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Biomedical subjects

Y Iwamoto

Publications and source records attributed to Y Iwamoto.

At least 109 records · Page 6Linked to original sources
PubMed2000

TCR-independent activation of extrathymically developed, self antigen-specific T cells by IL-2/IL-15.

Naive intrathymically developed T cells, which express foreign Ag-specific TCR, do not express IL-2R. After antigenic stimulation, they express high affinity IL-2R, which enables IL-2 to be used as an autocrine growth factor. On the contrary, extrathymically developed T cells, which express self Ag-specific TCR but are unresponsive to antigenic stimulation, spontaneously express low affinity IL-2R. In this study, we compared the responses of these two subsets of T cells to IL-2R stimulation and examined the influences of TCR-mediated signaling on the responses. IL-2 or IL-15 augmented the proliferative response of Ag-stimulated, intrathymically developed T cells. On the other hand, extrathymically developed T cells proliferated in response to IL-2 or IL-15, independently of Ag stimulation. Furthermore, both IL-2 and IL-15 induced IFN-gamma production of these T cells, which is strikingly augmented by the presence of IL-12. These results revealed functional differences between intrathymically developed, foreign Ag-specific T cells and extrathymically developed, self Ag-specific T cells. The latter can be activated by some inflammatory cytokines, in an Ag-independent manner, similar to NK cells.

Animals↗
PubMed2000

Prognostic value of the preserved expression of the E-cadherin and catenin families of adhesion molecules and of beta-catenin mutations in synovial sarcoma.

This study addresses the immunohistochemical expression of the E-cadherin and catenin families and mutations of the beta-catenin gene detected by PCR-SSCP in synovial sarcoma. Immunohistochemical analysis was performed for 72 cases, with follow-up data available on 62. The prognostic value of the expression of these proteins was evaluated. Reduced immunoreactivity for E-cadherin and alpha-catenin was significantly correlated with a poor survival rate (p=0.0040 and 0.0053, respectively). According to multivariate analysis, low AJC stage (stages I and II: p<0.0001), the preservation of alpha-catenin expression (p=0.0001), and a low necrotic rate (<50%: p=0.0139) were independent favourable prognostic factors. Widespread aberrant staining of beta-catenin protein within cytoplasm and/or nuclei was observed in 28 cases (38.9%) and was significantly correlated with poor survival (p=0.0122). In addition, there was a trend towards a correlation between widespread aberrant staining of beta-catenin and the MIB-1 labelling index (p=0.0535). Mutational analysis of exon 3 of the beta-catenin gene was performed for 49 cases. Nucleotide sequencing analysis revealed that four (8.2%) contained point mutations (three in codon 32, GAC to TAC; one in codon 37, TCT to TTT). Survival data were available for three out of four cases with beta-catenin mutations; two of these patients died within 1 year (died of disease at 6 and 11 months, respectively). These results suggest that E-cadherin and alpha-catenin undertake important roles as intercellular adhesion molecules; their preserved expression is associated with a better overall survival rate in synovial sarcoma and may have prognostic value. Abnormal levels of beta-catenin, with or without mutation, could contribute to the development and progression of synovial sarcoma, through increasing the proliferative activity of the tumour cells.

Cadherins↗
PubMed2000

Markers of joint tissue turnover in joint fluids from hips with osteonecrosis of the femoral head.

Osteonecrosis of the femoral head often results in secondary osteoarthritis of the hip joint; however, the pathologic processes underlying the destruction of articular cartilage are not fully understood. Molecular markers in the hip joint fluids were measured to examine the changes in turnover of cartilage and other joint tissues. Marker data were related to clinical, radiological, and histopathological changes in the articular cartilage of the hip. Forty-five patients (median age: 43 years) were studied. The median time between the onset of symptoms and sampling of hip synovial fluid was 6 months. Aggrecan fragments, C-propeptide of type-II collagen, matrix metalloproteinase-3, and tissue inhibitor of metalloproteinases-1 levels in joint fluid were determined by immunoassay. Osteonecrosis of the femoral head was graded by radiology as minimal collapse of the femoral head (stage 2: 26 patients), severe collapse (stage 3: 15 patients), or severe collapse with osteoarthritis (stage 4: four patients). Histological changes of the articular cartilage, consistent with early-stage osteoarthritis, were evident at stage 3 and were more advanced at stage 4. The average concentrations of proteoglycan fragments and C-propeptide of type-II collagen were 207 (SD 182) microg/ml and 19.6 (SD 19.3) ng/ml, respectively. The average concentrations of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1 were 177 (SD 291) nM and 23.0 (SD 9.9) nM, respectively. Measurable levels for all markers assayed were noted in the earliest stage of the disease, only a few months after the onset of symptoms and well before the appearance of radiological changes. Levels of matrix metalloproteinase-3 and molar ratios of matrix metalloproteinase-3/tissue inhibitor of metalloproteinases-1 were higher in early stage disease than in later stage disease.

Adult↗
PubMed2000

Mixture of hyaluronic acid and phospholipid prevents adhesion formation on the injured flexor tendon in rabbits.

Dipalmitoyl phosphatidylcholine, a highly surface-active polar lipid, has been implicated as a potential boundary lubricant for synovial joints. We examined the effects of dipalmitoyl phosphatidylcholine on the flexor tendon and its protective effect against postoperative adhesion in two experimental steps. First, the flexor digitorum fibularis and the distal pulley of rabbits were set for a friction test. The test was performed with saline solution, sodium hyaluronate, or a mixture of dipalmitoyl phosphatidylcholine and sodium hyaluronate as the lubricant. The friction coefficient was significantly lower with the mixture of dipalmitoyl phosphatidylcholine and sodium hyaluronate than with saline solution or sodium hyaluronate. We concluded that the decreased friction coefficient indicates that dipalmitoyl phosphatidylcholine could complement the boundary-lubricating ability of the tendon. In the second experiment, we used an experimental adhesion model of the flexor digitorum fibularis in the rabbit. During the operation, either saline solution, sodium hyaluronate, or a mixture of dipalmitoyl phosphatidylcholine and sodium hyaluronate was injected into the tendon sheath. The specimen was sent to another tester, and the work required to tear off the adhesion was measured. The work required was significantly greater for the tendons that had been injected with saline solution than for those given injections of dipalmitoyl phosphatidylcholine and sodium hyaluronate. Our findings suggest that dipalmitoyl phosphatidylcholine plays an important role in the boundary lubrication of the tendon and that after tendon injury, the administration of a mixture of dipalmitoyl phosphatidylcholine and sodium hyaluronate may improve tendon lubrication and prevent adhesion formation.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2000

Nerve sheath ganglion of the ulnar nerve.

We report a case of a nerve sheath ganglion of the ulnar nerve at the canal of Guyon. This case involved a ganglion which was confined to the epineurium of the ulnar nerve. and it was completely excised without any damage to the nerve fiber. A nerve-sheath ganglion is rare, but it should be considered in the differential diagnosis of any tumor which is causing neural disturbance.

Adult↗
PubMed2000

Aminobisphosphonate (YM175) inhibits bone destruction in rat adjuvant arthritis.

This study was designed to examine the effects of an aminobisphosphonate (YM175, which is also called incadronate) on bone destruction in rat adjuvant arthritis (AA). Thirty-five female Lewis rats were given an intradermal injection of heat-killed Mycobacterium butyricum and randomly allocated to five groups (seven rats/group). In the three YM175-treated (0.01, 0.1 and 1 mg/kg per day) groups, YM175 was injected subcutaneously every day from day 0 to day 42. The effects of YM175 in AA rats were evaluated according to an arthritis score, hind paw volume, and radiological and histological examinations. The results showed that YM175 suppressed the radiological and histopathological changes, as well as the joint swelling, in rat AA in a dose-dependent manner. The number of tartrate-resistant acid phosphatase (TRAP)-positive cells (osteoclasts and preosteoclasts or osteoclast precursors) in bone mar-row spaces and granulation tissue in the YM175-treated groups was also reduced in a dose-dependent manner. This study provides the first evidence that YM175, among aminobisphosphonates, not only inhibits bone destruction in rat AA, probably by reducing osteoclast numbers, but that it also suppresses joint inflammation. These results suggest that YM175 may be a useful drug for the prophylactic treatment of both bone destruction and joint inflammation in patients with rheumatoid arthritis.

Animals↗
PubMed2000

No diabetes-associated mutations in the coding region of the hepatocyte nuclear factor-4gamma gene (HNF4G) in Japanese patients with MODY.

AIMS/HYPOTHESIS: Mutations in the transcription factor hepatocyte nuclear factor (HNF)-4alpha are the cause of one form of maturity-onset diabetes of the young, MODY1. The HNF-4gamma is structurally related to HNF-4alpha and is expressed together with HNF-4alpha in pancreatic islets. We therefore tested the hypothesis that genetic variation in the HNF-4gamma gene (HNF4G) is associated with MODY in Japanese subjects. METHODS: We screened the protein coding region of HNF4G (exons 3-11) for mutations in 57 unrelated Japanese subjects with MODY by amplifying each exon and adjacent intron region using the polymerase chain reaction (PCR) and specific primers and then directly sequencing the PCR products. The frequency of each variant was compared between patients with MODY and a group of non-diabetic subjects. RESULTS: We found ten sequence variants, two of these were located in exons: exon 6, a silent substitution in codon 144, c.432A/G and exon 7, a G-to-A substitution in codon 190 (c.570G/A) resulting in a conservative Met-to-Ile substitution (M/I190) in the putative ligand-binding region of HNF-4gamma protein. The remaining eight variants were located in introns. There was no significant difference in the frequency of these polymorphisms between subjects with MODY and non-diabetic control subjects. CONCLUSION/INTERPRETATION: Genetic variation in the coding region of HNF4G is unlikely to be a major cause of MODY in Japanese people.

Amino Acid Sequence↗
PubMed2000

Comparison of the fasting and the 2-h glucose criteria for diabetes in different Asian cohorts.

AIMS/HYPOTHESIS: The American Diabetes Association recommended that only a single fasting plasma glucose of greater than or equal to 7.0 mmol/l should be used for diagnosing diabetes in epidemiological studies and did not recommend using a 2-h oral glucose tolerance test. We evaluated the effect of diagnostic changes on the prevalence of diabetes and on the choice of subjects diagnosed with diabetes. METHODS: Existing epidemiological data collected from Asian people between 30 and 89 years of age, was re-analysed separately in 11 population-based studies (n = 17,666), 6 pre-selected hyperglycaemic cohorts (n = 12,221) and one suspected diabetic cohort (n = 8382). RESULTS: Among the 11 population-based studies, the new fasting glucose criteria resulted in an overall reduction of 1.8% in the prevalence of diabetes, which ranged from a reduction of 4.8% to an increase of 1.7% in the different studies. Of 1215 subjects diagnosed with diabetes by either criteria, only 449 met both criteria, a concordance of 37%. More than half of the diabetic subjects had isolated post-challenge hyperglycaemia and three quarters of the subjects with impaired glucose tolerance, according to the 2-h glucose criteria, were normal according to the fasting glucose criteria. Subjects diagnosed as diabetic based only on the 2-h glucose criteria were, on average, older than those with diabetes according to the fasting criteria. CONCLUSION/INTERPRETATION: The fasting and the 2-h glucose criteria diagnose different groups of subjects. It would therefore be inappropriate to use the fasting glucose criteria alone for screening diabetes in Asian populations.

Adult↗
PubMed2000

Anatomic variations should be considered in total knee arthroplasty.

The effect of anatomic variations on the operative techniques used in total knee arthroplasty (TKA) was assessed. In 133 Japanese patients with medial osteoarthritis (OA), six parameters were measured on anteroposterior radiographs of the lower extremities taken with the patients in the supine position. The results showed that the characteristics of the knees were bowing of the femoral shaft and proximal tibia vara, with lateral offset of the tibial shaft with respect to the center of the tibial plateau. The angle between a perpendicular to the mechanical axis and the tangent to the distal femoral condyles can be used in determining the external rotation of the femoral component. This angle was more than 3 degrees in 20% of the patients. The femoral component should therefore be externally rotated more than 3 degrees relative to the posterior condylar line in such patients. Because the center of the tibial plateau is located medial to the central line of the tibial shaft in knees with medial OA, the central point of the tibial articular surface should not be used for alignment of the tibial component. The medial offset stem of the tibial component may impinge against the medial wall. Anatomic variations should be evaluated before TKA is attempted.

Aged↗
PubMed2000

Histological findings of bone marrow edema pattern on MRI in osteonecrosis of the femoral head.

Sequential magnetic resonance imaging (MRI) was performed on a 38-year-old woman with systemic lupus erythematosus who had received corticosteroid and had developed non-traumatic osteonecrosis of the femoral head. The initial MR finding was a band lesion on the T1-weighted image, which had been present before the onset of symptoms. At the onset of symptoms, a diffuse bone marrow edema pattern, with a low signal intensity on T1 and high signal intensity on T2-weighted images, was noted around the band lesion, extending to the femoral neck. Histopathologically, this region was found to consist of serous exudate, focal interstitial hemorrhage, and mild fibrosis, without any evidence of extension of osteonecrosis. It should be noted that extension of a low signal intensity area on MRI after the onset of hip pain may not be the result of the extension of osteonecrosis, but may represent concomitant edema due to collapse.

Adult↗
PubMed2000

Expression of hepatocyte growth factor (HGF)/scatter factor and its receptor c-MET correlates with poor prognosis in synovial sarcoma.

The hepatocyte growth factor (HGF)/c-MET signaling system plays an important role in the carcinogenesis of various organs. We investigated the expression of HGF and its receptor c-MET by immunohistochemistry (IHC) in 69 cases of synovial sarcoma and compared the findings with clinicopathologic parameters, proliferating activities evaluated by MIB-1 labeling index (MIB-1 LI), and patients' prognosis. Furthermore, mRNA analysis of HGF, c-MET, and SYT-SSX fusion gene was performed by reverse transcriptase-polymerase chain reaction (RT-PCR) in 22 concordant frozen materials. Twenty-one of 69 (30.4%) tumors showed positive reaction for c-MET, whereas 22 tumors (31.9%) were positive for HGF. In 10 cases, co-expression of HGF and c-MET was observed; however, there was no significant correlation between HGF and c-MET expression. HGF expression was correlated with female patients, large tumors (more than 5 cm), the presence of rhabdoid cells, low frequency of mast cells (<20/10 HPF), high nuclear grade (grade III), and high American Joint Committee (AJC) stage (III and IV). Conversely, c-MET expression was only correlated with large tumors. However, the coexpression of HGF and c-MET was significantly correlated with large tumor size, the existence of rhabdoid cells, and high AJC stage. Both the expression of HGF and the co-expression of HGF and c-MET showed a significantly high MIB-1 LI and were correlated with poor prognosis according to univariate analysis. Multivariate Cox analysis showed that high AJC stage, the expression of HGF, and a high MIB-1 LI (12.0>) independently had a negative impact on overall survival. In 22 frozen material cases evaluated by both IHC and RT-PCR, a statistically significant correlation was found between the 2 techniques. SYT-SSX fusion transcripts were detected in all 22 cases. Three tumors had SYT-SSX2 fusion transcripts, whereas 19 had SYT-SSX1 phenotype. Our results suggest that HGF/c-MET paracrine signaling may contribute to tumorigenesis and progression in synovial sarcoma.

Adult↗
PubMed2000

Delapril versus manidipine in hypertensive therapy to halt the type-2-diabetes-mellitus-associated nephropathy.

Thirty-nine hypertensive patients with type 2 diabetes mellitus were followed under long-term treatment (mean, 20.7 months) with manidipine hydrochloride, a Ca antagonist, or delapril hydrochloride, an ACE inhibitor, at nine institutions. Both the treatments showed similar antihypertensive effects, although slight but significantly larger decreases were observed in systolic and mean blood pressures at months 12 and 24 in the patients treated with manidipine (P < 0.02). The urinary albumin excretion index (AEI) tended to increase throughout the study in both treatment groups, but no significant difference in AEI was observed between the two treatment groups at any time point. Overt albuminuria developed in four patients on manidipine but did not appear in any of the patients on delapril. The risk of progression to overt albuminuria was significantly different between manidipine and delapril groups (P = 0.011). No increase in serum creatinine (Cr) was observed with delapril. The average excretion indexes of tubular markers such as beta2-microglobulin, alpha1-microglobulin, and NAG tended to be higher in the patients on manidipine than in those on delapril. Taken in sum, these findings suggest that the ACE inhibitor delapril is more beneficial than the Ca antagonist manidipine in the treatment of diabetic renal diseases via mechanisms other than the blood pressure regulation, partly through their different effects on tubular function. In conclusion, delapril was significantly more effective than manidipine in inhibiting progression to overt albuminuria in hypertensive type 2 diabetes mellitus patients.

Adult↗
PubMed2000

Worldwide differences in the incidence of insulin autoimmune syndrome (Hirata disease) with respect to the evolution of HLA-DR4 alleles.

The relationship between the geographic distribution of susceptibility genes to insulin autoimmune syndrome (IAS) and the incidence of insulin autoimmune syndrome was investigated in order to examine the distribution of the genetic background to susceptibility to certain diseases. The HLA-DR4 allele, DRB1*0406, is associated with increased susceptibility to IAS among Japanese, while the DRB1*0403 and DRB1*0407 alleles are not (the odds ratio of which are 1.6 and 1.1, respectively). The worldwide geographic distribution of the three DR*04 alleles showed that the distribution of DRB1*0403 encompassed that of DRB1*0406 and DRB1*0407. Taken together with the findings that Glu at position 74 in the DRB1 molecule is shared by the three DRB1*04 alleles, there are only a few differences between the DRB1 molecule-nucleotide sequences of DRB1*0403, DRB1*0406 and DRB1*0407, and that all the three DRB1*04 alleles are carried by the same class II haplotype, DQA1*0301/DQB1*0302, it may be considered that DRB1*0403 is the ancestral allele of DRB1*0406 and DRB1*0407. Therefore, populations with a higher prevalence of DRB1*0406 have a higher risk of developing IAS. The extremely low prevalence of IAS among Caucasians can be explained by the low prevalence of DRB1*0406 in this population. This is a good example of the association between the predisposition to risk of development of certain diseases and the evolution of susceptibility genes.

Alleles↗
PubMed2000

A device for removal of femoral distal cement plug during hip revision arthroplasty: a high-powered drill equipped with a centralizer.

A removal procedure of a femoral cement mantle in hip revision arthroplasty has a risk of causing perforation or fracture, especially when removing a well-fixed distal cement plug. A high-powered drill equipped with a centralizer was developed to remove the distal cement plug safely. Using the drill equipped with a centralizer, the cement plug was removed well enough to insert a new component without causing perforation during the operation.

Arthroplasty, Replacement, Hip↗
PubMed2000

A comparative study of fibrous dysplasia and osteofibrous dysplasia with regard to Gsalpha mutation at the Arg201 codon: polymerase chain reaction-restriction fragment length polymorphism analysis of paraffin-embedded tissues.

Fibrous dysplasia and osteofibrous dysplasia are both benign fibro-osseous lesions of the bone and are generally seen during childhood or adolescence. Histologically, the features of these bone lesions sometimes look quite similar, but their precise nature remains controversial. Mutation of the alpha subunit of signal-transducing G proteins (Gsalpha), with an increase in cyclic adenosine monophosphate (cAMP) formation, has been implicated in the development of multiple endocrinopathies of the Albright-McCune syndrome and in the development of fibrous dysplasia. We studied Gsalpha mutation at the Arg201. codon in seven cases of fibrous dysplasia (six monostotic lesions and one polyostotic lesion) and seven cases of osteofibrous dysplasia using formalin-fixed, paraffin-embedded tissue, by means of polymerase chain reaction-restriction fragment length polymorphism and direct sequencing analysis. All of the seven cases of fibrous dysplasia showed missense point mutations in Gsalpha at the Arg201 codon that resulted in Arg-to-His substitution in three cases and Arg-to-Cys substitution in four cases. On the other hand, the seven cases of osteofibrous dysplasia and the normal bone used as a control showed no such mutation. These data suggest that fibrous dysplasia and osteofibrous dysplasia have different pathogeneses and that the detection of Gsalpha mutation at the Arg201 codon is quite useful for distinguishing between these lesions.

Adolescent↗
PubMed2000

Novel norsesquiterpenoids from the roots of Phyllanthus emblica.

Three ester glycosides, named phyllaemblicins A (3), B (4), and C (5), and a methyl ester (2), of a highly oxygenated norbisabolane, phyllaemblic acid (1), were isolated from the roots of Phyllanthus emblica, along with 15 tannins and related compounds. The structures of 2-5 were established by spectral and chemical methods.

China↗
PubMed2000

Antioxidants inhibit TNFalpha-induced motility and invasion of human osteosarcoma cells: possible involvement of NFkappaB activation.

Osteosarcoma is the most frequent malignant bone tumor in children. It is highly invasive, however, the mechanisms behind osteosarcoma cell invasion are as yet still unknown. In the present study, treatment with TNFalpha enhanced the invasiveness of two human osteosarcoma cell lines, OST and MNNG. TNFalpha treatment also induced tumor cell motility, adhesion to laminin, the expression of matrix metalloproteinase 9 (MMP9), and the nuclear translocation of nuclear factor kappaB (NFkappaB) in the osteosarcoma cells. Moreover, antioxidants inhibited TNFalpha-induced osteosarcoma cell invasion, motility and NFkappaB nuclear translocation, but not adhesion to laminin or MMP9 expression. NFkappaB decoy, another NFkappaB inhibitor, also inhibited TNFalpha-induced osteosarcoma cell invasion and motility. Therefore, motility and NFkappaB activation were possibly related to TNFalpha-induced osteosarcoma cell invasion. However, adhesion to laminin or MMP did not demonstrate any correlation with TNFalpha-induced osteosarcoma cell invasion. Although NFkappaB is known to regulate TNFalpha-induced phenotypes, it may influence only motility and invasion, but not the MMP or laminin-mediated adhesion of these osteosarcoma cells.

Antioxidants↗