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H Nagano

Publications and source records attributed to H Nagano.

At least 91 records · Page 5Linked to original sources
PubMed1998

Coronary arteriosclerosis after T-cell-mediated injury in transplanted mouse hearts: role of interferon-gamma.

This study evaluated the contribution of acute parenchymal rejection and interferon (IFN)-gamma to the development of graft arterial disease (GAD) in totally allogeneic murine cardiac transplants. BALB/c (H-2d) hearts were transplanted into wild-type C57BL/6 (B6, H-2b) or B6 IFN-gamma-deficient (GKO) recipient mice. Assessing the role of acute parenchymal rejection in the GAD process involved two different immunosuppression protocols using anti-CD4 and -CD8 monoclonal antibodies (MAbs): virtually complete long-term immunosuppression (denoted as complete immunosuppression) was achieved by administering both MAbs 6, 3, and 1 day before transplantation and weekly thereafter; in contradistinction, a single, early, transient episode of rejection (transient rejection) was attained by administering MAbs beginning 4 days after transplant and then at weekly intervals. The extent and duration of T cell depletion under these two regimens were evaluated using flow cytometric analysis of peripheral blood lymphocytes. After a single injection of MAbs, peripheral blood CD4+ and CD8+ T cell depletion was approximately 98% at 1 week and approximately 88% at 2 weeks. After three injections (analogous to days 6, 3, and 1 before transplant), peripheral blood CD4+ and CD8+ T cell depletion was >98% at 2 weeks and approximately 87% at 4 weeks. Functioning cardiac allografts were removed at 8 and 12 weeks after transplant and analyzed by hematoxylin and eosin, elastic tissue, and immunohistochemical stains, and the severity of parenchymal rejection versus GAD was scored. With complete immunosuppression (antibody before and after transplant), BALB/c allografts showed little parenchymal rejection or GAD, suggesting that persistent depletion of T cells blocked subsequent development of GAD. However, even a single transient acute rejection episode allowed the subsequent development of GAD accompanied by augmented major histocompatibility complex (MHC) class II, VCAM-1, and ICAM-1 expression at 12 weeks; these allografts showed no residual CD4+ or CD8+ T cells. In comparison, allografts undergoing transient rejection in GKO recipients did not develop GAD, despite persistent macrophage and natural killer cell (NK) infiltrates comparable to those seen in wild-type recipients. Moreover, the arterioles of hearts transplanted into GKO recipients showed no or minimal increases in MHC class II, ICAM-1, and VCAM-1 relative to baseline expression. In conclusion, a single episode of allogeneic injury mediated by T cells suffices to evoke subsequent graft arteriosclerosis, even in the absence of additional T-cell-mediated injury, and the process appears to depend on IFN-gamma.

Animals↗
PubMed1997

Infection-associated macrophage activation accelerates chronic renal allograft rejection in rats.

BACKGROUND: The influence of infection-associated cellular activation on chronic rejection of kidney grafts was assessed in an established rat model by administration of lipopolysaccharide (LPS), an endotoxin and a potent stimulator of various cell populations including mononuclear cells and renal epithelial cells. METHODS: Lewis recipients of F344 kidneys were treated with low-dose cyclosporine (1.5 mg/kg/day x 10 days). Animals with well-functioning grafts received a single dose of LPS (2 mg in 1 ml of NaCl, intraperitoneally) at 4 or 8 weeks after engraftment. Untreated control rats, which later experienced chronic rejection, were given 1 ml of NaCl. RESULTS: Administration of LPS during the early quiescent phase of chronic rejection accelerated the chronic process, functionally (proteinuria), morphologically, immunohistologically, and by reverse-transcriptase polymerase chain reaction as compared with untreated controls. Infiltration of macrophages and their associated factors was especially affected. CONCLUSIONS: As the later events of chronic rejection seem to be mediated primarily by macrophages and their products, administration of LPS accelerated the tempo and activity of these cells in the development of chronic rejection. These findings may explain the clinical observation that infection may be an important risk factor for chronic allograft rejection.

Animals↗
PubMed1997

Interferon-gamma deficiency prevents coronary arteriosclerosis but not myocardial rejection in transplanted mouse hearts.

We have hypothesized that T cell cytokines participate in the pathogenesis of graft arterial disease (GAD). This study tested the consequences of IFN-gamma deficiency on arterial and parenchymal pathology in murine cardiac allografts. Hearts from C-H-2(bm12)KhEg (bm12, H-2(bm12)) were transplanted into C57/B6 (B6, H-2(b)), wild-type, or B6 IFN-gamma-deficient (GKO) recipients after immunosuppression by treatment with anti-CD4 and anti-CD8 mAbs. In wild-type recipients, myocardial rejection peaked at 4 wk, (grade 2. 1+/-0.3 out of 4, mean+/-SEM, n = 9), and by 8-12 wk evolved coronary arteriopathy. At 12 wk, the GAD score was 1.4+/-0.3, and the parenchymal rejection grade was 1.2+/-0.3 (n = 8). In GKO recipients of bm12 allografts, myocardial rejection persisted at 12 wk (grade 2.5+/-0.3, n = 6), but no GAD developed (score: 0.0+/-0.0, n = 6, P < 0.01 vs. wild-type). Mice treated with anti-IFN-gamma mAbs showed similar results. Isografts generally showed no arterial changes. In wild-type recipients, arterial and parenchymal cells showed increased MHC class II molecules, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 compared to normal or isografted hearts. The allografts in GKO recipients showed attenuated expression of these molecules (n = 6). Thus, development of GAD, but not parenchymal rejection, requires IFN-gamma. Reduced expression of MHC antigens and leukocyte adhesion molecules may contribute to the lack of coronary arteriopathy in hearts allografted into GKO mice.

Animals↗
PubMed1997

Sequential cellular and molecular kinetics in acutely rejecting renal allografts in rats.

The initial (0-24 hr), early (3-5 days), and late (7-14 days) events occurring in LBNF1 renal allografts transplanted into Lew recipients were examined to define precisely the sequential cellular and molecular kinetics during acute rejection. Grafts and spleens were harvested at 3, 6, 12, and 24 hr, and at 3, 5, 7, and 14 days and processed for morphology, immunohistology, and reverse transcriptase-polymerase chain reaction. Various factors (mRNA) were up-regulated sequentially in the allografts over time. In the initial phase, E-selectin and complement (C1 and C3) expression was noted within 6 hr, peaking by 24 hr. RANTES (regulated upon activation, normal T cell expressed and secreted) increased within 6 hr, and then again between 3 and 6 days. By immunohistology, MHC class II was up-regulated consistently after day 1. Intercellular adhesion molecule-1 expression increased after day 3; lymphocyte function-associated antigen-1+ infiltrating leukocytes peaked at day 5. Infiltrating CD8+ T lymphocytes increased strikingly between days 1 and 3, peaking at day 5; CD4+ cells infiltrated more slowly until day 5. The kinetics of ED1+ macrophages were similar to those of lymphocyte function-associated antigen-1+ cells. The CD4+ T cell-derived product, interleukin (IL)-2, peaked at 7 days. Interferon-gamma increased progressively up to 14 days. By 3 days, the macrophage-associated factor, transforming growth factor-beta, peaked; this was followed by increased IL-6 expression by day 5. IL-1, tumor necrosis factor-alpha, and inducible nitric oxide synthase increased slowly until day 7, declining thereafter. Endothelin increased progressively over the 14-day follow-up period. Cytokine dynamics occurring in host spleen were similar to those noted in the allografts. Although acute rejection is primarily T cell mediated, adhesion molecules, macrophages, and their associated products may influence initial and later changes. The brisk expression of complement, E-selectin, and RANTES within the first few hours after engraftment may occur secondary to ischemic injury and trigger subsequent immunological events. Macrophages and their products may play a larger role in the process than hitherto appreciated.

Animals↗
PubMed1997

Treatment of node-positive endometrial cancer with complete node dissection, chemotherapy and radiation therapy.

We assessed the therapeutic significance of systematic aortic and pelvic lymphadenectomy followed by adjuvant therapy in node-positive endometrial carcinoma. Among 173 stage I-III patients, 30 (17%) had positive nodes: ten in the pelvic region alone (group P) and 20 in the aortic region alone or in both regions (group A). The adjuvant therapy was administered as follows: subjects in group P received 50 Gy pelvic radiation, including three post-surgical T3 (pT3) patients who received either one or three cycles of cisplatin-based chemotherapy before radiation. Subjects in group A were given three cycles of chemotherapy followed by 50 Gy pelvic and 50 Gy extended field periaortic radiation using a four-field or conformational technique. Five-year survival was 95% for 143 patients with negative nodes and 84% for 30 patients with positive nodes (100% for group P and 75% for group A). In group A, 5-year survival was 38% for eight patients with both pT3 and histology other than endometrioid type G1, and 91% for the remaining 12 patients. Either way, both group P and group A patients had a better prognosis than previously reported. In summary, aortic and pelvic lymphadenectomy and subsequent chemotherapy and radiation therapy based on node status seem to improve the survival of endometrial cancer patients with positive nodes.

Adenocarcinoma, Clear Cell↗
PubMed1997

Chronic allograft failure: the clinical problem.

Long-term survival statistics for organ allografts have not improved substantially over time, despite improved immunosuppression and organ preservation and better surgical and perioperative management. Chronic rejection is the most important long-term limitation in allografts and increasingly seems to be caused by a multifactorial series of antigen-dependent and antigen-independent factors. Early injury is critical to late events, whether antigen driven (early acute rejection episodes and human leukocyte antigen mismatching) or antigen independent (ischemia/reperfusion injury and brain death). Ongoing alloimmunologic injury to the host and inadequate organ mass functioning (donor age, gender, race, and organ size) also seem to be important to this persisting process. Associated recipient conditions, which includes hypertension and hyperlipidemia, and postoperative complications, which include drug nephrotoxicity and infections, may affect this late-phase graft loss. These deleterious risk factors for chronic rejection of long-functioning allografts are an important subject for future investigation.

Graft Rejection↗
PubMed1997

Candesartan cilexetil reduces chronic renal allograft injury in Fisher-->Lewis rats.

OBJECTIVES: To determine the effects of the angiotensin II receptor antagonist, candesartan cilexetil, on glomerular and systemic blood pressures and the development of renal injury in Lewis rat recipients of a single Fisher kidney (F334--> LEW transplantation), an established rat model of chronic renal allograft failure. DESIGN: Recent studies have shown that chronic injury of renal allografts in F334-->LEW rats may be virtually abrogated by supplying the Lewis recipients with two Fisher kidneys or, alternatively, by retaining a native kidney. These findings imply a major contribution from processes associated with nephron loss to the pathogenesis of chronic renal allograft failure, a notion supported by the observation that transplanting two kidneys also normalizes glomerular capillary pressure (PGC) in F344-->LEW rats. Thus, a pharmacological reduction in PGC, by blocking the effects of angiotensin II, should also lessen renal injury in F344-->LEW rats. MATERIALS AND METHODS: Bilaterally nephrectomized F344--> LEW rats were treated with the angiotensin II receptor blocker candesartan cilexetil (TCV-116) at 40 mg/l or with vehicle, administered in drinking water. Proteinuria and systolic blood pressure were assessed monthly, and histological studies were carried out after 24 weeks. The glomerular filtration rate and glomerular pressures were determined after 10 weeks in additional rats by clearance and micropuncture studies. RESULTS: Treatment with candesartan cilexetil lowered systemic blood pressure, normalized PGC at 10 weeks and greatly reduced proteinuria and allograft glomerulosclerosis at 24 weeks. CONCLUSIONS: These data indicate that the development of renal injury in F344-->LEW renal allografts can be prevented by the pharmacological blockade of angiotensin II receptors using candesartan cilexetil. This suggests that angiotensin-dependent processes contribute significantly to chronic injury in this model of late renal allograft failure.

Angiotensin Receptor Antagonists↗
PubMed1997

[Enterohemorrhagic Escherichia coli O157 outbreak in Obihiro-city--biological and molecular characteristics among O157 isolates].

The outbreak of enterohaemorrhagic Escherichia coli (EHEC) O157:H7 infection in Obihiro City, Japan, occurred in late October 1996. The infection affected a total of 169 kindergarten pupils and school staff members in a private kindergarten. Twenty-one children (12.4%) progressed into hemolytic uremic syndrome (HUS). Moreover, the person-to-person infections in 9 families and the duration of excretion of EHEC in 13 patients were observed. The contaminated food was identified as the potato-salad served at lunch. Analysis of biological characteristics, the ability of toxin production, and the DNA analysis by PCR-based fingerprinting, the RAPD tests, among all clinical isolates, clarified a homologous origin of contamination.

Adult↗
PubMed1997

Deletion of the C-terminal 33 amino acids of cucumber mosaic virus movement protein enables a chimeric brome mosaic virus to move from cell to cell.

The movement protein (MP) gene of brome mosaic virus (BMV) was precisely replaced with that of cucumber mosaic virus (CMV). Infectivity tests of the chimeric BMV on Chenopodium quinoa, a permissive host for cell-to-cell movement of both BMV and CMV, showed that the chimeric BMV failed to move from cell to cell even though it replicated in protoplasts. A spontaneous mutant of the chimeric BMV that displayed cell-to-cell movement was subsequently obtained from a local lesion during one of the experiments. A cloned cDNA representing the genomic RNA encoding the MP of the chimeric BMV mutant was analyzed and found to contain a mutation in the CMV MP gene resulting in deletion of the C-terminal 33 amino acids of the MP. Directed mutagenesis of the CMV MP gene showed that the C-terminal deletion was responsible for the movement capability of the mutant. When the mutation was introduced into CMV, the CMV mutant moved from cell to cell in C. quinoa, though the movement was less efficient than that of the wild-type CMV. These results indicate that the CMV MP, except the C-terminal 33 amino acids, potentiates cell-to-cell movement of both BMV and CMV in C. quinoa. In addition, since C. quinoa is a common host for both BMV and CMV, these results suggest that the CMV MP has specificity for the viral genomes during cell-to-cell movement of the virus and that the C-terminal 33 amino acids of the CMV MP are involved in that specificity.

Amino Acids↗
PubMed1997

Effects of candesartan cilexetil (TCV-116) and enalapril in 5/6 nephrectomized rats.

The renal protective properties of candesartan cilexetil (TCV-116), an angiotensin II type 1 receptor antagonist (AT1A), and enalapril, an angiotensin I converting enzyme inhibitor (ACEI), were investigated in 5/6 nephrectomized (NX) rats. Candesartan cilexetil (1 mg/kg/day) and enalapril (10 mg/kg/day) were administered orally to 5/6 NX rats for four weeks (during the early phase of disease development) or 16 weeks (through the late phase). In vehicle-treated rats, proteinuria, glomerulosclerosis, interstitial mononuclear cell (MNC) infiltration and interstitial fibrosis developed. Moreover, immunohistological studies showed enhanced expression of transforming growth factor-beta 1 (TGF-beta 1) in the injured glomeruli. Both drugs inhibited these adverse changes in the early phase. In the late phase, the progressive proteinuria, interstitial MNC infiltration were attenuated by both drugs. However, candesartan cilexetil significantly inhibited the progression of glomerulosclerosis, the expression of TGF-beta 1 and the interstitial fibrosis, while enalapril did not. Candesartan cilexetil and enalapril showed comparable hypotensive effects after the 16-week administration. These results indicate that candesartan cilexetil shows a more potent protective effect than enalapril against the progression of renal injury in the late phase. Thus, an AT1A might be more useful than an ACEI for the treatment of patients with chronic renal failure.

Angiotensin II↗
PubMed1997

Long-term results of Charnley low-friction arthroplasty for coxarthrosis with congenital hip dysplasia. 15 year follow-up study.

We studied more than fifteen-years' follow-up results of cases treated with low-friction arthroplasty (LFA) for coxarthrosis with congenital hip dysplasia. Thirty-four LFAs in 32 patients (2 males and 30 females) were followed up for an average of 18.8 years (range: 15 to 23.3 years). The mean age at surgery was 53 years (range: 36 to 67 years). In three patients, 4 hips needed revision surgery due to loosening of the prostheses. At the final follow up, using Hodgkinson's criteria, type 0 demarcation of the socket appeared in 9 cases, type 1 in 5 cases, type 2 in 4 cases, type 3 in 4 cases, and type 4 in 12 cases. According to Harris' criteria, there was no sign of loosening of the stem in 16 cases, however there was a possibility of loosening in 8 cases, probability in 2 cases, and definite loosening in 8 cases. The survival rate with socket loosening as the end point was 76.5% at the 10 year follow-up, 67.6% at 15-years' follow-up, and 50.9% at 20-years' follow-up. The survival rate with stem loosening as the end point was 82.4% at 10-years' follow-up, 79.4% at 15-years' follow-up, and 63.8% at 20-years' follow-up. The survival rate with prostheses loosening either socket or stem as the end point was 64.7% at 10-years' follow-up, 55.9% at 15-years' follow-up, and 34.6% at 20-years' follow-up. The survival rate with revision surgery as the end point was 100% at 10-years' follow-up, 94% at 15-years' follow-up, and 85.1% at 20-years' follow-up.

Adult↗
PubMed1996

Anti-HIV-1 activity of thiadiazole derivatives: structure-activity relationship, reverse transcriptase inhibition, and lipophilicity.

The structure-activity relationship of the non-nucleoside HIV-1-specific reverse transcriptase (RT) inhibitors 4-phenyl-1,2,5-thiadiazol-3-yl N,N-dialkylcarbamate (TDA) derivatives was investigated with respect to their anti-HIV-1 activity, RT inhibition, and lipophilicity. 4-Phenyl-1,2,5-thiadiazol-3-yl N,N-dimethylcarbamate inhibited HIV-1-induced cytopathic effect (CPE) by 50% at a concentration of 28.8 microM in MT-4 cells. The activity increased more than 100-fold when the hydrogens at the 2-position and the 6-position in phenyl moiety were substituted by chlorines. However, the derivative with a chlorine at the 4-position of phenyl moiety did not show any inhibition of HIV-1 replication at its non-toxic concentrations. All of the 4-(2,6-dichlorophenyl)-1,2,5-thiadiazol-3-yl N-methyl-N-alkylcarbamates proved inhibitory to HIV-1 replication in the nanomolar concentration range. The TDA derivatives that showed anti-HIV-1 activity also inhibited RT activity in an enzymatic assay. However, the TDA derivatives did not show any specific inhibition of a non-nucleoside RT inhibitor (NNRTI)-resistant mutant and its RT activity. When the TDA derivatives were examined for their inhibitory effect on HIV-1 replication in the presence of 50% human serum, the activity significantly decreased depending on-their lipophilicity.

Anti-HIV Agents↗
PubMed1996

Association of multiple human papillomavirus types with vulvar neoplasias.

OBJECTIVE: The purpose of this study was to clarify the association of multiple genital human papillomavirus (HPV) types with vulvar neoplasias. METHODS: We examined vulvar neoplasias by the polymerase chain reaction (PCR) method, which can detect almost all genital HPV types sensitively (L1-PCR). RESULTS: Eight HPV types (types 6, 11, 16, 18, 52, 53, 56, and 68) were detected in 52 of 53 (98.1%) vulvar condylomas; 2 HPV types (types 16 and 18) were detected in all 6 Grade-3 vulvar intraepithelial neoplasias; and 5 HPV types (types 6, 16, 18, 51, and 56) were detected in 8 of 11 (72.7%) invasive vulvar carcinomas. Detection of HPV types 52, 53, 56, and 68 in vulvar condylomas and detection of HPV types 51 and 56 in vulvar carcinomas are the first examples ever reported. CONCLUSION: This study suggests that more HPV types are associated with the generation of vulvar neoplasias than was thought to be the case up to now.

Adolescent↗
PubMed1996

Dose distribution and shrinkage of acoustic neurinomas 2 years after Gamma Knife treatment.

To examine the relationship between dose distribution and tumor shrinkage of acoustic neurinomas, correlation coefficients between distribution probabilities of some dose areas and residual tumor ratios of 21 cases were studied at 2 years. Approximating a dose-volume histogram to beta-distribution, two essential dose areas for tumor control were extracted: a dose area from 14.2 to 24.7 Gy contributed to tumor shrinkage, whereas a dose area from 27.3 to 29.4 Gy was contraindicated. Given that there are at least two different dose areas with reverse characters, a formula with two opposing logistic components is proposed to predict tumor control. With this formula, Gamma Knife treatment of acoustic neurinomas may be optimized.

Adult↗
PubMed1996

[Trends in asthma-related death among adults in Japan, 1986-1991--analysis of responses to questionnaires sent to hospitals with at least 200 beds].

The death rate among patients with asthma in Japan has been reported by Japan's Ministry of Health and Welfare to approximately 5/100,000 population. Over the past 15 years, this rate has remained relatively constant, but it is higher than that in western countries. To clarify recent trends in adult asthma mortality, the Japan Asthma Death Investigation Committee studied the clinical characteristics of 649 patients who died of asthma between 1986 and 1991. The annual number of deaths decreased slightly: from 145 in 1986 to 89 in 1991. There was a large difference between sexes: the male:female ratio was 3:2. Most patients ranged in age from 50 to 70 years old. It is noteworthy that in one third of the patients death was caused by asphyxic-type asthma, while status asthmaticus was the cause in only 23.7%. The number of patients with mild or moderate asthma was slightly increased, although patients with severe asthma accounted for at least 70% of all deaths. The main causes of fatal asthma attacks were airway infections, fatigue, and stress. Other responses on the questionnaires indicated the following areas of concern: deficiencies in patient education, delays in treatment with corticosteroids and other antiasthma drugs, and delays in provision of emergency treatment.

Adolescent↗
PubMed1996

[Liver resection in a case of multiple liver metastases of gastric cancer following hepatic arterial infusion chemotherapy].

A 61-year-old-man underwent subtotal gastrectomy (D2) for advanced gastric cancer with multiple liver metastases. After the operation, repeated hepatic arterial infusion chemotherapy was performed employing implantable catheter and port system with CDDP and MMC. The result was that the liver tumors showed a remarkable regression in size, and the serum CA 19-9 level decreased within normal range. But the tumor in the lateral segment grew and the CA 19-9 level increased again. There was no evidence of metastasis or recurrence except in the liver, and the metastatic tumors in right lobe became smaller by hepatic arterial infusion chemotherapy at this time. Therefore, lateral segment resection was performed for reductive surgery 14 months after the first operation. After that, the liver tumors did not grow and CA 19-9 kept within the normal range, while hepatic arterial infusion chemotherapy could be given. Thus, it seems that liver resection for reduction surgery following hepatic arterial infusion chemotherapy should be considered as a treatment for multiple liver metastases.

Adenocarcinoma↗
PubMed1995

Role of micro-chimerism in inducing immunological tolerance by intraportal injection of donor spleen cells in rats.

Recently, we reported that intraportal (IP) injection of donor spleen cells (SPCs) prevented liver allograft rejection. Moreover, we developed a new method using polymerase chain reaction (PCR)-mediated restriction fragment length polymorphism (RFLP) analysis, and demonstrated micro-chimerism (MC) at the DNA level in the spleen 14 days after IP injection. In the present study, the long-term presence of injected allogeneic SPCs was investigated at the cellular level by immunofluorescence staining as well as the DNA level using RFLP analysis. Male ACI (RT1a) rats were used as the donors and Lewis (RT1(1)) rats as the recipients. After DNA preparation from the lymphoid organs, RT1B beta domain 1 region was amplified by PCR, and RFLP analysis was performed with PvuII restriction enzyme. In the immunofluorescence staining, the monoclonal antibody, MN4-91-6, was used to detect the injected donor ACI SPCs in a frozen specimen. We did not detect MC in Lewis rats intravenously injected with 5 x 10(7) ACI SPCs on day 14. On the other hand, stable chimerism in the spleen was observed in intraportally injected rats up to 28 days after injection at not only the DNA level but also the cellular level. No chimerism was detected in other organs (including the thymus, lymph nodes, and liver). In conclusion, the long-term presence of injected allogeneic SPCs in the spleen was demonstrated after IP injection but not after IV injection, and this phenomenon may be one of the mechanisms involved in portal venous immunosuppression.

Animals↗