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Biomedical subjects

T Toda

Publications and source records attributed to T Toda.

At least 217 records · Page 12Linked to original sources
PubMed1994

A rare case of achalasia coexistent with sigmoid megacolon and associated with epilepsy.

A case of achalasia coexistent with sigmoid megacolon in a 38-year-old man with known epilepsy is described. The patient was referred to the Ryukyu University Hospital with a 4-year history of dysphagia and heartburn and a 1-year history of abnormal bowel movement. On admission, upper gastrointestinal (GI) series demonstrated a dilated, tortuous thoracic esophagus with a flask-type configuration. Barium enema studies showed a dilated sigmoid colon from the rectosigmoid junction to the descending colon. Myotomy (modified Jekler-Lhotka's procedure) for achalasia and simple sigmoidectomy for sigmoid megacolon were carried out. The biopsied wall of the narrowed esophageal segment at operation showed decreased numbers of ganglion cells in Auerbach's plexus and atrophy of the muscle fibers. The resected dilated sigmoid colon revealed degeneration and markedly decreased numbers of ganglion cells in Auerbach's and Meissner's plexuses. The patient's postoperative course was uneventful and he has been doing well since surgery. The present case is very interesting and to our knowledge, such a case is rare in the literature. We believe that the abnormalities of the ganglion cells may be due to the same etiologic factor as the sigmoid megacolon. The association of the two pathologic processes is discussed, together with a brief review of the literature.

Adult↗
PubMed1994

Confocal scanning laser microscopy of morphometric human sperm parameters: correlation with acrosin profiles and fertilizing capacity.

OBJECTIVES: To develop quantitative criteria for assessing sperm morphology and to determine the correlation between the percentage of morphologically normal spermatozoa and the outcome of the sperm hypo-osmotic swelling test, sperm acrosin profile, and sperm capacity for fertilization. DESIGN: The maximal length and width of the sperm head, the length of the midpiece and principal piece of the sperm tail, and the ratio of the surface of the acrosomal region to the total surface of the head were determined in specimens obtained from a group of infertile men and a group of fertile men using a confocal scanning laser microscope. Group A consisted of 53 infertile men who were participating in an IVF program, and group B consisted of 98 fertile men. The mean +/- 2 SD of the morphometric parameters in group B was established as representing the lowest and highest normal values in both groups. A normal spermatozoon was defined as one with morphometric parameters within normal levels. The lowest percentage of morphologically normal spermatozoa, hypo-osmotic swelling test result, and acrosin activity in group B were also taken as the lowest normal values in group A. SETTING: In vitro fertilization program at the Tottori University School of Medicine, Yonago, Japan. MAIN OUTCOME MEASURES: Sperm morphometric parameters, percentage of morphologically normal spermatozoa, hypo-osmotic swelling test, and acrosin activity. RESULTS: The length of the midpiece, ratio (x 100) of the surface of the acrosomal region to the total surface of the sperm head, percentage of morphologically normal spermatozoa, outcome of hypo-osmotic swelling test, and acrosin activity were significantly higher in group B than in group A. The maximal width of the head was significantly lower in group B than in group A. Strongly positive correlations were observed between percentage of morphologically normal spermatozoa or length of midpiece and the proportion of fertilized oocytes in group A and between ratio (x 100) of the surface of the acrosomal region to the total surface of the head and acrosin activity in groups A and B. Sperm morphology showed high positive and negative predictive values for acrosin activity (normal/abnormal) and fertility potential (present/absent). CONCLUSIONS: Using quantitative strict criteria, we found that sperm morphology was an important predictor of sperm fertilizing capacity. The confocal scanning laser microscope provided useful information about the sperm cytoskeleton and its importance in fertilization.

Acrosin↗
PubMed1994

Isolation and characterization of a novel gene encoding nuclear protein at a locus (D11S636) tightly linked to multiple endocrine neoplasia type 1 (MEN1).

To identify a gene responsible for multiple endocrine neoplasia type 1 (MEN1), we attempted to isolate potentially transcribable fragments from cosmid clones derived from a region on chromosome 11q13 where genetic linkage studies and analyses of loss of heterozygosity in MEN1-associated tumors have localized the MEN1 gene. By an exon-amplification method, we recovered three exon-like sequences from one of these clones, cCI11-367, and using these sequences as probes we were able to isolate new clones from cerebrum, cerebellum, and fetal-liver cDNA libraries. Sequence analysis of these cDNA clones revealed that the transcribed gene, designated ZFM1, encodes a novel 623-amino-acid protein containing domains with interesting structural properties including a nuclear transport domain, a metal binding motif, and glutamine- and proline-rich regions. Analysis by the reverse-transcriptase polymerase chain reaction (RT-PCR) indicated that this gene is expressed in various tissues including endocrine organs such as thyroid gland, pancreas, adrenal gland, and ovary. These data suggest that ZFM1 might be a candidate for mutations that cause MEN1.

Amino Acid Sequence↗
PubMed1994

The inhibitory effects of cephalosporin and dipeptide on ceftibuten uptake by human and rat intestinal brush-border membrane vesicles.

The types of inhibitory effects caused by compound V (an analogue of ceftibuten) and alanylproline (dipeptide) on the uptake of ceftibuten by brush-border membrane vesicles (BBMV) prepared from human and rat small intestine were analysed. In the presence of an inward H(+)-gradient, the initial uptake rate of ceftibuten by both human and rat intestinal BBMV was concentration-dependent with apparent Km and Vmax values of 0.35 mM and 2.052 nmol (mg protein)-1 min-1 for human BBMV, and 0.50 mM and 3.056 nmol (mg protein)-1 min-1 for rat BBMV, respectively. For both human and rat BBMV, kinetic analysis by Dixon and Lineweaver-Burk plots demonstrated that the uptake of ceftibuten was competitively inhibited by compound V, whereas inhibition by alanylproline was noncompetitive or partially competitive. These results suggest that there is a stereospecific transport system which is common to ceftibuten and compound V, and that this system is not identical to the carrier system for the dipeptide, alanylproline.

Animals↗
PubMed1994

Fission yeast protein kinase C gene homologues are required for protoplast regeneration: a functional link between cell wall formation and cell shape control.

Two novel protein kinase C (n PKC) gene homologues, pck1+ and pck2+ were isolated from the fission yeast Schizosaccharomyces pombe (Toda et al. (1993) EMBO J. 12, 1987). We examined the functional differences of pck1+ and pck2+ in cell wall formation and actin organization of S. pombe. Regenerating protoplasts of a wild-type strain, single gene disruptants of pck1+ (delta pck1) and pck2+ (delta pck2) were used as a simple model to examine the functional links between PKC, cell wall formation and actin organization. Protoplasts of the wild-type strain and those of delta pck1 reverted to intact cells in osmotically stabilized liquid medium. A close spatial association between new cell wall formation and actin was observed in these two strains. In delta pck2, protoplasts did not revert to intact cells: (1) scarcely any new cell wall material was formed; (2) actin was not reorganized; and (3) nuclear division and an increase in the amount of cytoplasm were observed in the regenerating protoplasts. These findings demonstrate that the pck2+ gene has a function essential for protoplast regeneration but the pck1+ gene does not. Involvement of n PKCs in cell wall formation and actin organization was also clarified. The effect of staurosporine (a potent inhibitor of protein kinases) on regenerating protoplasts of the three strains confirmed the assumption that the pck2 protein is an in vivo target of staurosporine in the fission yeast.

Actins↗
PubMed1994

A calcineurin-like gene ppb1+ in fission yeast: mutant defects in cytokinesis, cell polarity, mating and spindle pole body positioning.

A calcineurin (type 2B)-like protein phosphatase gene designated ppb1+ was isolated from the fission yeast Schizosaccharomyces pombe. The predicted amino acid sequence was 57% identical to rat PP2B alpha. ppb1 null mutant could form colonies at 33 degrees C but the size of the colonies was small at 22 degrees C. Cytokinesis was greatly delayed at 22 degrees C, and a large number of multi-septate cells were produced. The cell polarity control was impaired, causing branched cells. ppb1 null was virtually sterile. These phenotypes were rescued by a plasmid carrying the ppb1+ gene. Multi-septate cells were also produced in wild type at 22 degrees C by cyclosporin A, an inhibitor of calcineurin. This drug effect was enhanced in stst1 null mutant, which was hypersensitive to various drugs and cations. ppb1 null was not affected by cyclosporin A, consistent with the hypothesis that ppb1 is its target. Double-mutant analysis indicated that ppb1 had a function related to that of two other phosphatases, type 1-like dis2 and 2A-like ppa2.ppb1 null-sts1 null showed the severe multi-septate phenotype in the absence of cyclosporin A. ppb1+ and sts1+ gene functions are related. The double mutant ppb1-sts5 was lethal, indicating that the ppb1+ gene shared an essential function with the sts5+ gene. Overexpression of ppb1+ caused anomalies in cell and nuclear shape, microtubule arrays and spindle pole body positioning in interphase cells. Thus the ppb1+ gene appears to be involved in cytokinesis, mating, transport, nuclear and spindle pole body positioning, and cell shape.

Amino Acid Sequence↗
PubMed1994

Development of a thermoelectric cooling apparatus for high-voltage isoelectric focusing on a cellulose acetate membrane.

To develop an isoelectric focusing apparatus using a cellulose acetate membrane (Separax EF), we have designed a thermoelectric cooling isoelectric apparatus. This apparatus has two characteristics. Firstly, the cooling system was switched to a thermoelectric cooling system from an ice-cooling system. Secondly, the chamber lid of the electrophoretic apparatus was also devised so that samples could be applied without opening the chamber lid. With this apparatus we could perform the isoelectric focusing without worrying about room temperature and humidity in the laboratory. Applying 2000 V for an extra 5 min with our module cooling system, we achieved a much higher degree of resolution with three sheets of cellulose acetate membrane (Separax EF) overlaid for simultaneous electrophoresis. Thus, three types of information could be obtained from only one electrophoretic procedure.

Biocompatible Materials↗
PubMed1994

Effect of 20-methylcholanthrene on the development of atherosclerosis in LAP quails.

We studied the effect of 20-methylcholanthrene, a carcinogen, on atherosclerosis in the ascending aorta and brachiocephalic arteries of hyperlipidemic and atherosclerosis-prone (LAP) quail. A total of 66 quails were divided into 6 groups and fed the following diets: Group I, basal; Group II, basal+low dose of carcinogen; Group III, basal + high dose of carcinogen; Group IV, basal + 0.2% cholesterol; Group V, basal + 0.2% cholesterol + low dose of carcinogen; and Group VI, basal + 0.2% of cholesterol + high dose of carcinogen. The carcinogen was dissolved in corn oil at 2 mg/ml and 4 mg/ml as low and high doses respectively, and was given orally twice weekly. Marked elevation of the serum cholesterol level and significant lipid-rich aortic lesions were observed in all the cholesterol-fed groups after 12 weeks. Although the serum cholesterol level in Group VI was lower than that in Group IV, the severity of the atherosclerotic lesion was greater in the former than in the latter. An immunohistochemical study showed a positive reaction of DBA, PHA and OKM-1 with the lipid-containing cells of aortic intimal lesions.

Animals↗
PubMed1994

The anion-binding exosite is critical for the high affinity binding of thrombin to the human thrombin receptor.

The thrombin receptor has been shown to be a novel member of the family of G-protein coupled receptors (Vu, T.-K. H., Hung, D.T., Wheaton, V.I., and Coughlin, S.R. (1991) Cell 64, 1057-1068). This receptor appears to be activated through a thrombin-mediated proteolytic mechanism which exposes a "tethered ligand" responsible for receptor activation. In order to investigate the initial interactions of thrombin with this receptor, we have constructed cell lines which express high levels of the human thrombin receptor and studied the binding of various forms of thrombin to the cell surface. Analysis of transfected cells with thrombin receptor monoclonal antibodies identified a particular cell line (clone #5-18) which displayed > 150,000 thrombin receptors per cell. Clone #5-18 appeared to express functional receptors since treatment with thrombin resulted in both a 15-20 fold increase of cytoplasmic phosphoinositide levels and a comparable shift in the EC50 of thrombin-mediated calcium mobilization when compared to non-transfected CHO cells. Binding of 125I-alpha-thrombin to clone #5-18 did not reach equilibrium at 37 degrees C. However, direct binding studies of 125I-alpha-, 125I-diisopropylphospho (DIP)-alpha-, and 125I-beta-thrombin to clone #5-18 demonstrated that binding at 4 degrees C was saturable and reversible for each ligand. Analysis of the binding data revealed Kd's of 0.8 nM, 0.7 nM and 9.7 nM for 125I-alpha-, 125I-DIP-alpha- and 125I-beta-thrombin respectively. Association of 125I-alpha-, DIP-alpha, and beta-thrombin could be competed by unlabelled alpha- and DIP-alpha-thrombin. Unlabelled beta-thrombin, which has a modified anion-binding exosite, was a poor competitor for 125I-alpha- and 125I-DIP-alpha-thrombin, but did compete for 125I-beta-thrombin. In addition, the hirudin54-65 peptide competed at submicromolar concentrations for the binding of alpha- and DIP-alpha-thrombin, but not for beta-thrombin. This peptide binds specifically at the anion-binding exosite of alpha-thrombin and has been shown to have a lower affinity for beta-thrombin. These results demonstrate directly a high affinity interaction between thrombin and its receptor, and suggest that an important component is the high affinity association of the thrombin receptor with the anion-binding exosite of thrombin.

Amino Acid Sequence↗
PubMed1994

[An autopsy case of periarteritis nodosa associated with disseminated strongyloidiasis].

An autopsy case of periarteritis nodosa associated with disseminated strongyloidiasis in a 59-year-old woman is reported. The patient had unknown fever of 38 degrees C and marked impairment of renal function, for which pulse therapy of steroid was performed. Electromyogram showed myogenic pattern, and biopsy of the biceps presented necrotizing angitis of small arteries. Renal biopsy showed marked infiltration of lymphocytes in the stroma, and frequent hyalinosis and crescent formation of the glomeruli. Two months after admission, the patient died of respiratory failure associated with sepsis and disseminated intravascular coagulopathy. Postmortem examination disclosed strongyloides stercolaris and fungi in both lungs with extensive hemorrhage. Terminal ileum and ascending colon had multiple erosions, extensive hemorrhage, numerous strongyloides stercolaris, and frequent necrotizing angitis in the mucosa. Necrotizing angitis was also demonstrated in both kidneys.

Animals↗
PubMed1994

[Expression of PDGF-A and -B in human coronary atherosclerotic lesion: immunohistochemical and in situ hybridization study].

We studied the role of platelet-derived growth factor (PDGF) on the development of atherosclerosis of human coronary arteries of 63 autopsied cases. Smooth muscle cells in fibrocellular intimal thickening lesion showed no significant immunohistochemical reaction of antibodies for PDGF-A or PDGF-B or PDGF-receptor. In atherosclerotic lesions, foam cells derived from macrophages and smooth muscle cells showed intense immunohistochemical reaction with antibodies of PDGF-B and PDGF-receptor, but not with that of PDGF-A. By in situ hybridization, no significant signals of PDGF-A or PDGF-B or PDGF-receptor were demonstrated in proliferating intimal smooth muscle cells in fibrocellular intimal thickening lesions. Uncomplicated atherosclerotic lesions expressed significant amount of m-RNA of c-sis protooncogene and PDGF-B receptor in foam cells. However, no significant signals of PDGF-A were observed in uncomplicated atherosclerotic lesions. These results suggest that foam cells-producing PDGF-B play an important role for the progression of atherosclerotic lesions in human coronary arteries.

Coronary Artery Disease↗
PubMed1994

Refined mapping of a gene responsible for Fukuyama-type congenital muscular dystrophy: evidence for strong linkage disequilibrium.

Fukuyama-type congenital muscular dystrophy (FCMD), the second most common form of childhood muscular dystrophy in Japan, is an autosomal recessive severe muscular dystrophy associated with an anomaly of the brain. After our initial mapping of the FCMD locus to chromosome 9q31-33, we further defined the locus within a region of approximately 5 cM between loci D9S127 and CA246, by homozygosity mapping in patients born to consanguineous marriages and by recombination analyses in other families. We also found evidence for strong linkage disequilibrium between FCMD and a polymorphic microsatellite marker, mfd220, which showed no recombination and a lod score of (Z) 17.49. A "111-bp" allele for the mfd220 locus was observed in 22 (34%) of 64 FCMD chromosomes, but it was present in only 1 of 120 normal chromosomes. This allelic association with FCMD was highly significant (chi 2 = 50.7; P < .0001). Hence, we suspect that the FCMD gene could lie within a few hundred kilobases of the mfd220 locus.

Chromosome Mapping↗
PubMed1993

The inhibitory effect of substance P antagonist, CP-96,345, on the late discharges of nociceptive neurons in the rat superficial spinal dorsal horn.

The effects of local spinal applications of the substance P antagonist, CP-96,345, on the electrically-evoked discharges of nociceptive neurons were examined in the superficial spinal dorsal horn of adult rats anesthetized with sodium pentobarbital. Extracellular single-unit recordings were made from lumbar spinal dorsal horn neurons which were excited by noxious mechanical stimulation and had early and late discharges evoked by A- and C-fiber inputs, respectively, following transcutaneous electrical stimulation. CP-96,345 was applied directly onto the surface of the spinal cord close to the recording sites. A dose of 50 nmol of CP-96,345 drastically inhibited the late discharges of 80% of neurons, without affecting early discharges significantly. This study demonstrated the specific inhibitory effect of CP-96,345 on the late discharges of a restricted population of spinal dorsal horn neurons. These results illustrate the important role of substance P in nociceptive transmission mediated by primary afferent C-fibers in normal acute pain.

Animals↗
PubMed1993

Lipoprotein and apoprotein profile of Japanese quail.

The present study delineated the lipoprotein and apoprotein distribution in Japanese quail. Quail lipoprotein was composed of three fractions: VLDL, d < 1.020; LDL, 1.020 < d < 1.081; HDL, 1.081 < d < 1.210. When animals were fed the cholesterol-free diet, HDL was the predominant form, LDL intermediate, VLDL and chylomicron were smallest in amount. Feeding of cholesterol induced a marked change in the lipoprotein profile: VLDL or chylomicron predominated over HDL and LDL. An apoprotein of 26 kD (molecular weight) was the major protein moiety comprising more than 50% of total apoprotein in the entire density range of lipoprotein class. Amino acid composition of 26 kD protein was similar to hen, rat and human apo A-I. N-Terminal 36 amino acid sequence of 26 kD protein showed 92% homology to chicken apo A-I and 11% homology to human apo A-1. The 26 kD protein did not react with the antibody raised against human apo A-I. These observation showed that the 26 kD protein was partially identical to apo A-I.

Amino Acid Sequence↗
PubMed1993

A second form (beta isoform) of nucleoside diphosphate kinase from rat. Isolation and characterization of complementary and genomic DNA and expression.

Complementary and genomic clones for a second form (the beta isoform) of rat nucleoside diphosphate kinase were isolated. Structural studies revealed that nucleotide and deduced amino acid sequences of the beta isoform were quite similar to those of the alpha isoform (identities were 82 and 89%, respectively), which were delineated in our previous study (Kimura, N., Shimada, N., Nomura, K., and Watanabe, K. (1990) J. Biol. Chem. 265, 15744-15749). The gene encoding the beta isoform, covering 10 kilobases and comprising five exons, was located in tandem in the immediate vicinity (at a 3-kilobase distance) of the 5' upstream of the alpha isoform gene which was recently reported from this laboratory (Ishikawa, N., Shimada, N., Munakata, Y., Watanabe, K., and Kimura, N. (1992) J. Biol. Chem. 267, 14366-14372), suggesting their generation by gene duplication. The exon-intron junctions were exactly conserved between the two genes. Southern blot analyses showed that unidentified fragments cross-reacted with the beta isoform cDNA probe besides those containing the genuine gene, and at least two of them were identified as possible processed pseudogenes. Northern and dot blot hybridization studies demonstrated that the alpha isoform was more expressed than the beta isoform in rat tissues examined except brain, from which the isoform designation was derived. These results suggest independent expression and specific roles of these isoforms in the cell. Comparative studies between rat and human isoforms indicate that the isoforms could have differentiated before the two species evolutionally diverged.

Amino Acid Sequence↗