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Biomedical subjects

K Yanagi

Publications and source records attributed to K Yanagi.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effect of weak electric current on reducing oral bacteria in vitro.

The ions generated by weak electric current may be used for removal of dental plaque. Also, it has been judged from changes in the viable bacterial cell count and the amount of adenosine triphosphate (ATP) in the saliva that the passage of such a current also has a bactericidal effect on the oral microflora. We confirmed in vitro that 0.5 and 1.0 mA currents that passed for 10 min through phosphate buffered saline containing salivary bacteria were effective in killing the bacteria.

Adenosine Triphosphate↗
PubMed2001

Anti-alpha-fodrin antibodies in Sjögren's syndrome in children.

OBJECTIVE: To investigate the prevalence of anti-alpha-fodrin antibody specific for adult Sjögren's syndrome (SS) in patients with juvenile onset SS. METHODS: Serum anti-alpha-fodrin antibody was examined in 15 patients with juvenile SS (11 cases of primary SS and 4 secondary SS) and in 16 children with systemic lupus erythematosus (SLE) by Western blot analysis using a recombinant 120 kDa alpha-fodrin fusion protein. RESULTS: All the 15 serum samples from patients with SS reacted with a recombinant alpha-fodrin fusion protein in Western blot analysis. In contrast, reactivity was found in only 2 of the 16 patients with SLE. The clinical features of the 15 patients with juvenile onset SS were very specific; only 4 patients complained of dryness, while 6 had abnormal excretion ability. Salivary gland enlargement was the most common clinical manifestation. Characteristic laboratory findings in juvenile onset SS included a higher prevalence of antinuclear antibodies, anti-SSA/Ro antibodies, and rheumatoid factor, as well as increased erythrocyte sedimentation rate and hypergammaglobulinemia. CONCLUSION: The pathogenesis of juvenile SS seems to be the same as that of adult SS, although subjective symptoms of dryness are less frequent in juvenile cases. This discrepancy may indicate that SS is a slowly progressive disease with a long time span. The anti-alpha-fodrin antibody is likely to be a reliable diagnostic marker for juvenile SS.

Adolescent↗
PubMed2001

Glycyrrhizin increases survival of mice with herpes simplex encephalitis.

We examined the effect of glycyrrhizin (GR), a component of licorice root extract, on herpetic encephalitis that was inflicted on mice by inoculation of herpes simplex virus 1 (HSV-1) onto their cornea. Intraperitoneal (i.p.) administration of GR to mice suffering from herpetic encephalitis increased their survival rate in average about 2.5 times (from 37.5-29.0% to 81.8-83.3%; mean values from 2 experiments) while it reduced HSV-1 replication in the brain to 45.6% of the control. These results demonstrate a stimulative effect of GR on the mouse defense system(s) against HSV-1 infection.

Animals↗
PubMed2000

The human homolog of Saccharomyces cerevisiae Mcm10 interacts with replication factors and dissociates from nuclease-resistant nuclear structures in G(2) phase.

Mcm10 (Dna43), first identified in Saccharomyces cerevisiae, is an essential protein which functions in the initiation of DNA synthesis. Mcm10 is a nuclear protein that is localized to replication origins and mediates the interaction of the Mcm2-7 complex with replication origins. We identified and cloned a human cDNA whose product was structurally homologous to the yeast Mcm10 protein. Human Mcm10 (HsMcm10) is a 98-kDa protein of 874 amino acids which shows 23 and 21% overall similarity to Schizosaccharomyces pombe Cdc23 and S. cerevisiae Mcm10, respectively. The messenger RNA level of HsMcm10 increased at the G(1)/S-boundary when quiescent human NB1-RGB cells were induced to proliferate as is the case of many replication factors. HsMcm10 associated with nuclease-resistant nuclear structures throughout S phase and dissociated from it in G(2) phase. HsMcm10 associated with human Orc2 protein when overexpressed in COS-1 cells. HsMcm10 also interacted with Orc2, Mcm2 and Mcm6 proteins in the yeast two-hybrid system. These results suggest that HsMcm10 may function in DNA replication through the interaction with Orc and Mcm2-7 complexes.

Amino Acid Sequence↗
PubMed2000

Autoantigen-specific CD4+CD28low T cell subset prevents autoimmune exocrinopathy in murine Sjögren's syndrome.

Organ-specific autoimmune exocrinopathy resembling Sjögren's syndrome (SS) that spontaneously develops in NFS/sld mutant mice thymectomized 3 day after birth is dependent on Th1-type CD4+ T cells. We previously reported that a cleavage product of 120-kDa alpha-fodrin may be an important autoantigen in the pathogenesis of SS in both an animal model and the patients. We demonstrate that in an animal model of SS with overt exocrinopathy, a unique CD4+ T cell subset expressing CD28low is dramatically increased in spleen cells before the disease onset, but that the CD4+ T cells of diseased mice were virtually all CD28high. We found that the spleen cells in these mice before the disease onset showed a significant increase in autoantigen-specific T cell proliferation. Analysis of in vitro cytokine production by spleen cells indicated, before the disease onset, severely impaired production of IL-2 and IFN-gamma in the animal model, whereas high levels of IL-4 were observed. Expression of cytokine genes, including IL-4, IL-10, and TGF-beta, was detected in FACS-sorted CD4+CD28low T cells by RT-PCR analysis. Transfer of CD4+CD28low T cells into the animal model actually prevented the development of autoimmune lesions including autoantibody production. These results suggest that a CD4+CD28low T cell subset that is continuously activated by an organ-specific autoantigen may play a regulatory role in the development of organ-specific autoimmune disease in an animal model of SS.

Adoptive Transfer↗
PubMed2000

A synthetic antagonist for the peroxisome proliferator-activated receptor gamma inhibits adipocyte differentiation.

While searching for natural ligands for the peroxisome proliferator-activated receptor (PPAR) gamma, we identified a synthetic compound that binds to this receptor. Bisphenol A diglycidyl ether (BADGE) is a ligand for PPARgamma with a K(d(app)) of 100 microM. This compound has no apparent ability to activate the transcriptional activity of PPARgamma; however, BADGE can antagonize the ability of agonist ligands such as rosiglitazone to activate the transcriptional and adipogenic action of this receptor. BADGE also specifically blocks the ability of natural adipogenic cell lines such as 3T3-L1 and 3T3-F442A cells to undergo hormone-mediated cell differentiation. These results provide the first pharmacological evidence that PPARgamma activity is required for the hormonally induced differentiation of adipogenic cells.

1-Methyl-3-isobutylxanthine↗
PubMed2000

Epstein-barr virus nuclear antigen-1 binds to nuclear transporter karyopherin alpha1/NPI-1 in addition to karyopherin alpha2/Rch1.

We searched for cellular proteins that interact with Epstein-Barr (EBV) virus nuclear antigen-1, which is a latent EBV origin-binding protein detected in all EBV latently infected cells and essential for maintenance of the latent EBV genome, by a yeast two-hybrid screening of a B lymphocyte cDNA library in this study. Interaction of polypeptides synthesized from three selected cDNA clones with EBNA-1 proteins was confirmed in vitro using their glutathione-S-transferase-fusion polypeptides and by coimmunoprecipitation analyses of B cell extracts with anti-EBNA-1 monoclonal antibodies and monospecific antibodies against cellular proteins of interest. We report the following: (i) Karyopherin alpha (karyopherin alpha1, hSRP1, and NPI-1), an adaptor subunit of nuclear localization signal receptors, which direct proteins to the nuclear pore, interacted with EBNA-1. (ii) EBNA-1 proteins endogenous in the B cell line Raji of Burkitt lymphoma origin bound to another adaptor protein, karyopherin alpha2 (hSRP1alpha, hRch1), interactions of which to recombinant EBNA-1 polypeptides were previously reported. (iii) Nearly 90% of all the cDNA clones examined was p32 (SF2-associated P32, p32/TAP, and gC1q-R), and endogenous EBNA-1 proteins in the Raji cells bound to p32, a potential of which to affect localization of EBNA-1 in transfected Vero cells has been recently suggested. These results suggest that EBNA-1, which has the unique NLS containing Lys-Arg and overlapping with one of the phosphorylation domains, is recognized and transported to the nuclei by these two distinct karyopherin alpha proteins, which are differentially expressed in different cell types, implying a regulatory localization system for EBNA-1.

B-Lymphocytes↗
PubMed2000

A new model of lung metastasis for intravital studies.

We created anexperimental model of pulmonary metastasis based on subcutaneously implanted Lewis lung cancer in mice and observed in vivo the microcirculation of spontaneously metastasized tumors in the lung. The mice lung was held by a small handmade suction ring to stop cardiac and respiratory movement. Using fluorescent microscopy, tumor microcirculation and normal lung microcirculation in the same lung lobe were compared by measuring microvessel diameter and blood flow velocity [red blood cell (rbc) velocity]. In normal microcirculation, the mean values of microvessel diameter and rbc velocity were 10.4 +/- 2.7 microm and 188 +/- 63 microm/s, respectively. In tumor microcirculation, the mean values of the same were 10.6 +/- 3.3 microm and 105 +/- 40 microm/s. The rbc velocity in normal microcirculation was significantly higher (P < 0.001) than that in tumor microcirculation. The calculated shear rates of normal microcirculation and tumor microcirculation were 73.4 +/- 23.4 (/s) and 41.2 +/- 16.1 (/s), respectively. The shear rate of the tumor microcirculation was significantly slower (P < 0.001) than that of the normal microcirculation. We demonstrated a feasibility of observation and measurement of tumor microcirculation in the lung and confirmed that the physiologic data were compatible to those in the brain or in the liver reported by others. This model might be useful for studying metastatic tumor pathophysiology in the lung microcirculation.

Animals↗
PubMed2000

Total anomalous pulmonary venous connection with bronchogenic cyst in neonatal period.

Here, we report a case of a two-day-old neonate with total anomalous pulmonary venous connection to the innominate vein and a bronchogenic cyst arising from the trachea. Antenatal echocardiography had delineated both cardiac and extracardiac lesions, and a repeated examination on the day of birth disclosed progressive enlargement in the cyst in a manner so as to obstruct the innominate vein. On the second day of life, the patient underwent complete correction of the cardiac lesion and total excision of the cyst. The patient recovered uneventfully and was discharged on the thirteenth postoperative day.

Brachiocephalic Veins↗
PubMed2000

The cytotoxic effects of bile acids in crude bile on human pancreatic cancer cell lines.

Pancreatic cancer frequently causes extrahepatic cholestasis. To identify the direct effects of bile acids in jaundiced serum on pancreatic cancer, the proliferation of PANC-1 and MIA PaCa-2 cells as well as the ultrastructural alteration of PANC-1 cells cultured in crude bile modified media were studied. The growth of these cells in the RPMI-1640 media with or without 1%, 2%, and 4% of the refined crude bile was assessed after 48 and 96 h of incubation. The ultrastructure of PANC-1 cells was investigated by scanning and transmission electron microscopy after 24 and 48 h of incubation. The proliferation of both cell lines in the bile-treated media was greatly inhibited. The inhibitory rates of bile on PANC-1 ranged from 24.1% +/- 3.3% to 66.9% +/- 6.6% (P < 0.01) and those on MIA PaCa-2 ranged from 16.7% +/- 3.8% to 50.7% +/- 5.5%. (P < 0.01). When the bile-added media were replaced, the cells were able to restore their proliferating ability. The PANC-1 cells incubated in the bile-supplied media indicated that the mirovilli, mitochondria, and other organelles had thus been injured. These results suggest that bile acids appear to inhibit the proliferation of PANC-1 and MIA PaCa-2 cells, and the probable inhibitory mechanism is mainly considered to be due to the cytotoxicity of such bile acids.

Bile Acids and Salts↗
PubMed2000

Severe destructive autoimmune lesions with aging in murine Sjögren's syndrome through Fas-mediated apoptosis.

When we evaluated the age-associated changes in autoimmune exocrinopathy in a NFS/sld murine model for primary Sjögren's syndrome (SS), severe destructive autoimmune lesions developed in the salivary and lacrimal glands in the aged mice, compared with those observed in the younger model. We detected a decreased secretion of saliva and tear flow in the aged group. A significant increase of TUNEL(+)-apoptotic epithelial duct cells in the salivary glands was detected in the aged SS animal model. A higher proportion of mouse salivary gland cells bearing Fas was found in the aged group, whereas no significant changes were seen on tissue-infiltrating CD4(+) T cells bearing FasL in the salivary glands from young and aged mice. We detected an increased cleavage product of organ-specific autoantigen, 120-kd alpha-fodrin, in the aged salivary gland tissues on immunoblotting, and an increase in serum autoantibody production against 120-kd alpha-fodrin by enzyme-linked immunosorbent assay. An increase in the proliferative response of splenic T cells against organ-specific autoantigen was observed, whereas nonspecific concanavalin A responsiveness was decreased in the aged mice. In addition, a decrease in Fas expression was found on splenic CD4(+) T cells in the aged mice, and anti-Fas mAb-stimulated apoptosis was down-regulated on CD4(+) T cells. These results indicate that age-associated dysregulation of CD4(+) T cells may play a crucial role on acceleration of organ-specific autoimmune lesions in a murine model for primary SS through Fas-mediated apoptosis.

Aging↗
PubMed2000

Treatment with anti-CD86 costimulatory molecule prevents the autoimmune lesions in murine Sjögren's syndrome (SS) through up-regulated Th2 response.

Intraperitoneal administration with anti-CD86 (B7.2) MoAb into the murine model for primary SS in NFS/sld mutant mice resulted in dramatically inhibitory effects on the development of autoimmune lesions, while no significant effects were observed when the mice were administered with anti-CD80 (B7.1) MoAb. We found that spleen cells in the murine SS model treated with anti-CD86 MoAb showed a significant impairment of autoantigen-specific T cell proliferation. T cell activation markers (CD44high, CD45RBlow, Mel-14low) were significantly down-regulated in the spleen cells gated on CD4 in anti-CD86-treated mice. We detected a higher level of cytokine production of IL-4 from splenic T cells in anti-CD86-treated mice, but not of IL-2, and interferon-gamma (IFN-gamma), compared with those in the anti-CD80- and PBS-treated SS model. Moreover, serum autoantibody production against alpha-fodrin autoantigen was almost entirely suppressed in anti-CD86-treated mice. These data provide strong evidence that in autoimmune exocrinopathy resembling SS in NFS/sld mutant mice, the CD86 costimulatory molecule plays a crucial role in the initiation and subsequent progression of Th1-mediated autoimmunity in the salivary and lacrimal glands.

Animals↗
PubMed2000

Mechanisms of neonatal tolerance induced in an animal model for primary Sjögren's syndrome by intravenous administration of autoantigen.

Neonatal exposure to autoantigen is believed to induce effective antigen-specific T-cell tolerance in experimental models of autoimmunity. We have identified 120 kDa alpha-fodrin autoantigen in an animal model for primary Sjögren's syndrome (SS), that has been determined as a candidate autoantigen in both an animal model and the patients with primary SS. We demonstrate here that neonatal injection of autoantigen induce relevant tolerance when treated with intravenous (i.v.) administration within 24 h after birth, but not with i.v. injection after the thymectomy or with intraperitoneal injection. Autoantigen-specific T-cell response was significantly reduced in mice induced neonatal tolerance, and the activation markers of splenic CD4+ T cells were down-regulated in mice treated with neonatal administration. Because we detected that neonatal i.v. injection of autoantigen prevented Th1 response, it is possible that the autoantigen administration within 24 h after birth induce regulatory T cells that had a protective effect against Th1-mediated autoimmune diseases. These results indicate that the prevention of the spontaneous anti-120 kDa alpha-fodrin response in vivo, by tolerization of the autoantigen-reactive T cells, blocked the development of autoimmune lesions in an animal model for primary SS.

Animals↗
PubMed2000

Saccharin test of maxillary sinus mucociliary function after endoscopic sinus surgery.

OBJECTIVES: To determine the usefulness of the saccharin time (ST) test for evaluating the mucociliary function of the maxillary sinus after endoscopic sinus surgery (ESS) for chronic sinusitis. STUDY DESIGN METHODS: This study was conducted on 88 maxillary sinuses of 74 patients after ESS. The maxillary sinus fontanel was broadly opened via the middle meatus using an endoscope, and a saccharin granule was adhered to the bottom of the maxillary sinus mucosa The time until the patient recognized the sweet taste was recorded. Before the ST test, the bilateral maxillary sinuses were classified into the following four groups on the basis of the post-ESS severity of mucosal edema and swelling as revealed by endoscopic observation: normal (45 sinuses), mild mucosal edema and swelling (24), moderate mucosal finding (14), and severe mucosal finding or filling of the sinus with a polyp(s) (5). RESULTS: The mean ST values in the normal group and the groups with mild, moderate, and severe mucosal edema and swelling were 35.7, 38.1, 63.6, and 88.0 minutes, respectively. Thus the ST increased with the post-ESS severity of the mucosal lesion. However, for the group with mild mucosal edema and swelling, scanning electron microscopic observation of three maxillary sinuses in which the ST exceeded 120 minutes and four sinuses in which the ST was 40 minutes revealed extensive cilia loss in the former sinuses, but not in the latter. A second post-ESS endoscopic observation was performed in 17 patients, revealing improvement in 11 sinuses, no change in 5 sinuses, and aggravation in 1 sinus (compared with the initial test). The ST test was also repeated, revealing that the ST became shorter in most of the endoscopically improved sinus group. However, a few sinuses showed a discrepancy between the change in the endoscopic findings and the ciliary function (ST). CONCLUSION: Measurement of the maxillary sinus ST is a simple, accurate, and useful technique for assessing the post-ESS mucociliary function in conjunction with endoscopy, and the information gained can help in deciding subsequent therapy.

Adolescent↗
PubMed2000

Effect of angiostatin on liver metastasis of pancreatic cancer in hamsters.

The liver is the most common site of metastasis in pancreatic cancer, and there are no promising strategies to treat it. Angiostatin, a kringle-containing fragment of plasminogen, is a potent inhibitor of angiogenesis. The effect of angiostatin on liver metastasis in pancreatic cancer was investigated by using our established hamster model of liver metastasis. Pancreatic cancer cells (PGHAM-1, 1 x 10(6)) derived from N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic tumor in Syrian golden hamsters were transplanted into the spleen of female hamsters, and the animals were subcutaneously injected with angiostatin and saline. Subsequently, the macroscopic appearance of liver surface metastases was evaluated. In addition, histological sections of the liver metastases were analyzed for neovascularization, proliferation, and apoptosis on the basis of von Willebrand factor, argyrophilic nucleolar organizer region (Ag-NOR), and TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining, respectively. The results showed significant tumor growth retardation and inhibition of angiogenesis in metastatic liver tumors in response to treatment with angiostatin. Moreover, the metastases remained in a nearly dormant state due to a balance between apoptosis and proliferation of the tumor, with no detectable side effects. This is the first experimental trial of angiostatin on pancreatic cancer and liver metastasis. The results suggest that angiostatin therapy could be effective against liver metastases of pancreatic cancer.

Angiogenesis Inhibitors↗
PubMed2000

[Management of unilateral renal cystine calculi via percutaneous nephrolithotripsy in a child with a contralateral non-functional kidney--a case report].

A 2-year old boy visited our clinic with a chief complaint of high fever. A past history of acute renal failure due to cystine stones and cystinuria was expressed. Abdominal rentogenograms and CT demonstrated a right ureteral stone and a left renal stone. Furthermore renogram evaluation indicated non-function of the right kidney and dysfunction in the left kidney. Since right ureteral stone moved into bladder seven days post-admission, right ureteroscopy, left PNL, and cystolithotripsy were performed. Considering that right ureteral stenosis was determined by ureteroscopy, balloon dilation against the stenotic ureteral wall was performed. Left PNL and cystolithotripsy were successfully performed. No intraoperative complications occurred and no symptoms of signs of recurrence of the underlying metabolic disease were evident four months postoperatively.

Child, Preschool↗
PubMed2000

[Extragonadal germ cell tumor coexisted with renal cell carcinoma--a case report].

A patient was 31-year-old man with the chief complaint of 38 degrees C fever. He was pointed out left renal tumor by abdominal ultrasonography and computerized tomography (CT). CT revealed left infraclavicular, mediastinal and retroperitoneal lymph nodes swelling and left renal tumor. Serum alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (HCG-beta) level were elevated. The diagnosis of extragonadal germ cell tumor and left renal cell carcinoma was confirmed pathologically by infraclavicular lymph node and renal biopsy. He was treated with 4 courses of BEP regimen and interferon-alpha, cimetidine therapy for 2 weeks preoperatively. After serum tumor markers were normal level, he underwent left radical nephrectomy and left infraclavicular, mediastinal and retroperitoneal lymph node dissection. The histology of all lymph nodes was necrotic tissue, but operation was incomplete. Therefore VIP therapy was performed postoperatively. This is the first case of extragonadal germ cell tumor coexisted with renal cell carcinoma in the world.

Adult↗