Biomedical subjects

T Ushijima

Publications and source records attributed to T Ushijima.

At least 55 records · Page 3Linked to original sources

PubMed1998

No direct correlation between mutant frequencies and cancer incidence induced by MeIQ in various organs of Big Blue mice.

The carcinogenicity of 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) was examined in Big Blue female mice with the genetic background of C57BL/6N. With the administration of 300 ppm of MeIQ in their diet for 92 weeks, the Big Blue female mice developed intestinal tumors and hepatocellular carcinomas. The incidences of adenocarcinomas were 42% (8/19) in the colon and 68% (13/19) in the cecum. The incidence of hepatocellular carcinomas was 84% (16/19). No carcinomas of the intestine or the liver were induced in the control group. As we previously reported, administration of 300 ppm of MeIQ in a diet for 12 weeks induced lacI mutants at the highest frequency in colonocytes, and at only less than one-tenth of the colon in cells of the liver, forestomach and bone marrow, indicating no direct correlation between the lacI mutant frequency (MF) and cancer incidence (CI). The fate of cells with lacI mutation in each organ should be taken into consideration to validate MF as an indicator of carcinogenic potency of a chemical in different organs.

Animals↗

PubMed1998

[Removal of infected pacemaker lead through sternotomy without cardiopulmonary bypass].

A 66-year-old man, who had undergone DDD pacemaker implantation for complete A-V block two years ago, was admitted because of endocarditis with septicemia and renal failure. His blood culture revealed Staphylococcus aureus. We tried to remove the infected cardiac pacemaker lead. But we failed to remove the atrial lead because it was strongly adhered with the right atrial appendage. Antibiotic therapy was ineffective. In the last resort, we operated through median sternotomy three months after the initial infectious episode. In intraoperative inspection, we found it difficult to remove the lead by traction because of atrial residual lead sticking out of the right atrial appendage. We applied a purse string suture on the right appendage and obtained successful removal of infected lead without the cardiopulmonary bypass. His postoperative course has been uneventful. He is totally asymptomatic and doing well up to now. In case of such local infection, we conclude that all transvenous leads should be removed and recommend a simultaneous implantation of the epicardial pacemaker system.

Aged↗

PubMed1998

Generation of polymorphic markers tightly linked to the thymus enlargement loci by phenotype-directed representational difference analysis.

To obtain genetic markers linked to a specific genetic locus, genomic subtraction with a DNA pool of backcross or F2 intercross animals with a specific genotype at the locus is known to be effective. To determine whether the pooling strategy is also effective for isolation of genetic markers linked to a quantitative phenotype that can potentially be controlled by multiple genetic loci, we tested the ability of representational difference analysis (RDA) to isolate genetic markers linked to the thymus enlargement observed in the BUF/Mna (BUF) rat. This is known to be controlled by single major and minor genes, Ten1 and Ten2, on Chromosomes (Chrs) 1 and 13, respectively, both of which have dose effects on the normal WKY/Ncj (WKY) allele. DNA from an inbred WKY rat was used as the tester, and the driver was prepared from a DNA pool of 12 (WKY x BUF)F1 x BUF backcross rats with high thymus ratios (thymus weight/body weight), expected to have dominance of the BUF allele in the responsible loci. By two RDA series with the restriction enzymes BglII and BamHI, respectively, 28 polymorphic markers were isolated, and 8 of them were shown to be linked to Ten1, and one to Ten2. One of the 8 markers linked to Ten1 demonstrated no recombination in 18 rats with high thymus ratios. RDA with a DNA pool based on a quantitative phenotype (phenotype-directed RDA) can thus be considered an efficient approach for direct isolation of polymorphic markers linked to a quantitative trait.

Animals↗

PubMed1998

Isolation of 48 genetic markers appropriate for high throughput genotyping of inbred rat strains by B1 repetitive sequence-representational difference analysis.

Mapping of genetic suppressors, modifiers, and quantitative trait loci (QTLs) requires genetic markers that can be efficiently and inexpensively genotyped for a large number of individuals. To isolate rat genetic markers suitable for this purpose, representational difference analysis (RDA) was performed with amplicons prepared by PCR with the B1 repetitive sequence used as the primer (B1-amplicons). In total, 48 polymorphic DNA fragments were isolated by five series of RDA, subtracting the B1-amplicons prepared from an ACI/N (ACI) rat from those prepared from BUF/Nac (BUF), and vice versa. All the polymorphic fragments detected "presence-or-absence" polymorphisms with B1-amplicons prepared from ACI, BUF, and their F2 progeny, and each fragment was linkage mapped. Dot-blotting amplicons onto filters at a high density and hybridization of the filters with these B1-RDA markers made it possible to genotype a large number of rats simultaneously for multiple loci. These B1-RDA markers were polymorphic between two given inbred strains of rat at frequencies between 30% and 70%. This is the first report on the isolation of B1-RDA markers among inbred strains of rats.

Animals↗

PubMed1998

Developmental changes in carbonic anhydrase II in the rat kidney.

We examined the distribution and maturational changes of carbonic anhydrase I (CAI) and carbonic anhydrase II (CAII) in microdissected nephron segments of Sprague-Dawley rats. CAI and CAII proteins were measured by enzyme-linked immunosorbent assay. CAI was not detected in any nephron segment in 7-week-old rats. CAII was present in the collecting ducts, proximal tubules, and thick ascending limbs of loop of Henle in 7-week-old rats. CAII contents were significantly higher in the early proximal tubules (S1) than in second (S2) and late (S3) portions of the proximal tubules, while the contents in S1 were less than in cortical collecting ducts (CCD), outer stripe and inner stripes of the outer medullary collecting ducts (OMCDo and OMCDi). CAII content in each of S1, CCD, and OMCD of 1-week-old rats was only 14% or less of that of adults, but increased steeply during the 2nd and 3rd weeks of life, reaching almost 40% at 3 weeks of age and 97% at 7 weeks. Our results indicate that CAII is present throughout the entire nephron of the rat, and that CAII content in S1, CCD, and OMCD increases exponentially during the first 7 weeks of life. Our data suggest that the immature low levels of CAII may explain, at least in part, the limited capacity of urinary acidification during neonatal life. Further studies are necessary to establish the role of such changes in CAII content in acid-base homeostasis during neonatal life.

Animals↗

PubMed1998

Allograft rejection of small bowel transplantation in pigs.

Small bowel allograft rejection in large animals has yet to be well defined. There are no specific early signs of graft rejection. The present experiments were undertaken to compare acute small bowel allograft rejection in pigs with and without FK506 and also to examine the usefulness of mucosal biopsies. Thirty-six outbred Large-White pigs were divided into (1) group 1 (n = 9): nonimmunosuppressed recipients; (2) group 2 (n = 8): FK506-immunosuppressed recipients; (3) group 3 (n = 2): autotransplant controls; and (4) donors (n = 17). Orthotopic small bowel transplantations were performed with Thiry-Vella loops for daily biopsies. The survival rate of group 2 was significantly longer than that of group 1 (P < 0.05). One best survivor in group 2 was killed at postoperative day (POD) 365. Treatment by FK506 prevented rejection, but most of the pigs died of pneumonia. In group 1, rejection began on POD 3 and progressed to severe rejection rapidly within 7 days. In group 2, rejection began from POD 6 to POD 8, but either remained mild or spontaneously improved. The differences in the routine laboratory data and the tumor necrosis factor-alpha level were not evident between the groups. Histological studies of repeated graft biopsies are thus considered to be essential for detecting signs of graft rejection.

Animals↗

PubMed1998

Glomerular thromboxane contributes to pressor response in deoxycorticosterone acetate-salt hypertension.

To assess the role of renal thromboxane in a salt sensitive pressor response in hypertension, urinary excretion of thromboxane and its release from isolated glomeruli and renal papillae were examined in deoxycorticosterone acetate treated rats with normal (0.6%, n = 12) and high (4%, n = 12) salt diets for 8 weeks. Mean blood pressure, measured directly by an implanted aortic catheter, was higher in the high salt diet group than in the normal salt diet group (146 +/- 2 vs 119 +/- 2 mmHg, P<0.01). Urinary excretion of thromboxane B2 and 6-keto-prostaglandin F1alpha in the high salt group were significantly higher than those in the normal salt diet group, but there was no difference in urinary excretion of prostaglandin E2 between the two groups. Release of thromboxane B2, 6-keto-prostaglandin F1alpha, and prostaglandin E2 from isolated glomeruli in the high salt diet group increased significantly by 104%, 55%, and 74%, respectively, compared with the normal salt diet group. Stepwise multiple linear regression analysis showed that significant contributory factors for mean blood pressure in deoxycorticosterone acetate treated rats were urinary excretion of sodium (F=14.187, P<0.01) and release of thromboxane B2 from isolated glomeruli (F=4.135, P<0.05). The unstandardized coefficient (R) calculated from the regression function using these two factors was 0.875 and R2 was 0.765. The manifest synthesis of thromboxane in renal glomeruli has an important role on salt sensitive pressor response in deoxycorticosterone acetate-salt hypertension of rats.

6-Ketoprostaglandin F1 alpha↗

PubMed1998

DNA adduct level induced by 2-amino-3,4-dimethylimidazo[4,5-f]-quinoline in Big Blue mice does not correlate with mutagenicity.

In previous experiments we analyzed the mutant frequency (MF) and mutational types in various organs of lacI transgenic mice which were fed a diet containing 300 p.p.m. 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), a food-borne mutagen/carcinogen. To clarify the relationships between mutational type and adduct molecular species and between adduct level and MF we analyzed adducts in the same DNA samples. The DNA adduct in the liver, heart, colon, forestomach and bone marrow was determined by the modified intensification method of 32P-post-labeling at time points 1, 4 and 12 weeks. Only a single spot corresponding to N2-(deoxyguanosin-8-yl)MeIQ 5'-monophosphate was detected in DNA from all organs at all time points examined, with a recovery of 48%. The difference in mutation type between bone marrow and other organs detected in the previous experiment was not explained by adduct molecular species. At 4 and 12 weeks administration the adduct levels were highest in the liver and then heart, colon, forestomach and bone marrow in decreasing order, with values of 28.3, 8.4, 3.3, 1.3 and 0.4 molecule/10(7) nucleotides at 12 weeks. Based on our previously reported data, lacI MF was highest in the colon and those in the liver, bone marrow and forestomach were 10-60% of that of the colon; no increase in MF was detected in the heart, where no DNA replication is expected except for vascular endothelial cells. There was no direct relationship between MF and adduct level. The MF may be the product of adduct level and cell proliferation rate.

Animals↗

PubMed1998

Linkage mapping of the Bra, Brb and Brg genes for rat protein phosphatase 2A 55 kDa B-regulatory subunit isotypes.

We previously identified the rat Bra, Brb and Brg genes, which encode alpha, beta and gamma isotypes of the 55 kDa B-regulatory subunit of protein phosphatase 2A. Polymerase chain reaction-single strand conformation polymorphism analysis in the present study identified polymorphisms in Bra, Brb and Brg between the ACI and BUF, ZI and TM, and BN and WTC strains, respectively. Linkage analysis using mapping panels composed of F2 or back-crosses of these strains allowed Bra, Brb and Brg to be assigned to chromosomes 15, 18 and 14, respectively. Furthermore, it was revealed that Bra is located close to the Rb1 locus. Using polymorphism in Bra, loss of heterozygosity (LOH) was analyzed for rat mammary tumors induced in (SD x F344) F1 female rats by a food-borne carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, and a typical mammary carcinogen, 7,12-dimethylbenz[a]anthracene. No LOH was detected at the Bra locus.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1998

[Surgical technique of endoscopic transthoracic sympathicotomy: axillary approach].

A total of 181 endoscopic transthoracic sympathicotomy were performed at our hospital from December, 1992 to March, 1997. After single-lumen endotracheal intubation for general anesthesia, the patient was placed in half sitting position. A small (1 cm) incision was made in the anterior axillary line through the third intercostal space and an apical pneumothorax was created by insufflation of 1.8 L of CO2 in the pleural cavity through a Surgineedle. A 24 Fr. urological transurethral electroresectoscope was introduced through the same incision. The sympathetic chain could be observed through parietal pleura riding on the costovertebral junctions. In palmar hyperhidrosis the second and third thoracic sympathetic ganglia were electrocoagulated. In axillary hyperhidrosis the forth ganglion was included. The lung was expanded by limiting expiration and sucking CO2. The operation was repeated on the other side. Endoscopic transthoracic sympathicotomy was an efficient, safe and low invasive surgical procedure for the treatment of palmar, axillary hyperhidrosis, Raynaud's disease and Buerger disease.

Axilla↗

PubMed1998

[Pitfall of minimally invasive direct coronary artery bypass].

Six thoroughly selected patients underwent minimally invasive direct coronary artery bypass grafting (MIDCAB). While monitoring left ventricular function with transesophageal echocardiography, MIDCAB was done by performing small left thoracotomy through the fourth intercostal space, dissection of the left internal thoracic artery without thoracoscopy, ischemic preconditioning, and grafting of the internal thoracic artery to the left anterior descending coronary artery with 8-0 polypropylene continuous suture. A home-made cardiac stabilizer and Visuflow enabled us to perform precise suturing of the internal thoracic artery. The patency of all grafts was confirmed by early transthoracic Doppler echocardiography and selective angiography. A new stenosis of the coronary artery distal to the anastomosis was detected probably due to coronary snaring in one patient. The anastomosis sites were confined to the distal segments of the left anterior descending coronary artery in MIDCAB patients. The optimal anastomosis site may be missed in the patients with proximal left anterior descending artery disease. An experimental study of myocardial tissue oxygen saturation using near infrared spectroscopy showed that two times of coronary occlusion and reperfusion provided satisfactory effects of ischemic preconditioning. Measurement of the myocardial tissue oxygen saturation may be helpful for confirming effective ischemic preconditioning and a safe coronary occlusion during MIDCAB. Although MIDCAB is an attractive procedure, we should consider the accuracy of anastomosis, the risk of possible incomplete revascularization, the indications, and long-term results.

Aged↗

PubMed1998

[A case report of cavernous hemangioma of the left atrial epicardium].

Cardiac hemangioma is a rare benign vascular tumor. A 44-year-old woman with hemangioma arising from the left atrium and transient atrial fibrillation is reported. Echocardiography, computed tomography and magnetic resonance imaging suggested a hypervascular tumor with clear borders in the pericardial cavity. Selective coronary angiography demonstrated feeding arteries arising from the right and left circumflex coronary arteries. Under cardiopulmonary bypass the tumor was successfully resected. Pathological examination showed a cavernous hemangioma. There is no evidence of recurrence and the patient is doing well three years after the operation.

Adult↗

PubMed1998

[Evaluation of the effect of ischemic preconditioning using near-infrared spectroscopy].

Ischemic preconditioning (IP) protects the myocardium from subsequent sustained ischemic insults. Temporary occlusion of the coronary artery is indispensable for anastomosing the graft vessel during coronary artery bypass operation without cardiopulmonary bypass. In the canine model of ischemia and reperfusion, we measured myocardial tissue oxygen saturation (SO2) continuously using near-infrared spectroscopy to determine the effect of IP on myocardial oxygen metabolism. Nine dogs underwent occlusion of the left descending coronary artery for three 5-minute periods, followed by three 5-minute periods of reperfusion. The dogs were then subjected to a 20-minutes periods of sustained coronary artery occlusion, followed by prolonged reperfusion. The myocardial SO2 was 82 +/- 2% at the baseline before coronary occlusion and was decreased to 74 +/- 2%, 76 +/- 2%, 77 +/- 3%, 77 +/- 3% at the first, second, third and sustained coronary occlusion, respectively. The increase in the minimum myocardial SO2 value at the second and third coronary occlusion suggested the effect of IP. Near-infrared spectroscopy is a useful method of continuously monitoring myocardial oxygenation and of evaluating the effect of IP during off-pump heart surgery.

Animals↗

PubMed1997

BRCA1 and BRCA2 Germline Mutations in Japanese with Hereditary Breast Cancer Families.

We examined germline mutations in BRCA1 and BRCA2 in 23 Japanese breast cancer families, using PCR-SSCP analysis. The same nonsense mutation (exon 5, Leu63ter) of BRCA1 was detected in two defferent families. Three different mutations resulting in a truncated BRCA2 protein (exon 9, 20, 24) were detected in three different families, including one male case of breast cancer. One base substitution mutation in BRCA2, A10462G, was detected in the other two families. Although the mean age of onset for breast cancer in families with the BRCA1-mutation was 50 years, the age of onset in families with the BRCA2-mutation was from 28 to 43 years. Among the 23 families examined, two families had members with ovarian cancers, three had members with prostate cancers, and one had a pancreatic cancer. However, none of these families was positive for the BRCA1 orBRCA2 mutation. Histopathologically, we observed a prevalence of histological grade 3 in BRCA1/2-associated familial breast cancers, because of nuclear atypia, structural atypia and mitotic activity. It is suggested that BRCA2 may play a more important role than BRCA1 in Japanese familial breast cancers, and these mutations are related to the aggressive nature and highly proliferative activity of the tumors.

Journal Article↗

PubMed1997

Effects of gender and species on spectra of mutation induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in the lacI transgene.

Feeding of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) to F344 rats induces colon tumors specifically in male rats. Mutant frequencies and mutational spectra of the lacI transgene were studied in male and female Big Blue transgenic rats after feeding 400 ppm of PhIP in the diet for 60 days. Mutant frequencies in the colon mucosa were increased 20-25 times compared with those of the control rats, being 661.4 +/- 33.3 x 10(-6) and 718.2 +/- 16.9 x 10(-6) in males and females, respectively. No significant differences in types and distribution of the mutations were detected between males and females. One-base deletions were the most frequent mutation, including the characteristic guanine deletion at 5'-GGGA-3' which is also seen in the Apc gene of rat colon cancers induced by PhIP. Comparison of the lacI mutations in the rat colon with those previously identified in the mouse colon showed that the rate of G to T transversions was significantly higher in the mouse. This is the first report stating that there exist differences in the mutation specificity on the same gene, among mammalian species. However, the characteristic guanine deletion was recovered in both the mouse and the rat. These findings do not offer a mechanistic explanation of the gender specificity of PhIP-induced colon cancer in rats, though the universality of the guanine deletion suggests that this alteration may prove a useful indicator of human exposure.

Animals↗

PubMed1997

Primary gastric T-cell lymphoma with and without human T-lymphotropic virus type 1.

BACKGROUND: Gastric T-cell lymphomas are rare, and their incidence and viral status have not yet been fully clarified. METHODS: Sixty-seven cases of surgically resected gastric lymphomas from city hospitals in Tokyo were evaluated. The surface phenotype was determined by immunohistochemistry, gene rearrangement by Southern blot hybridization, association with Epstein-Barr virus (EBV) by EBV-encoded small RNAs in situ hybridization, and the presence of human T-cell lymphotropic virus type 1 (HTLV-1) by serology, Southern blot hybridization, and polymerase chain reaction analysis. RESULTS: Five of the 67 cases were T-cell lymphoma (7%): 3 cases were HTLV-1 negative (-) and 2 were HTLV-1 positive (+). Systemic eosinophilia was observed in the three HTLV-1(-) gastric lymphomas. Neoplastic cells were morphologically similar in both groups, but a granulomatous reaction with marked eosinophilia was observed only in the two cases of HTLV-1(-) lymphoma. They also had characteristics of natural killer (NK) cell-like T-cell lymphoma, expressing NK markers and TCRgamma gene rearrangement. Positivity with HML-1 (specific for intestinal epithelial T-cells lymphoma was observed in one HTLV-1(+) lymphoma. The EBV gene was detected in only one case of B-cell lymphoma but not in any case of T-cell lymphoma. CONCLUSIONS: Gastric T-cell lymphoma occurs in 7% of gastric lymphomas in Japan and is comprised of HTLV-1-related lymphomas and lymphomas unrelated to HTLV-1, including NK cell-like lymphomas with eosinophilia.

Adult↗

PubMed1997

Genetic changes induced by heterocyclic amines.

Clarification of the mutational fingerprints of HCAs offers a promising approach in the investigation of the role of heterocyclic amines (HCAs) in human carcinogenesis. We analyzed mutations in the tumor related genes of tumors induced by HCAs, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), which mainly yield DNA-adducts of C8-guanine. The G-->T transversion at codon 13-2nd position in Ha-ras was predominantly observed in mouse forestomach and rat Zymbal gland tumors induced by MeIQ. In contrast, various types of mutation were detected in the ras family genes of rat Zymbal gland tumors induced by IQ; the presence of a methyl group at position 4 of imidazo[4,5-f]quinoline gave rise to a remarkable difference in the mutational fingerprint. Apc mutations were detected in PhIP- and IQ-induced rat colon tumors, with incidences of 50% (4/8) and 15% (2/13), respectively. All five mutations detected in the four PhIP-induced tumors consisted of a guanine deletion from the 5'-GGGA-3' sequence, in contrast with T to C and C to T mutations in IQ-induced tumors. Four of these five mutations shared seven common nucleotides, -GTGGGAT- surrounding the guanine; indicating that PhIP leaves a characteristic mutational fingerprint in Apc. Colon tumors induced by PhIP were also found to have mutations in their microsatellite sequences, and similar results were detected in mammary gland tumors induced by PhIP, contrasting with no mutations in IQ-induced colon tumors and a very low frequency of mutations in 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors. Although the mechanisms involved in the induction of microsatellite mutations are not known yet, microsatellite mutations which can also be detected in sporadic human tumors, including colon and breast tumors, were indicated to be a characteristic of PhIP. Mammary tumors induced by PhIP showed loss of heterozygocity (LOH) at the distal part of chromosome 10, which shows synteny with the distal part of human chromosome 17, where LOH frequently occurs in human breast cancer. In conclusion, each heterocyclic amine leave a mutational fingerprint which is specific to each compound. Since the tumor-related genes involved in PhIP-induced tumors have characteristics in common with those in human cancers, further detailed analysis will provide us with useful information on mutational fingerprints, and on the possible contribution of PhIP to human colon cancer.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1997

BRCA2 germline mutations in Japanese breast cancer families.

Germline mutations of BRCA2 were examined in 20 Japanese breast cancer families without BRCA1 mutations, including one demonstrating cancer development in a male. Three different mutations, resulting in truncation of the BRCA2 protein, were detected in 3 different families. They were 9474insA (exon 24, termination at codon 3110), C8729A (exon 20, S2834 ter) and 982del4 (exon 9, termination at codon 275). The 982del4 mutation was detected in the family with a case of male breast cancer. Age at onset was young, with a range of 28-43 years, in the 2 female breast cancer families with truncation mutations. One probable missense mutation, A10462G (13412V), was further detected in 2 families, although cosegregation of this allele with the breast cancer phenotype was not complete. The rate of BRCA2 mutations in Japanese families was suggested to be almost the same as in Western countries, and larger than it is the case for BRCA1.

Adult↗