Search PubMed⌕ Search

Biomedical subjects

J Luo

Publications and source records attributed to J Luo.

At least 235 records · Page 13Linked to original sources

Plasma lipids and fatty acid synthase activity are regulated by short-chain fructo-oligosaccharides in sucrose-fed insulin-resistant rats.

The aim of this study was to evaluate the chronic effects of a short-chain fructo-oligosaccharide (FOS)-containing diet on plasma lipids and the activity of fatty acid synthase (FAS) in insulin-resistant rats. Normal male Sprague-Dawley rats, 5 wk old, were randomly assigned to two groups and fed either a sucrose-rich diet (S, 575 g sucrose /kg diet and 140 g lipids/kg diet) or a sucrose-rich diet supplemented with 10 g/100 g short-chain fructo-oligosaccharides (S/FOS). A third reference group (R) was fed a standard nonpurified diet (g/kg, 575 g starch, 50 g fat). After 3 wk the sucrose-fed rats (compared with the R group) were characterized by the following: 1) higher insulin responses after a glucose challenge (P < 0.05); 2) heavier liver (P < 0.001) and retroperitoneal adipose tissue (P < 0.01); 3) hypertriglyceridemia (P < 0.0001) and higher plasma free fatty acids (P < 0.0001); and 4) higher fatty acid synthase activity in the liver but a low activity in the adipose tissue (P < 0.001). The addition of FOS to the diet resulted in 11% lower liver weight than in the S group (P < 0.05) and tended to result in lower adipose tissue weight (P < 0.11). Plasma triglycerides and plasma free fatty acids were lower in S/FOS- than in S-fed rats (P < 0.05). Chylomicrons + VLDL, and intermediate density lipoprotein (IDL) concentrations did not differ between groups, nor was plasma cholesterol influenced by diet. Hepatic FAS activity was lower in S/FOS-fed rats than in the S-fed rats (P < 0.05). In adipose tissue, however, this activity tended to be greater in rats fed S/FOS than in rats fed the S diet (P < 0.07). In conclusion, in a rat model of diet-induced (57.5% sucrose and 14% lipids) insulin resistance, the addition of short-chain FOS prevented some lipid disorders, lowered fatty acid synthase activity in the liver and tended to raise this activity in the adipose tissue. Short-chain FOS, in addition to being a nondigestible sweetener with good bulking capacity, might be useful in the treatment of insulin resistance and hyperlipidemia.

Animals↗

Interaction between iron metabolism and 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice with variants of the Ahr gene: a hepatic oxidative mechanism.

The binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) with the aryl hydrocarbon (AH) receptor and subsequent changes in gene expression have been studied intensively, but the mechanisms by which these lead to toxicity are unclear. We investigated the influence of iron, previously implicated in TCDD-induced hepatic porphyria, in mice with alleles of Ahr that encode receptors with varied affinity for TCDD. The administration of iron to Ahrb-1 C57BL/6J (AH-responsive) mice before a single dose of TCDD (75 micrograms/kg) markedly potentiated not only the hepatic porphyria but also general hepatocellular damage and elevation of plasma hepatic enzymes. The formation of hydroxylated and peroxylated derivatives of uroporphyrins formed from uroporphyrinogen and the induction of a mu-glutathione transferase (GST) were consistent with the operation of an oxidative mechanism. In a comparison of C57BL/6J mice with Ahrb-2 BALB/c (AH-responsive) and Ahrd SWR and DBA/2 (AH-nonresponsive) mice, iron overcame the weak hepatic porphyria and toxicity responses in BALB/c and SWR strains but not in DBA/2. CYP1A isoforms are strongly implicated in the mechanism of porphyria, but activities were lowered by 20-30% with iron treatment, and a comparison of levels between strains did not fully account for the resistance of DBA/2 mice. Studies with the use of gel shift assays and cytosolic aconitase of the capacity of the iron regulatory protein controlling the translation of some iron metabolism proteins showed a significant difference between C57BL/6J and DBA/2 mice after the administration of TCDD. We conclude that iron potentiates both the hepatic porphyria and toxicity of TCDD in susceptible mice in an oxidative process with disturbance of iron regulatory protein capacity. Iron even overcomes the AH-nonresponsive Ahrd allele in the SWR strain but not in DBA/2 mice, which remain resistant.

Alleles↗

Subunit composition of N-methyl-D-aspartate receptors in the central nervous system that contain the NR2D subunit.

The N-methyl-D-aspartate (NMDA) receptor is assembled using proteins from two gene families, NR1 and NR2. Although a few studies have examined the composition of NMDA receptors containing NR1, NR2A, and NR2B, the composition of native NMDA receptors that incorporate the NR2D subunit is not known. The goal of the current study was to examine the subunit composition of native NMDA receptors that contain the NR2D subunit in the rat central nervous system by immunoprecipitation of assembled NMDA receptors from rat brain tissues using specific antibodies against NR1, NR2A, NR2B, and NR2D subunits. NMDA receptors were solubilized using either nondenaturing (native) conditions, in which the subunits remain assembled in complexes, or denaturing conditions, in which the NMDA subunits are dissociated from one another. Each of the antibodies selectively and quantitatively immunoprecipitated only the corresponding subunit when the subunits were solubilized using denaturing conditions. In contrast, when NMDA receptors were solubilized under nondenaturing conditions, immunoprecipitation followed by quantitative immunoblot analysis of the resulting pellets show that the majority of the NR2D protein is associated with the NR1 subunit. In addition, the NR2D subunit forms a heteromeric assembly with NR1, as well as with NR2A and/or NR2B subunits, reflecting ternary complex formation. Finally, a binary complex composed of only NR1/NR2D subunits was found in the thalamus but not in the midbrain, where the complexes always contained either NR2A or NR2B, demonstrating that in the central nervous system, different subtypes of NR2D-containing NMDA receptors are present that vary in spatial expression, perhaps indicating distinct physiological and behavioral roles.

Animals↗

Differential regulation of single CFTR channels by PP2C, PP2A, and other phosphatases.

Cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel activity declines rapidly when excised from transfected Chinese hamster ovary (CHO) or human airway cells because of membrane-associated phosphatase activity. In the present study, we found that CFTR channels usually remained active in patches excised from baby hamster kidney (BHK) cells overexpressing CFTR. Those patches with stable channel activity were used to investigate the regulation of CFTR by exogenous protein phosphatases (PP). Adding PP2A, PP2C, or alkaline phosphatase to excised patches reduced CFTR channel activity by > 90% but did not abolish it completely. PP2B caused weak deactivation, whereas PP1 had no detectable effect on open probability (Po). Interestingly, the time course of deactivation by PP2C was identical to that of the spontaneous rundown observed in some patches after excision. PP2C and PP2A had distinct effects on channel gating Po declined during exposure to exogenous PP2C (and during spontaneous rundown, when it was observed) without any change in mean burst duration. By contrast, deactivation by exogenous PP2A was associated with a dramatic shortening of burst duration similar to that reported previously in patches from cardiac cells during deactivation of CFTR by endogenous phosphatases. Rundown of CFTR-mediated current across intact T84 epithelial cell monolayers was insensitive to toxic levels of the PP2A inhibitor calyculin A. These results demonstrate that exogenous PP2C is a potent regulator of CFTR activity, that its effects on single-channel gating are distinct from those of PP2A but similar to those of endogenous phosphatases in CHO, BHK, and T84 epithelial cells, and that multiple protein phosphatases may be required for complete deactivation of CFTR channels.

Animals↗

In vivo antidiabetic drug discovery.

All of the glucose-lowering agents available today for the treatment of diabetes resulted from the in vivo antidiabetic drug discovery approach. This is not surprising given the limited understanding of the biochemical basis of diabetes. With new developments in the elucidation of the biochemistry and physiology of diabetes, along with the ever-increasing number of drug discovery technologies, screening tests have shifted from in vivo to in vitro and from a cellular to a molecular level. However, there are concerns with this shift because diabetes, especially type 2 diabetes, has multiple and independent molecular defects and most of the molecular targets currently used await clinical validation. One approach (employed by Shaman) has used focused in vivo screening and has been successful in avoiding or minimising the drawbacks of in vivo testing, while maintaining the benefits. It is hoped that the combined use of in vivo and in vitro approaches will generate new breakthroughs in diabetes.

Journal Article↗

Moderate intake of n-3 fatty acids for 2 months has no detrimental effect on glucose metabolism and could ameliorate the lipid profile in type 2 diabetic men. Results of a controlled study.

OBJECTIVE: To evaluate the effect of a moderate dose of fish oil on glycemic control and in vivo insulin action in type 2 diabetic men with elevated plasma triacylglycerols and to determine the effect of the same treatment on gene expression of GLUT4, lipoprotein lipase (LPL), and hormone-sensitive lipase (HSL) in the abdominal adipose tissue. RESEARCH DESIGN AND METHODS: A total of 12 type 2 diabetic men were randomly allocated to 2 months of 6 g daily of either fish oil or sunflower oil, separated by a 2-month washout interval, in a double-blind crossover design. RESULTS: For glucose metabolism, 2 months of fish oil supplementation compared with sunflower oil led to similar fasting plasma insulin, glucose, and HbA1c. Basal hepatic glucose production did not increase after fish oil. There was no difference in insulin suppression of hepatic glucose production nor in insulin stimulation of whole-body glucose disposal measured by the euglycemic-hyperinsulinemic clamp. Fish oil did not ameliorate the low mRNA level of GLUT4 in adipose tissue of these patients. For lipid profile, fish oil lowered plasma triacylglycerol more than sunflower oil (P < 0.05) and tended to increase the amount of mRNA of both LPL and HSL in adipose tissue. CONCLUSIONS: A moderate dose of fish oil did not lead to deleterious effects on glycemic control or whole-body insulin sensitivity in type 2 diabetic men, with preserved triacylglycerol-lowering capacities.

Basal Metabolism↗

[Expression of telomerase in acute leukemia].

To understand the expression patterns of telomerase activity in different types of acute leukemia(AL) and during remission state, the mono-nuclear cells of different bone marrow samples were isolated by desity gradient centrifugation. Telomerase activity of the samples was assayed by telomeric repeat amplification protocol(TRAP) with the cell extracts and the TRAP products were resolved in PAGE. The results showed that the telomerase activity was at higher levels in the acute leukemia compared with the normal controls. Of the acute nonlymphocytic leukemia(ANLL), the telomerase activity presented as M2a > M5b > M1 > M3b. Of the acute lymphocytic leukemia(ALL), the activity presented as L1 > L2. The activity assayed in M2a and L2 remission was as high as that in the normal group. It indicated that the expression of telomerase was enhanced differently among the subtypes of ANLL and ALL, and was down-regulated during the AL remission. It implicates that the expression patterns of telomerase activity in AL is associated with the different proliferation states and differentiation properties of the AL cells.

Adolescent↗

[Changes of blood supply from portal system after transcatheter arterial chemoembolization in huge hepatocellular carcinoma].

OBJECTIVE: Blood supply changes of the portal venous system to the tumor mass before and after transcatheterarterial chemoembolization(TACE) in a series of 22 patients with huge hepatocellular carcinoma were monitored to study the necessity of intervention via portal vein. METHODS: Twenty-two selected patients with huge hepatocellular carcinoma were enrolled in the study. Elscint double helical CT was used to scan liver during the maximum concentration of contrast medium in portal venous system. CT Angiography and MIP(Maximum Intensity Projection) were used to image formation of the portal venous system. RESULTS: The technique of scan and image formation were excellent to evaluate the attribution of portal venous blood supply to HCC. The portal venous blood supply was mainly the tumor periphery distribution (P < 0.01). After treatment of TACE, the portal venous blood supply to tumor periphery increased significantly (P < 0.05), and some did appear signs of enriched blood supply around the tumor. Negative correlation between the degree of reduction in tumor and portal venous blood supply to the tumor periphery before TACE was evident. CONCLUSION: The attribution of portal venous blood supply to HCC was in the tumor periphery, and regression of tumor after TACE was affected by portal venous blood supply to the tumor, thus it is reasonable to suggest interventional therapy via portal vein.

Adult↗

[The clinical significance of multidrug resistance associated protein(MRP) gene expression in acute leukemia].

OBJECTIVE: To investigate the relationship between the expression of the multidrug resistance-associated protein(MRP) gene and clinical drug resistance in acute leukemia(AL). METHODS: Semi-quantitative reverse transcriptase polymerase chain reaction was used to examine the expression of MRP gene in 65 bone marrow aspirates of AL patients and 15 normal volunteer's peripheral blood mononuclear cells. The expression level of MRP were expressed as ratio of MRP/beta 2M(beta 2-microglobulin) and the ratio of MRP/beta 2M > or = 0.3 was defined as MRP positive. RESULTS: The level of MRP mRNA and the positive percentage of MRP in relapsed-refractory group were significantly higher than that in normal control group. In newly diagnosed group, the first complete remission rate of MRP negative patients(84%) was significantly higher than that of MRP positive(25%) patients. MRP expression level was different in leukemia sub-type. MRP and mdr-1 genes were examined simultaneously in 65 AL patients, the mean expression level and positive percentage of MRP and mdr-1 in clinical resistance group were significantly higher than those in non-resistance group. No significant correlation was found between the MRP and mdr-1 expression(rs = 0.1683). CONCLUSION: High expression of MRP leads to drug resistance and it is an unfavorable factor to prognosis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Effect of turmeric volatile oil on the respiratory tract].

OBJECTIVE: Researching the effect of turmeric volatile oil on functions of the respiratory tract. METHOD: The action of turmeric volatile oil on sputum removing, cough and asthma relieving was observed by vapour inhaling. RESULT: The volatile oil is significantly active in removing sputum, relieving cough and preventing asthma. CONCLUSION: Turmeric volatile oil may be an efficacious drug for the treatment of respiratory diseases.

Animals↗

[A computer system for bone age measurement of hand radiographs].

OBJECTIVE: This study was to development a computer system for assessing bone age which would analyse children's growth level accurately and quickly. METHODS: It used the standards of estimating skeletal maturity for Chinese (CHN) scoring method to assess the bone age of Chinese children. We applied image enhancement techniques for imprving the quality of the hand-wrist radiographs, while an automated system was developed to implement this method. RESULTS: Users could get a clear and reliable radiograph through image processing, compare each bone of the hand-wrist radiograph with that of the scanned image of the standard radiographs, then generate the stage of bone maturity. The computer would give out individual and total bone score and a value of bone age. CONCLUSION: This system implemented evaluation of bone age rapidly and accurately, it would help orthodontist to choose the best time of treatment.

Age Determination by Skeleton↗

[Rotating gamma stereotactic radiosurgery system].

A new rotating gamma system and its clinical applications are introduced, and we compare it with stationary Gamma Knife. The results demonstrate that the former has more advantages than stationary Gamma Knife on radiation dose, processing and cost, etc.

Arteriovenous Malformations↗

[Effects of herba Pogostemonis on gastrointestinal tract].

The effects of the three extracts (Decoction, oil-free decoction and volatile oil) of Herba Pogostemonis on gastrointestinal tract were studied. The results showed that all the three extracts inhibited the automatic contraction and Ach, BaCl2-induced spasmodic contraction of isolated rabbit intestine, among the three extracts the volatile oil was the most potent. In vivo the decoction and the oil-free decoction could depress gastric evacuation and inhibit the normal and neostigmine-induced intestinal propellent movement in mice, but the volatile oil could not. The decoction and the oil-free decoction also increased gastric secretion of acid and activity of pepsin and amylase. Furthermore, the decoction and the oil-free decoction reduced the incidence of diarrhea induced by senna but volatile oil enhanced cooperatively. All the three extracts relieved the gripping pain induced by abdominal administration of acetic acid, and the effect of decoction was more potent that the others. The above results revealed that the effective components of Herba Pogostemonis may be mainly water-solube.

Animals↗

Abdominal aortic aneurysm repair via percutaneous endovascular stenting in the swine model.

Abdominal aortic aneurysms (AAAs) are the 13th leading cause of death in the United States. Endovascular stent grafts are currently being investigated in clinical trials as an alternative method for treatment of AAA. Twelve pigs underwent creation of AAA using the abdominus rectus fascia. Postoperatively, all 12 animals underwent angiography, which demonstrated turbulent flow within the created aneurysms. Four of the animals were not stented and served as controls. Eight animals underwent subsequent percutaneous placement of a covered endovascular stent via a right femoral sheath, and the stents were deployed between the renal arteries and the aortic bifurcation. The animals were maintained for 120 days before sacrifice and necropsy. Unstented animals (4) died within 6 days, 3 from rupture. Eight animals underwent endovascular stenting: 5 survived without complications, 3 deaths within 2 days were related to technical complications. The 5 surviving animals were sacrificed at 120 days, and necropsy was conducted with in situ dissections of the aorta and intact stent: 3 experimental animals had correct anatomic positioning of the stent, and 2 had inexact stent placement but survived 120 days with AAA thrombosis. Treatment of AAA in this swine model has been demonstrated via placement of a percutaneous covered stent.

Animals↗

Dopaminergic neurotoxin administration to the area of the suprachiasmatic nuclei induces insulin resistance.

Dopaminergic neuron neurotoxin (6-hydroxydopamine; 6-OHDA) administration directed to the hypothalamic area of the mammalian pacemaker, the suprachiasmatic nuclei (SCN), was carried out on lean, glucose tolerant hamsters to investigate the possibility that dopaminergic input to the vicinity of the SCN is necessary to maintain this metabolic condition. Glucose tolerance tests (GTT, 3 g glucose/kg) were performed 4 days prior to and 16 days after neurotoxin lesioning. 6-OHDA administration to the area of the SCN resulted in both a significant 58% increase in daily food consumption by the 16th day post-lesioning, and a 85% increase in weight gain 4 and 8 weeks after lesioning relative to controls. Such treatment also significantly increased the total areas under the GTT glucose and insulin curves by 48% and 400% respectively, compared with controls. These findings indicate that body weight gain, glucose intolerance and insulin resistance result from decreased dopaminergic input to the area of the SCN.

Analysis of Variance↗

Basic fibroblast growth factor- and platelet-derived growth factor-mediated cell proliferation in B104 neuroblastoma cells: effect of ethanol on cell cycle kinetics.

In vivo studies show (a) that early exposure to ethanol depletes neurons in the central nervous system (CNS) and (b) that a primary target of ethanol in the developing nervous system is proliferating neuronal precursors. We used a neuronal cell line (B 104 neuroblastoma cells) as an in vitro model for the effects of ethanol on the proliferation of neuronal precursors to test the hypothesis that ethanol interferes with growth factor-regulated proliferation of neuron-like precursors. The effects of ethanol on the mitogenic activity of two growth factors, basic fibroblast growth factor (bFGF) and platelet-derived growth factor AA and BB (PDGF-AA and PDGF-BB), were examined. Cell proliferation was monitored by tracing the change in the numbers of cultured cells over 4-5 days and in the cell cycle kinetics was determined using a cumulative labeling technique with bromodeoxyuridine (BrdU). Western immunoblots and immunohistochemical preparations show that B104 cells expressed the high affinity receptors for bFGF, PDGF-AA and PDGF-BB. The three growth factors were potent mitogens for the B104 cells; they promoted an increase in cell number even when the cells were grown in serum-free medium. Ethanol depressed the bFGF-, PDGF-AA- and PDGF-BB-mediated cell proliferation without altering the incidence of cell death. These changes in proliferation were concentration-dependent; at a concentration of 100 mg/dl, ethanol partially, but significantly inhibited growth factor-stimulated proliferation and higher ethanol concentrations (400 mg/dl or more) completely abolished growth factor-regulated cell proliferation. The effects of ethanol on cell growth were a result of ethanol-induced changes in growth factor-regulated cell cycle kinetics, principally the total length of the cell cycle and the fraction of the population that was actively cycling (the growth fraction). Ethanol completely negated the action of bFGF, but only partially blocked PDGF-promoted cycling activity. Thus, B104 cells are a suitable model for studying the effects of ethanol on neuronal proliferation. The blockage of bFGF- and PDGF-mediated cell proliferation by ethanol supports the hypothesis that growth factors are a target of ethanol neurotoxicity. Furthermore, the differential actions and effects of ethanol on the two growth factors mirror effects observed in vivo.

Anticoagulants↗

Noncoded amino acid replacement probes of the aspartate aminotransferase mechanism.

The primary role of Tyr225 in the aspartate aminotransferase mechanism is to provide a hydrogen bond to stabilize the 3'O- functionality of bound pyridoxal phosphate. The strength of this hydrogen bond is perturbed by replacement of Tyr225 with 3-fluoro-L-tyrosine (FlTyr) by in vitro transcription/translation. This mutant enzyme exhibits kcat/values that are near to those of wild type enzyme; however, the kcat/vs pH profile is much sharper with similar pKas of approximately 7.5 for both the ascending and descending limbs. The pKas are assigned to the endocyclic proton of the internal aldimine and to the bridging hydrogen bond, respectively. The pKas in the kcat vs pH profile of 7.2 and 8.7 are assigned to the epsilon-NH3+ of lysine 258 and to the endocyclic protons of the ketimine complex, respectively. Arginine 292 forms a salt bridge with the beta-COOH of the substrate, aspartate. An improvement on the earlier attempt to invert the substrate charge specificity via R292D mutation-induced arginine transaminase activity [Cronin, C. N., & Kirsch, J. F. (1988) Biochemistry 27, 4572-4579] is described. Here Arg292 is replaced with homoglutamate (R292hoGlu). This construct exhibits 6.8 x 10(4)-fold greater activity for the cationic substrate D,L-[Calpha-3H]-alpha-amino-beta-guanidinopropionic acid (D,L-[Calpha-3H]AGPA) than does wild type enzyme. The gain in selectivity for this substrate is at least 4500-fold greater than that achieved in the 1988 experiment, i.e., [(kcat/KM)R292hoGlu/(kcat/KM)WT (D,L-[Calpha-3H]AGPA)] >/= 4500 x [(kcat/KM)R292D/(kcat/KM)WT (L-arginine)]. The value of (kcat/KM)R292D is 0.43 M-1 s-1 with L-Arg while (kcat/KM)R292hoGlu is 29 M-1 s-1 with D,L-[Calpha-3H]AGPA (it is assumed that the D-enantiomer is unreactive). The latter value is the lower limit because of the uncertain value of 3H kinetic isotope effect.

Alanine↗