and the formation of blood vessels were evaluated by gelatin zymography, in situ film zymography and immunostaining. LLC cells secreted MMP-2 and MMP-9, thereby distributing large amounts of MMPs around a solid tumor. The newly developed blood vessels were also found in a solid LLC tumor. The anticancer drug conjugate (mPEG-GPLGV-DOX) was synthesized by conjugating doxorubicin with Gly-Pro-Leu-Gly-Val (GPLGV) peptide and poly(ethylene glycol) methyl ether (mPEG). GPLGV pentapeptide was used as a substrate for MMP-2 and MMP-9, where the cleavage of Gly-Val bond by MMP was expected. In addition, mPEG was grafted to peptide-doxorubicin conjugate to increase the circulation time in the body and to reduce the cytotoxicity of the anticancer drug. The mPEG-GPLGV-DOX conjugate formed a micelle structure in aqueous solution, with a critical micelle concentration (CMC) of about 0.25 mg/ml and a diameter of 73.1 +/- 12.7 nm at 1 mg/ml. In an in vivo experiment, mPEG-GPLGV-DOX showed 20% chemotherapeutic activity compared with free doxorubicin. Although a 50 mg/kg dose of mPEG-GPLGV-DOX showed similar therapeutic effects to a 10 mg/kg dose of doxorubicin, the life span of mice in the conjugate group was significantly increased. Therefore, an efficient anticancer drug-delivery system could be created by increasing therapeutic efficiency and decreasing drug-toxicity by optimizing the degradation rate of the peptide link by MMP and circulation time in the body.

Angiogenesis Inhibitors↗

Introgression of a quantitative trait locus for yield from Glycine soja into commercial soybean cultivars.

The value of exotic germplasm in broadening the genetic base of most crops has been demonstrated many times. However, the difficulties involved in working with exotic germplasm have limited their utility in plant breeding. Unwanted linkages often thwart the successful incorporation of beneficial exotic genes into commercial lines. Thus, the use of exotics in traditional breeding makes the process of crop improvement a tedious, time-consuming and expensive endeavor. The availability of molecular markers makes it possible to isolate specific genomic regions and transfer them into commercial varieties with minimal linkage drag. We found a yield-enhancing quantitative trait locus (QTL) from Glycine soja (Siebold and Zucc.) by evaluating a population of 265 BC(2) individuals from a cross between HS-1 and PI 407305. The yield QTL was located on linkage group B2(U26) of the soybean [Glycine max (L.) Merrill] genetic linkage map. In a 2-year, multi-location study, individuals carrying the PI 407305 haplotype at the QTL locus demonstrated a 9.4% yield advantage over individuals that did not contain the exotic haplotype. When tested in a more uniform "HS-1-like" background in two locations, we observed an 8% yield advantage for lines that carry the PI 407305 haplotype. We further assessed the QTL effect in various elite soybean genetic backgrounds. The yield effect was consistently observed in only two of six genetic backgrounds. Individuals carrying the PI 407305 haplotype at the QTL locus had a 9% yield advantage in yield trials across locations. Despite the limited adaptability of this yield-QTL across genetic backgrounds, this study demonstrates the potential of exotic germplasm for yield enhancement in soybean.

Alleles↗

Scaling breakdown: a signature of aging.

We prove that the Lévy walk is characterized by bilinear scaling. This effect mirrors the existence of a form of aging that does not require the adoption of nonstationary conditions.

Journal Article↗