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Biomedical subjects

M Toda

Publications and source records attributed to M Toda.

At least 19 recordsLinked to original sources
PubMed2005

Effect of coffee intake on blood flow and maternal stress during the third trimester of pregnancy.

OBJECTIVE: To investigate the effects of maternal ingestion of an ordinary dose of coffee on maternal stress and placental and fetal blood circulation during the third trimester of pregnancy. METHODS: We performed a Doppler blood flow analysis for 10 women in the third trimester of pregnancy before and after they drank a cup of coffee. Salivary samples were collected from the 10 pregnant women and 14 nonpregnant controls just before coffee intake and 30 min later. Salivary cortisol levels and chromogranin A titers were determined. RESULTS: Coffee intake had no effect on maternal or fetal blood flow. Among the pregnant women, Salivary cortisol levels were significantly reduced after coffee intake but salivary chromogranin A concentration was not significantly different before and after coffee intake. CONCLUSION: The reduced salivary cortisol levels suggest that coffee intake decreases maternal stress during pregnancy.

Arteries↗
PubMed2003

Intractable malleolar bursitis treated with lateral calcaneal artery adipofascial flap.

Infections of the malleolar bursa, which is an adventitious bursa, rarely progress to intractable infectious bursitis. We present two cases of intractable malleolar bursitis. We performed successful transplantation of the lateral calcaneal artery adipofascial flap that resulted in healing of the bursitis. We discuss classification of bursae, treatments for bursitis and characteristics of the lateral calcaneal artery adipofascial flap.

Aged↗
PubMed2003

Contrasting patterns of genetic variation in the two sympatric geckos Gekko tawaensis and G. japonicus (Reptilia: Squamata) from western Japan, as revealed by allozyme analyses.

Allozyme variation in two congeneric sympatric geckos, Gekko tawaensis and G. japonicus, from western Japan was examined. These species show similar densities and spatial arrangements of populations in this region, and their genetic structures are thus expected to have been formed under the influences of comparable geohistorical, environmental, and demographic factors. Results of the analyses, however, revealed strikingly different genetic patterns in the two species. Populations of G. tawaensis invariably showed a remarkably lowered heterozygosity (0-0.017) compared to G. japonicus (0.089-0.124). On the other hand, the genetic heterogeneity among populations is much greater in G. tawaensis (F(ST)=0.726) than in G. japonicus (F(ST)=0.101). The Mantel test failed to detect any significant correlations between log (estimated migration rate) and log (geographic distance) in either species, or between matrices of interpopulation pairwise F(ST) for the two species. These results suggest that, in each species, formation of the current genetic structure in western Japan has been chiefly influenced by stochastic factors, rather than the geohistorical architecture of this region. The high F(ST) and low heterozygosity in G. tawaensis suggest the effects of severe local fragmentation. On the other hand, the relatively low F(ST) and high heterozygosity in G. japonicus imply extensive gene flow among populations. Absence of significant correlations between the estimated migration rate and geographic distance in G. japonicus may suggest that such gene flow is promoted by human-mediated transport of this primarily house-dwelling lizard.

Animals↗
PubMed2003

Analysis of sequential immunoglobulin E-binding epitope of Japanese cedar pollen allergen (Cry j 2) in humans, monkeys and mice.

BACKGROUND: Japanese cedar (Cryptomeria japonica; CJ) pollinosis has been reported to occur naturally in Japanese monkeys (Macaca fuscata) as well as in humans. Most human patients and monkeys with pollinosis have specific IgE for Cry j 2, a major allergen of CJ pollen. OBJECTIVE: The main purpose of this study was to identify IgE B cell epitopes of Cry j 2 using a synthetic peptide in humans, monkeys and mice. METHODS: We synthesized 38 overlapping peptides that span the entire length of Cry j 2. We examined the B cell epitopes of Cry j 2 that are recognized by IgE in the sera of human patients and monkeys with pollinosis and immunized mice using synthetic peptides of Cry j 2. We also examined the reaction of Cry j 2-specific mouse monoclonal IgG antibodies to the peptides. Furthermore, we conducted a histamine release assay with leucocytes from a pollinosis patient using human serum albumin (HSA) conjugated with the peptides as a B cell epitope. RESULTS: We found that 16 of the 20 pollinosis patients who had specific IgE to Cry j 2 also exhibited IgE reaction with some Cry j 2 peptides. Of these 16 patients, 10 exhibited IgE reaction with Cry j 2 peptide no. 13 (121GQCKWVNGREICNDRDRPTA140). Five of the seven monkeys with CJ pollinosis exhibited a reaction with peptide no. 13. Furthermore, IgE in mice immunized with Cry j 2 and two mouse monoclonal IgG antibodies reacted with peptide no. 13. Peptide no. 13-conjugated HSA showed the release of histamine from basophils. Furthermore, to determine the minimum epitope in peptide no. 13, we conducted an enzyme-linked immunosorbent assay inhibition test. The core of the epitope in humans, monkeys and mice was 124KWVNGREI131. CONCLUSION: We found that 124KWVNGREI131 is an important B cell epitope recognized by IgE in humans, monkeys and mice.

Animals↗
PubMed2001

Increase of oligodendrocyte progenitor cells after spinal cord injury.

The reaction of oligodendrocyte progenitor cells (OPCs) after spinal cord injury (SCI) is poorly understood. In this study, we examined oligodendroglial reactions after contusion SCI in adult rats by immunohistochemistry. OPCs were identified by staining with monoclonal antibodies (mAbs) A2B5 and O4. Each of the A2B5-, O4-positive OPCs and galactocerebroside-positive oligodendrocytes dramatically increased in the lesion of the dorsal posterior funiculus. Bromodeoxyuridine (BrdU) incorporation studies showed that most O4-positive cells in the lesion were labeled with BrdU, suggesting that these OPCs were proliferative. In contrast, the expression of myelin basic protein was decreased in the lesion compared with controls that received laminectomy only. From the injured cord, OPCs were isolated by immunopanning with mAb A2B5. We observed an increased number of OPCs from the injured spinal cords compared with those isolated from controls and unoperated animals. After several days in culture, the OPCs from the lesion expressed galactocerebroside. These results suggest that OPCs are induced and can differentiate following SCI in the adult rat.

Animals↗
PubMed2001

Structure-activity study and analgesic efficacy of amino acid derivatives as N-type calcium channel blockers.

The synthesis and structure-activity relationship (SAR) study of a novel series of N-type calcium channel blockers are described. L-Cysteine derivative 2a was found to be a potent and selective N-type calcium channel blocker with IC(50) 0.63 microM on IMR-32 assay. Compound 2a showed analgesic efficacy in the rat formalin-induced pain model by intrathecal and oral administration.

Amino Acids↗
PubMed2001

Design and synthesis of a highly selective EP2-receptor agonist.

EP2-receptor selective agonist 3 was identified by the structural hybridization of butaprost 1a and PGE(2) 2a. Based on this information, a chemically more stabilized 4 was discovered as another highly selective EP2-receptor agonist, iv administration of which to anesthetized rats suppressed uterine motility, while PGE(2) 2a stimulated uterine motility.

Alprostadil↗
PubMed2001

Development of orally active nonpeptidic inhibitors of human neutrophil elastase.

5-Amino-2-phenylpyrimidin-6-ones, some of their desamino derivatives, and miscellaneous derivatives were synthesized and biologically evaluated on both in vitro activity and oral activity in an acute hemorrhagic assay. These compounds contained an alpha-keto-1,3,4-oxadiazole moiety to bind covalently to the Ser-195 hydroxy group of human neutrophil elastase (HNE). Among those tested, compounds 11a-c,e,i-l(F), 11d,e,k(H), 21d,e,k(F), and 21d,e(H) showed a good oral profile. RS-Mixture 3(H) was selected for clinical evaluation based on its oral potency, duration of action, enzyme selectivity, safety profile, and ease of synthesis. Structure-activity relationships (SARs) are discussed.

Administration, Oral↗
PubMed2001

Expression of the neural RNA-binding protein Musashi1 in human gliomas.

Tumor cells arising from a particular tissue may exhibit the same gene expression patterns as their precursor cells. To test this proposition, we have analyzed the expression of a neural RNA-binding protein, Musashi1, in primary human central nervous system (CNS) tumors. In rodents, Musashi1 is expressed predominantly in proliferating multipotent neural precursor cells, but not in newly generated postmitotic neurons. The expression of Musashi1 is downregulated with the successive progression of neurogenesis. In normal adult human tissues, we detected low levels of Musashi1 expression in brain and testis by RT-PCR analysis. In an RNA panel of 32 cancer tissues and cell lines, elevated expression of Musashi1 was seen in all five malignant gliomas studied, in contrast to the slight expression seen in other tumor cells, including those in several melanomas and a prostate cancer. Western blot analysis showed strong Musashi1 expression in malignant gliomas compared with nonneoplastic brain tissue. Glioblastomas, the most malignant form of glioma, showed higher Musashi1 expression than less malignant gliomas by immunohistochemical analysis. Tumors with strong Musashi1 expression tended to have high proliferative activity. Thus, the expression of Musashi1 correlated with the grade of the malignancy and proliferative activity in gliomas. These results suggest that primary CNS tumors may share gene expression patterns with primitive, undifferentiated CNS cells and that Musashi1 may be a useful marker for the diagnosis of CNS tumors.

Adult↗
PubMed2001

Analysis of the canine IgE-binding epitope on the major allergen (Cry j 1) of Japanese cedar pollen with anti-Cry j 1 monoclonal antibodies.

In our previous study [Immunology 91 (1997) 161] using monoclonal antibodies (mAbs) specific to Cry j 1, a major allergen in Japanese cedar (Cryptomeria japonica) pollen, we identified five independent epitopes (EP-1-EP-5) on the molecule and found that EP-1 and EP-5 are the predominant allergic epitopes for humans and monkeys, respectively. In this study, we analyzed the epitopes recognized by IgE in the sera of 10 dogs sensitive to C. japonica pollen allergen using an IgE-ELISA inhibition method with these mAbs. The IgE reaction patterns varied among dogs. In eight of the 10 dogs, IgE recognized EP-5 which is a predominant allergic epitope for monkeys with the pollenosis. In four dogs, IgE recognized EP-1 which is a predominant allergic epitope for human patients with the pollenosis. In three dogs, IgE recognized EP-4 which is a heat-stable epitope. EP-5 is a predominant allergic epitope for dogs and some, but not all, dogs have IgE reaction patterns to the epitopes similar to those of humans.

Allergens↗
PubMed2001

Usefulness of endoscopic ultrasonography (EUS) in diagnosing esophageal infiltration of thyroid cancer.

Pre-operative evaluation of esophageal infiltration is sometimes difficult in patients with advanced thyroid cancer even with recent imaging modalities. We evaluated the accuracy of endoscopic ultrasonography (EUS) in diagnosing esophageal infiltration of thyroid cancer. Twenty-nine patients with advanced thyroid cancer underwent EUS and other imaging examinations before surgery. The diagnostic accuracy of EUS was compared with that of magnetic resonance imaging (MRI) and esophagography based on pathologic findings in 27 of the 29 cases. EUS clearly demonstrated the 5-layer structure of the esophageal wall. EUS detected cancer invasion into the muscularis propria of the esophagus correctly in 8 of 10 patients diagnosed pathologically with muscular infiltration. EUS was significantly more accurate than MRI and esophagography (88.9% vs 63.0% and 66.7%, respectively). The specificity of EUS was also significantly better than the specificities of MRI or esophagography (94.1% vs 58.8% and 64.7%, respectively). The sensitivity, positive predictive value and negative predictive value of EUS tended to be better than those of MRI and esophagography. EUS is useful in evaluating the esophageal infiltration of thyroid cancer. This method has the further advantage of detecting the exact depth of cancer invasion into the esophageal wall.

Adenocarcinoma, Follicular↗
PubMed2001

The crystal structure of the complex of non-peptidic inhibitor of human neutrophil elastase ONO-6818 and porcine pancreatic elastase.

The crystal structure of a new inhibitor of human neutrophil elastase (HNE), N-[2-[5-(tert-butyl)-1,3,4-oxadiazol-2-yl]-(IRS)-1-(methylethyl)-2-oxoethyl]-2-(5-amino-6-oxo-2-phenyl-6H-pyrimidin-1-ly)acetamide (ONO-6818, 1) complexed to porcine pancreatic elastase (PPE) has been determined at 1.86 A resolution. Analytical results provided evidence of a 1:1 complex in which the electrophilic ketone of 1 covalently bound to O gamma of Ser195 at the active site of PPE. The role of the unique electron-withdrawing ketone of 1 has been elucidated.

Animals↗
PubMed2001

Design and synthesis of new orally active inhibitors of human neutrophil elastase.

To identify new orally active inhibitors, further modification of 1 (ONO-6818) was performed. Peptidic derivatives 4b, 4c and 4n showed more potent inhibitory activity than nonpeptidic derivatives 3a-c. As a result, a series of peptidic inhibitors, 4a-s and 5a-v, were discovered. Among these N-aryl derivatives 5a-g, 5i, 5m and 5o-v showed oral activity. Their oral activity showed good correlation with their metabolic stability. Compounds 5h and 5j-l, which were extremely metabolically unstable in hamster plasma, did not show oral activity. Oral activity was considered to be determined by a combination of at least two factors: oral absorption and metabolic stability.

Administration, Oral↗
PubMed2001

Predictive risk factors for postoperative tetany in female patients with Graves' disease.

BACKGROUND: Postoperative tetany occurs in patients with secondary hyperparathyroidism caused by a deficiency in calcium and vitamin D concomitant with transient hypoparathyroidism induced by surgery. In the present study, we further clarified the risk factors by referring to serum 25-hydroxyvitamin D [25(OH)D] and alkaline phosphatase. STUDY DESIGN: The serum levels of intact parathyroid hormone, calcium and other electrolytes, and 25-hydroxyvitamin D [25(OH)D] were measured preoperatively in 178 female patients with Graves' disease who underwent subtotal thyroidectomy. RESULTS: Of the 178 female patients, 15 (8.4%) developed tetany. Univariate analysis of 16 possible risk factors showed that 2 were statistically significant: serum 25(OH)D and alkaline phosphatase levels. The incidence of tetany according to the serum levels of 25(OH)D and alkaline phosphatase was 19.1% (9/47) in patients with 25(OH)D < or = 25 nmol/L and alkaline phosphatase > 155, 11.8% (4/34) in those with 25(OH)D < or = 25 nmol/L and alkaline phosphatase < or = 155, 6.7% (2/30) in those with 25(OH)D > 25 nmol/L and alkaline phosphatase > 155, and 0% (0/50) in those with 25(OH)D > 25 nmol/L and alkaline phosphatase < or = 155. CONCLUSIONS: Patients with Graves' disease who have vitamin D deficiency with high serum alkaline phosphatase levels are the highest-risk group for postoperative tetany. Serum 25(OH)D and alkaline phosphatase should be monitored in patients with Graves' disease.

Adolescent↗
PubMed2001

Immunologic tolerance maintained by CD25+ CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance.

There is accumulating evidence that T-cell-mediated dominant control of self-reactive T-cells contributes to the maintenance of immunologic self-tolerance and its alteration can cause autoimmune disease. Efforts to delineate such a regulatory T-cell population have revealed that CD25+ cells in the CD4+ population in normal naive animals bear the ability to prevent autoimmune disease in vivo and, upon antigenic stimulation, suppress the activation/proliferation of other T cells in vitro. The CD25+ CD4+ regulatory T cells, which are naturally anergic and suppressive, appear to be produced by the normal thymus as a functionally distinct subpopulation of T cells. They play critical roles not only in preventing autoimmunity but also in controlling tumor immunity and transplantation tolerance.

Animals↗
PubMed2001

Combination suicide/cytokine gene therapy as adjuvants to a defective herpes simplex virus-based cancer vaccine.

We have used syngeneic, established bilateral subcutaneous tumor models to examine the antitumor activity of herpes simplex virus (HSV) vectors, including the induction of an immune response against non-inoculated distant tumors. In such a model with CT26 murine colon adenocarcinoma, unilateral intratumoral inoculation of replication-deficient HSV-1 tsK inhibited the growth of both the inoculated and noninoculated established tumors. To enhance this limited antitumor immune response, we generated a defective HSV vector, dvIL12-tk encoding both interleukin-12 (IL-12) and HSV thymidine kinase (TK), with tsK as the helper virus. In a 'suicide gene' strategy, ganciclovir (GCV) treatment after intratumoral inoculation of dvlacZ-tk/tsK, encoding E. coli lacZ instead of IL-12, resulted in enhanced antitumor activity. Antitumor activity was also enhanced by local expression of IL-12 from dvIL12-tk/tsK. The combination of IL-12 cytokine therapy with GCV treatment was the most efficacious approach, with significantly greater inhibition of tumor growth than IL-12 or TK + GCV alone. These results illustrate the power of combining different cancer therapy approaches; 'suicide gene' therapy, cytokine therapy, and HSV vector infection. HSV vectors are particularly well suited to this because they can accommodate the insertion of large and multiple gene sequences.

Adenocarcinoma↗