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Biomedical subjects

K Ota

Publications and source records attributed to K Ota.

At least 307 records · Page 17Linked to original sources
PubMed1993

[A clinicopathological study of patients with immune complex type and pauci immune type rapidly progressive glomerulonephritis].

We made clinicopathological studies of twelve patients with rapidly progressive glomerulonephritis (RPGN) treated at our department of Okayama University Medical School Hospital for the last eight years. By immunofluorescence microscopy, seven cases were immune complex (IC) type and five were pauci immune type. By light microscopy, the mean percentage of glomeruli with crescents was seventy five, and cellular and fibro-cellular crescents were dominant in eleven cases. Combined therapy including methylprednisolone pulse or oral steroid was effective in eleven. Hemodialysis was performed in four patients with severe uremia and three of them recovered from hemodialysis. Two cases of RPGN associated with systemic lupus erythematosus died of cerebral hemorrhage. We conclude that IC type and pauci immune type RPGN have good prognosis when treated at their active stage with intensive combined therapy and with hemodialysis if necessary.

Adult↗
PubMed1993

[Cisplatinum compounds].

New cisplatinum derivatives of 254-S, DWA2114R and NK121 developed in Japan were reviewed. These three compounds have less nephrotoxicity and nausea/vomiting than cisplatinum, but have more myelotoxicity. 254-S showed activities against carcinomas of the head and neck, lung, esophagus, urinary tract, prostate, testis, ovary and cervix. DWA2114R showed activities against carcinoma of the ovary, prostate, testis and breast. NK121 is under phase II study. A randomized controlled study of 254-S for non-small-cell lung cancer and DWA2114R for ovarian cancer was performed compared to cisplatinum. The antitumor activity of these compounds was not different from cisplatinum, however the hydration was much less than cisplatinum. These cisplatinum derivatives of 254-S and DWA2114R were thought to be useful for QOL of the patients treated with cisplatinum compound.

Adult↗
PubMed1993

Macromolecules that are colocalized with deposits of beta 2-microglobulin in hemodialysis-associated amyloidosis.

BACKGROUND: Common elements in many different types of amyloid may have important roles in amyloidogenesis. The proteinaceous tissue deposits have a common appearance in polarized light and other similar features. The present investigation describes for the first time the relation between beta 2-microglobulin (beta 2-M)-type amyloidosis and colocalized materials, as demonstrated using specific antibodies and hyaluronan-binding protein. EXPERIMENTAL DESIGN: Amyloid-rich carpal tunnel synovium was obtained surgically from 28 patients who were being treated by maintenance hemodialysis. Serial sections were examined using a hyaluronan (hyaluronic acid)-binding protein and antibodies against heparan sulfate-glycosaminoglycan, chondroitin sulfate-proteoglycan, dermatan sulfate-proteoglycan, alpha 1-antichymotrypsin, alpha 1-antitrypsin, inter-alpha-trypsin inhibitor, haptoglobin, and ubiquitin. RESULTS: Accumulation of hyaluronan was of three types, namely, localization around beta 2-M deposits, colocalization with deposition of beta 2-M itself and localization at a small distance from beta 2-M deposits. Immunostaining for heparan sulfate glycosaminoglycan was demonstrated at the sites of beta 2-M plaques. Chondroitin sulfate-proteoglycan did not show specific patterns of immunostaining, resembling hyaluronan rather than heparan sulfate. The other materials tested, alpha 1-antichymotrypsin, alpha 1-antitrypsin, inter-alpha-trypsin, haptoglobin and ubiquitin, were not immunostained at sites of beta 2-M plaques. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting revealed that the molecular weight of heparan sulfate-glycosaminoglycan was 16,000. CONCLUSIONS: These results suggest that HS has an important role in hemodialysis-associated amyloidosis as it does in other types of amyloidosis. Moreover, accumulation of hyaluronan may be an indication of inflammation of the carpal synovium.

Amyloidosis↗
PubMed1993

[Phase I study of 5-fluorouracil and l-leucovorin].

Leucovorin, given usually by i.v. injection or orally changes to 5, 10-methylene tetrahydrofolate in tumor as well as normal cells. And in normal FdUMP, an active metabolite of 5-FU, binds tightly to thymidylate synthase in the presence of cofactor, 5, 10-methylene tetrahydrofolate. This interaction leads to potentiate the cytotoxic effect of 5-FU by prolonged inhibition of thymidylate synthase. Phase I study using l-leucovorin (l-LV), an active form of leucovorin, combined with 5-FU, was conducted. In the weekly schedule, 5-FU was fixed to 600mg/m2, and l-LV dose was escalated from 125 mg/m2 to 250mg/m2, if toxicity was acceptable. On the other hand, in the five consecutive-day schedule, 5-FU was fixed to 370mg/m2 and l-LV was escalated from 25mg/m2 to 50mg/m2, 100mg/m2 and 200 mg/m2. l-LV 10mg/m2 was tested as reference. On weekly schedule of l-LV 250mg/m2, grade III diarrhea was seen in 2 cases and grade IV leucopenia was seen in one. In five consecutive-day schedule, at each dose of l-LV, stomatitis, nausea plus vomiting, anorexia, anemia and leucopenia were seen. However, the increase of toxicities were not seen by dose escalation of l-LV. Then, we have been conducted a randomized early phase II study using 250 mg/m2 of l-LV weekly (arm A) and 100mg/m2 (arm B) or 10mg/m2 (arm C) of l-LV for 5 consecutive days in gastric and colorectal cancer by multicenter cooperative study. Plasma concentrations of l-LV were maintained > 10(-5) mol/L for over 5 hrs. after 2 hrs. infusion of 250 mg/m2 of l-LV and for over one hr. after a rapid injection of 100mg/m2 of l-LV.

Adult↗
PubMed1992

Usefulness of 31P-MRS as a method of evaluating the viability of preserved and transplanted rat liver.

We used phosphorus-31 magnetic resonance spectroscopy (31P-MRS) to evaluate the viability of transplanted rat liver. Wistar rats were used as donors and recipients. The donor livers were preserved in saline (group 1), Euro-Collins solution (group 2), or in University of Wisconsin (UW) solution (group 3) for 3 and 6 h in groups 1, 2 and 3 and for 9 h in groups 2 and 3. Thereafter the livers were orthotopically transplanted. 31P-MRS spectra were measured after portal reperfusion. Finally, all the recipients were divided into survivors and non-survivors. Survival rates were better in group 3 than in groups 1 and 2. In the 9-h-preserved livers, the livers in group 3 showed a significantly higher beta-ATP/Pi ratio than those in group 2. Comparing survivors and non-survivors in the 6-h-preserved livers in group 2, survivors' livers showed significantly higher beta-ATP/Pi ratio than those of non-survivors. We concluded that 31P-MRS is a useful method for assessing viability of rat liver grafts.

Adenosine Triphosphate↗
PubMed1992

Multicentre trial of ABO-incompatible kidney transplantation. Japanese Biosynsorb ABO-incompatible kidney transplant study group.

A multicentre study of ABO incompatible kidney transplantation using Biosynsorb was started in Japan in November 1989. A total of 51 cases were registered comprising 23 cases of A incompatibility, 26 cases of B incompatibility and two cases of AB incompatibility. The removal of antibodies (IgG and IgM) was carried out using Biosynsorb in 16 cases, plasmapheresis in four cases and use of both combined in 31 cases. The treatment using Biosynsorb was repeated 3.4 times on average. Serum titres of anti-A (IgG and IgM) antibodies decreased to 4.9 +/- 5.0 and 2.7 +/- 1.7 and for anti-B titres decreased to 2.8 +/- 3.5 and 2.4 +/- 3.2. Rejection was found in 33 cases: hyperacute one, accelerated acute five, and acute 27. In two cases rejection was developed concomitantly with a steep elevation in antibody titres. Three patients died, two with functioning grafts. Eight grafts were lost. Patient and graft survivals at 2 years were 94.1% and 84.3%, respectively. From these results it is concluded that: 1. Biosynsorb and plasmapheresis are effective in removing anti-A and anti-B antibodies; 2. graft and patient survivals are similar to those in ABO compatible cases; 3. anti-A and anti-B titres less than 16 are recommended at the time of transplantation; 4. anti-A and anti-B titres higher than 128 may be considered as a risk factor for rejection in the early stages after transplantation.

ABO Blood-Group System↗
PubMed1992

Effect of prostaglandin E1 on graft function of kidneys from living related donors.

Prostaglandin E1 (PGE1) was used in renal transplant recipients with living related donors. The drug was given intravenously from day 1 to day 7 after transplantation at a dose of 40 microg/kg twice a day. A total of 45 patients were studied divided into two groups: 25 patients were treated with PGE1 (group B) and the remaining 20 patients did not receive the drug (group A). In group B, 24-h creatinine clearance (Ccr) was 66 +/- 12.8 ml/min compared with 40.3 +/- 13.4 ml/min in group A on the fifth postoperative day (P < 0.05). Urinary levels of N-acetyl-beta-D-glucosaminidase (NAG) and serum levels of platelet factor 4 (PF4) in group B were significantly lower than in group A. On the fourth postoperative day, the urinary excretion of thromboxan B2 (TxB2) in group A was higher than in group B, but not significantly (5.1 +/- 3.0 ng/day and 2.8 +/- 1.1 ng/day, respectively). Acute rejection occurred in four patients in group B and in 10 patients (40%) in group A. The percentage of Leu2a-positive lymphocytes in group B was higher than in group A. We conclude that postoperative administration of PGE1 improves graft function in kidneys from living related donors.

Adult↗
PubMed1992

The Japanese Interferon Study Group (JISG) has established the efficacy of human interferon-beta for serious CMV pneumonitis in kidney recipients. Japanese Interferon Study Group.

The Japanese Interferon Study Group (JISG) is a research organization formed by 30 special hospitals for organ transplantation. A joint multi-centre, double-blind trial was conducted in order to investigate the efficacy of human interferon-beta (HuIFN-beta) against serious cytomegalovirus pneumonitis in kidney recipients.

Acute Disease↗
PubMed1992

The use of granulocyte colony-stimulating factor to shorten the interval between cycles of mitomycin C, vindesine, and cisplatin chemotherapy in non-small-cell lung cancer.

We investigated the possibility of shortening the interval between courses of the commonly prescribed 28-day MVP (mitomycin C, vindesine, and cisplatin) regimen in patients with non-small-cell lung cancer (NSCLC). We conducted a nonrandomized phase II study using recombinant human granulocyte colony-stimulating factor (G-CSF, Chugai) to explore the possibility of shortening the cycle length to 21 days and compared the results with those obtained in historical controls who had received the standard 28-day regimen. A total of 40 patients, 37 of whom were evaluable, were entered in the 21-day treatment group of the trial and were compared with 38 historical controls who had received standard 28-day cycles of MVP at our institution. Patients in the 21-day group received mitomycin C at 8 mg/m2 on day 1, vindesine at 3 mg/m2 on days 1 and 8, and cisplatin at 80 mg/m2 on day 1, with the schedule being repeated every 21 days. Controls had received the same regimen, albeit at 28-day intervals. G-CSF was given s.c. to the patients in the 21-day group at a daily dose of 2 micrograms/kg from day 2 to day 21 of every MVP cycle. The administration of G-CSF to these patients accelerated neutrophil recovery as compared with that observed in the historical controls. Significant differences were found between the two groups in terms of mean neutrophil nadirs (2666/microliters in the first cycle and 1369/microliters in the second for the G-CSF group vs 416/microliters in the first cycle and 685/microliters in the second cycle for the control group; P < 0.0001) and the mean duration of neutropenia (< or = 1000/microliters; 1.0 day in the first cycle and 1.7 days in the second for the G-CSF group vs 8.0 days in the first cycle and 6.9 days in the second for the control group; P < 0.0001). This enabled 32 (86%) of 37 patients in the G-CSF group to complete > or = 2 cycles on schedule. In 10 patients, the bone marrow aspirates taken after G-CSF administration showed increases in band neutrophil and myelocyte percentages. In conclusion, MVP treatment of patients with NSCLC at 21-day intervals is possible with the support of G-CSF.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Clinical trials of bestatin for leukemia and solid tumors.

A new immunomodulating agent, bestatin (INN: ubenimex) has low toxicity after long-term oral administration and significantly modifies immunological responses. Prolongation of remission duration and survival was achieved in adult acute nonlymphocytic leukemia with bestatin immunotherapy combined with remission maintenance chemotherapy. Patients with myelodysplatic syndrome (MDS) and chronic myelogenous leukemia (CML) responded to bestatin, and it is noted that cytogenetic remission was obtained in CML. MDS and CML are thought to be a family of clonal malignant disorders in which malignant transformations occurs at the level of the pluripotent stem cell. Bestatin may be capable of modifying the biological-proliferative disequilibrium of the disease, and the therapy opens new and promising prospects in the treatment of both MDS and CML. Randomized controlled studies of bestatin immunotherapy were performed in solid tumors including malignant melanoma, carcinoma of the lung, stomach, bladder, head and neck, and esophagus, and therapeutic benefits on disease free-interval or survival were observed in certain types of these cancers. However, the adjuvant activity of bestatin immunotherapy for these cancers should be further investigated to confirm its activity.

Humans↗
PubMed1992

Detection of multiple hormones and their mRNAs in human neuroblastoma cell line NB-1 using in situ hybridization, immunocytochemistry and radioimmunoassay.

The production and secretion of multiple peptide hormones and tyrosine hydroxylase by the human neuroblastoma cell line NB-1 and the effects of dibutyryl cAMP (Bt2cAMP) and phorbol esters such as 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on them were investigated. The presence of messenger RNAs (mRNAs) of vasoactive intestinal peptide (VIP)/peptide histidine methionine (PHM), preprotachykinin, and tyrosine hydroxylase was detectable in the cytoplasm of cultured NB-1 cells by in situ hybridization. Treatment with Bt2cAMP and TPA markedly increased the number of cells immunoreactive to VIP, PHM, neuropeptide Y, Met-enkephalin, substance P and tyrosine hydroxylase and also the contents of VIP and Met-enkephalin in the culture medium. Bt2cAMP and TPA induced morphological changes characteristic of endocrine differentiation, such as an increase in neuroendocrine granules and the development of rough endoplasmic reticulum and Golgi apparatus. The results indicated that treatment with Bt2cAMP and TPA induces the expression of multiple genes of peptide hormone and tyrosine hydroxylase and increases hormone production and secretion through morphological changes into endocrine cells.

Bucladesine↗
PubMed1992

Optimum albumin concentration of supplementation fluid for double filtration plasmapheresis.

Until recently, the albumin concentration of supplementation fluid for double filtration plasmapheresis (DFPP) has been empirically determined. Inadequate albumin infusion often leads to hypoproteinemic symptoms such as edema. In the current study, an aimed condensation coefficient (CCaimed) was introduced in an attempt to estimate the appropriate plasma albumin level for each patient. This coefficient is theoretically derived from a one-compartment model for the patient's plasma albumin: CCaimed = CS/CD = 1 - (1 - CR)/[1 - exp(- CC.VR)] where CD and CS are albumin concentrations in discarded plasma and supplementation fluid. CR is the change ratio of albumin concentration in the patient's plasma during a DFPP treatment, and VR(= VS/VP) is the ratio of supplementation fluid volume (VS) to the patient's total plasma volume (VP). And CC denotes the albumin condensation coefficient in a DFPP line, which depends on the filtration fraction of the plasma fractionator (FFPF) and the sieving coefficients of both the plasma separator (SCPS) and the plasma fractionator (SCPF): CC = CD/CP = SCPS.(1 - FFPF.SCPF)/(1 - FFPF) where CP is the albumin concentration of the patient's plasma. From the above relations, CS can be determined as follows: CS = CC.CCaimed.CP Because many kinds of proteins are removed during a single DFPP treatment, a slightly higher albumin concentration in the supplementation fluid is needed to maintain an appropriate plasma level. Therefore, the CR value should be more than unity. For a patient with hematocrit (HCT) of 30%, body weight (BW) of 50 kg, and CP of 3.0 g/dl, who is receiving a DFPP treatment using AP-05H (SCPS of 0.970) and Evaflux 2A (SCPF of 0.526) under FFPF of 0.8 with VS of 500 ml, VP = BW(1- HCT/100)/13 = 50 x (1 - 30/100)/13 = 2.69 L, VR = 500/(2.69 x 1,000) = 0.186, CC = 2.81, and CCaimed = 1.25 assuming 1.1 for CR. Therefore, CS = 2.81 x 1.25 x 3.0 = 10.5 g/dl using the above equations.

Albumins↗
PubMed1992

Interaction of ANP with endothelin on cardiovascular, renal, and endocrine function.

To assess the interaction of endothelin (ET) with atrial natriuretic peptide (ANP) on cardiovascular and renal function, arginine vasopressin (AVP) release, and the renin-angiotensin-aldosterone system, either a low or high dose of ET (4 or 12 pmol.kg-1.min-1) was administered with ANP (26 pmol.kg-1.min-1) for 45 min after the initial infusion of ANP alone in anesthetized dogs. In the other groups, either ANP or saline alone was administered for 90 min. ANP alone decreased blood pressure (BP), cardiac output (CO), plasma aldosterone, and plasma renin activity (PRA), increased urinary Na and K excretion (UNaV and UKV, respectively) and urine flow (UF), but did not affect plasma AVP. The low dose of ET had no effect on these ANP-induced changes. However, the high dose of ET curtailed the responses to ANP, increased BP and PRA, and decreased UNaV, UKV, and UF associated with decreased renal plasma flow and glomerular filtration rate. High ET also further potentiated the decrease in CO and the increase in total peripheral resistance induced by ANP and increased plasma AVP. These results indicate that a dose of ET one-half that of ANP (on the molar ratio) may have completely counteracted vascular, hormonal, and renal responses to ANP.

Aldosterone↗
PubMed1992

Central effects of endothelin-1 on vasopressin release, blood pressure, and renal solute excretion.

To assess central effects of endothelin-1 (ET-1) on plasma arginine vasopressin (AVP), plasma atrial natriuretic peptide (ANP), blood pressure, heart rate, and renal solute excretion, ET-1 dissolved in the artificial cerebrospinal fluid was infused intracerebroventricularly (icv) at a dose of either 0.35 ng.kg-1.min-1 (0.14 pmol; LET) or 3.5 ng.kg-1.min-1 (1.4 pmol; HET) for 45 min in conscious rats. In the control study, ET-1 was omitted from the vehicle. Moreover, [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid),2-O-methyl-tyrosine]AVP (TMeAVP), a V1-blocker, and prazosin, an alpha 1-blocker, were peripherally administered. In the LET group, mean arterial blood pressure (MABP) increased without any changes in heart rate, plasma AVP and ANP, and renal solute excretion. In the HET group, MABP markedly increased with rises in plasma AVP and ANP, but urine flow, urinary osmolality, and urinary Na and K excretion decreased. TMeAVP attenuated the pressor response to ET-1, abolished rises in plasma ANP, and partially restored falls in urine flow. Prazosin after TMeAVP obviated the pressor response to ET-1. In the control, these parameters did not change, except for an increase in urinary solute excretion. These results showed that icv ET-1 stimulates the sympathetic nervous activity and plasma AVP, leading to increased blood pressure and renal vasoconstriction, with a reduction in renal water and electrolyte excretion.

Analysis of Variance↗
PubMed1992

Alpha 2-adrenergic receptors are involved in the suppression of luteinizing hormone release during acute fasting in the ovariectomized estradiol-primed rats.

It has been previously reported that the adrenergic system is involved in the control of feeding behavior and LH release. In the present study, the role of the adrenergic receptors in the suppression of LH release during acute fasting are examined by injecting the alpha 1-antagonist (prazosin), alpha 2-antagonists (idazoxan, SKF 86466-A, piperoxan), or beta-antagonist (propranolol) into the third ventricle of unfasted and 48 h fasted ovariectomized estradiol-treated rats. Blood samples were collected every 6 min for 3 h and the drugs were administered after the first hour of the sampling period. Prazosin caused a significant suppression of LH release in the unfasted animals while idazoxan and propranolol had no significant effects. In contrast, all alpha 2-antagonists blocked the inhibitory effect of fasting on LH release and significantly reinstated the suppressed LH release while prazosin and propranolol had no significant effects. We conclude from these results that the suppression of LH release during acute fasting is mediated by alpha 2-adrenergic receptors but not alpha 1- or beta-adrenergic receptors.

Adrenergic alpha-Antagonists↗