Biomedical subjects

Takashi Kinoshita

Publications and source records attributed to Takashi Kinoshita.

15 recordsLinked to original sources

PubMed2006

An integrated database of flavonoids.

Flavonoids are polyphenolic compounds that occur ubiquitously in foods of plant origin. Some of these molecules exhibit various physiological activities. Among existing drugs, there are a huge number of compounds bearing a flavonoid-related skeleton. Because of the relevance for pharmaceutical research, it would be beneficial to collect these compounds into a database. Recently, various databases of chemicals were compiled to help biological and/or chemical research, but no comprehensive database of flavonoids with chemical structures and physicochemical parameters, supposedly related to their activity, is available yet. The aim of this research was to merge the information about flavonoids of plant origin and flavonoids used as medicines into a database. Moreover, predictions of activities against various targets were performed using a virtual screening procedure to demonstrate a possible application of the database for pharmaceutical research.

Chemistry, Physical↗

PubMed2006

Effect of a conjugated quercetin metabolite, quercetin 3-glucuronide, on lipid hydroperoxide-dependent formation of reactive oxygen species in differentiated PC-12 cells.

To assess the efficacy of conjugated quercetin metabolites as attenuators for oxidative stress in the central nervous system, we measured the 13-hydroperoxyoctadecadienoic acid (13-HPODE)-dependent formation of reactive oxygen species (ROS) in pheochromocytoma PC-12 cells in the presence of quercetin 3-O-beta-glucuronide (Q3GA) and related compounds. A 2',7'-dichlorofluorescin (DCFH) assay showed that Q3GA significantly suppressed the formation of ROS, when it was coincubated with 13-HPODE (coincubation system). However, it was less effective than quercetin aglycon in the concentration range from 0.5 to 10 microM. In an experiment in which the cells were incubated with the test compounds for 24 h before being exposed to 13-HPODE, Q3GA was also effective in suppressing the formation of ROS in spite that little Q3GA was taken up into the cells. These results suggest that antioxidative metabolites of quercetin are capable of protecting nerve cells from attack of lipid hydroperoxides.

Animals↗

PubMed2005

Thioredoxin suppresses airway hyperresponsiveness and airway inflammation in asthma.

Thioredoxin (TRX) is a 12-kDa redox (reduction/oxidation)-active protein that has a highly conserved site (-Cys-Gly-Pro-Cys-) and scavenges reactive oxygen species. Here we examined whether exogenously administered TRX modulated airway hyperresponsiveness (AHR) and airway inflammation in a mouse asthma model. Increased AHR to inhaled acetylcholine and airway inflammation accompanied by eosinophilia were observed in OVA-sensitized mice. Administration of wild-type but not 32S/35S mutant TRX strongly suppressed AHR and airway inflammation, and upregulated expression of mRNA of several cytokines (e.g., IL-1alpha, IL-1beta, IL-1 receptor antagonist, and IL-18) in the lungs of OVA-sensitized mice. In contrast, TRX treatment at the time of OVA sensitization did not improve AHR or airway inflammation in OVA-sensitized mice. Thus, TRX inhibited the asthmatic response after sensitization, but did not prevent sensitization itself. TRX and redox-active protein may have clinical benefits in patients with asthma.

Animals↗

PubMed2005

Clinical utility of lipoarabinomannan antibody in pleural fluid for the diagnosis of tuberculous pleurisy.

We studied the clinical utility of the detection of lipoarabinomannan antibody, using MycoDot, in pleural fluid for the diagnosis of tuberculous pleurisy. Nine patients with active tuberculous pleurisy, 1 patient with chronic tuberculous empyema, and 16 patients with nontuberculous pleural effusions were studied. The results were positive in 5 patients with tuberculous pleural disease. Sensitivity was 50% (5 of 10; including the 1 patient with chronic tuberculous empyema) and specificity was 93.8% (15 of 16). Detection of lipoarabinomannan antibody using MycoDot in pleural fluid is a specific diagnostic tool for tuberculous pleurisy; furthermore, this diagnostic method is simple, rapid, and cost-effective.

Adolescent↗

PubMed2005

Helicobacter pylori infection rate in patients with nontuberculous mycobacteriosis who are on longterm combination chemotherapy of clarithromycin and rifampicin.

Clarithromycin resistance in Helicobacter pylori has increased the incidence of eradication failure. Clarithromycin is a key drug in the current treatment regimens for H. pylori infection, and it is also used for nontuberculous mycobacteriosis (NTM). The rate of H. pylori infection in 15 patients with NTM who were on longterm clarithromycin, rifampicin, and other drug therapy was examined, using the [(13)C] urea breath test. H. pylori was detected in 5 of the 15 patients (33.3%), which was significantly lower than the prevalence of H. pyloriin subjects who had routine upper gastrointestinal endoscopy in Japan (P = 0.0006). Thus, H. pylori resistance to clarithromycin is suggested to be low in patients with longterm administration, and the possibility exists of a combination of clarithromycin and rifampicin as a second-line therapy for the eradiation of H. pylori.

Aged↗

PubMed2005

Approach to novel functional foods for stress control: 1. Toward structure-activity relationship and data mining of food compounds by chemoinformatics.

Over the past several decades, thousands of natural organic compounds have been isolated from foods, and the information about their structures and biological activities has been accumulated. Despite the long research history of food products and their potential great promise as a medicine and functional food, the systematic research and development have not been carried out extensively. For understanding of the comprehensive structure-activity relationship, we have developed the database system of flavonoids, which are frequently found in vegetables and fruits. We also plan to execute a virtual screening of flavonoids with antidepressant activity by using the database and an advanced chemoinformatic tool. In this section, we will briefly describe (1) flavonoid database and (2) virtual screening of antidepressant compounds.

Antidepressive Agents↗

PubMed2005

Construction of a novel database for flavonoids.

Flavonoids are polyphenolic compounds that exist ubiquitously in foods of plant origin. Flavonoids show various interesting biological activities, such as removal of oxygen radical, anti-cancer action, improvement of high blood pressure, antibacterial, antibiotic and anti-allergy actions. So far, over 4000 structurally unique flavonoids have been isolated from plant sources. Recently, databases of chemicals have been utilized in to help chemical and biological researches, however the comprehensive database of flavonoids with information about structural, biological and physicochemical properties not yet available. We have constructed the integrated database of flavonoids for nutrition research.

Chemical Phenomena↗

PubMed2005

Virtual screening models for finding novel antidepressants.

Virtual screening was carried out against various biological targets related to depression by support vector machine classification using the atom-type descriptors. The models were effective as over 75 and 95% of the molecules in external test datasets could be correctly classified, depending on target. Antidepressant compounds had predicted activity against 2.3 targets, on average. An introduction is given to virtual screening and the results of classification experiments are presented.

Algorithms↗

PubMed2004

Clinical features of acute respiratory infections associated with the Streptococcus milleri group in the elderly.

The Streptococcus milleri group are becoming increasingly recognized as important pulmonary pathogens which may lead to the development of empyema or lung abscesses. Although several small series have been reported, the clinical and laboratory features of Streptococcus milleri infection have yet to be fully characterized in the elderly. We retrospectively examined the clinical features of 19 patients with Streptococcus milleri pulmonary disease who were admitted to our hospital between 2000 and 2002, based on their clinical records and laboratory data. The microbiological diagnosis was based on the results of quantitative sputum culture and other invasive procedures, including transthoracic needle aspiration or bronchoscopic examinations. There were thirteen cases of pneumonia, two of contaminant pneumonia and pleuritis, one of bronchitis, two of pulmonary abscess, and one of empyema. The patients ranged in age from 65 to 91. The most common symptoms at presentation were shortness of breath, coughing, sputum, and weight loss. An underlying disease existed in 14 of the 19 cases. We conclude that the Streptococcus milleri group is a more important cause of pulmonary infections than has been previously recognized.

Acute Disease↗

PubMed2003

A case of adult-onset Alexander disease with Arg416Trp human glial fibrillary acidic protein gene mutation.

Heterozygous point mutations in the coding region of the human glial fibrillary acidic protein (GFAP) gene have been reported in patients with various forms of Alexander disease (AD). We report a case of genetically confirmed adult-onset AD with palatal myoclonus, pyramidal tract signs, cerebellar signs, and marked atrophy of the medulla oblongata and spinal cord, autonomic dysfunction and heterozygous R416W GFAP mutation. Interestingly, this R416W mutation has also been reported in both infantile and juvenile forms of Alexander disease. The fact that a R416W mutation causes various types of AD suggests that clinical severities of AD are due not only to the different sites and nature of mutations in GFAP, but also to other modifying factor(s).

Adult↗

PubMed2003

Visualization of pulmonary arteriovenous malformation by three dimensional computed tomography: a case report.

Pulmonary arteriovenous malformation (PAVM) is an anomaly condition characterized by abnormal vascular communications between arteries and veins in the lungs. Hereby we describe a 60-year-old female with PAVM. Although the patient was asymptomatic, an abnormal round opacity was found on a chest X-ray film. Computed tomography (CT) of the lung disclosed nodules connected with enlarged vessels. Because PAVM was suspected, the patient was further evaluated by spiral CT coupled with three dimensional reconstruction of the images (3D-CT). As a result, PAVM was clearly visualized and invasive procedures such as angiography was not performed. The present case illustrates that 3D-CT is a diagnostic procedure of choice when PAVM is suspected.

Arteriovenous Fistula↗

PubMed2003

[A case of primary nasopharyngeal tuberculosis].

BACKGROUND: Although the prevalence of nasopharyngeal tuberculosis has decreased after the wide use of anti-tuberculous agents, recently the number of reports with the disease has slightly increased in accordance with advances in the diagnostic tools. A case of nasopharyngeal tuberculosis without any tuberculous lesions in other organs (primary nasopharyngeal tuberculosis) was reported. CASE REPORT: A 74-year-old female complained of vertigo and cervical masses, and naso-pharygo-laryngoscopy disclosed a polypoid lesion on her nasopharynx. The biopsy from the mass revealed epithelioid cell granulomas with caseous necrosis and multinucleated giant cells consistent with tuberculosis. Since there were no tuberculous lesions in other organs except cervical lymph nodes in clinical examinations, we diagnosed the case as primary nasopharyngeal tuberculosis with tuberculous cervical lymphadenitis. The nasopharyngeal manifestation disappeared after four months chemotherapy with INH, RFP and EB. DISCUSSION: Most reported case of nasopharyngeal tuberculosis were in the young age group. A rare case of old woman complicated with cervical tuberculous lymphadenitis was reported.

Adolescent↗

PubMed2002

Zerumbone, a Southeast Asian ginger sesquiterpene, markedly suppresses free radical generation, proinflammatory protein production, and cancer cell proliferation accompanied by apoptosis: the alpha,beta-unsaturated carbonyl group is a prerequisite.

Zerumbone (ZER), a sesquiterpene from the edible plant Zingiber zerumbet Smith, has recently been found to suppress tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Epstein-Barr virus activation in a potent manner. In the present study, we evaluated the anti-inflammatory and chemopreventive potentials of ZER in a variety of cell culture experiments. ZER effectively suppressed TPA-induced superoxide anion generation from both NADPH oxidase in dimethylsulfoxide-differentiated HL-60 human acute promyelocytic leukemia cells and xanthine oxidase in AS52 Chinese hamster ovary cells. The combined lipopolysaccharide- and interferon-gamma-stimulated protein expressions of inducible nitric oxide synthase and cyclooxygenase (COX)-2, together with the release of tumor necrosis factor-alpha, in RAW 264.7 mouse macrophages were also markedly diminished. These suppressive events were accompanied with a combined decrease in the medium concentrations of nitrite and prostaglandin E(2), while the expression level of COX-1 was unchanged. ZER inhibited the proliferation of human colonic adenocarcinoma cell lines (LS174T, LS180, COLO205, and COLO320DM) in a dose-dependent manner, while the growth of normal human dermal (2F0-C25) and colon (CCD-18 Co) fibroblasts was less affected. It also induced apoptosis in COLO205 cells, as detected by dysfunction of the mitochondria transmembrane, Annexin V-detected translocation of phosphatidylserine, and chromatin condensation. Intriguingly, alpha-humulene, a structural analog lacking only the carbonyl group in ZER, was virtually inactive in all experiments conducted, indicating that the alpha,beta-unsaturated carbonyl group in ZER may play some pivotal roles in interactions with unidentified target molecule(s). Taken together, our results indicate that ZER is a food phytochemical that has distinct potentials for use in anti-inflammation, chemoprevention, and chemotherapy strategies.

Adenocarcinoma↗

PubMedDate not supplied

Screening for new antidepressant leads of multiple activities by support vector machines.

Virtual screening was carried out against 21 biological targets related to depression by support vector machine classification using the same atom-type descriptors. The models were effective as 0.2-0.8 of theoretical enrichments of the external test data sets could be achieved, depending on the target. The set of predicted active molecules had large diversity and contained examples with high dissimilarity to the compounds of training sets. Filtering the database of known antidepressants by all 21 models it was found that on average compounds were classified active for 2.3 targets.

Antidepressive Agents↗

PubMedDate not supplied

Topical application of Bifidobacterium-fermented soy milk extract containing genistein and daidzein improves rheological and physiological properties of skin.

The authors examined the effects of Bifidobacterium-fermented soy milk extract (BE) containing genistein and daidzein on the hyaluronic acid (HA) content and rheological and physiological properties of hairless mouse and/or human skin. Topical application of BE for six weeks significantly restored changes in the elasticity and viscoelasticity of mouse skin, increased the HA content, and hydrated and thickened mouse skin. Also, topical application of a gel formula containing 10% BE to the human forearm for three months significantly lessened the decrease in skin elasticity. Therefore, BE is expected to become a new cosmetic ingredient to prevent the loss of skin elasticity through enhancement of HA production.

Administration, Topical↗