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Biomedical subjects

B Luo

Publications and source records attributed to B Luo.

At least 19 recordsLinked to original sources

Diabetes induces rapid suppression of adaptive immunity followed by homeostatic T-cell proliferation.

Surprisingly, the effect of acute diabetes on immunity has not been examined in detail. We, herein, show for the first time that untreated acute diabetes causes rapid lymphopenia followed by homeostatic T-cell proliferation. The diabetes-induced lymphopenia was associated with an immunosuppressed state that could be sufficiently strong to allow engraftment of fully allogeneic beta-cells or block rejection of islet transplants. In contrast, homeostatic proliferation and recovery of T-cell numbers were associated with islet rejection. Thus, the timing of islet transplant challenge in relation to diabetes induction was critical in determining whether islets were accepted or rejected. In addition, we tested whether diabetes-related immunosuppression could result in an overestimation of the efficacy of a tolerance-inducing protocol. Consistent with this possibility, a protocol targeting CD40L and ICOS that we have shown induces tolerance in diabetic recipients was unable to induce tolerance in non-diabetic recipients. The data uncover a previously unrecognized suppressive effect of diabetes on adaptive immunity. Furthermore, they suggest that the standard methods of testing new tolerance-inducing protocols in islet transplantation require modification and that diabetes itself can contribute to homeostatic proliferation, a process associated with autoimmunity and a resistance to tolerance induction.

Animals↗

Absence of GABA type A signaling in adult medial habenular neurons.

Neural inhibition in the brain is mainly mediated by ionotropic GABA type A receptors. Apart from the GABA type A receptors, both K(+)-Cl(-) cotransporter isoform 2 and the GABA-synthesizing enzyme, glutamic acid decarboxylase, are essential determinants for GABA type A receptor-mediated inhibition. By using immunofluorescent staining, we observed that K(+)-Cl(-) cotransporter isoform 2, GABA type A receptor beta2/3 subunits and a presynaptically localized glutamic acid decarboxylase isoform, glutamic acid decarboxylase 65, were all absent in adult Sprague-Dawley rat medial habenular nucleus, while immunopositive staining for glutamic acid decarboxylase 67, GABA and GABA type B receptor type 2 subunit were present in the medial habenular nucleus. Consistent with the lack of GABA type A signaling as detected by immunohistochemistry, GABA (100 muM) evoked no measurable currents in the medial habenular nucleus but induced bicuculline-sensitive currents in the lateral habenular nucleus and in the CA1 area of hippocampus. We also failed to record miniature inhibitory postsynaptic currents in medial habenular nucleus neurons. These results support the idea that GABAergic transmission in medial habenular nucleus is probably not mediated by any of the most common GABA type A receptor subtypes. Our data suggest that GABA type B receptor-mediated inhibition may play a role in balancing neuronal excitation in this special region. Further exploration for factors determining medial habenular nucleus neural inhibition will lead to a more complete understanding of control of synaptic balance in the CNS.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Toward quantifying the effectiveness of water trading under uncertainty.

This paper presents a methodology for quantifying the effectiveness of water-trading under uncertainty, by developing an optimization model based on the interval-parameter two-stage stochastic program (TSP) technique. In the study, the effectiveness of a water-trading program is measured by the water volume that can be released through trading from a statistical point of view. The methodology can also deal with recourse water allocation problems generated by randomness in water availability and, at the same time, tackle uncertainties expressed as intervals in the trading system. The developed methodology was tested with a hypothetical water-trading program in an agricultural system in the Swift Current Creek watershed, Canada. Study results indicate that the methodology can effectively measure the effectiveness of a trading program through estimating the water volume being released through trading in a long-term view. A sensitivity analysis was also conducted to analyze the effects of different trading costs on the trading program. It shows that the trading efforts would become ineffective when the trading costs are too high. The case study also demonstrates that the trading program is more effective in a dry season when total water availability is in shortage.

Agriculture↗

A simulation-based interval two-stage stochastic model for agricultural non-point source pollution control through land retirement.

This study presents a simulation-based interval two-stage stochastic programming (SITSP) model for agricultural non-point source (NPS) pollution control through land retirement under uncertain conditions. The modeling framework was established by the development of an interval two-stage stochastic program, with its random parameters being provided by the statistical analysis of the simulation outcomes of a distributed water quality approach. The developed model can deal with the tradeoff between agricultural revenue and "off-site" water quality concern under random effluent discharge for a land retirement scheme through minimizing the expected value of long-term total economic and environmental cost. In addition, the uncertainties presented as interval numbers in the agriculture-water system can be effectively quantified with the interval programming. By subdividing the whole agricultural watershed into different zones, the most pollution-related sensitive cropland can be identified and an optimal land retirement scheme can be obtained through the modeling approach. The developed method was applied to the Swift Current Creek watershed in Canada for soil erosion control through land retirement. The Hydrological Simulation Program-FORTRAN (HSPF) was used to simulate the sediment information for this case study. Obtained results indicate that the total economic and environmental cost of the entire agriculture-water system can be limited within an interval value for the optimal land retirement schemes. Meanwhile, a best and worst land retirement scheme was obtained for the study watershed under various uncertainties.

Agriculture↗

An inexact fuzzy two-stage stochastic model for quantifying the efficiency of nonpoint source effluent trading under uncertainty.

Reduction of nonpoint source (NPS) pollution from agricultural lands is a major concern in most countries. One method to reduce NPS pollution is through land retirement programs. This method, however, may result in enormous economic costs especially when large sums of croplands need to be retired. To reduce the cost, effluent trading can be employed to couple with land retirement programs. However, the trading efforts can also become inefficient due to various uncertainties existing in stochastic, interval, and fuzzy formats in agricultural systems. Thus, it is desired to develop improved methods to effectively quantify the efficiency of potential trading efforts by considering those uncertainties. In this respect, this paper presents an inexact fuzzy two-stage stochastic programming model to tackle such problems. The proposed model can facilitate decision-making to implement trading efforts for agricultural NPS pollution reduction through land retirement programs. The applicability of the model is demonstrated through a hypothetical effluent trading program within a subcatchment of the Lake Tai Basin in China. The study results indicate that the efficiency of the trading program is significantly influenced by precipitation amount, agricultural activities, and level of discharge limits of pollutants. The results also show that the trading program will be more effective for low precipitation years and with stricter discharge limits.

Agriculture↗

Tachykinin NK3-receptor deficiency does not inhibit pulmonary eosinophilia in allergic mice.

Tachykinins are important in the development of pulmonary inflammation in mice but the tachykinin receptor subtype mediating this response has not been defined. To elucidate the role of tachykinin NK3-receptors on allergen-induced pulmonary inflammation, studies were performed on ovalbumin (OVA) sensitized and challenged mice with genetic disruption of the tachykinin NK3-receptor (NK3-/-). Aerosol OVA (0.5%) challenge produced eosinophil influx into the bronchoalveolar lavage fluid and lung tissue, goblet cell hyperplasia and damage to the airway epithelium of both NK3-/- mice and in wild type control mice (NK3+/+). There was no difference in the magnitude of these allergic inflammatory pulmonary responses between NK3-/- and NK3+/+ mice. These results find no role for tachykinin NK3-receptors on the pulmonary eosinophilia and lung damage after antigen challenge in mice.

Animals↗

Microenvironment-driven changes in the expression profile of hematopoietic cobblestone area-forming cells.

Studies with ex vivo cultures of bone marrow have indicated the importance of the adherent layer as a primary reservoir of the most primitive hematopoietic stem cells, from which derivative stem cells and more differentiated progenitors are continuously generated. We used the Affymetrix GeneChip to analyze the mRNA expressions between bone marrow-derived hematopoietic progenitor cells in the cobblestone areas (CA) and the free-floating cells released from the CA formations. Mouse bone marrow hematopoietic progenitor cell line FDCP-Mix and S17 stromal cells were used in this study. Of the 12,000 genes on the chip, only 29 showed more than fivefold higher in CAFC; and for cells in the supernatant, only 55 showed fivefold higher expressions than in the cobblestone area-forming cells (CAFC). The hematopoietic cells in CAFC expressed genes associated with homing, adhesion, and suppression of differentiation, while the free-floating hematopoietic cells showed mature lineage markers and differentiation-specific genes. This confirmed the more primitive nature of the hematopoietic cells in the adherent layer. Of interest in the findings were the discoveries of many secreted and surface protein expressions in CA hematopoietic cells. This may imply interactions among the hematopoietic cells, stromal cells, and the extracellular matrix in CA, which drive the growth, maturation, and differentiation of the hematopoietic cells.

Animals↗

[Surgical treatment to an old patient with right coronary artery aneurysm; report of a case].

The patient was 75-year-old woman. The patient was referred to our hospital for operation due to a developing right coronary artery aneurysm. The coronary artery angiography showed that the aneurysm was 3 cm in diameter which had not existed two years previously, and with a 75% distal stenosis. The operation was made during cardiac arrest. A sapheous vein graft was used to bypass to the distal artery first. Then the aneurysm was resected, and both proximal and distal arteries were ligated. The pacemaker was implanted on the third postoperative day for sick sinus syndrome, the patient got a better recovery. Surgical treatment should be recommended to coronary artery aneurysm, and sapheous vein was a good selection for bypass graft when the diameter of native artery was relatively large.

Aged↗

Rapamycin and T cell costimulatory blockade as post-transplant treatment promote fully MHC-mismatched allogeneic bone marrow engraftment under irradiation-free conditioning therapy.

Hematopoietic macrochimerism, established by bone marrow transplantation, can be used as an approach for treating autoimmune disease and inducing transplant tolerance. In this study, we investigated whether a stable, high level of fully MHC-mismatched hematopoietic macrochimerism can be induced by using irradiation-free protocols, and whether rapamycin and T cell costimulatory blockades (anti-CD40L monoclonal antibody (mAb) and CTLA4Ig) as post-transplant treatment promote bone marrow engraftment. Donor-specific blood transfusion (DST), anti-lymphocyte serum (ALS), busulfan, and cyclophosphamide were given pretransplantation. Balb/c (H-2(d)) bone marrow cells, at a dose of 4 x 10(7), were infused into each C57BL/6 mouse (H-2(b)). Rapamycin, anti-CD40L mAb, and CTLA4Ig were then administered, either alone or in combination. Without ALS or busulfan and cyclophosphamide, macrochimerism can only rarely be induced. Donor-specific transfusion (DST) enhances induction of hematopoietic macrochimerism. Rapamycin, anti-CD40L mAb and CTLA4Ig, alone or in combination, induce a stable and high level of hematopoietic macrochimerism. In the chimeric mice, donor-derived cells were detected in all lymphohematopoietic tissues and donor-specific tolerance was induced in vitro. We conclude that a stable and high level of fully MHC-mismatched hematopoietic macrochimerism can be induced in mice after transplanting a single modest dose of bone marrow cells without irradiation. Rapamycin and T cell costimulatory blockade as post-transplant treatment promote bone marrow engraftment.

Animals↗

Bis(dimethylamido) complexes of alkyl- and phenylgallium. Useful precursors to the RGa(2+) synthon.

Alkyl- and phenylbis(dimethylamido)gallium, [RGa(NMe(2))(2)](2) [R = Me (1), Et (2), (n)Bu (3), (n)Hx (4), and Ph (5)], were synthesized by reactions of LiNMe(2) with (RGaCl(2))(2). The crystal structure of compound 1 was a disordered mixture of anti and syn isomers, with the ratio of anti/syn being 64:36, which was consistent with the ratio (57:43) found in the (1)H NMR spectrum. The Ga(2)N(2) cores of the anti and syn structures were nonplanar. (1)H NMR spectra indicated the presence of both anti and syn isomers for all of the other substituents. (1)H NMR and mass spectra indicated that a species with the general formula of R(3)Ga(2)(NMe(2))(3) was formed when these compounds were heated at high temperatures.

Journal Article↗

Gallane complexes with amido-amine ligands.

Gallane complexes bearing amido-amine ligands -N(R)CH2CMe2CH2NMe2 [R = H or SiMe3 (TMS)], (H2Ga[N(H)CH2CMe2CH2NMe2])2, 1, H2Ga[N(TMS)CH2CMe2CH2NMe2], 2, (H(Cl)Ga[N(H)CH2CMe2CH2NMe2])2, 3, ([(TMS)2N](H)Ga[N(H)CH2CMe2CH2NMe2])2, 4, and HGa[N(TMS)CH2CMe2CH2NMe2]2, 5, were synthesized from the reactions of the quinuclidine adducts of mono- and dichlorogallane with the corresponding lithium amides. Structural determinations of compounds 1, 3, and 4 showed all were dimeric with bridging amido groups. Rather than bond to gallium the tertiary amine groups in 1 and 4 were hydrogen-bonded to the amino N-H. In the structure of compound 3 the amine group occupied an axial position in the trigonal bipyramidal geometry of the five-coordinate gallium. The results were rationalized in terms of the steric and electronic properties of gallium ligands.

Journal Article↗

Peptides that mimic glycosaminoglycans: high-affinity ligands for a hyaluronan binding domain.

BACKGROUND: Hyaluronan (HA) is a non-sulfated glycosaminoglycan (GAG) that promotes motility, adhesion, and proliferation in mammalian cells, as mediated by cell-surface HA receptors. We sought to identify non-carbohydrate ligands that would bind to and activate cell-surface HA receptors. Such analogs could have important therapeutic uses in the treatment of cancer, wound healing, and arthritis, since such ligands would be resistant to degradation by hyaluronidase (HAse). RESULTS: Peptide ligands that bind specifically to the recombinant HA binding domain (BD) of the receptor for hyaluronan-mediated motility (RHAMM) were obtained by screening two peptide libraries: (i) random 8-mers and (ii) biased 8-mers with alternating acidic side chains, i.e. XZXZXZXZ (X=all-L-amino acids except Cys, Lys, or Arg; Z=D-Asp, L-Asp, D-Glu, or L-Glu). Selectivity of the peptide ligands for the HABD was established by (i) detection of binding of biotin- or fluorescein-labeled peptides to immobilized proteins and (ii) fluorescence polarization of FITC-labeled peptides with the HABD in solution. HA competitively displaced binding of peptides to the HABD, while other GAGs were less effective competitors. The stereochemistry of four biased octapeptides was established by synthesis of the 16 stereoisomers of each peptide. Binding assays demonstrated a strong preference for alternating D and L configurations for the acidic residues, consistent with the calculated orientation of glucuronic acid moieties of HA. CONCLUSIONS: Two classes of HAse-resistant peptide mimetics of HA were identified with high affinity, HA-compatible binding to the RHAMM HABD. This demonstrated that non-HA ligands specific to a given HA binding protein could be engineered, permitting receptor-specific targeting.

Amino Acid Sequence↗

Biliary cyst fluid from common bile duct-ligated rats stimulates endothelial nitric oxide synthase in pulmonary artery endothelial cells: a potential role in hepatopulmonary syndrome.

The hepatopulmonary syndrome (HPS) results from pulmonary microvascular dilatation in cirrhosis and is associated with increased pulmonary endothelial nitric oxide synthase (eNOS) levels. In the common bile duct ligation (CBDL) model, endothelin-1 (ET-1) released from the liver contributes to the rise in pulmonary eNOS and intrapulmonary vasodilatation. Whether substances, including ET-1, are found in the biliary tree and selectively enter the circulation after CBDL to influence the pulmonary vasculature is unknown. We assessed if control bile and fluid obtained from the obstructed biliary tree in CBDL animals contains ET-1 and alters eNOS expression and activity in bovine pulmonary artery endothelial cells (BPAECs). Control bile and biliary cyst fluid contained concentrations of ET-1 25- to 42-fold normal plasma levels, and hepatic venous concentrations of ET-1 were selectively increased after CBDL. Biliary cyst fluid caused a dose-dependent induction of eNOS messenger RNA (mRNA) (1.9-fold control), protein (2.5-fold control), and enzyme activity (2.2-fold control) maximal at a 1:10 dilution. The increases were associated with enhanced nitric oxide (NO) production (3.1-fold control) and were inhibitable with an ET(B) receptor antagonist. Bile from sham and portal vein-ligated animals did not increase eNOS expression and at dilutions of 1:100 and 1:10 caused cell toxicity. These results show that bile and biliary cyst fluid contain high concentrations of ET-1 that are specifically increased in hepatic venous blood after CBDL. Biliary cyst fluid increases eNOS expression and activity in an ET(B) receptor-dependent manner in BPAECs. The findings suggest a novel mechanism for the susceptibility of CBDL animals to the HPS.

Animals↗

Effect of anti-mIL-9 antibody on the development of pulmonary inflammation and airway hyperresponsiveness in allergic mice.

Interleukin (IL)-9 is a T-cell-derived cytokine with pleiotropic activities on T helper 2 cells, B cells, and mast cells. IL-9 may therefore play an important role in the development of allergic pulmonary inflammatory diseases. In this study, an antimouse IL-9 (anti-mIL-9) antibody (Ab) was evaluated against pulmonary eosinophilia, histopathologic changes in lung tissues, serum immunoglobulin (Ig) E levels, and airway hyperresponsiveness (AHR) to methacholine in mice sensitized and challenged with ovalbumin (OVA). Additionally, steady-state levels of IL-4, IL-5, IL-13, and interferon-gamma messenger RNA (mRNA) in the lungs were measured. The anti-mIL-9 Ab (200 microg/mouse, intraperitoneally) was given as either four doses during the sensitization period or as a single dose before OVA challenge. Sensitized mice challenged with OVA displayed marked pulmonary eosinophilia, epithelial damage, and goblet cell hyperplasia. OVA challenge also increased mRNA levels of IL-4, IL-5, and IL-13 in the lungs. AHR was also increased twofold in sensitized, challenged mice. Treatment of sensitized, challenged mice with four doses of anti-mIL-9 Ab significantly reduced pulmonary eosinophilia, serum IgE levels, goblet cell hyperplasia, airway epithelial damage, and AHR, but had no effect on IL-4, IL-5, and IL-13 mRNA levels in the lungs. A single dose of the antibody was ineffective on all measures. These results indicate that an antibody to mIL-9 inhibits the development of allergic pulmonary inflammation and AHR in mice.

Animals↗

[Grafting and concomitant left ventricular myotomy-myectomy in a patient with coronary artery disease associated with hypertrophic obstructive cardiomyopathy].

A 44-year-old man complained of chest oppression and systolic murmur. Echocardiography showed subaortic stenosis with outflow gradient of 135 mmHg, interventricular septal thickness of 21 mm, left ventricular posterior wall thickness of 11 mm, and 2/4 mitral regurgitation. Selective coronary angiography demonstrated 75% stenosis in left anterior desending branch. Coronary artery revasculization comcomitant with left ventricular myotomy-myectomy was performed. He had a good recovery from operation, and was discharged in 19th days in NYHA class I. Echocardiography one month after operation showed mild outflow pressure gradient, light systolic anterior motion of mitral anterior leaflet, and 1/4 mitral regurgitation. Careful operative management, including myocardial protection, avoiding perporation of ventricular septum, and postoperative medical care are mandatory to this group of patients. The use of cathecholamine and Ca-blocker will be attentioned because of the increasing the left ventricular pressure gradient.

Adult↗

[The study of PAI-1 promotor region gene polymorphism in cerebrovascular disease].

OBJECTIVE: To investigate the relationship between the plasminogen activator inhibitor-1(PAI-1) gene polymorphism and cerebrovascular disease and detect whether it plays an important role in the pathogenesis of cerebrovascular disease. METHODS: Peripheral blood leukocytes samples were collected from 60 normal controls, 65 patients with acute cerebral infarction (CI) and 31 hypertensives complicated with cerebral hemorrhage. The 4G/5G allele polymorphism in the PAI-1 gene promotor region of the leukocytes was genotyped by polymerase chain reaction. The plasma PAI-1 activity was assayed by ELISA. RESULTS: The plasma PAI-1 activity level in the CI group was significantly higher than those in the other two groups. PAI-1 level in 4G allele homozygous genotype was significantly higher than the PAI-1 levels in 4G/5G heterozygous and 5G homozygous. Although PAI-1 level was higher in 4G/5G heterozygous genotype than in 5G homozygous, the difference was not statistically significant. There were significant differences between acute cerebral infarction PAI-1 gene polymorphism and controls (P<0.05), and the frequencies of 4G/4G genotype in patients with acute cerebral infarction (43.08%) were higher than those in normal controls (20.00%, P<0.05). There were no significant differences between hypertensives complicated with hemorrhage (25.81%) and controls (P>0.05), and the PAI-1 levels of the 4G/4G genotype in the female patients with CI were higher than those in the male patients with CI of the same genotype. CONCLUSION: The results suggest that PAI-1 gene polymorphism may be a susceptible factor to acute cerebral infarction in Chinese, and 4G allele homozygous genotype may be the major risk factor for acute cerebral infarction, and it may be especially an independent risk factor of cerebral infarction in female patients.

Cerebral Hemorrhage↗

[Treatment of severe hepatitis with artificial liver support system and liver transplantation].

OBJECTIVE: To observe and investigate the efficacy of the hybrid artificial liver support system plus liver transplantation in the treatments of patients with severe viral hepatitis. METHODS: Eight severe viral hepatitis patients with metaphase and advanced stage liver failure received the artificial liver support using a self-command extracorporeal hybrid artificial liver support system and orthotopic liver transplantation after the artificial support for 3-14 days. RESULTS: The liver failure of the 8 patients was controlled by the hybrid artificial liver support effectively. All patients were successfully bridged to orthotopic liver transplantation. Four out of the eight patients survived after transplantation. Four patients died of pulmonary infection or hepatorenal syndrome. CONCLUSIONS: Artificial liver support system combined with liver transplantation can be regarded as an efficient measure for the treatment of metaphase and advanced stage patients of severe viral hepatitis.

Adult↗

[Clinicopathologic analysis of ovarian serous and mucinous borderline tumors].

OBJECTIVE: To understand the clinicopathological features of ovarian borderline tumors and evaluate the significance of various histological appearances. METHODS: Forty-five patients with borderline tumors were analyzed retrospectively. The stage distribution was stage I, 34 patients, stage II, 4 patients and stage III, 7 patients. RESULTS: Forty-five cases of borderline tumors accounted for 25.4% of ovarian epithelial malignant tumors. The ratio of serous borderline tumors (SBTs) to mucinous borderline tumors (MBTs) was approximately 1:1.3. Nine of eleven SBTs with exophytic growth presented peritoneal implants, of which two were invasive and seven noninvasive. Two SBTs and 1 MBT recurred after 5, 4, and 1 years respectively. Thirty-three cases were followed from 2 to 9 years. The 5-year survival rate was 100% (Kaplan-Meir method). CONCLUSIONS: The prognosis of the SBTs is favorable. SBTs with exophytic growth are often associated with peritoneum implants.

Adenocarcinoma, Mucinous↗