PubMed Health⌕ Search

Biomedical subjects

C Yasunaga

Publications and source records attributed to C Yasunaga.

At least 37 records · Page 2Linked to original sources
PubMed1997

Acute hemorrhagic gastritis associated with acetazolamide intoxication in a patient with chronic renal failure.

Acetazolamide (Diamox) is a carbonic anhydrase inhibitor commonly used in patients with glaucoma in order to reduce intraocular pressure. Acetazolamide (AZ) is mostly excreted in the urine, therefore, the blood levels of AZ often tend to increase in patients with chronic renal failure. We experienced a case of chronic renal failure in a patient suffering from acute hemorrhagic gastritis associated with AZ intoxication. A 66-year-old female with chronic renal failure was referred to our hospital because of drowsiness and an acute deterioration of renal function. She had been treated with AZ, 500 mg per every day for eleven days for the treatment of glaucoma. Laboratory studies showed leukocyturia, thrombocytopenia, severe anemia, and tarry stools. The serum concentration of AZ was elevated to a maximum of 76.5 mg/ml. She was thus diagnosed as having AZ intoxication. On further examination, acute extensive hemorrhagic gastritis was also found by gastroscopy. Despite of the administration of intensive therapies, she died of disseminated intravascular coagulation (DIC) and septic shock due to bone marrow depression 6 days after admission. It is generally known that excessive blood levels of AZ inhibit not only the gastric juices but also prostaglandin levels and HCO3- excretion in the gastric mucosal barrier. We thus concluded that an excessive dose of AZ had probably destroyed the gastric mucosal barrier or thrombocytopenia due to bone marrow disorder and thus eventually led to the development of hemorrhagic gastritis. As far as we know, this is the first case report of acute hemorrhagic gastritis associated with AZ intoxication. Even though AZ tends to strongly bind to plasma protein and its clearance is generally poor by hemodialysis (HD), in our patient, HD was observed to be rather effective since the clearance of AZ was 45.8 ml/min on HD and 66 ml/min on direct hemoperfusion (DHP). DHP often reduces the number of platelets, also DHP needs a lot of heparin, therefore, we should have performed HD alone instead of DHP. In patients with an impaired renal function, AZ should therefore be administered very carefully in order to avoid an accumulation of the drug. In addition, HD alone should be used to remove any excessive amounts of AZ from the blood.

Acetazolamide↗
PubMed1997

Systemic lupus erythematosus in a patient with remitting minimal change nephrotic syndrome.

Minimal change nephrotic syndrome (MCNS) developed in a 17-year-old female and spontaneously remitted. One month later the nephrotic syndrome relapsed. Prednisolone therapy, 60 mg/day, was started and resulted in a full remission within a week and the prednisolone dose was subsequently tapered. Seven months later, when 10 mg/day of prednisolone was being administered, she developed erythematous rash with photosensitivity and polyarthralgia without exacerbation of the nephrotic syndrome, and fulfilled four of the American College of Rheumatology criteria for classification of systemic lupus erythematosus (SLE). Avoidance of direct sunlight ameliorated the erythematous rash and the polyarthralgia disappeared even though the prednisolone dose was decreased further. This is the first reported case of SLE developed in a patient with remitting MCNS.

Adolescent↗
PubMed1996

The effects of electrolyte, lactate, high-concentrated glucose, and dialysate on peritoneal mesothelial cells.

In order to investigate which component of dialysate is responsible for mesothelial cell damage, we studied the chronic cytotoxicity to mesothelial cells by using four types of solution. Four different types of solution (Ringer's solution, lactate, high-concentrate glucose, and 4.25% Dianeal) were prepared and injected into the abdominal cavity of five ddY-mice, 5 mL every day for one month. The monolayer of the mesothelial cells was carefully removed from the liver surface by the imprint technique. Then, the mesothelial cell damage was evaluated by using trypan blue staining and comparing the results. Trypan blue-stained cells in 100 mm2 were observed in 7.0% of the control, 15.4% of the Ringer's solution, 18.7% of the lactate, 23.2% of the high-concentrate glucose, and 22.4% of the 4.25% Dianeal group, respectively. The damaged cells were significantly (p < 0.05) greater in the 4.25% Dianeal group than in the control group, and those in the high-concentrate glucose group also appeared to be greater in number compared to the control group It is concluded from these results that damage to the mesothelial cells is induced by chronic exposure to high-glucose dialysate, and its pathogenesis is deeply related to high concentration of glucose.

Animals↗
PubMed1995

The use of a pig liver xenograft for temporary support of a patient with fulminant hepatic failure.

A 26-year-old female patient with fulminant hepatic failure and a history of autoimmune hepatitis was heterotopically transplanted with a pig hepatic xenograft to provide temporary metabolic support prior to transplantation with a human donor organ. Circulating natural antipig antibodies were removed prior to transplantation by plasmapheresis and ex vivo en bloc perfusion of the donor pig kidneys. The liver xenograft functioned after transplantation as measured by active bile production, stabilization of prothrombin levels, and reduction in the circulating levels of lactic acid and the enzymes AST and ALT. Despite the removal of greater than 90% of the recipient's natural xenoantibodies prior to transplantation, the levels of antibody rapidly returned and were associated with antibody and complement-mediated rejection of the donor graft. Immunohistochemical evidence of graft rejection could be detected by the deposition of antibody, complement components including properdin, and endothelial swelling as early as 3 hr posttransplantation. These lesions progressed in severity and were accompanied by evidence of thrombosis and ischemic necrosis of the liver xenograft by 34 hrs posttransplantation. The main portal vein, hepatic artery, and vena cava were patent. The placement of the liver graft did not result in any improvement in the neurological status of the patient and she died 34 hr after xenografting due to irreversible brain damage. The information derived from this case has renewed interest in the clinical use of bioartificial devices and whole organ perfusion using xenogeneic tissue for temporary bridging of patients prior to allografting.

Adult↗
PubMed1995

Differential patterns of reaction of human natural antibodies to pig hepatocytes and vascular endothelium.

We have recently conducted a series of experiments to characterize the pattern of reaction of human natural antibodies (NA) with individual pig liver cells. Pooled normal human serum (PHS) was incubated with cultured pig hepatocytes (HEP), aortic endothelial cells (AEC), and portal endothelial cells (PEC), and the reaction of NA to different cell types was measured by antibody-mediated cytotoxic (MTT assay), antibody binding (ELISA), and flow cytometric analysis. The human NA displayed a differential pattern of binding with hepatocytes exhibiting a more limited expression of xenoantigen expression than either aortic or portal endothelial cells. These differences in reaction patterns were also noted for Western blot analysis of individual cell membrane extracts. Preincubation of the pig cells with anti-pig MHC antibodies did not inhibit the binding of human IgM natural antibodies to the pig cells. Comparison of the pattern of NA absorption following the use of bioartificial liver support in patients with acute hepatic failure demonstrated limited ability of pig hepatocytes to absorb substantial amounts of NA. These studies indicate that pig hepatocytes are less vulnerable to NA cytotoxicity than pig vascular endothelial cells and that pig vascular endothelial cells express xenoantigens that are unique and not found on hepatocytes.

Animals↗
PubMed1995

The inhibitor cytokine interleukin-1 receptor antagonist synergistically augments cyclosporine immunosuppression in a rat cardiac allograft model.

Interleukin-1 receptor antagonist (IL-1ra) competes with IL-1 for binding of the IL-1 receptor, but does not elicit a cellular immune response. This study was designed to evaluate the effectiveness of IL-1ra in the immune and inflammatory responses to rat heart allografts. Experimental design was as follows: Group I HTx was syngeneic, BN to BN. The remaining groups were DA (RT 1a) to BN (RT 1n) allogeneic HTx. Group II was transplanted without immunosuppression. Group III received a low-dose IL-1ra regimen via osmotic pump into the peritoneum. Group IV recipients were similarly treated with a higher dose IL-1ra regimen. Group V rats received subtherapeutic cyclosporine (CsA) therapy while Group VI was treated with both CsA and low-dose IL-1ra. Group I rats survived indefinitely. Group II rats rejected their grafts at 5.33 +/- 1.37 days. Group III grafts survived for 7.16 +/- 0.48 days, and Group IV grafts for 8.16 +/- 0.75 days, both significantly longer than in Group II (P < 0.01). Group V animals treated with low-dose CsA had graft survival of 7.7 +/- 1.6 days, but combined therapy with CsA and IL-1ra in Group VI yielded significantly prolonged graft survival of 17.2 +/- 1.3 days (P < 0.0001). Histologic examination in treated recipients revealed delayed appearance of mononuclear cell infiltration. IL-1ra-treated recipients all demonstrated significantly reduced numbers of graft-infiltrating leukocytes; all phenotype subsets were equally affected. This study demonstrates the effectiveness of IL-1ra, in combination with low-dose CsA, in reducing the inflammatory response and rejection in the transplant setting.

Animals↗
PubMed1995

Superficial repositioning of the artery for chronic hemodialysis: indications and prognosis.

Superficial repositioning of the artery (SRA) is a modality of the blood access operation for chronic hemodialysis that has been previously used in cases of cardiac failure. We performed 42 SRAs from 1986 to 1993; thereafter, we retrospectively investigated the operative indications, postoperative complications, and long-term results. Superficial repositioning of the artery was indicated for the lack of an appropriate vein (17 cases; 40%), frequent and early access failure due to arteriovenous fistula or polytetrafluoroethylene grafts (six cases; 14%), venous hypertension (five cases; 12%), and cardiac failure (two cases; 5%). The patency rates of the SRAs were 87% at 3 years and 58% at 4.5 years. There was some difficulty in finding the returning veins in five of 28 functioning SRAs (18%). The SRA is thus considered to be a secondary-selected blood access operation; however, it also may be used as an efficient blood access for an extended period of time without any serious complications.

Adult↗
PubMed1994

Regeneration-induced accelerated rejection in reduced-size liver grafts.

Liver regenerative processes are associated with enhanced expression of alloantigens. Accordingly, we tested the hypothesis that such enhanced surface expression of alloantigens during regeneration of reduced-size liver grafts is associated with accelerated rejection. Our OLT model was LEW (RT1) to BN (RT1n), with donor liver resected by 50%. The study group consisted of reduced-size allografts. Control groups were syngeneic reduced-size isografts and full-size allografts. Reduced-size isograft recipients survived indefinitely. Both isografts and allografts regenerated to their prereduction size within 12 days. Recipients of reduced-size allografts died of accelerated rejection within 12.2 +/- 0.8 days, significantly earlier than recipients receiving full-size allografts (36.2 +/- 4.1 days, P < 0.01). The accelerated rejection in the regenerating allografts was mediated both by cellular and humoral mechanisms, evidenced by earlier lymphocytic invasion of the graft, enhanced donor MHC class II expression, and the emergence of IgM antibodies, directed specifically against donor endothelial antigens. These data suggest that regeneration of reduced-size allografts is accompanied by accelerated cellularly and humorally mediated alloreactivity. Recipients of reduced-size allografts may, therefore, benefit from more potent immunosuppression during the period of active liver regeneration.

Animals↗
PubMed1993

Removal of natural human xenoantibodies to pig vascular endothelium by perfusion of blood through pig kidneys and livers.

We have examined the nature of the binding of human xenoantibodies to pig liver and kidney vascular endothelium. Our results demonstrate that human serum contains IgM and IgG xenoantibodies that bind to pig vascular endothelium, and that the pattern of antibody binding is similar for both livers and kidneys. Immunohistochemical analysis of pig kidneys after perfusion with human blood demonstrated the binding of both IgM and IgG xenoantibodies, complement (C3), and fibrinogen to the vascular and glomerular endothelium. An ELISA assay of the perfusate after perfusion of 500 ml of human blood through a single pig kidney for 60 min demonstrated a significant reduction in the amount of human IgM (67%) and IgG (55%) binding to pig aortic endothelium. Similar perfusion experiments conducted with pig livers were associated with minimal immunohistochemical evidence of the binding of human xenoantibodies to liver vascular endothelium. Immunofluorescence staining for IgM, IgA, C3, and C1q was negative or minimally positive in the liver vascular endothelium. Sinusoidal endothelium were weakly positive for IgG and fibrinogen. The perfusion of the pig liver with human blood was, however, associated with a significant reduction in the subsequent binding of IgM and IgG to pig kidney vascular endothelium. Pig liver perfusion was also responsible for the removal of both IgM and IgG xenoantibodies capable of reacting with pig aortic endothelium, as measured by an ELISA assay of the perfusate. These results suggest that both pig kidney and livers are capable of absorbing the xenoantibodies that may be responsible for mediating a hyperacute rejection of pig xenografts and that the distribution of the target antigens for these antibodies is similar in the two organs.

Animals↗
PubMed1993

Pig aortic endothelial cell antigens recognized by human IgM natural antibodies.

Human-to-pig xenoantibodies may constitute a major obstacle to the successful use of pigs as xenograft donors for human transplantation. Our studies demonstrate that normal human serum contains antibodies, primarily IgM, that are cytotoxic for pig aortic endothelial cells (PAECs). These antibodies bind to several antigens isolated from PAECs, lymphocytes, platelets, red blood cells, and the kidney. Absorption of human serum with pig lymphocytes removes the cytotoxic activity to PAECs and some, but not all, of the IgM antibodies capable of binding in an ELISA assay to the PAECs. The cytotoxic antibodies are inactivated by 2-mercaptoethanol, suggesting that they are primarily IgM. Whole cell extracts of PAEC, lymphocytes, platelets, red blood cells, and kidney were prepared and analyzed by Western blots to establish the cellular distribution of the xenoantigens that react with human IgM in pooled human serum. Results showed that several of the most intensely stained bands migrated between 24 and 66 kDa. High molecular weight bands (> 100 kDa) were observed only in kidney, platelet, and PAEC preparations. Human IgM xeniantibodies also reacted strongly in Western blots to endothelial cell membranes proteins with molecular weights of 62, 48, 42, 36, 34, 28, and 26 kDa. Absorption of human serum with pig lymphocytes removes IgM binding to all bands except for a 34-kDa Treatment of the PAEC membrane proteins with proteinase K disrupts the binding of the human IgM antibodies. Similar treatment with glycosidase F) resulted in a decrease in molecular weight of the 28- and 26-kDa bands, suggesting that these xenoantigens are glycoproteins and that antibody binding to some xenoantigens may not require glycosylation.

Animals↗
PubMed1993

The prevention of accelerated cardiac allograft rejection in sensitized recipients after treatment with brequinar sodium.

Brequinar sodium (BQR) is a novel immunosuppressive agent that is highly effective in preventing B lymphocyte-mediated antibody production. We have examined the effects of BQR treatment in sensitized recipients on graft survival, donor-specific antibody responses (IgM and IgG), and the appearance of immunopathological lesions present in the grafts. LEW rat recipients were sensitized with single ACI skin graft on day 7 and received heterotopic ACI cardiac grafts on day 0. The recipients rejected the cardiac grafts in an accelerated fashion at day 2.5 post-transplantation, compared to day 7.0 in unsensitized recipients. The animals were treated with low (3 mg/kg/day) or high (12 mg/kg/3x weekly) doses of BQR during skin graft sensitization and/or after challenge with ACI heart allografts. All groups treated with BQR showed significant prolongation of graft survival in the sensitized recipients. The best survival was observed following high-dose BQR therapy during both sensitization and effector phases (median survival time = 40.0 days, P << 0.001). Daily treatment with BQR (3 mg/kg/day) prevented IgM (but not IgG) antibody responses. Treatment with higher doses of BQR (12 mg/kg/3x weekly) before and after skin graft sensitization was effective in preventing both IgM and IgG production. In general, BQR treatment resulted in effective suppression of anti-donor antibody responses, stable graft function, and a reduction in the severity of the acute vascular lesions in the graft. The effectiveness of BQR in preventing accelerated graft rejection when used at 12 mg/kg/3x weekly was comparable to that seen with treatment of sensitized animals with CsA at 15 mg/kg/day for 30 days. Daily treatment with cyclophosphamide at 5 or 15 mg/kg/day was ineffective for preventing graft rejection in sensitized recipients. These results indicated that BQR may provide an important addition to treatment protocols designed to prevent transplantation rejection in presensitized patients. BQR has the ability to significantly inhibit host cellular and humoral immune responses to the donor graft and this facet of the immunosuppressive activity of the drug may be responsible for preventing this aggressive form of rejection.

Animals↗