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Biomedical subjects

T Nomoto

Publications and source records attributed to T Nomoto.

At least 55 records · Page 3Linked to original sources

Prevalence of verotoxin-producing Escherichia coli harbored in the intestine of cattle in Japan.

The production of verotoxin was examined in 2152 Escherichia coli isolates from 387 cattle in Japan from 1992 to 1994. The toxin was detected in 263 isolates from 94 cattle (detection rate: 24.3%). Verotoxin-producing E. coli (VTEC) was isolated from the cattle in 15 out of 17 prefectures, and the strains were divided into 33 serotypes. E. coli O157:H7 was isolated from 7 out of 387 cattle (detection rate: 1.8%) in four prefectures. These results suggest that VTEC is widely distributed in Japan and include a wide variety of serotypes.

Animals↗

[A case of Pryce type I intrapulmonary sequestration].

A twenty-year-old asymptomatic man hospitalized because of a vascular murmur and abnormal shadow in the left lower lung on X-ray film. An aortogram revealed an abnormal artery arising from the descending thoracic aorta and supplying the left basal segment, which had no other pulmonary arteries. Although lung ventilation scintigraphy demonstrated reduced ventilation to the left lower lobe, bronchogram showed an almost normal bronchial tree except that peripheral branches were slightly thin. A clinical diagnosis of Pryce type I intrapulmonary sequestration was made, and left lower lobectomy was performed successfully. We have analyzed 31 cases of Pryce type I intrapulmonary sequestration in Japan. A vascular murmur is often heard, and a chest X-ray usually shows either a mass shadow or increased vascular markings. In most of those cases, an abnormal artery arises from the descending thoracic aorta and it supplies the left basal segment. Because this type of sequestration causes hemoptysis and infections, surgical intervention is indicated.

Adult↗

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↗

Two-stage repair for aortic regurgitation with interrupted aortic arch.

We performed two-stage repair for a rare adult case of interrupted aortic arch with aortic regurgitation and sinus of Valsalva aneurysm. A lateroisthmic bypass was established with minimal thoracotomy and partial clamping of the descending aorta to preserve collateral circulation. This was followed by aortic root reconstruction with a prosthetic graft and valve for aortic regurgitation with sinus of Valsalva aneurysm. This less invasive two-stage repair for such a rare pathology may facilitate smooth recovery of the patient.

Adult↗

Monitoring of regional cerebral oxygenation by near-infrared spectroscopy during continuous retrograde cerebral perfusion for aortic arch surgery.

OBJECTIVE: To assess the value of monitoring of regional cerebral oxygen saturation (rSO2) during aortic arch surgery using continuous retrograde cerebral perfusion (CRCP) in conjunction with profound hypothermic circulatory arrest (HCA). METHODS: The rSO2 of 12 consecutive patients was monitored non-invasively using near-infrared spectroscopy (NIRS) and the data were analyzed statistically. RESULTS: The mean duration of HCA with CRCP was 62-/+14.1 min. The mean CRCP flow rate was 226+/-163 ml/min. Surgical outcomes were favorable with only a single hospital death (8.3%). However, the rSO2 decreased gradually in all patients during HCA, even combined with CRCP, and fell to 46+/-8.7% on average. It did not change so greatly before HCA and returned finally to its initial level at the end of re-warming. Only one patient developed a permanent neurologic deficit; this patient showed the greatest decrease of rSO2 from 56% to 29% after the longest HCA of 88 min. Two parameters, End-rSO2 (the ratio of post- to pre-HCA rSO2) and delta-rSO2 (the rate of decrease from preto post-HCA rSO2) were obtained since the initial values of rSO2 before surgery differed. There were linear correlations between the CRCP flow rate and each of these two parameters. A multiple regression analysis also revealed a linear equation relating the parameters, which allowed prediction of the safe duration of HCA in different conditions of CRCP and a more favorable adjustment of the CRCP condition in each patient. CONCLUSIONS: The study suggests that the combination of HCA and CRCP has a limit of safe duration in spite of its potential usefulness for brain protection, and that rSO2 monitored by NIRS is useful in testing for adequate brain protection. It is hoped that monitoring of rSO2 can facilitate prediction of the safe duration of HCA with CRCP and a more favorable adjustment of CRCP.

Aortic Aneurysm, Thoracic↗

Characterization of a human small-cell lung cancer cell line resistant to a new water-soluble camptothecin derivative, DX-8951f.

DX-8951f, a water-soluble and non-pro-drug analogue of camptothecin, exhibits a strong inhibitory action on DNA topoisomerase I (Topo I) and in vitro cytotoxicity against various human cancer cell lines. In order to elucidate the mechanisms of its cytotoxicity, we established a DX-8951f-resistant cell line, SBC-3/DXCL1, from human small cell lung cancer cells (SBC-3) by stepwise exposure to DX-8951f. SBC-3/DXCL1 cells were approximately 400 times more resistant to DX-8951f than parent cells. The SBC-3/DXCL1 cells showed a high degree of cross-resistance to other Topo I inhibitors such as CPT-11, SN-38 and camptothecin, but not to non-Topo I targeting agents such as cisplatin, adriamycin, etoposide, and vincristine. The mechanisms of resistance of SBC-3/DXCL1 cells to DX-8951f were examined. Intracellular accumulation of DX-8951f by SBC-3 and SBC-3/DXCL1 cells did not differ significantly. Although the Topo I activity of nuclear extracts obtained from SBC-3/DXCL1 cells was the same as that of the parent cells, the Topo I of SBC-3/DXCL1 cells was resistant to the inhibitory effects of DX8951f and SN-38. Immunoblotting using anti-Topo I antibody demonstrated similar protein levels of Topo I in SBC-3 and SBC-3/DXCL1 cells. The active Topo I protein of SBC-3/DXCL1 was eluted by a high concentration of NaCl (0.4 N) compared with that of SBC-3 (0.3 N). DX-8951f stabilized the DNA-Topo I cleavable complex from SBC-3 cells, as measured by Topo I-mediated cleavage assay. In SBC-3/DXCL1 cells, DX-8951f also stabilized the DNA-Topo I complex, but with a 10-fold lower efficiency. These results suggest that a qualitative change in Topo I contributes, at least partially, to the resistance to DX-8951f in SBC-3/DXCL1 cells. Therefore, SBC-3/DXCL1 cells may have a unique mechanism of resistance to Topo I-directed antitumor drugs.

Antineoplastic Agents, Phytogenic↗

NADH-dependent inhibition of branched-chain fatty acid synthesis in Bacillus subtilis.

Addition of NADH to crude but not to pure branched-chain alpha-keto acid decarboxylase decreased the CO2 production from alpha-keto-beta-methylvalerate (KMV) suggesting the presence of an NADH dependent inhibitor in the crude enzyme from Bacillus subtilis. This NADH-dependent decarboxylase inhibitor was purified to homogeneity by a fast protein liquid chromatography system. The purified inhibitor was identical with leucine dehydrogenase as to N-terminal amino acid squence (35 residues) and molecular weight, and catalyzed the oxidative deamination of three branched chain amino acids (BCAAs), valine, leucine, and isoleucine. The decarboxylase inhibitor was therefore identified as leucine dehydrogenase. A decreased substrate availability caused by leucine dehydrogenase thus reasonably accounted for the NADH dependent inhibition of the decarboxylation. In turn, the observation that leucine dehydrogenase competes with the decarboxylase for branched-chain alpha-keto acid (BCKA) suggested an involvement of this enzyme in the branched chain fatty acid (BCFA) biosynthesis. This view was supported by the observation that addition of NAD to crude fatty acid synthetase increased the incorporation of isoleucine into BCFAs. Pyridoxal-5'-phosphate and alpha-ketoglutarate, cofactors for BCAA transaminase, modulated BCFA biosynthesis from isoleucine in vitro, suggesting also the involvement of transaminase reaction in BCFA biosynthesis.

Acyltransferases↗

Persistent primitive hypoglossal artery complicated by atrial septal defect and congenital intrahepatic shunts.

During early embryogenesis, anastomoses are formed between the carotid artery and the basilar or the vertebral artery, and subsequently, these anastomoses regress. In some cases, these anastomoses remain as persistent carotid-basilar or carotid-vertebral anastomoses. Atrial septal defect (ASD), a communication between the atria at the septal level, is a congenital heart anomaly. Intrahepatic venous shunts between the portal and hepatic veins are very rare and only some are considered congenital. We present the first case report of a patient with an ASD, a persistent primitive hypoglossal artery, and congenital portahepatic shunts.

Aged↗

Spontaneous retrograde dissection of the entire thoracic aorta originating in the abdominal aorta. Case report and review of the literature.

Spontaneous retrograde thoracic extension of the abdominal aortic dissection is extremely rare and difficult to manage. Only five cases have been previously reported in the English literature (dissection reaching the ascending aorta in four, dissection limited in the descending thoracic aorta in one), and all the cases of dissection which reached the ascending aorta were lethal. We herein report one case of a 37-year-old man who was operated on for spontaneous retrograde dissection of the entire thoracic aorta originating in the suprarenal abdominal aorta. Preoperative aortogram revealed the site of the intimal tear just above the celiac artery. He urgently underwent graft replacement of the descending thoracic aorta and the abdominal aorta with reimplantation of the thoracoabdominal visceral arteries. Although the patient had to undergo the second operation for the dissection of the remaining thoracic aorta four months postoperatively, he has been doing well 18 months after the second operation.

Adult↗

Coronary artery bypass grafting for an adult with coronary disease due to Kawasaki disease.

Surgical treatment for patients over the age of forty with coronary aneurysms associated with Kawasaki disease is rare. We report on a 47-year-old man who underwent coronary artery bypass grafting using the left internal thoracic arteries (ITA) and right gastroepiploic (GEA). The postoperative course was uneventful. One month later, the normal stress thallium-201 myocardial perfusion imaging was normal and coronary angiography showed good patency for the ITA, GEA, and saphenous vein grafts. He had some coronary risk factors including smoking, hypertension and hyperlipidemia. Histological examination of a sample shows that the coronary artery sequelae of Kawasaki disease have already become part of increasing burden of adult ischemic heart disease.

Coronary Angiography↗

Aortic valve replacement in a patient with previous coronary artery bypass grafting.

Gaining a sufficient exposure for aortic valve surgery after previous coronary artery bypass grafting (CABG) has been a problem due to the patent saphenous vein grafts. Although a patient had had CABG twice we performed aortic valve replacement (AVR) with almost the usual exposure. We attached the proximal anastomosis in a more distal position of the ascending aorta than usual, at the first CABG, as he was diagnosed to have mild aortic valve stenosis prior to surgery. We consider this method allows easier AVR after previous CABG when the patient is diagnosed with mild aortic valve stenosis before CABG.

Angina Pectoris↗

Circumvention of glutathione-mediated mitomycin C resistance by a novel mitomycin C analogue, KW-2149.

A novel antitumor antibiotic 7-N-[2-[[2-(gamma-L-glutamylamino)ethyl]dithio]ethyl] mitomycin C (KW-2149), an analogue of mitomycin C (MMC), is activated by thiol molecules, such as glutathione (GSH). To clarify the relationship between cellular GSH levels and the cytotoxicity of KW-2149, a murine fibroblast cell line (NIH/3T3) was transfected with human gamma-glutamylcysteine synthetase (gamma-GCS) cDNA, which codes a rate-limiting enzyme of GSH synthesis. Transfected cells (3T3/GCS) displayed increased gamma-GCS mRNA levels, gamma-GCS activity and GSH content, compared with NIH/3T3 cells. 3T3/GCS cells exhibited a 4.4-fold resistance to MMC, but not to KW-2149 (x 0.69), using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, suggesting that the increased cellular GSH levels did not affect the growth-inhibitory effect of KW-2149. KW-2149 exerted a greater growth-inhibitory effect than MMC on cisplatin- and doxorubicin-resistant cells with cross-resistance to MMC. KW-2149 exhibited a greater growth inhibitory effect than MMC not only on cells with GSH-mediated MMC resistance but also on cells with acquired resistance. We thus conclude that KW-2149 might be a clinically useful drug.

3T3 Cells↗

Identification of cis-acting DNA elements of the human gamma-glutamylcysteine synthetase heavy subunit gene.

Transcriptional activity of the 5'-flanking sequence of the human gamma-glutamylcysteine synthetase heavy subunit (gamma-GCSh) gene was investigated in COS7 cells transfected with hGH reporter constructs having successively deleted 5'-flanking sequence of the gamma-GCSh gene. Transcriptional activity was determined by the amounts of hGH secreted from the reporter constructs. Deletion of the sequence from -1,413 to -664 or -315 base pairs (bp) increased transcriptional activity from 100 to 138 or 136%. Further deletion from -315 to -241 bp, which contained an AP1 site, decreased transcriptional activity to 87%. Mutations introduced into the AP1 decreased transcriptional activity from 136 to 105%. These findings suggested that the AP1 increased transcriptional activity. When the sequence from -241 to -192 bp was deleted, transcriptional activity was restored from 87 to 128%. When this sequence was linked to the thymidine kinase promoter, it also decreased transcriptional activity by 38%. Deletion from -192 to -149, -116, or -108 bp did not significantly alter transcriptional activity. Further deletion of the GC-rich sequences from -108 to -70 and -28 bp dramatically decreased transcriptional activity from 135 to 87 and 34%, respectively. These findings indicate that multiple DNA elements, especially those in the proximal GC-rich sequences, are involved in the regulation of transcriptional activity of the gamma-GCSh gene.

Base Composition↗

Mitral valve repair in a patient with severe porcelain aorta.

We repaired the mitral valve in a patient with severe porcelain aorta. Significant mitral regurgitation developed in a 66-year-old woman with heavy calcification throughout the whole aorta. At operation, cardiopulmonary bypass was properly established by combined axillary and femoral arterial cannulations for sufficient systemic flow. Likewise, the combination of a superior mitral approach and profound hypothermic fibrillatory arrest in conjunction with low-flow cardiopulmonary bypass allowed us to repair the mitral valve successfully.

Aged↗

A case of type A dissection involving right aortic arch.

Aortic dissection involving right aortic arch (RAA) is quite rare. A patient with RAA and aberrant left subclavian artery (type 3 RAA) developed type A dissection, but successfully underwent ascending and hemiarch replacement under hypothermic circulatory arrest with continuous retrograde cerebral perfusion. We approached the lesion through a midline sternotomy and could reconstruct the first two arch vessels involved by the dissection. We would have added bilateral thoracotomy, if the distal arch vessels had required reconstruction. To our knowledge, this is the first report of successful surgical repair for type A dissection involving RAA.

Aortic Dissection↗

Constrictive pericarditis caused by an old hematoma.

A 46-year-old woman was admitted for surgery after diagnosis of a constrictive pericarditis. She had suffered from acute pericarditis and undergone pericardiocentesis to relieve pericardial effusion several times 10 years previously. Cardiac catheterization showed elevated mean right-atrial and pulmonary wedge pressures. Chest CT revealed only a calcified mass in the retrosternal space. At surgery, there was no severe adhesion between the pericardium and the epicardium, and the pericardium was thin and almost normal except over the right artio-ventricular groove, where a hard mass with an atheromatous content adhered to the epicardium. After resection of the mass, central venous pressure and pulmonary wedge pressure decreased. The mass was found to be an old hematoma by pathological examination. The patient was subsequently discharged from hospital in good condition.

Female↗

Defective stimulation of thyroxine 5'-deiodinase activity by cold exposure and norepinephrine in brown adipose tissue of monosodium glutamate-obese mice.

In order to examine the possible change in the thyroid hormone metabolism in the monosodium glutamate (MSG)-obese mice, we determined the iodothyronine deiodinase activity of brown adipose tissue (BAT), liver and kidney of male and female mice. There was no significant difference in the type II thyroxine 5'-deiodinase (T4 5'DII) activity in BAT between MSG-obese and control mice when they were kept at the ambient temperature of 22 degrees C. T4 5'DII activity in BAT of control mice increased markedly after exposure to cold (4 degrees C) for 4 h; however, the extent of cold-induced increase in T4 5'DII activity in BAT of MSG-obese mice was greatly reduced. Injection of norepinephrine (NE) (0.8 mg/kg, s.c.) 4 h previously increased T4 5'DII activity in BAT of control mice, but NE-induced increase in T4 5'DII activity was also markedly reduced in BAT of MSG-obese mice. Both cold- and NE-induced increase in T4 5'DII activity was greater in female, although similar tendency was obtained in male mice. Type I 3,3',5'-triiodothyronine deiodinase (rT3 5'DI) activity of liver and kidney, and serum thyroxine (T4) and 3,5,3'-triiodothyronine (T3) levels in MSG-obese mice were essentially the same as those of the control male and female mice irrespective of cold exposure. These results suggest that defective stimulation of T4 5'DII activity of BAT by cold in the MSG-obese mice is due to deficient sympathetic input to BAT and/or to diminished response of BAT to NE, and may contribute to a possible cause of inability of MSG-obese mice to maintain body temperature under cold exposure.

Adipose Tissue, Brown↗