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Y Fujino

Publications and source records attributed to Y Fujino.

At least 145 records · Page 8Linked to original sources

Role of adenosine in preservation by the two-layer method of ischemically damaged canine pancreas.

The purpose of this study was to clarify the role of adenosine in preservation of ischemically damaged pancreas by the two-layer (Euro-Collins solution [EC]/perfluorochemical [PFC]) method using a canine model. Twenty-four-hour preservation of the pancreas graft subjected to 60-min warm ischemia was successful by the two-layer (EC with adenosine/PFC) method (4/5, 80%), but neither simple cold storage in EC (0/5, 0%), nor EC with adenosine (1/5, 20%), nor the two-layer (EC/PFC) method (0/3, 0%) was successful. Tissue ATP concentrations at the end of preservation by the two-layer (EC with adenosine/PFC) method were significantly higher compared with the two-layer (EC/PFC) method (7.23 +/- 2.17 vs. 1.56 +/- 0.40 mumol/g dry weight, P < 0.01). Studies with [2-3H]adenosine demonstrated that only part of adenosine was converted to inosine, hypoxanthine, and adenine, whereas the remainder was incorporated into adenine nucleotides in the pancreas graft. In addition, hypoxanthine, inosine, and adenine did not substitute for adenosine. We conclude that provision of adenosine to ischemically damaged pancreas during preservation by the two-layer (EC/PFC) method allows ATP synthesis within the graft via direct phosphorylation of adenosine. Metabolic processes vital to repair damaged cells and maintain cellular integrity can be maintained, which makes it possible to preserve ischemically damaged pancreas.

Adenosine↗

Protective effect of preservation of canine pancreas by the two-layer (University of Wisconsin solution/perfluorochemical) method against rewarming ischemic injury during implantation.

Rewarming ischemia during implantation severely compromises posttransplant pancreas graft survival because the graft has already been subjected to warm and cold ischemia before implantation. The purpose of this study was to examine whether preservation of the pancreas graft by the two-layer method ameliorates rewarming ischemic injury of the graft during implantation using a canine model. After flushing with cold University of Wisconsin solution (UW), the pancreas grafts were preserved by the two-layer (UW/perfluorochemical [PFC]) method (group 1) or simple cold storage in UW (group 2) for 24 hr and then autotransplanted. In control, the pancreas grafts were flushed out with cold UW and immediately autotransplanted without preservation (group 3). After completion of vascular anastomosis, vascular clamp was not released until 90, 120, or 150 min of rewarming ischemia, including anastomosis time, had elapsed. After 90 min of rewarming ischemia, graft survival rates were 5/5, 100%, 5/5, 100%, and 5/5, 100%, in groups 1, 2, and 3, respectively. After 120 min, all the grafts in groups 2 and 3 failed (0/5, 0%, and 0/5, 0%, respectively); however, all the grafts in group 1 survived (5/5, 100%). Even after 150 min, 1 of 3 grafts in group 1 survived (1/3, 33%). After 24 hr preservation, tissue ATP levels of the grafts in group 1 were about 2-fold the reference values before harvesting (8.23 +/- 0.72 vs. 4.44 +/- 0.49 mumol/g dry weight, P < 0.05) and significantly higher compared with group 2 (8.23 +/- 0.72 vs. 1.76 +/- 0.52 mumol/g dry weight, P < 0.01). After 120 min of rewarming ischemia, tissue ATP levels in group 1 were 84% of the reference values and significantly higher compared with group 2 (3.75 +/- 0.25 vs. 1.57 +/- 0.48 mumol/g dry weight, P < 0.05). Two hours after reperfusion, ATP levels in group 1 were 42% of reference values but significantly higher compared with group 2 (1.86 +/- 0.36 vs. 1.03 +/- 0.18 mumol/g dry weight, P < 0.05). We conclude that the two-layer (UW/PFC) method ameliorates rewarming ischemic injury of the pancreas graft during implantation by increasing tissue ATP contents during preservation and consequently maintaining tissue ATP levels during implantation.

Adenosine↗

Murine experimental autoimmune uveoretinitis induced by interphotoreceptor retinoid-binding protein and Klebsiella pneumoniae 03 lipopolysaccharide (K03-LPS): a relation between H-2 haplotype and EAU induction.

The pathogenicity of interphotoreceptor retinoid-binding protein (IRBP) in the mouse and H-2 restriction of IRBP-induced experimental autoimmune uveoretinitis (EAU) was tested by repeated immunization using Klebsiella pneumoniae 03 lipopolysaccharide (K03-LPS) as an adjuvant. It was shown that IRBP had a greater capacity to induce EAU than S-antigen. Based on the incidence of EAU induction using B10 congenic mice and other strains, the susceptibility to EAU was, at least in part, controlled by the I-Ak haplotype of the H-2 subregion. The results also indicated that non-major histocompatibility complex (MHC) genes play some role in disease susceptibility.

Animals↗

Preoperative diagnosis of a rudimentary uterine horn.

Two cases of rudimentary uterine horn were able to be diagnosed prior to operation. The case of rudimentary horn with cavity non-communicating to unicornuate uterus was easy to diagnose. Transabdominal ultrasonography and computed tomography (CT) demonstrated the uterus to have binodular structure and two uterine lumina. However, the case with pregnancy was difficult to diagnose. In this case, thick myometrium could be seen by ultrasonography to enclose the sac. In both cases hysterosalpingography revealed unicornuate uterus.

Adult↗

Presence of laminin B chain-like protein in bovine and rat adrenal chromaffin granules.

The presence of a glycoprotein laminin in bovine adrenal chromaffin granules was examined by SDS-PAGE followed by immunoblotting. The two chromaffin granule membrane fractions were obtained by linear sucrose gradient centrifugation followed by freezing and thawing and gel-filtration of the chromaffin granule-rich fraction, respectively. The purity of the granules in these fractions was examined by electron microscopy. These fractions contained laminin B chain-like immunoreactivity as a major immunoreactive component against anti-laminin. Laminin A chain-like immunoreactive protein was undetectable. The soluble fraction of the chromaffin granules contained no immunoreactive peptide. The presence of laminin-like immunoreactivity in the chromaffin granules was confirmed by immunocytochemical study. Laminin B chain-like immunoreactivity was also identified in the rat adrenal chromaffin granule fraction. Laminin A chain was hardly detected, as in the case of bovine adrenals. Structure of laminin in chromaffin granules in bovine and rat adrenals may be different from that of mouse Englebrethe-Holm-Swarm sarcoma laminin. The functional significance of laminin B chain-like protein in the granules is unknown at present.

Adrenal Medulla↗

Lack of the response to nicotine in 21-day-old rat adrenal chromaffin cells in vivo.

Response to nicotine of adrenal chromaffin cells was studied in suckling and young adult male rats in vivo. When 5 mg/kg of nicotine was injected subcutaneously to 8-week-old rats, the content of adrenaline and noradrenaline in the chromaffin granule fraction decreased about by 36 and 45%, respectively, 2 min after the administration. In electron microscopy, the number of chromaffin granules in the perinuclear region of adrenaline-storing cells decreased markedly. The number of vacuoles, probably produced by membrane recycling resulting from exocytosis, increased significantly in adrenaline- and noradrenaline-storing cells. Omega-shaped profiles (exocytosis) were frequently observed both in adrenaline- and noradrenaline-storing cells. On the other hand, nicotine injection did not significantly alter the catecholamine content in the 21-day-old rat chromaffin granule fraction, although severe convulsion was evoked. In electron microscopy, the changes indicative of exocytosis mentioned above were scarcely observed. Cholinergic nerve fibers of mature appearance were observed in the adrenal medulla of 21-day-old rats. These results indicate that the responsiveness of the chromaffin cells to nicotine in 21-day-old rats differs from that in 8-week-old rats.

Adrenal Glands↗

Evaluation of cyclosporine, mycophenolate mofetil, and Brequinar sodium combination therapy on hamster-to-rat cardiac xenotransplantation.

We examined the effect of CsA, mycophenolate mofetil (MM), and Brequinar sodium (BQR) combination therapy on hamster-to-rat cardiac xenotransplantation survival. Since the mechanism of rejection in concordant cardiac xenotransplantation may be antibody mediated as well as cellularly (CD4) mediated, we also examined the effect of these agents on antidonor antibody levels. In untreated controls, rejection occurred within 4 days, with elevation of cytotoxic antibody titers and severe humoral destruction of the xenografted hearts. It involved both IgM and IgG antibody-mediated humoral immunity. CsA alone (20 mg/kg/day) could not modify this pattern of rejection. High-dose MM (40/20 mg/kg/day)+BQR (12/6 mg/kg 3 times a week) combination therapy achieved slight prolongation of survival and suppressed the elevation of cytotoxic antibody titers relative to controls. While these grafts were rejected within 2 weeks, humoral destruction in the rejected xenografts and antibody deposition were reduced. Combination of CsA (20 mg/kg/day) with BQR (3 or 12 ng 3 times/week) dramatically increased graft survival. When CsA (20 mg/kg/day) was combined with MM (20 mg/kg/day) and BQR (3 mg/kg/day), xenograft survival was significantly prolonged (P < 0.002); however, significant toxicity was observed. Cytotoxic antibody formation was delayed for 1 month in most cases. Histological examination revealed cellular rejection with little evidence of humoral rejection. Thus, combination therapy consisting of CsA and BQR or CsA, MM, and BQR was effective in delaying the rejection of hamster-to-LEW rat concordant cardiac xenografts. The mechanism of prolonged graft survival may involve delayed humoral response and prevention of the cellular response.

Animals↗

Metabolic intervention to affect canine pancreas recovery following ischemia during preservation by the two-layer method.

We have demonstrated that a high adenosine triphosphate (ATP) level in a canine pancreas during preservation by the two-layer method is an important determinant for the ultimate success of pancreatic transplantation. In this study, we investigated (a) the effect of factors that seemed to have an influence on energy metabolism in the canine pancreas at the tissue ATP level and (b) graft viability during preservation by the two-layer method. ATP tissue concentration was determined by high-performance liquid chromatography and graft viability was assessed on the basis of survival rate following autotransplantation. First, the pancreas was harvested from either 72-h-fasted (n = 5) or fed dogs (n = 5) and preserved by the two-layer Euro-Collins solution (EC)/perfluorochemical (PFC) method for 24 h. All the pancreatic grafts were viable in both fed and fasted groups. There was also no significant difference in ATP tissue concentration between the two groups (7.48 +/- 0.55 vs. 7.03 +/- 0.74 micromol/g dry weight, NS). Second, the pancreatic grafts subjected to 60 min of warm ischemia were preserved by either the two-layer (EC/PFC) or (EC + adenosine/PFC) method for 24 h. Without adenosine, ATP tissue concentration did not recover (1.62 +/- 0.26 after warm ischemia vs. 1.56 +/- 0.40 micromol/g dry weight after preservation, NS) and all the pancreatic grafts failed. However, provision of adenosine led to restoration of ATP tissue levels (1.90 +/- 0.53 vs. 7.23 +/- 2.17 micromol/g dry weight, P < 0.01) and four of five grafts functioned immediately and maintained normoglycemia after transplantation. These results clearly demonstrated that the nutritional state of the pancreatic graft before procurement had no influence on ATP tissue level as well as graft viability during 24-h preservation by the two-layer method. On the other hand, provision of adenosine during 24-h preservation enhanced ATP synthesis of the pancreatic tissue, thereby improving viability of the ischemically damaged pancreas.

Adenosine↗

Difference in energy metabolism between fresh and warm ischemic canine pancreases during preservation by the two-layer method.

We have demonstrated that adenosine triphosphate (ATP) is synthesized within a canine pancreas during preservation by the two-layer method and there is a direct correlation between a high ATP tissue level and good posttransplant outcome. The purpose of this study was to examine the difference in energy metabolism between fresh and warm ischemic pancreases during preservation by this method. First, fresh pancreases were preserved with simple cold storage in Euro-Collins solution (EC; group 1A), or by the two-layer method using EC (group 1B), EC with 2,4 dinitrophenol (DNP; group 1C), an uncoupler of oxidative phosphorylation, or modified EC (ECM; group 1d), which contained mannitol in place of glucose for 48 h. ATP tissue concentrations in group 1B were significantly higher than in group 1A (7.91 +/- 1.21 vs. 1.21 +/- 0.31 micromol/g dry weight, P < 0.01) but almost equal to group 1d (7.91 +/- 1.21 vs. 7.59 +/- 0.97 micromol/g dry weight, NS). DNP (group 1C) caused a significant decrease in tissue ATP levels in group 1A (0.61 +/- 0.07 vs. 7.91 +/- 1.21 micromol/g dry weight, P < 0.01). Second, pancreases subjected to 60 min of warm ischemia were preserved by simple cold storage with EC (group 2A) or the two-layer method using EC (group 2B) or EC with adenosine (group 2C) for 24 h. ATP tissue levels in groups 2A and 2B after preservation were 1.40 +/- 0.46 and 1.56 +/- 0.40 micromol/g dry weight and graft survival rates were 0/5 (0%) and 0/3 (0%), respectively. However, tissue ATP levels in group 2C after preservation were significantly higher compared with the value before preservation (7.23 +/- 2.17 vs. 1.90 +/- 0.53/g dry weight, P < 0.01) and graft survival rate was 4/5, 80%. Other nucleosides, hypoxanthine, inosine, and adenine did not substitute for adenosine. In addition, studies with [2-3 H] adenosine demonstrated that almost all of the adenosine was converted to adenine nucleotides. This study clearly demonstrated that fresh grafts synthesize ATP mainly via mitochondrial oxidative phosphorylation using endogenous substrates. However, after significant warm ischemia, pancreases produce ATP mainly via direct phosphorylation of exogenous adenosine during preservation by the two-layer method.

2,4-Dinitrophenol↗

S-antigen specific T cell clones from a patient with Behçet's disease.

The isolation and characterisation of T cell clones or lines specific to retinal antigens are valuable tools to clarify the underlying mechanisms of autoimmunity to retinal antigens as a contributing factor in ocular inflammation. Patients with Behçet's disease have been reported to be sensitised to S-antigen (S-Ag). In the present study, four T cell clones established from the peripheral blood of a patient with Behçet's disease were analysed. A CD4+ T cell clone (clone 2) and a CD8+ T cell clone (clone 10) proliferated specifically to bovine S-Ag. Although these S-Ag specific T cell clones proliferated vigorously to the intact antigen, their responses to S-Ag derived synthetic peptides M and G were weak, suggesting that the sites of human T cell recognition of S-Ag may be different from those established in the experimental model. The proliferative responses of both clones (2 and 10) were inhibited by anti-HLA-DR monoclonal antibody but not by anti-HLA-class 1 monoclonal antibody. The other two clones studied, clones 6 and 30, were CD3+, CD4-, CD8-, and they did not proliferate specifically to S-Ag. Clone 6 expressed gamma delta T cell receptors (TCR) and showed non-specific cytotoxic activity toward K562 and Daudi cell lines. Clone 30 expressed alpha beta TCR, and was devoid of cytotoxic activity. Human T cell lines and clones specific to retinal antigens will provide the framework necessary to examine the events that lead to ocular inflammation.

Adult↗

Comparative evaluation of diaphragmatic activity during pressure support ventilation and intermittent mandatory ventilation in animal model.

The aim of the present study is a comparative evaluation of the effects of pressure support ventilation (PSV) and intermittent mandatory ventilation (IMV) on diaphragmatic activity in rabbit model of neonate. The animals were divided into a PSV group and an IMV group. In the IMV group, spontaneous breathing and four kinds of IMV rate (5, 10, 15, and 20/min) were applied (Ventilator: Bear BP200, peak inspiratory pressure [PIP]: 12 cm H2O, inspiratory time: 0.6 s). In the PSV group, spontaneous breathing and four levels of PSV (3, 6, 9, and 12 cm H2O) were applied (Ventilator: VIP Bird, flow triggering). Airway pressure (Paw), flow (V), esophageal pressure (Pes), integrated diaphragmatic electromyogram (Edi), and arterial gas data were measured. Amplitudes of Pes and Edi were expressed as percentages (% Edi and % Pes) of the control value during spontaneous breathing to evaluate diaphragmatic activity. Lower IMV rates did not reduce diaphragmatic activity. Approximately half of diaphragmatic activity of control remained even at IMV 15/min. Diaphragmatic activity disappeared at IMV20/min. In contrast, PSV reduced Edi and Pes linearly according to support level. In conclusion, diaphragmatic activity could be reduced more gradually with PSV than IMV by altering ventilatory support level.

Animals↗

[Early cytomegalovirus retinitis].

We report the clinical course of cytomegalovirus (CMV) retinitis associated with acquired immunodeficiency syndrome (AIDS) from the initial onset. The patient was a 40-year-old human immunodeficiency virus antibody-positive male with hemophilia A. He was diagnosed as having AIDS on the basis of pneumocystis carinii pneumonia. Ophthalmoscopic examination disclosed a small white punctate lesion at the macular area in his right eye. Because the lesion enlarged gradually with hemorrhages, it was suspected to be CMV retinitis. However, further examination was impossible due to his severe general condition. He died five months later and the autopsy disclosed disseminated CMV infection. Ocular histopathological examination revealed CMV retinitis. The earliest sign of CMV retinitis is supposed to be a white punctate retinal lesion, which becomes a small white patchy lesion resembling a cotton-wool spot. It may gradually progress to diffuse retinal involvement, frequently associated with hemorrhages.

Acquired Immunodeficiency Syndrome↗

[Anesthetic management of patients with dilated cardiomyopathy].

Anesthetic management of patients with dilated cardiomyopathy (DCM) was analyzed. From January 1991 to June 1993, we had 7 patients with DCM; 5 patients received general anesthesia and 2 patients received spinal anesthesia. General anesthesia was induced and maintained generally with diazepam and fentanyl. There were two patients who suffered from intraoperative arrhythmia. One patient who received spinal anesthesia suffered from ventricular fibrillation suddenly before the operation and we performed cardiopulmonary resuscitation successfully but the operation was cancelled. One patient who underwent emergency operation for gastric perforation suffered supraventricular tachycardia during the operation, and we were required to use antiarrhythmic agent that was thought to be deleterious to cardiac function. There was no patient who died perioperatively. There was one patient in the group IV of classification of Inoh which predicts the highest risk of dying from cardiac failure. In conclusion, it is important to control arrhythmia during the management of patients with DCM under anesthesia.

Adult↗

[General anesthesia for patients with hypertrophic cardiomyopathy].

General anesthesia was given to six surgical patients with hypertrophic cardiomyopathy on eight occasions from 1990 to 1992. Anesthetic courses were uneventful in five patients diagnosed previously as hypertrophic cardiomyopathy. However, a patient without a diagnosis of hypertrophic cardiomyopathy had intractable cardiac arrest. A slight hypotension caused by epidural anesthesia had a devastating effect on the patient. The above experiences stress the importance of early diagnosis and careful observation in perioperative period.

Aged↗

Influence of HLA-DRB1 gene variation on the clinical course of Vogt-Koyanagi-Harada disease.

PURPOSE: To investigate the difference, if any, in the immunogenetic backgrounds between two clinical subtypes of Vogt-Koyanagi-Harada disease (VKH). METHODS: HLA-DR4 gene variations were investigated in 46 Japanese patients, 28 with the prolonged type and 18 with the nonprolonged type of VKH. HLA-DR4 genes were amplified with polymerase chain reaction (PCR) and then analyzed for its variation with single-strand conformation polymorphism (SSCP) and restriction fragment length polymorphism (RFLP) methods. RESULTS: Significant differences were found in the DR4 gene variation in the two clinical subtypes. All the patients with the prolonged type had either the DRB1*0405 or DRB1*0410 variant, whereas 39% of the patients with the nonprolonged type had neither of them. This difference in frequency was statistically highly significant (P = 0.00059, Pc = 0.0041). DRB1*0405 was also more frequent in the prolonged type (93%) than in the nonprolonged type (56%) (P = 0.0044, Pc " 0.030). In the prolonged type, relative risk was highest for DRB1*0405/0410 (128), whereas in the nonprolonged type it was highest for DR4 (8.6). CONCLUSION: This preliminary study showed that DR4 gene variants differed significantly between the two subtypes of VKH, suggesting that the clinical course of VKH is determined partly by the patient's HLA-DR gene variation.

Base Sequence↗

HLA class II genes in Vogt-Koyanagi-Harada disease.

PURPOSE: Vogt-Koyanagi-Harada disease (VKH) is an autoimmune disorder causing a bilateral diffuse granulomatous uveitis, often with several associated extraocular manifestations. Strong association of human leukocyte antigens (HLA) antigens with the disease has been documented. The details of all HLA class II genotypes were investigated in Japanese patients with VKH to demonstrate the immunogenetic background of the disease. METHODS: Human leukocyte antigen tissue typing was performed in 57 Japanese patients with VKH by the modified two-stage complement-dependent microcytotoxicity method. DNA analyses were done by polymerase chain reaction (PCR)-single-strand conformation polymorphism and PCR-restriction fragment-length polymorphism methods. RESULTS: The frequencies of HLA-DR4 and HLA-DQ4 were 93% and 83% among the patients with VKH, compared with 43% and 32% among the controls, respectively (relative risks, 17.4 and 9.9; Pc < 1.0 x 10(-10)). At the genomic level, all patients had the HLA-DQA1*0301 genotype, which was present in only 67% of the normal controls (relative risk, 56.5; Pc < 1.0 x 10(-5)). With allelic combinations, -DQA1*0301/-DR4 showed the greatest relative risk ratio. Conversely, DQB1*0604 genotype was not detected among the patients. CONCLUSION: It can be postulated that VKH is a disease of combined allelic predisposition in which DQA1*0301 acts as the primary and HLA-DR4 acts as an additive factor in the development of the disease. Based on the negative association of DQB1*0604, we propose that DQB1*0604 provides considerable protection, possibly by altering other factors in the pathogenesis of VKH in the Japanese.

Base Sequence↗