Biomedical subjects

Lu Wang

Publications and source records attributed to Lu Wang.

At least 73 records · Page 4Linked to original sources

PubMed2005

[Coexpression of human complement regulatory protein genes, CD59 and MCP in transgenic mice protects isolated mouse heart function in ex vivo human plasma perfusion model].

OBJECTIVE: To investigate if the expression of human complement regulatory protein genes in transgenic donor protects against hyperacute rejection (HAR) in the recipient. METHODS: Kunming mice were transfected with 2 human complement regulatory protein genes, CD59 and MCP, so as to establish a transgenic hCD59/hMCP mouse model. Eight hCD59 expression mice, 11 hMCP expression mice, and 8 hCD59/hMCP expression mice were used as experimental groups, and 10 transgenic negative littermates were used as control group. The hearts of the mice were taken out to be perfused with 10% pooled human blood of B type. During the perfusion electrocardiography was carried out to observe the beating time. After the hearts stopped beating, immunofluorescence staining and immunohistochemistry were used to detect the deposition of complements C(9) and C(3c) in the heart tissue. RESULTS: The mean heart beating time was 138 +/- 25 minutes in the hCD59/hMCP expression group, 78 +/- 27 minutes in the hCD59 expression group, 43 +/- 21 minutes in the hMCP group, and 20 +/- 12 minutes in the wild type nontransgenic control group (all P < 0.01, Dennett's T test for all 3 other groups relative to the hCD59/hMCP group). Deposition of the complement C(9) and that of C(3c) were not found in the hearts of the hCD59/hMCP group, however, could be found in the hearts of the 2 monotransgenic groups and nontransgenic group. CONCLUSION: The coexpression of human complement regulatory protein genes, CD59 and MCP in the xenografts effectively inhibits the complement of xenograft-mediated HAR.

Animals↗

PubMed2005

Improved solvent-free microwave extraction of essential oil from dried Cuminum cyminum L. and Zanthoxylum bungeanum Maxim.

Solvent-free microwave extraction (SFME) is a recently developed green technique which is performed in atmospheric conditions without adding any solvent or water. SFME has already been applied to extraction of essential oil from fresh plant materials or dried materials prior moistened. The essential oil is evaporated by the in situ water in the plant materials. In this paper, it was observed that an improved SFME, in which a kind of microwave absorption solid medium, such as carbonyl iron powders (CIP), was added and mixed with the sample, can be applied to extraction of essential oil from the dried plant materials without any pretreatment. Because the microwave absorption capacity of CIP is much better than that of water, the extraction time while using the improved SFME is no more than 30 min using a microwave power of 85 W. Compared to the conventional SFME, the advantages of improved SFME were to speed up the extraction rate and need no pretreatment. Improved SFME has been compared with conventional SFME, microwave-assisted hydrodistillation (MAHD) and conventional hydrodistillation (HD) for the extraction of essential oil from dried Cuminum cyminum L. and Zanthoxylum bungeanum Maxim. By using GC-MS system the compositions of essential oil extracted by applying four kinds of extraction methods were identified. There was no obvious difference in the quality of essential oils obtained by the four kinds of extraction methods.

Chromatography, Liquid↗

PubMed2005

Slit-like 2, a novel zebrafish slit homologue that might involve in zebrafish central neural and vascular morphogenesis.

Nervous and vascular systems grow as parallel networks, indicating common cues in distal targets. We have identified a novel zebrafish gene slit-like 2 (slitl2) that might involve in zebrafish central neural and vascular morphogenesis. Whole-mount in situ hybridization of zebrafish embryo detected distinct signals of slitl2 transcripts in zebrafish midline structure of central nervous system similar to that of slits. Strong expression is also observed in zebrafish vasculature. Zebrafish slitl2 shares amino acid sequence identity of 41% with Homo sapiens slitl2 (vasorin) and Mus musculus slitl2, and 35%, 33% with Danio rerio slit3, slit2. Analysis of zebrafish slitl2 cripto growth factor domain, extracellular matrix protein slit domain, and putative signal peptide confirms that as a secreted and cell-surface protein slitl2 may be essential in axon guidance, vessel development, and axis patterning. These results provide evidence that slitl2 may play important roles in zebrafish central nervous system and vascular morphogenesis.

Amino Acid Sequence↗

PubMed2005

Insulin promotes sinusoidal endothelial cell proliferation mediated by upregulation of vascular endothelial growth factor in regenerating rat liver after partial hepatectomy.

AIM: To determine whether insulin could promote sinusoidal endothelial cell (SEC) proliferation mediated by upregulation of vascular endothelial growth factor (VEGF) in regenerating rat liver after partial hepatectomy (PHx). METHODS: Adult male Sprague-Dawley rats undergoing 70% PHx were injected with insulin (300 MU/kg) or saline via the tail veins every 8 h after surgery for 7 d and killed at 0, 24, 48, 72, 96, 120, 144, and 168 h after surgery. Proliferation of both hepatocytes and SECs was monitored by evaluating the proliferating cell nuclear antigen (PCNA) labeling index (LI). The expression of VEGF protein was evaluated by immunohistochemistry. The mRNA expressions of VEGF and its receptors Flt-1 and Flk-1 were evaluated by semi-quantitative reverse transcription-PCR. RESULTS: Insulin markedly increased the expression of VEGF mRNA between 24 and 120 h after hepatectomy compared to controls. Similarly, insulin significantly increased the expression of Flt-1 between 24 and 96 h. However, insulin had no significant effect on Flk-1. Furthermore, the immunohistochemical staining revealed that expression of VEGF protein increased in the insulin groups. Insulin significantly increased the PCNA LI of hepatocytes and SECs compared to controls. CONCLUSION: Exogenous insulin may promote SEC proliferation with an enhanced expression of VEGF and its receptor Flt-1 in regenerating rat liver after PHx.

Animals↗

PubMed2005

[Increases of intracranial pressure and changes of blood flow velocity due to acupressure, needle and laser needle acupuncture?].

BACKGROUND: Pressure on the acupoints St.7 and SJ.22 can lead to significant, reversible increases in intracranial pressure (ICP) in patients with elevated ICP. OBJECTIVE: In this study, we investigated whether changes in cerebral parameters in healthy volunteers can also be registered, when the mentioned acupoints associated with ICP, are stimulated. SUBJECTS AND METHODS: We investigated a total of 34 volunteers (24 females, 10 males) and a 15-year-old intensive care patient after severe head injury. The mean age of volunteers was 25.2 +/- 3.4 years (range 20-35). Stimulation was performed using acupressure techniques, manual needle and laser needle methods. We evaluated the main parameter of mean blood flow velocity in the middle cerebral artery (left and right) as well as the pulsatility index. In addition, near infrared spectroscopy and blood pressure parameters were registered. RESULTS: Acupressure, manual needle acupuncture and laser needle acupuncture partially led to significant changes in the main goal values. CONCLUSION: Acupressure as well as acupuncture (needle and laser needle) can evoke reproducible functional changes in the brain. These accompanying effects are not to be ignored, in particular in patients with increased ICP.

Acupressure↗

PubMed2005

Identification of a repressor in the first intron of the human alpha2(I) collagen gene (COL1A2).

The human and mouse genes that code for the alpha2 chain of collagen I (COL1A2 and Col1a2, respectively) share a common chromatin structure and nearly identical proximal promoter and far upstream enhancer sequences. Despite these homologies, species-specific differences have been reported regarding the function of individual cis-acting elements, such as the first intron sequence. In the present study, we have investigated the transcriptional contribution of the unique open chromatin site in the first intron of COL1A2 using a transgenic mouse model. DNase I footprinting identified a cluster of three distinct areas of nuclease protection (FI1-3) that span from nucleotides +647 to +760, relative to the transcription start site, and which contain consensus sequences for GATA and interferon regulatory factor (IRF) transcription factors. Gel mobility shift and chromatin immunoprecipitation assays corroborated this last finding by documenting binding of GATA-4 and IRF-1 and IRF-2 to the first intron sequence. Moreover, a short sequence encompassing the three footprints was found to inhibit expression of transgenic constructs containing the COL1A2 proximal promoter and far upstream enhancer in a position-independent manner. Mutations inserted into each of the footprints restored transgenic expression to different extents. These results therefore indicated that the unique open chromatin site of COL1A2 corresponds to a repressor, the activity of which seems to be mediated by the concerted action of GATA and IRF proteins. More generally, the study reiterated the existence of species-specific difference in the regulatory networks of the mammalian alpha2(I) collagen coding genes.

Animals↗

PubMed2005

[The prognostic significance of preoperative plasma level of osteopontin in combination with intercellular adhesion molecule-1 for patients with hepatocellular carcinoma].

OBJECTIVE: To investigate the enhanced predictive activity of preoperative plasma osteopontin (OPN) level in combination with intercellular adhesion molecule-1 (ICAM-1) for recurrence and prognosis of patients after resection of hepatocellular carcinoma (HCC). METHODS: A total of 75 patients received liver resection for HCC from August 2001 to December 2001 in authors' institute were enrolled in this study. The preoperative plasma levels of OPN and ICAM-1 were detected by ELISA, and the association of them combination with the recurrence and prognosis of HCC patients was analyzed. RESULTS: OPN and ICAM-1 could be detected in all of the plasma samples of the tested patients. A significantly higher OPN level and ICAM-1 level were found in plasma of patients who were found to have HCC recurrence during the follow-up time compared with those without recurrence (210.40 vs. 154.86 ng/ml, P = 0.001; 1011.23 vs. 747.49 ng/ml, P = 0.027). A significant difference of OS and DFS were found in different subgroups with higher or lower level of OPN (625 vs. 808 days, P = 0.0006; 433 vs. 674 days, P = 0.0003); and a similar situation was found in patients of high- and low- ICAM-1 levels (651 vs. 794 days, P = 0.0269; 489 vs. 642 days, P = 0.0248). The 2-year recurrence rates of the patients with higher and lower plasma levels of both OPN and ICAM-1 were 87.50% and 28.00% (P < 0.001), respectively; and the 2-year OS rates were 37.50% and 88.00% (P = 0.001), and the 2-year DFS rates were 12.50%, and 76.00 (P = 0.001), respectively. CONCLUSIONS: The evaluation of preoperative plasma level of OPN or ICAM-1 may be helpful to predict the recurrence and prognosis of HCC patients in advance. The assessment of OPN level in combination with ICAM-1 could stratify patients into groups with different potentials of HCC recurrence and different outcomes more accurately than OPN or ICAM-1 individually.

Adult↗

PubMed2005

Maturation of guinea pig tracheal strip stiffness.

Previously, we showed the shortening velocity of guinea pig tracheal strips was the greatest in juvenile (3-wk-old) compared with infant (1-wk-old) and adult animals (3-mo-old). The greatest shortening velocity was associated with the least resistance to shortening calculated from force-velocity curves among the three age groups. It remained to be verified if the stiffness of tracheal tissue, a measure of tissue response to geometrical deformations, is different among the three age groups. We hypothesized that stiffness of intact tracheal strips is lowest in the juvenile group and that this can explain the ontogeny of airway smooth muscle resistance to shortening and shortening velocity. Static stiffness measured through stepwise deformations showed no age-related differences. Evaluation of tissue response to oscillatory deformations showed that the dynamic stiffness of unstimulated tracheal strips was 8.35 +/- 0.88, 4.15 +/- 1.09, and 8.21 +/- 1.57 kPa, and the phase angle was 10.3 +/- 2.93, 2.46 +/- 0.67, and 7.87 +/- 1.77 degrees in infant, juvenile, and adult, respectively. Unstimulated juvenile strips were significantly lower in dynamic stiffness and phase angle compared with unstimulated infant or adult strips. This maturational profile was independent of muscle strip preset length or oscillation mode/amplitude but was abolished at peak of contraction to either carbachol or electric field stimulation. These results suggest that the noncontractile components of tracheal strips are less stiff and contain fewer viscous/frictional elements in juvenile than in other age groups. This may provide a functional basis for reduced resistance to length changes in juvenile airway smooth muscle.

Aging↗

PubMed2005

Length oscillation induces force potentiation in infant guinea pig airway smooth muscle.

Deep inspiration counteracts bronchospasm in normal subjects but triggers further bronchoconstriction in hyperresponsive airways. Although the exact mechanisms for this contrary response by normal and hyperresponsive airways are unclear, it has been suggested that the phenomenon is related to changes in force-generating ability of airway smooth muscle after mechanical oscillation. It is known that healthy immature airways of both humans and animals exhibit hyperresponsiveness. We hypothesize that the profile of active force generation after mechanical oscillation changes with maturation and that this change contributes to the expression of airway hyperresponsiveness in juveniles. We examined the effect of an acute sinusoidal length oscillation on the force-generating ability of tracheal smooth muscle from 1 wk, 3 wk, and 2- to 3-mo-old guinea pigs. We found that the length oscillation produced 15-20% initial reduction in active force equally in all age groups. This was followed by a force recovery profile that displayed striking maturation-specific features. Unique to tracheal strips from 1-wk-old animals, active force potentiated beyond the maximal force generated before oscillation. We also found that actin polymerization was required in force recovery and that prostanoids contributed to the maturation-specific force potentiation in immature airway smooth muscle. Our results suggest a potentiated mechanosensitive contractile property of hyperresponsive airway smooth muscle. This can account for further bronchoconstriction triggered by deep inspiration in hyperresponsive airways.

Actins↗

PubMed2005

Hepatitis C virus E2 protein promotes human hepatoma cell proliferation through the MAPK/ERK signaling pathway via cellular receptors.

Dysregulation of mitogen-activated protein kinase (MAPK) signaling pathways by various viruses has been shown to be responsible for viral pathogenicity. The molecular mechanism by which hepatitis C virus (HCV) infection caused human liver diseases has been investigated on the basis of abnormal intracellular signal events. Current data are very limited involved in transmembrane signal transduction triggered by HCV E2 protein. Here we explored regulation of the MAPK/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway by E2 expressed in Chinese hamster oval cells. In human hepatoma Huh-7 cells, E2 specifically activated the MAPK/ERK pathway including downstream transcription factor ATF-2 and greatly promoted cell proliferation. CD81 and low density lipoprotein receptor (LDLR) on the cell surface mediated binding of E2 to Huh-7 cells. The MAPK/ERK activation and cell proliferation driven by E2 were suppressed by blockage of CD81 as well as LDLR. Furthermore, pretreatment with an upstream kinase MEK1/2 inhibitor U0126 also impaired the MAPK/ERK activation and cell proliferation induced by E2. Our results suggest that the MAPK/ERK signaling pathway triggered by HCV E2 via its receptors maintains survival and growth of target cells.

Animals↗

PubMed2005

The prognostic factor for outcome following second resection for intrahepatic recurrence of hepatocellular carcinoma with a hepatitis B virus infection background.

PURPOSE: Second resection has been proved to be a safe and effective treatment for patients with intrahepatic recurrent HCC after primary resection; however, preoperative prognostic factors for outcome following second resection in patients with a hepatitis B virus (HBV) infection background remains to be clarified. METHODS: Fifty-seven patients with intrahepatic recurrent an HCC and HBV infection background received second resection from 1997 to 2003 in our institute. All of them were negative for anti-hepatitis C virus (HCV) and positive regarding HBV profile. Patient and tumor factors were analyzed. RESULTS: At the time of preparing this paper, 31 had re-recurrence and 21 patients had died. No postoperative mortality was noted. The 1-, 3-, and 5-year overall survival after second resection were 69.9%, 61.2%, and 30.6%, respectively. Univariate and multivariate analysis showed that vascular invasion and time to recurrence were the independent prognostic factors for overall survival following second resection. The 3- and 4-year overall survival after second resection were 57.7% and 46.6% in patients with the presence of any of two risk factors (n = 46), and 100% and 100% in those with absence of both risk factors (n = 11, P = 0.008). CONCLUSIONS: Vascular invasion and time to recurrence were the prognostic factors for overall survival following second resection of intrahepatic recurrent HCC.

Adult↗

PubMed2005

Impact of the 2002 Canadian forest fires on particulate matter air quality in Baltimore city.

With increasing evidence of adverse health effects associated with particulate matter (PM), the exposure impact of natural sources, such as forest fires, has substantial public health relevance. In addition to the threat to nearby communities, pollutants released from forest fires can travel thousands of kilometers to heavily populated urban areas. There was a dramatic increase in forest fire activity in the province of Quebec, Canada, during July 2002. The transport of PM released from these forest fires was examined using a combination of a moderate-resolution imaging spectroradiometer satellite image, back-trajectories using a hybrid single-particle Lagrangian integrated trajectory, and local light detection and ranging measurements. Time- and size-resolved PM was evaluated at three ambient and four indoor measurement sites using a combination of direct reading instruments (laser, time-of-flight aerosol spectrometer, nephelometer, and an oscillating microbalance). The transport and monitoring results consistently identified a forest fire related PM episode in Baltimore that occurred the first weekend of July 2002 and resulted in as much as a 30-fold increase in ambientfine PM. On the basis of tapered element oscillating microbalance measurements, the 24 h PM25 concentration reached 86 microg/m3 on July 7, 2002, exceeding the 24 h national ambient air quality standard. The episode was primarily comprised of particles less than 2.5 microm in aerodynamic diameter, highlighting the preferential transport of the fraction of PM that is of greatest health concern. Penetration of the ambient episode indoors was efficient (median indoor-to-outdoor ratio 0.91) such that the high ambient levels were similarly experienced indoors. These results are significant in demonstrating the impact of a natural source thousands of kilometers away on ambient levels of and potential exposures to air pollution within an urban center. This research highlights the significance of transboundary air pollution and the need for studies that assess the public health impacts associated with such sources and transport processes.

Air Movements↗

PubMed2005

Ontogenesis of myosin light chain phosphorylation in guinea pig tracheal smooth muscle.

Increased airway responsiveness occurs in normal young individuals compared to adults. A maturation of airway smooth muscle (ASM) contractility is likely a mechanism of this juvenile airway hyperresponsiveness. Indeed, we showed in guinea pig tracheal smooth muscle (TSM) that maximum shortening velocity decreases dramatically after the first 3 weeks of life. Because the phosphorylation of the 20-kDa myosin light chain (MLC(20)) was shown to be a key event in ASM contractility, in the present work we sought to investigate it during ontogenesis. In three age groups (1-week-old, 3-week-old, and adult guinea pigs), we assessed the amount of MLC(20) phosphorylation achieved either in TSM crude protein homogenates exposed to Mg(2+) . ATP . CaCl(2) or in tracheal strips during electrical field stimulation (EFS). Phosphorylated and unphosphorylated MLC(20) were separated on nondenaturing 10% polyacrylamide gels, and the ratio of phosphorylation was obtained by densitometric analysis of chemiluminescent Western immunoblots. Maximum MLC(20) phosphorylation (% of total MLC(20)) in TSM tissue homogenate was, respectively, 32.6 +/- 5.7, 32.2 +/- 5.7, and 46.8 +/- 5.8 in 1-week, 3-week, and adult guinea pigs. Interestingly, in nonstimulated intact tracheal strips, we found a substantial degree of MLC(20) phosphorylation: respectively, 42.2 +/- 5.8, 36.5 +/- 7.8, and 46.4 +/- 4.7 in 1-week, 3-week, and adult guinea pigs. Maximal EFS-induced MLC(20) phosphorylation (% increase over baseline) in the 3-week age group was attained after 3 sec of EFS, and was 161.2 +/- 17.6, while in 1-week and adult guinea pigs, it was attained at 1.5 sec of EFS and was, respectively, 133.3 +/- 9.3 and 110.2 +/- 3.9 (P < 0.05). We conclude that MLC(20) phosphorylation in guinea pig intact tracheal strips correlates with ontogenetic changes in shortening velocity and changes in myosin light chain kinase content. These results further suggest that the maturation of ASM contractile properties plays a role in the greater airway responsiveness reported in children and young animals.

Animals↗

PubMed2005

IL-5 up-regulates the expression of TGF-beta1 in human blood eosinophils in vitro.

To investigate the effects of IL-5 on the expression of TGF-beta1 in eosinophils in vitro, eosinophils were incubated in the presence of the same concentrations of 1L-4, IL-5 and IFNgamma, different concentrations of IL-5 in vitro and changes of eosinophil viability were assessed by trypan blue exclusion. Non-cytokine was employed as a negative control. 16 h after the cultivation, supernatants and cells were assayed by using TGF-beta1 specific ELISA and RT-PCR. The mRNA expression and protein expresssion of TGF-beta1 in eosinophils stimulated with different cytokines was observed. The expression of TGF-beta1 protein in eosinophils was increased significantly by IL-4 (433.67 +/- 9.86 vs 228.9 +/- 2.87) and IL-5 (403.72 +/- 7.60 vs 228.9 +/- 2.87, P < 0.05), while decreased by IFNgamma (178.47 +/- 2.60 vs 228.9 +/- 2.87). At the same time, the results demonstrated that the basal level of TGF expression was enhanced by IL-5 in all samples (P < 0.05). The expression of TGF-beta1 mRNA was 1.42, 1.70, 1.76-folds higher than that of the non-stimulated controls. It is concluded that IL-5 can up-regulate the expression of TGF-beta1 in eosinophils in vitro, which might have effect in eosinophil-associated chronic rejection.

Cells, Cultured↗

PubMed2005

GATA-4 binds to an upstream element of the human alpha2(I) collagen gene (COL1A2) and inhibits transcription in fibroblasts.

Chromatin analyses have identified two DNase I hypersensitive sites (HS1 and HS2) at comparable distances (-130 bp and -2.3 kb) from the transcription start site of the human and mouse alpha2I collagen gene. Whereas the DNA region encompassing HS1 has been extensively characterized using protein binding and functional assays, nothing is yet known about the contribution of the HS2 sequence to alpha2I collagen gene transcription. Here we report that the HS2 sequence of the human alpha2I collagen (COL1A2) gene is a binding site for a transcriptional repressor in fibroblasts. DNase I footprinting identified a single site of nuclease protection around HS2, which corresponds to a sequence potentially capable of forming a 13 bp long hairpin structure with a 4 bp interruption in the middle. Gel mobility shift assays revealed that two GATA consensus sequences embedded within the hairpin are specifically bound by GATA-4 in fibroblasts. They also showed that formation of the HS2 protein complex requires the integrity of the whole hairpin sequence. Transient transfections of luciferase reporter gene constructs in fibroblasts correlated the HS2 element with transcriptional repression of the -2.3 kb promoter sequence. This last observation was further corroborated by showing that forced overexpression of GATA-4 in cultured fibroblasts leads to decreased transcription from the co-transfected -2.3 kb promoter/reporter construct, as well as reduced expression of the endogenous collagen gene. Finally, a chromatin immunoprecipitation assay documented GATA-4 ability to bind to the HS2 element in vivo. These results are therefore the first to implicate GATA-4 in regulating constitutive COL1A2 gene expression in fibroblasts.

Animals↗

PubMed2005

Dosimetric advantage and clinical implication of a micro-multileaf collimator in the treatment of prostate with intensity-modulated radiotherapy.

This paper investigates the dosimetric benefits of a micro-multileaf (4-mm leaf width) collimator (mMLC) for intensity-modulated radiation therapy (IMRT) treatment planning of the prostate cancer and its potential application for dose escalation and hypofractionation. We compared treatment plans for IMRT delivery using 2 different multileaf collimator (MLC) leaf widths (4 vs. 10 mm) for 10 patients with prostate cancer. Treatment planning was performed on the XknifeRT2 treatment planning system. All beams and optimization parameters were identical for the mMLC and MLC plans. All of the plans were normalized to ensure that 95% of the planning target volume (PTV) received 100% of the prescribed dose (74 Gy). The differences in dose distribution between the 2 groups of plans using the mMLC and the MLC were assessed by dose-volume histogram (DVH) analysis of the target and critical organs. Significant reductions in the volume of rectum receiving medium to higher doses were achieved using the mMLC. The average decrease in the volume of the rectum receiving 40, 50, and 60 Gy using the mMLC plans was 40.2%, 33.4%, and 17.7%, respectively, with p-values less than 0.0001 for V40 and V50 and 0.012 for V60. The mean dose reductions for D17 and D35 for the rectum were 20.0% (p < 0.0001) and 18.3% (p < 0.0002), respectively, when compared to those with the MLC plans. There were consistent reductions in all dose indices studied for the bladder. The target dose inhomogeneity was improved in the mMLC plans by an average of 32%. In the high-dose range, there was no significant difference in the dose deposited in the "hottest" 1 cc of the rectum between the 2 MLC plans for all cases (p > 0.78). Because of the reduction of rectal volume receiving medium to higher doses, dose to the prostate target can be escalated by about 20 Gy to over 74 Gy, while keeping the rectal dose (either denoted by D17 or D35) the same as those with the use of the MLC. The maximum achievable dose, derived when the rectum is allowed to reach the tolerance level, was found to be in the range of 113-172 Gy (using the tolerance value of D17). We conclude that the use of the mMLC for IMRT of the prostate may facilitate dose hypofractionation due to its dosimetric advantage in significantly improving the DVH parameters of the prostate and critical organs. When used for conventional fractionation scheme, mMLC for IMRT of the prostate may reduce the toxicity to the critical organs.

Equipment Design↗

PubMed2005

Mechanisms of airway smooth muscle relaxation during maturation.

Greater airway responsiveness in healthy juveniles is considered a factor in the higher asthma prevalence at a young age compared with adults. We have developed a guinea pig maturational model that utilizes tracheal strips from 1-week-, 3-week-, and 3-month-old guinea pigs to study the role of airway smooth muscle (ASM) in juvenile airway hyperresponsiveness. Because a reduced ability of ASM to spontaneously relax may contribute to airway hyperresponsiveness by maintaining bronchospasm and thus high airway resistance, we have employed this model to study ASM spontaneous relaxation during electrical field stimulation (EFS). Since relaxation during EFS had been neither described nor quantified during maturation, we developed new indices that allowed an appropriate comparison of the relaxing response from strips of different age animals. Using these indices we found that, whereas strips from adult animals relax to a level of tension similar to that found in the absence of stimulation, this ability to spontaneously relax is essentially absent in trachealis from infant animals. These results confirmed that maturation of ASM relaxation may play a role in juvenile airway hyperresponsiveness and that our maturational model is suitable to study the mechanisms regulating spontaneous relaxation in physiological conditions. We investigated the role of prostanoids in ASM relaxation and showed that cyclooxygenase inhibition increases relaxation in infant ASM to levels similar to adults. These results suggest that prostanoids regulate the ability of ASM to spontaneously relax, i.e., they reduce relaxation. We have produced preliminary data suggesting a maturational change in the level of prostanoids. Moreover, the possible action of acetylcholinesterase on maturation of ASM relaxation is discussed here on the basis of a preliminary study. We suggest that impairment of ASM relaxation likely contributes to increased airway responsiveness.

Aging↗

PubMed2005

A maturational model for the study of airway smooth muscle adaptation to mechanical oscillation.

It has been shown that mechanical stretches imposed on airway smooth muscle (ASM) by deep inspiration reduce the subsequent contractile response of the ASM. This passive maneuver of lengthening and retraction of the muscle is beneficial in normal subjects to counteract bronchospasm. However, it is detrimental to hyperresponsive airways because it triggers further bronchoconstriction. Although the exact mechanisms for this contrary response by normal and hyperresponsive airways are unclear, it has been suggested that the phenomenon is related to changes in ASM adaptability to mechanical oscillation. Healthy immature airways of both human and animal exhibit hyperresponsiveness, but whether the adaptative properties of hyperresponsive airway differ from normal is still unknown. In this article, we review the phenomenon of ASM adaptation to mechanical oscillation and its relevance and implication to airway hyperresponsiveness. We demonstrate that the age-specific expression of ASM adaptation is prominent using an established maturational animal model developed in our laboratory. Our data on immature ASM showed potentiated contractile force shortly after a length oscillation compared with the maximum force generated before oscillation. Several potential mechanisms such as myogenic response, changes in actin polymerization, or changes in the quantity of the cytoskeletal regulatory proteins plectin and vimentin, which may underlie this age-specific force potentiation, are discussed. We suggest a working model of the structure of smooth muscle associated with force transmission, which may help to elucidate the mechanisms responsible for the age-specific expression of smooth muscle adaptation. It is important to study the maturational profile of ASM adaptation as it could contribute to juvenile hyperresponsiveness.

Actins↗