Biomedical subjects

T Toda

Publications and source records attributed to T Toda.

At least 127 records · Page 7Linked to original sources

PubMed1998

pmp1+, a suppressor of calcineurin deficiency, encodes a novel MAP kinase phosphatase in fission yeast.

Calcineurin is a highly conserved and ubiquitously expressed Ca2+- and calmodulin-dependent protein phosphatase. The in vivo role of calcineurin, however, is not fully understood. Here, we show that disruption of the calcineurin gene (ppb1(+)) in fission yeast results in a drastic chloride ion (Cl-)-sensitive growth defect and that a high copy number of a novel gene pmp1(+) suppresses this defect. pmp1(+) encodes a phosphatase, most closely related to mitogen-activated protein (MAP) kinase phosphatases of the CL100/MKP-1 family. Pmp1 and calcineurin share an essential function in Cl- homeostasis, cytokinesis and cell viability. Pmp1 phosphatase dephosphorylates Pmk1, the third MAP kinase in fission yeast, in vitro and in vivo, and is bound to Pmk1 in vivo, strongly suggesting that Pmp1 negatively regulates Pmk1 MAP kinase by direct dephosphorylation. Consistently, the deletion of pmk1(+) suppresses the Cl--sensitive growth defect of ppb1 null. Thus, calcineurin and the Pmk1 MAP kinase pathway may play antagonistic functional roles in the Cl- homeostasis.

Amino Acid Sequence↗

PubMed1998

TMIG-2DPAGE: a new concept of two-dimensional gel protein database for research on aging.

Cellular proteins of a normal human diploid fibroblast line (TIG-3) at various stages of replicative aging were resolved by horizontal isoelectric focusing on an immobilized pH gradient, followed by vertical sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE). Spot proteins were visualized by silver staining and quantitated by image processing. All corresponding spots were matched among two-dimensional gel images, and variation profiles in relative abundance of individual proteins during in vitro aging were classified into five categories, i.e., (i) increase, (ii) decrease, (iii) increase followed by decrease, (iv) decrease followed by increase, and (v) irregular or nonsignificant variation. The new concept of the Tokyo Metropolitan Institute of Gerontology two-dimensional gel protein database (TMIG-2DPAGE) was prepared from the above data to support research on cellular aging. The database was put on our World Wide Web home page at the URL of http://www.tmig.or.jp/2D/ to allow free access through the Internet. The individual protein data entries were linked to the standard spot protein map of the two-dimensional gel image in order to be accessible by clicking the mouse on it.

Aging↗

PubMed1998

Representation of the midline trunk, bilateral arms, and shoulders in the monkey postcentral somatosensory cortex.

Single neuronal activities were recorded in the arm/trunk region of the postcentral gyrus in awake Japanese monkeys. A total of 1608 units were isolated from four hemispheres of two animals, and receptive fields (RFs) and submodalities were identified in 1162 units. Deep or skin submodality neurons were dominant in area 3a or area 3b, respectively. The deep/skin ratio increased as the recording site moved from area 3b to the more caudal areas. In areas 3a and 3b, neuronal RFs were almost exclusively on either the arm or trunk. In areas 2 and 5, neurons with RFs on the trunk decreased and those with RFs on the hand or covering more than one body part, etc. increased. We found a total of 107 neurons with bilateral RFs and 56 with ipsilateral RFs, while the rest (n=999) were with contralateral RFs. Bilateral or ipsilateral neurons of skin submodality (n=37) were found in areas 1, 2, and 5. Twenty six (70%) had RFs on the trunk and/or occiput, five on the forelimb, and the rest (n=6) on both the trunk and forelimb (the combined type). Among 33 skin bilateral neurons, 90% (n=30) had RFs across the midline. Bilateral or ipsilateral neurons responding to joint manipulation (n=104) were found in areas 2 and 5. Most of them were activated by manipulation of the shoulder and/or elbow (the proximal type, n=72, 69%). There were 25 neurons of the combined type (both the proximal and distal joints were effective, 24%). Bilateral or ipsilateral neurons of deep-others submodality (n=20) were found in areas 1, 2, and 5. The forelimb type (n=12, 60%) was dominant in this category. The combined-type neurons in both the skin- and joint-manipulation categories were found only or mostly in area 5. These results indicate the presence of hierarchical processing for bilateral as well as contralateral information within the arm/trunk region of the postcentral gyrus.

Animals↗

PubMed1998

Large synovial cyst of the pelvis containing rice bodies. A case report.

Although synovial pelvic cysts are very uncommon they enter into the differential diagnosis of presacral and ovarian cysts. In the elderly male whom we report, a large cyst arose from the hip and extended during a five year period to involve the entire pelvic cavity. The cyst, which contained a large number of "rice bodies" was excised surgically.

Aged↗

PubMed1998

Founder-haplotype analysis in Fukuyama-type congenital muscular dystrophy (FCMD).

Fukuyama-type congenital muscular dystrophy (FCMD) is an autosomal recessive, severe muscular dystrophy associated with brain anomalies. After our initial mapping of the FCMD locus to 9q31-33, we performed linkage disequilibrium analysis, which led us to suspect that the FCMD gene lay within a region of less than 100 kb containing D9S2107. In the present study, we developed two new microsatellites (D9S2170 and D9S2171) in close vicinity to D9S2107 and examined haplotypes of FCMD chromosomes by using four markers (cen-D9S2105-D9S2170-D9S2171-D9S2107-tel). As 82% of the FCMD chromosomes that we examined shared the founder haplotype (138-192-147-183) and 94% of the FCMD patients in our panel carried founder haplotypes on one or both chromosomes, the data supported the hypothesis of a single founder of this disease in the Japanese population. Eight haplotypes different from the founder's were observed in FCMD chromosomes, indicating that eight different FCMD mutations in addition to the founder's have occurred in Japan. Moreover, we have detected several historical recombinations that have disrupted the founder haplotype at D9S2105 or D9S2170 and conclude that the FCMD gene is probably located just centromeric to D9S2170.

Chromosomes, Human, Pair 9↗

PubMed1998

Crm1 (XpoI) dependent nuclear export of the budding yeast transcription factor yAP-1 is sensitive to oxidative stress.

BACKGROUND: The yAP-1 transcription factor is crucial for the oxidative stress response of the budding yeast Saccharomyces cerevisiae; its activity is induced in response to oxidative stress, and as a consequence the expression of a number of target genes is enhanced. We have shown previously that yAP-1 is mainly found in the cytoplasm, but that upon the imposition of oxidative stress it localizes to the nucleus. In this study, we addressed the mechanism through which yAP-1 nuclear localization is regulated. RESULTS: Here we show that yAP-1 localization is mediated by active export from the nucleus, resulting from the activity of Crm1 (XpoI), a conserved protein that functions as an export receptor which recognizes the nuclear export signal (NES). When Crm1 expression was repressed, yAP-1 was localized in the nucleus and induced the expression of a yAP-1 dependent target gene. Our results also suggest that the cysteine rich domain (CRD), at the C-terminus of yAP-1, functions as an export recognition sequence. yAP-1 and Crm1 interact in vivo and this interaction is reduced in response to oxidative stress. CONCLUSIONS: These results suggest a novel regulatory mechanism of nucleocytoplasmic transport which is dependent upon a redox sensitive nuclear export pathway.

Bacterial Proteins↗

PubMed1998

Two F-box/WD-repeat proteins Pop1 and Pop2 form hetero- and homo-complexes together with cullin-1 in the fission yeast SCF (Skp1-Cullin-1-F-box) ubiquitin ligase.

BACKGROUND: In the ubiquitin-dependent proteolysis pathway, a ubiquitin ligase (E3) is responsible for substrate selectivity and timing of degradation. A novel E3, SCF (Skp1-Cullin-1/Cdc53-F-box) plays a pivotal role in cell cycle progression. In fission yeast, F-box/WD-repeat protein Pop1 regulates the level of the CDK (cyclin-dependent kinase) inhibitor Rum1 and the S phase regulator Cdc18. RESULTS: We have cloned and characterized the pop2+ gene which encodes the Pop1-related F-box/WD-repeat protein. Pop2 plays a role which overlaps with Pop1 in the degradation of Rum1 and Cdc18. However, these two proteins are not functional homologues. Pop1 and Pop2 form hetero-as well as homo-dimers in the cell. We have analysed two fission yeast cullin members and found that cullin-1 functions as a component of SCFPop1,2, whilst cullin-3 is involved in the distinct stress-response pathway. CONCLUSIONS: Fission yeast SCF is composed of Pop1 and Pop2, two structurally related but functionally independent F-box/WD-repeat proteins. By forming three distinct complexes, SCFPop1/Pop1, SCFPop1/Pop2 and SCFPop2/Pop2, SCF has evolved a sophisticated mechanism to control the level of Rum1 and Cdc18. Fission yeast SCF also contains cullin-1 as a universal scaffold and each cullin member plays a distinct biological role.

Amino Acid Sequence↗

PubMed1998

Affinity of four lectins for endocervical and endometrial non-neoplastic and neoplastic glandular epithelium.

AIMS: Endocervical and endometrial tissues were stained with four lectins to determine the difference in staining pattern between non-neoplastic and neoplastic conditions of these tissues. METHODS AND RESULTS: The lectins used were Ulex europaeus agglutinin (UEA), Dolicho biflorus agglutinin (DBA). Concanavalin A (Con A), and Phaseolus vulgaris agglutinin (PHA). Endocervical tissues included normal endocervical glands, microglandular hyperplasia, minimal deviation adenocarcinoma and endocervical adenocarcinoma, well to poorly differentiated types. Endometrial tissues were collected from normal endometrium, simple glandular hyperplasia, complex hyperplasia, atypical hyperplasia and adenocarcinoma grades 1-3. Non-neoplastic and neoplastic endocervical and endometrial glandular epithelium showed positive reaction for UEA, Con A and PHA. Non-neoplastic glands showed mild to moderate intensity and apical and/polar type of staining pattern for all lectins. Endocervical adenocarcinoma including minimal deviation adenocarcinoma (MDC) and adenocarcinoma well to moderately differentiated type showed diffuse cytoplasmic type of staining pattern for all lectins, but poorly differentiated adenocarcinoma of endocervix showed only a stromal pattern for all lectins. Endometrial hyperplasia and adenocarcinoma grades 1-3 showed positive reaction for all lectins except for DBA. The staining pattern of endometrial hyperplasia was variable, but adenocarcinoma grades 1-3 showed diffuse type. CONCLUSION: Intensity and staining patterns of lectins are helpful in distinguishing between endocervical and endometrial non-neoplastic and neoplastic lesions. Intense positive reaction of MDC, especially for Con A and PHA, can differentiate this lesion from normal endocervical glands. The stromal type of staining pattern of poorly differentiated endocervical adenocarcinoma can also have diagnostic significance. Negative reactions of DBA lectin for endometrial adenocarcinoma can be used for differentiating it from endocervical adenocarcinoma.

Adenocarcinoma↗

PubMed1998

Sealing ability of composite resin placed over calcium hydroxide and calcium sulphate plugs in the repair of furcation perforations in mandibular molars: a study in vitro.

The purpose of this study was to evaluate in vitro the sealing ability of various materials in the repair of furcation perforations in mandibular molars by measuring coronal microleakage with Indian ink. Ninety extracted mandibular molars were embedded individually into a plaster of Paris block, with the roots surrounded by a simulated periodontal ligament of silicone. Subsequently, a standard coronal access opening was prepared, the root canal orifices were located and a perforation was made with a size 012 round bur in a water-cooled high-speed handpiece directly into the centre of the floor of the pulp chamber. The perforations were repaired with amalgam, composite resin, calcium sulphate under composite resin and calcium hydroxide under composite resin. The teeth were coated with two layers of nail polish, leaving the access opening area uncovered, and immersed in Indian ink for 4 days at 37 degrees C. The teeth were sectioned longitudinally and dye penetration measured from the coronal level of the repair material to the apical end of the perforation. All experimental groups revealed dye penetration in varying degrees, but there was no significant difference amongst them (Kruskal-Wallis test P < 0.05). Calcium sulphate and calcium hydroxide prevented overextrusion of composite resin when used under this repair material.

Analysis of Variance↗

PubMed1998

Identification of novel temperature-sensitive lethal alleles in essential beta-tubulin and nonessential alpha 2-tubulin genes as fission yeast polarity mutants.

We have screened for temperature-sensitive (ts) fission yeast mutants with altered polarity (alp1-15). Genetic analysis indicates that alp2 is allelic to atb2 (one of two alpha-tubulin genes) and alp12 to nda3 (the single beta-tubulin gene). atb2(+) is nonessential, and the ts atb2 mutations we have isolated are dominant as expected. We sequenced two alleles of ts atb2 and one allele of ts nda3. In the ts atb2 mutants, the mutated residues (G246D and C356Y) are found at the longitudinal interface between alpha/beta-heterodimers, whereas in ts nda3 the mutated residue (Y422H) is situated in the domain located on the outer surface of the microtubule. The ts nda3 mutant is highly sensitive to altered gene dosage of atb2(+); overexpression of atb2(+) lowers the restrictive temperature, and, conversely, deletion rescues ts. Phenotypic analysis shows that contrary to undergoing mitotic arrest with high viability via the spindle assembly checkpoint as expected, ts nda3 mutants execute cytokinesis and septation and lose viability. Therefore, it appears that the ts nda3 mutant becomes temperature lethal because of irreversible progression through the cell cycle in the absence of activating the spindle assembly checkpoint pathway.

Alleles↗

PubMed1998

Prenatal diagnosis of Fukuyama-type congenital muscular dystrophy by microsatellite analysis.

We applied microsatellite analysis to prenatal diagnosis of Fukuyama-type congenital muscular dystrophy (FCMD), an autosomal recessive severe muscular dystrophy associated with brain malformations. Recent identification of the FCMD gene locus at 9q31-q33 provided the basis for prenatal diagnosis and carrier detection. We recently developed new microsatellite markers which are closer to the FCMD gene and improved the phenotype probability. Nine fetuses in eight unrelated FCMD families, including a twin pregnancy, were analysed using the newly developed markers. Four fetuses showed over 99% probability of being healthy either as normal homozygote (n = 1) or heterozygote carrier (n = 3) and were born without signs of FCMD. The other five fetuses were diagnosed with a probability of FCMD of 99% or greater; all of the latter parents decided to terminate the pregnancies. Brain malformations characteristic of FCMD in one of the aborted fetuses confirmed the diagnosis of FCMD at 19 weeks of gestation.

Adult↗

PubMed1998

Ooplasmic injection of elongating spermatids for the treatment of non-obstructive azoospermia.

We applied the technique of ooplasmic elongating spermatid injection to the treatment of non-obstructive azoospermia. Mature oocytes were injected with elongating spermatids isolated from testicular biopsy material obtained from 13 non-obstructed azoospermic men. Seventy-three oocytes were successfully injected with elongating spermatids and were then cultured for 36 h. At 13 h post-injection 68 oocytes were found to be activated and 52 of them were fertilized. Forty-one 2- to 4-cell stage embryos developed from normally fertilized oocytes were transferred. At least two embryos were transferred to each female partner. Two pregnancies were achieved. Elongating spermatid injection may have a role in the treatment of non-obstructive azoospermia.

Adult↗

PubMed1998

Two canals in mesiobuccal roots of maxillary molars.

The purpose of this study was to examine extracted root canal treated maxillary molars cleared for: (i) the presence of a mesiopalatal (MP) canal in both first and second molars, (ii) the extension of MP canal from the pulp to the apical area, and (iii) the incidence of two foramina in the MB root. Seventy-two extracted maxillary molars (42 first and 30 second molars) were root canal treated by graduate students. The mesiobuccal (MB) roots of these samples were rendered transparent using a clearing technique. The results demonstrated that 52.3% of first and 40% of second molars had two canals obturated in the MB root. After clearing the same roots, the presence of MP canals rose to 80.9% and 66.6%, respectively. The MP canals were root canal treated as far as the foramen in 35.2% of first and 35% of second molars. However, after making them transparent, 91.1% and 90% showed the presence of this canal to the anatomical apex. The MB roots of the root canal treated first molars showed the presence of two foramina in 47% of cases but in 88.2% after clearing. The second molars showed 50% and 70%, respectively. The differences between root canal treated teeth before and after clearing were significantly different in almost all comparisons in both first and second molars. The only exception was when the presence of two foramina was compared before and after the clearing process in second molars (McNemar test P < 0.05).

Coloring Agents↗

PubMed1998

Preventive effects of the plant isoflavones, daidzin and genistin, on bone loss in ovariectomized rats fed a calcium-deficient diet.

The effects of the plant isoflavones, daidzin and genistin, on bone loss in ovariectomized (ovx) rats fed a calcium-deficient diet were investigated. Daidzin and genistin were orally administered to ovx rats for 4 weeks. The femurs of these rats showed significantly lower density, strength (breaking forces), ash weight and calcium and phosphorus content (p<0.01) in comparison with those of sham-operated rats. These changes were largely prevented in animals receiving oral daidzin or genistin for 4 weeks at a dose of 50 mg/kg/d and in animals receiving subcutaneous estrone (7.5 microg/kg/d) as a positive control. Ovariectomy caused atrophy of the uterus and increased the ratio of the urinary excretion of pyridinoline and deoxypyridinoline to endogenous creatinine excretion. This was prevented by administration of daidzin or estrone, but, interestingly, not genistin. The preventive effect of daidzin treatment on bone loss in ovariectomized rats appears to be due to suppression of bone turnover. Genistin has a different mechanism of action from daidzin.

Adipose Tissue↗

PubMed1998

Atrial natriuretic peptide as a preload depressor in acute renal failure secondary to congestive heart failure.

The present study was undertaken to verify the hypothesis that infusion of atrial natriuretic peptide (ANP) might lower preload and be beneficial in the treatment of pulmonary congestion even without a diuresis in patients with acute renal failure (ARF) secondary to severe congestive heart failure (CHF). We studied 22 patients with ARF secondary to CHF. The mean age of the patients (14 men and 8 women) was 72 years (range 36 to 85 years). Seven of the patients had dilated cardiomyopathy, ten had ischemic heart disease, and five had valvular heart disease. ANP was infused intravenously and the following data before and 1 hour after the start of ANP infusion were recorded; urinary output, systemic blood pressure (SBP), pulmonary blood pressure (PBP), right atrial pressure (RAP), cardiac index (CI), heart rate (HR), and arterial blood oxygen partial pressure. Diastolic PBP were employed as pulmonary capillary wedge pressure. Urinary output did not change. Mean SBP decreased from 92 to 85 mmHg (p < 0.05), and mean PBP decreased from 34 to 28 mmHg (p < 0.01). Mean RAP decreased from 11 to 9 mmHg (p < 0.01) and diastolic PBP decreased from 25 to 19 mmHg (p < 0.01). HR did not change significantly and CI increased 2.4 to 2.5 mi/min/m2 (p < 0.05). Arterial blood oxygen partial pressure increased significantly from 71 to 82 mmHg (p < 0.05). In conclusion, ANP decreased preload and improved arterial blood oxygen partial pressure, though diuretic response to ANP is attenuated in ARF secondary to CHE. Infusion of ANP will be very beneficial in cases in which dyspnea and pulmonary edema due to elevation of preload are the principal clinical problems.

Acute Kidney Injury↗

PubMed1998

Setting time and sealing ability of alpha-tricalcium phosphate cement containing titanic oxide.

We developed a new type of calcium phosphate cement for clinical use in endodontics as a root canal sealer or pulp cupping agent. The solid phase of the sealer is composed of 70% of alpha-tricalcium phosphate (alpha-TCP) and 30% of titanic oxide (TiO2), and the liquid phase is 37% citric acid, 5% tannic acid and 58% distilled water. TiO2 was added to control setting time and handling of the cement. We used commercially available calcium phosphate root canal sealer as a control. ISO standards specify that new endodontic products should be examined thoroughly before clinical use. It is important to carry out in vitro cytotoxicity and in vivo histocompatibility tests. We first did in vitro test of setting time and root canal sealing ability of the cement. We found that this developed calcium phosphate cement had an appropriate setting time and excellent sealing ability as a root canal sealer, and concluded that it was suitable for clinical use as a root canal sealer.

Calcium Phosphates↗

PubMed1998

Laparoscopic repair for perforation of duodenal ulcer with omental patch: report of initial six cases.

We report our initial experience with perforated duodenal ulcer treated by laparoscopic repair with omental patch in six patients, and the results are compared with those of other procedures retrospectively. The average operative time was 85.0 min, and the estimated blood loss was 13.7 ml. The estimated blood loss of laparoscopic repair was significantly less than that of gastrectomy (p < 0.01). However, although all patients with gastrectomy or open omental patch needed administration of analgesia, only half of patients require analgesia in laparoscopic repair. No postoperative complication was encountered, and the recurrence of ulcer was not recognized in a mean follow-up of 10 months. We recognized this procedure to be safe and feasible. Although a larger number of patients with longer follow-up is needed, this procedure may become one of the treatments for perforated duodenal ulcer.

Adult↗

PubMed1998

Change in body fat, but not body weight or metabolic correlates of obesity, is related to symptomatic relief of obese patients with knee osteoarthritis after a weight control program.

OBJECTIVE: To determine the variable most closely related to symptomatic relief of osteoarthritis (OA) of the knee in response to a weight control program. METHODS: Twenty-two patients diagnosed with knee OA whose body mass index (BMI) was more than 26.4 were treated with a low calorie diet, an appetite suppressant, and nonsteroidal antiinflammatory drugs for 6 weeks. The patients were instructed to follow a walking program. We analyzed BMI, percent body fat, the average number of steps per day by pedometer, and the metabolic correlates of obesity (blood pressure, fasting blood serum glucose, total cholesterol, triglycerides, and serum insulin) at the beginning and end of therapy. The correlation between the change in each variable and the remission score (delta score) using the Severity Index of Lequesne, et al was evaluated. RESULTS: Delta score of knee OA was more strongly associated with reduction in percent body fat (p= 0.0013, r=0.62) than other variables. Significant correlation was also observed between the number of steps per day and delta score (p=0.0031, r=-0.58). No other variable, including weight loss, was significantly correlated with delta score. There was a significant correlation between delta percent body fat and the number of steps per day (p=0.012, r=-0.62). CONCLUSION: In a weight control program, decreasing body fat and increasing physical activity are more important than body weight loss or decreasing other indices of obesity in producing symptomatic relief of knee OA, although there is not necessarily a cause and effect relationship between body fat and OA score.

Adipose Tissue↗