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Abstract Background An epidemiological study conducted in Italy indicated that coffee has the greatest antioxidant capacity among the commonly consumed beverages. Green coffee bean is rich in chlorogenic acid and its related compounds. The effect of green coffee bean extract (GCBE) on fat accumulation and body weight in mice was assessed with the objective of investigating the effect of GCBE on mild obesity. Methods Male ddy mice were fed a standard diet containing GCBE and its principal constituents, namely, caffeine and chlorogenic acid, for 14 days. Further, hepatic triglyceride (TG) level was also investigated after consecutive administration (13 days) of GCBE and its constituents. To examine the effect of GCBE and its constituents on fat absorption, serum TG changes were evaluated in olive oil-loaded mice. In addition, to investigate the effect on hepatic TG metabolism, carnitine palmitoyltransferase (CPT) activity in mice was evaluated after consecutive ingestion (6 days) of GCBE and its constituents (caffeine, chlorogenic acid, neochlorogenic acid and feruloylquinic acid mixture). Results It was found that 0.5% and 1% GCBE reduced visceral fat content and body weight. Caffeine and chlorogenic acid showed a tendency to reduce visceral fat and body weight. Oral administration of GCBE (100 and 200 mg/kg· day) for 13 days showed a tendency to reduce hepatic TG in mice. In the same model, chlorogenic acid (60 mg/kg· day) reduced hepatic TG level. In mice loaded with olive oil (5 mL/kg), GCBE (200 and 400 mg/kg) and caffeine (20 and 40 mg/kg) reduced serum TG level. GCBE (1%), neochlorogenic acid (0.028% and 0.055%) and feruloylquinic acid mixture (0.081%) significantly enhanced hepatic CPT activity in mice. However, neither caffeine nor chlorogenic acid alone was found to enhance CPT activity. Conclusion These results suggest that GCBE is possibly effective against weight gain and fat accumulation by inhibition of fat absorption and activation of fat metabolism in the liver. Caffeine was found to be a suppressor of fat absorption, while chlorogenic acid was found to be partially involved in the suppressive effect of GCBE that resulted in the reduction of hepatic TG level. Phenolic compounds such as neochlorogenic acid and feruloylquinic acid mixture, except chlorogenic acid, can enhance hepatic CPT activity.

BACKGROUND: An epidemiological study conducted in Italy indicated that coffee has the greatest antioxidant capacity among the commonly consumed beverages. Green coffee bean is rich in chlorogenic acid and its related compounds. The effect of green coffee bean extract (GCBE) on fat accumulation and body weight in mice was assessed with the objective of investigating the effect of GCBE on mild obesity. METHODS: Male ddy mice were fed a standard diet containing GCBE and its principal constituents, namely, caffeine and chlorogenic acid, for 14 days. Further, hepatic triglyceride (TG) level was also investigated after consecutive administration (13 days) of GCBE and its constituents. To examine the effect of GCBE and its constituents on fat absorption, serum TG changes were evaluated in olive oil-loaded mice. In addition, to investigate the effect on hepatic TG metabolism, carnitine palmitoyltransferase (CPT) activity in mice was evaluated after consecutive ingestion (6 days) of GCBE and its constituents (caffeine, chlorogenic acid, neochlorogenic acid and feruloylquinic acid mixture). RESULTS: It was found that 0.5% and 1% GCBE reduced visceral fat content and body weight. Caffeine and chlorogenic acid showed a tendency to reduce visceral fat and body weight. Oral administration of GCBE (100 and 200 mg/kg. day) for 13 days showed a tendency to reduce hepatic TG in mice. In the same model, chlorogenic acid (60 mg/kg. day) reduced hepatic TG level. In mice loaded with olive oil (5 mL/kg), GCBE (200 and 400 mg/kg) and caffeine (20 and 40 mg/kg) reduced serum TG level. GCBE (1%), neochlorogenic acid (0.028% and 0.055%) and feruloylquinic acid mixture (0.081%) significantly enhanced hepatic CPT activity in mice. However, neither caffeine nor chlorogenic acid alone was found to enhance CPT activity. CONCLUSION: These results suggest that GCBE is possibly effective against weight gain and fat accumulation by inhibition of fat absorption and activation of fat metabolism in the liver. Caffeine was found to be a suppressor of fat absorption, while chlorogenic acid was found to be partially involved in the suppressive effect of GCBE that resulted in the reduction of hepatic TG level. Phenolic compounds such as neochlorogenic acid and feruloylquinic acid mixture, except chlorogenic acid, can enhance hepatic CPT activity. [ABSTRACT FROM AUTHOR]

We studied the atomic and electronic structures of ultrathin Bi(111) films grown on Bi2Te3 by means of angle-resolved photoemission, first-principles calculations, and low-energy electron diffraction. These Bi films were found to be strained due to the influence of the substrate. Accordingly, the band structure is affected and Bi undergoes a topological phase transition; it is shown that the Z2 topological invariant in three dimensions switches from +1 (trivial) to -1 (nontrivial or topological). This was clearly confirmed from the change in the surface-state dispersion near the Fermi level. Our discovery offers a method to produce novel topological systems from simple materials. [ABSTRACT FROM AUTHOR]

Amyloid-β (Aβ) accumulation in the brain triggers the onset of Alzheimer's disease (AD), and its prevention and elimination are high priorities for anti-AD therapeutic strategies. Microglia, the resident immune cells in the brain, promote Aβ clearance by phagocytosis. Previously, we demonstrated that injection of primary cultured rat microglia and mouse bone marrow-derived microglia-like cells into the brain decreases the level of Aβ and that intrahippocampal injection of these cells ameliorates cognitive impairment in a mouse model of AD. To advance this cell therapeutic strategy to the clinical stage, less invasive ways of preparing autologous microglia-like cells from elderly patients are required. In this study, we demonstrated that hematopoietic stem cells mobilized from the bone marrow to peripheral blood by administering granulocyte colony-stimulating factor and a CXCR4 antagonist to mice differentiated into microglia-like cells upon stimulation with colony-stimulating factor 1 and interleukin-34. The peripheral blood-derived microglia-like (PBDML) cells expressed microglial markers and engaged in Aβ phagocytosis. Although PBDML cells were in an anti-inflammatory state under nonstimulated conditions, they expressed mRNAs encoding proinflammatory cytokines following lipopolysaccharide treatment. PBDML cells injected into the hippocampi of a mouse AD model survived for at least 36 days while phagocytosing Aβ, contributed to a reduction in brain Aβ burden, and ameliorated cognitive impairment in the mice. These results strongly suggest that PBDML cells are a promising source for the development of a novel cell therapy against AD.

The reactions of a dichloro( p -cymene)ruthenium(ii) dimer, [RuCl 2 ( p -cymene)] 2 , with citric acid and sulfur-containing amino acids gave only [Ru(L)( p -cymene)]-type complexes (L = citrate (Cit), l-penicillaminate (l-Pen), S -methyl-l-cysteinate ( S -Me-l-Cys) and l-methioninate (l-Met)) in aqueous solutions at various pHs and molar ratios of the reactants, where Cit and the amino acids act as a tridentate ligand. These sulfur-containing amino acid complexes with bound nitrogen, oxygen and sulfur atoms and η 6 - p -cymene take S absolute configuration around Ru(ii) selectively, having the α-proton oriented in the opposite direction from the Ru(ii) center. The concentration dependences of the observed pseudo-first-order rate constants were provided for the substitution reactions of the citrato complex, [Ru(Cit)( p -cymene)], with a large excess of the sulfur-containing amino acids at various temperatures at pH 7.3, where solvolysis path was observed for S -Me-l-Cys and l-Met as an intercept but not for l-Pen. The activation parameters for the substitution reactions by the direct attack of the amino acids were changed significantly, indicating that the reaction mechanism varies sensitively with the amino acids from an associative mechanism to an interchange one. The pH dependences of the rate constants of the substitution reactions suggest that the carboxylate group is an attacking group for S -Me-l-Cys and l-Met under neutral conditions and the thiol group of l-Pen acts as an entering group constantly at any pH showing a considerably smaller activation energy compared with S -Me-l-Cys and l-Met. Differences in stabilities of the amino acid complexes were obtained from the equilibrium constants for the substitution reactions between the amino acids. These results indicate that the activation energies for the substitution reactions of the citrato complex with the amino acids are moderately correlated with the stabilities of the formed amino acid complexes., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

We performed in situ magnetotransport measurements on ultrathin Bi(111) films [4-30 bilayers (BLs), 16-120 Å thick] to elucidate the role of bulk or surface states in the transport phenomena. We found that the temperature dependence of the film conductivity shows no thickness dependence for the 6-16 BL films and is affected by the electron-electron scattering, suggesting surface-state dominant contribution. In contrast, the weak antilocalization effect observed by applying a magnetic field shows clear thickness dependence, indicating bulk transport. This apparent inconsistency is explained by a coherent bulk-surface coupling that produces a single channel transport. For the films thicker than 20 BLs, the behavior changes drastically which can likely be interpreted as a bulk dominant conduction.

The patient was a 70-year-old man who had been given a diagnosis of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome and had been placed on low-dose steroid therapy in the Department of Orthopedics. During treatment, sudden fever, hypoxemia and chest radiography-confirmed interstitial shadows throughout the lung fields were noted, and the patient was referred to the Department of Internal Medicine. RS3PE complicated by interstitial pneumonia was diagnosed, and steroid pulse therapy and immunosuppressant therapy were initiated. In the present case, soluble interleukin-2 receptor (sIL-2R) proved useful for assessing symptoms. To the best of our knowledge, RS3PE syndrome complicated by pulmonary lesions and accompanied by severe acute respiratory failure requiring noninvasive positive-pressure ventilation has not previously been reported, and this rare case is discussed with reference to the literature.

We report a case of a ground glass opacity (GGO) transforming into advanced lung cancer, which we followed chronologically by CT. On November 2001, a chest CT was performed due to chest pain. Due to incidental discovery of a GGO of 11mm in the left S6, we decided to monitor its course with CT. At the time, the patient did not have respiratory symptoms, and his tumor markers were within normal limits. In a CT conducted on September 2003, a slight enlargement of the GGO as well as an increased density within it was observed. At that point, the patient refused an exploratory thoracotomy. On October 2006, a chest CT was conducted due to the possibility of pneumonia. At that time, the GGO found in the past CT had become a solid nodule. In addition, enlargement of the hilar and mediastinal lymph nodes were observed, based on which we made a diagnosis of advanced lung cancer.

A 43-year-old woman developed dyspnea on effort in January 1996. She was treated with various antibiotics but developed dyspnea and pretibial edema. She was referred to our hospital and admitted on February 20, 1996. On the basis of the clinical course and radiological findings, she was diagnosed as having idiopathic pulmonary fibrosis with right-side heart failure. After high-dose steroid therapy (methylprednisolone, 1,000 mg/day for 3 days) and the administration of a diuretic, oral prednisolone therapy was initiated. Her condition gradually recovered. To obtain a definite diagnosis, an open lung biopsy was recommended but the patient refused the procedure. She was discharged from the hospital and placed on home oxygen therapy. After her informed consent was obtained, she became a candidate recipient for the nationwide Central Lung Transplant Evaluation Committee on August 7, 1998. Her name was then listed in the Japan Organ Transplant Network. The patient was admitted to our hospital in October 1998 because of respiratory failure. She underwent left lung transplantation at Osaka University Hospital on March 29, 2000. After the lung transplantation, she was discharged and is presently doing well without the need for supplementary oxygen. A differential diagnosis of the removed lung as nonspecific interstitial pneumonia (NSIP) group III or UIP was required. We finally diagnosed NSIP group III because of the temporal uniformity and diffuse distribution of the fibrosis. In this report, we also describe the background of the clinical diagnosis, the indications for lung transplantation and the clinical course before and after transplantation.

We report a case of chronic thromboembolic pulmonary hypertension based on essential thrombocythemia. A 72-year-old woman was admitted to our hospital with dyspnea. The hematologic workup revealed a platelet count of 99.2 x 10(4)/microliter. Chest radiographic examination revealed cardiomegaly with bilateral pulmonary artery enlargement. A perfusion lung scan suggested and pulmonary angiography confirmed--multiple pulmonary embolism. Pulmonary artery pressure was 90/30 (51) mmHg. Thrombolytic therapy was performed successfully, and a diagnosis of essential thrombocythemia was made on the basis of the criteria proposed by the Polycythemia Vera Study Group. The therapy of essential thrombocythemia including ranimustine was effective, and one year later, the essential thrombocythemia and chronic respiratory failure had improved. To our knowledge, this case of chronic thromboembolic pulmonary hypertension based on essential thrombocythemia is a very rare one.

Severe pneumococcal pneumonia may precipitate both respiratory failure and neutropenia. The prognoses are considered to be very poor in such cases. We encountered three patients with pneumococcal pneumonia presenting respiratory failure and neutropenia, and successfully treated two. All three patients showed disseminated intravascular coagulation, and respiratory failure requiring mechanical ventilation. Neutropenia was treated with granulyte-colony stimulating factor (G-CSF), with methylpredonisolone administered by pulse therapy for 3 days to treat severe respiratory failure during the clinical course. All 3 patients were relieved of their respiratory failure at least for a few days following treatment. As a result of treatment with antibiotics and G-CSF, pneumococci disappeared from the patients' sputum. However, it has been reported that disintegration of the bacterial cell walls can release inflammatory components capable of causing secondary inflammatory reactions in the lung tissue. This suggested that the worsening respiratory failure experienced by our patients during their clinical course was a result of such reactions, and that methylpredonisolone was effective as the treatment of inflammation.

Pulmonary involvement is generally recognized to be an important determinant of the clinical course in cases of polymyositis. A patient with bilateral pleural effusion as an initial symptom developed respiratory failure due to muscle weakness. Polymyositis was diagnosed on the basis of a muscle biopsy. A chemotherapy regimen consisting of methyl prednisolone (1 g/day for 3 days) followed by prednisolone (60 mg/day) alleviated, the pleural effusion and respiratory failure. Though pleural complications in polymyositis have been described mostly in association with concomitant interstitial lung disease, our patient exhibited only bilateral pleural effusion. Given that pleural effusion can be an initial symptom of polymyositis, it seems necessary that polymyositis be taken into consideration by differential diagnoses of pleural effusion of unknown etiology.

To examine the mechanism of starch degradation in legume cotyledons and the physiological role of α-glucosidase, mung bean seeds were germinated in the presence of Bay m 1099, an α-glucosidase inhibitor. Bay m 1099 (10 μg/ml medium), which minimized the growth deterioration of the mung bean seedlings, caused no changes in the overall rate of starch degradation and of soluble carbohydrate production in the cotyledons, although α-glucosidase activity had been completely suppressed. Total amylase and phosphorylase activities were not influenced by Bay m 1099. These results suggest that the mung bean α-glucosidase is less responsible for starch degradation, unlike wheat α-glucosidase [Konishi et al., Biosci. Biotech. Biochem., 58, 135-139 (1994)].

We examined the capacity of interleukin-4 (IL) production from lymphocytes and basophils, isolated from the peripheral blood of allergic patients sensitive to house dust mite, after stimulation with mite extract. IL-4 production was measured by a sensitive bioassay based on coculture with CT.h4S (a human IL-4-responsive cell line). Lymphocytes and basophils from patients with elevated serum IgE specific to mite allergen [radioallergosorbent test (RAST) score > 3] could produce detectable levels of IL-4 in response to mite extract, whereas those from patients with a RAST score of less than 2 or normal volunteers could not. The sensitivity of basophils to mite extract was high, so that a lower concentration of mite extract (1-10 ng/ml) could induce maximal IL-4 production. On the other hand, a higher concentration (10 micrograms/ml) was required for maximal IL-4 production from the lymphocytes. These findings demonstrate that allergen-specific IL-4-producing cells, lymphocytes and basophils, are generated in vivo in allergic patients and also that there exist characteristic differences between lymphocytes and basophils related to the in vivo source of IL-4.

We examined the capacity of T cells from normal individuals and allergic patients with very high IgE to differentiate into interleukin-4(IL-4)-producing cells in vitro. T cells incubated with anti-CD3 monoclonal antibody plus IL-4 or plus anti-IL-4 antibody in the presence of antigen-presenting cells for 7 days were restimulated and their capacity to express IL-4 mRNA was examined by RT-PCR. In T cells from normal individuals, there was a marked increase in the expression of IL-4 mRNA following the addition of IL-4. After fractionation of normal T cells into naive T (CD45RA+) and memory T (CD45RO+) cells, induction of the increase of IL-4 mRNA was restricted to the naive T cell population. In contrast, in T cells from allergic patients, the stimulation of whole or naive T cells with anti-CD 3 monoclonal antibody in the presence of IL-4 induced much less IL-4 mRNA. These findings suggest the presence of a functional abnormality in IL-4-dependent development of IL-4-producing T cells in the peripheral-blood naive T cells from allergic patients.

IgE synthesis by purified human B cells is induced by two signals: a class switching factor, most commonly interleukin (IL)-4, and the engagement of CD40, which is activated through its interaction with CD40 ligand (CD40L) expressed on activated T cells. Thus, the combination of IL-4 and anti-CD40 monoclonal antibody (mAb) has been shown to stimulate IgE production in vitro by highly purified B cells. In this T cell-independent system, strong homotypic aggregation of B cells is observed prior to the production of IgE. Flow cytometric analysis and cell binding assays showed that the stimulation of purified B cells with anti-CD40 mAb plus IL-4 resulted in a striking increase of intercellular adhesion molecule (ICAM)-1(CD54) expression, an induction of CD43 and an avidity change of lymphocyte functional antigen (LFA)-1(CD11a/CD18), with little augmentation of CD18 expression. Addition of anti-ICAM-1 mAb caused an inhibition of homotypic aggregation but augmented IgE synthesis by B cells stimulated with anti-CD40 mAb and IL-4, although it did not affect B cell proliferation or IL-6 production by the B cells. Among the mAb against counter-receptors for ICAM-1 tested, anti-CD11a mAb suppressed IgE synthesis, while anti-CD18 mAb and anti-CD43 mAb had little effect. The enhancing or inhibitory effect of anti-ICAM-1 mAb or anti-CD11a mAb on IgE production was achieved by the increased or decreased expression of germline C epsilon transcripts by B cells stimulated with anti-CD40 mAb and IL-4. These results indicate that B cell-B cell interaction through ICAM-1 and one of its counter receptors, LFA-1, regulates IgE synthesis by modulating C epsilon germ-line transcription.

To examine the significance of α-glucosidase in starch metabolism in vivo, wheat seedlings and seeds were treated with Bay m 1099 (Miglitol, N-hydroxyethyl-1-deoxynojirimycin), an α-glucosidase inhibitor. Bay m 1099 did not affect germination, but it inhibited growth of seedlings at the high dosage (100 μg/ml medium). Treatment of normally grown seedlings with Bay m 1099 (10 and 100 μg/ml) decreased α-glucosidase activity with a dose response and caused accumulation of maltose in tissues with decreases in glucose. The decrease in glucose formation would inhibit plant growth, which was observed particularly at higher dosages of the inhibitor. When wheat seeds were treated with Bay m 1099 at 10 μg/ml for 4 days, under which the growth of the plants after germination was minimized, the induction of α-glucosidase, but not amylase, in kernels was considerably suppressed during germination and maltose metabolism to glucose was disturbed. In addition, the Bay m 1099 treatment decreased the initial rate of starch degradation by 48%, compared with the control. These results suggest that wheat α-glucosidase participates in maltose hydrolysis as well as in the onset of starch degradation with collaboration of amylase.

The significance of sFc epsilon RII in IgE-mediated allergic disease was examined. sFc epsilon RII in serum was found to decrease following clinical improvement, suggesting sFc epsilon RII in serum may be an indicator of allergic diseases. Significant proportions of sFc epsilon RII in serum were present as complexes with IgE in normals as well as in atopic patients, and these complexes were more prominent in the former than in the latter group. From these observations, attempts were made to inhibit IgE-mediated allergic reactions in vitro employing recombinant sFc epsilon RII. sFc epsilon RII inhibited IgE-binding as well as IgE-mediated release of chemical mediators from Fc epsilon RI and Fc epsilon RII expressing cells. These results show the functional significance of sFc epsilon RII in the negative regulation of IgE-mediated allergic reactions.

Utilizing an enzyme-linked immunosorbent assay, we detected markedly elevated serum levels of soluble interleukin-2 (IL-2) receptors in patients with untreated pulmonary tuberculosis. In these patients, we also found that serum levels of soluble IL-2 receptors were closely correlated with serum adenosine deaminase levels (r = 0.869, p less than 0.001). Therefore, serum soluble IL-2 receptors appear to reflect the existence of active cell-mediated immunity in pulmonary tuberculosis and may prove to be a useful immunological marker for pulmonary tuberculosis.