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Biomedical subjects

L J Wang

Publications and source records attributed to L J Wang.

At least 37 records · Page 2Linked to original sources

[Effects of adaptive changes of vestibular system on cardiovascular regulation and orthostatic tolerance].

Astronauts may experience Space Adaptation Syndrome at the primary period in spaceflight. It is widely accepted that it is mainly caused by vestibular adaptive changes. The reverse changes of adaptation present after the return from weightlessness to normal 1 G. It may cause astronauts' postural instability and orthostatic intolerance. Evidences from animal model and some data from humans suggest that the vestibular system have influences on the sympathetic nervous system and cardiovascular control. The inputs that appear to be critical in producing these responses come from otolith receptors. The important medical problem--orthostatic intolerance in space medicine is mainly caused by cardiovascular abnormal control. It is possible that vestibular adaptive changes under microgravity may have its influence on the cardiovascular function and orthostatic intolerance.

Adaptation, Physiological↗

Enhancement of the activity of l-aspartase from Escherichia coli W by directed evolution.

l-Aspartase was modified by directed evolution. After four rounds of error-prone PCR and three rounds of DNA shuffling, an evolved enzyme purified from the final round showed a 28-fold increased k(cat)/K(m) and 4.6-fold decreased K(m). The thermostability and stable pH range were also enhanced. The DNA sequence of the evolved aspartase gene showed seven base changes, resulting in three amino acid changes from the native enzyme: N217K, T233R, V367G. The mechanism of the enhancement of activity was analyzed.

Aspartate Ammonia-Lyase↗

A study of postoperative radiotherapy in patients with non-small-cell lung cancer: a randomized trial.

PURPOSE: To study the value of postoperative radiotherapy for non-small-cell lung cancer (NSCLC) with positive regional lymph metastases (NI or N2) after radical surgery. MATERIALS AND METHODS: From February 1982 to October 1995, 366 patients with NSCLC and N1 or N2 disease were randomized into postoperative radiotherapy (S + R) (183 patients) and no further treatment (S alone) (182 patients). Postoperative radiotherapy (RT) was administrated 3-4 weeks after radical operation. Irradiated fields covered the bronchial stump, ipsilateral hilum, and most of the mediastinum. The midplane dose was 6000 cGy/30 fractions/6 weeks, with the spinal cord limited to 4000 cGy/20 fractions/4 weeks or less. One hundred thirty-four patients in S + R group and 162 patients in S alone group were evaluated. Clinical data were comparable in both arms, except for the numbers of N2 patients. RESULTS: The 3-year and 5-year overall survival rates were 51.9% and 42.9% in the S + R group and 50.2% and 40.5% in the S alone Group (p = 0.56). The 3-year and 5-year disease-free survival rates were 50.7% +/- 4.7% and 42.9% +/- 5.2% in the S + R group vs. 44.4% +/- 4.3% and 38.2% +/- 4.5% in the S alone group (p = 0.28), respectively. In the patients with NI or T3-4 tumors, there was a trend toward improved survival in the S + R group, especially in the patients with T3-4N1M0. These patients demonstrated 20% improvement in overall survival (p = 0.092) and greater than 20% better disease-free survival (p = 0.057). Postoperative RT reduced local recurrence but had no impact on distant metastases. CONCLUSION: Postoperative RT significantly reduced local relapses, but did not improve overall survival, due to a high frequency of distant metastases in this patient group.

Carcinoma, Non-Small-Cell Lung↗

The impact of overall treatment time on outcomes in radiation therapy for non-small cell lung cancer.

PURPOSE: A retrospective study was carried out to evaluate the impact of overall treatment time (OTT) on the results of radiation therapy for non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: From Jan. 1990 to Dec. 1996, 256 patients with stages I-IIIb NSCLC entered this analysis. All patients received definitive radiotherapy. Biologically effective dose (BED) was used to standardize the irradiation effects. The correlation between OTT and local progression-free survival was analyzed by linear-regression and Cox proportional hazard models. The prognostic variables for survival and distant metastasis were also briefly studied. RESULTS: OTT had been shortened in 64 patients because of an accelerated hyperfractioned irradiation, while OTT was prolonged i n 114 patients due to interruptions of irradiation courses. The main ca uses of interruption were machine breakdown or delayed preparations of c errobend block for boost fields (55%), holidays (11%) and treatment toxi city and side effects (34%). Patients tre ated with prolonged OTT (> 45 days) had significant poorer local progression-free survival than whom with OTT of </=45 days, 1, 3 and 5 year actuarial local progression-free survivals being 49, 17 and 15% for the former, and 74, 35 and 25% for the latter, respectively (P<0.001). BED-T that contained the factor of OTT correlated directly to local controls, which implied that BED-T represented radiobiological effects accurately, in other words, OTT had played a role in determining the radiobiological effects. Linear-regression on 103 cases treated with BED of 80-85 Gy(10) showed that 3 year local progression-free survival decreased by 9% per week with prolongation of OTT, or vice versa it increased by 9% per week with shortening OTT in an OTT range of 30-76 days. Cox multivariate analyses confirmed that OTT was an independent prognostic factor for local controls. CONCLUSION: OTT may have played an important role in determining local controls in radiotherapy for NSCLC. One should always keep in mind to make the OTT as short as possible, provided the patients can tolerate it, and to reduce irradiation interruptions for whatever reasons to a minimum.

Adult↗

Preparation and evaluation of insulin-loaded polylactide microspheres using factorial design.

The aim of this work was to study the influence of the concentration and molecular weight of poly(DL-lactide) (PLA) on the characteristics and in vivo biological activity of protein-loaded microspheres. At the same time, an attempt was made to achieve further optimization of the formulation. In the study, insulin was chosen as a model of protein drugs. Nine formulations of injectable insulin-loaded PLA microspheres were prepared using an emulsification and solvent evaporation process according to a factorial design. The trapping efficiency, drug loading, and the drop percentages of blood glucose levels at 24 hr and 72 hr in mice were used to evaluate the formulations. The results showed that PLA molecular weight and, especially, PLA concentration exerted influences on the characteristics and in vivo biological activity of insulin-loaded microspheres. The drug-trapping efficiency increased with the increase of the polymer concentration. The drug loading decreased with the increase of the polymer concentration and was not obviously affected by PLA molecular weight. The drop percentage of blood glucose level at 24 hr increased with the increase of polymer concentration and molecular weight. At 72 hr, the drop percentages of blood glucose levels were slightly increased with the increase of PLA concentration and then significantly decreased after the PLA concentration was above 150 mg/ml. An optimized formulation was prepared with PLA-10k at a concentration of 200 mg/ml. The experimental values of the response variables were close to the predicted values. The results suggest that the in vivo release behavior should be taken into consideration in the design of protein-loaded PLA microspheres.

Biocompatible Materials↗

Mortality after successful transcatheter arterial embolization in patients with unstable pelvic fractures: rate of blood transfusion as a predictive factor.

BACKGROUND: To determine the factors predictive of mortality in patients with unstable pelvic fractures after successful transcatheter arterial embolization. METHODS: A retrospective study of pelvic fractures between May of 1995 and April of 1998 was performed. Of 507 patients, 17 who were unstable underwent embolization. The success rate of embolization and the mortality rate after successful embolization were reviewed. Predictive factors (contrast medium extravasation, initial blood pressure, Injury Severity Score, timing of external fixation, time to angiography, volume of blood transfusion, rate of blood transfusion) of the final outcome were statistically analyzed. RESULTS: Embolization was 100% effective in stopping pelvic hemorrhage. The mortality of patients treated successfully with embolization was 17.6%. Among the predictive factors analyzed, only the rate of blood transfusion before embolization, 11.3 +/- 11.0 units/h (death) versus 3.2 +/- 1.9 units/h (survival) showed statistical significance with an odds ratio of 1.62 (95% confidence interval, 1.07-2.46). CONCLUSION: The success rate of embolization was 100% in stopping arterial hemorrhage of unstable pelvic fractures. The survival rate after successful embolization was 82.4%. Patients who had rapid blood transfusion before embolization had a poor final outcome. The risk of dying increased by 62% for every 1 unit/h increase of transfusion rate.

Adolescent↗

[c-fos expression in rat's vestibular nucleus under eccentric rotational stimulation].

OBJECTIVE: To investigate the c-fos expression in rat's vestibular nucleus under eccentric rotational stimulation and the effects of anti-motion sickness drug (PAPM) on this expression. METHOD: 19 SD rats were divided into three groups: A, B and C. A received as control. B was stimulated by eccentric rotation for 60 minutes. C received injection of PAPM through cavun abdominis 45 min before eccentric rotation. Immunohistochemical method and computerized image analysis were used to map locations of c-fos protein appeared in four vestibular nucleus and to count the masculine cells. RESULT: c-fos protein appeared in four vestibular nucleus areas after stimulation, and PAPM had no influence on this expression. CONCLUSION: It suggests that c-fos expression in vestibular nucleus is one of the important way in which vestibular nervous system reacts to outside stimulation and this expression has no direct relationship with the generation and development of motion sickness.

Aerospace Medicine↗

[Effects of some physical training on vestibular function].

Objective. To study the effects of active vestibular conditioning by some physical training on the vestibular function. Method. 10 subjects were given five kinds training gyro wheel, hanging ladder, ripple wood, four column swing and rotating swing for two weeks. Vestibular experimental tests were given before and after training. Result. After physical training, subjects' linear acceleration tolerance time increased significantly, the result of computer dynamic equilibrium posturegraphy demonstrated that the sway of body center of gravity decreased significantly when subjects maintained their equilibrium by both vestibular and visual information. Conclusion. The linear acceleration physical training methods used in this experiment have positive effects, while the methods of angular acceleration training need further investigation.

Acceleration↗

[Physiological evaluation of vestibular training load].

Objective. To evaluate the effects of vestibular training by observing the variations of the physiological indices. It is helpful in grasping the training load, setting down and implementing the training plan. Method. 10 healthy subjects received linear acceleration, continuous Coriolis acceleration and discontinuous Coriolis acceleration stimuli on different dates. The stimulus was stopped when there were slight autonomic nervous symptoms, ECG, EGG and BP were recorded before during and after the stimuli. Computerized Dynamic Posturography (correction of Postrograph) (CDP) was tested before and after experiment. Result. One subject finished the training of the three stimuli with only slight autonomic nervous symptoms. The CDP tests pre- and post-experiment indicated that for most subjects the contribution of vestibular function in maintaining dynamic posture equilibrium increased after the linear acceleration stimuli, but decreased after continuous Coriolis acceleration stimuli, and there was great individual difference after discontinuous Coriolis acceleration stimuli because the stimulation was relatively heavy. The equilibrium score in SOT2 decreased significantly after linear acceleration stimuli, and increased significantly after discontinuous Coriolis acceleration stimuli. Conclusion. The training methods we designed and used in this experiment are feasible, and the required training load can be reached. EGG, BP and the percentage of LF (low frequency) in ECG R-R power spectrum can reflect the subject's condition when the period stimuli stopped. It provided important reference in the determination of training stimulation load.

Acceleration↗

[Mechanism of anti-inflammatory action of Huanglian Jiedu decoction a traditional Chinese prescription].

OBJECTIVE: To elucidate the mechanism of anti-inflammatory action of Huanglian Jiedu Decoction (HJD). METHODS: An acute inflammatory air-pouch was established in mice by s.c. injecting air and 1% carrageenan. A mouse endotoxeamia induced by lipopolysaccharide was also used. Splenocyte proliferation was quantified with 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetery. NO2- concentration was examined by a Griess reagent and interleukin-1 activity was evaluated in thymocyte proliferation. RESULTS: HJD significantly inhibited the leukocyte infiltration and PGE2 production in the mouse air-pouch model. In the in vitro assay, HJD significantly inhibited concanavalin A(Con A)-induced transformation of spleen cells isolated from the endotoxeamia mice, but did not influence that from the normal mice. HJD did not affact Con A-induced interleukin-2 production in splenocytes in either normal or endotoxeamia mice. HJD remarkably reduced interleukin-1 and NO production in peritoneal macrophages elicited by lipopol ysaccharide. CONCLUSION: HJD displays an anti-inflammatory effect mainly through inhibiting the production of inflammatory cytokines including IL-1, NO and PGE2.

Animals↗

S-adenosylmethionine synthetase is overexpressed in murine neuroblastoma cells resistant to nucleoside analogue inhibitors of S-adenosylhomocysteine hydrolase: a novel mechanism of drug resistance.

S-Adenosylmethionine (AdoMet) synthetase (EC 2.5.1.6), which catalyzes the synthesis of AdoMet from methionine and ATP, is the major methyl donor for transmethylation reactions and propylamino donor for the biosynthesis of polyamines in biological systems. We have reported previously that wild-type C-1300 murine neuroblastoma (wMNB) cells, made resistant to the nucleoside analogue (Z)-5'-fluoro-4',5'-didehydro-5'-deoxyadenosine (MDL 28,842), an irreversible inhibitor of S-adenosylhomocysteine (AdoHcy) hydrolase (EC 3.3.1.1), express increased AdoMet synthetase activity (M. R. Hamre et al., Oncol. Res., 7: 487-492, 1995). In the present study, immunoblot analyses of AdoMet Synthetase with isoform-specific (MATII) antibodies demonstrated an elevation in the AdoMet synthetase immunoprotein in nucleoside analogue-resistant MNB cells (rMNB-MDL) when compared to wild-type, nonresistant MNB cells. An increase of 2.1-fold was observed in the alpha2/alpha2' catalytic subunit, which differed significantly from the much smaller increment in the noncatalytic beta-subunit of AdoMet synthetase. Densitometric analyses revealed that an increased expression of AdoMet synthetase in rMNB-MDL cells was due to overexpression of the alpha2 (Mr 53,000; 2.6-fold) and alpha2' (Mr 51,000; 1.8-fold) subunits. AdoMet synthetase mRNA expression in rMNB-MDL cells was remarkably greater than wMNB cells, as determined by quantitative competitive reverse transcription-PCR (QC-PCR) analysis. DNA (cytosine) methyl transferase expression, measured by reverse transcription-PCR analysis, was also elevated significantly in rMNB-MDL cells. In contrast, Western blot analyses demonstrated down-regulation (1.6-fold) of AdoMet synthetase in doxorubicin-resistant human leukemia cells (HL-60-R) expressing multidrug resistance protein when compared with wild-type, nonresistant HL-60 cells. The resistance of rMNB-MDL cells to nucleoside analogue inhibitors of S-adenosylhomocysteine hydrolase correlates directly with overexpression of the alpha2/alpha2' subunits of AdoMet synthetase. Cellular adaptation allows sufficient AdoMet to be synthesized, so that viability of the MNB cells can be maintained even in the presence of high AdoHcy concentrations. This novel mechanism of drug resistance does not appear to require multidrug resistance protein (P-glycoprotein) overexpression.

Adenosine↗

Study of prognostic predictors for non-small cell lung cancer.

BACKGROUND: The outcome of treatment in non-small cell lung cancer (NSCLC) remains poor. One of the reasons is that in many patients its biological behavior does not follow a definite pattern, and can not be accurately predicted prior to treatment. In the present study we have examined the significant prognostic predictors. METHODS: One hundred and fifty-eight patients with NSCLC entered this study. They received surgery alone (95 cases) or combined therapy with postoperative irradiation (63 cases). Three types of data have been collected: (1) clinical characteristics: age, sex, Karnofsky performance status, weight loss, T stage, and N stage; (2) histopathology studies: histological types, tumor differentiation, status of vascular and lymphatic vessel invasions; (3) laboratory measurements by immunohistochemistry assay: oncoprotein overexpression, including pan-ras, c-myc, neu, epidermal growth factor receptor (EGFR) and p53, and tumor cell proliferation by proliferating cell nuclear antigen (PCNA). RESULTS: For the entire group, 5-year actuarial survival, local control and distant metastasis rates were 44, 63 and 40%, respectively. In the univariate analyses, T stage, N stage and lymphatic vessel invasion correlated to survival; T stage and N stage to local control; N stage, lymphatic vessel invasion and pan-ras protein positive stain to distant metastasis. When the index of oncoprotein positive stains was used, the higher index was associated with a higher distant metastasis rate. In the multivariate analyses, T stage, N stage and lymphatic vessel invasion could be independent predictors for survival; T stage for local control; N stage, lymphatic vessel invasion and index of positive oncoprotein stains for distant metastasis. CONCLUSIONS: Late T and N stages, lymphatic vessel invasion and multi-oncoprotein positive stains would predict poor prognoses for NSCLC.

Actuarial Analysis↗

Foliar modifications induced by inhibition of polar transport of auxin.

The effects of auxin polar transport inhibitors, 9-hydroxy-fluorene-9-carboxylic acid (HFCA); 2, 3, 5-triiodobenzoic acid (TIBA) and trans-cinnamic acid (CA) on leaf pattern formation were investigated with shoots formed from cultured leaf explants of tobacco and cultured pedicel explants of Orychophragmus violaceus, and the seedlings of tobacco and Brassica chinensis. Although the effective concentration varies with the inhibitors used, all of the inhibitors induced the formation of trumpet-shaped and/or fused leaves. The frequency of trumpet-shaped leaf formation was related to the concentration of inhibitors in the medium. Histological observation of tobacco seedlings showed that there was only one main vascular bundle and several minor vascular bundles in normal leaves of the control, but there were several vascular bundles of more or less the same size in the trumpet-shaped leaves of treated ones. These results indicated that auxin polar transport played an important role on bilateral symmetry of leaf growth.

Biological Transport↗

Skeletal muscle calcium channel ryanodine binding activity in genetically unimproved and commercial turkey populations.

The biochemical basis for the incidence of pale, soft, exudative (PSE) turkey meat was investigated by conducting ryanodine binding experiments on sarcoplasmic reticulum (SR) vesicles prepared from genetically unimproved and commercial turkeys. Ryanodine binding to the Ca2+ channel protein in SR vesicles from both populations of turkeys was activated at a threshold concentration of approximately 0.2 microM Ca2+, reached a plateau over the range of 3 to 30 microM free Ca2+, and was only slightly inhibited at 1 mM Ca2+. The SR fractions, enriched in the Ca(2+)-channel protein, from commercial turkeys exhibited a higher (P < 0.05) mean affinity for ryanodine when compared to that from unimproved turkeys (Kd = 12.2 vs 20.5 nM, respectively). A fourfold difference (P < 0.05) in mean Ca(2+)-channel protein content or Bmax (1.10 pmol/mg vs 4.01 pmol/mg) was observed between commercial and unimproved turkey SR fractions. The apparent difference in channel protein content between the two populations may be partially accounted for by the high abundance of a 75-kDa protein, as yet unidentified, observed in most commercial turkey samples on SDS polyacrylamide gels. The differences in ryanodine binding activity between these two populations of turkeys suggest that altered SR calcium channel protein activity, or altered channel regulation, may be associated with the increased incidence of PSE meat from turkeys selected for growth characteristics.

Animal Husbandry↗

Regulation of the renal Na-HCO(3) cotransporter. XI. Signal transduction underlying CO(2) stimulation.

We have previously shown that CO(2) stimulation of the renal Na-HCO(3) cotransporter (NBC) activity is abrogated by general inhibitors of protein tyrosine kinases. The more selective inhibitor herbimycin also blocked this effect at concentrations known to preferentially inhibit Src family kinases (SFKs). We therefore examined a role for SFKs in CO(2)-stimulated NBC activity. To this end, we engineered OK cells to express the COOH-terminal Src kinase (Csk), a negative regulator of SFKs. CO(2) stimulated NBC activity normally in beta-galactosidase-expressing and untransfected control cells. In contrast, Csk-expressing cells had normal baseline NBC activity that was not stimulated by CO(2). CO(2) stimulation increased both total SFK activity and specific tyrosine phosphorylation of Src. The specific MEK1/2 inhibitor PD-98059 completely inhibited the CO(2) stimulation of NBC activity as well as the accompanying phosphorylation and activation of ERK1/2. Our data suggest the involvement of both SFKs, probably Src, and the "classic" MAPK pathway in mediating CO(2)-stimulated NBC activity in renal epithelial cells.

Animals↗

Velvet antler polypeptides promoted proliferation of chondrocytes and osteoblast precursors and fracture healing.

AIM: To study the effects of velvet antler (VA) total polypeptides (VATP) and VA polypeptides, VAP-A, VAP-B, and VAP-C on proliferation of chondrocytes and osteoblast precusors. METHODS: Chondrocytes (rabbit and human fetus) and osteoblast precusors (chick embryo) were incubated in the culture medium containing VATP or VAP-A, VAP-B, and VAP-C. [3H]TdR incorporation into DNA was measured. Fracture healing-promoting action of VATP was determined in rats. RESULTS: VATP 50-200 mg.L-1 and VAP-B 12.5, 25, and 50 mg.L-1 showed most marked proliferation-promoting activity for rabbit costed chondrocytes and increased incorporation of [3H]TdR from (73 +/- 9) Bq (control group) to (272 +/- 55), (327 +/- 38), and (415 +/- 32) Bq, respectively (P < 0.01). The activity of VAP-A was weaker than that of VAP-B, and VAP-C had no activity. VATP 10 and 20 mg.kg-1 by local injection into the cross-section fracture area accelerated healing of radial fracture. The healing rate of VATP-treated group was higher (75%) than that of control group (25%) (P < 0.05). CONCLUSION: VATP accelerated fracture healing by stimulating proliferation of chondrocytes and osteoblast precursors.

Animals↗

[Ocular counterrolling as an indicator of vestibular otolith function].

Space Motion Sickness (SMS) occurred in the first few days of space flight correlated with the vestibular function. As the main influence of weightlessness in space focused on the otolith receptors. The test of otolith function is of great importance. Although there are a lot of methods to test otolith function, at present ocular counterrolling is the only relative pure indicator of otolith function. It provide a valid method for predicting SMS susceptibility, it has great application prospect in the research of the SMS mechanism and the readaptability of vestibular function after space flight, it also provides great reference in the clinical diagnosis of vestibular problems.

Aerospace Medicine↗