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Biomedical subjects

J Hu

Publications and source records attributed to J Hu.

At least 19 recordsLinked to original sources

Callus formation enhanced by BMP-7 ex vivo gene therapy during distraction osteogenesis in rats.

This study was designed to observe the effects of bone morphogenetic protein-7 (BMP-7) ex vivo gene therapy on callus formation during rat mandibular distraction osteogenesis (DO). Fifty-four Sprague-Dawley rats underwent osteodistraction of the right mandible and were then randomly divided into three groups. Immediately after distraction, autologous bone marrow mesenchymal stem cells (MSCs) transfected with BMP-7, MSCs untransfected with BMP-7, and physiological saline were injected into the distraction gaps of the mandibles in groups A, B, and C, respectively. Nine animals from each group were euthanized at 2 and 6 weeks after completion of distraction. The distracted mandibles were removed and processed for radiographic, histological, immunohistochemical, and scanning electron microscopic examinations as well as Ca/P ratio analysis. Group A animals showed greater bone formation and earlier mineralization in the distracted callus when compared with group B. Similarly increased callus formation was found in group B than group C. Positive immunostaining of BMP-7 was observed in the distracted callus in all groups. However, BMP-7 expression was much stronger in group A compared with groups B and C. The results of this study suggest that BMP-7-mediated ex vivo gene transfer based on MSCs may accelerate callus formation in distraction osteogenesis and facilitate consolidation. Local gene therapy may ultimately be an alternative or supplemental approach to DO enhancement, especially for patients whose osteogenic potentials are compromised by diseases such as osteoporosis, severe trauma, and postoncologic irradiation.

Animals↗

Measurements and simulation of forest leaf area index and net primary productivity in Northern China.

Large scale process-based modeling is a useful approach to estimate distributions of global net primary productivity (NPP). In this paper, in order to validate an existing NPP model with observed data at site level, field experiments were conducted at three sites in northern China. One site is located in Qilian Mountain in Gansu Province, and the other two sites are in Changbaishan Natural Reserve and Dunhua County in Jilin Province. Detailed field experiments are discussed and field data are used to validate the simulated NPP. Remotely sensed images including Landsat Enhanced Thematic Mapper plus (ETM+, 30 m spatial resolution in visible and near infrared bands) and Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER, 15m spatial resolution in visible and near infrared bands) are used to derive maps of land cover, leaf area index, and biomass. Based on these maps, field measured data, soil texture and daily meteorological data, NPP of these sites are simulated for year 2001 with the boreal ecosystem productivity simulator (BEPS). The NPP in these sites ranges from 80 to 800 gCm(-2)a(-1). The observed NPP agrees well with the modeled NPP. This study suggests that BEPS can be used to estimate NPP in northern China if remotely sensed images of high spatial resolution are available.

Biomass↗

Dietary intake of fruit and vegetable and lung cancer risk: a case-control study in Harbin, northeast China.

BACKGROUND: We studied the relationship between dietary intake of vegetables and fruit and lung cancer risk in Harbin, Heilongjiang province, northeast China, an area with a very high baseline risk of lung cancer in both sexes. PATIENTS AND METHODS: We used data from a case-control study, conducted from 1987 to 1990, among 218 cases with incident, histologically confirmed lung cancer and 436 controls admitted to the same hospitals as cases with non-neoplastic, non-lung diseases unrelated to smoking and other potential risk factors for lung cancer. RESULTS: Compared with the lowest tertile of intake of vegetables, fruit or both, the multivariate odds ratios (ORs) for the highest tertile of intake were 0.39 [95% confidence interval (CI) 0.25-0.62], 0.73 (95% CI 0.48-1.11) and 0.40 (95% CI 0.25-0.63), respectively. In particular, high intake of Chinese cabbage (OR = 0.53), chives (OR = 0 .54), carrots (OR = 0.51) and celery (OR = 0.40) was inversely associated with lung cancer. The OR was more than six-fold elevated for smokers reporting low intake of vegetables, and more than four-fold elevated for smokers reporting low intake of fruit, as compared with never smokers reporting high intake of these items. CONCLUSION: In agreement with previous studies, we found an inverse relation between vegetable and fruit intake and lung cancer risk in both strata of current and never smokers.

Case-Control Studies↗

Changes in the inferior alveolar nerve following sagittal split ramus osteotomy in monkeys: a comparison of monocortical and bicortical fixation.

We aimed to observe the changes in the inferior alveolar nerve (IAN) after bilateral sagittal split ramus osteotomy (SSRO) using monocortical or bicortical screw fixation. Bilateral SSRO for setback of the mandible was done in 12 monkeys, and monocortical or bicortical fixation was applied on opposing sides of each mandible. Sensory nerve action potentials were tested before and immediately after operation, and at 2, 4, 8, and 12 weeks. Six animals selected randomly were killed at 4 and 12 weeks after the operation. Specimens of nerve were harvested and processed for histological examination and electron microscopic analysis. Obvious prolongation of latency and diminution of amplitude in the IAN were found postoperatively. At 4 weeks after operation, Wallerian degeneration was apparent, and there were signs of axonal regeneration in the nerves. The IAN had more abnormalities of evoked potentials and pathological changes after bicortical than after monocortical fixation. Although considerable recovery was found after both forms of fixation at 12 weeks, the function of the nerve after plate fixation was better than after screw fixation. Our results suggest that the nerve damage during SSRO could be temporary and reversible, and monocortical fixation may result in restoration of the nerve function sooner than bicortical fixation.

Action Potentials↗

A novel mitochondrial DNA missense mutation at G3421A in a family with maternally inherited diabetes and deafness.

OBJECTIVE: Mutations in mtDNA are thought to be responsible for the pathogenesis of maternally inherited diabetes. Here, we report a family with maternally inherited diabetes and deafness whose members did not harbour the mtDNA A3243G mutation, the most frequent point mutation in mitochondrial diabetic patients. This study aimed to investigate a possible other mtDNA mutation and its prevalence in type 2 diabetic patients. METHODS: Height, body weight, waistline, and hip circumference were measured and serum biochemical marks determined in all members of the family. In addition, a 75 g oral glucose tolerance test and electric listening test were conducted in these members. Genomic DNA was prepared from peripheral leukocytes. Direct sequencing of PCR products was used to detect the mtDNA mutation in this family. The prevalence of mtDNA G3421A nucleotide substitutions was investigated by restriction fragment length polymorphism analysis in 1350 unrelated type 2 diabetic patients recruited by random cluster sampling from the central city area of Shanghai, China. RESULTS: (1) A new missense homoplasmic mutation of mtDNA G3421A was found in a maternally inherited diabetic family and existed neither in 1350 unrelated type 2 diabetic patients nor in 50 non-diabetic individuals. (2) The mode of mutation and diabetes transmission was typical maternal inheritance in this family. (3) All diabetic family members were found to have an onset at 35-42 years of age, accompanied by deafness of varying degrees. CONCLUSION: mtDNA G3421A (Val39Ile) found in a family with maternally inherited diabetes and deafness is a novel missense mutation. Whether this is a diabetogenic mutation and its effect on mitochondrial function needs to be further studied.

Adolescent↗

A magnetoelastic resonance biosensor immobilized with polyclonal antibody for the detection of Salmonella typhimurium.

Mass-sensitive, magnetoelastic resonance sensors have a characteristic resonant frequency that can be determined by monitoring the magnetic flux emitted by the sensor in response to an applied, time varying, magnetic field. This magnetostrictive platform has a unique advantage over conventional sensor platforms in that measurement is wireless and remote. A biosensor for the detection of Salmonella typhimurium was constructed by immobilizing a polyclonal antibody (the bio-molecular recognition element) onto the surface of a magnetostrictive platform. The biosensor was then exposed to solutions containing S. typhimurium bacteria. Binding between the antibody and antigen (bacteria) occurred and the additional mass of the bound bacteria caused a shift in the sensor's resonant frequency. Sensors with different physical dimensions were exposed to different concentrations of S. typhimurium ranging from 10(2) to 10(9)CFU/ml. Detection limits of 5x10(3) CFU/ml, 10(5) CFU/ml and 10(7) CFU/ml were obtained for sensors with the size of 2 mmx0.4 mmx15 microm, 5 mmx1 mmx15 microm and 25 mmx5 mmx15 microm, respectively. Good agreement between the measured number of bound bacterial cells (as measured by scanning electron microscopy (SEM)) and frequency shifts was obtained.

Animals↗

PIPATH: an optimized algorithm for generating alpha-helical structures from PISEMA data.

An optimized algorithm for finding structures and assignments of solid-state NMR PISEMA data obtained from alpha-helical membrane proteins is presented. The description of this algorithm, PIPATH, is followed by an analysis of its performance on simulated PISEMA data derived from synthetic and experimental structures. pipath transforms the assignment problem into a path-finding problem for a directed graph, and then uses techniques of graph theory to efficiently find candidate assignments from a very large set of possibilities.

Algorithms↗

A proteomic analysis reveals the loss of expression of the cell death regulatory gene GRIM-19 in human renal cell carcinomas.

Gene associated with retinoid interferon-induced mortality (GRIM)-19, an inhibitor of transcription factor STAT3, was originally identified as a critical regulatory protein in a genetic screen that was designed to identify the gene products necessary for Interferon (IFN)-beta- and retinoic acid-induced cell death. Over expression of GRIM-19 activates cell death. Conversely, inactivation of its expression promotes cell growth. STAT3 is a transcription factor that regulates gene expression in response to multiple extra cellular growth factors. In contrast to its normal feedback inhibition, a constitutive activation of STAT3 has been documented in several tumors. Although many STAT3-inhibitors are described, their relevance to human cancer is unclear. In an attempt to define the molecular alterations associated with human renal cell carcinoma (RCC) using mass spectrometry, we have discovered that expression of GRIM-19 is lost or severely depressed in a number of primary RCC and in some urinogenital tumors. Using an RCC cell line, we show that down regulation of GRIM-19 promotes tumor growth via an augmentation of STAT3-dependent gene expression. These studies for the first time show a tumor-suppressor like activity of GRIM-19.

Apoptosis Regulatory Proteins↗

Iptakalim inhibits nicotinic acetylcholine receptor-mediated currents in dopamine neurons acutely dissociated from rat substantia nigra pars compacta.

Iptakalim hydrochloride, a novel cardiovascular ATP-sensitive K(+) (K(ATP)) channel opener, has shown remarkable antihypertensive and neuroprotective effects in a variety of studies using in vivo and in vitro preparations. We recently found that iptakalim blocked human alpha4-containing nicotinic acetylcholine receptors (nAChRs) heterologously expressed in the human SH-EP1 cell line. In the present study, we examined the effects of iptakalim on several neurotransmitter-induced current responses in single DA neurons freshly dissociated from rat substantia nigra pars compacta (SNc), using perforated patch-clamp recordings combined with a U-tube rapid drug application. In identified DA neurons under voltage-clamp configuration, glutamate-, NMDA-, and GABA-induced currents were insensitive to co-application with iptakalim (100 microM), while whole-cell currents induced by ACh (1 mM+1 microM atropine) or an alpha4beta2 nicotinic acetylcholine receptors relatively selective agonist, RJR-2403 (300 microM), were eliminated by iptakalim. Iptakalim inhibited RJR-2403-induced current in a concentration-dependent manner, and reduced maximal RJR-2403-induced currents at the highest agonist concentration, suggesting a non-competitive block. In current-clamp mode, iptakalim failed to affect resting membrane potential and spontaneous action potential firing, but abolished RJR-2403-induced neuronal firing acceleration. Together, these results indicate that in dissociated SNc DA neurons, alpha4-containing nAChRs, rather than ionotropic glutamate receptors, GABA(A) receptors or perhaps K-ATP channels are the sensitive targets to mediate iptakalim's pharmacological roles.

Acetylcholine↗

A new approach to repairing cleft palate and acquired palatal defects with distraction osteogenesis.

Cleft palate (CP) is one of the most common human congenital deformities, and acquired palate defects after trauma or tumour resection are also common. In this study, distraction osteogenesis (DO) for CP and other palatal bone defects was evaluated. Twenty cats were assigned randomly to 3 groups of (1) 15, (2) 3 and (3) 2 cats. In groups 1 and 2, a rectangular ostectomy, in the posterior of the palatal bone shelf, was performed in the sagittal axis to establish the CP defect model. At the same time, a pure titanium intraoral distractor was fixed to molar teeth with brackets and to the palatal bone shelf across the defect with titanium miniscrews bilaterally. Four weeks later, a secondary transport disc (TD) osteotomy was performed, and gradual DO treatment started at 0.4mm twice a day, after 6 days of latency. DO was performed until the TD reached the opposite margin over the gap in 5-6 days. Three cats each of group 1 were killed at 2, 4, 6, 8 and 12 weeks after completion of DO. In group 2, the bone and soft-tissue defects were untreated until death 6 weeks later. Group 3 cats (control) were killed after 6 weeks. The TD successfully recombined with the opposite palatal bone stump, and proportional expansion of the overlay mucoperiosteal flap was achieved. Intramembranous bone formation was revealed: parallel collagen bundles gradually deposited on new bone trabeculae while the proliferative osteoblasts produced bone matrix. The bone defect was finally reconstructed by de novo osteogenesis. The control group was observed to have no spontaneous repairing. These results suggest that the CP defect was reconstructed by osteogenesis in situ, and the soft tissues expanded simultaneously to achieve functional correction. The intraoral distractor provided both effective distraction and stability.

Animals↗

Measurement of two- and three-nucleon short-range correlation probabilities in nuclei.

The ratios of inclusive electron scattering cross sections of 4He, 12C, and 56Fe to 3He have been measured at 1 < xB <. At Q2 > 1.4 GeV2, the ratios exhibit two separate plateaus, at 1.5 < xB < 2 and at xB > 2.25. This pattern is predicted by models that include 2- and 3-nucleon short-range correlations (SRC). Relative to A = 3, the per-nucleon probabilities of 3-nucleon SRC are 2.3, 3.1, and 4.4 times larger for A = 4, 12, and 56. This is the first measurement of 3-nucleon SRC probabilities in nuclei.

Journal Article↗

Eta' photoproduction on the proton for photon energies from 1.527 to 2.227 GeV.

Differential cross sections for the reaction gamma p --> eta' p have been measured with the CLAS spectrometer and a tagged photon beam with energies from 1.527 to 2.227 GeV. The results reported here possess much greater accuracy than previous measurements. Analyses of these data suggest for the first time the coupling of the eta'N channel to both the S11(1535) and P11(1710) resonances, known to couple strongly to the etaN channel in photoproduction on the proton, and the importance of J = 3/2 resonances in the process.

Journal Article↗

Developmental changes in the expression of calbindin and potassium-channel subunits Kv3.1b and Kv3.2 in mouse Renshaw cells.

One class of spinal interneurons, the Renshaw cells, is able to discharge at very high frequencies in adult mammals. Neuronal firing at such high frequencies requires voltage-gated potassium channels to rapidly repolarize the membrane potential after each action potential. We sought to establish the pattern of expression of calbindin and potassium channels with Kv3.1b and Kv3.2 subunits in Renshaw cells at different developmental stages of postnatal mice. The pattern of expression of calbindin changed dramatically during early postnatal development. An adult pattern of calbindin reactive neurons started to emerge from postnatal day 10 to postnatal day 14, with cells in laminae I and II of superficial dorsal horn and the ventral lamina VII. Renshaw cells were identified immunohistochemically by their expression of calbindin and their location in the ventral horn of the spinal cord. Western blot results of the lumbar spinal cord showed that Kv3.1b expression became faintly evident from postnatal day 10, reached a maximum at postnatal day 21 and was maintained through postnatal day 49. Double labeling results showed that all Renshaw cells expressed Kv3.1b weakly from postnatal day 14, and strongly at postnatal day 21. Western blot results showed that Kv3.2 expression became detectable in the lumbar cord from postnatal day 12, and increased steadily until reaching an adult level at postnatal day 28. In contrast to the Kv3.1b results, Kv3.2 was not expressed in Renshaw cells, although some neurons located at laminae VIII and VI expressed Kv3.2. We conclude that Renshaw cells express Kv3.1b but not Kv3.2 from postnatal day 14.

Age Factors↗

Acellular extracellular matrix for inguinal hernia repair.

To investigate the clinical safety and effectiveness of acellular extracellular matrix (AEM) for inguinal hernia repair, 53 well-conducted and well-chosen sequential cases with inguinal hernia (56 inguinal hernias) were included in our multi-center study. All the inguinal hernias were repaired using conventional tension-free surgical procedures after being classified with Gilbert methods. No rejection was observed after operation. All the incisions healed well and no recurrence was found at the sixth month follow-up. At the seventh month after operation, one case of recurrence of right-side bilateral inguinal hernia (type IV) and another case of recurrence of left-side inguinal hernia (type V) were found. No other recurrence was observed at the 18th month follow-up. The AEM material has good histocompatibility and biomechanics characters and can be used for inguinal hernia repair. We observed no infection, chronic pain, funiculotesticular reaction, local nodular or feeling of discomfort after operation. But a further study of the usage of AEM in the repair of type IV and V inguinal hernias is still needed.

Adolescent↗

Intensity and mosaic spread analysis from PISEMA tensors in solid-state NMR.

The solid-state NMR experiment PISEMA, is a technique for determining structures of proteins, especially membrane proteins, from oriented samples. One method for determining the structure is to find orientations of local molecular frames (peptide planes) with respect to the unit magnetic field direction, B0. This is done using equations that compute the coordinates of this vector in the frames. This requires an analysis of the PISEMA function and its degeneracies. As a measure of the sensitivity of peptide plane orientations to the data, we use these equations to derive a formula for the intensity function in the powder pattern. With this function and other measures, we investigate the effect of small changes in peptide plane orientations depending on the location of the resonances in the powder pattern spectrum. This gives us an indication of the change in lineshape due to mosaic spread and a way to interpret these in terms of an orientational error bar.

Ion Channels↗

Unscheduled CDK1 activity in G1 phase of the cell cycle triggers apoptosis in X-irradiated lymphocytic leukemia cells.

Cyclin-dependent kinase 1 (CDK1) is a major component of the cell cycle progression engine. Recently, several investigations provided evidence demonstrating that unscheduled CDK1 activation may also be involved in apoptosis in cancerous cells. In this article, we demonstrate that X-ray irradiation induced G1 arrest in MOLT-4 lymphocytic leukemia cells, the arrest being accompanied by reduction in the activity of CDK2, but increased CDK1 activity and cell apoptosis in the G1 phase. Interestingly, this increase in CDK1 and apoptosis by ionizing radiation was prevented by pretreatment with the CDK1 inhibitor, roscovitine, suggesting that CDK1 kinase activity is required for radiation-induced apoptotic cell death in this model system. Furthermore, cyclin B1 and CDK1 were detected co-localizing and associating in G1 phase MOLT-4 cells, with the cellular lysates from these cells revealing a genotoxic stress-induced increase in CDK1 phosphorylation (Thr-161) and dephosphorylation (Tyr-15), as analyzed by postsorting immunoprecipitation and immunoblotting. Finally, X-irradiation was found to increase Bcl-2 phosphorylation in G1 phase cells. Taken together, these novel findings suggest that CDK1 is activated by unscheduled accumulation of cyclin B1 in G1 phase cells exposed to X-ray, and that CDK1 activation, at the wrong time and in the wrong phase, may directly or indirectly trigger a Bcl-2-dependent signaling pathway leading to apoptotic cell death in MOLT-4 cells.

Apoptosis↗