Search PubMed⌕ Search

Biomedical subjects

T Sugiyama

Publications and source records attributed to T Sugiyama.

At least 37 records · Page 2Linked to original sources

Hypertrophy of vascularized bone isograft in rats treated with cyclosporine A.

The aim of this study was to investigate the effects of cyclosporine A (CsA) on vascularized tibio-fibula isograft between 12-week-old male Lewis rats. After transplantation, 45 rats were randomly allocated to one of the following 7 treatment groups: (1) 4-week vehicle (n = 5), (2) 4-week CsA (n = 5), (3) 8-week vehicle (n = 10), (4) 8-week CsA (n = 10), (5) 4-week CsA followed by 4-week vehicle (n = 5), (6) 16-week vehicle (n = 5), or (7) 4-week CsA followed by 12-week vehicle (n = 5). In soft X-ray and micro-computed tomography examination, hypertrophic change of the grafted bones was apparent in the 4- and 8-week CsA groups. Mineral apposition rate and bone formation rate of the grafted bones in the 4-week CsA group were markedly higher than those in the 4-week vehicle group. In the 4- and 8-week CsA groups, however, bone mineral density (BMD) of the grafted bones was lower and strength of the reconstructed bones was weaker than the 4- and 8-week vehicle groups. Urinary deoxypyridinoline (DPD) level was higher in the 4- and 8-week CsA groups than in the 4- and 8-week vehicle groups. The group of 4-week CsA followed by 4-week vehicle had a level of urinary DPD equal to the 8-week vehicle group, but their BMD of the grafted bones was lower and strength of the reconstructed bones was weaker than the 8-week vehicle group. By contrast, the group of 4-week CsA followed by 12-week vehicle had BMD of the grafted bones and strength of the reconstructed bones similar to the 16-week vehicle group. These findings demonstrate that short-term CsA treatment induces hypertrophic change of vascularized bone graft with high-turnover bone loss, and strength of the reconstructed bone is gradually restored after the cessation of CsA treatment.

Amino Acids↗

Characterization of the development of ectopic chondroid/bone matrix and chondrogenic/osteogenic cells during osteoinduction by rhBMP-2: a histochemical and ultrastructural study.

OBJECTIVE: To investigate the characteristics of ectopic chondroid/bone matrix and chondrogenic/osteogenic cells induced by recombinant human bone morphogenetic protein-2 (rhBMP-2). MATERIALS AND METHODS: rhBMP-2 (5 microg) combined with atelocollagen was implanted into calf muscles of rats and removed on days 7, 10, 14, 21, or 28. Tissue sections were examined using: (i) hematoxylin/Alcian blue/Sirius red stain, (ii) enzyme histochemistry for alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase activity, (iii) immunohistochemistry for types I, II, and X collagen, and (iv) electron microscopy. RESULTS: On day 7, numerous fibroblast-like cells with ALP activity were present on the pellet rim. On day 10, chondroid matrix (CM) had formed, contained both type I collagen and proteoglycans, and often continued into the BMP pellet. On day 14, bone-like matrix formed around hypertrophic chondrocytes simultaneously with endochondral ossification. Coexpression of types I and II collagen within chondrocytes and osteocytes was observed throughout the time course of the experiment. CONCLUSION: These results suggest that fibroblast-like cells invading the pellet differentiate into chondrocytes and form CM under the scaffold of the carrier component. It appears that some chondrocytes change their phenotype to produce the bone-like matrix and remain within the endochondral bone. This process enables rapid osteogenesis to occur.

Acid Phosphatase↗

Plural transformation-processes from spiral to coccoid Helicobacter pylori and its viability.

OBJECTIVES: Helicobacter pylori (H. pylori), present in a half of the world's population, is a very successful pathogen. The infection by this bacterium causes several gastric diseases in human. H. pylori is morphologically divided into two types; a spiral and a coccoid form. Both types are observed in human stomach. Although the former is converted into the latter in vitro, the process of coccoid formation remains obscure. Furthermore, whether coccoid forms possess viability arouses much controversy among scientists. We investigated both the process of coccoid formation by electron microscopy and the viability of coccoid H. pylori. METHODS: A laboratory strain, ATCC43504, was cultured in liquid medium (Brucella Broth medium with 10% heat inactivated horse serum) for seven days. In each culture day, the organisms were observed by scanning-, conventional transmission- and immuno-electron microscopy and were simultaneously examined the culturability of H. pylori to identify the viability of coccoid form. RESULTS: As the days went by, spiral forms were replaced by coccoid forms in each medium which possessed culturability to some degree until the 4th day. By the detailed observation of ultrastructural features, coccoid forms were classified into two types on the ground that represents different transformation-processes and distinctive ultrastructures. One was the coccoid form that we named Type A with an irregularly surface- and intracytoplasmic-structure which adhered to one another. The other was Type B having a smooth surface with flagella coiled around its own body and the strictly membranous structure. This type was not adhered to another organism. In later days, each type came to be similar external structure and lost the culturability. CONCLUSIONS: The coccoid forms of H. pylori can be classified into two types by electron microscopy which represent different transformation-processes and consist of the dying bacteria, the living ones with culturability and the viable but non-culturable ones.

Culture Media↗

Head and neck cancer arising after endoscopic mucosal resection for squamous cell carcinoma of the esophagus.

BACKGROUND AND STUDY AIMS: It is well known that patients with head and neck cancer often have synchronous or metachronous squamous cell carcinoma of the esophagus. However, the prevalence of subsequent head and neck cancer in patients with early-stage esophageal cancer is still unknown. The aims of this study were to analyze the frequency of metachronous head and neck cancer after endoscopic mucosal resection (EMR) for esophageal cancer and to investigate whether minute iodine-unstained areas, often associated with squamous cell carcinomas, would be an index for metachronous head and neck cancer. PATIENTS AND METHODS: 99 patients with esophageal squamous cell carcinoma who underwent EMR were studied. Based on the iodine-staining pattern at initial EMR, they were categorized into those with uniform (group U) and scattered (group S) types of background mucosa. Patients were monitored endoscopically and otolaryngologically (group U, median 46 months, range 12-83 months; group S, median 44 months, range 13-80 months). RESULTS: In total, 5/99 patients (5.1 %) were found to have metachronous head and neck cancer during the follow-up, including 4/20 patients (20 %) in group S. In three cases laryngeal or hypopharyngeal cancer was found by endoscopic examination. The cumulative proportion of metachronous head and neck cancer-free subjects was significantly lower in group S than group U (P = 0.0007). CONCLUSIONS: Among patients who undergo EMR for esophageal carcinoma, those with scattered-type iodine staining of the background mucosa have an increased risk of metachronous head and neck cancer, and should therefore be closely observed. Careful endoscopic observation led to early detection of laryngeal and hypopharyngeal cancer.

Aged↗

Fc gamma receptor II polymorphism in Vietnamese patients with systemic lupus erythematosus.

The polymorphism of the Fc receptor for IgG class IIA (Fc gammaRIIA) in Vietnamese patients with systemic lupus erythematosus (SLE) was examined by using the polymerase chain reaction (PCR) method with genomic DNA and allele-specific primers. In the frequency of Fc gammaRIIA genotypes, the homozygosity of Fc gammaRIIA-H131 was four (8.3%) of 48 SLE patients and 16 (37.2%) of 43 healthy controls (P < 0.01). The allele frequency of Fc gammaRIIA-H131 in SLE patients was also significantly lower than that in the controls (P < 0.05). The unusual distribution of Fc gammaRIIA polymorphism suggested that Fc gammaRIIA might be involved in the development of SLE in Vietnamese patients.

Adolescent↗

Effects of cerivastatin on vascularized allogenic bone transplantation in rats treated with cyclosporine A.

The aim of the present study was to investigate the effects of oral cerivastatin (0.1 mg/kg/day) on vascularized allogenic transplanted bone that is treated with cyclosporine A (CsA) (10 mg/kg/day) and on vascularized isogenic transplanted bone that is not treated with CsA. Allogenic transplantation was performed on 12-week-old male DA rats with the major histocompatibility antigen (MHC) RT1a (as the donor) and age-matched male Lewis rats with MHC RT1l (as the recipient), and isogenic transplantation was performed on 12-week-old male Lewis rats. After transplantations, 20 rats (10 rats in each transplantation) were randomized into four groups to receive the following treatment for 16 weeks: (1) CsA plus cerivastatin vehicle or (2) CsA plus cerivastatin in the allogenic transplanted rats, and (3) CsA vehicle plus cerivastatin vehicle or (4) CsA vehicle plus cerivastatin in the isogenic transplanted rats. Bone biochemical markers, mineral density, and strength were measured at the end of the study period. Serum levels of osteocalcin (OC) and parathyroid hormone (PTH) and urinary deoxypyridinoline (DPD) level were higher in the allogenic transplanted rats than in the isogenic transplanted rats. In the allogenic transplanted rats, the cerivastatin treatment decreased urinary DPD levels, but not serum OC nor PTH levels. Furthermore, the cerivastatin treatment improved bone mineral density of the allogenic transplanted bones and bone strength of the allogenic reconstructed bones. In contrast, no effect of the cerivastatin treatment was observed in the isogenic transplanted rats. These results suggest that the cerivastatin treatment improves CsA-induced high-turnover osteopenia mainly through the inhibition of bone resorption.

Amino Acids↗

Effects of vitamin D analog, 22-oxa-1,25-dihydroxyvitamin D(3), on bone reconstruction by vascularized bone allograft.

We previously reported that vascularized bone allograft using immunosuppressants, such as cyclosporine A (CsA), is one approach for reconstruction of large bone defects in both experimental animals (Microsurgery 15:663; 1994) and clinically in humans (Lancet 347:970, 1996). Because immunosuppressive agents such as CsA induce significant side effects, including bone loss, other therapeutic agents supporting successful vascularized bone allografts have been sought after. We investigated the effects of 22-oxa-1,25-dihydroxyvitamin D(3) (OCT) on vascularized bone allograft, and compared its effects with CsA. Twelve-week-old DA rats with the major histocompatibility antigen (MHC) RT-1(a) were used as donors and age-matched Lewis rats with MHC RT-1(l) used as recipients. Allografted bones in rats treated with vehicle were rejected completely. Soft X-ray examination demonstrated that administration of OCT (0.5 microg/kg per day) for 12 weeks after bone graft induced bone union as effective as treatment for 12 weeks with CsA (10 mg/kg per day). Transplanted bones in OCT-treated rats showed higher bone mineral density than that in CsA-treated rats. Histologically, transplanted bones in OCT-treated rats at 12 weeks were nonvital, but these bones united with recipient vital bones. After cessation of 12 week treatment with OCT, new bone formation occurred around the grafted nonvital bones during a 9 month period. Transplanted bones in CsA-treated rats were vital and formed union with recipient bones, whereas cortical bones became thin when compared with nonvital bones in OCT-treated rats. Urinary deoxypyridinoline levels in rats treated with CsA were significantly higher than levels in rats treated with OCT, suggesting accelerated bone resorption in CsA-treated rats. These results suggest that OCT exerts an anabolic action on bone reconstruction by allogeneic bone transplantation.

Amino Acids↗

Sensitivity of biopsy site in evaluating regression of gastric atrophy after Helicobacter pylori eradication treatment.

BACKGROUND: Helicobacter pylori infection is a major cause of the progress of gastric glandular atrophy, a high-risk background factor in the development of gastric cancer. Regression of gastric atrophy is critical to prevention of cancer by H. pylori eradication treatment. However, it is controversial whether gastric atrophy regresses after H. pylori eradication. AIM: To determine the most sensitive and appropriate biopsy site for evaluation of regression of atrophy after treatment. SUBJECTS AND METHODS: Thirty-eight patients who showed regression of gastric atrophy in histology after treatment were investigated. Four biopsy specimens from the lesser and greater curvatures in the antrum and corpus were evaluated before and after treatment according to the Updated Sydney System. RESULTS: Regression of atrophy after treatment was seen in 30 of 38 biopsy specimens from the lesser curvature of the corpus (79%), and this site was most sensitive. Odds ratio of this site to the others was 8.28. Regression of atrophy in this site was observed at 12.2 months in the younger patients and 15.9 months in the elder patients. CONCLUSION: Biopsy sampling from the lesser curvature of the corpus is the most sensitive and appropriate for evaluation of regression of gastric atrophy after H. pylori eradication treatment.

Adult↗

Antenatal diagnosis and treatment of a case of fetal goitrous hypothyroidism associated with high-output cardiac failure.

A case of fetal goitrous hypothyroidism associated with high-output cardiac failure is presented. At 32 weeks of gestation, the antenatal diagnosis of goiter was made based on ultrasound examination, and the fetal thyroid function was examined by amniocentesis and cordocentesis. Color and pulsed Doppler examinations demonstrated a high vascular flow pattern in the goiter and marked elevation of the maximum velocity in the common carotid artery at the level of the neck. It was suspected that arteriovenous shunting through the large goiter resulted in high-output cardiac failure with cardiomegaly and pleural effusion. The fetus was treated by injection of levothyroxine sodium into the amniotic fluid at 33 weeks of gestation and the goiter thereafter decreased in size, with subsequent improvement of the high-output cardiac failure. The maximum velocity in the common carotid artery fell rapidly before the shrinkage of the fetal goiter and in parallel with the fetal level of thyroid stimulating hormone.

Adult↗

The relationship between consumption of antimicrobial agents and the prevalence of primary Helicobacter pylori resistance.

BACKGROUND: Primary and acquired resistance to the antimicrobial agents is a primary reason for the failure of Helicobacter pylori eradication therapies. We assessed the primary antibiotic resistance rates of H. pylori to three different antibiotics and its relationship due to the annual antibiotic consumption in Japan during the period prior to approval of anti-H. pylori therapy in Japan. MATERIALS AND METHODS: Antibiotic susceptibility was tested using the agar dilution method for clarithromycin, amoxicillin and metronidazole. Isolates were considered resistant when the MIC value was > 8 mg/l for metronidazole, > 1 mg/l for clarithromycin and < 0.5 mg/l for amoxicillin. RESULTS: Helicobacter pylori isolates were obtained from 593 Japanese patients from 1995 to 2000. Primary resistance of H. pylori to clarithromycin, metronidazole and amoxicillin was found in 11%, 9% and 0.3% strains, respectively. The proportion with clarithromycin resistance significantly increased from 7% in 1997-98 to 15.2% in 1999-2000 (p =.003). During the same period the metronidazole resistance rate also increased from 6.6% in 1997-98 to 12% in 1999-2000 (p =.02). The prevalence of clarithromycin and metronidazole was related to the annual consumption of these antimicrobial agents. CONCLUSION: Resistance rates for both clarithromycin and metronidazole appear to reflect the annual consumption of these agents. The high rate of clarithromycin resistance in Japan suggests that the effectiveness of clarithromycin-based therapies may be compromised in the near future.

Anti-Bacterial Agents↗

Analysis of glucose tolerance in twin gestations using an oral glucose load.

The effect of twin gestation on carbohydrate metabolism was evaluated using a 75 g oral glucose tolerance test (75 g OGTT). A 75 g OGTT was performed in 63 twin gestations and 3 791 singleton gestations during the third trimester. Plasma glucose concentrations were measured in the pregnant women under fasting conditions as well as 30 min, 1 h, and 2 h after ingestion of glucose (75 g oral load), and serum insulin concentrations were measured in fasting and 30 min post-ingestion samples. Women with twin gestations showed significantly lower plasma glucose concentrations during fasting and 30 min after the glucose load in the samples taken than those with singleton gestations. No significant difference in serum glucose concentrations was found in the other specimens. There were no cases of gestational diabetes mellitus in our study. Although women with twin gestations demonstrated lower plasma glucose concentrations than women with singleton gestations, the difference observed was subtle. We could not find any significant differences in these plasma glucose values as used to define a pathologic OGTT between twin and singleton pregnancies, with the exception of the fasting value.

Adult↗

An antibody to VacA of Helicobacter pylori in cerebrospinal fluid from patients with Guillain-Barre syndrome.

OBJECTIVE: To detect antibodies to recombinant vacuolating cytotoxin (r-VacA) of Helicobacter pylori in cerebrospinal fluid (CSF) from patients with Guillain-Barre syndrome (GBS). METHODS: CSF samples from 13 patients with GBS (electrophysiologically classified as eight acute inflammatory demyelinating polyradiculoneuropathy (AIDP), four acute motor axonal neuropathy (AMAN), and one unexcitable nerve conduction) and eight disease control patients were studied. The r-VacA protein was separated by SDS/PAGE, and Western blot analysis was carried out. RESULTS: Six of the 13 patients with GBS had a specific IgG antibody to VacA of H pylori, which was confirmed by absorption experiments using r-VacA. Every patient with positive CSF anti-r-VacA IgG had AIDP. CONCLUSION: The sequence homology previously found between VacA and human (Na(+)+K(+))-ATPase A subunit suggests that antibodies to VacA involve ion channels in abaxonal Schwann cell plasmalemma resulting in demyelination in some patients with GBS.

Adult↗

Involvement of CCAAT/enhancer-binding protein in regulation of the rat serine:pyruvate/alanine:glyoxylate aminotransferase gene expression.

In the rat liver, transcription of the serine:pyruvate/alanine:glyoxylate aminotransferase (SPT/AGT) gene occurs from two sites, +1 and +66, in exon 1, resulting in the formation of two mRNAs, one for a precursor of mitochondrial SPT/AGT and the other for peroxisomal SPT/AGT, respectively. In this study, we attempted to characterize the downstream promoter responsible for generation of peroxisomal SPT/AGT. The minimal downstream promoter was confined to the +21-+90 region. We demonstrated that C/EBPalpha and C/EBPbeta bound around the downstream start site (+66) contribute to the promoter activity. The downstream promoter activity is also regulated positively by a short inverted repeat, located 20-30 bp upstream of the downstream start site, through a protein factor(s) bound to this region. On the other hand, the sequence just downstream of the start site may negatively regulate the promoter activity.

Animals↗

Synthesis of a set of di- and tri-sulfated galabioses.

Among cell-adhesion molecules, L-selectin recognizes sulfated sLe(x) with relatively low affinity. Here, we aimed at artificial mimics by synthesizing a set of di- and tri-sulfated galabioses, which may surpass the affinity of sulfated sLe(x). As a strategy to obtain 3',6',6-tri-O-sulfogalabioses, regioselective reductive cleavage of 4,6- and 4',6'-di-O-benzylidenegalabioses was employed. Two suitably protected galactose precursors were conjugated to yield alpha and beta anomers (48 and 18%, respectively) by using a pentenyl galactoside donor and iodinium di-sym-collidine perchlorate as the catalyst. For synthesizing the 3',6-di-O-sulfogalabiose, however, a trichloroacetimidate donor was superior (52%) to the pentenyl one (30%).

Acetamides↗

Impaired delay but normal trace eyeblink conditioning in PLCbeta4 mutant mice.

To elucidate the functional role of phospholipase Cbeta4 (PLCbeta4), which is highly expressed in the Purkinje cells of the rostral cerebellum, cerebellar long-term depression (LTD) and delay and trace eyeblink conditioning were investigated in PLCbeta4-deficient mice. Rostral cerebellar LTD and delay eyeblink conditioning were severely impaired, whereas trace eyeblink conditioning was not. These results indicate that PLCbeta4 is essential for LTD in the rostral cerebellum and delay conditioning, but not trace conditioning. Rostral cerebellar LTD may be required as a neural substrate for delay conditioning, but is not required for trace conditioning.

Afferent Pathways↗

Enhancement of the activity of doxorubicin by inhibition of glutamate transporter.

Theanine enhanced doxorubicin (DOX) induced antitumor activity by increasing the concentration of DOX in the tumor through the inhibition of efflux of DOX from tumor cells. As theanine reduced the level of glutamate via suppression of the glutamate transporter in tumor cells, we studied the change in the intracellular concentration of glutathione (GSH) and the correlation with the GSH S-conjugate export (GS-X) pump. The reduction in the concentration of glutamate in tumor cells caused by theanine, induced decreases in the intracellular GSH and GS-DOX levels. The expression of MRP5 in M5076 cells, was confirmed. We concluded that the GS-DOX conjugate was transported extracellularly via the MRP5/GS-X pump in M5076 cells and that theanine affected this route. Namely, theanine increases the concentration of DOX in a tumor in vivo through inhibition of the glutamate transporter via the GS-X pump.

Amino Acid Transport System X-AG↗

Phospholipase Cbeta4 and protein kinase Calpha and/or protein kinase CbetaI are involved in the induction of long term depression in cerebellar Purkinje cells.

Activation of the type-1 metabotropic glutamate receptor (mGluR1) signaling pathway in the cerebellum involves activation of phospholipase C (PLC) and protein kinase C (PKC) for the induction of cerebellar long term depression (LTD). The PLC and PKC isoforms that are involved in LTD remain unclear, however. One previous study found no change in LTD in PKCgamma-deficient mice, thus, in the present study, we examined cerebellar LTD in PLCbeta4-deficient mice. Immunohistochemical and Western blot analyses of cerebellum from wild-type mice revealed that PLCbeta1 was expressed weakly and uniformly, PLCbeta2 was not detected, PLCbeta3 was expressed predominantly in caudal cerebellum (lobes 7-10), and PLCbeta4 was expressed uniformly throughout. In PLCbeta4-deficient mice, expression of total PLCbeta, the mGluR1-mediated Ca(2+) response, and LTD induction were greatly reduced in rostral cerebellum (lobes 1-6). Furthermore, we used immunohistochemistry to localize PKCalpha, -betaI, -betaII, and -gamma in mouse cerebellar Purkinje cells during LTD induction. Both PKCalpha and PKCbetaI were found to be translocated to the plasmamembrane under these conditions. Taken together, these results suggest that mGluR1-mediated activation of PLCbeta4 in rostral cerebellar Purkinje cells induced LTD via PKCalpha and/or PKCbetaI.

Animals↗