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Biomedical subjects

S Oda

Publications and source records attributed to S Oda.

At least 73 records · Page 4Linked to original sources
PubMed2000

Identification of a novel myosin-Va mutation in an ataxic mutant rat, dilute-opisthotonus.

Mutations of the myosin-Va gene (Myo5a) cause diluted coat color in mice and are occasionally associated with severe neurological disorders. Dilute-opisthotonus (dop) is a spontaneous gene mutation in the rat, and phenotypes of the homozygote (dop/dop) are similar to those of the Myo5a-deficient mouse, suggesting that the mutation resides in the rat Myo5a gene. To elucidate the molecular basis of the dop mutation, we cloned the rat Myo5a cDNA from the wild type and the dop/dop. The wild-type rat Myo5a cDNA contained a 5487-bp ORF and showed higher homology with Myo5a of the other species than Myr6 (Myo5b) in the rat. A 141-bp in-frame deletion was detected in the head region in the dop cDNA. An intragenic rearrangement consisting of a 306-bp inversion associated with 17-bp and 217-bp deletions were identified in the Myo5a gene of the dop genome. This rearrangement involved a 141-bp exon, which was skipped in the dop transcript. The MyoVA protein expression was severely impaired in the dop/dop brain. This is the first report to define the dop mutation as the Myo5a gene abnormality in the rat.

Amino Acid Sequence↗
PubMed2000

Differential growth inhibition by 5-fluorouracil in human colorectal carcinoma cell lines.

The effects of 5-fluorouracil (5-FU) on cell growth were investigated using a primary culture of human fibroblasts, MRC-5, and three established human colon cancer cell lines, DLD-1, LoVo and SW620. Detailed flow cytometric analyses revealed differential growth inhibition among these cell lines including three modes of cell growth modulation: (a) loss or accumulation of S phase cells; (b) G2/M block; and (c) G1-S arrest. From analyses on the amount of 5-FU incorporated into cellular RNA and the activity of thymidylate synthase (TS), suppression of TS and depletion of dTTP, a possible consequence of the former, was considered to be the major action of 5-FU in these cells. Differences in the cellular responses to the nucleotide pool imbalance appeared to make the cell growth modulation diverse. Loss of S phase cells and G1-S phase arrest were evident in p53 wild-type cells, MRC-5 and LoVo. Cells proficient in DNA mismatch repair, SW620 and MRC-5, showed marked modulations in S-G2/M progression. These findings suggest that multiple factors, including p53 and DNA mismatch repair, participate in diverse cell growth modulations in cells treated with 5-FU. Cellular resistance to 5-FU correlated well with a loss of modulations in S-G2/M progression, rather than with a defect of G1-S arrest, which suggests the significance of DNA mismatch repair as a factor affecting the sensitivity of cells to 5-FU.

Antimetabolites, Antineoplastic↗
PubMed2000

In vitro evaluation of Er:YAG laser scaling of subgingival calculus in comparison with ultrasonic scaling.

The purpose of the present study was to evaluate the effectiveness of Er:YAG laser scaling and the morphological and histological changes of the laser-scaled root surface in comparison with the effectiveness and root surface changes produced by conventional ultrasonic scaling. Fifty-three periodontally involved human extracted teeth with a band of subgingival calculus were used. The teeth were divided randomly into 2 groups for laser scaling and ultrasonic scaling. Laser irradiation was performed at an energy output of 40 mJ/pulse and 10 pulses/s under water spray, with the probe tip contacted obliquely to the root surface. Ultrasonic scaling was performed at a clinically standard power setting. The time required for scaling, the scaled area and the temperature changes were determined using both methods of treatment. The features of the scaled surfaces were examined by histological and scanning electron microscope (s.e.m.) observations. The Er:YAG laser provided subgingival calculus removal on a level equivalent to that provided by the ultrasonic scaler, without major thermal elevation. Macroscopically, the laser-treated root surface was somewhat rougher than or similar to the ultrasonically scaled root. However, the efficiency of the laser scaling was lower than that of the ultrasonic scaling. In addition, histological examination revealed a thin deeply stained zone on the lased root surface, and s.e.m. analysis revealed a characteristic microroughness on the lased surface. The laser scaling provided a level of calculus removal that was similar to that provided by the ultrasonic scaling. However, the Er:YAG laser produced superficial, structural and thermal microchanges on the root cementum.

Dental Calculus↗
PubMed2000

The gamete fusion process is defective in eggs of Cd9-deficient mice.

The cell-surface molecule Cd9, a member of the transmembrane-4 superfamily, interacts with the integrin family and other membrane proteins. and is postulated to participate in cell migration and adhesion. Expression of Cd9 enhances membrane fusion between muscle cells and promotes viral infection in some cells. Fertilization also involves membrane fusion, between gametes. In mammals, the sperm binds to microvilli on the egg surface, and sperm-egg membrane fusion first occurs around the equatorial region of the sperm head12. The fused membrane is then disrupted, and the sperm nucleus as well as the cytoplasm is incorporated into the egg. Cd9 is expressed on the plasma membrane of the mouse egg, and an anti-Cd9 monoclonal antibody inhibits sperm-egg surface interactions. We generated Cd9 mice and found that homozygous mutant females were infertile. Sperm-egg binding was normal, but sperm-egg fusion was almost entirely inhibited in eggs from Cd9 females. Intracellular Ca2 oscillations, which signal fertilization, were absent in almost all mutant eggs; in rare cases, a response occurred after a long time period. In normal animals, Cd9 molecules were expressed on the egg microvilli and became densely concentrated at the sperm attachment site. Thus, our results show that Cd9 is important in the gamete fusion process at fertilization.

Animals↗
PubMed2000

Time trends of surgical treatment and the prognosis for Japanese patients with gastric cancer.

The incidence of gastric cancer is much higher in Japan than in other countries even though diagnostics and treatments of such patients have improved. The objective of this study was to present an overview of the past, present and future of surgical treatment for our patients with gastric cancer. We analysed data on 2152 Japanese men and women with gastric cancer who underwent surgical resection from 1965 to 1995 at Kyushu University in Fukuoka, Japan, based on a univariate and the multivariate analysis. We focused on time trends of surgical treatment and the postoperative outcome. Over the years, there have been favourable changes in the numbers of patients with early gastric cancer. In all cases of gastric cancer, the rate of 18% in the first six year period (group 1) was 57% in the last 5 year period (group 6). Size of the tumour was smaller, well-differentiated tumour tissue was more common, and lymphatic involvement was less frequent. Lymph node metastasis, liver metastasis and peritoneal dissemination all decreased. Extensive lymph node dissection was more frequently done and the rate of curative resection (curability A and B) increased. With increases in identifying the early stage of cancer and better perioperative care, mortality rates 30 days after the surgery greatly decreased. Multivariate analysis revealed that the 10 factors of depth of invasion, lymph node metastasis, lymph node dissection, tumour size, liver metastasis, peritoneal dissemination, lymphatic invasion, vascular invasion, lesion in the whole stomach and lesion in the middle stomach were independent factors for determining the prognosis. Detection of the tumour in an early stage, standardized surgical treatment, including routine lymph node dissection, close follow-up schedules and better perioperative management are expected to increase survival time for patients with this malignancy.

Female↗
PubMed2000

Detection of female carriers of congenital color-vision deficiencies by visual pigment gene analysis.

PURPOSE: Congenital color-vision deficiencies are frequent among males, 4.7-8.0%, suggesting that female carriers are present at a frequency of 9-15%. The purpose of this study was to determine whether carriers could be detected by analysis of the visual pigment genes. METHODS: DNA from 29 males with congenital color-vision deficiencies, from their mothers, and from 117 randomly-selected females was analyzed. The most upstream genes, the downstream genes, and the most downstream genes in the red/green pigment gene arrays were amplified separately by PCR. Exon 5 of each gene was analyzed by single-strand conformation polymorphisms (SSCP). RESULTS: Analysis of the visual pigment genes suggests that one of the 29 mothers examined is a female protan and two others are carriers of both protan and deutan defects. The remaining 26 mothers were confirmed to be carriers of congenital color-vision deficiencies. Unusual patterns were observed in 15 (13%) of the randomly-selected females; among them, 5 appeared to be protan carriers and at least 4 to be deutan carriers. CONCLUSIONS: Female carriers of congenital color-vision deficiencies can be detected by analysis of the visual pigment genes. Since the proportion of females showing unusual patterns was slightly higher than expected, some must be false-positives and require more detailed examination.

Color Perception↗
PubMed2000

Multiplicities and some enzymatic characteristics of ape pepsinogens and pepsins.

Pepsinogen levels in ape stomachs were comparable to those in macaques and significantly higher than those in the stomachs of other mammals, including carnivores and ruminants. The occurrence of multiple forms of pepsinogens was remarkable. Nine, sixteen, eight, and fourteen pepsinogens were purified or partially purified from the gastric mucosa of a gibbon, orang-utan, gorilla, and chimpanzee, respectively. Most of these were type-A pepsinogens, and only one type-C pepsinogen was identified in each ape. The two types could be readily distinguished by staining for proteolytic activity on polyacrylamide gel electrophoresis (PAGE) in the presence/absence of pepstatin. Type-A pepsinogens were further divided into two subtypes. One subtype, constituting a major group of pepsinogens in apes, exhibited high hemoglobin-digestive activity. The other subtype was specified by a relatively high content of Lys and low hemoglobin-digestive activity. It is likely that pepsinogen-A genes have been duplicated several times as hominoids, including humans, evolved in the primate lineage. The presence of multiple pepsinogens in apes might be advantageous in the efficient digestion of a wide variety of foods.

Amino Acids↗
PubMed2000

Frequency of microsatellite instability inBreast cancer determined by high-resolution fluorescent microsatellite analysis.

In breast cancer, the rates of positivity for microsatellite instability (MSI), vary greatly in the literature. Using high-resolution fluorescent microsatellite analysis (HFRMA), we studied microsatellite alterations in 75 patients with sporadic breast cancer. In this system, several devices were prepared to improve reproducibility of polymerase chain reaction products, migration accuracy of electrophoresis, and characteristics of the detection system. Precise and objective analyses of microsatellite alterations are made feasible using HRFMA. Seven of the 75 cases were judged to be positive for MSI, the rate of positivity being 9. 3%. This rate is relatively low compared to the data in the literature. All the microsatellite changes observed in this system can be classified into two types: type A with relatively small changes in microsatellite sequences observed in limited loci and type B with drastic and widely dispersed changes. The former was thought to be connected to abnormal activity in DNA mismatch repair (MMR). Among the 7 cases, 6 (8.0%) had type A alterations, which means that the tumors may have an abnormal MMR activity. Application of precise and objective systems for microsatellite analysis is expected to be clinically useful to detect patients at high risk for cancers.

Adult↗
PubMed2000

Robertsonian metacentrics of the house musk shrew (Suncus murinus, Insectivora, Soricidae) lose the telomeric sequences in the centromeric area.

The house musk shrew, Suncus murinus, is polymorphic for five Robertsonian translocations (Rb8.17, 9.13, 10.12, 11.16, 14.15). Fluorescence in situ hybridisation with a biotin-labelled oligonucleotide, (TTAGGG)7, was performed to localise the telomeric DNA sequences at Rb chromosomes of heterozygous shrews. Hybridisation signals were observed at both ends of all chromosomes, but not at the pericentromeric areas of any of the Robertsonian metacentrics. Our results indicate a complete loss of the telomeric sequences at the fusion points of the Rb metacentrics in S. murinus.

Animals↗
PubMed2000

The alcohol tests for drunken criminals using psychological tests.

In the alcohol test for drunken criminals, we introduced Bender-Gestalt test and Rorschach test for the assessment, and examined their usefulness for the evaluation of intoxication patterns according to Binder's classification. The subjects were 24 drunken criminals who were examined by Mental Hygiene Group, Tsukuba University, for psychiatric evidences. The subjects were divided into the ordinary intoxication group (OI group) and the complicated intoxication group (CI group) on the basis of the behavioral assessment, and the psychological tests were performed before and after drinking. The following results were obtained. 1) Alcohol intoxication induced decrease in R1T, W and VIII + IX + X/R and increase of BGT scores and P%, which indicates that subjects become unable to make comprehensive and delicate responses to the external stimuli. 2) When we classified subjects into increasing and decreasing type on the pattern of changes in the BGT score from before to immediately after drinking in each subject, we found the ratio of increasing type in complicated intoxication is more than in ordinary intoxication significantly. And we found significant group x drinking interaction in F+% and At% of Rorschach test. The F+% significantly decreased only in CI group. The At% in CI group tended upward, but downward in OI group. These findings indicated that complicated intoxication reduced the subject's reality testing, while not in ordinary intoxication. 3) Comparing the effects of personality and intoxication factors in complicated intoxication, intoxication factors were considered to play primary roles. 4) We found association between high BAL and reduction of ego function and imagination, which is represented as significant peak of BALx drinking interaction in the BGT scores, M and FM + m. These observations suggest that the psychological tests as part of the alcohol tests are useful for the evaluation and research of intoxication.

Adult↗
PubMed1999

Abnormal expression of tyrosine hydroxylase immunoreactivity in Purkinje cells precedes the onset of ataxia in dilute-lethal mice.

Expression of tyrosine hydroxylase (TH) immunostaining in the cerebellum was examined in dilute-lethal mice (DL) prior to and following the onset of ataxia. DL walked normally on postnatal days 7 and 8. Falling over when walking was exhibited by about 20% of DL on day 9 and by all DL by day 10. TH-positive Purkinje cells in lobules IX and X of the vermis of either ataxic or non-ataxic DL were clearly observed on day 9 when compared to control mice, and had drastically increased by day 10. These results revealed that abnormal TH expression occurred in some Purkinje cells of DL cerebella, preceding the onset of ataxia.

Animals↗
PubMed1999

Spatiotemporal dynamics of the [Ca2+]i rise induced by microinjection of sperm extract into mouse eggs: preferential induction of a Ca2+ wave from the cortex mediated by the inositol 1,4,5-trisphosphate receptor.

Hamster sperm extract (SE) possessing Ca2+ oscillation-inducing activity was microinjected into the peripheral or central region of mouse eggs, and the first increase in intracellular Ca2+ concentration ([Ca2+]i), together with the spread of fluorescence-labeled SE in the ooplasm, was investigated by imaging with confocal microscopy. Injection into the periphery always induced a Ca2+ wave that started from the injection site after a delay of 5 to 30 s depending on the concentration of SE. The diluted SE caused a wave of two-step [Ca2+]i rises, which was always observed at fertilization. Injection into the center could induce a radial Ca2+ wave with relatively high dose of SE, but lower dose of SE caused a [Ca2+]i rise after a longer delay which was initiated synchronously over the ooplasm or was preceded in a peripheral area. Injection of diluted SE remarkably prolonged the delay time and reduced the rate of [Ca2+]i rise. The critical concentration of SE needed to induce [Ca2+]i rise was significantly lower in the periphery. These results indicate that the sensitivity to SE is higher in the cortex. SE-induced [Ca2+]i rises were blocked by an antibody against the type 1 inositol 1,4,5-trisphosphate receptor (InsP3R). The cortex was substantially more sensitive to injected InsP3 induction of Ca2+ release than the center. It is suggested that the cortex of mouse eggs may involve a functionally specialized organization of InsP3Rs and Ca2+ pools in which a cytosolic sperm factor(s) could act upon sperm-egg fusion to cause Ca2+ release, leading to the Ca2+ wave at fertilization.

Animals↗
PubMed1999

Morphologic investigation of rolling mouse Nagoya (tg(rol)/tg(rol)) cerebellar Purkinje cells: an ataxic mutant, revisited.

Rolling mouse Nagoya (rolling: tg(rol)) is a neurologic mutant mouse exhibiting severe ataxia. Two alleles of the rolling mutation, tottering (tg) and leaner(tg(la)), have been identified as mutations in the voltage-dependent calcium channel alpha1A subunit. No specific light and electron microscopic findings have been reported for the rolling mouse cerebellum except a decreased number of granule cells, while altered Purkinje cell/parallel fiber synapses have been observed in tottering and leaner cerebella. Rolling mouse cerebella were analyzed using anti-calbindin-D immunohistochemistry and transmission electron microscopy to investigate Purkinje cell morphology and synaptic contacts between Purkinje cell dendritic spines and parallel fiber varicosities. Multiple Purkinje cell dendritic spines synapsing with single parallel fiber varicosities were frequently observed in rolling cerebella. The correlation between the presence of altered Purkinje cell synapses and ataxia in rolling mice warrants further investigation.

Alleles↗
PubMed1999

Mutated gene-specific phenotypes of dinucleotide repeat instability in human colorectal carcinoma cell lines deficient in DNA mismatch repair.

Mutations in DNA mismatch repair (MMR) genes in hereditary non-polyposis colon cancer (HNPCC) patients revealed the importance of MMR deficiency as a risk for carcinogenesis. Since diverse mutations occur in several MMR genes, the instability of repeat sequences dispersed in the genome, which are also governed by the MMR system, is a well used marker. However, the relationship between repeat sequence instability and MMR gene mutation in human cells has not been well defined mainly because precise systems to analyse repeat sequences have not been available. Using our newly developed system, we analysed alteration of dinucleotide repeats in human cell lines which harbour mutations in MMR genes. Among 24 subclones of DLD-1 cells (hMSH6-) only one had a dinucleotide repeat alteration in only one microsatellite locus, while LoVo cells (hMSH2-/hMSH6-) exhibited marked dinucleotide repeat instability (DRI). HCT116 cells, a hMLH1-mutant, showed an ultimate DRI phenotype. Interestingly, SW48 cells lacking hMLH1 expression also demonstrated DRI, albeit the extent of diversity being significantly lower than HCT116. These data suggest that the DRI phenotype in human cells is highly dependent on mutated MMR genes and on forms of mutation. The results of DRI analyses used to detect MMR-deficiency should be interpreted with caution.

Adaptor Proteins, Signal Transducing↗
PubMed1999

The p53 tumor suppressor gene in anticancer agent-induced apoptosis and chemosensitivity of human gastrointestinal cancer cell lines.

PURPOSE: While the target of many anticancer agents has been identified, the processes leading to killing of the cancer cells and the molecular basis of resistance to the drugs are not well understood. We used human gastrointestinal cancer cell lines and examined how anticancer agents induced cell killing and how the chemosensitivity of these lines was determined. METHODS: Twelve gastrointestinal cancer cell lines were examined for the presence of either a wild-type or mutant p53 gene by direct sequencing. We also determined whether or not cell killing would occur when the cell lines were exposed to anticancer drugs. The sensitivity to the anticancer agents was determined based on colony formation. RESULTS: All 12 gastrointestinal cancer cell lines carried either a wild-type or mutant p53 gene. Three lines, MKN45, MKN74 and COLO320, carried the wild-type p53 gene, and nine carried the mutant p53 gene. When three lines were exposed to the anticancer agents etoposide, doxorubicin (DXR) or 5-fluorouracil (5-FU), cell death ensued. In these cells, the population of cells in G1 phase increased after exposure to high-dose anticancer agents, but cells in G2 phase increased when exposed to low-dose anticancer agents. Our observations support the concept that cells carrying the wild-type p53 gene tend to be sensitive to etoposide and DXR and, in particular, deletion of the p53 function results in a greater resistance to anticancer agents. CONCLUSION: Based on our findings, human gastrointestinal cancer-related cell death apparently occurs via a p53-dependent pathway. A relationship was observed between the induction of cell death and chemosensitivity.

Antineoplastic Agents↗
PubMed1999

Relaxation effects in humans of underwater exercise of moderate intensity.

In this study we investigated the effects of underwater exercise in warm water (34 degrees C) on physiological and psychological relaxation. Eight healthy young men (aged 20-26 years) volunteered for the experiment. The experiment consisted of the following three successive segments: a pre-exercise period of 20 min, during which the subjects rested in a semi-supine posture with their eyes closed for the final 10 min; an underwater exercise period of approximately 60 min, during which the subjects performed gymnastic exercises or aerobic dancing with occasional movements or jumping; a post-exercise recovery of 20 min, which was similar to the pre-exercise rest period. We compared the relative power values (power %) of the electroencephalogram alpha bands (8-13 Hz) and profile of moods states (POMS) before and after the underwater exercise. We also estimated the percentage of maximal heart rate (%HRmax) throughout the experiment to ascertain the intensity of the underwater exercise. The results of %HRmax indicated that the intensity of underwater exercises practised in the experiments ranged from low to moderate. The power % of EEG alpha bands had increased significantly after the underwater exercise compared with the pre-exercise rest (P<0.05). From the POMS results, we observed that positive mood (vigour) increased and negative mood (tension and anxiety, depression and dejection) decreased significantly after the underwater exercise (P<0.05). This study found that the subjects showed increased physiological and psychological indices of relaxation after underwater exercise.

Adult↗
PubMed1999

Purification and characterization of goat pepsinogens and pepsins.

Three type-A and two type-C pepsinogens, namely, pepsinogens A-1, A-2, A-3, C-1, and C-2, were purified from adult goat abomasum. Their relative levels in abomasal mucosa were 27, 19, 14, 25, and 15%, respectively. Amino acid compositions were quite similar between isozymogens of respective types, but different between the two types especially in the Glx/Asx and Leu/Ile ratios. NH2-terminal amino acid sequences of pepsinogens A-3 and C-2 were SFFKIPLVKKKSLRQNLIEN- and LVKIPLKKFKSIRETM-, respectively. Pepsins A and C showed maximal hemoglobin-digestive activity at around pH 2 and 3, respectively, and specific activities of pepsins C were higher than those of pepsins A. Two subtypes of pepsin A were obvious, namely pepsin A-2/3 which maintains its activity in the weakly acidic pH region over pH 3 and pepsin A-1, which does not. Hydrolysis of oxidized insulin B chain by goat pepsins A occurred primarily at Ala14-Leu15 and Leu15-Tyr16 bonds.

Abomasum↗