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Biomedical subjects

R Tanaka

Publications and source records attributed to R Tanaka.

At least 73 records · Page 4Linked to original sources
PubMed2001

Polymorphisms of renin-angiotensin system genes in childhood IgA nephropathy.

We investigated whether polymorphisms of the renin-angiotensin system genes are involved in IgA nephropathy in Japanese children. We identified the M235T polymorphism of the angiotensinogen (AGT) gene, the I/D polymorphisms of the angiotensin-converting enzyme (ACE) gene, and the A1166C polymorphism of the angiotensin II type 1 receptor gene in 95 Japanese children with IgA nephropathy and 99 healthy Japanese adults. There were no differences in the genotype and allele frequencies of these genes between patients with IgA nephropathy and controls. Urinary protein excretion at the time of biopsy was significantly greater in patients with the TT genotype of the AGT gene than in those with the MM/MT genotypes of the AGT gene (1.32 +/- 1.42 versus 0.75 +/- 0.78 g/day; P = 0.01) and in patients with the ID/DD genotypes of the ACE gene than in those with the II genotype of the ACE gene (1.45 +/- 1.50 versus 0.63 +/- 0.56 g/day; P = 0.001). Thus, the TT genotype of the AGT gene and the ID/DD genotype of the ACE gene are associated with increased severity of proteinuria, suggesting that AGT and ACE gene polymorphisms may play a significant role in the progression of IgA nephropathy in Japanese children.

Adolescent↗
PubMed2001

Pathophysiology and treatment of IgA nephropathy in children.

IgA nephropathy is the most-common primary glomerulonephritis worldwide, and about 20%-50% of patients develop progressive renal failure. The pathogenesis is still unknown and treatment has not yet been established. Knowledge concerning childhood IgA nephropathy has expanded greatly in the last 10 years, and its importance as the major form of glomerulonephritis and major contributor to end-stage renal disease is also becoming apparent in children. This review focuses on the pathophysiology and treatment of IgA nephropathy in children.

Child↗
PubMed2001

Recovery from cyclosporine-associated arteriolopathy in childhood nephrotic syndrome.

Cyclosporine (CS) is well recognized to be effective in the treatment of children with steroid-dependent and steroid-resistant nephrotic syndrome (NS), but its use can result in chronic nephrotoxicity. The histological changes that occur after CS discontinuation are unknown. Therefore, we examined the histological changes [CS-associated arteriolopathy (CAA), tubulointerstitial lesions, and focal glomerular lesions] in renal biopsy specimens after the drug had been discontinued in eight children with idiopathic nephrotic syndrome (NS). These children had been treated with long-term moderate-dose CS and had shown mild-to-moderate chronic CS nephrotoxicity. The degree of CAA improved significantly after CS discontinuation (mean CAA grade from 1.30+/-0.46 to 0.25+/-0.46, P=0.028). CAA disappeared in six of these children after CS discontinuation. However, the tubulointerstitial lesions and the focal glomerular lesions did not change after CS discontinuation. In conclusion, in children with idiopathic NS, CAA is improved by discontinuation of CS, but tubulointerstitial changes and focal glomerular lesions do not regress with drug discontinuation.

Arteries↗
PubMed2001

Neurohypophyseal germinoma traced from its earliest stage via magnetic resonance imaging: case report.

BACKGROUND: We report a case in which magnetic resonance imaging (MRI) documented the formation of a neurohypophyseal germinoma from its earliest stage. CASE DESCRIPTION: A 9-year-old girl presented with polyuria, polydipsia, and growth retardation. Urinary and endocrinological examination indicated diabetes insipidus (DI) and growth hormone deficiency. No clear evidence of a mass in the hypothalamo-pituitary area was apparent on the first MRI scan. Follow-up MRIs and endocrinological examinations revealed that a tumor, arising from the stalk and posterior lobe of the pituitary gland, formed a mass and caused anterior pituitary function to deteriorate. Histologic diagnosis was germinoma based on open biopsy. CONCLUSION: Radiologic findings in this case indicated the primary site of this intrasellar germinoma to be the hypothalamo-neurohypophyseal region, designating this a "neurohypophyseal germinoma."

Child↗
PubMed2001

Trichosporon species infection in bone marrow transplanted patients.

Trichosporon species are emerging as opportunistic agents that cause systemic diseases in immunocompromised patients. Patients undergoing bone marrow transplant are submitted to intense and prolonged periods of neutropenia and consequently to several risk factors to fungal infections as the use of broad spectrum antibiotics and invasive devices. Two cases of fungal infections caused by Trichosporon asahii var. asahii and T. inkin in patients with bone marrow transplant are described T. asahii var. asahii was responsible for fungemia and the identification of this microorganism was later performed. T. inkin caused vascular accesses infection and was recovered from an implanted Hickman-Broviac catheter. Both patients were under oral fluconazole prophylaxis. The patient with systemic infection died despite the therapy with amphotericin B and the patient with catheter-related infection recovered from the fungal infection after catheter removal. Difficulties in the identification of this microorganism lead to delays in treatment and post-mortem diagnosis.

Adult↗
PubMed2001

Anti-tumor promoting diterpenes from the stem bark of Thuja standishii (Cupressaceae).

Three new labdane-type diterpenoids, labda-8(17),13-dien-15,12R-olid-19-oic acid (1), 12S-hydroxylabda-8(17),13(16),14-trien-19-oic acid (2) and 13-ethoxylabda-8(17),11,14-trien-19-oic acid (3), along with known diterpenoids, trans-communic acid (4), totarol (5), 12-methoxyabieta-8,11,13-trien-11-ol (6), and 7 alpha,8 alpha-epoxy-6 alpha-hydroxyabieta-9(11),13-dien-12-one (7) were isolated from the stem bark of Thuja standishii. The structures of 1--3 were established by spectroscopic methods and chemical conversion. These compounds together with standishinal (8), 12-hydroxy-6,7-seco-abieta-8,11,13-trien-6,7-dial (9) and 6 alpha-hydroxysugiol (10) were tested for their inhibitory effects on Epstein--Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), as a test for potential cancer chemopreventive agents. Compound 10 showed strong inhibitory effect on EBV-EA induction (100% inhibition at 1000 mol ratio/TPA), and compounds 2 and 6 showed moderate inhibitory effects on EBV-EA induction. In addition, 15-oxolabda-8(17),11Z,13E-trien-19-oic acid (11) was found to exhibit the anti-tumor promoting activity in two-stage mouse skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene and TPA.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2001

Structure and stereochemistry of epoxyserratanes from the cuticle of Piceajezoensis var. jezoensis.

Three new epoxytriterpenes, 14 beta,15 beta-epoxy-21 beta-hydroxyserratan-3-one (1), 13 alpha,14 alpha-epoxy-21 alpha-methoxyserratan-3-one (2), and 13 alpha,14 alpha-epoxy-3 beta-methoxyserratan-21 beta-ol (3), were isolated together with two known triterpenoids, 21 alpha-methoxyserrat-13-en-3-one (4) and 21 beta-hydroxyserrat-14-en-3-one (5), from the cuticle of Picea jezoensis var. jezoensis. The structures of these new compounds were established on the basis of spectral data (NMR, MS) and single-crystal X-ray analyses (1 and 2) and partial synthesis (2 and 3).

Chromatography, Thin Layer↗
PubMed2001

Screening of triterpenoids isolated from Phyllanthus flexuosus for DNA topoisomerase inhibitory activity.

DNA topoisomerases (Topos) are enzymes that play a crucial role in DNA metabolism events such as replication, transcription, recombination, and chromosome segregation at mitosis. Thus, Topo inhibitors could be expected to have antitumor effects. Naturally occurring lupane- and oleanane-type triterpenoids isolated from the bark of Phyllanthus flexuosus were screened for human Topos I and II inhibitory activities. Olean-12-en-3 beta,15 alpha-diol (1), olean-12-en-3 beta,15 alpha,24-triol (3), lupeol (4), and betulin (6) were found to be selective catalytic inhibitors of human Topo II activity with IC(50) values in the range of 10-39 microM.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Early interleukin 4-dependent response can induce airway hyperreactivity before development of airway inflammation in a mouse model of asthma.

In experimental models of bronchial asthma with mice, airway inflammation and increase in airway hyperreactivity (AHR) are induced by a combination of systemic sensitization and airway challenge with allergens. In this report, we present another possibility: that systemic antigen-specific sensitization alone can induce AHR before the development of inflammation in the airway. Male BALB/c mice were sensitized with ovalbumin (OVA) by a combination of intraperitoneal injection and aerosol inhalation, and various parameters for airway inflammation and hyperreactivity were sequentially analyzed. Bronchial response measured by a noninvasive method (enhanced pause) and the eosinophil count and interleukin (IL)-5 concentration in bronchoalveolar lavage fluid (BALF) gradually increased following the sensitization, and significant increase was achieved after repeated OVA aerosol inhalation along with development of histologic changes of the airway. In contrast, AHR was already significantly increased by systemic sensitization alone, although airway inflammation hardly developed at that time point. BALF IL-4 concentration and the expression of IL-4 mRNA in the lung reached maximal values after the systemic sensitization, then subsequently decreased. Treatment of mice with anti-IL-4 neutralizing antibody during systemic sensitization significantly suppressed this early increase in AHR. In addition, IL-4 gene-targeted mice did not reveal this early increase in AHR by systemic sensitization. These results suggest that an immune response in the lung in an early stage of sensitization can induce airway hyperreactivity before development of an eosinophilic airway inflammation in BALB/c mice and that IL-4 plays an essential role in this process. If this early increase in AHR does occur in sensitized human infants, it could be another therapeutic target for early prevention of the future onset of asthma.

Allergens↗
PubMed2001

Prompt and durable hematopoietic reconstitution by unrelated cord blood transplantation in a child with Fanconi anemia.

We describe here the case of an 8-year-old girl with Fanconi anemia (FA) whose hematopoiesis was successfully restored by unrelated umbilical cord blood (UCB) transplantation. The patient became resistant to androgen therapy, and developed intracranial hemorrhage and dyserythropoiesis. Her hematopoietic recovery after the transplantation was excellent and a complete chimerism has been durably maintained. UCB should be considered as a stem cell source for transplantation when a patient with FA does not have an HLA-identical unaffected sibling donor.

Child, Preschool↗
PubMed2001

Induction of therapeutic antitumor antiangiogenesis by intratumoral injection of genetically engineered endostatin-producing Semliki Forest virus.

Antiangiogenic therapy using Semliki Forest virus (SFV) carrying Endostatin gene for malignant brain tumor was investigated to improve the therapeutic efficacy. The efficiency of SFV-mediated gene delivery was first evaluated for B 16 cells and compared with the efficiency in cells of endothelial origin (HMVECs). HMVECs are more susceptible to SFV infection than B 16 cells. For the in vivo treatment model, phosphate-buffered saline, SFV-LacZ, retrovirus vector GCsap-Endostatin, and SFV-Endostatin were injected to mice bearing B 16 brain tumors. A very significant inhibition of tumor growth was observed in the group that had been treated with SFV-Endostatin. A marked reduction of intratumoral vascularization was seen in the tumor sections from the SFV-Endostatin group compared with tumor sections from the SFV-LacZ or GCsap-Endostatin groups. Moreover, at day 7 after intravenous administration of SFV-Endostatin, the serum level of endostatin was augmented more than 3-fold compared to that after intravenous administration of GCsap-Endostatin. The results indicated that treatment with SFV-Endostatin inhibited the angiogenesis with established tumors. Gene therapy with Endostatin delivered via SFV may be a candidate for the development of new therapy for brain tumors.

Animals↗
PubMed2001

Numerical, morphological and phenotypic changes in Langerhans cells in the course of murine graft-versus-host disease.

BACKGROUND: In the course of graft-versus-host disease (GVHD) or diseases that histologically mimic GVHD (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome), it is known that epidermal Langerhans cells (LCs) are depleted from the epidermis. However, the mechanism and significance of LC depletion is not well known. OBJECTIVES: To investigate the numerical, morphological and phenotypic changes in LCs and apoptosis of LCs in the course of GVHD using a non-irradiated mouse GVHD model. METHODS: BALB/c nu/nu mice and C57BL/6 mice were used as recipients and donors, respectively. Recipient mice were injected with T-cell-enriched donor spleen cells. Skin samples were harvested at various times after the inoculation. The numerical and morphological changes were examined by an immunofluorescence study of epidermal sheets. Apoptosis was studied by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling method and flow cytometric analysis using annexin V. Phenotypic change was studied by flow cytometric analysis of epidermal cell suspensions. The mixed epidermal cell lymphocyte reaction (MELR) was performed to examine functional changes in the epidermal cells. RESULTS: Five days after inoculation, a graft-versus-host reaction occurred. Epidermal LCs began to decrease from the sixth day. On the fifth day, the LCs became larger and had prominent dendrites. Immediately before the LCs began to decrease, many LCs became round in shape, with scanty dendrites. LC apoptosis was not observed in the epidermis either on the fifth or seventh day. Phenotypically, the expression of CD40, CD80, CD86 and major histocompatibility complex class II antigen on the LCs was upregulated on the fifth and seventh day. Epidermal cells from GVHD mice showed an increased allostimulatory capacity in the secondary MELR. CONCLUSIONS: These results suggest that at early GVHD onset, most LCs may not undergo apoptosis in the epidermis but are phenotypically activated, resulting in further activation of alloreactive T cells and aggravation of the disease.

Animals↗
PubMed2001

Increased resistance of mice to Salmonella enterica serovar Typhimurium infection by synbiotic administration of Bifidobacteria and transgalactosylated oligosaccharides.

AIMS: The anti-infectious activity of Bifidobacteria in combination with transgalactosylated oligosaccharides (TOS) against Salmonella enterica serovar Typhimurium LT-2 in an opportunistic antibiotic-induced murine infection model in mice was examined. METHODS AND RESULTS: B. breve (strain Yakult) with natural resistance to streptomycin sulphate (SM, MIC: > 4 mg ml(-1)), when given daily at a dose of 108 cfu/mouse orally under SM treatment was constantly excreted at 10(10) cfu g(-1) faeces so long as SM was administered, even at 2 weeks after discontinuing administration of B. breve. Explosive intestinal growth and subsequent extra-intestinal translocation of orally infected LT-2 under SM treatment were inhibited by B. breve colonization, and this anti-infectious activity was strengthened by synbiotic administration of TOS with B. breve. Comparison of anti-Salmonella activity among several Bifidobacterium strains with natural resistance to SM revealed that strains such as B. bifidum ATCC 15696 and B. catenulatum ATCC 27539T conferred no activity, even when they reached high population levels similar those of effective strains such as strain Yakult and B. pseudocatenulatum DSM 20439. Both the increase in the concentration of organic acids and the lowered pH in the intestine due to bifidobacterial colonization correlated with the anti-infectious activity. Moreover, the crude cecal extract of B. breve-colonized mice exerted growth-inhibitory activity against LT-2 in vitro, whereas that of the ineffective B. bifidum-colonized cecum showed much lower activity. CONCLUSIONS: Intestinal colonization by bifidobacteria given exogenously together with TOS during antibiotic treatment prevents the antibiotic-induced disruption of colonization resistance to oral infection with S. enterica serovar Typhimurium, and the metabolic activity needed to produce organic acids and lower the intestinal pH is important in the anti-infectious activity of synbiotics against enteric infection with Salmonella. SIGNIFICANCE AND IMPACT OF THE STUDY: These results indicate that certain bifidobacteria together with prebiotics may be used for the prophylaxis against opportunistic intestinal infections with antibiotic-resistant pathogens.

Animals↗
PubMed2001

Overexpression of chlorophyllide a oxygenase (CAO) enlarges the antenna size of photosystem II in Arabidopsis thaliana.

The light-harvesting efficiency of a photosystem is thought to be largely dependent on its photosynthetic antenna size. It has been suggested that antenna size is controlled by the biosynthesis of chlorophyll b. To verify this hypothesis, we overexpressed the enzyme for chlorophyll b biosynthesis, chlorophyllide a oxygenase (CAO), in Arabidopsis thaliana by transforming the plant with cDNA for CAO under the control of the 35S cauliflower mosaic virus promoter. In the early de-etiolation phase, when the intrinsic CAO expression is very low, the chlorophyll a: b ratio was drastically decreased from 28 to 7.3, indicating that enhancement of chlorophyll b biosynthesis had been successfully achieved. We made the following observations in full-green rosette leaves of transgenic plants. (1) The chlorophyll a : b ratio was reduced from 2.85 to 2.65. (2) The ratio of the peripheral light-harvesting complexes (LHCII) to the core antenna complex (CPa) resolved with the green-gel system increased by 20%. (3) The ratio of the light-harvesting complex II apoproteins (LHCP) to 47-kDa chlorophyll a protein (CP47), which was estimated by the results of immunoblotting, increased by 40%. These results indicated that the antenna size increased by at least 10-20% in transgenic plants, suggesting that chlorophyll b biosynthesis controls antenna size. To the best of our knowledge, this is the first report on enlargement of the antenna size by genetic manipulations.

Apoproteins↗
PubMed2001

Cerebriform colonies of Paracoccidioides brasiliensis isolated from nine-banded armadillos (Dasypus novemcinctus) at room temperature.

Twelve isolates of Paracoccidioides brasiliensis generated cerebriform colonies at room temperature on potato glucose agar slants (PDA). These isolates contained abundant chlamydospores and yeast-like cells and are a subset of the 65 isolates obtained from nine-banded armadillos (Dasypus novemcinctus). They grew as a yeast form with typical multiple buddings at 37 degrees C on brain heart infusion agar supplemented with 1% glucose. After replating on PDA and culturing at room temperature for 2 months, the mutants appeared as cottonous colonies, which indicated that the morphological characteristics were unstable.

Animals↗
PubMed2001

Identification and subtyping of Trichophyton mentagrophytes by random amplified polymorphic DNA.

Trichophyton mentagrophytes is one of the most common pathogens for human and animal dermatophytoses and known as a complex species with variable morphology, and ecologic and genetic backgrounds. We performed random amplified polymorphic DNA (RAPD) analysis on 43 human and 18 animal isolates of T. mentagrophytes along with other 10 anamorphic species of dermatophytes and three teleomorphic species of T. mentagrophytes. Using RAPD analysis with primer 5'-ATGGATC(G,C)(G,C)C-3' (ATGS), all T. mentagrophytes strains produced identical band patterns with those of Arthroderma vanbreuseghemii, one of the teleomorphs of T. mentagrophytes, regardless of their phenotypes. Therefore, T. mentagrophytes could be identified by RAPD analysis with primer ATGS. Using RAPD analysis with primer 5'-ATGGATCGGC-3' (ATG) on T. mentagrophytes, human isolates yielded two distinct subgroups related by their colony morphologies at the time of primary isolation from patients. Three morphologic types--cottony, powdery and persicolor--revealed identical bands whereas the granular type lacked one minor band (0.74 kbp). Animal isolates of T. mentagrophytes produced five band patterns and some of them were identical with those of human isolates. With primer 5'-GAAGGCTCCC-3' (OPAO-15), animal isolates of T. mentagrophytes showed diverse band patterns in contrast to the uniform band pattern of human isolates. These results suggest that RAPD analysis may be a useful tool to identify and subtype T. mentagrophytes complex.

Animals↗
PubMed2001

Triterpene constituents from the stem bark of Pinus luchuensis and their DNA topoisomerase II inhibitory effect.

Nine lanostane and serratane-type triterpenes including two unknown compounds were isolated from the stem bark of Pinus luchuensis. These new compounds were characterized as 3-oxolanost-9(11)-ene-24S,25-diol (1) and 29-acetoxy-3beta-methoxyserrat-14-en-21alpha-ol (2) on the basis of spectroscopic evidence. Some of these triterpenes were tested for the inhibitory effect on DNA topoisomerase II activity. Compound 1 showed a slightly less potent inhibitory activity with an IC(50) value of 186 microM.

Acetyl-CoA C-Acyltransferase↗