Search PubMed⌕ Search

Biomedical subjects

L Li

Publications and source records attributed to L Li.

At least 361 records · Page 20Linked to original sources
PubMed2001

Chronic hypoxia decreases K(V) channel expression and function in pulmonary artery myocytes.

Activity of voltage-gated K+ (KV) channels regulates membrane potential (E(m)) and cytosolic free Ca2+ concentration ([Ca2+](cyt)). A rise in ([Ca2+](cyt))in pulmonary artery (PA) smooth muscle cells (SMCs) triggers pulmonary vasoconstriction and stimulates PASMC proliferation. Chronic hypoxia (PO(2) 30-35 mmHg for 60-72 h) decreased mRNA expression of KV channel alpha-subunits (Kv1.1, Kv1.5, Kv2.1, Kv4.3, and Kv9.3) in PASMCs but not in mesenteric artery (MA) SMCs. Consistently, chronic hypoxia attenuated protein expression of Kv1.1, Kv1.5, and Kv2.1; reduced KV current [I(KV)]; caused E(m) depolarization; and increased ([Ca2+](cyt)) in PASMCs but negligibly affected KV channel expression, increased I(KV), and induced hyperpolarization in MASMCs. These results demonstrate that chronic hypoxia selectively downregulates KV channel expression, reduces I(KV), and induces E(m) depolarization in PASMCs. The subsequent rise in ([Ca2+](cyt)) plays a critical role in the development of pulmonary vasoconstriction and medial hypertrophy. The divergent effects of hypoxia on KV channel alpha-subunit mRNA expression in PASMCs and MASMCs may result from different mechanisms involved in the regulation of KV channel gene expression.

Animals↗
PubMed2001

Capsaicin inhibits activation of voltage-gated sodium currents in capsaicin-sensitive trigeminal ganglion neurons.

Capsaicin, the pungent ingredient in hot pepper, activates nociceptors to produce pain and inflammation. However, repeated exposures of capsaicin will cause desensitization to nociceptive stimuli. In cultured trigeminal ganglion (TG) neurons, we investigated mechanisms underlying capsaicin-mediated inhibition of action potentials (APs) and modulation of voltage-gated sodium channels (VGSCs). Capsaicin (1 microM) inhibited APs and VGSCs only in capsaicin-sensitive neurons. Repeated applications of capsaicin produced depolarizing potentials but failed to evoke APs. The capsaicin-induced inhibition of VGSCs was prevented by preexposing the capsaicin receptor antagonist, capsazepine (CPZ). The magnitude of the capsaicin-induced inhibition of VGSCs was dose dependent, having a K(1/2) = 0.45 microM. The magnitude of the inhibition of VGSCs was proportional to the capsaicin induced current (for -I(CAP) < 0.2 nA). Capsaicin inhibited activation of VGSCs without changing the voltage dependence of activation or markedly changing channel inactivation and use-dependent block. To explore the changes leading to this inhibition, it was found that capsaicin increased cAMP with a K(1/2) = 0.18 microM. At 1 microM capsaicin, this cAMP generation was inhibited 64% by10 microM CPZ, suggesting that activation of capsaicin receptors increased cAMP. The addition of 100 microM CPT-cAMP increased the capsaicin-activated currents but inhibited the VGSCs in both capsaicin-sensitive and -insensitive neurons. In summary, the inhibitory effects of capsaicin on VGSCs and the generation of APs are mediated by activation of capsaicin receptors. The capsaicin-induced activation of second messengers, such as cAMP, play a part in this modulation. These data distinguish two pathways by which neuronal sensitivity can be diminished by capsaicin: by modulation of the capsaicin receptor sensitivity, since the block of VGSCs is proportional to the magnitude of the capsaicin-evoked currents, and by modulation of VGSCs through second messengers elevated by capsaicin receptor activation. These mechanisms are likely to be important in understanding the analgesic effects of capsaicin.

Animals↗
PubMed2001

Rho-kinase activation is involved in hypoxia-induced pulmonary vasoconstriction.

Rho-associated serine/threonine kinase (Rho-kinase) is a downstream effector of small GTPase RhoA that has recently been shown to play an important role in regulating smooth muscle contraction. The present study investigated the role of Rho/ Rho-kinase in hypoxia-induced pulmonary vasoconstriction (HPV). Small pulmonary resistance vessels and cultured pulmonary arterial smooth muscle cells (PASMCs) from the rat were used. PASMCs exposed to hypoxia (PO(2) = 26 +/- 2 mm Hg) showed a significant increase in Rho-kinase activity. Exposure to hypoxia for 20, 40, 60, 90, and 120 min also resulted in a significant increase in myosin light chain (MLC) phosphorylation at all time points in PASMCs. Hypoxia-induced MLC phosphorylation was inhibited by Y-27632 (a Rho-kinase inhibitor), exoenzyme C3 (a specific Rho inhibitor), or toxin B (an inhibitor for Rho proteins). In addition, hypoxia-induced Rho-kinase activation was blocked by C3 and toxin B. Small rat intrapulmonary arterial rings, which were made hypoxic (PO(2) = 30 +/- 3 mm Hg), showed a slow sustained contraction, and Y-27632 caused a significant relaxation during the sustained phase of HPV in a concentration-dependent manner. In summary, the data show that Rho-kinase is activated by hypoxia in PASMCs, and Rho/Rho-kinase is functionally linked to hypoxia-induced MLC phosphorylation and plays a role in the sustained phase of HPV.

Animals↗
PubMed2001

Antibacterial effect of human V gamma 2V delta 2 T cells in vivo.

V gamma 2V delta 2 cells, a class of T cells found only in primates, are reactive to nonpeptide organophosphate and alkylamine antigens secreted by bacteria and parasites. These cells make up 2-5% percent of human peripheral blood T cells but expand to make up 8-60% of peripheral blood T cells during bacterial and parasitic infections. We show here, using a chimeric severe combined immunodeficiency (SCID) mouse (hu-SCID) model, that human V gamma 2V delta 2 T cells mediate resistance to extracellular gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli and Morganella morganii) bacteria, as assessed by survival, body weight, bacterial loads, and histopathology. Surprisingly, this bacterial resistance was evident 1 day after infection, and bacteria were cleared well before gamma delta T cell expansion was detected 6 days after infection. Decreased resistance in V delta 2 T cell-depleted hu-SCID mice correlated with decreased serum IFN-gamma titers. Intravenous treatment of infected, reconstituted hu-SCID mice with pamidronate, a human V gamma 2V delta 2 T cell-specific aminobisphosphonate antigen, markedly increased the in vivo antibacterial effect of V gamma 2V delta 2 T cells. Therefore, this large pool of antigen-specific, yet immediately reactive memory human V gamma 2V delta 2 T cells is likely to be an important mediator of resistance against extracellular bacterial infection and may bridge the gap between innate and acquired immunity.

Animals↗
PubMed2001

The localization of periodontal-disease-associated bacteria in human periodontal pockets.

Some Gram-negative anaerobes are associated with the incidence and progression of periodontal disease. In periodontal pockets, however, the localization of those bacteria is unknown. We investigated the localization of 5 bacterial species in human periodontal pockets. Fifteen teeth with a part of periodontal pockets from 10 adult periodontitis patients were obtained, and the localization of bacteria was examined immunohistochemically. Positive reactions with anti-Prevotella nigrescens antibody were located at the epithelium-associated plaque area in the middle pocket zones. In the middle and deep pocket zones, Fusobacterium nucleatum and Treponema denticola were especially localized in the unattached plaque area, but Eikenella corrodens was observed in the tooth-attached plaque area. Actinobacillus actinomycetemcomitans, detected in 2 of 15 samples examined, was found in the unattached plaque area, in the middle pocket zone. The present findings indicated that the 5 bacterial species examined localized at distinct regions in human periodontal pockets.

Adult↗
PubMed2001

Promotion of beta-cell regeneration by betacellulin in ninety percent-pancreatectomized rats.

Betacellulin is thought to promote growth and differentiation of pancreatic beta-cells. We investigated the effect of betacellulin on regeneration of pancreatic beta-cells in 90%-pancreatectomized rats. Ninety percent pancreatectomy was performed in male Wistar rats and betacellulin (0.5 microg/g body weight) or saline was administered daily for 10 d starting immediately after pancreatectomy. In pancreatectomized rats, the morning-fed plasma glucose was significantly lower and the plasma insulin concentration was significantly higher in betacellulin-treated rats than those in control rats for up to 4 wk. Thirty days after pancreatectomy, a glucose tolerance test was performed. Betacellulin reduced the plasma glucose response to ip glucose loading. In control rats, the plasma insulin concentration was significantly lower and did not respond to glucose. In contrast, the plasma insulin concentration increased slightly but significantly in betacellulin-treated rats. Thirty days after pancreatectomy, the beta-cell mass was greater and the insulin content was significantly higher in betacellulin-treated rats than those in control rats. The numbers of islet cell-like cluster and bromodeoxy uridine/insulin double- positive cells in both islet cell-like cluster and islets were significantly higher in betacellulin-treated rats. These results indicate that administration of betacellulin improves glucose metabolism by promoting beta-cell regeneration in 90%-pancreatectomized rats.

Animals↗
PubMed2001

New 11(15-->1)abeotaxane, 11(15-->1),11(10-->9)bisabeotaxane and 3,11-cyclotaxanes from Taxus yunnanensis.

Chemical examination of the seeds of Chinese yew, Taxus yunnanensis Cheng et L. K. Fu resulted in the isolation of an 11(15-->1)abeotaxane, an 11(15-->1), 11(10-->9)bisabeotaxane and two 3,11-cyclotaxanes. The structures of these new taxoids were established as 13alpha-acetoxy-5alpha-cinnamoyloxy-11(15-->1)abeotaxa-4(20),11-diene-9alpha,10beta,15-triol (1), 20-acetoxy-2alpha-benzoyloxy-4alpha, 5alpha, 7beta, 9alpha, 13alpha-pentahydroxy-11(15-->1), 11(10-->9) bisabeotax-11-eno-10,15-lactone (2), 2alpha,10beta-diacetoxy-5alpha-cinnamoyloxy-9alpha-hydroxy-3,11 -cyclotax-4(20)-en-13-one (3) and 10beta-acetoxy-2alpha,5alpha,9alpha-trihydroxy-3,11-cyclotax-4(20)-en-13-one (4) on the basis of spectral analyses.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Relative wall thickness is an independent predictor of left ventricular systolic and diastolic dysfunctions in essential hypertension.

The objective of this study was to elucidate the relationship between left ventricular geometry and left ventricular (LV) function in patients with untreated essential hypertension. We evaluated LV systolic and diastolic functions by M-mode echocardiography in 24 normotensive control subjects (NC) and 129 patients with essential hypertension. Patients were divided into four groups according to the relative wall thickness and LV mass index: a normal left ventricle (n=57), a concentric remodeling (n=7), a concentric hypertrophy (n=31), and an eccentric hypertrophy (n=34) group. LV systolic function as measured by midwall fractional shortening (FS) was significantly decreased in both the concentric remodeling and concentric hypertrophy groups; no differences were observed for endocardial FS. LV diastolic function as measured by isovolumic relaxation time (IRT) was also decreased in both the concentric remodeling and concentric hypertrophy groups. In multivariate analysis, relative wall thickness (p<0.0001), end-systolic wall stress (p<0.0001), and systolic blood pressure (p=0.002) were independently associated (r2=0.72) with midwall FS in a model including age, LV mass index, body mass index, diastolic blood pressure and IRT. In addition, relative wall thickness (p=0.0008) and age (p<0.0001) were independently associated (r2=0.31) with IRT in a model including LV mass index, end-systolic wall stress, body mass index, systolic and diastolic blood pressures and midwall FS. We conclude that LV geometry as evaluated by relative wall thickness may provide a further independent stratification of LV systolic and diastolic functions in essential hypertension.

Adult↗
PubMed2001

Growth hormone is permissive for skeletal adaptation to mechanical loading.

The Lewis dwarf (DW) rat was used as a model to test the hypothesis that growth hormone (GH) is permissive for new bone formation induced by mechanical loading in vivo. Adult female Lewis DW rats aged 6.2 +/- 0.1 months (187 +/- 18 g) were allocated to four vehicle groups (DW), four GH treatment groups at 32.5 microg/100 g body mass (DWGH1), and four GH treatment groups at 65 microg/100 g (DWGH2). Saline vehicle or GH was injected intraperitoneally (ip) at 6:30 p.m. and 6:30 a.m. before mechanical loading of tibias at 7:30 a.m. A single period of 300 cycles of four-point bending was applied to right tibias at 2.0 Hz, and magnitudes of 24, 29, 38, or 48N were applied. Separate strain gauge analyses in 5 DW rats validated the selection of loading magnitudes. After loading, double-label histomorphometry was used to assess bone formation at the periosteal surface (Ps.S) and endocortical surface (Ec.S) of tibias. Comparing left (unloaded) tibias among groups, GH treatment had no effect on bone formation. Bone formation in tibias in DW rats was insensitive to mechanical loading. At the Ec.S, mechanically induced lamellar bone formation increased in the DWGH2 group loaded at 48N (p < 0.05), and no significant increases in bone formation were observed among other groups. The percentage of tibias expressing woven bone formation (Wo.B) at the Ps.S was significantly greater in the DWGH groups compared with controls (p < 0.05). We concluded that GH influences loading-related bone formation in a permissive manner and modulates the responsiveness of bone tissue to mechanical stimuli by changing thresholds for bone formation.

Adaptation, Physiological↗
PubMed2001

Effect of voluntary wheel-running on insulin sensitivity and responsiveness in high-fat-fed rats.

The effect of voluntary wheel-running on insulin resistance was studied in high-fat-fed rats. A sequential hyperinsulinemic euglycemic clamp procedure was employed (insulin infusion rates: 3 and 30 mU/kg BW/min) in 14 high-fat-fed rats and 7 chow-fed rats under the awake condition. The high-fat-fed rats were further divided into a sedentary (n=7) and a voluntary wheel-running (n=7) groups. Blood glucose was clamped at the fasting level in each rat. Plasma insulin levels during the 3- and 30-mU/kg BW/min insulin infusions were 40-50 and 450-550 microU/ml, respectively. At both 3 and 30 mU/kg BW/min insulin infusions, high-fat-feeding showed a significant decrease in glucose infusion rate (GIR), compared with the chow-fed rats. However, decreased GIRs were restored by the 4-wk wheel-running and reached similar levels as the chow-fed rats. Therefore, it could be concluded that voluntary wheel-running prevents insulin resistance induced by high-fat feeding.

Animals↗
PubMed2001

Measurement of DNA damage in mammalian cells exposed in vitro to radiofrequency fields at SARs of 3-5 W/kg.

In the present study, we determined whether exposure of mammalian cells to 3.2-5.1 W/kg specific absorption rate (SAR) radiofrequency fields could induce DNA damage in murine C3H 10T(1/2) fibroblasts. Cell cultures were exposed to 847.74 MHz code-division multiple access (CDMA) and 835.62 frequency-division multiple access (FDMA) modulated radiations in radial transmission line (RTL) irradiators in which the temperature was regulated to 37.0 +/- 0.3 degrees C. Using the alkaline comet assay to measure DNA damage, we found no statistically significant differences in either comet moment or comet length between sham-exposed cells and those exposed for 2, 4 or 24 h to CDMA or FDMA radiations in either exponentially growing or plateau-phase cells. Further, a 4-h incubation after the 2-h exposure resulted in no significant changes in comet moment or comet length. Our results show that exposure of cultured C3H 10T(1/2) cells at 37 degrees C CDMA or FDMA at SAR values of up to 5.1 W/kg did not induce measurable DNA damage.

Animals↗
PubMed2001

Predictors of low back pain onset in a prospective British study.

OBJECTIVES: This study examined predictors of low back pain onset in a British birth cohort. METHODS: Univariate and multivariate analyses focused on individuals who experienced onset of low back pain at 32 to 33 years of age (n= 571) and individuals who were pain free (n = 5210). Participants were members of the 1958 British birth cohort. RESULTS: Incident pain was elevated among those with psychological distress at 23 years of age (adjusted odds ratio [OR] = 2.52, 95% confidence interval [CI] = 1.65, 3.86) and among persistent moderate or heavy smokers (adjusted OR = 1.63, 95% CI = 1.23, 2.17). Significant univariate associations involving other factors (e.g., social class, childhood emotional status, body mass index, job satisfaction) did not persist in multivariate analyses. CONCLUSIONS: This prospectively studied cohort provides evidence that psychological distress more than doubles later risk of low back pain, with smoking having a modest independent effect. Other prospective studies are needed to confirm these findings before implications for low back pain prevention can be assessed.

Adult↗
PubMed2001

The involvement of calcium mobilization in the calcium-activated potassium currents activated by hyposmotic swelling in gastric antral circular myocytes of the guinea-pig.

In our study of the effects of hyposmotic swelling on the Ca(2+)-activated potassium currents [I(K(Ca))] and its mechanism, we employed the whole-cell patch clamp technique using the gastric antral circular myocytes of the guinea-pig. Hyposmotic swelling efficiently increased I(K(Ca)), and the extent of changes in I(K(Ca)) was sharply dependent on the osmolarity of the perfusion solutions. When the calcium-free solution (EGTA 10 microM added in calcium-free solution) was superfused, I(K(Ca)) was not increased by the hyposmotic swelling. Gadolinium (Gd(3+)) 100 nM, a blocker of the stretch-activated nonselective cation channel, blocked the activation of I(K(Ca)) induced by hyposmotic swelling, but nicardipine 5 microM (the L-type calcium channel blocker) did not. Heparin 3 mg/ml, a potent inhibitor of inositol triphosphate receptor (InsP(3)R), did not inhibit the response, and caffeine 1 mM (the agonist for calcium-induced calcium release [CICR]) imitated the effect of hyposmotic swelling. Ryanodine (15 microM), markedly inhibited the effect. These results suggest that hyposmotic swelling activates I(K(Ca)), and the activation is associated with CICR, which is triggered by extracellular calcium influx through the stretch-activated channel (SA channel).

Animals↗
PubMed2001

Multi-modal antigen specific therapy for autoimmunity.

Peripheral tolerance, represents an attractive strategy to down-regulate previously activated T cells and suppress an ongoing disease. Herein, immunoglobulins (Igs) were used to deliver self and altered self peptides for efficient peptide presentation without costimulation to test for modulation of experimental allergic encephalomyelitis (EAE). Accordingly, the encephalitogenic proteolipid protein (PLP) sequence 139-151 (referred to as PLP1) and an altered form of PLP1 known as PLP-LR were genetically expressed on Igs and the resulting Ig-PLP1 and Ig-PLP-LR were tested for efficient presentation of the peptides and for amelioration of ongoing EAE. Evidence is presented indicating that Ig-PLP1 as well as Ig-PLP-LR given in saline to mice with ongoing clinical EAE suppresses subsequent relapses. However, aggregation of both chimeras allows crosslinking of Fcgamma receptors (FcgammaRs) and induction of IL-10 production by APCs but does not promote the up-regulation of costimulatory molecules. Consequently, IL-10 displays bystander suppression and synergizes with presentation without costimulation to drive effective modulation of EAE. As Ig-PLP1 is more potent than Ig-PLP-LR in the down-regulation of T cells, we conclude that peptide affinity plays a critical role in this multi-modal approach of T cell modulation.

Animals↗
PubMed2001

[Mannose-binding protein gene polymorphism influences the patterns of glomerular immune deposition in IgA nephropathy].

OBJECTIVE: To investigate the relationship between mannose-binding protein(MBP) gene codon 54 (GGC/GAC) polymorphism and the patterns of glomerular immune deposition in IgA nephropathy (IgAN) and explore its functional significance. METHODS: IgAN patients were divided into two groups according to the pattern of glomerular immune deposition. Group A included 77 patients with glomerular IgA and C3 deposits. Group AGM consisted of 70 patients with glomerular IgA, IgG, IgM, C3 and Clq deposits. One hundred and forty healthy adults were used as normal controls. MBP genotypes were investigated by PCR-RFLP. Serum MBP levels of some subjects with different genotypes were also assayed by ELISA simultaneously. RESULTS: The genotype frequency of GAC heterozygotes was significantly higher in group AGM than in group A (41.4% vs. 19.5%, P<0.01) or normal subjects (41.4% vs. 26.4%, P<0.05), while no difference was found in the distribution of MBP genotypes between group A and normal subjects. The allele frequency of GAC mutation was also higher in group AGM than in group A (0.236 vs. 0.136, P<0.05) or normal subjects (0.236 vs. 0.146, P<0.05). The variant allele (GAC) was markedly associated with group AGM (OR=1.95, 95%CI: 1.06-3.58). In both group A and group AGM, more patients carrying the variant allele had episodes of upper respiratory or gastrointestinal infections prior to the onset or exacerbation of IgAN than wild homozygotes. In addition, a significant difference in serum MBP level was also observed among the three genotypes (GGC/GGC>GGC/GAC>GAC/GAC) (P<0.0001) for all groups, while there were no differences in serum MBP levels for subjects with the same genotypes among the three groups (P>0.05). CONCLUSION: The above findings provide evidence that IgAN patients with abundant immune deposits in glomeruli show a higher frequency of MBP gene variation which is associated with a high frequency of infection and a low serum MBP level. This genetic deficiency may lead to an impaired first-line defense and a less effective clearance of immune complex than those without this mutation and thereafter accelerate glomerular immune deposition during the process of disease.

Adolescent↗
PubMed2001

[Study on effect of ABA, PEG4000 and AgNO3 on number of somatic embryos of Larix Principis-Rupprechtii by 311-A regression design].

This paper, the effects of ABA, PEG400 and AgNO3 on the number of somatic embryos of Larix Principis-Rupprechtii were carried out by 311-A regression design. The regression equation was established which expresses the number of somatic embryos of Larix Principis-Rupprechtii as function, and the ABA, PEG400 and AgNO3 on as variable respectively. Using the regression equation, the single factor effect and mutual effect between the number of somatic embryos of Larix Principis-Rupprechtii and ABA, PEG400 and AgNO3 was studied; the optimum concentration recipes can be obtained by computer processing, that are ABA: 18.9138 mg/L, PEG400: 88.8007 g/L and AgNO3: 10.7513 mg/L, the target somatic embryos number is 107.5278 each gram callus. The results of experiment showed that this method is simple, practical and rapid for selecting several hormone category and concentration recipes media of conifer somatic embryogenesis.

Abscisic Acid↗
PubMed2001

[A permanent implantable pulsatile impeller heart with a specially devised needle bearing].

The author's implantable pulsatile impeller pump can assist the circulation of the calves for several months. The termination of the experiments was related to wear of the mechanical bearing, which resulted in vibration of the rotor and pump failure. It seemed as if the experiments could have lasted indefinitely if the bearing had not failed. To solve the problem of bearing wear, a specially devised rolling bearing was investigated and applied to the impeller pump. Its service life is more than 10 years due to the wear-proof roller made of ultra-highmolecular weight polythene. This newly devised impeller heart promises to have long-term and permanent applications. Compared with the magnetic bearing, the rolling bearing has the advantages of simpler construction and control, no consumption of energy, and better reliability.

Animals↗