Biomedical subjects

K Sano

Publications and source records attributed to K Sano.

At least 19 recordsLinked to original sources

PubMed2006

Co-localization of TFF2 with gland mucous cell mucin in gastric mucous cells and in extracellular mucous gel adherent to normal and damaged gastric mucosa.

Trefoil factor 2 (TFF2) is mucin associated peptide that has a mucosal barrier function in addition to participating in repair and healing. We examined the localization of TFF2 and gastric mucins in gastric mucous cells, the surface mucous gel layer (SMGL) adherent to normal gastric mucosa, and in the mucoid cap covering gastric erosions. Carnoy's solution, or formalin/picric acid-fixed paraffin embedded materials from resected stomachs and formalin-fixed paraffin embedded gastric biopsy materials were used. Sections were immunostained for the TFF2 and histochemically stained for gastric mucins. In addition, thick sectioned gastric mucosa fixed in Carnoy's solution were stained with FITC-labeled GSA-II lectin specific for gland mucous cell mucin and examined for three-dimensional images of the SMGL using a confocal laser scanning microscope. The TFF2 and gland mucous cell mucin were found intermixed together in the gastric gland mucous cells, in the SMGL in laminated layers, and in the mucoid cap. A laminated arrangement of continuous sheets of gland mucous cell mucin in the SMGL was demonstrated in the three-dimensional images. Co-localization of the TFF2 with gland mucous cell mucin suggests a physical interaction between the TFF2 and gland mucous cell mucin. The TFF2 trapped in the adherent mucins may be responsible for mucosal defense, healing, and repair.

Biopsy↗

PubMed2006

The mutation in the ATP-binding region of JAK1, identified in human uterine leiomyosarcomas, results in defective interferon-gamma inducibility of TAP1 and LMP2.

The presentation of human leukocyte antigens (HLA) class I requires the coordinated expression of numerous components involved in antigen presentation. Tumor cells may alter the antigen presentation by HLA class I, allowing them to evade antitumor immunity. In many cases, the lack of antigen presentation can be attributed to the downregulation of genes needed for antigen processing, such as the transporters associated with antigen processing (TAP) 1, and the proteasomal component, low molecular weight proteins (LMP) 2. The TAP1 and LMP2 genes are transcribed from a shared bidirectional promoter containing an interferon (IFN)-gamma-response factor element; thus, the IFN-gamma-signal strongly induces both TAP1 and LMP2 expression. Low molecular weight proteins2-deficient mice exhibited the development of uterine leiomyosarcomas. Here, the differential responsiveness to IFN-gamma of the SKN human uterine leiomyosarcomas cell line was investigated. We now identify the G871E mutation in the ATP-binding region of Janus kinases 1, suggesting that the loss of TAP1 and LMP2 induction is a defect in the earliest steps of the IFN-gamma-signal pathway, resulting in the inability of SKN cells to upregulate the antigen-processing pathway. Understanding the mechanisms by which these tumors circumvent cytokine signalling, thereby evading antitumor-specific immunity, would greatly aid the efficacy of immunotherapy for treating uterine leiomyosarcomas.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

Down regulation of the L-type Ca2+ channel, GRK2, and phosphorylated phospholamban: protective mechanisms for the denervated failing heart.

We previously found that a canine model of selective surgical ventricular denervation (VD), which does not permit increased sympathetic tone during the pathogenesis of heart failure (HF), tolerated the development of HF better than controls. To investigate the cellular mechanisms, we examined cellular contraction and L-type Ca(2+) channel currents (I(Ca)) and their responses to beta-adrenergic receptor (beta-AR) stimulation in left ventricular myocytes from 1) control, 2) VD, 3) HF induced by rapid pacing, and 4) HF induced in VD (VD-HF) dogs. The magnitude of myocyte contraction and rate of relaxation in VD were similar to control but were depressed in both HF and VD-HF. These changes were associated with reduced protein expression of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) and protein kinase A phosphorylated phospholamban (PLB), which was reduced in HF, but essentially abolished in VD-HF. beta-AR kinase (GRK2) was increased in HF but reduced in VD-HF. Basal I(Ca) density did not differ among control, VD, and HF groups, but VD-HF myocytes showed a markedly reduced I(Ca) density (approximately 40%). Compared to controls, the sensitivity of I(Ca) to isoproterenol (ISO), was significantly higher in VD, but reduced in HF. While I(Ca) responses to ISO in VD-HF were maintained at control levels, the amplitude of the ISO-stimulated I(Ca) was significantly smaller (approximately 50%) compared with HF myocytes. The relative decrease in Ca(2+) influx due to downregulation of I(Ca) density may contribute to the cardioprotective effects in VD-HF hearts by preventing Ca(2+) overload during the development of HF. These findings, in combination with the virtual abolition of phosphorylated PLB in VD-HF and the decrease in GRK2, may explain, in part, why VD dogs tolerate the development of HF better than control dogs.

Animals↗

PubMed2006

Chromosomal change during 6-mercaptopurine (6-MP) therapy in juvenile myelomonocytic leukemia: the growth of a 6-MP-refractory clone that already exists at onset.

Among 11 JMML children, two had an abnormal karyotype, and nine had a normal karyotype at onset. In one patient with trisomy 8 and four patients with a normal karyotype, a new clone with an aberrant karyotype emerged 1-14 months after 6-mercaptopurine (6-MP) therapy as shown by G-banding analyses. Fluorescence in situ hybridization disclosed that an abnormal clone existed in approximately 3-6% of bone marrow cells at onset or before 6-MP therapy in all the four cases examined, and increased to approximately 12-90% during the treatment. In culture with granulocyte-macrophage colony-stimulating factor, cytogenetically abnormal clones that proliferated during 6-MP therapy possessed significantly less sensitivity to the antimetabolite, compared with cells that decreased in numbers after the therapy. A PTPN11 mutation was detected in all of granulocyte-macrophage colonies irrespective of karyotypic aberration in one patient, whereas approximately 80% of erythroid colonies and 20% of mixed colonies possessed neither a PTPN11 mutation nor chromosomal abnormalities. The appearance of chromosomal aberrations shown by G-banding during 6-MP therapy in some JMML cases may result, in part, from the growth of a 6-MP-refractory clone that already exists at onset. It is possible that treatment with 6-MP promotes progression of the disease.

Antineoplastic Agents↗

PubMed2006

Rehabilitation by means of osseointegrated implants in oral cancer patients with about four to six years follow-up.

This paper describes the reconstruction of mandibular defects in four oral cancer patients using iliac crest bone grafts and osseointegrated implants. In three patients, reconstructive surgery using a reconstruction plate and free forearm skin flap was performed following tumour and segmental mandibular resection. After 7-9 months, mandibular reconstruction with a free iliac bone graft was carried out. In one patient, reconstructive surgery was performed with vascularized iliac bone grafting with an anterolateral thigh flap at the same time as the tumour resection. Fixtures were placed in the transplanted bone, and abutments were connected 6-9 months later together with vestibuloplasty. Gingival grafts were used to replace the skin flap around abutments. All implants survived throughout the approximately 4-6 years observation time. Marginal bone loss of the graft was originally several millimetres but less than 1.5 mm. Bone loss as well as management of peri-implant soft tissue was also discussed.

Aged↗

PubMed2006

Novel cynomolgus macaque MHC-DPB1 polymorphisms in three South-East Asian populations.

Cynomolgus macaques (Macaca fascicularis, Mafa), alias the crab-eating monkeys or long-tailed macaques, live across a vast range of South-East Asia. These non-human primates have emerged as important animal models in infectious and chronic diseases and transplantation studies, necessitating a more extensive characterization of their major histocompatibility complex polymorphic regions. The current information on the polymorphic variation or diversity of the Mafa-DPB1 locus is largely limited in comparison with the more commonly studied rhesus macaque DPB1 locus. In this article, to better elucidate the degree and types of polymorphisms and genetic differences of Mafa-DPB1 locus among three South-East Asian populations and to investigate how the allele differences between macaques and humans might affect their respective immune responses, we identified 40 alleles within exon 2 of the Mafa-DPB1 locus by DNA sequencing using 217 individuals. We also performed evolutionary and population analyses using these sequences to reveal some population-specific alleles and trans-species allelic conservation between the cynomolgus macaques and the rhesus macaques. Of the 40 new alleles, eight belong to a newly identified lineage group not previously found in the rhesus macaque species. This allele information will be useful for medical researchers using the cynomolgus macaques in disease and immunological studies.

Alleles↗

PubMed2006

Influence of administration methods on the accumulation of ALA-induced Pp-IX in mouse tongue tumors.

OBJECTIVE: 5-Aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) has been used as a photosensitizer in photodynamic therapy (PDT) for oral cancer. This study investigates the optimal method of administrating ALA by analyzing PpIX fluorescence in tongue tumor tissue. METHODS: Protoporphyrin IX intensities in the mouse (C3H)-transplanted tongue cancer (NR-S1) were compared with those in normal tongue after intraperitoneal (i.p.), oral (p.o.) or topical administration of ALA. Tongues were sampled at various times after ALA administration. PpIX intensities were obtained from frozen sections of each sample by using a spectrophotometer. RESULTS: Protoporphyrin IX intensity in the tumor group peaked at 3 h after the i.p. and 5 h after the p.o. administration of ALA, and these levels were about twice as high as those in the normal group. Maximum PpIX accumulation in the tongue tumor tissue was seen at 5 h after p.o. administration of ALA. In contrast, the topical administration of 20% ALA cream was associated with the lowest PpIX accumulation in the tumor throughout the experiments. CONCLUSION: These results suggested that p.o. administration of ALA was the most effective method in ALA-PDT for oral cancer.

Administration, Oral↗

PubMed2005

Randomized clinical trial of the effect of a saline-linked radiofrequency coagulator on blood loss during hepatic resection.

BACKGROUND: Use of a saline-linked radiofrequency coagulator (dissecting sealer) has been suggested to reduce blood loss during hepatic resection. A randomized clinical trial was conducted to assess the effects of using the device on the amount of blood loss. METHODS: Patients scheduled to undergo hepatic resection were randomly assigned to either use of the dissecting sealer or the clamp crushing method. The primary outcome measure was blood loss during liver parenchymal division. Multivariate analysis was also performed. RESULTS: Ninety-four consecutive patients underwent hepatic resection and 40 patients were assigned to each group. There were no significant differences between the dissecting sealer and clamp crushing groups in blood loss during liver parenchymal division (median 373 versus 535 ml; P = 0.252) or total intraoperative blood loss (665 versus 733 ml; P = 0.450). Multivariate analysis revealed that use of the dissecting sealer offered no protection against blood loss compared with the clamp crushing method (odds ratio 1.17 (95 per cent confidence interval 0.39 to 3.53); P = 0.777), whereas number of resections, thoracotomy and type of resection had a significant effect. CONCLUSION: Use of a dissecting sealer offered no substantial benefit over the clamp crushing method in reducing blood loss during hepatic resection.

Adult↗

PubMed2005

Sentinel surveillance for international Shigella by a quarantine station in Japan.

The Japanese quarantine system monitors incoming passengers to detect imported pathogens at international airports. At one airport, we found that 74% of 13 315 travellers returning with diarrhoea had visited only one country before entering Japan. On the basis of our results, we hypothesized that the international distribution and potential source of bacterial strains could be inferred by analysing strains isolated from travellers returning to Japan. In order to demonstrate the potential for this system, we randomly selected five Shigella sonnei strains and examined their restriction fragment length polymorphism patterns. One set of strains appeared to be closely related, while three sets, isolated from travellers who visited different countries were possibly related. These results suggest that international distributions and potential sources of S. sonnei may be inferred by monitoring isolates from passengers arriving at a Japanese quarantine station.

Aircraft↗

PubMed2005

CD2+ acute promyelocytic leukemia is associated with leukocytosis, variant morphology and poorer prognosis.

The T cell-lineage marker CD2 is sometimes expressed in acute promyelocytic leukemia (APL), and CD2 expression is reported to correlate with some clinical characteristics. However, the significance of CD2 expression in APL has not been fully elucidated. We evaluated CD2 expression in APL treated by the same treatment strategy in a single institute, and whether it had any special characteristics. Among 29 APL, 6 were positive for CD2. Patients with CD2+ APL tended to have a higher leukocyte count than CD2- APL (34.5 +/- 13.1/l vs. 6.8 +/- 2.1/l), morphological characteristics as variant-APL (50 vs. 0%). They also showed poor clinical prognosis. The CR rate of CD2- APL was 87.0% while that of CD2+ APL was 50 %. The mortality was 13.0 and 66.7%, respectively, and the survival rate was significantly lower in CD2+ APL. CD2 expression was proven to be a risk factor associated with death in addition to the morphological characteristics of variant-APL and leukocytosis. These results indicated that CD2 expression might have a significant impact on the prognosis of APL. Whether CD2+ APL should be characterized as a special clinical entity should be discussed in a larger patient population.

Adult↗

PubMed2004

Paroxysmal dysarthria and ataxia after midbrain infarction.

The authors describe a patient who showed paroxysmal dysarthria and right-limb ataxia after midbrain infarction. SPECT imaging showed marked hypoperfusion in the left parietal lobe while the patient was having frequent paroxysmal attacks. After treatment with phenytoin, the symptoms and hypoperfusion in SPECT imaging improved. The authors conclude that dysfunction of the cerebellothalamocortical pathway after midbrain infarction may cause paroxysmal dysarthria and ataxia.

Aged↗

PubMed2004

Comparison of thrombin-catalyzed fibrin polymerization and factor XIIIa-catalyzed cross-linking of fibrin among three recombinant variant fibrinogens, gamma 275C, gamma 275H, and gamma 275A.

BACKGROUND AND OBJECTIVES: We have previously reported that recombinant gamma 275Cys fibrinogen exhibits a marked impairment of functions as well as aberrant fibrin clot and bundle structures, as compared with wild-type, gamma 275Arg, and plasma fibrinogen from a heterozygous proband. Since gamma Arg275His mutations have also been reported in 10 families, we synthesized recombinant gamma 275His fibrinogen and gamma 275Ala fibrinogen (as a control) and analyzed and compared them with gamma 275Cys and gamma 275Arg. METHODS: A variant gamma-chain expression plasmid was transfected into Chinese hamster ovary cells expressing normal human fibrinogen A alpha- and B beta-chains. After purification of the recombinant variant fibrinogens, we performed functional analyzes for thrombin-catalyzed fibrin polymerization and factor XIIIa (FXIIIa)-catalyzed gamma-gamma dimer formation from fibrin or fibrinogen and also ultrastructural analysis of fibrin clots and bundles. RESULTS: By comparison with both gamma 275His and gamma 275Ala fibrinogens, recombinant gamma 275Cys fibrinogen exhibited a more impaired gamma-gamma dimer formation from fibrin or fibrinogen, a more aberrant fibrin clot structure, and thicker fibers in fibrin bundles. In 1 : 1 mixtures of gamma 275Arg and gamma 275Cys fibrinogens or gamma 275Arg and gamma 275His fibrinogens, thrombin-catalyzed fibrin polymerization and both fibrin clot and fiber structures showed some compensation (as compared with gamma 275Cys or gamma 275His alone). CONCLUSION: These results strongly suggest that an amino acid substitution of gamma 275Arg alone disrupts D:D interactions in thrombin-catalyzed fibrin polymerization and the formation of fibrin bundles and fibrin clots. Moreover, the existence of a subsequent disulfide-linked Cys in gamma 275C fibrinogen augments the impairment caused by a His or Ala substitution.

Alanine↗

PubMed2004

Alterations in enzyme histochemical characteristics of the masseter muscle caused by long-term soft diet in growing rabbits.

OBJECTIVE: Recently young people have an increasing tendency to intake an easily chewable diet and spend less time on mastication. The aim of the present study was to investigate the histochemical effects of long-term soft diet on the masseter muscle in growing rabbits. MATERIALS AND METHODS: Twelve young male Japanese white rabbits were divided into two groups (n = 6 each) at weaning (1 month after birth) and fed a solid diet (control group) or a powder diet (soft-diet group). The duration of the experimental period was 6 months. Masseter fibers from the superficial and the deep portions were histochemically defined as type 1, 2A, 2B, or 2C fibers. RESULTS: As compared with that of the control, the deep masseter of the soft-diet group showed a significantly lower ratio of type 1 fiber cross-sectional area to total area (6.3 and 10.1% for the soft-diet and control group, respectively), significantly more type 2A fibers (74.0%vs 50.3%) and significantly fewer type 2B fibers (4.3%vs 12.5%). However, fiber size did not differ between the two groups. NADH-tetrazolium-reductase (NADH-TR) of the masseter was less reactive in the soft-diet group, reflecting a lower oxidative capacity. CONCLUSIONS: These findings indicate that the alteration of the functional activities contributed to selective disuse influences on the type 1 and type 2B fibers, and a resultant increase in type 2A fibers. This study suggests that long-term alteration of jaw function induced by a soft diet can lead to adaptations of the masseter muscle.

Adaptation, Physiological↗

PubMed2004

Operative treatment of hip fracture in haemodialysed patients.

PURPOSE: To study operative treatment and postoperative clinical outcomes of hip fracture in haemodialysed patients. METHODS: In 12 patients (8 men and 4 women) undergoing haemodialysis, 14 hip fractures were treated. Of these, 8 hips were treated with bipolar hip arthroplasty, one hip with total hip arthroplasty, 4 hips with a compression hip screw, and one hip with a gamma nail. The mean duration of dialysis treatment until fracture was 7 years. During a mean postoperative follow-up period of 17 months (range, 1-44 months), the patients' renal condition, type of fracture, and level of activities of daily living before and after surgery were assessed. RESULTS: Of the 7 patients who died during a mean follow-up period of 17 months, 2 died from myocardial infarction, 2 from sepsis, and one each from gastric cancer, pulmonary oedema, and liver failure. Five of the 8 patients with diabetic nephropathy died, whereas 6 of the 8 patients who underwent bipolar hip arthroplasty or total hip arthroplasty died. Most of the patients had declined level of activities of daily living postoperatively. CONCLUSION: For haemodialysed patients with fractures, it is essential to select the most suitable operating method and to conduct vigilant management before and after the operation.

Aged↗

PubMed2003

Comparative antimicrobial activities of gatifloxacin, sitafloxacin and levofloxacin against Mycobacterium tuberculosis replicating within Mono Mac 6 human macrophage and A-549 type II alveolar cell lines.

Mycobacterium tuberculosis (MTB) is capable of invading not only macrophages (Mphis) but also type II pneumocytes. In this study, we compared the antimicrobial activities of fluoroquinolones, including gatifloxacin, sitafloxacin and levofloxacin, against the MTB replication in the Mono Mac 6 human Mphi cell line (MM6-Mphis) and the A-549 human type II alveolar epithelial cell line (A-549 cells). When test quinolones were added at the MIC (0.125, 0.06 and 0.25 mg/l for gatifloxacin, sitafloxacin and levofloxacin, respectively) to the culture media of MTB-infected cells, these drugs exerted growth-inhibitory activity against intracellular organisms in the order of sitafloxacin > gatifloxacin > levofloxacin. On the other hand, when test quinolones were added at Cmax in the blood (1.7, 1.0 and 2.0 mg/l for gatifloxacin, sitafloxacin and levofloxacin, respectively), these drugs exhibited bactericidal activity against intracellular MTB in the order of gatifloxacin > sitafloxacin > or = levofloxacin. In addition, when test drugs were added at 1/8 C(max) to 1/2 C(max), the efficacy was in the order of sitafloxacin > gatifloxacin > levofloxacin. Thus, it appears that the MIC values of fluoroquinolones are not always predictive of their antimicrobial activity against intracellular MTB. In this context, it was also found that intracellular uptake of these quinolones by MM6-Mphis and A-549 cells was in the order of sitafloxacin > gatifloxacin > levofloxacin. This implies that the cellular permeability of these quinolones is an important factor that determines their efficacy to eliminate intracellular MTB organisms.

Anti-Infective Agents↗

PubMed2003

Duct-to-duct biliary reconstruction for living donor liver transplantation: experience of 92 cases.

Bile duct-to duct reconstruction is now performed in living donor liver transplantation (LDLT) for adult patients. To confirm the feasibility, the results after the reconstruction were retrospectively analyzed. The subjects were 92 adult patients who underwent LDLT at the University of Tokyo Hospital. During the observation period (median 546 days), biliary complications were observed in 28 cases (30%). The complications included bile juice leakage in 11, stenosis at the anastomotic site in 9, and tube trouble in 8. Of these, 20 patients required surgical revision. The results suggest that duct-to-duct reconstruction provides satisfactory results, although long-term observation will be necessary.

Bile Ducts↗

PubMed2003

Survey of Vibrio cholerae O1 and its survival over the winter in marine water of Port of Osaka.

The survey of Vibrio cholerae O1 in marine area was carried out in the Port of Osaka, Japan in 1987-2001, and 51 V. cholerae O1 strains were isolated. All strains were identified to be of El Tor biotype, Ogawa serotype and classic Ubon Kappa-phage type, and were cholera toxin (CT)-negative and CT gene-negative. In order to clarify certain ecological aspects of V. cholerae O1 in the marine environment of the temperate zone, we performed molecular analysis of the isolated strains using pulsed-field gel electrophoresis (PFGE) with NotI and SfiI restriction enzymes. We found the indistinguishable strains by DNA analysis using PFGE with strains passed for 1 year, and also found the closely related strains with that passed for 3 and 12 years. Those results indicated that V. cholerae O1 can survive over one winter at least, and that it survives in marine water for a long time by undergoing continuous mutation.

Adaptation, Physiological↗

PubMed2002

Collagen-binding heat shock protein HSP47 expression during healing of fetal skin wounds.

Wounds in fetal animals are known to heal without scar formation, but the mechanism involved remains unclear. Scar tissue is characterized by disorganized collagen bundles. The 47-kDa heat shock protein (HSP47) is a molecular chaperone that specifically targets collagen processing. However, the role of HSP47 in scar formation is poorly understood. We studied the relation of HSP47 expression in skin to scar formation during fetal wound healing. Immunohistochemical analysis demonstrated HSP47-positive cells in the epidermal cell layer of fetal and neonatal rat skin and the absence of such cells in subcutaneous tissue. After induction of a wound on the back of fetal and neonatal rats, the message of collagen type I was increased only in neonatal skin but not in fetal skin. HSP47-positive cells consistently increased for 7 days after wound induction in neonatal rats. In contrast, HSP47-positive cells and HSP47 protein were unchanged in fetal rats. We conclude that the scarless healing of fetal skin wounds is related to lack of change in HSP47 expression. HSP47 may thus be an important determinant of scar formation during wound healing.

Animals↗