h-BN nanosheets as simple and effective additives to largely enhance the activity of Au/TiO2 plasmonic photocatalysts.

The activity of Au nanoparticle-loaded P25 TiO2 (Au/P25) plasmonic photocatalysts, evaluated by the oxidative decomposition of formic acid in water under visible light irradiation, was enhanced up to 3 times by simply mixing Au/P25 with photocatalytically inactive h-BN nanosheets as a result of electron transfer from photoexcited Au/TiO2 to the h-BN nanosheets and retardation of the charge recombination.

Bioactive TiNbSn alloy prepared by anodization in sulfuric acid electrolytes.

The bioactivity of anodized near-ß TiNbSn alloy with low Young's modulus prepared in sulfuric acid electrolytes was examined to explore the osseointegration mechanism with a focus on the role of anodic oxide. Hydroxyapatite (HA) precipitated on the surface of anodic oxide following immersion in Hank's solution, and precipitation accelerated with increase in the sulfuric acid concentration of the electrolyte. HA is formed on the surface of as-anodized oxide without subsequent annealing or hot water (HW) treatment. This outcome differs from that of a previous study using anodized TiNbSn alloy prepared in acetic acid electrolytes requiring for subsequent HW treatment. It was found that the oxide anodized in sulfuric acid electrolyte contains a large amount of internal pores and is highly crystallized thick TiO2, whereas the same prepared in the acetic acid electrolyte is low crystalline thin TiO2 containing a small amount of pores. The present anodized TiNbSn alloy is preferred for maintaining the low Young's modulus of the alloy and eliminating the subsequent treatment to increase the Young's modulus. A model to rationalize the bioactivity of the present anodic oxide is proposed based on the series of studies. It is concluded that the sulfuric acid electrolyte is favorable for both HA formation and low Young's modulus, and the bioactivity is attributed to the anodic TiO2 that facilitates incorporation of bone ingredients.

Trp64Arg mutation of beta3-adrenoceptor gene deteriorates lipolysis induced by beta3-adrenoceptor agonist in human omental adipocytes.

The recently described variant of the human beta3-adrenergic receptor (AR) gene located mainly in visceral adipocytes is associated with earlier onset of NIDDM, abdominal obesity, insulin resistance, and an increased capacity to gain weight. We investigated whether lipolysis in human omental adipocytes induced by a potent and selective human beta3-AR agonist (L-755,507) was affected by the Trp64Arg mutation of the beta3-adrenoceptor, using 18 omental fat samples obtained during total hysterectomy. The Trp64Arg mutation was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. Arg64 homozygous (n = 4) had a lower median effective concentration (EC50) and lower responsiveness compared with wild-type (n = 8) (EC50: -6.55 +/- 0.21 vs. -7.53 +/- 0.35 log mol/l, P = 0.007; responsiveness: 3.48 +/- 0.32 vs. 5.76 +/- 0.36 micromol x 10(5) cells(-1) x 90 min(-1), P = 0.014, respectively), although there was no difference in lipolysis induced by isoproterenol or CGP12177. Trp64Arg heterozygous (n = 6) also had a significantly lower EC50 and lower responsiveness (EC50: -6.18 +/- 0.09 log mol/l; responsiveness: 4.17 +/- 0.33 micromol x 10(5) cells(-1) x 90 min(-1)). We concluded that the Trp64Arg mutation of the beta3-AR gene is associated with lower lipolytic activities.

Beta 3-adrenoreceptor gene polymorphism: a newly identified risk factor for proliferative retinopathy in NIDDM patients.

Proliferative diabetic retinopathy is an important cause of visual impairment. We investigated whether the polymorphism of the beta 3-adrenoreceptor (beta 3-AR) gene, which is associated with insulin resistance and an earlier onset of NIDDM, was associated with proliferative diabetic retinopathy (PDR) in 215 Japanese NIDDM patients with a duration of diabetes of > or = 10 years. The polymorphism of the beta 3-AR gene was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. The Trp64Arg allele of the beta 3-AR gene was significantly more frequent in the NIDDM patients with PDR (P = 0.002), but not in those with non-PDR (P = 0.151), than in NIDDM patients without diabetic retinopathy. Those with the mutation had an earlier onset of diabetes, a longer duration of diabetes, and higher current and maximal BMI values, compared with those without the mutation. Moreover, this mutation was also associated with higher serum triglyceride and decreased HDL-cholesterol levels. When adjustment was made for age, age at diagnosis, duration of diabetes, current BMI, systolic blood pressure, HbA1e, and serum lipids in a multiple regression analysis, a significant association was found between the Trp64Arg allele and diabetic retinopathy (P = 0.039). The Arg/Arg or Arg/Trp genotype was significantly associated with PDR, compared with the Trp/Trp genotype, with an odds ratio of 2.55 (95% CI 1.25-5.16). We concluded that the beta 3-AR gene polymorphism is a newly identified risk factor for PDR.

Effects of Trp64Arg mutation in the beta 3-adrenergic receptor gene on weight loss, body fat distribution, glycemic control, and insulin resistance in obese type 2 diabetic patients.

OBJECTIVE: To investigate the effects of Trp64Arg mutation in the beta 3-adrenergic receptor gene on weight loss, body fat distribution, glycemic control, and insulin resistance in obese type 2 diabetic patients. RESEARCH DESIGN AND METHODS: We measured body weight, waist-to-hip ratio (WHR), adjusted resting metabolic rate, fasting blood glucose, fasting serum insulin levels, insulin resistance index (fasting glucose x fasting insulin/22.5), and HbA1c levels before and after 12 weeks of obesity treatment in 61 obese women with type 2 diabetes. The MvaI polymorphism of the beta 3-adrenergic receptor gene was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: Of obese type 2 diabetic patients, those with the mutation (n = 24) had a higher WHR (P < 0.001), a lower adjusted metabolic rate, and higher blood glucose levels, serum insulin levels, insulin resistance index (P < 0.001), and HbA1c levels (P = 0.016). Furthermore, patients with the mutation had smaller decreases in body weight, WHR, insulin resistance index, and HbA1c levels after the weight-loss program compared with patients without the mutation (n = 37), even though food intake, exercise, and serum thyroid hormone levels were similar in both groups. CONCLUSIONS: These present findings show that the Trp64Arg allele of the beta 3-adrenergic receptor gene may predict difficulty in losing body weight, lowering WHR, and improving glycemic control and insulin resistance in obese patients with type 2 diabetes.

Complement-activating properties of IgM rheumatoid factors reacting with IgG subclasses.

To estimate the complement-activating property (CAP) of IgM rheumatoid factor (RF), which was purified from synovial fluids of patients with rheumatoid arthritis, in a reaction with each IgG subclass, the activation and binding of C4 in the classical pathway of complement by IgM RF was measured in an enzyme-linked immunosorbent assay using biotinylated F(ab')2 antibody to human C4. The CAP of IgM RF reacting with IgG3 was significantly higher than that of IgM RFs bound to the other IgG subclasses (P < 0.01). These results suggest that IgM RF reacting with IgG3 in synovial fluid could induce a greater degree of complement-dependent inflammation in RA synovium than IgM RF reacting with other IgG subclasses.

A case of Werner's syndrome associated with systemic lupus erythematosus.

The case of a 40-year-old woman with Werner's syndrome associated with systemic lupus erythematosus (SLE) is reported. The patient exhibited short stature, slender extremities, thinned hair, high-pitched voice, cataracts, ulceration of the fingers, and mental retardation. Malar erythema, photosensitivity, and proteinuria had been noted since age 34. The serum contained high titers of antibodies to dsDNA, Sm, nRNP, and SS-A/Ro. The simultaneous presence of Werner's syndrome and SLE could be a coincidental occurrence of the two diseases, although it might be due to an abnormality in replication or degeneration of DNA leading to the development of both diseases.

Detection of antibodies to 65 KD heat shock protein and to human superoxide dismutase in autoimmune hepatitis-molecular mimicry between 65 KD heat shock protein and superoxide dismutase.

The antibody to 65 KD mycobacterial heat shock protein (HSP65) and antibody to human superoxide dismutase (H-SOD) were measured by ELISA in patients with autoimmune hepatitis (AIH), and results were compared with those of patients with chronic active hepatitis C (CAH-C) or systemic lupus erythematosus (SLE) and normal subjects (NS). Patients with AIH had significantly higher OD values of anti-HSP65 antibody and anti-H-SOD antibody compared with those of patients with CAH-C or SLE and NS. OD values of anti-HSP65 antibody were correlated with those of anti-SOD antibody. Affinity-purified anti-SOD antibody reacted with HSP65. Analysis of the amino acid sequence of human SOD showed that 7 segments, corresponding to r to 25 amino acid residues, exhibited 50 to 71% homology with that of my mycobacterial HSP65.

[A case of inoperable advanced gastric cancer remarkably responding to combined chemotherapy with UFT-E, MMC and PSK].

A 55-year-old male consulted a local doctor with the complaint of epigastralgia. Examination of the upper gastrointestinal tract revealed gastric cancer (Borrmann Type II) and he was referred to our hospital for operation. A few lymph nodes were palpable in the left supraclavicular fossa, and the biopsy of those lymph nodes revealed metastatic adenocarcinoma. The CT scan of the abdomen showed enlargement of paraaortic lymph nodes. Then, the patient was determined inoperable (T3, N4, H02 P01, M1 stage IVb). He was treated as an outpatient with UFT-E (300 mg/day, orally), Krestin (PSK 3.0 g/day, orally) and Mitomycin C (MMC 6 or 8 mg once a week, intravenously repeated interval of 4 weeks). The total dose of UFT-E, PSK and MMC was 219 g, 1,095 g and 136 mg, respectively. One month later, lymph nodes in the supraclavicular fossa disappeared, and the lesion in the stomach completely responded. We have followed the patient for more than one year. He visits our the outpatient department and has kept working until now.

Proliferative response of synovial fluid mononuclear cells of patients with rheumatoid arthritis to mycobacterial 65 kDa heat shock protein and its association with HLA-DR+.gamma delta+ T cells.

OBJECTIVE: The proliferative response of mononuclear cells (MNC) in synovial fluid (SF) and peripheral blood (PB) of patients with rheumatoid arthritis (RA) to mycobacterial 65 kDa heat shock protein (HSP65) was tested and the response compared with the percentage of HLA-DR+.gamma delta+ T cells in lymphocytes of SFMNC or PBMNC: METHODS: Proliferative response of MNC was measured by means of 3H-thymidine incorporation and expressed by means of the stimulation index. Percentage of HLA-DR+.gamma delta+ T cells in lymphocytes was measured by means of the 2-color flow cytometry method. RESULTS: Higher response of SFMNC than PBMNC to HSP65 was noted in 14 of 19 patients with RA. Stimulation indexes of RA-SFMNC correlated significantly with HLA-DR+.gamma delta+ T cell percentage in lymphocytes. CONCLUSION: In the SF of patients with RA, an accumulation of HSP65 reactive and HLA-DR+.gamma delta+ T cells was noted.

Complement activating properties of monoreactive and polyreactive IgM rheumatoid factors.

OBJECTIVES: To estimate the complement activating properties of monoclonal, monoreactive, and polyreactive IgM rheumatoid factors derived from Epstein-Barr virus transformed B cells isolated from peripheral blood and synovial tissue of patients with rheumatoid arthritis (RA). METHODS: An enzyme linked immunosorbent assay (ELISA) was used to measure the activation of the classical pathway of complement by monoclonal IgM rheumatoid factor. Monoclonal IgM rheumatoid factor was bound to IgG Fc adsorbed onto microtitre plates and then reacted with diluted normal human serum as a source of complement. The activation and binding of C4 were measured with F(ab')2 antibody to human C4. The complement activating property of IgM rheumatoid factor bound to IgG Fc was tentatively expressed as the ratio of the amount of bound C4 to the amount of bound IgM rheumatoid factor. RESULTS: The complement activating property of monoreactive IgM rheumatoid factor was shown to be about three times higher than that of polyreactive IgM rheumatoid factor. CONCLUSIONS: Monoreactive IgM rheumatoid factor with the higher complement activating property would result in a greater degree of complement dependent inflammation and might have a more important pathogenic role in RA than polyreactive IgM rheumatoid factor.

Effects of growth hormone (GH) on mRNA levels of uncoupling proteins 1, 2, and 3 in brown and white adipose tissues and skeletal muscle in obese mice.

We have investigated whether GH treatment influences the expression of UCP1, 2 and 3 mRNA in a KK-Ay obese mouse model. KK-Ay mice (n = 10) and C57Bl/6J control mice (n = 10) were injected subcutaneously with human GH (1.0 mg/kg/day and 3.5 mg/kg/day) for 10 days, and compared with mice injected with physical saline. The KK-Ay obese mice weighed significantly less (p < 0.01 : 1.0 mg/kg/day, p < 0.05 : 3.5 mg/kg/day) and had smaller inguinal subcutaneous and perimetric white adipose tissue (WAT) pads (p < 0.05 : 3.5 mg/kg/day), but increased skeletal muscle weight (p < 0.05). The brown adipose tissue (BAT) weight did not change significantly. Not only plasma free fatty acid and glucose levels but also plasma insulin levels decreased. The reduced HOMA-IR (homeostasis model assessment-insulin resistance) values suggested that insulin resistance was improved by GH treatment. UCP1 mRNA levels increased after the 3.5 mg GH treatment by 2.8-fold (p < 0.01 vs. saline controls) and 2.0-fold (p < 0.05 vs. 1 mg GH treatment) in BAT, and by 6.0-fold in subcutaneous WAT (p < 0.05 vs. controls). UCP2 mRNA levels increased 2.2-fold (p < 0.05 vs. control) and 2.1-fold (p < 0.05 vs. 1 mg GH treatment) in BAT, and 2.0-fold (p < 0.05 vs. controls) in skeletal muscle. One mg GH administration also stimulated UCP1 mRNA expression by 2.5-fold (p < 0.05 vs. controls) and UCP3 mRNA expression by 2.8-fold (p < 0.05 vs. controls) in the muscle. On the other hand, lean mice showed no significant difference in body composition or plasma parameters. UCP1, 2 and 3 mRNA expression in lean mice did not show any significant change after treatment with GH. We conclude that GH treatment increased mRNA levels for not only UCP1, but also UCP 2 and 3 in BAT, WAT and muscle in a KK-Ay obese mouse model. These findings suggest that GH-induced thermogenesis may contribute to the reduction in WAT and energy expenditure.

Synoviocyte proliferation in joints of SCID mice induced by toxic shock syndrome toxin-1 stimulated T cells from patient with rheumatoid arthritis.

OBJECTIVE: To investigate the histopathological arthropathy in severe combined immunodeficient (SCID) mice given intraarticular injection of toxic shock syndrome toxin-1 (TSST-1) stimulated T cells from patients with rheumatoid arthritis (RA). METHODS: Unstimulated or TSST-1 stimulated T cell blasts (TB-TSST) of synovial fluid mononuclear cells from patients with RA (RASFMC) were intraarticularly injected into the knee joint of SCID mice. Four weeks later, the knee joints were histopathologically examined and the numbers of fibroblasts in the synovial tissues were compared with those of controls. Total RNA of the SCID mouse knee joints was isolated and Southern analysis for human T cell receptor (TCR) V beta 2 and human tumor necrosis factor-alpha (TNF-alpha) was carried out. RESULTS: Hyperplasia and increased numbers of the fibroblasts as well as neovascularization of the synovial tissues were observed in the SCID mouse knee joint tissues injected with TB-TSST of RASFMC compared with those injected with unstimulated T cells from RASFMC or with TB-TSST from peripheral blood of healthy controls. Messenger RNA for human TCR V beta 2 and TNF-alpha were detected in the SCID mouse knee joint tissues injected with TB-TSST from RASFMC. CONCLUSION: Superantigen TSST-1 stimulated T cells from RASFMC have the ability to induce chronic arthropathy with fibroblast proliferation and neovascularization in the SCID mouse.

Nicotine induces uncoupling protein 1 in white adipose tissue of obese mice.

OBJECTIVE: To test the hypothesis that nicotine not only activates uncoupling protein1 (UCP1) in brown adipose tissue (BAT), but also induces UCP1 in white adipose tissue (WAT), which contributes to the mitigation of obesity in obese mice. DESIGN: Weights of the whole body, the gastrocnemius muscle, interscapular BAT and subcutaneous and retroperitoneal WAT, food intake and the mRNA and protein of UCP1 in these tissues were measured and immunohistochemistry using antiserum against UCP1 was also performed in obese yellow KK mice treated with nicotine for 6 months and control mice treated with physiological saline. RESULTS: Obese mice treated with nicotine for 6 months, compared with those injected with saline, weighed significantly less (P < 0.01) and had smaller subcutaneous and retroperitoneal WAT pads (P < 0.01), while obese mice that received nicotine ate less (P < 0.05) than those injected with saline. In mice treated with nicotine, the mRNA and protein of UCP1 was detected not only in BAT, but also in subcutaneous and retroperitoneal WATs. Immunohistochemically, the BAT of obese mice contained large lipid droplets and appeared rather WAT-like, but changed to typical brown adipocytes after nicotine treatment. The fat pads of nicotine-treated mice contained many multilocular cells that were positive for UCP1. CONCLUSION: Nicotine not only activates UCP1 in BAT, but also induces UCP1 in WAT and decreases food intake, which contributes to the mitigation of obesity.

Acute and chronic regulation of ob mRNA levels by beta3-adrenoceptor agonists in obese Yellow KK mice.

The inhibitory effect of beta3-adrenoceptor agonists on the ob gene in brown adipose tissue (BAT) and white adipose tissue (WAT) is now well documented both in vivo in lean animals and in vitro, but the reported effects of beta3-adrenoceptor agonists on ob gene expression in obese animals remain controversial. We investigated whether ob gene expression in BAT and WAT is reduced by acute and chronic administrations of a beta3-adrenoceptor agonist, CL316,243 (CL). The ob gene mRNA levels in BAT, perimetric and inguinal WAT of obese Yellow KK mice were about 4-fold higher than those of lean controls. Acute exposure (6 h) to CL decreased ob gene mRNA levels in three fat depots in both animals. Chronic exposure (10 days) to CL also decreased ob gene mRNA levels in BAT, perimetric, and inguinal WAT in both animals. We concluded that acute and chronic regulation by a beta3-adrenoceptor agonist suppressed ob gene expression in obese Yellow KK mice and lean controls.