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Biomedical subjects

T Wada

Publications and source records attributed to T Wada.

At least 163 records · Page 9Linked to original sources
PubMed2000

Calcium/calmodulin inhibits the binding of specific [125I]omega-conotoxin GVIA to chick brain membranes.

The effect of Ca2+/calmodulin (CaM) on the specific binding of [125I]omega-conotoxin GVIA (125I-omega-CTX) to crude membranes from chick brain was investigated. When we examined the effects of the activation of various endogenous protein kinases on specific [125I]omega-CTX binding to crude membranes, we observed that Ca2+/CaM had an inhibitory effect regardless of whether or not the standard medium contained ATP (0.5 mM). Ca2+/CaM also had an inhibitory effect in a simple binding-assay medium containing HEPES-HCl buffer, BSA, Ca2+ and CaM, and this effect was dependent on the concentration of Ca2+. The effect of Ca2+/CaM was attenuated by the CaM antagonists W-7 and CaM-kinase II fragment (290-309). An experiment with modified ELISA using purified anti omega-CTX antibody indicated that Ca2+/CaM did not affect the direct binding of [125I]omega-CTX and CaM. These results suggest that Ca2+/CaM either directly or indirectly affects specific [125I]omega-CTX binding sites, probably N-type Ca2+ channels in crude membranes from chick whole brain.

Animals↗
PubMed2000

Anti-metastatic efficacy and safety of MMI-166, a selective matrix metalloproteinase inhibitor.

The anti-metastatic efficacy and safety of a newly-developed matrix metalloproteinase (MMP) inhibitor were examined. MMI-166, a N-sulfonylamino acid derivative, inhibited the enzyme activity of MMP-2, 9, and 14 but not MMP-1, 3 or 7. Daily oral administration of MMI-166 resulted in potent inhibition of metastatic lung colonization of Lewis lung carcinoma injected via the tail vein and liver metastasis of C-1H human colon cancer implanted into the spleen at inhibition levels of 43% and 63%, respectively. Daily administration of MMI-166 also resulted in prolonged survival of mice given intraperitoneal implantation of Ma44 human lung cancer cells. The anti-metastatic activity of MMI-166 was as effective as that of other MMP inhibitors with broad inhibitory spectrum. MMI-166 did not affect in vitro tumor cell growth. Neither body weight losses nor hematotoxicity was observed during long-term treatment, indicating the safety of MMI-166 in mice. These results indicate that the selective MMP inhibitor MMI-166 has therapeutic potential as an anti-metastasis agent.

Animals↗
PubMed2000

Characteristics of the inhibitory effect of calmodulin on specific [125i]omega-conotoxin GVIA binding to crude membranes from chick brain.

The characteristics of the inhibitory effect of calcium ion (Ca2+)/calmodulin (CaM) on specific [125I]-omega-conotoxin GVIA (125I-omega-CTX) binding and on the labeling of 125I-omega-CTX to crude membranes from chick brain were investigated. The inhibitory effect of Ca2+/CaM depended on the concentrations of free Ca2+ and CaM. The IC50 values for free Ca2+ and CaM were about 2.0 x 10(-8) M and 3.0 microg protein/ml, respectively. The inhibitory effect of Ca2+/CaM was attenuated by the CaM antagonists W-7, prenylamine and CaM-kinase II fragment (290-309), but not by the calcineurin inhibitor FK506. Ca2+/CaM also inhibited the labeling of a 135-kDa band (which was considered to be part of N-type Ca2+ channel alpha1 subunits) with 125I-omega-CTX using a cross-linker. These results suggest that Ca2+/CaM affects specific 125I-omega-CTX binding sites, probably N-type Ca2+ channel alpha1 subunits, in crude membranes from chick whole brain.

Animals↗
PubMed2000

Characterization of immune function and analysis of RAG gene mutations in Omenn syndrome and related disorders.

Omenn syndrome was recently found to be caused by missense mutations in RAG1 or RAG2 gene that result in partial V(D)J recombination activity. Although the clinical hallmarks of the disease are well defined, there have been several cases with clinical findings similar to, but distinct from Omenn syndrome. The data on immune functions and RAG gene mutations of such cases are limited. We described five Japanese infants from four unrelated families, including two cases of Omenn syndrome and three cases of related disorders. Sibling cases with typical Omenn phenotype were found to be compound heterozygotes of R396C and L885R mutations in RAG1. The former has been reported in European cases and may constitute a hot spot. The latter is a novel missense mutation. Infants with related disorders exhibited erythroderma, eosinophilia, hypogammaglobulinaemia, decreased number of B cells and skewing to Th2, and their lymph node specimens showed architectural effacement, lymphocyte depletion and histiocytic hyperplasia, each of which is seen characteristically in Omenn syndrome. However, in these cases serum IgE levels were low or undetectable. We found no mutation in RAG genes except for a K820R substitution in RAG1, which was regarded to be a functional polymorphism, in two of these cases. Our study suggests that RAG missense mutation may be a genetic abnormality unique to Omenn syndrome with characteristic clinical and laboratory findings. Variations of Omenn syndrome, or related disorders, may represent a different type of immunodeficiency, distinct from abnormalities in lymphoid-specific recombinase activity.

Apoptosis↗
PubMed2000

Up-regulation of monocyte chemoattractant protein-1 in tubulointerstitial lesions of human diabetic nephropathy.

BACKGROUND: We previously described that monocyte chemoattractant protein-1 (MCP-1) plays an important role in progressive glomerular and interstitial damage in inflammatory renal diseases. However, the expression of MCP-1 in diabetic nephropathy remains to be investigated. METHODS: We examined whether locally expressed MCP-1 participates in human diabetic nephropathy via recruiting and activating monocytes/macrophages (Mphi). Urinary and serum MCP-1 levels were measured by enzyme-linked immunosorbent assay in 45 patients with diabetic nephropathy. The presence of MCP-1 in diseased kidneys was determined by immunohistochemical and in situ hybridization analyses. RESULTS: Urinary MCP-1 levels were significantly elevated in patients with diabetic nephrotic syndrome and advanced tubulointerstitial lesions. Moreover, urinary levels of MCP-1 were well correlated with the number of CD68-positive infiltrating cells in the interstitium. In contrast, serum MCP-1 levels remained similar to those of healthy volunteers. Furthermore, we detected the MCP-1-positive cells in the interstitium of diabetic nephropathy via both immunohistochemical and in situ hybridization analyses. CONCLUSION: These observations suggest that locally produced MCP-1 may be involved in the development of advanced diabetic nephropathy, especially in the formation of tubulointerstitial lesions possibly through Mphi recruitment and activation. Moreover, up-regulation of MCP-1 may be a common pathway involved in the progressive tubulointerstitial damage in diabetic nephropathy as well as inflammatory renal diseases.

Adolescent↗
PubMed2000

Preprimed artificial lung for emergency use.

We investigated the possibility of preprimed storage of an artificial lung (AL), aiming at facilitating its emergency use. Test ALs, consisting of a special microporous hollow fiber membrane made of polyolefin in which direct blood-gas contact was completely eliminated, were preprimed with saline solution, sterilized by gamma-ray irradiation, and evaluated after 1-3 months of storage at room temperature. A small amount of bubble was noted in the priming solution after storage in some ALs, which most likely originated from the air dissolved in the priming solution or persisted in the liquid compartment at priming. Although the preprimed solution contained several polyolefin-breakdown products due to irradiation, including ethyl alcohol, n- and t-butyl alcohol, acetone, and carbon dioxide, the levels of these substances were at concentrations known to be not toxic. Endotoxin concentration was negligible. In SEM observation, no perceptible microstructural change was observed in the hollow fibers after preprimed storage. Maximum tensile stress and ultimate elongation of the hollow fiber in the test ALs were reduced by approximately 20% and 3%, respectively, from those of the control AL. The influence of preprimed storage on gas-exchange function was examined in a venoarterial bypass animal study using a goat. Oxygen transfer function was well preserved whereas carbon dioxide removal function was slightly lowered according to the storage term in the stored ALs compared with those of a nonpreprimed control AL. On the basis of these results, we conclude that preprimed storage of the AL with gamma-ray sterilization is basically feasible and realistic.

1-Butanol↗
PubMed2000

Evaluation of the vestibular aqueduct in vestibulocochlear disorders by magnetic resonance imaging.

The visibility of the vestibular aqueduct (VA) was examined using magnetic resonance imaging (MRI) in 95 patients: 15 patients with Meniere's disease, 4 with vestibular Meniere's disease, 4 with cochlear Meniere's disease and 72 patients with other vestibular and/or cochlear disorders. In order to visualize the VA, the T2-weighted image (T2WI) and the proton-density weighted image (PDWI) were obtained in the sagittal plane with a head coil. The visibility of the VA was classified into 4 grades, i.e. grade 0 (not visible), grade 1 (partially visible with PDWI), grade 2 (partially visible with T2WI) and grade 3 (clearly visible with T2WI). The visibility of the VA was significantly lower bilaterally in Meniere's disease, vestibular Meniere's disease, cochlear Meniere's disease and idiopathic bilateral sensorineural hearing loss (IBSNHL) than in the other diseases. The differences among Meniere's disease, vestibular Meniere's disease and cochlear Meniere's disease were not significant. The significance of decreased visibility in IBSNHL is unknown so far. The VA studies using MRI strongly suggest that the pathogenesis of Meniere's disease, vestibular Meniere's disease, cochlear Meniere's disease and IBSNHL is, at least in part, related to the findings of the VA.

Adolescent↗
PubMed2000

Myxofibrosarcoma with an infiltrative growth pattern: a case report.

Myxofibrosarcoma, also known as a myxoid variant of malignant fibrous histiocytoma, is one of the most common sarcomas in the extremities of elderly people and is characterized by a high frequency of local recurrence. We report a case of myxofibrosarcoma, intermediate grade, involving the thigh along the fascial plane and between the muscles without the formation of an apparent nodular lesion. On microscopic examination, the tumor lacked areas of necrosis and pronounced cellular pleomorphism, but it was highly cellular with proliferation of spindle cells which contained large elongated, hyperchromatic and irregularly shaped nuclei, slightly eosinophilic cytoplasm and indistinct cell margins, arranged in both interlacing fascicles and a storiform pattern. Immunohistochemically, many of the tumor cells showed intense reactivity to vimentin and CD34. More than 20% of the cells were positive for p53 protein and the MIB-1 labeling index was approximately 30%. Desmin, alpha-smooth muscle actin, muscle-specific actin, S-100 protein, cytokeratin, epithelial membrane antigen, bcl-2 protein and neurofilament were negative. The absence of a discrete mass lesion and diffuse infiltrative nature precluded early recognition of tumor. Seven years after hindquarter amputation, the patient has been alive without evidence of local recurrence or distant metastasis. This case indicates that myxofibrosarcoma can demonstrate a highly infiltrative growth pattern. It is possible that this infiltrative nature is associated with a high rate of local recurrence of the tumor. A careful radiological examination of the extension of the tumor prior to surgery is mandatory considering the infiltrative nature of myxofibrosarcoma.

Aged↗
PubMed2000

Enantiodifferentiating Z-E photoisomerization of cyclooctene sensitized by DNA and RNA.

DNA and RNA have been shown for the first time to function as chiral photosensitizers in aqueous solution, to effect the enantiodifferentiating photoisomerization of (Z)-cyclooctene (1Z), giving the chiral (E)-isomer in enantiomeric excesses (ee's) of up to 15%. In order to elucidate the effect of nucleotide sequence, enantiodifferentiating photoisomerization of 1Z was also performed using oligo and homopolynucleotides as chiral sensitizer. The -18.8% ee was observed by using d(T)15.d(A)15 as sensitizer, whereas sensitization by the poly(U).poly(A) duplex gave only racemic (E)-cyclooctene. From these results, oligothymidine sequence is essential for efficient enantioselective photoisomerization of 1Z.

Animals↗
PubMed2000

Solid-phase synthesis of deoxyribonucleotides having a cap structure analog.

In this study, the solid-phase synthesis of oligodeoxyribonucleotides having a guanosine pyrophosphate cap structure (Gpp-) was achieved by using a new guanosine monophosphate unit having the DMTr group capable of estimation of coupling efficiency of the pyrophosphate bond formation. Since 7-methylguanosine base was unstable under basic conditions, Gpp-capped DNA oligomers were synthesized by using a new linker having a silanediyl bond, which allowed to release the DNA chain from the solid support by treatment with fluoride anion under neutral conditions.

Methods↗