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Biomedical subjects

B Li

Publications and source records attributed to B Li.

At least 613 records · Page 34Linked to original sources

Intragraft expression of IL-10 messenger RNA: a novel correlate of renal allograft rejection.

A major conceptual advance is the formulation that type I cytokines (such as IL-2 and IFN-gamma) enhance cellular immunity and are host-protective, and that type II cytokines (such as IL-4 and IL-10) dampen cellular immunity and facilitate the progression of infection. We have explored the intragraft expression of type I and type II cytokines during human renal allograft rejection. RNA was isolated from 98 allograft biopsies, and reverse transcription-PCR was used to amplify and identify intragraft expression of mRNA encoding IL-2, IFN-gamma, IL-4, or IL-10. Intragraft expression of IL-7 mRNA and TGF-beta 1 mRNA was also investigated. Our investigation demonstrated that: (a) intragraft expression of IL-10 mRNA and IL-2 mRNA are significant correlates of acute rejection; (b) IL-4, IL-7, IFN-gamma and TGF-beta 1 mRNA expression do not correlate with acute rejection; and (c) IL-10 does not prevent in vivo expression of IFN-gamma, IL-2, IL-7, or TGF-beta 1. Our studies identify, for the first time, a significant association between intragraft IL-10 mRNA expression and acute rejection, and suggest that treatment strategies capable of constraining IL-10 expression might be of value in the prevention of acute rejection.

Base Sequence↗

Effect of nutrition intervention on intermediate endpoints in esophageal and gastric carcinogenesis.

A nutrition intervention trial involving > 3000 participants was conducted in Linxian, China, where the esophageal and stomach cancer mortality rates are among the highest in the world and suspicion exists that chronic deficiencies of multiple nutrients are etiologically involved. The trial was randomized, double-blind, and placebo-controlled and tested the effect of multivitamin and multimineral supplements in reducing cancer incidence and mortality in adults with cytologically detected esophageal dysplasia. Endoscopic and cytologic examinations of samples of trial participants during the intervention allowed evaluation of intermediate endpoints in esophageal and gastric carcinogenesis, including asymptomatic histologic precancerous lesions and early invasive cancer, epithelial proliferation, and cytologic abnormalities. Results from these ancillary studies suggest that multivitamin and multimineral supplementation may decrease proliferation and enhance cytologic reversion to nondysplasia.

Adult↗

The Linxian trials: mortality rates by vitamin-mineral intervention group.

Two randomized nutrition intervention trials were conducted in Linxian, an area of north central China with some of the world's highest rates of esophageal and stomach cancer and a population with a chronically low intake of several nutrients. One trial used a factorial design that allowed us to assess the effects in nearly 30,000 participants of daily supplementation with four nutrient combinations: retinol and zinc; riboflavin and niacin; vitamin C and molybdenum; and beta-carotene, alpha-tocopherol, and selenium. The second trial provided daily multiple vitamin-mineral supplementation or placebo in 3318 persons with esophageal dysplasia, a precursor to esophageal cancer. After supplements were given for 5.25 y in the general population trial, small but significant reductions in total [relative risk (RR) = 0.91] and cancer (RR = 0.87) mortality were observed in subjects receiving beta-carotene, alpha-tocopherol, and selenium but not the other nutrients. The reductions were greater in women than men, and in those under compared with over the age of 55; however, differences by sex or age were not significant. After multiple vitamin and mineral supplements were given for 6 y in the smaller dysplasia trial, reductions in total (RR = 0.93) and cancer (RR = 0.96) mortality were observed but these were not significant. The largest reductions were for cerebrovascular disease mortality, but the effects differed by sex: a significant reduction was observed in men (RR = 0.45) but not women (RR = 0.90). Restoring adequate intake of certain nutrients may help to lower the risk of cancer and other diseases in this high-risk population.

Adult↗

Possible immunologic involvement of antioxidants in cancer prevention.

The people of Linxian County, China have one of the world's highest rates of esophageal cancer. Two intervention trials were conducted to determine whether supplementation with specific vitamins and minerals could lower mortality from or incidence of cancer in this population and whether supplementation with multiple vitamins and minerals would reduce esophageal and gastric cardia cancer in persons with esophageal dysplasia. About 30,000 general population (GP) subjects in the GP trial were randomly assigned to one of eight intervention groups according to a one-half replicate of a 2(4) factorial experimental design and were supplemented for 5.25 y with four combinations of micronutrients at doses from one to two times the US recommended dietary allowance (RDA). About 3000 subjects in whom dysplasia was diagnosed in the dysplasia trial were randomly assigned to groups receiving daily supplementation with 14 vitamins and 12 minerals at two to three times the US RDA or placebo for 6 y. Results of the dysplasia trial indicate that in individuals with esophageal dysplasia, micronutrient supplementation had little effect on T lymphocyte responses. In contrast, male participants in the GP trial who were supplemented with beta-carotene, vitamin E, and selenium showed significantly (P < 0.05) higher mitogenic responsiveness of T lymphocytes in vitro than those not receiving these micronutrients.

Adult↗

Synthesis and characterization of covalent adducts derived from the binding of benzo[a]pyrene diol expoxide to a -GGG- sequence in a deoxyoligonucleotide.

Direct synthesis and purification procedures are described for the preparation of adducts derived from the covalent binding of 7R,8S-dihydroxy-9S,10R-epoxy-7,8,9,10-tetrahydro-benzo[a]pyrene [(+)-anti-BPDE or (+)-BPDE 2] to each of the three guanine residues (trans-N2-dG lesions) in the oligodeoxyribonucleotide d(CTATG1G2G3TATC). The positions of the modified Gs are defined by Maxam-Gilbert sequencing techniques. Six different oligonucleotides with one or two precisely positioned (+)-anti-BPDE residues are identified. The absorbance, circular dichroism and fluorescence characteristics are changed upon formation of duplexes with the complementary strands d(GATACCCATAG). In the doubly-modified oligonucleotides, a broad, excimer-like long wavelength fluorescence emission band is observed with a maximum near 455 nm only if the two (+)-anti-BPDE-modified Gs are adjacent to one another. The covalently attached (+)-anti-BPDE residues decrease the thermodynamic stabilities of the duplexes; their melting points are markedly dependent on the position of the lesions, being highest with the (+)-anti-BPDE residue at G1 (Tm = 40 degrees C, only 2 degrees C lower than in the case of the unmodified oligonucleotide) and lowest when it is situated at G3 (Tm = 29 degrees C). The implications of these and other physical characteristics are discussed. The facile synthesis of these or similar site-specific and stereochemically defined (+)-trans-anti-BPDE-N2-dG lesions in runs of contiguous guanines in oligodeoxyribonucleotides of specified base sequence should be useful for the design of site-directed mutagenesis studies in vitro and in vivo.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

In vitro and ex vivo activities of antimicrobial agents used in combination with clarithromycin, with or without amikacin, against Mycobacterium avium.

MICs of clarithromycin, amikacin, isoniazid, rifabutin, ciprofloxacin, sparfloxacin, ethambutol, and clofazimine were determined for six isolates of Mycobacterium avium complex (MAC) from AIDS patients both by the radiometric method and by an ex vivo model of infection in human macrophages. The median MICs in macrophages were similar or slightly lower than values found in broth, except for amikacin, which had slightly higher MICs inside the cells. Combinations of clarithromycin with other antimicrobial agents showed that clarithromycin-clofazimine and clarithromycin-rifabutin were synergistic on five of six strains while clarithromycin-amikacin and clarithromycin-isoniazid were antagonistic on one and two strains, respectively. The addition of amikacin made the combinations of clarithromycin-clofazimine and clarithromycin-ethambutol synergistic against all the MAC strains. In the macrophage model, the combination of clarithromycin-clofazimine (mean survival, 21%) and clarithromycin-rifabutin (mean survival, 29%) showed a strong reduction in viable counts compared with single drugs, while clarithromycin-amikacin was less active than single drugs alone. In general, the addition of amikacin did not improve the activity of the combinations, except for clarithromycin-isoniazid-amikacin (mean survival, 19%), which was significantly more active than either clarithromycin-isoniazid or clarithromycin-amikacin. The use of the macrophage model can suggest new combinations of antimicrobial agents with anti-MAC activity which, on the basis of their in vitro effectiveness, would probably be disregarded for assay in animal models.

Amikacin↗

Purification and Characterization of a Cellulose-Binding (beta)-Glucosidase from Cellulose-Degrading Cultures of Phanerochaete chrysosporium.

Extracellular (beta)-glucosidase from cellulose-degrading cultures of Phanerochaete chrysosporium was purified by DEAE-Sephadex chromatography, by Sephacryl S-200 chromatography, and by fast protein liquid chromatography (FPLC) using a Mono Q anion-exchange column. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic (SDS-PAGE) analysis of FPLC-purified (beta)-glucosidase indicated the presence of three enzyme forms with molecular weights of 96,000, 98,000, and 114,000. On further fractionation with a microcrystalline cellulose column, the 114,000-molecular-weight (beta)-glucosidase, which had 82% of the (beta)-glucosidase activity, was bound to cellulose. The (beta)-glucosidases with molecular weights of 96,000 and 98,000 did not bind to cellulose. The cellulose-bound (beta)-glucosidase was eluted completely from the cellulose matrix with water. Cellulose-bound (beta)-glucosidase catalyzed p-nitrophenylglucoside hydrolysis, suggesting that the catalytic site is not involved in cellulose binding. When the cellulose-binding form was incubated with papain for 20 h, no decrease in the enzyme activity was observed; however, approximately 74% of the papain-treated glucosidase did not bind to microcrystalline cellulose. SDS-PAGE analysis of the nonbinding glucosidase produced by papain indicated the presence of three bands with molecular weights in the range of 95,000 to 97,000. On the basis of these results, we propose that the low-molecular-weight (96,000 and 98,000) non-cellulose-binding (beta)-glucosidase forms are most probably formed from the higher-molecular-weight (114,000) cellulose-binding (beta)-glucosidase via extracellular proteolytic hydrolysis. Also, it appears that the extracellular (beta)-glucosidase from P. chrysosporium might be organized into two domains, a cellulose-binding domain and a catalytic domain. Kinetic characterization of the cellulose-binding form is also presented.

Journal Article↗

Myocyte performance during evolution of myocardial infarction in rats: effects of propionyl-L-carnitine.

To determine whether alterations in the mechanical properties and calcium transients of myocytes are important factors in the evolution of the postinfarcted heart, these physiological parameters were measured in the viable muscle cells of the left ventricle 6 h, 2-3 days, 1 wk, and 1 mo after coronary artery occlusion and the documentation of left ventricular failure. In addition, the effects of propionyl-L-carnitine (PLC) on shortening properties and calcium dynamics of single myocytes were established to demonstrate whether the potential increase in ATP generation by this intervention improved myocyte cell function. Myocardial infarction was associated with a progressive increase in length of the spared myocytes, whereas the changes in myocyte diameter were apparent only at the 1-mo interval. Mechanically, myocyte shortening was decreased 43% at 6 h, 34% at 2-3 days, 26% at 1 wk, and 41% at 1 mo after infarction. Similar abnormalities were noted in the velocity of myocyte shortening. Peak systolic calcium was decreased at all intervals after infarction. In contrast, diastolic calcium remained within control values. PLC was capable of ameliorating the mechanical behavior and calcium transients of myocytes, particularly 1 mo after infarction. Thus alterations in muscle cell performance may be important determinants in the development and progression of ischemic cardiomyopathy, and interventions improving myocyte contractility may interfere with the unfavorable outcome of the disease.

Animals↗

Exposure-response relationship between passive smoking and adult pulmonary function.

The effects of exposure to environmental tobacco smoke (ETS) on pulmonary function were investigated in a random sample of 1,033 adults aged 40 to 69 yr from a residential area in Beijing. Compared with those not exposed, those exposed to ETS either at home or at work were associated with a 102-ml (SE = 40 ml) reduction in FEV1 and a 151-ml (SE = 44 ml) reduction in FVC after adjustment for confounding factors. Home and work ETS exposure was respectively associated with a 102-ml (SE = 33 ml) and 61-ml (SE = 34 ml) reduction in FEV1. When the subjects were grouped into three exposure categories (none, home only or work only, and both), the deficits in FEV1 and FVC in the third category were the greatest and statistically significant. The adverse effects of ETS were consistently observed in stratified analyses according to sex, occupational exposure, indoor use of coal stoves, and education. When ETS exposure was measured by the cigarettes smoked by other household members at home per day, an exposure-response association with FEV1 and FVC was again statistically significant. In conclusion, this study demonstrated that there is a significant association between exposure to ETS and reduced levels of FEV1 and FVC in adults, and such an association is dose-dependent.

Adult↗

Stretch-induced programmed myocyte cell death.

To determine the effects of loading on active and passive tensions, programmed cell death, superoxide anion formation, the expression of Fas on myocytes, and side-to-side slippage of myocytes, papillary muscles were exposed to 7-8 and 50 mN/mm2 and these parameters were measured over a 3-h period. Overstretching produced a 21- and a 2.4-fold increase in apoptotic myocyte and nonmyocyte cell death, respectively. Concurrently, the generation of reactive oxygen species increased 2.4-fold and the number of myocytes labeled by Fas protein 21-fold. Moreover, a 15% decrease in the number of myocytes included in the thickness of the papillary muscle was found in combination with a 7% decrease in sarcomere length and the inability of muscles to maintain stable levels of passive and active tensions. The addition of the NO-releasing drug, C87-3754, prevented superoxide anion formation, programmed cell death, and the alterations in active and passive tensions with time of overloaded papillary muscles. In conclusion, overstretching appears to be coupled with oxidant stress, expression of Fas, programmed cell death, architectural rearrangement of myocytes, and impairment in force development of the myocardium.

Animals↗

Air pollution and unscheduled hospital outpatient and emergency room visits.

We conducted a time-series analysis of daily hospital visits and air pollution data to assess acute effects of air pollution on daily unscheduled outpatient visits to internal medicine, pediatric, and emergency departments in the No. 3 Affiliated Hospital of Beijing Medical University in Beijing, China. Sulfur dioxide was marginally significantly associated with total outpatient visits (beta = 41.5, SE = 24.2) and significantly associated with internal medicine (beta = 14.6, SE = 6.7), pediatric (beta = 12.7, SE = 3.7), and emergency room visits (beta = 6.8, SE = 2.7). Total suspended particulates (TSP) was a significant predictor for total outpatient (beta = 21.1, SE = 7.7) and pediatric visits (beta = 3.4, SE = 1.3) and a marginally significant predictor of internal medicine visits (beta = 4.2, SE = 2.2). In a season-specific analysis, SO2 was a significant predictor for total hospital outpatient visits in summer, although the mean daily SO2 concentration was only 17 micrograms/m3 (maximum = 51 micrograms/m3). In winter, SO2 was significantly associated with internal medicine, pediatric, and emergency room visits, and TSP was associated with total outpatient visits. This study suggests an exposure-response relationship between TSP and SO2 and hospital outpatient visits, both at high air pollution levels and at levels well below air quality standards recommended by the World Health Organization.

Air Pollution↗

Induction of systemic and mucosal immune responses following immunization with somatostatin-avidin complexes incorporated into ISCOMS.

Synthetic, biotinylated somatostatin-14 (Somatotropin Release-Inhibiting Factor; SRIF) was conjugated to avidin, and the resulting complex incorporated into immune-stimulating complexes (ISCOMS). The ISCOMS were used to study the systemic and mucosal immune responses induced by parenteral and gastrointestinal vaccination. Mice were immunized by intraperitoneal (IP) and intragastric (IG) routes and subsequently by either IP or IG secondary immunizations (groups-IP/IP; IP/IG; IG/IG). Antigen specific IgG and IgA antibody secreting cells (ASC) from the spleen, mesenteric lymph nodes (MLN) and Peyer's patches (PP's) were studied by an enzyme-linked immunospot assay (ELISPOT). Specific proliferative responses of spleen cells to avidin and to SRIF were measured. Immunization IP/IP evoked the highest serum IgG levels to avidin and to SRIF as well as the highest numbers of splenic IgG isotype ASC. The greatest IgA response in MLN and PP's was induced by IP/IG immunization. Only marginal mucosal immunity and no splenic cell specific proliferative responses were found by IG/IG immunization. These results indicate that ISCOMS are an effective delivery system for protein-peptide antigens. The ISCOMS system described elicited systemic and mucosal antibody immune responses, and primed specific proliferative response when administered IP/IG. This offers another approach for the design and delivery of mucosally administered peptide vaccines.

Administration, Oral↗

cGMP inhibits L-type Ca2+ channel currents through protein phosphorylation in rat pinealocytes.

In this study, the effect of cGMP on the dihydropyridine-sensitive (L-type) Ca2+ current was investigated using the whole cell version of the patch-clamp technique in rat pinealocytes. Dibutyryl-cGMP (1 x 10(-4) M) induced a pronounced inhibition of the L-type Ca2+ channel current. The dibutyryl-cGMP effect was concentration dependent. Elevation of cGMP by nitroprusside had a similar inhibitory action on the L-type Ca2+ channel current. Norepinephrine, which increased cGMP in rat pinealocytes, also inhibited this current. The action of cGMP was independent of cAMP elevation since the cAMP antagonist, Rp-cAMPs, had no effect on the inhibitory action of dibutyryl-cGMP. The involvement of cyclic GMP-dependent protein kinase was suggested by the blocking action of two protein kinase inhibitors, (1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7) and N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA1004), on the dibutyryl-cGMP effect on the L-type Ca2+ channel current. Taken together, these results suggest that (1) cGMP modulates L-type Ca2+ channel currents in rat pinealocytes, causing inhibition of this current; (2) the action of cGMP appears to be independent of cAMP elevation; and (3) phosphorylation by cGMP-dependent protein kinase may be involved.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

O6-methylguanine-DNA methyltransferase in human brain tumors detected by activity assay and monoclonal antibodies.

O6-methylguanine-DNA methyltransferase (MGMT) activity was measured in 68 tissue samples taken from brain. A wide range in activity among samples was observed, with all nonmalignant samples showing transferase activity (Mer+) but approximately 15% of WHO grade II low-grade astrocytomas and WHO grade IV glioblastoma multiformes lacking activity (Mer-). On average, astrocytomas and glioblastomas showed less transferase activity than either nonmalignant tissue or meningiomas. Monoclonal antibodies specific for MGMT showed both cytoplasmic and nuclear staining of Mer+ brain tumor cells in culture but no staining of Mer- cells in culture. In pathology specimens from anaplastic astrocytomas, glioblastoma multiformes, and meningiomas, antibody staining revealed both cytoplasmic and nuclear MGMT, while one sample showed little or no MGMT-specific staining. These results help explain why nitrosoureas have been among the most successful agents in treatment of brain tumors and indicate the subcellular localization for the repair activity, which may be relevant to nitrosourea resistance.

Antibodies, Monoclonal↗

Surgical treatment of hallux valgus by reconstruction of metatarsal arch and modified McBride operation (40 cases report).

72 feet with hallux valgus among 40 patients treated by reconstruction of metatarsal arch and modified McBride operation are reported in this paper. After an average of 4.5 years of postoperative follow-up, the results showed an overall 9 degrees and 3 degrees correction of the hallux abductus angle and the intermetatarsal angle, respectively. 95% of the cases of bunions disappeared, 66% calli under the heads of the first and second metatarsal disappeared, and 91% patients were satisfied with the changes of their feet appearance.

Adult↗