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Biomedical subjects

K Ota

Publications and source records attributed to K Ota.

At least 199 records · Page 11Linked to original sources

The in vivo cytoprotection of ascorbic acid against ischemia/reoxygenation injury of rat liver.

The in vivo effects of ascorbic acid on the reoxygenated liver tissue were examined, with regard to the following effects: (i) the effects of scavenging radicals and/or reducing peroxidative reactions, and (ii) the effects of the chelation with low-molecular-weight iron and increasing its reactivity (radical production). Ascorbic acid is one of the water-soluble vitamins known to have various physiological effects involving both chelating and reducing properties at once. Lipid peroxidation of the reoxygenated liver tissue estimated by the production of TBARS (thiobarbituric acid-reactive substance) and LPO (lipid hydroperoxides) was suppressed effectively by the preischemic intraperitoneal administration of ascorbic acid. Ascorbic acid also showed this anti-oxidant effect in a dose-dependent manner. The analysis of the levels of ascorbic acid and glutathione of the liver tissue revealed that ascorbic acid works as an anti-oxidant probably by being oxydized finally to dehydroascorbic acid just after the reoxygenation. The latter was reduced to ascorbic acid again, coupled with the conversion of GSH to GSSG in the postischemic time course. The predominant effect of ascorbic acid on the reoxygenated liver tissue seems to be caused by the scavenging radicals and/or reducing peroxidative reactions, rather than by chelating iron and increasing its reactivity (radical production). Cellular integrity (estimated by the release of GOT, GPT, and LDH) and the energy state of the postischemic liver tissue (estimated by the tissue ATP level) were also well preserved by the administration of ascorbic acid.

Adenosine Triphosphate↗

Current status of renal replacement therapy in Japan.

The study of the current status of renal replacement therapy in Japan is based on the analysis of data from the registry reports for regular dialysis therapy and kidney transplantation. The total number of patients receiving regular dialysis therapy was 123,926 at the end of 1992: 117,809 (95.1%) on hemodialysis and 6,117 (4.9%) on peritoneal dialysis. The primary diseases of newly accepted patients were chronic glomerulonephritis (42.2%), diabetic nephropathy (28.4%), nephrosclerosis (5.9%), polycystic kidney disease (2.7%), chronic pyelonephritis (1.6%), and others. The number of kidney transplant patients in Japan was 8,384 at the end of 1991: 6,154 (73.4%) received a living donor transplantation and 2,230 (26.9%) received a cadaver donor transplantation. Overall 5-year survival rates of dialysis patients were 60.4%: 69.7% for chronic glomerulonephritis, 41.7% for diabetic nephropathy, 39.6% for nephrosclerosis, 73.6% for diffuse polycystic kidney disease, and 66.6% for chronic pyelonephritis. The causes of death of dialysis patients were heart failure (31.1%), cerebrovascular accident (13.6%), infectious diseases (11.3%), malignancies (7.1%), cachexia/uremia (6.7%), myocardial infarction (5.8%), and others. The gross mortality rate of dialysis patients was increased in cases of less than 4 hours of the average length of each dialysis session, less than 4% and more than 9% of the average weight loss during each dialysis session, less than 1.0 of Kt/V, and less than 0.9 and more than 1.7 g/kg/d of protein catabolic rate. Overall 5-year patient and graft survival rates of kidney transplant patients since 1964 were 82.7% and 60.3%: 84.4% and 65.0% in living donor cases, and 77.4% and 46.2% in cadaver donor case, respectively. Those since 1983 were 90.1% and 68.2%: 91.3% and 72.6% in living donor cases, and 87.8% and 59.3%, respectively. Graft survival rates were superior in cases treated with combined steroid, cyclosporine and azathioprine or mizoribine, to those treated with other immuno-suppressive regimens, and they decreased as the number of HLA-A, -B and -DR increased.

Actuarial Analysis↗

Effect of poly(ADP-ribose) synthetase on the expression of major histocompatibility complex (MHC) class II genes.

We have studied the effect of poly(ADP-ribose) synthetase on the interferon-gamma (IFN-gamma)-inducible expression of major histocompatibility complex (MHC) class II molecules. We constructed an expression plasmid capable of expressing either a sense RNA (MT-ARS) or an antisense RNA (pAS-FL or pAS-5') for poly(ADP-ribose) synthetase. We transfected the plasmid into mouse or human macrophage tumor cells and examined the effect on the expression of MHC class II molecules. The IFN-gamma-inducible expression of MHC class II gene was considerably reduced in transformant clones (A-2, B-2), in which the synthetase was highly expressed, whereas the depletion of the synthetase due to the expression of antisense RNA for the synthetase amplified the expression of MHC class II molecules. The results indicate that the level of the synthetase critically regulates the IFN-gamma-inducible MHC class II molecules. Next, we analyzed DNase I hypersensitive sites (DHS) of mouse MHC class II, I-A beta gene and found two sites, one in the promoter region and the other one in the first intron. The DHS in first intron was less sensitive towards DNase I attack in transformant clones (A-2, B-2) in which the synthetase was synthesized in a large quantity. Thus we constructed two beta-galactosidase reporter genes, one (A beta 2.0kb-lac z) containing the promoter region to a part of the second exon of the class II gene, and the other (A beta pro-lac z) containing the promoter region of the class II gene alone. The expression of the reporter gene was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) and found that the expression of A beta 2.0kb-lac z was suppressed in the transformant clones (A-2, B-2) relevant to control cells but the expression of A beta pro-lac z was the same level among those cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Preventive effect of pirfenidone against experimental sclerosing peritonitis in rats.

We investigated the preventive effect of pirfenidone (PFD), a newly developed anti-fibrotic agent, on experimental sclerosing peritonitis (sp) which we had established in rats. Male Wistar rats (150-250 g) were divided into the following two groups; 7 rats were treated with daily intraperitoneal (i.p.) injection of 0.1% chlorhexidine gluconate (CH) and 15% ethanol solved in 2 ml of saline for 26 days as a control of SP model (CH group) and 6 rats were treated daily with peroral (p.o.) administration of 350 mg/kg of PFD in addition to the daily i.p. injection of aforementioned CH-ethanol-saline solution for 26 days (CH + PFD group). Macroscopic intraperitoneal changes and histological fibrotic changes were graded by scoring in a blind manner. Actual subserosal thickness was measured by observation under light microscope. Body weight gain was significantly greater in CH + PFD group than in CH group (P < 0.05). Macroscopic intraperitoneal adhesion changes in CH + PFD group were significantly fewer than in CH group (P < 0.05). Fibrotic changes were fewer and subserosal thickness in liver and intestine were smaller in CH + PFD group with statistical significance (p < 0.1). We concluded that PFD markedly inhibited or prevented fibrotic changes in the experimental sclerosing peritonitis induced by CH.

Animals↗

Maintaining low concentrations of plasma beta 2-microglobulin through continuous slow haemofiltration.

As a first step in the development of a future wearable artificial kidney, we conducted three forms of treatment with continuous haemofiltration (CHF) on a group of 10 patients in an attempt to determine what plasma values of small molecules and beta 2-microglobulin (beta 2-M) could be maintained. In the first system, one ordinary 4-h haemodialysis, followed by 7-day CHF with 51 exchange per day, was repeated. The second system consisted of CHF with 51 exchange/day and thrice weekly slow nocturnal dialysis. The third system used CHF with 101 exchange per day. The first, second and third systems were used with three, four and four patients, respectively, for at least 4 weeks each. PAN-DX and FH-66 haemofilters were used eight and three times, respectively, with continuous infusion of heparin at 500-700 units/h. In the first system, the pre-CHF plasma beta 2-M was 45.5 +/- 3.1 mg/l, against a much lower 18.8 +/- 1.0 mg/l 4 weeks later. With the second system, this decrease was from 43.5 +/- 5.7 mg/l to 18.1 +/- 1.1 mg/l with 4 weeks treatment, and from 44.7 +/- 3.4 mg/l to 18.1 +/- 1.4 mg/l with 3 weeks treatment. Pre-haemodialysis treatment levels of urea nitrogen, plasma creatinine and uric acid in the first system were greater than ordinary pre-haemodialysis levels. On the second system, these were kept at -54 +/- 8.3%, -52.2 +/- 6.7% and -47.6 +/- 4.4% of the ordinary pre-haemodialysis levels, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

ABO incompatible kidney transplantation in children.

We have performed 7 pediatric kidney transplantations from living related donors of ABO incompatibility. All patients preoperatively underwent plasmapheresis with or without immunoadsorption to reduce anti-A and/or anti-B antibodies. Immunosuppression initially consisted of methylprednisolone, cyclosporine, azathioprine, antilymphocyte globulin and deoxyspergualin. At transplantation splenectomy was simultaneously performed in all patients. Median followup is 44 months (range 31 to 58). Patient and graft survival rates are 100% to date. There were no uncontrollable vascular rejection episodes, and post-transplant anti-A and/or anti-B antibody titers were always less than 1:32. Transplantation across the ABO blood barrier remains challenging today. However, our small series clearly shows that the preoperative reduction of ABO antibody, simultaneous splenectomy and strict immunosuppressive therapy cause successful long-term results in children.

ABO Blood-Group System↗

Clinical trial of new polyurethane vascular grafts for hemodialysis: compared with expanded polytetrafluoroethylene grafts.

We developed a new polyurethane vascular access graft coated with gelatin and reinforced with knitted polyester fibers (PE-PEUG). Advantages over expanded-polytetrafluoroethylene graft (E-PTFEG) were previously reported in experimental studies. Between May 1990 and August 1992, 39 PE-PEUGs including 34 loop and 5 straight and 18 E-PTFEGs including 18 loop were implanted to create arteriovenous (AV) fistulas in a total of 52 adult patients on maintenance hemodialysis (HD). They were followed up until October 1994. Hemostasis on the suture line was achieved within 3 min in all patients implanted with PE-PEUGs. Bleeding from the needle holes of PE-PEUG stopped within 10 min with gentle finger pressure. Minimal local edema developed in only a few patients implanted with PE-PEUG while most patients implanted with E-PTFEG developed moderate local edema. One seroma formation was found in an E-PTFE case. Aneurysmal dilatations were observed twice in a PE-PEUG patient 9 and 17 months after the implantation and once in a E-PTFEG patient 2 years after the implantation. The cumulative patency rate at 1 year in the PE-PEUG and E-PTFEG groups were 53.2 and 70.8%, respectively. Our clinical study showed that the PE-PEUG had several advantages over E-PTFEG: prompt hemostasis, no persistent edema and no formation of seroma, no change in elasticity, and sufficient mechanical strength. However, the cumulative patency rate was inferior to that with E-PTFEG implanted in our series. Further modifications are therefore necessary to improve the patency rate.

Adult↗

The effect of total blood exchange with PHP solution on cardiac xenotransplantation.

Prevention of hyperacute rejection is a difficult and unsolved problem in xenotransplantation. Natural antibodies and complement activation have been known to play an important role in the xenotransplantation between discordant species pairs. In the present study, total blood exchange (TBE) was performed with pyridoxalated-hemoglobin-polyoxyethylene conjugate (PHP) solution (Ajinomoto Co., Inc., Kawasaki, Japan) before cardiac xenotransplantation in order to remove the immunoglobulins and prolong xenograft survival time. Guinea pigs and rats were used as the discordant species combination for donor and recipient. Two groups were established: Group 1, untreated control (n = 8) and Group 2, TBT with PHP solution (n = 8). The exchange blood transfusion was carried out at the rate of 15-20 ml/h utilizing PHP solution using a blood pump. After the blood exchange was processed, hematocrit (Ht) levels dropped to 4 or 5%, and a cardiac xenotransplantation was performed within 24 h. The levels of serum IgA, IgM, and IgG were decreased to less than 25, 25, and 10% of the base line, respectively, after blood exchange. A mean xenograft survival time in Group 2 was prolonged to 472 +/- 74 min and to 10.4 +/- 1.8 min in Group 1 (p < 0.01). A titer of the anti-guinea pig lymphocytotoxic antibody in rat serum was decreased to almost nil. The data from this study suggest that total blood exchange with PHP solution may be useful in preoperative removal of xenograft antibodies in xenotransplantation.

Animals↗

Escape of red blood cells through gaps in glomerular basement membrane in a patient with mixed connective tissue disease.

Hematuria in patients with glomerulonephritis seems to result from the passage of red blood cells through anatomical gaps in the glomerular basement membrane. However, such morphological evidence has rarely been demonstrated. A patient with mixed connective tissue disease associated with membranous glomerulonephritis is described in whom the renal biopsy specimen showed an escape of red blood cells through a gap in the basement membrane. These findings support the morphological basis of hematuria in glomerulonephritis.

Adult↗

Acute hemorrhagic cystitis caused by adenovirus after kidney transplantation.

We report on 10 kidney transplant patients with acute hemorrhagic cystitis caused by adenovirus, accompanied by the deterioration of kidney function. They developed macrohematuria with urgency, frequency and micturition pain for more than 7 days within 1 year after transplantation. Adenovirus type 11 was isolated from the urine of 6 patients, and complement-fixing antibody became positive in 9 patients. Hematuria and irritative voiding symptoms disappeared without any specific treatment; however, serum creatinine rapidly increased. The histological findings of the biopsy specimens indicated that renal impairment was attributed to acute rejection in some cases and virus-associated nephropathy in other cases. Acute hemorrhagic cystitis caused by adenovirus is an interesting complication after kidney transplantation, especially with regard to kidney impairment and treatment.

Adenoviridae Infections↗

Effects of V1- and V2-vasopressin (AVP) antagonists on the pressor, AVP and atrial natriuretic peptide responses to a hypertonic saline infusion in conscious anephric rats.

To examine the role of vasopressin (AVP) receptors in the regulation of the hemodynamics and release of atrial natriuretic peptide (ANP), and the participation of renal nerve inputs in the osmotic AVP release, hypertonic saline (HS) was infused into conscious, bilaterally nephrectomized rats with non-peptide, selective antagonists for the V1-receptor or V2-receptor of AVP. In the control group, HS alone increased mean arterial pressure, plasma ANP and AVP, plasma volume and plasma osmolality, and decreased the heart rate. In the V1-receptor antagonist group, an increase in the mean arterial pressure and a decrease in heart rate were completely abolished and an increase in plasma ANP was attenuated. In the V2-receptor antagonist group, increases in mean arterial pressure and plasma ANP and a decrease in heart rate were attenuated. However, the ratio of the changes in heart rate to the changes in mean arterial pressure in the V2-receptor antagonist group is significantly higher than that in the control group. In both experimental groups, increases in plasma AVP, plasma volume and plasma osmolality were not different from those in the control group. These results suggest that a HS-induced increase in mean arterial pressure is mediated by the pressor effect of AVP, mainly through V1-receptors, and that the depressor effect of AVP through V2-receptors may not influence tonically HS-induced hypertension. Moreover, HS-induced increase in plasma ANP is mediated mainly by increases in plasma volume and blood pressure, but may not be affected by a direct action of AVP to the heart. Renal afferent nerve inputs may not have effects on the regulation of osmotic AVP release.

Animals↗

Chlorpropamide-induced ADH release, hyponatremia and central pontine myelinolysis in diabetes mellitus.

Chlorpropamide (CPM) has been reported to produce impaired water excretion due to the enhancement of renal vasopressin (ADH) action and/or due to centrally enhanced ADH release, but it is still unknown whether CPM gives rise to ADH release with a subsequent hyponatremia in diabetes mellitus (DM), which, in turn, causes an impairment of the central nervous system. In 3 patients with DM, who developed hyponatremia during the treatment with CPM, an acute water load (WL) was carried out in the presence and absence of the drug, and plasma ADH was determined with plasma and urine osmolalities. Moreover, in 2 cases, MRI scans of the brain were taken. In all the patients, acute WL tests failed to suppress completely ADH release in response to changes in plasma osmolality in the presence of CPM, which, in turn, resulted in the impaired water excretion. In the absence of CPM, an acute WL normally suppressed plasma ADH leading to the diuresis. MRI scans illustrated the presence of central pontine myelinolysis. It is likely that CPM might stimulate ADH release in DM with a subsequent hyponatremia and brain damages.

Aged↗

Changes in plasma vasopressin levels and cardiovascular function due to postural changes in diabetic neuropathy.

Decreases in blood pressure are well known to increase the release of vasopressin. Studies were carried out to investigate whether vasopressin responses to postural changes in blood pressure are maintained in diabetic patients with orthostatic hypotension [DM-OH(+)] as well as non-diabetic patients with orthostatic hypotension [nonDM-OH(+)] and these responses were compared with those observed in normal subjects and diabetic patients without orthostatic hypotension [DM-OH(-)]. After 30 min in the supine position, the upright posture for 40 min was maintained and then the supine for 10 min. Blood pressure and heart rate (HR) were measured every 5 min and plasma vasopressin levels (plasma AVP) were determined every 10 min. In normal subjects and DM-OH(-), mean arterial blood pressure (MABP) did not change, but HR increased significantly by the upright position. Plasma AVP did not change in these groups. On the other hand, in DM-OH(+) MABP fell abruptly and remained to decrease during the upright posture. The HR responses in this group, however, were similar to those in normal control and DM-OH(-). Plasma AVP in DM-OH(+) significantly increased only at 30 min during upright. These increases were significantly greater than those in normal and DM-OH(-). There were significant correlation in changes in MABP (delta MAP) and plasma AVP (delta AVP) in DM-OH(+) (delta AVP = -0.13 MABP + 1.5, r = -0.32, p < 0.01). Relationship between delta MABP and delta AVP in nonDM-OH(+) was similar to that in DM-OH(+). It is concluded that AVP responses to orthostatic hypotension in diabetic and non-diabetic neuropathies were attenuated, but heart rate responses in these patients ware well reserved.

Adult↗

Role of atrial natriuretic peptide in interleukin 1 beta-induced natriuresis in conscious rats.

To assess whether atrial natriuretic peptide (ANP) plays a role in the natriuresis induced by interleukin 1 beta (IL-1 beta), the following experiments were carried out. Experiment (Ex) I: IL-1 beta (7.5 micrograms/kg BW) was given intravenously (i.v.) in conscious hydrated rats (n = 6). Plasma ANP, vasopressin (AVP) osmolality (Posm), Na and K, urine Na (UNa V) and K excretion (UK V), osmolality and flow (UF), and mean arterial blood pressure (MABP) and heart rate were simultaneously determined. In the control group (n = 6), the drug was omitted, and the same protocols were carried out. Ex II: Three mg/kg BW of the specific ANP antagonist, HS-142-1 (HS), was administered i.v. and then, IL-1 beta (7.5 micrograms/kg BW) was given i.v. (n = 6). In the HS alone group (n = 6), IL-1 beta was omitted. The experimental protocols were the same as those in Ex I. IL-1 beta increased significantly plasma ANP and AVP and UNa V, but not UF, accompanied by decreases in Posm and UKV and increases in MABP (ExI). HS inhibited the natriuresis mediated by IL-1 beta, despite increases in plasma ANP and had no influence on plasma AVP and MABP. In the control (ExI) and HS alone (ExII) groups, these parameters did not change, except for decreases in Posm in both groups and increased plasma ANP in the latter. These results suggest that plasma ANP may play an essential role in the IL-1 beta-mediated natriuresis.

Animals↗

Crohn's disease associated with growth hormone secretory dysfunction.

A 10-year-old boy presented in 1989 with repeated episodes of vomiting, abdominal distension and severe growth retardation. Endocrinologic examination indicated growth hormone (GH) secretory dysfunction. Administration of recombinant human GH (rhGH) led to growth, but the patient discontinued treatment. He was readmitted to our hospital in 1993, at the age of 16. His stature was very short. Laboratory findings suggested malnutrition. Radiologic examination revealed regional stenosis and a cobblestone appearance of the intestine. The histologic diagnosis was compatible with Crohn's disease. Administration of prednisolone alleviated gastrointestinal symptoms with the improvement of GH secretory function.

Child↗