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Biomedical subjects

J L Wang

Publications and source records attributed to J L Wang.

At least 91 records · Page 5Linked to original sources

Cyclooxygenase-2-selective inhibitors impair glomerulogenesis and renal cortical development.

BACKGROUND: Antenatal exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) has been associated with renal dysgenesis in humans. METHODS: These studies characterized cyclooxygenase-2 (COX-2) versus COX-1-selective inhibition on nephrogenesis in the rodent using histomorphometry, immunohistology, and in situ hybridization. RESULTS: Administration of a COX-2-selective inhibitor (SC58236), started during pregnancy until weaning, significantly impaired development of the renal cortex and reduced glomerular diameter in both mice and rats. An identical phenotype was demonstrated in COX-2 -/- mice. In contrast to its effects on the developing kidney, a COX-2 inhibitor had no effect on glomerular volume in adult mice. This effect was specific for COX-2 because maternal administration of a COX-1-selective inhibitor (SC58560) did not affect renal development despite significantly inhibiting gastric mucosal prostaglandin E2 (PGE2) synthesis in pups. The expression of COX-2 immunoreactivity peaked in the first postnatal week and was localized to S-shaped bodies and the macula densa in the cortex. Treatment with a COX-2 inhibitor during this period (from postnatal day 0 to day 21) severely reduced glomerular diameter, whereas treatment limited to pregnancy did not affect glomerular size. CONCLUSION: These data demonstrate an important role for COX-2 activity in nephrogenesis in the rodent, and define a specific time period of susceptibility to these effects.

Animals↗

Radiographic parameters for evaluating the neurological spaces in experimental thoracolumbar burst fractures.

It is important to know the condition of neural spaces during the nonoperative treatment of thoracolumbar burst fractures. The goals of the current study were to identify the correlation between the degree of deformity of a fractured vertebra and the encroachment of neural spaces, and to determine how the encroachment and the deformity can be improved by the extension posture simulating the postural reduction. Experimental burst fractures were produced in L1 vertebrae of nine human thoracolumbar spine segments (T11-L3) with neural spaces lined with tiny steel balls. Lateral radiographs were taken in neutral and extended posture before and after the trauma. Anterior vertebral height, posterior vertebral height, vertebral height ratio, vertebral kyphotic angle, posterior vertebral body angle, and the cross diagonal angle were the geometric parameters used to describe the vertebral deformity. The canal diameter and superior and inferior intervertebral foramen areas were defined as the neural spaces. All parameters were measured on the scanned images of radiographs, as seen on the computer screen. Among the vertebral body parameters, the posterior vertebral height, posterior vertebral body angle, and cross diagonal angle showed significantly higher correlations with the canal encroachment. The extended posture did not improve the canal and intervertebral foramen encroachments. The kyphotic deformity (vertebral kyphotic angle and anterior vertebral height) was improved but the deformity of the vertebral posterior wall (posterior vertebral height and posterior vertebral body angle) was not improved because of the extended posture.

Adult↗

Calorigenic actions of leptin are additive to, but not dependent on, those of thyroid hormones.

We examined a possible mechanistic interaction between leptin and thyroid hormones in rats with hypothyroidism induced by thyroidectomy (TX) and propylthiouracil administration. In study 1, the TX rats were treated by vehicle (V, n = 9) or by recombinant murine leptin (L, 0.3 mg. kg(-1). day(-1), n = 9) or were pair-fed (PF, n = 9) against L. In study 2, the TX rats were all given 3, 3'5'-triiodo-L-thyronine (T(3)) replacement (T, 5 microg. kg(-1). day(-1)) to correct hypothyroidism. They were then subdivided into three groups, namely, vehicle (T+V, n = 9), leptin (T+L, n = 10), and pair-feeding (T+PF, n = 9), similar to study 1 except for T(3) (T). Reduced food consumption and weight gain in the TX rats were reversed by T(3) replacement. Leptin suppressed food intake in the TX rats regardless of T(3) replacement. O(2) consumption (VO(2)) and CO(2) production (VCO(2)) were reduced in TX rats (P < 0.05 vs. normal) but were normalized by either T(3) or leptin treatment. T+L additively increased VO(2) and VCO(2) (P < 0.05 vs. TX, T(3), and L). The respiratory exchange ratio was unaltered in TX rats, with and without T(3), but was significantly reduced by L or T+L treatments. These results indicate that the metabolic actions of leptin are not dependent on a normal thyroid status and that the effects of leptin and T(3) on oxidative metabolism are additive.

Animals↗

Nitric oxide regulates renal cortical cyclooxygenase-2 expression.

We have previously shown that cyclooxygenase-2 (COX-2) is localized to the cortical thick ascending limb of the loop of Henle (cTALH)/macula densa of the rat kidney, and expression increases in response to low-salt diet and/or angiotensin-converting enzyme (ACE) inhibition. Because of the localization of neuronal nitric oxide synthase (nNOS) to macula densa and surrounding cTALH, the present study investigated the role of nitric oxide (NO) in the regulation of COX-2 expression. For in vivo studies, rats were fed a normal diet, low-salt diet or low-salt diet combined with the ACE inhibitor captopril. In each group, one-half of them were treated with the nNOS inhibitors 7-nitroinidazole (7-NI) or S-methyl-thiocitrulline. Both of these NOS inhibitors inhibited increases in COX-2 mRNA and immunoreactive protein in response to low salt and low salt+captopril. For in vitro studies, COX-2 expression was studied in primary cultures of rabbit cTALH cells immunodisssected with Tamm-Horsfall antibody. Basal COX-2 immunoreactivity expression was stimulated by S-nitroso-N-acetyl-penicillamine (SNAP), an NO donor, and intracellular cGMP concentration. The cultured cells expressed immunoreactive nNOS, and 7-NI inhibited basal COX-2 immunoreactivity expression, which could be partially overcome by cGMP. In summary, these studies indicate that NO is a mediator of increased renal cortical COX-2 expression seen in volume depletion and suggest important interactions between the NO and COX-2 systems in the regulation of arteriolar tone and the renin-angiotensin system by the macula densa.

Angiotensin-Converting Enzyme Inhibitors↗

Role of p38 in the regulation of renal cortical cyclooxygenase-2 expression by extracellular chloride.

We have previously shown that in renal cortex, COX-2 expression is localized to macula densa and surrounding cortical thick ascending limb of Henle (cTALH). Dietary salt restriction increases local expression of COX-2, which mediates renin production and secretion. Given that decreased luminal chloride [Cl(-)] at the level of the macula densa increases renin production and secretion, we investigated the role of extracellular ion concentration on COX-2 expression. Quiescent rabbit cTALH cells were incubated in a physiological salt solution containing high or low levels of NaCl. Immunoreactive COX-2 expression increased significantly in the low NaCl solution. COX-2 expression also increased after administration of the Na(+)/K(+)/2Cl(-) cotransport inhibitor, bumetanide. Selective substitution of chloride led to increased COX-2 expression, whereas selective substitution of sodium had no effect. The p38 MAP kinase inhibitor PD169316 decreased low NaCl-induced COX-2 expression. Low-salt or low-chloride medium induced cultured cTALH to accumulate >/= 3-fold higher levels of pp38, the activated (phosphorylated) form of p38; low-salt medium also increased pJNK and pERK levels. Feeding rats a low-salt diet for 14 days induced a significant increase in renal cortical pp38 expression, predominantly in the macula densa and cTALH. These results suggest that reduced extracellular chloride leads to increased COX-2 expression, which may be mediated by activation of a p38-dependent signaling pathway.

Animals↗

Major depression and quality of life in individuals with multiple sclerosis.

OBJECTIVE: To compare the Quality of Life (QOL) of multiple sclerosis (MS) patients with and without lifetime major depression. METHOD: Data on 136 MS subjects sampled from the University of Calgary MS Clinic were collected. The WHO's Composite International Diagnostic Interview (CIDI) was used to diagnose lifetime major depression. The MSQOL-54 was administered to evaluate QOL of the subjects. RESULTS: Thirty one (22.8 percent) of the 136 MS subjects had lifetime major depression, However, only 6 of these had a current episode at the time of data collection. MS patients with lifetime major depression had significantly lower MSQOL-54 scores in the QOL domains of Energy, Mental Health, Cognitive Function, General Quality of Life, Sexual Function, and Role Limitation-Emotional than the MS patients without lifetime major depression. CONCLUSIONS: Lifetime major depression may have a substantial impact on the QOL of people with MS. Alternatively, MS patients with poor QOL may be at greater risk of major depression.

Activities of Daily Living↗

Human colon cancer cells express multiple glycoprotein ligands for E-selectin.

The interaction between the colon tumor cell surface and the endothelial cell layer is an important component of tumor intravasation, extravasation, and metastasis. Multiple studies suggest that tumor cells may bind to E-selectin expressed on endothelial cells during these processes. To identify possible E-selectin ligands on tumor cells that may participate in this mechanism, we used E-selectin-Ig chimera affinity chromatography to isolate glycoproteins from the human colon cancer cell line Colo-205. Binding of these cells to E-selectin was specific, required the presence of calcium, and could be blocked by antibodies against E-selectin. We identified LAMP-1 (lysosomal membrane glycoprotein-1), LAMP-2, and two high molecular weight glycoproteins (>400 kDa and 300 kDa) as the main E-selectin ligands on Colo-205 cells. Treatment of the cells with N-glycanase and O-sialoglycoprotease abolished their binding to E-selectin. The high MW glycoproteins contained sialyl Lewis X and/or sialyl Lewis A glycoconjugates, and appeared to be either alternatively spliced or alternatively glycosylated forms of MUC-1 (mucin-1).

Animals↗

[Genetic studies of blast resistance of indica variety Zhefu 802].

One indica variety, Zhefu 802, was studied for its inheritance of blast resistance by inoculation of two strains Ken54-04 and 95-t2. The B1F1 and F2 populations from cross of Zhefu 802(R) x Lijiangxintuanheigu (S) and related parents were inoculated by spray inoculation method with the two above mentioned strains to determine R:S ratio of segregating populations of this cross. The results indicated that Zhefu 802 has two dominant resistance genes to strain Ken 54-04. One of the two genes showed resistant reaction and the other is susceptible to strain 95-t2. The allelism test indicated that one gene in Zhefu 802, which showed resistant reaction to strain 95-t2, is allelic to Pi-i gene locus and non-allelic to loci of Pi-a, Pi-sh, Pi-k, Pi-z, Pi-ta, Pi-b, Pi-t. The other gene in this variety was also estimated to be different from all of the known genes. So it may be an unknown gene. But this point needs to be confirmed further.

Chromosome Mapping↗

[Preliminary study on the purification of IL-2].

Interleukin-2 (IL-2) which is produced by T-lymphocytes is a protein molecule with the molecular weight of 15,420-Daltons. It has good functions in curing a lot of diseases such as cancer and AIDS even with a small quantity. A new method for purification of IL-2 by preparative high performance liquid chromatography is described. It was the first time to use hydroxyapatite as the packing to separate IL-2. IL-2 has one disulphide bridge (between 58th Cys and 105th Cys) and one free cysteine. In order to prevent aggregation and formation of wrong disulphide bond, 50 mumol/L Cu2+ and 1.5 mol/L guanidine hydrochloride was used for autoxidation and denaturing. Then we used mainly two chromatographic steps: First, Sephadex G-25 Gel permeation chromatography was used to separate guanidine hydrochloride and small molecules. Second, large scale preparative HPLC was used to separate impure protein from IL-2. Gradient elution was performed with phosphate buffer (pH 6.8). Its purity was examined by SDS-PAGE. Its activity reached 1 x 10(6) U/mg by CTLL-2 cell MTT method. The results showed that it is a suitable method for the large-scale purification of IL-2.

Chromatography, High Pressure Liquid↗

Automated gas chromatography with cryogenic/sorbent trap for the measurement of volatile organic compounds in the atmosphere.

An automated gas chromatographic system was constructed to easily adapt either the cryogenic trap or chemical sorbent trap for preconcentrating ambient levels of volatile organic compounds. Remarkable similarity in chromatograms from C3 to C10 was found between these two enrichment methods, except that the sorbent trap did not quantitatively trap the C2-hydrocarbons. In contrast to cryogenic trapping, the chromatographic conditions for more volatile compounds were substantially improved using the sorbent trap. Water interference on the porous-layer open tubular column was also better managed using the sorbent trap for the continuous analysis of humid room air. The similarity in peak profiles between the GC-flame ionization detection (FID) and a commercial GC-MS system, regardless of concentration levels, facilitated compound identification on the FID chromatograms based on a field mission involving analysis of 106 air samples.

Adsorption↗

Loosening at the screw-vertebra junction in multilevel anterior cervical plate constructs.

STUDY DESIGN: An in vitro biomechanical study of one-level and three-level corpectomy and anterior cervical plate models. OBJECTIVE: To investigate the failure of the screw-vertebra interfaces in one- and three-level corpectomy models. SUMMARY AND BACKGROUND DATA: Although there are several biomechanical studies of strength and stability of anterior cervical plating, there has been no investigation into clinically observed failures. METHODS: One- and three-level models (corpectomy, strut graft, and anterior plate) were constructed from eight cadaveric specimens (C2-T1). Multidirectional flexibility tests (1.0 Nm moments) performed before and after fatigue (1000 cycles, 1.0 Nm flexion-extension, 0.14 Hz) documented the screw-vertebra motions at upper and lower ends. Ranges of motion and neutral zones were determined. Analysis of variance was used to evaluate significant differences between the upper and lower ends of the plates and changes caused by fatigue loading (P < 0.05). RESULTS: Extension motion at the lower ends was more than at the upper ends in both models. Fatigue increased three-level model ranges of motion at the lower end by 171% in flexion, 164% in extension, 153% in lateral bending, and 115% in axial rotation. Similar increases were observed in neutral zones. Fatigue loading produced no significant changes in one-level models. CONCLUSION: There was excessive screw-vertebra motion caused by fatigue at the lower end of the three-level corpectomy model. These findings of loosening may explain clinically observed failures at the caudal end of long anterior cervical plate constructs. Longer screws, larger diameter screws, and supplemental posterior fixation may decrease screw-vertebra loosening.

Biomechanical Phenomena↗

Export of galectin-3 from nuclei of digitonin-permeabilized mouse 3T3 fibroblasts.

Galectin-3 is a galactose-/lactose-binding protein (M(r) approximately 30,000), identified as a required factor in the splicing of pre-mRNA. Immunofluorescence staining revealed that galectin-3 distributes differentially between the nucleus and the cytoplasm, depending on the proliferative state of the cells under analysis. Using digitonin-permeabilized mouse 3T3 fibroblasts, we provide evidence that galectin-3 is rapidly and selectively exported from the nucleus. Although both phosphorylated and nonphosphorylated isoforms of galectin-3 are found in the nuclear fraction, only phosphorylated galectin-3 is identified in the exported fraction, implying that phosphorylation is important for the nuclear export of the protein. The rate of galectin-3 export is temperature dependent and is decreased by the addition of wheat germ agglutinin. More strikingly, galectin-3 export can be inhibited by the addition of leptomycin B, a drug that disrupts the interaction between the leucine-rich nuclear export signal and its receptor, CRM1 (chromosome maintenance region 1). Indeed, a putative leucine-rich nuclear export signal can be found in residues 241-249 of the murine galectin-3 sequence. Finally, gel filtration of the exported material showed that galectin-3 can be found in at least two high molecular weight complexes (approximately 650 and approximately 60 kDa), both of which can be disrupted by lactose.

3T3 Cells↗

Stabilizing potential of anterior cervical plates in multilevel corpectomies.

STUDY DESIGN: An in vitro investigation of three-dimensional kinematics of cervical spine models of one- and three-level corpectomy with anterior plate fixation. OBJECTIVES: To evaluate the capability of an anterior plate to stabilize the reconstructed cervical spine under simulated physiologic motions, and to study the effects of fatigue loading. SUMMARY OF BACKGROUND DATA: Clinical studies have found high failure rates of multilevel anterior cervical plate fusions, indicating suboptimal stabilization. However, no biomechanical studies have been done to investigate the stabilizing capabilities of long-plate instrumentations in corpectomy models. METHODS: Seven fresh human cadaveric cervical spine specimens (C2-T1) were used. Flexibility tests consisted of flexion, extension, and bilateral torsion, and lateral bending, each with a pure moment of 0.25, 0.5, 0.75, and 1.0 Nm. Stabilizing potential indices [(MotionIntact-MotionInstrumented)/MotionIntact] for ranges of motion and neutral zones obtained from the flexibility tests, were measured when the specimen was intact and after one-level (C5) and three-level (C4, C5, and C6) corpectomies and anterior plate stabilizations). The stabilizing potential indices were re-measured after a 1000-cycle fatigue loading (1 Nm flexion and extension moments at C5 vertebra at 0.14 Hz). RESULTS: The differences in stabilizing potential indices of range of motion and neutral zone between one-level and three-level plates were not significant before fatigue. However, after fatigue, the stabilizing potential indices significantly decreased (P < 0.05) for the three-level model, but not for the one-level plate model. CONCLUSIONS: The capability of an anterior cervical plate to stabilize the spine after three-level corpectomy was significantly reduced with fatigue loading.

Adolescent↗

Direct effects of prolactin on corticosterone release by zona fasciculata-reticularis cells from male rats.

The role of prolactin (PRL) in the male is not fully defined. The aim of this study was to investigate the function and mechanism of PRL on the production of corticosterone by zona fasciculata-reticularis (ZFR) cells in vitro. The ZFR cells were obtained from male rats under normal, hyperprolactinemic, or hypoprolactinemic situation. PRL stimulated the corticosterone release in a dose-dependent pattern in the ZFR cells from normal male rats. The cellular adenosine 3'-5'-cyclic monophosphate (cAMP) concentration positively correlated with PRL concentration in the presence of forskolin or 3-isobutyl-1-methylxanthine (IBMX). PRL enhanced the stimulatory effects of cAMP mimetic reagents, i.e., forskolin, 8-bromo-adenosine 3',5'-cyclic monophosphate (8-Br-cAMP), and IBMX on the release of corticosterone. The adenylate cyclase inhibitor (SQ22536) inhibited the corticosterone release in spite of presence of PRL. Nifedipine (L-type calcium channel blocker) did not inhibit corticosterone release. The hyperprolactinemic condition was actualized by transplantation of donor rat anterior pituitary glands (APs) under kidney capsule. By comparison with the cerebral cortex (CX)-grafted group, AP-graft resulted in an increased release of corticosterone, 3beta-hydroxysteriod dehydrogenase (HSD) activity and cAMP production by ZFR cells. Acute hypoprolactinemic status was induced by bromocriptine for 2 days. The results showed the productions of corticosterone were lower in hypoprolactinemic group than in control group, which were persistent along with different ACTH concentrations. These results suggest that PRL increase the release of corticosterone by ZFR cells via cAMP cascades and 3beta-HSD activity.

1-Methyl-3-isobutylxanthine↗

Distinct effect of intracerebroventricular and intrathecal injections of nociceptin/orphanin FQ in the rat formalin test.

Nociceptin/orphanin FQ (nociceptin/OFQ), a newly discovered heptadecapeptide has been regarded as an endogenous ligand for orphan opioid receptor. The present study was designed to investigate the effect of nociceptin/OFQ on pain response and opioid analgesia in the rat formalin test. The results showed that intracerebroventricular injection of 1 microg nociceptin/OFQ enhanced the pain response, and 0.1 or 0.5 microg nociceptin/OFQ had no effect on formalin-induced pain. When 0.1 or 1 microg nociceptin/OFQ were used together with mu-, delta-, or kappa-opioid receptor agonists, endomorphin-1, DSLET or U50488H, respectively, it attenuated mu- and kappa- but not delta-receptor mediated analgesia. On the other hand, intrathecal injection of nociceptin/OFQ (0.1, 1 and 5 microg) reduced the pain response in the formalin test. In conclusion, nociceptin/OFQ potentiated formalin-induced pain response and antagonized opioid analgesia in the rat brain but inhibited pain response in the spinal cord.

Amino Acid Sequence↗

Mortality oscillations induced by periodic starvation alter sex-mortality differentials in Mediterranean fruit flies.

Sex-specific mortality rates of medflies were monitored in cages containing individuals of both sexes and with food (either sugar-only or full diet) removed every 2nd, 3rd, or 4th day (plus ad libitum controls). The general finding is that periodic starvation led to marked oscillations in raw mortality rates. The specific findings are as follows: (i) female medflies live longer than male medflies when they are subjected to periodic starvation; (ii) male medflies maintained on a full diet experience a catastrophic increase in mortality (40%) on the first day food is removed. This mortality surge was not observed for females on either diet or for males maintained on a sugar-only diet; (ii) life expectancy is inversely related to the amplitude of mortality oscillations caused by food deprivation; and (iv) the large perturbations in mortality at younger ages caused by periodic starvation has little effect on the amplitude of mortality at older ages. In general, our data shed new light on the complexity of the mortality response of medflies to both the type and availability of food and thus provide a complimentary perspective to findings from dietary restriction studies on both vertebrate and invertebrate systems.

Adaptation, Physiological↗

Endothelin-1 enhances plasminogen activator inhibitor-1 production by human brain endothelial cells via protein kinase C-dependent pathway.

The effects of endothelin-1 (ET-1) on the production of plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (t-PA) by human brain-derived endothelial cells in culture were studied. At 100 nmol/L, ET-1 increased PAI-1 production by 88+/-6% within 72 hours, and increased PAI-1 mRNA expression within 1 hour of stimulation; there was no significant effect on t-PA production. PAI-1 activity was also examined and found to increase with ET-1 treatment. Suboptimal concentrations of ET-1 and tumor necrosis factor-alpha (TNF-alpha) acted synergistically to increase PAI-1 production. ET-1 activated protein kinase C and cAMP-dependent protein kinase pathways within 3 to 5 minutes of treatment, with the peak at 10 minutes. Activation of protein kinase C by phorbol-12-myristate-13-acetate (PMA) resulted in increased PAI-1 production, whereas activation of the cAMP-dependent protein kinase by forskolin or dibutyryl cAMP (dBu-cAMP) significantly decreased PAI-1 production. However, simultaneous activation of protein kinase C by PMA and cAMP-dependent protein kinase by dBu-cAMP only slightly attenuated PMA-induced PAI-1 increase. Inhibition of protein kinase C by GF-109213X abolished the effects of ET-1. These results demonstrate that ET-1 and TNF-alpha function synergistically to induce procoagulant activity of brain endothelial cells in a process that involves a protein kinase C-dependent pathway.

Brain↗