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Biomedical subjects

K Okazaki

Publications and source records attributed to K Okazaki.

At least 37 records · Page 2Linked to original sources
PubMed2002

Fibroblasts from the inner granulation tissue of the pseudocapsule in hips at revision arthroplasty induce osteoclast differentiation, as do stromal cells.

BACKGROUND: It has previously been shown that many osteoclast precursors are included in the granulation tissue within the pseudocapsule obtained at revision arthroplasty from hips with osteolysis. In vitro culture of only cells isolated from the granulation tissue has been previously shown to generate many mature osteoclasts. OBJECTIVE: To investigate the presence or otherwise of supporting cells, similar to stromal cells, which differentiate osteoclasts within the granulation tissue. METHODS: Cells isolated from the granulation tissue were cultured alone, and after four weeks fibroblast-like cells (granulation fibroblasts) remained. Rat non-adherent bone marrow cells (NA-BMCs) were co-cultured with the granulation fibroblasts with or without 1alpha,25(OH)2D3 (10(-8) M) or heat treated ROS 17/2.8 cell conditioned medium (ht ROSCM), or both. Multinucleated cells (MNCs), which formed, were assessed by biochemical and functional characterisation of osteoclasts. Receptor activator of NFkappaB ligand (RANKL) was investigated by immunohistochemistry. RESULTS: Co-culture of NA-BMCs and granulation fibroblasts caused the formation of tartrate resistant acid phosphatase (TRAP) positive MNCs, which had the calcitonin receptor (CTR), the Kat-1 antigen, which is specific to the surface of rat osteoclasts, and the ability to form pits in the presence of both 1alpha,25(OH)2D3 and ht ROSCM or in the presence of just ht ROSCM. RANKL was detected in fibroblast-like cells in the granulation tissue. CONCLUSION: These data suggest that granulation fibroblasts support osteoclast differentiation, as do osteoblasts/stromal cells, and may play a part in aseptic loosening.

Aged↗
PubMed2002

Autoimmune related pancreatitis.

Since the first documented case of a particular form of pancreatitis with hypergammaglobulinaemia, similar cases have been reported, leading to the concept of an autoimmune related pancreatitis or so-called "autoimmune pancreatitis". Although it has not yet been widely accepted as a new clinical entity, the present article discusses the recent concept of autoimmune pancreatitis.

Autoimmune Diseases↗
PubMed2002

Regression of fundic gland polyps following acquisition of Helicobacter pylori.

The prevalence of Helicobacter pylori infection is very low in patients with fundic gland polyps (FGPs) of the stomach. We report here two cases with multiple FGPs that regressed following new H pylori acquisition. Patient Nos I and II had multiple FGPs in normal fundic mucosa without inflammatory changes or atrophy. Both were not infected with H pylori. Following acquisition of H pylori infection however, all FGPs in both patients completely disappeared except for one FGP in patient No I. Although the size of the remaining polyp in patient No I was greatly reduced after H pylori acquisition, it became enlarged again after eradication. Interestingly, in the remaining polyp, we found an activating beta-catenin gene mutation whereas no such mutations were detected in FGPs of patient No II. Thus H pylori infection may have an inhibitory effect on the development of FGPs.

Adult↗
PubMed2001

Oxindole derivatives as orally active potent growth hormone secretagogues.

A series of substituted oxindole derivatives was synthesized and evaluated for growth hormone (GH) releasing activity using cultured rat pituitary cells. (+)-6-Carbamoyl-3-(2-chlorophenyl)-(2-diethylaminoethyl)-4-trifluoromethyloxindole (SM-130686, 37S) was found to have potent activity (EC(50) = 3.0 nM), while the other enantiomer 37R had reduced activity. The absolute configuration of 37S was confirmed by X-ray crystallographic analysis. Compound 37S showed a good pharmacokinetic profile in rats with 28% oral bioavailability at 10 mg/kg and excellent in vivo activity as evidenced by a significant weight gain after 4 days of oral administration at 10 mg/kg twice a day. Compound 37S displaced the binding of (35)S-MK-677 to human GHS-R with an IC(50) value of 1.2 +/- 0.2 nM.

Administration, Oral↗
PubMed2001

Rectal immunization with antigen-containing microspheres induces stronger Th2 responses than oral immunization: a new method for vaccination.

The rectum as an effective site for induction of systemic and local immunity has received little attention. Rectal immunization with microspheres-containing ovalbumin (MS-OVA) was tested for its ability to elicit systemic and mucosal immune responses. Rectal immunization with MS-OVA enhanced both Th2 dominant OVA-specific IgG levels in the serum and OVA-specific IgA levels in fecal extracts more prominently than did oral immunization. Cytokine analysis of CD4(+) T cells indicated a predominant induction of Th2-type responses compared to Th1-type responses following rectal immunization compared to oral immunization. These results demonstrate that rectal immunization with microspheres could be an effective new vaccination method.

Administration, Oral↗
PubMed2001

Evaluation of the effect of 90Sr beta-radiation on human blood cells by chromosome aberration and single cell gel electrophoresis (comet assay) analysis.

Among various environmental genotoxins, ionizing radiation has received special attention because of its mutagenic, carcinogenic and teratogenic potential. In this context and considering the scarcity of literature data, the objective of the present study was to evaluate the effect of 90Sr beta-radiation on human cells. Blood cells from five healthy donors were irradiated in vitro with doses of 0.2-5.0Gy from a 90Sr source (0.2Gy/min) and processed for chromosome aberration analysis and for comet assay. The cytogenetic results showed that the most frequently found aberration types were acentric fragments, double minutes and dicentrics. The alpha and beta coefficients of the linear-quadratic model, that best fitted the data obtained, showed that 90Sr beta-radiation was less efficient in inducing chromosome aberrations than other types of low linear energy transfer (LET) radiation such as 3H beta-particles, 60Co gamma-rays, 137Cs and 192Ir and X-rays. Apparently, 90Sr beta-radiation in the dose range investigated had no effect on the modal chromosome number of irradiated cells or on cell cycle kinetics. Concerning the comet assay, there was an increase in DNA migration as a function of radiation dose as evaluated by an image analysis system (tail moment) or by visual classification (DNA damage). The dose-response relation adequately fitted the non-linear regression model. In contrast to the cytogenetic data, 90Sr beta-radiation induced more DNA damage than 60Co gamma-radiation when the material was analyzed immediately after exposures. A possible influence of selective death of cells damaged by radiation was suggested.

Adult↗
PubMed2001

Cytoplasmic occurrence of the Chk1/Cdc25 pathway and regulation of Chk1 in Xenopus oocytes.

Chk1, a nuclear DNA damage/replication G2 checkpoint kinase, phosphorylates Cdc25 and causes its nuclear exclusion in yeast and mammalian cells, thereby arresting the cell at the G2 phase until DNA repair/replication is completed. Chk1 is also involved, at least in part, in the natural G2 arrest of immature Xenopus oocytes, but it is unknown how Chk1 inhibits Cdc25 function and undergoes regulation during oocyte maturation. By using enucleated oocytes, we show here that Chk1 inhibits Cdc25 function in the cytoplasm of G2-arrested oocytes and that Cdc25 is activated exclusively in the cytoplasm of maturing oocytes. Moreover, we show that Chk1 activity is not appreciably altered during maturation, being maintained at basal levels, and that C-terminal truncation mutants of Chk1 have very high kinase activities, strong abilities to inhibit maturation, and altered subcellular localization in oocytes. These results, together with other results, suggest that the Chk1/Cdc25 pathway is involved cytoplasmically in G2 arrest of Xenopus oocytes, but moderately and independent of the G2 checkpoint, and that the C-terminal region of Chk1 negatively regulates its kinase activity and also determines its subcellular localization. Based on these results, we discuss the possibility that Chk1 (with the basal activity) may function as an ordinary regulator of Cdc25 in oocytes (and in other cell types) and that Chk1 might be hyperactivated in response to the G2 checkpoint via its dramatic conformational change.

14-3-3 Proteins↗
PubMed2001

A repeated 28-day oral dose toxicity study of methoxychlor in rats, based on the 'enhanced OECD test guideline 407' for screening endocrine-disrupting chemicals.

In association with the international validation project to establish an OECD Enhanced Test Guideline 407, we performed a 28-day repeated-dose toxicity study of methoxychlor, a chlorinated hydrocarbon pesticide with pro-estrogenic and anti-androgenic activities. Attention was paid to the sensitivity of certain additional parameters for detecting endocrine related effects of endocrine disrupting chemicals based on the existing TG 407. Seven-week-old Crj:CD(SD)IGS rats were allocated to one of four groups, each consisting often males and ten females, and methoxychlor was administered once daily by gavage at doses of 0 (control), 20, 100 or 500 mg/kg body weight per day. Male rats were killed on the day after the 28th administration. Female rats were killed on the day of the diestrus stage during 4 days after the 28th administration. Male rats receiving methoxychlor showed mainly atrophy of mammary acinus in the 20 mg/ kg and higher groups, together with decreases in prostate and seminal vesicle weights, and atrophy of epididymis, prostate, seminal vesicle and coagulating gland in the 100 and 500 mg/kg groups. In addition, decrease in serum testosterone level, increase in follicle-stimulating hormone level, decrease in testis and epididymis weights, atrophy of semiferous tubules and Leydig cells, decrease in the number of sperm in the caudal epididymis and their motility were observed in the 500 mg/kg group. Female rats receiving methoxychlor showed mainly abnormal estrous cycles, decrease in serum luteinizing hormone level, decrease in ovary weight, proliferation of mammary acinus, atrophy of ovary due to decrease in follicles and corpus luteum in histopathology, hypertrophy of endometrial epithelium of uterus and vagina epithelium in the 100 and 500 mg/kg groups. Among the parameters tested in the present experimental system, effects of methoxychlor on endocrine-related organs were detected with regard to serum hormone, organ weights, histopathological examination in both sexes, estrus cycle in females and sperm examination in males. Based on these results, a no-observed-adverse-effect level (NOAEL) in the present study was estimated to be below 20 mg/kg per day. In particular, the adverse effects were effectively detected in organ weights of accessory sex organs and histopathological examination.

Administration, Oral↗
PubMed2001

Endurance training under 2500-m hypoxia does not increase myoglobin content in human skeletal muscle.

The present study was carried out to determine whether myoglobin (Mb) concentration ([Mb]) in human skeletal muscle is influenced by 8 weeks of endurance training under normal conditions, and under hypoxic conditions equivalent to an altitude of 2500 m. Fourteen healthy but sedentary male adults who did not participate in any regular exercise program took part in this study. They were divided into two groups according to the training regime to which they were submitted: the N group, who exercised under normobaric conditions, and the H group, who exercised under hypobaric conditions. All subjects performed an incremental cycling exercise at sea level to evaluate their maximal O2 uptake (VO2max) before and after the 8-week endurance training course period. Muscle tissue samples were obtained by needle biopsy from the vastus lateralis muscle for histochemical and biochemical analysis. Training induced an increase in VO2max in both the N and H groups (P < 0.05), although there was no significant difference in these changes between groups. The 8-week training had no effect on [Mb] in either group. Muscle fiber composition was also unaffected by the training course. In contrast, citrate synthase activity in both groups increased by [mean (SD)] 28.2 (33.3)% (N: P < 0.01) and 32.0 (18.2)% (H: P < 0.05) after training, and the number of capillaries (capillary:fiber ratio) increased by 47.7 (33.8)% (N: P < 0.01) and 32.3 (20.6)% (H: P < 0.05). There were no significant differences in these parameters between the N and H groups. These results suggest that significant improvement of aerobic potential as a result of endurance training are not accompanied by increases in [Mb] in human skeletal muscle. In addition, a lower absolute workload may not be sufficient to stimulate Mb synthesis in humans, even where endurance training is carried out under hypoxia.

Adult↗
PubMed2001

Budd-Chiari syndrome and extrahepatic portal obstruction associated with congenital antithrombin III deficiency.

We report a patient with Budd-Chiari syndrome (BCS) and extrahepatic portal obstruction (EHO) associated with congenital antithrombin (AT) III deficiency. A 35-year-old man was admitted to Nishi Kobe Medical Center for evaluation of abnormal intrahepatic veins. By various imaging modalities, BCS and EHO were diagnosed. Laboratory data revealed parallel decreases in activity and antigen concentration of AT III despite normal liver function. Taken together, the etiology of both BCS and EHO was considered to be thrombosis, associated with congenital AT III deficiency. Two years after beginning warfarin therapy, the patient has no symptoms and his liver function remains normal. Anticoagulant therapy is considered useful for preventing progression of the disease.

Adult↗
PubMed2001

Immature osteoblastic cells express the pro-alpha2(XI) collagen gene during bone formation in vitro and in vivo.

Type XI collagen is predominantly found in cartilage. However, expression of the pro-alpha2(XI) collagen gene (COL11A2) has recently been detected in various non-cartilaginous tissues. We identified the differentiation stage at which COL11A2 was expressed in cultured fetal rat calvarial (FRC) cells and in rat femoral fracture calluses in order to investigate the involvement of COL11A2 during bone formation in vitro and in vivo. We also studied the alternative splicing of exons 6-8 in FRC cells and fracture calluses. In FRC cells, mineralized nodules stained with von Kossa stain were observed from day 9 after confluence. COL11A2 was highly expressed on days 0 and 5, but the expression levels were rapidly decreased on day 9 by Northern blot analysis. During rat femoral fracture repair, intramembranous ossification proceeded and newly formed woven bone was observed on the cortex on day 7 after fracture. In situ hybridization showed that COL11A2 signals were detected in osteoblastic cells in the newly formed woven bone. According to the maturation and remodeling of the woven bone into the trabecular bone, the distribution of the signal for COL11A2 mRNA was limited to the superficial osteoblastic cells of the newly formed trabecular bone. These results demonstrated that COL11A2 was expressed in relatively immature osteoblastic cells during bone formation in vitro and in vivo. RT-PCR showed that the shortest band corresponding to mRNA lacking exons 6-8 was clearly detected when using RNA from soft calluses. In contrast, the largest band corresponding to mRNA with exons 6-8 was predominant when using RNA from FRC cells or from hard calluses on days 7 and 14. These results indicate that the splicing pattern of exons 6-8 in osteoblastic cells is different from the pattern in chondrocytes.

Alternative Splicing↗
PubMed2001

Therapeutic effects on intestinal Behçet's disease of an intravenous drug delivery system using dexamethasone incorporated in lipid emulsion.

Recurrent intestinal ulcer is a frequent problem in the management of Behçet's disease. However, no standard therapy for intestinal Beheçt's disease has been established. We report two patients with intestinal Behçet disease and recurrent ileal ulcers who were treated successfuly with a lipid emulsion of dexamethasone. In one patient, the cecal ulcer did not relapse after the intravenous administration initiation of a lipid emulsion of dexamethasone once a week, despite the discontinuation of prednisolone. In the other patient, the cecal ulcer showed a healing tendency, and oral administration of prednisolone was reduced from 40 to 15 mg/day after intravenous administration of a lipid emulsion of dexamethasone. Both patients experienced no complications associated with the administration of the emulsion. These results suggest that an intravenous drug delivery system using a lipid emulsion of dexamethasone is useful for treatment of intestinal Behçet's disease.

Anti-Inflammatory Agents↗
PubMed2001

A critical role for IL-7R signaling in the development of Helicobacter felis-induced gastritis in mice.

BACKGROUND & AIMS: Interleukin (IL)-7 is a critical cytokine in the development of T and B cells and is involved in gastrointestinal pathophysiology. The aim of this study was to investigate the involvement of IL-7 receptor (IL-7R) signaling in Helicobacter-induced gastritis. METHODS: C57BL/6 mice (n = 40) were inoculated with H. felis. Twenty mice were injected intraperitoneally with neutralizing IL-7R antibody (A7R34) every seventh day for 3 months. Histology, serum anti-H. felis antibody, and gene expression of IL-7, IL-7R, and proinflammatory cytokines in the gastric mucosa were evaluated. RESULTS: Seventeen of 20 (85%) infected mice without A7R34 developed severe atrophic gastritis, whereas there was no gastritis in A7R34-treated infected mice. There was no difference in the serum levels of anti-H. felis antibody between the 2 groups. IL-7, IL-7R, IL-1alpha, tumor necrosis factor alpha, and interferon gamma messenger RNA expressions were up-regulated in control infected mice, whereas only IL-7 messenger RNA was up-regulated in A7R34-treated infected mice. Immunohistochemistry indicated positive cytoplasmic staining of IL-7 in the gastric epithelial cells. CONCLUSIONS: These data suggest a critical role for IL-7 receptor signaling in the development of Helicobacter-induced gastritis in mice.

Animals↗
PubMed2001

Lysyl oxidases: expression in the fetal membranes and placenta.

The cross-linking of the connective tissues in the fetal membranes and placenta is important for their tensile strength and elasticity. We have studied the expression of lysyl oxidase (LOX) because it is the classical enzyme responsible for the cross-linking of collagen and elastin. We have also studied the two recently described, genetically distinct lysyl oxidase-like genes and proteins, lysyl oxidase-like (LOXL) and lysyl oxidase-like 2 (LOXL2), of unknown functions. Specific antisera have been used for immunolocalization in fetal membranes and placentae from early pregnancy terminations and after caesarean section at both preterm and term, prior to labour. In addition, the steady state mRNA levels of the three genes has been quantitated in separated amnion, chorion, decidua and placentae collected at term before labour. The immunocytochemistry shows that the spatial expression of the three lysyl oxidases is similar in early pregnancy in both the fetal membranes and placentae. However, by preterm this pattern had diverged and becomes greatest at term. The expression of the genes found at term was similar to the results of protein expression obtained by immunocytochemistry, with the exception of LOXL which had high placental gene expression, but low levels of immunolocalized protein. Thus by term, LOX was expressed predominantly in the amniotic epithelium, with little expression in the placenta, while LOXL showed highest gene expression in the placenta and lowest expression in the amnion. LOXL2 expression was again different and was expressed predominantly in the chorionic cytotrophoblast of the membranes with low expression in both the amnion and placentae. These results suggest that these three members of the lysyl oxidase family may have similar roles in early pregnancy during the development of the placenta and fetal membranes, but their divergence as pregnancy advances to term, may reflect changes in substrate specificity and connective tissue composition.

Abortion, Legal↗
PubMed2001

Successful treatment with steroids of upper gastrointestinal acute graft vs. host disease after hematopoietic stem cell transplantation.

A 39-year-old man with acute myeloid leukemia underwent completely matched related hematopoietic stem cell transplantation. On post-transplantation day 83 he was diagnosed as having upper gastrointestinal graft-versus-host disease (GVHD) by endoscopic examination and pathological examination of endoscopic biopsy specimens, and daily administration of 60 mg of water-soluble prednisolone and 50 mg of cyclosporine was started. After steroid therapy, the symptoms of upper gastrointestinal GVHD disappeared completely and endoscopic findings dramatically improved.

Acute Disease↗
PubMed2001

Characterization of monoclonal antibodies specific for feline serum amyloid (SAA) protein.

Serum amyloid A (SAA) has been characterized as an inflammatory marker in many species. In this study, we have developed and characterized monoclonal antibodies (MAbs) against feline SAA (fSAA) derived from culture hybridomas. These hybridomas were produced from the fusion of Balb/c-derived myeloma s/p20-Ag14 and splenocytes from mice immunized with purified recombinant feline SAA (rfSAA). Six hybridomas secreting MAbs, M2, M5, M7, M8, M13, and M15, were selected and subcloned on the basis of their specificity to rfSAA by enzyme-linked immunoabsorbent assay (ELISA), and confirmed based on their specificity to rf-SAA by immunoblot analysis. Out of six clones, two clones (M5 and M7) showed higher reactivity with rf-SAA, and were selected for further analysis of ELISA additivity and Western blot cross-reactivity tests. As a result, M5 and M7 clones recognized the same or excessively near epitopes on rfSAA and reacted with rfSAA, fSAA and equine recombinant SAA, but showed no reaction with human recombinant SAA. Because of their specificity, these MAbs may be usefully applied in studying the measurement of SAA concentration in cat serum.

Amino Acid Sequence↗