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Biomedical subjects

Y Fujino

Publications and source records attributed to Y Fujino.

At least 163 records · Page 9Linked to original sources

[Relation between the clinical course of Vogt-Koyanagi-Harada's disease and human leukocyte antigen (HLA)-DR4 subtypes].

Vogt-Koyanagi-Harada's disease (VKH) is an autoimmune disorder affecting melanocyte-containing tissues. VKH is strongly related to human leukocyte antigen (HLA)-DR4, a heterogeneous HLA specificity consisting of at least 12 different genotypes. The disease has two types: prolonged and non-prolonged, depending upon the clinical course. Fifty-four Japanese patients comprising 27 with the prolonged type, 15 with the non-prolonged type, and 12 new cases of VKH were included in this study. Ninety-three percent of the patients with all types had HLA-DR4. All 27 patients with the prolonged type had either the DRB1*0405 or *0410 genotype, and the non-prolonged type included two DR4-negative and four DRB1*0405 and *0410 negative patients. Our results indicate that the clinical course of VKH is determined partly by the patient's HLA genotype.

Adult↗

[Foscarnet for cytomegalovirus retinitis in a patient with acquired immunodeficiency syndrome].

A 41-year-old man with acquired immunodeficiency syndrome (AIDS) developed cytomegalovirus (CMV) retinitis. Intravenous administration of ganciclovir arrested progression of the retinitis, but it was discontinued due to side effects of severe anemia, neutropenia, and thrombocytopenia. Reactivation of CMV retinitis occurred two weeks after stopping ganciclovir, and then forscarnet was given intravenously. The response was prompt with resolution of the retinitis. There was no progression of retinitis during the treatment. The patient experienced renal dysfunction as a side effect of foscarnet, but it was reversible. As with ganciclovir, foscarnet appeared to be an effective drug for CMV retinitis associated with AIDS. Both drugs have severe adverse events: foscarnet causes renal dysfunction and ganciclovir causes myelosuppression, that necessitated discontinuation of the therapy. We suggest that alternating ganciclovir and foscarnet administration, switching to other treatment on the basis of the clinical response and side effects of the drugs, is an efficacious regimen for the treatment of CMV retinitis associated with AIDS.

AIDS-Related Opportunistic Infections↗

[Clinical significance of DNA ploidy heterogeneity in early gastric cancers].

To evaluate the clinical significance of DNA ploidy heterogeneity (DH), four or more fresh tissue specimens were obtained from a tumor in 68 resected early gastric cancers. DNA content was measured by flow cytometry and the presence of DH was prospectively investigated. The incidence of DH correlated to invasion depth (m < sm), lymph vessel invasion (negative < positive) and tumor size (10 mm or less in diameter < more than 10). When the criteria of indication for minimum surgery were determined as the intramucosal cancer without n, ly and v factor, 85% of contraindication cases demonstrated DH. These results indicate that DH is a useful marker of tumor progression in early gastric cancer and will be an aid for determining indications for minimum resection.

Aged↗

[Flow cytometric analysis of DNA ploidy in intramucosal gastric carcinoma].

In order to investigate whether or not DNA ploidy was altered in intramucosal gastric carcinomas, nuclear DNA content of biopsy specimen was measured using flow cytometry in 38 intramucosal carcinomas. DNA aneuploidy was detected in 27 of 38 lesions (71.1%), and noted more frequently in differentiated carcinomas than in undifferentiated ones (83.0% vs. 20.0%, p < 0.01). There was no significant relationship between the frequency of DNA aneuploidy and macroscopical type or tumor size. DNA aneuploidy was even found in two of three minute carcinomas (5 mm or less in diameter). DNA indices showed 1.2 or lower values in 40% of the lesions with DNA aneuploidy. The average value of DNA index was significantly larger in depressed type than in elevated type (p < 0.01). In conclusion, DNA ploidy is altered in most differentiated intramucosal carcinomas. A high resolution method is essential for accurate determination of DNA ploidy in intramucosal carcinomas, especially elevated ones.

Adenocarcinoma, Papillary↗

[Flow cytometric DNA analysis of colorectal carcinoma in adenoma].

We evaluated the DNA ploidy in 23 lesions of colorectal carcinoma in adenoma (CIA) and 90 adenomas without carcinomas by flow cytometry using fresh samples. DNA ploidy of carcinoma and adenoma components were assessed, respectively, with 17 paraffin-embedded samples of CIAs. The incidence of DNA aneuploidy (AP) was significantly higher in CIAs than in adenomas (47.8% vs. 12.2%, p < 0.01). Even in adenoma components of CIAs, AP tended to be found more frequent than in adenomas (41.2% vs. 12.2%). The incidence of AP in adenoma components was similar to that in carcinoma components (35.3%) in CIAs. In conclusion, DNA aneuploidy in adenomas may be a marker of malignant potential.

Adenoma↗

Behçet's disease associated with one of the HLA-B51 subantigens, HLA-B* 5101.

The strong association of Behçet's disease with HLA-B51 in several ethnic groups is well known. Because the HLA-B51 antigen has been recently identified to comprise three alleles, HLA-B* 5101, HLA-B* 5102, and HLA-B* 5103, we sought to investigate whether there is any correlation of one particular allele among them with B51-positive patients with Behçet's disease. Forty-six Japanese patients with Behçet's disease and HLA-B51 were typed by using the alloantisera, which allowed the subdivision of B51 antigen by the microlymphocyte toxicity assay. All the patients were found to carry HLA-B* 5101. This result suggests that amino acid substitutions at residue 167 or 171 prevent the development of Behçet's disease, because HLA-B* 5101 differs from HLA-B* 5102 and HLA-B* 5103 by single amino acid substitution at residues 171 and 167, respectively, or that another non-HLA gene tightly linked to the HLA-B* 5101-associated haplotype around the HLA class I gene region is responsible for the susceptibility to Bechçet's disease. This study provides insight into the molecular mechanism underlying an HLA association with Behçet's disease.

Alleles↗

Cryoprotective effect of egg yolk in cryopreservation of porcine embryos.

The objective of the present study was to assess the effect of egg yolk supplementation in solutions for either cooling or freezing of porcine embryos. In Experiment 1, porcine embryos collected on Day 3 to 7 (Day 0 = onset of estrus) were allocated to 12 experimental groups according to their developmental stages (four-cell to compact morula, early blastocyst to blastocyst, expanded blastocyst, and hatched blastocyst) and the concentrations of egg yolk (0, 5, and 10% (v/v)) for cooling to 0 degrees C. Whereas no embryos ranging from four-cell to blastocyst survived, the 10-min exposure to 0 degrees C despite egg yolk supplementation, expanded blastocysts and hatched blastocysts allocated to egg yolk-supplemented groups survived cooling to 0 degrees C. In Experiment 2, porcine expanded and hatched blastocysts collected on Day 6 or 7 were assigned to six experimental groups according to their developmental stages and the type of cryoprotectant used (10% glycerol, 11% Me2SO, and 10% propylene glycol) for freezing at -196 degrees C. All freezing solutions contained either 5 or 10% egg yolk. The embryos were equilibrated with one of the freezing solutions, cooled from 25 to -7 degrees C at 1 degree C/min, seeded at that temperature, then cooled to -36 degrees C at 0.3 degree C/min, and finally plunged into liquid nitrogen for storage. The frozen embryos were thawed by immersion in 37 degrees C water. After the cryoprotectants were removed by dilution, the embryos were cultured for 48 h to evaluate their viability.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effect of prostaglandin E1 during cardiopulmonary bypass on renal function after cardiac surgery.

We have evaluated the effect of prostaglandin E1 (PGE1) on renal function after cardiac surgery with cardiopulmonary bypass in 20 patients, ten of whom received 0.02 microgram.kg-1.min-1 of PGE1 by infusion into the oxygenator during bypass; ten patients served as controls. Serum beta 2-microglobulin fell significantly and urine beta 2-microglobulin increased significantly after surgery in both groups. Urine N-acetyl-beta-D-glucosaminidase was high after surgery in both groups, but it was significantly lower in the PGE1 group. Free water clearance fell significantly on the 1st, 3rd, and 5th postoperative days compared with preoperative values in the control but not in the PGE1 group. These results suggest that PGE1 may prevent renal dysfunction after cardiopulmonary bypass.

Acetylglucosaminidase↗

Recruitment of antigen-nonspecific cells plays a pivotal role in the pathogenesis of a T cell-mediated organ-specific autoimmune disease, experimental autoimmune uveoretinitis.

Experimental autoimmune uveoretinitis (EAU) is a prototypic T cell-mediated autoimmune disease, whose target tissue is the neural retina, that is used as a model for a number of human blinding ocular diseases of a presumed autoimmune nature. EAU in rats can be induced by adoptive transfer of small numbers of retinal antigen-specific CD4+ T cell lines. Although recruitment mechanisms were assumed to play a role in the immunopathogenesis of uveitis, there is no direct evidence that would permit assessment of the importance of recruited non-antigen-specific T cells in retinal autoimmunity. In the present study, we addressed this question by using congenitally athymic Lewis rats (LEW.rnu/rnu), that are deficient in functional endogenous T cells, but are otherwise syngeneic with the euthymic Lewis rats that develop characteristically severe EAU. The uveitogenic stimulus was delivered in the form of phenotypically and functionally homogeneous pathogenic T cell lines, specific to the major pathogenic epitope of either the intracellular photoreceptor protein, S-Ag, or the extracellular photoreceptor matrix protein, IRBP. Depending on the T cell line used, EAU in athymic rats was either drastically reduced in severity (IRBP), or essentially absent (S-Ag). Susceptibility was restored when the athymic animals were reconstituted with immunocompetent T cells from syngeneic euthymic donors. While the intraocular infiltrate in euthymic rats was predominantly lymphocytic, with smaller numbers of monocyte/macrophages and even fewer neutrophils, the sparse infiltrate in athymics was largely monocytic, and with a relatively high proportion of neutrophils and eosinophils. Reconstituted animals had an intermediate histological picture with respect to the infiltrating cell types and disease severity. Our data are consistent with the interpretation that recruitment of naive T cells constitutes an amplification mechanism that is central to the expression and pathogenesis of uveitis. The extent of dependence on this phenomenon appears to be influenced by the antigenic specificity of the T cell line, and could be connected to the 'accessibility' of the target antigen in vivo.

Animals↗

The effect of fasting and exogenous adenosine on ATP tissue concentration and viability of canine pancreas grafts during preservation by the two-layer method.

We have demonstrated a direct correlation between a high ATP level in a canine pancreas graft after preservation by the two-layer method and good posttransplant outcome. The purpose of this study was to examine the effect of fasting and exogenous adenosine on the ATP tissue level and viability of the canine pancreas graft during preservation by the two-layer method. Graft viability was judged by graft survival following autotransplantation. Maintenance of normoglycemia for 5 days post-transplant was considered graft survival. The pancreas was harvested from either 72-hr-fated (n = 3) or -fed dogs (n = 4) and preserved by the two-layer (Euro-Collins' solution [EC]/perfluorochemical [PFC]) method for 24 hr. Graft survival rates in fed and fasted groups were 4/4 (100%) and 3/3 (100%), respectively. There was no significant difference in ATP tissue concentrations between the two groups (7.48 +/- 0.55 vs. 7.03 +/- 0.74 mumol/g dry wt, NS). The pancreas was subjected to 60 min warm ischemia and then was preserved by the two-layer method using EC or EC containing 5 mM adenosine for 24 hr. Without adenosine, graft survival rate was 0/3 (0%) and ATP tissue levels were not changed during preservation (1.62 +/- 0.26 vs. 1.56 +/- 0.40 mumol/g dry wt, NS). However, provision of adenosine to the graft during preservation led to the restoration of ATP tissue levels (1.90 +/- 0.54 vs. 8.13 +/- 0.98 mumol/g dry wt, P < 0.01) in 4 of 5 grafts, and these grafts functioned immediately and maintained normoglycemia after transplantation. Graft survival rate was 4/5 (80%). One of 5 grafts, however, did not survive, and the ATP tissue level was not adequately recovered during preservation compared with viable grafts (3.67 vs. 8.13 +/- 0.98 mumol/g dry wt). This study clearly demonstrates that the nutritional state of the donor has no influence on the ATP tissue level and viability of the graft during 24-hr preservation by the two-layer method. On the other hand, provision of adenosine to the graft during preservation stimulates ATP synthesis and improves the viability of the ischemically damaged pancreas.

Adenosine↗

Successful extended preservation of ischemically damaged pancreas by the two-layer (University of Wisconsin solution/perfluorochemical) cold storage method.

We have demonstrated that a two-layer (University of Wisconsin solution [UW]/perfluorochemical [PFC]) cold storage method restores the function of ischemically damaged pancreas during 24-hr preservation in canine autotransplantation model. The purpose of this study was to examine the possibility of a long-term preservation of the ischemically damaged pancreas by the two-layer (UW/PFC) method. After 60 or 90 min of warm ischemic time, pancreas grafts were preserved by the two-layer (UW/PFC) method or a simple cold storage in UW alone for up to 96 hr. A K value of i.v. glucose tolerance test more than 1.0 2 weeks after autotransplantation was considered successful preservation. After 60 min warm ischemia, limitation of preservation time by the simple cold storage in UW was 24 hr (5/5 100% and 0/5 0%; 24- and 48-hr preservation, respectively). However, the two-layer method made it possible to extend the preservation time up to 48 hr (5/5 100%, 5/5 100%, 2/5 40%, and 0/5 0%; 24-, 48-, 72-, and 96-hr preservation, respectively). After 90 min warm ischemia, the simple cold storage in UW was not effective even for 24-hr preservation (0/5 0%). However, 48-hr preservation was successful by the two-layer (UW/PFC) method (5/5 100%, 5/5 100%, and 0/5 0%; 24-, 48-, and 72-hr-preservation, respectively). After preservation by the two-layer (UW/PFC) method, ATP tissue concentrations of viable grafts were significantly higher compared with nonviable grafts (9.11 +/- 3.05 (n = 22) versus 5.22 +/- 1.02 (n = 13) mumol/g dry wt, P < 0.001). Based on analysis of individual ATP for each graft, if an ATP concentration of 6.0 mumol/g dry weight was determined as a critical value for doing the transplant, sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 84.6%, 91.7%, and 94.3%, respectively. This study clearly demonstrated that 48-hr preservation of the canine pancreas subjected to either 60 or 90 min warm ischemia was successfully achieved by the two-layer (UW/PFC) cold storage method, and ATP tissue concentration at the end of preservation by this method would predict the post-transplant outcome of the ischemically damaged pancreas just prior to transplantation.

Adenosine↗

Maternal/fetal dehydration: prolonged effects and responses to oral rehydration.

Dehydration induces marked alterations in maternal-fetal fluid homeostasis and accompanying fetal endocrine responses. We sought to determine if the increase in fetal plasma arginine vasopressin (AVP) levels during maternal dehydration is mediated by fetal plasma hypovolemia in addition to hyperosmolality and to examine maternal and fetal plasma atrial natriuretic factor (ANF) responses to maternal dehydration and oral rehydration. Seven pregnant ewes (127 +/- 1 day) were water deprived for 72-96 h, and five of these were orally rehydrated. Dehydration induced significant increases in maternal plasma osmolality (pOSM) (300 +/- 2 to 325 +/- 8 mosmol/kg) and AVP (3.0 +/- 0.4 to 18.9 +/- 4.0 pg/ml), and decreases in plasma ANF levels (28.1 +/- 3.1 to 19.7 +/- 3.1 pg/ml). Fetal pOSM (293 +/- 3 to 314 +/- 4 mosmol/kg), AVP (2.5 +/- 0.6 to 8.1 +/- 4.8 pg/ml), and urinary fractional sodium excretion increased significantly, whereas plasma ANF and fetal blood volume did not change. After maternal water access maternal plasma AVP decreased rapidly in comparison to the gradual decrease in maternal pOSM. Fetal plasma AVP levels did not change significantly and fetal pOSM decreased more slowly than maternal pOSM. Fetal plasma ANF increased in association with increased urine flow and glomerular filtration rate after maternal rehydration. These data indicate marked differences in fetal and maternal plasma ANF and AVP responses with dehydration-induced increases in fetal plasma AVP being secondary to plasma hyperosmolality, rather than hypovolemia. Rapid suppression of maternal plasma AVP may contribute to the slower equilibration of fetal pOSM during oral, as compared with intravenous, maternal rehydration.

Animals↗

Ovine fetal swallowing and behavioral state responses to sublingual water.

Ovine fetal swallowing primarily occurs in bouts of activity associated with low voltage electrocorticogram activity and breathing movements. Despite similar rates of electromyographic swallowing activity, there are significant differences in the net esophageal fluid flow among fetuses. To determine if variations in the volume of fluids accessible to the fetus (amniotic fluid, lung fluid, salivary secretions) affect fetal swallowing, we studied the effects of sublingual distilled water infusions on ovine fetal swallowing rates and esophageal flow. Seven pregnant ewes at 127 +/- 2 days gestation were chronically instrumented with maternal and fetal vascular catheters, fetal electrocortical, electro-ocular and electromyograph electrodes, an esophageal flow probe and a sublingual infusion catheter. Following a 2-hour control period, consecutive sublingual infusions of room temperature distilled water (10 and 20 ml/kg/h) were administered for 2 h each. In response to sublingual infusions, fetal plasma sodium (142.5 +/- 0.5 to 140.8 +/- 0.8 mEq/l), chloride concentrations (109.2 +/- 0.4 to 107.7 +/- 0.7 mEq/l) and osmolality (302 +/- 2 to 298 +/- 2 mOsm/kg) decreased significantly. Swallowing activity and esophageal flow did not change significantly from basal values (47 +/- 9 swallows/h, 19.2 +/- 4.2 ml/h) during the sublingual infusions. However, fetal low-voltage electrocortical activity increased significantly during both infusion periods (42 +/- 3 to 56 +/- 6%). Sublingual distilled water infusion decreases fetal plasma osmolality and alters fetal behavioral state without affecting swallowing frequency or esophageal flow.

Administration, Sublingual↗