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Biomedical subjects

H Nagano

Publications and source records attributed to H Nagano.

At least 73 records · Page 4Linked to original sources
PubMed1999

Evaluation of regional liver function by gadolinium-EOB-DTPA-enhanced MR imaging.

We evaluated the role of magnetic resonance (MR) imaging with gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA), in estimating regional liver function in a rat ischemia-reperfusion model. Ischemic liver damage was induced in the right lobe by vascular clamping for 0 (sham), 30 (I-30), 60 (I-60), and 90 min (I-90 group). The ischemic lobes in the I-60 and I-90 groups was clearly visualized as a high intensity area in the T1 images at late phase of Gd-EOB-DTPA enhancement, Moreover, the T1/2 of signal intensity in ischemic lobes significantly correlated with the duration of vascular clamping. We also observed significant correlation between T1/2 and ATP concentration in the liver tissue (r = -0.719, P = 0.04). Our results indicate that MR imaging with Gd-EOB-DTPA is useful for evaluation of regional liver function in rats.

Animals↗
PubMed1999

Both cell proliferation and apoptosis significantly predict shortened disease-free survival in hepatocellular carcinoma.

In this study, we investigated the proliferating cell index by the percentage of Ki-67 expressing cells (Ki-67 LI) and the apoptotic index (AI) by the number of morphologically apoptotic cells per 1000 carcinoma cells in haematoxylin and eosin sections of 76 hepatocellular carcinomas (HCC). Both indices showed excellent correlation with each other (P < 0.0001) and were significantly higher in cases of poor differentiation, of advanced stages, with portal invasion and with intrahepatic metastasis. Furthermore, cases with higher Ki-67 LI or higher AI displayed poor outcomes for disease-free survival (P = 0.0001 and P = 0.0005) by univariate analysis. By multivariate analysis, both indices could be regarded as independent prognostic factors. These results strongly suggest that Ki-67 LI and AI have very similar clinical significance, reflecting the existence of biologically aggressive phenotypes and poor disease-free survival rate in HCC.

Aged↗
PubMed1999

Effect of candesartan cilexetil (TCV-116) in rats with chronic renal failure.

BACKGROUND: Inhibition of the renin-angiotensin system by both angiotensin II type 1 receptor antagonists (AT1As) and angiotensin I-converting enzyme inhibitors (ACEIs) shows renoprotective effects in rats with chronic renal failure when treatment is started in the early phase of renal injury. In this study, we examined the renal protective effects of candesartan cilexetil (TCV-116), an AT1A, and enalapril, an ACEI, in the progressive phase of renal injury in 5/6 nephrectomized rats. METHODS: Candesartan cilexetil (1 mg/kg/day) and enalapril (10 mg/kg/day) were orally administered once a day for 4 weeks (the short-term experiment) or 16 weeks (the long-term experiment) to 5/6 nephrectomized rats beginning 15 weeks after the nephrectomy, that is, after they had already showed marked proteinuria. RESULTS: In vehicle-treated rats, proteinuria, glomerulosclerosis, and interstitial fibrosis developed. Moreover, enhanced expression of transforming growth factor-beta1 (TGF-beta1) in the injured glomeruli was observed. These adverse changes progressed with time, and in the short-term experiment, both drugs inhibited them. In the long-term experiment, the progressive proteinuria and the elevation of blood pressure were similarly attenuated by both drugs. However, candesartan cilexetil significantly inhibited the progression of glomerulosclerosis, the expression of TGF-beta1, and interstitial fibrosis, whereas enalapril did not. CONCLUSION: These results indicate that candesartan cilexetil shows potent and long-term preventive effects against the progression of previously developed renal injury.

Angiotensin Receptor Antagonists↗
PubMed1999

The effects of kallidinogenase on choroidal blood flow in a hypertensive rabbit model.

PURPOSE: The purpose of the present study was to investigate the effects of kallidinogenase on chorioretinal circulatory disorder, on the basis of chorioretinal blood flow and fundus findings, in a renal hypertensive rabbit model. METHODS: In a renal hypertensive rabbit model produced according to Goldblatt's method, chorioretinal blood flow was continuously measured by noncontact laser Doppler flowmetry (LDF). Ophthalmography was conducted before and 30 minutes after drug administration. RESULTS: Measurement by LDF revealed 16% reduction in chorioretinal blood flow in the hypertension group compared with the control group. The administration of kallidinogenase dose-dependently increased chorioretinal blood flow in both groups, the hypertension group being more sensitive to kallidinogenase than the control group. In contrast, none of the controls (vinpocetine and DL-alpha-tocopherol nicotinate) exerted effects on chorioretinal blood flow in the hypertension group. Fundus examination demonstrated narrowing of the choroidal arterioles following an increase in blood pressure, and expansion of the arterioles following the administration of kallidinogenase. CONCLUSION: Kallidinogenase was shown to improve ophthalmic circulation by increasing chorioretinal blood flow in renal hypertensive rabbits.

Animals↗
PubMed1999

Liver enriched transcription factors and differentiation of hepatocellular carcinoma.

The development of a complex organism relies on the precise temporal and spacial expression of its genome in many different cell types. The unique phenotype of hepatocytes arises from the expression of genes in a liver specific fashion, which is controlled primarily at the level of mRNA synthesis. By analysing DNA sequences implicated in liver specific transcription, it has been possible to identify members of the nuclear proteins, such as the liver enriched transactivating factors, hepatic nuclear factor 1(HNF-1), HNF-3, HNF-4, HNF-6, CCAAT/enhancer binding protein (C/EBP), and D binding protein (DBP), which are key elements in the liver specific transcriptional regulation of genes. Each of these factors is characterised by DNA binding domains that bind to unique DNA sequences (cis-acting factors) in the promoter and enhancer regions of genes expressed in terminally differentiated hepatocytes (such as, albumin, alpha 1-antitrypsin, transthyretin, alpha-fetoprotein). The determination of the tissue distribution of these factors and analysis of their hierarchical relations has led to the hypothesis that the cooperation of liver enriched transcription factors with the ubiquitous transactivating factors is necessary, and possibly even sufficient, for the maintenance of liver specific gene transcription. With the increase in information about transcriptional regulation, it should be possible to evaluate fully the clinicopathological usefulness of transcription factors in the diagnosis and treatment of hepatocellular carcinoma.

Carcinoma, Hepatocellular↗
PubMed1999

Genomic organization of the 260 kb surrounding the waxy locus in a Japonica rice

The present study was carried out to characterize the molecular organization in the vicinity of the waxy locus in rice. To determine the structural organization of the region surrounding waxy, contiguous clones covering a total of 260 kb were constructed using a bacterial artificial chromosome (BAC) library from the Shimokita variety of Japonica rice. This map also contains 200 overlapping subclones, which allowed construction of a fine physical map with a total of 64 HindIII sites. During the course of constructing the map, we noticed the presence of some repeated regions which might be related to transposable elements. We divided the 260-kb region into 60 segments (average size of 5.7 kb) to use as probes to determine their genomic organization. Hybridization patterns obtained by probing with these segments were classified into four types: class 1, a single or a few bands without a smeared background; class 2, a single or a few bands with a smeared background; class 3, multiple discrete bands without a smeared background; and class 4, only a smeared background. These classes constituted 6.5%, 20.9%, 3.7%, and 68.9% of the 260-kb region, respectively. The distribution of each class revealed that repetitive sequences are a major component in this region, as expected, and that unique sequence regions were mostly no longer than 6 kb due to interruption by repetitive sequences. We discuss how the map constructed here might be a powerful tool for characterization and comparison of the genome structures and the genes around the waxy locus in the Oryza species.

Journal Article↗
PubMed1999

Overexpression of cyclooxygenase-2 in carcinoma of the pancreas.

The level of cyclooxygenase (COX)-2 has been investigated recently in various human carcinomas. In the present study, we examined the distribution and extent of COX-2 protein in human pancreatic tumors using immunohistochemistry. A strong expression of COX-2 protein was present in 23 of 52 (44%) pancreatic carcinomas, a moderate expression was present in 24 of 52 (46%) pancreatic carcinomas, and a weak expression was present in 5 of 52 (10%) pancreatic carcinomas. In contrast, benign tumors showed weak expression or no expression of COX-2, and only islet cells displayed COX-2 expression in normal pancreatic tissues. Overexpression of COX-2 in carcinoma tissues was also confirmed by Western blot analysis. Furthermore, consistent with the results at protein levels, reverse transcription-PCR analyses indicated that COX-2 mRNA was overexpressed in 7 of 13 (54%) carcinomas, but in none of 3 benign tumors. Our findings suggest that COX-2 inhibitors might be potentially effective against pancreatic carcinomas and that COX-2 may be involved in certain biological processes in pancreatic islets.

Adenocarcinoma↗
PubMed1999

Nurses' perspectives concerning do-not-resuscitate (DNR) orders.

The purpose of this study was to investigate the views of the nursing staff concerning do-not-resuscitate (DNR) orders at the Tokai University Hospital where a controversial incident occurred several years ago. A 'Questionnaire on DNR Orders' was circulated and the anonymous answers were collected two weeks later. The questionnaire was returned by 706 of 780 (90.5%) nurses from every ward/specialty, which revealed that 87% of the nurses felt that DNRs were occasionally necessary, with more than 40% of the nurses answering that they took part in DNR. Further, 36% of the nurses stated that patient consent was indispensable, and 64% thought that the patient's family and physician could decide DNR in the event the patient was physically unable to give consent. Moreover, 66% of the nurses expected the establishment of a DNR order sheet to be formulated as a matter of hospital policy; only 5% of the nurses thought that such an order sheet would not be necessary. Comparing these results with a previous study polling physicians at the Tokai University Hospital, nurses are more likely than physicians to think that patient consent is indispensable, and want the establishment of a standardized DNR order sheet as hospital policy. There is, in fact, a "tacit understanding" between physicians and patients' families in medical practice in Japan. However, DNR is definitely a medical decision. Therefore it should be clearly stated in a standardized format, although such a procedure presently seems unlikely, in view of the Japanese traditional value system.

Adult↗
PubMed1999

[A case report of hepatocellular carcinoma with hepatic and portal venous tumor thrombus and multiple intrahepatic metastasis who survived over 1 year after the operation with combined locoregional chemotherapy].

Hepatocellular carcinoma (HCC) with vascular invasion and/or intrahepatic metastasis (IM) has a poor prognosis, so advanced HCC may be considered as a contraindication for hepatectomy. We experienced a case of HCC with hepatic venous and portal venous tumor thrombus and multiple IM who survived over 1 year after the operation with combined locoregional chemotherapy. (Case): A 67-year-old male patient was diagnosed with HCC with extracapsular invasion after transarterial embolization (TAE). CT scan revealed the HCC had a right portal venous tumor thrombus and multiple IM. Posterior lobectomy and thrombectomy of hepatic venous and portal venous tumor thrombus and placement of portal venous catheter ware performed. From the first day after operation the patient received continuous intravenous and intraportal 5-FU for 3 weeks. At the first month after operation, TAE and PEIT were given against residual IM. After discharge the patient received hepatic arterial infusion chemotherapy (MTX/CDDP/5-FU/Leucovorin). Fourteen months after operation, the patient is surviving in good physical condition.

Aged↗
PubMed1999

Molecular mechanism involved in increased expression of sialyl Lewis antigens in ductal carcinoma of the pancreas.

Increased expression of sialyl Lewis antigens, sLe(a) and sLe(x), is frequent during malignant transformation and tumor progression of gastrointestinal cancers and it is assumed to be correlated with the increased metastatic potential of tumor cells and, consequently, with poor patient survival. To determine the influence of the increased expression of these antigens in disease progression of ductal carcinoma of the pancreas, immunohistochemical expressions of sLe(x) and sLe(a) in 51 ductal carcinomas of the pancreas were examined. We also examined the expression of glycosyltransferase genes, which are involved in the synthetic pathways of these antigens to understand the molecular mechanism involved in the increased expression of these antigens. Of the 51 primary ductal carcinomas of the pancreas, 40 (78.4%) were sLe(a)-positive and 11 (21.6%) were sLe(a)-negative; 16 (31.4%) were sLe(x)-positive and 35 (68.6%) were sLe(x)-negative. Although there were no significant differences in any examined clinicopathological factors such as age, sex, histological type, tumor size, presence of lymph node metastasis, or presence of vessel invasion between the positive and negative groups with both the sLe(a) and sLe(x) antigens, patient survival tended to be worse in the antigens-positive group than in the antigens-negative group. Increased expression, however, was not dependent on the increased expression of a single glycosyltransferase gene examined among five such genes, which are postulated to be responsible for the synthesis of the sLe(a) and sLe(x) epitopes in the glycosylation pathway. Furthermore, the increased expression of these antigens was not closely associated with mutations status of the K-ras or p53 genes. These findings suggested that increased expression of sialyl Lewis antigens are involved in pancreatic tumorigenesis and that the accumulation of genetic alterations or epigenetic changes is responsible for the molecular mechanisms of increased expression of the sLe(a) and sLe(x) antigens in ductal carcinomas of pancreas.

Adenocarcinoma↗
PubMed1999

Increased expression of COX-2 in nontumor liver tissue is associated with shorter disease-free survival in patients with hepatocellular carcinoma.

Recent studies have shown increased levels of cyclooxygenase-2 (COX-2) in a variety of human malignancies including hepatocellular carcinoma (HCC), but little is known about the prognostic value of COX-2 in HCC or its associated nontumor liver tissue. We examined the expression of COX-2 protein by immunohistochemistry in 53 patients with HCCs whose corresponding nontumor tissues were hepatitis C virus-related chronic hepatitis (n = 21) and cirrhosis (n = 32). Samples of nine histologically normal livers and eight precancerous dysplasias were also analyzed. The level of COX-2 increased from normal liver to chronic hepatitis to cirrhosis. The majority of cirrhotic livers (81%) displayed marked COX-2 expression. In dysplasias, COX-2 expression was mainly moderate or strong (88%). In HCC, 17% of samples displayed a high COX-2 expression, and 37% of samples expressed COX-2 at a moderate level. Concordant results were obtained with reverse transcription-PCR and Western blot analyses. Clinicopathological survey indicated a significant correlation between COX-2 expression and differentiated carcinoma (P = 0.019). Although there was no correlation between COX-2 expression in HCC and prognosis, a striking difference was found between COX-2 expression in nontumor tissue and shorter disease-free survival (P = 0.0132). Moreover, high COX-2 expression in nontumor tissue was significantly correlated with the presence of active inflammation (P < 0.0001). The present findings suggest that COX-2 expression in nontumor tissue may play a positive role in relapse of HCC after surgery.

Blotting, Western↗
PubMed1998

Nucleotide sequence homology to bovine viral diarrhea virus 2 (BVDV 2) in the 5' untranslated region of BVDVs from cattle with mucosal disease or persistent infection in Japan.

Cytopathogenic and non-cytopathogenic bovine viral diarrhea viruses (BVDVs) were isolated from cattle with mucosal disease or persistent infection in Japan. These isolates were compared for antigenic properties by cross-neutralization tests with Japanese reference strains of BVDV belonging to classical type 1. Significantly low cross-reactivity to reference strains was noted, indicating the viruses to possibly represent a new serotype in Japan. Thus, to determine the genotype of the isolates, nucleotide sequences of the 5' untranslated region were determined and compared with those of previously reported BVDV 1 and 2. The isolates were clearly shown to belong to BVDV 2, not to BVDV 1.

Animals↗
PubMed1998

Pattern of graft- and host-specific MHC class II expression in long-term murine cardiac allografts: origin of inflammatory and vascular wall cells.

In solid-tissue allografts, donor vascular cells as well as recipient inflammatory cells can express MHC class II molecules. However, it is uncertain how much residual donor endothelium persists and to what extent donor versus recipient MHC class II expression can contribute to the ongoing immune response, especially in long-term grafts. To establish the origin of class-II-expressing cells in the allograft, we evaluated the expression of donor- or recipient-specific MHC class II molecules in murine cardiac allografts. Donor hearts from BALB/c (H-2d) mice were transplanted into C57BL/6 (B6, H-2b) recipients; B6 isografts served as controls. Untreated allografts ceased functioning at approximately 7 days with severe parenchymal rejection. Allografts from recipients treated with anti-CD4 and anti-CD8 MAbs after transplantation were explanted at 8 to 12 weeks and demonstrated intimal fibroproliferative lesions with a mild parenchymal mononuclear cell infiltrate. Class II expression in isografts was limited to epicardial macrophages. Both acutely rejecting and long-term allografts contained abundant macrophages expressing recipient class II molecules. Occasional cells (passenger leukocytes) in untreated, acutely rejecting allografts bore donor class II molecules; long-term allografts contained few such cells. In contrast, vascular endothelial and medial smooth muscle cells consistently expressed donor class II molecules. These results suggest that ongoing MHC class II expression in donor vascular cells, as well as in recipient macrophages, may contribute to sustained activation of host T cells with consequent release of cytokines that ultimately promote the development of graft arteriosclerosis.

Actins↗
PubMed1998

Interferon-gamma-secreting T-cell populations in rejecting murine cardiac allografts: assessment by flow cytometry.

Interplay between T-helper-1 (Th1) and T-helper-2 (Th2) cells is considered important in the development of acute allograft rejection and many other immune-mediated disease processes. Existing methods for evaluating expression of Th1 and Th2 cytokines, including reverse transcriptase polymerase chain reaction (RT-PCR), RNase protection assay (RPA), immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) all have limitations; alternate techniques to quantify cell populations expressing specific cytokine proteins, generate statistically analyzable data, and allow simultaneous identification of cytokine-secreting cell type are needed. To this end, we adapted a flow cytometric technique for intracellular cytokine immunofluorescence staining for use with cells isolated from solid tissue. To demonstrate the utility of the method, we determined the number of CD4+ and CD8+ cells secreting the prototypical Th1 and Th2 cytokines, interferon (IFN)-gamma, and interleukin (IL)-4 in acutely rejecting murine cardiac allografts. We also measured the cytokine production via ELISA, RPA, and semiquantitative competitive RT-PCR. The number of CD4+ cells producing IFN-gamma increased as rejection proceeded, in agreement with previous data; we detected no IL-4 production at any time, although relatively low numbers of IL-10-producing cells were identified. In addition, a high percentage of CD8+ cells, which outnumber CD4+ cells at day 6 after transplant, also produce IFN-gamma, suggesting that cytotoxic lymphocytes contribute significantly to the local cytokine milieu. This new application of intracellular cytokine staining provides a powerful methodology for studying transplantation immunology. The method may also be easily adapted to the study of other immune-mediated processes.

Animals↗
PubMed1998

Orthodontic treatment of an adult male after bilateral condylectomy of the mandible for injuries sustained in a traffic accident.

In recent years there have been many reports on studies related to the temporomandibular joint (TMJ) in orthodontic treatment, but an adequate system of diagnosis and treatment has yet to be established, and they often cause considerable difficulty clinically. The patient in this case report sustained generalized contusions, a cerebral concussion, a midline fracture of the mandibular corpus, and bilateral fractures of the condylar process of the mandible when he fell asleep while driving a car and collided with a truck. Because non-surgical reduction was impossible, mandibular condylectomy was performed, and when orthodontic treatment was attempted to improve the open bite that persisted as a sequela of the accident, the favorable results were obtained, as described below. 1. The open bite was corrected by the orthodontic treatment, and the impairment that remained as a sequela resolved. 2. The mandibular condyles were removed during surgical reduction, and the mouth opening disturbance, the TMJ pain, and the TMJ noise resolved. The patient was able to go about his everyday life unimpaired, with hardly any awareness of limitation of jaw movement, and this situation remained unchanged even after the orthodontic treatment was performed.

Accidents, Traffic↗
PubMed1998

[Trends of asthma death among adults in Japan 1992-1994. Analysis of 313 cases reported questionnaires sent to hospitals with more than 100 beds].

The Japan Asthma Death Investigation Committee sent questionnaires to hospitals with more than 100 beds, and studied the clinical characteristics of 313 reported cases who died of asthma between 1992 and 1994. Forty percent of them were at the age between 60 and 79. Deaths of young adults in the twenties tended to increase. One third of the deaths was due to asphyxia. More than half of the patients were classified infectious or mixed type of asthma and 43.9% were graded as severe asthma. The main causes of the fatal asthma attacks were respiratory infections, fatigue and stress. Insufficient education, low compliance, delay in treatment with corticosteroids and other drugs, delay in emergency treatment, past histories of life-threatening attacks and hospitalization due to severe attacks were suggested to be risk factors of adult asthma death. Pulmonary emphysema showed relatively high frequency as a complication.

Adult↗