Search PubMed⌕ Search

Biomedical subjects

T Chihara

Publications and source records attributed to T Chihara.

At least 19 recordsLinked to original sources
PubMed2005

Inhibitory effects of aloe carboxypeptidase fraction on streptozotocin-induced enhancement of vascular permeability in the pancreatic islets.

The protective actions of components isolated from Aloe arborescens Miller var. natalensis Berger (Kidachi aloe in Japanese) on streptozotocin (Sz)-induced necrosis of B cells in the pancreatic islets of the mouse were investigated to clarify its action mechanism involved in anti-diabetic effects. In this experiment, phenol low molecular weight components of aloin and aloin A that were anti-oxidants and derived from the leaf skin or pulp extract, an aloe carboxypeptidase fraction that is a inhibitor of enhanced vascular permeability and a glycoprotein component that decreases blood glucose were tested with mice precedently administered with Sz which is known as a cytotoxin specific to B cells. The results showed that the treatment group receiving Sz followed by the aloe carboxypeptidase fraction increased the inhibition of dye leakage by 75.8% (p<0.001) in the extract of whole pancreas in comparison to the control group and the aloe carboxypeptidase fraction group also increased the inhibition effect by 68.4% (p<0.001) in the extract of pancreatic islets as compared to the control group. The carboxypeptidase is an aloe-derived protease known to inhibit the acetic acid-related enhancement of intraperitoneal vascular permeability in mice. Further, the elevation of blood glucose in Sz-induced diabetic mice intraperitoneally given the aloe carboxypeptitase fraction was significantly (p<0.01-0.001) restrained at 3, 7 and 14 days after the injection as compared to the control group given solvent only. The results of this experiment suggested that the inhibitory effect on the enhancement of vascular permeability related to the vascular acute inflammatory response at Sz-induced lesions of pancreatic islets was involved in the action mechanism of this enzyme.

Aloe↗
PubMed2001

Determination of aloenin, barbaloin and isobarbaloin in aloe species by micellar electrokinetic chromatography.

Aloenin, barbaloin and isobarbaloin in JP Aloe, Aloe barbadensis (Aloe vera) and Aloe arborescens Miller var. natalensis Berger (Aloe arborescens Miller) were determined by micellar electrokinetic chromatography (MEKC) with 50 mM sodium dodecyl sulfate. Aloenin, barbaloin and isobarbaloin were well separated by MEKC and as little as 5.5 pg/11 nl of the three compounds could be detected. The determination took around 14 min.

Aloe↗
PubMed2001

Inhibition of azoxymethane-induced aberrant crypt foci formation in rat colorectum by whole leaf Aloe arborescens Miller var. natalensis Berger.

We examined the modifying effect of whole-leaf Aloe arborescens Miller var. natalensis Berger (designated as 'ALOE') on azoxymethane (AOM)-induced aberrant crypt foci (ACF), putative preneoplastic lesions, in the rat colorectum. Male F344 rats (4 weeks old) were fed the basal diet, or experimental diets containing 1% or 5% ALOE for 5 weeks. One week later, all rats except those in the vehicle-treated groups were injected s.c. with AOM (15 mg/kg, once weekly for 3 weeks). At 9 weeks of age, all the rats were killed, and the colorectum and liver were evaluated for ACF and cytosolic quinone reductase (QR; a phase 2 enzyme), respectively. In rats given AOM and ALOE (1% or 5% in diet) the numbers of ACF/colorectum, aberrant crypts/colorectum, aberrant crypts/focus and large ACF/colorectum were significantly decreased compared with those of rats given AOM alone (all p < 0.01). No ACF were found in rats treated without AOM. In addition, ALOE significantly increased cytosolic QR activity in the liver (p < 0.01). These results indicated that ALOE inhibited the development of AOM-induced ACF in the rat colorectum, with increased QR activity in the liver, and therefore suggested that ALOE might have a chemopreventive effect against colon carcinogenesis at least in the initiation stage.

Aloe↗
PubMed2000

Control of tracheal tubulogenesis by Wingless signaling.

The tubular epithelium of the Drosophila tracheal system forms a network with a stereotyped pattern consisting of cells and branches with distinct identity. The tracheal primordium undergoes primary branching induced by the FGF homolog Branchless, differentiates cells with specialized functions such as fusion cells, which perform target recognition and adhesion during branch fusion, and extends branches toward specific targets. Specification of a unique identity for each primary branch is essential for directed migration, as a defect in either the EGFR or the Dpp pathway leads to a loss of branch identity and the misguidance of tracheal cell migration. Here, we investigate the role of Wingless signaling in the specification of cell and branch identity in the tracheal system. Wingless and its intracellular signal transducer, Armadillo, have multiple functions, including specifying the dorsal trunk through activation of Spalt expression and inducing differentiation of fusion cells in all fusion branches. Moreover, we show that Wingless signaling regulates Notch signaling by stimulating delta expression at the tip of primary branches. These activities of Wingless signaling together specify the shape of the dorsal trunk and other fusion branches.

Animals↗
PubMed1999

Myeloid ELF-1-like factor up-regulates lysozyme transcription in epithelial cells.

Lysozyme is an important component of innate immunity against common pathogens at mucosal surfaces. We previously cloned and characterized the bovine lysozyme 5A (lys5A) promoter with the purpose of determining cis- and trans-acting elements controlling airway epithelial cell-specific expression. We found that such expression is controlled by protein binding to an ETS consensus sequence located approximately at -46 to -40 bp from the transcription start site. The identity of the ETS-related protein responsible for gene transactivation was unknown. In this study, we screened six ETS-related proteins by transient transfection into epithelial cells and fibroblasts. Results showed that among these factors, the myeloid Elf-1-like factor (MEF) was the most potent. Gel shift analysis of epithelial cell nuclear extracts using a lys5A probe including the ETS-binding site (-50/-31) yielded a single band with retarded mobility. This band was supershifted by an antibody directed against MEF. Supporting the possibility that MEF is responsible for functional transactivation of lysozyme in epithelial cells, we found that antisense MEF mRNA decreased lys5A promoter activity and that MEF overexpression in stably transfected cells increased lysozyme mRNA and protein expression. We conclude that MEF is required for epithelial cell transactivation of lysozyme.

Animals↗
PubMed1999

[Novel transcription factor MEF is associated with the function of lung epithelial cells].

Lysozyme is an important component of innate immunity against common pathogens at mucosal surfaces. We previously cloned and characterized the bovine lysozyme 5A (lys5A) promoter with the purpose of determining cis- and trans-acting elements controlling airway epithelial cell-specific expression. We found that such expression is controlled by protein binding to an ETS consensus sequence located approximately at -46 to -40 bp from the transcription start site. The identity of the ETS-related protein responsible for gene transactivation was unknown. In this study, we screened six ETS-related proteins by transient transfection into epithelial cells and fibroblasts. Results showed that among these factors, the myeloid Elf-I-like factor (MEF) was the most potent. Gel shift analysis of epithelial cell nuclear extracts using a lys5A probe including the ETS-binding site (-50/-31) yielded a single band with retarded mobility. This band was super-shifted by an antibody directed against MEF. Supporting the possibility that MEF is responsible for functional transactivation of lysozyme in epithelial cells, we found that antisense MEF mRNA decreased lys5A promoter activity and that MEF overexpression in stably transfected cells increased lysozyme mRNA and protein expression. We conclude that MEF is required for epithelial cell transactivation of lysozyme.

Animals↗
PubMed1998

Laparoscopic management of rudimentary horn pregnancy. A case report.

BACKGROUND: Rudimentary uterine horn pregnancy is a very rare condition. Removal of a rudimentary horn is required as soon as a pregnancy is confirmed because most pregnancies in a rudimentary uterine horn rupture in the first or second trimester. CASE: A 22-year-old woman was admitted to our hospital because an ectopic pregnancy was suggested by ultrasonographic examination at another hospital. A rudimentary uterine horn pregnancy was suspected from transvaginal ultrasonography. The patient was treated with laparoscopic surgery at 7 weeks of gestation. The pregnant rudimentary horn was removed laparoscopically by use of an automatic stapling device. The postoperative course was uneventful. CONCLUSION: This is the first report of laparoscopic resection of a pregnant rudimentary uterine horn. Laparoscopic management of such a pregnancy may reduce operating time and peritoneal damage.

Abortion, Induced↗
PubMed1996

Host defensive functions in a family manifesting early-onset periodontitis.

Family case studies help us identify host risk factors in periodontal disease. In this study we examine a family consisting of a mother (40 years old, with rapidly progressive periodontitis), her elder daughter (14 years old, with localized juvenile periodontitis), and younger daughter (13 years old, with simple gingivitis). We examined 1) the peripheral neutrophil functions (chemotactic migration, phagocytosis, superoxide production); 2) lymphocyte functions (proliferative activity and cytokine productivity of T cells, immunoglobulin [Ig] M productivity of B cells when stimulated with pokeweed mitogen); 3) phenotypic analyses of peripheral lymphocyte subpopulations; 4) serum IgG antibody titers against periodontopathic bacteria; and 5) serological type of HLA class II. All the subjects exhibited high T4/T8 ratios due to high percentage of CD4-positive cells, showed high IgG titers to Actinobacillus actinomycetemcomitans, and had a HLA DQw1 in common. The mother showed a slight deficiency of neutrophil chemotactic migration to N-formyl methyonyl leucyl phenylalanin (fMLP), raised interleukin-2 productivity of T cell, and high levels of IgG titers to Porphyromonus gingivalis and Fusobacterium nucleatum. Both daughters showed weak T cell proliferative response to anti-CD3 monoclonal antibody and low IgM productivity. Low lymphocyte responsiveness may be involved in the pathogenesis of periodontal disease of these daughters; therefore, the lymphocyte dysfunctions shown should be considered in relation to the progression of periodontal disease.

Adolescent↗
PubMed1996

[Amines and pteridines].

Polyamines (putrescine, spermidine and spermine) play important roles in cell proliferation and differentiation, and have been established as tumors markers. We and other workers have confirmed that N1-acetylspermidine in tumor tissues, spermidine and spermine in erythrocytes, and N1,N12-diacetylspermine in urine might be the most sensitive indicators for various forms of tumors. Neopterin is a marker of cell-mediated immunostimulation, and may be a helpful marker in monitoring cancer patients. HPLC and immunological assays of neopterin, biopterin, and N2-(3-aminopropyl)biopterin(oncopterin) in urine might be useful in the clinical study of pteridines, as cancer markers. Serum 5-S-cysteinyldopa level is a useful and specific biochemical marker for malignant melanoma.

Biomarkers, Tumor↗
PubMed1995

OPC-21268 antagonizes arginine vasopressin-induced vasoconstrictor response in the spinally-anesthetized dog.

We studied the antagonistic actions of OPC-21268 (1-(1-[4-(3-acetylaminopropoxy)-benzoyl]-4-piperidyl)-3,4-dihydro- 2(1H)-quinolinone) on the arginine vasopressin (AVP)-induced vasoconstrictor response in the spinally-anesthetized dog. OPC-21268 at doses of 0.3, 1.0 and 3.0 mg/kg, i.v. produced a rightward parallel shift of the dose-response curves for AVP in a dose-dependent manner. The doses of OPC-21268 were similar to those that inhibited the AVP-induced vasoconstrictor response in the rat. This observation suggests that OPC-21268 acts as a V1-AVP-receptor antagonist in peripheral resistance vessels in dogs as well as in rats.

Animals↗
PubMed1995

Clinical and laboratory studies on a patient with early onset periodontitis and her family members. A case report.

Extensive clinical, microbiological, hematological, and immunological studies were performed on a patient with early onset periodontitis (EOP) and two other members of the family. The proband, a 27-year-old female, had early onset periodontitis and a high level of serum rheumatoid factors (RF) with no diagnosable medical disease. Her mother had lost all her teeth at the age of 50 because of advanced periodontitis, while her elder sister was unaffected by periodontitis. Neither the proband's periodontally-affected mother nor her unaffected sister exhibited a detectable level of RF. In this study, we examined: 1) serum immunoglobulin G (IgG) antibody titers against putative periodontal pathogenic bacteria; 2) peripheral neutrophil functions; 3) phenotypic analyses of peripheral lymphocyte subpopulations; and 4) peripheral lymphocyte functions (T cell proliferative activity, ability of cytokine [interleukin (IL)-2, tumor necrosis factor-alpha, interferon-gamma, IL-6 and IL-8] and IgG and IgM productivity). High antibody titers to Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Campylobacter rectus were detected in the sera of the proband, as were high serum antibody titers to P. gingivalis in the mother and to C. rectus in the unaffected sister compared to the non-periodontitis affected subjects. The proband also showed enhanced neutrophil chemotaxis; a high percentage of pan-B cells; and high productivity of IL-6, IgG, and IgM compared to individuals who were not periodontally affected. The mother showed slightly low helper/induced T cells (Th/i) suppressor/cytotoxic T cells (Ts/c) ratios due to the elevated count of Ts/c, and high IFN-gamma productivity compared to control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

OPC-21268, a vasopressin V1 antagonist, produces hypotension in spontaneously hypertensive rats.

We studied the hypotensive effects of OPC-21268, an orally effective nonpeptide vasopressin V1 receptor antagonist, in spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP). OPC-21268 was given intravenously to conscious, freely moving SHR and SHRSP. We used young and aged animals to examine the contribution of vasopressin to the development and maintenance of hypertension in both types of rats. In SHR, hypertension was fully established at 38 weeks of age, and intravenous injection of OPC-21268 produced slight hypotensive effects at either 38 or 70 weeks of age. In SHRSP, hypertension developed at 25 weeks of age, and blood pressure was sustained at a high level (approximately 250 mm Hg systolic blood pressure) thereafter. Intravenous administration of OPC-21268 did not cause hypotensive effects in young rats at 15 weeks, but at 25 weeks a significant decrease in blood pressure was observed. Furthermore, in the malignant state of SHRSP (35 to 41 weeks), OPC-21268 significantly decreased mean blood pressure by 32.4 +/- 7.9 mm Hg (mean +/- SEM) at 3 mg/kg IV, and the decrease was dose dependent (0.3 to 3.0 mg/kg). Plasma vasopressin concentrations were increased in a more malignant phase of SHRSP at 45 weeks of age, whereas at other ages of SHRSP or in SHR, plasma vasopressin levels were not increased. These results suggest that vasopressin plays an important role through V1 receptors in the maintenance of hypertension, at least in the malignant phase of SHRSP, and OPC-21268 may be therapeutically useful in the treatment of some types of hypertension.

Animals↗
PubMed1993

Orally active, nonpeptide vasopressin V1 antagonists. A novel series of 1-(1-substituted 4-piperidyl)-3,4-dihdyro-2(1H)-quinolinone.

A series of compounds has been synthesized and demonstrated to be antagonists of V1 receptors both in vitro and in vivo. These compounds are structurally related to the 1-(4-piperidyl)-2(1H)-quinolinones, including OPC-21268, an orally bioavailable AVP V1 antagonist with high V1 specificity. It has been found that the introduction of an acetamide group on the terminal alkoxy chain of 41-44 leads to an increase in oral activity. Certain of these compounds may have efficacy in the study of AVP V1 receptors.

Administration, Oral↗
PubMed1993

The genetics of autoimmune diabetes. Approaching a solution to the problem.

Molecular genetics has had a substantial impact on our understanding of inherited susceptibility to insulin-dependent diabetes mellitus. Alleles at the HLA-DQA1 and DQB1 loci appear to have the greatest influence on diabetogenesis. Other promising loci are present on chromosome 11 in the vicinity of the insulin gene. We have sought not only to improve our prediction of insulin-dependent diabetes mellitus but also to reveal the underlying immune and nonimmune defects that predispose to autoimmune beta-cell destruction. Continued advances in the field of genetics will aid in the prevention of insulin-dependent diabetes mellitus, which is our ultimate goal.

Diabetes Mellitus, Type 1↗
PubMed1992

Characterization of a novel aquaretic agent, OPC-31260, as an orally effective, nonpeptide vasopressin V2 receptor antagonist.

1. OPC-31260, a benzazepine derivative, has been studied for its ability to antagonize the binding of arginine vasopressin (AVP) to receptors in rat liver (V1) and kidney (V2) plasma membranes, for antagonism of the antidiuretic action of AVP in alcohol-anaesthetized rats and for diuretic action in conscious normal rats. 2. OPC-31260 caused a competitive displacement of [3H]-AVP binding to both V1 and V2 receptors with IC50 values of 1.2 +/- 0.2 x 10(-6) M and 1.4 +/- 0.2 x 10(-8) M, respectively. 3. OPC-31260 at doses of 10 to 100 micrograms kg-1, i.v., inhibited the antidiuretic action of exogenously administered AVP in water-loaded, alcohol-anaesthetized rats in a dose-dependent manner. OPC-31260 did not exert an antidiuretic activity suggesting that it is not a partial V2 receptor agonist. 4. After oral administration at doses of 1 to 30 mg kg-1 in normal conscious rats, OPC-31260 dose-dependently increased urine flow and decreased urine osmolality. The diuretic action of OPC-31260 was characterized as aquaresis, the mode of diuretic action being different from previously known diuretic agents such as furosemide, hydrochlorothiazide and spironolactone. 5. The results indicate that OPC-31260 is a selective V2 receptor antagonist and behaves as an aquaretic agent. OPC-31260 will be a useful tool in studying the physiological role of AVP and in the treatment of various conditions characterized by water retention.

Administration, Oral↗
PubMed1992

Interleukin-8 is a major neutrophil chemotactic factor derived from cultured human gingival fibroblasts stimulated with interleukin-1 beta or tumor necrosis factor alpha.

Inflammatory mediators produced by cells in the gingiva have been implicated in the initiation and progression of periodontal disease, a common infectious disease. In this study, we examined the biological activity of neutrophil chemotactic factors and the kinetics of expression of interleukin-8 (IL-8) mRNA derived from normal gingival fibroblasts in response to inflammatory mediators in an in vitro model. Gingival fibroblasts stimulated by either recombinant human interleukin-1 beta or recombinant human tumor necrosis factor alpha produced neutrophil chemotactic factors after 4 h, whereas expression of cell-derived IL-8 mRNA was detected within 1 h after stimulation. Furthermore, in a neutralization assay, rabbit anti-recombinant human IL-8 antiserum inhibited neutrophil chemotactic activity to basal levels. These results provide evidence that gingival fibroblasts synthesize potent chemotactic factors such as IL-8 in the presence of the inflammatory mediators interleukin-1 beta and tumor necrosis factor alpha. The activity of these factors may contribute to neutrophil-mediated processes in the pathogenesis of periodontal disease.

Cells, Cultured↗