Biomedical subjects

K Ota

Publications and source records attributed to K Ota.

At least 19 recordsLinked to original sources

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

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↗

PubMed1992

Relationship between plasma levels of hyaluronic acid and amyloid-associated osteoarthropathy in chronic hemodialysis patients.

Plasma levels of hyaluronic acid (HA) and acute-phase reactants were determined in chronic hemodialysis patients with or without carpal tunnel syndrome (CTS) and/or shoulder pain, which are characteristic symptoms of amyloid-associated osteoarthropathy. While levels of acute-phase reactants tended to be higher in the patients with CTS and/or shoulder pain than in patients without these symptoms, the difference was not significant. However, plasma levels of HA were significantly higher in the patients with these symptoms. Analysis of plasma levels of HA in age-matched patients also demonstrated a significant correlation between elevated levels of HA and the presence of CTS and/or shoulder pain. Among the patients with CTS and/or shoulder pain, those patients with bone cysts in the carpal bone or humeral head had significantly higher plasma levels of HA than patients without bone cysts. Thus, there appears to be a relationship between elevated plasma HA and amyloid-associated osteoarthropathy in chronic hemodialysis patients that is more specific than any correlation with levels of acute-phase reactants.

Acute-Phase Proteins↗

PubMed1992

Serum concentrations of magnesium and parathyroid hormone in randomly selected hospital in-patients and out-patients, and in in-patients with dementia.

The relationship between hypomagnesaemia and the secretion of parathyroid hormone was studied. Serum parathyroid hormone (PTH) concentrations were measured in 63 randomly selected patients and 54 hospitalized demented patients using carboxyl-terminal PTH53-84 (h-PTH53-84), mid-region PTH44-68 (m-PTH44-68) and intact PTH1-84 kits. Both groups of patients were further subdivided into those with near normal serum magnesium concentrations (1.7 - 3.2 mEq/l) and those with hypomagnesaemia (1.2 - 1.6 mEq/l). Serum h-PTH53-84, m-PTH44-68 and PTH1-84 concentrations in both the randomly selected and the demented patients with hypomagnesaemia were significantly lower than those in the groups with near normal serum magnesium concentrations. The results suggest that parathyroid hormone secretion was inhibited in randomly selected patients and dementia patients with hypomagnesaemia.

Aged↗

PubMed1992

Clinical appraisal of vinpocetine for the removal of intractable tumoral calcinosis in haemodialysis patients with renal failure.

Previous studies have shown that vinpocetine [14-ethoxycarbonyl-(3 alpha, 16 alpha-ethyl)-14,15-eburnamenine] scavenges minerals and/or metals in the soft tissues of rabbits with artificially induced arteriosclerosis. The present study was carried out to determine whether or not vinpocetine would bring about the removal of intractable tumoral calcinosis in haemodialysis patients with renal failure. After administration of 15 mg/day vinpocetine for 3-12 months in haemodialysis patients with X-ray evidence of tumoral calcinosis, calcinosis was completely eliminated in all eight cases. Serum alkaline phosphatase and bone osteocalcin concentrations tended to decrease after treatment with vinpocetine compared with before treatment. Vinpocetine thus appears to be an effective scavenger of tumoral calcinosis in haemodialysis patients with renal failure without any side-effects during treatment.

Adult↗

PubMed1992

Effects of nicergoline on calcium and magnesium deposition in the central nervous system tissues of rats maintained on low-calcium diets.

Reduction of calcium intake leads to the mobilization of calcium and magnesium from the bone pool and to calcium deposition in the soft tissues, especially in the central nervous system (CNS). The effects of 10 alpha-methoxy-1,6-dimethylergoline-8 beta-methanol 5-bromonicotinate (nicergoline), an ameliorator of cerebral circulation and metabolism, on the deposition of calcium and magnesium in the CNS, heart, liver, kidney, muscle, abdominal aorta and bones were studied in rats maintained on standard and low-calcium diets. Rats were fed the following diets for 90 days: standard calcium (12.5 g/kg); standard calcium with 60 mg/kg nicergoline; low-calcium (30 mg/kg); and low-calcium with 60 mg/kg nicergoline. The presence of nicergoline did not affect blood chemistry but magnesium concentrations in the liver were significantly (P < 0.05) higher in rats fed standard diet with nicergoline. Magnesium concentrations in the occipital cortex, pons, cerebellum, liver, kidney, muscle and femur of nicergoline-treated rats fed low-calcium diet were significantly (P < 0.01-0.05) higher compared with those in the corresponding controls, whereas the calcium concentrations in the femur of nicergoline-treated rats fed both standard and low-calcium diets were significantly (P < 0.05) higher than those in the corresponding controls. In general, nicergoline tended to preserve the calcium content in the bone of rats fed a standard diet. Nicergoline may be implicated in calcium metabolism in rats fed low-calcium diets and may activate cerebral metabolism through the maintenance of magnesium concentrations in the CNS and soft tissues.

Animals↗

PubMed1992

Involvement of the gastric vagal nerve in the suppression of pulsatile luteinizing hormone release during acute fasting in rats.

Acute fasting has been shown to impair gonadotropin secretion in an estrogen-dependent manner in rats. The present study examined whether the vagus nerves have some role in the suppression of pulsatile LH release after 48-h fasting in ovariectomized estradiol-treated rats by performing complete subdiaphragmatic cutting of the nerves or selective sectioning of its branches (gastric, hepatic, or celiac) after the first hour of a 3-h blood sampling period. Vagotomy, alone, did not cause any changes in LH release in the unfasted animals. However, complete and gastric vagotomies restored pulsatile LH release that was suppressed before the nerves were cut in fasted animals. Neither hepatic nor celiac vagotomy restored pulsatile LH release, which remained suppressed throughout the sampling period in fasted animals. These results suggest that some mechanism involving the afferent vagal nerves, particularly the gastric vagus, has a major role in the suppression of pulsatile LH release during acute fasting in ovariectomized estradiol-primed rats.

Animals↗

PubMed1992

Prolongation of tetracaine spinal anesthesia by oral clonidine.

The effects of oral clonidine on the duration of isobaric tetracaine spinal anesthesia were studied in 30 patients undergoing urologic procedures. All patients received 15 mg of tetracaine intrathecally in isobaric saline solution. Group 1 (n = 10) received 0.25 mg of oral triazolam; group 2 (n = 10) received 0.15 mg of oral clonidine; and group 3 (n = 10) received 0.25 mg of oral triazolam and 0.75 mg of intrathecal phenylephrine. In group 1, the times for two- and four-segment regression of the level of analgesia to pin-prick were 80 +/- 17 and 123 +/- 22 min, respectively (mean +/- SD). The corresponding values of those measurements were 170 +/- 27 and 273 +/- 48 min in group 2 and 175 +/- 34 and 273 +/- 68 min in group 3. All the regression times in groups 2 and 3 were significantly longer than those in group 1. Regression times were not different between groups 2 and 3. The authors conclude that prolongation of tetracaine sensory analgesia may be produced by premedication with 0.15 mg of oral clonidine. The prolongation is similar to that produced by intrathecal phenylephrine.

Administration, Oral↗

PubMed1992

Impaired water diuresis in a patient with pseudo-Bartter syndrome.

A 32-year-old man was diagnosed as having pseudo-Bartter syndrome due to surreptitious habitual vomiting and to maldigestion related to decayed teeth. His chief complaints were muscle pain and weakness. In this case, metabolic alkalosis, hypokalemia, hypochloremia, increased plasma renin activity and aldosterone levels were noticed with marked decreases in urinary chloride excretion. Creatinine clearance (GFR) and renal plasma flow (RPF) were also decreased. Blood pressure was normal, but the pressor response to angiotensin II was attenuated. Before treatment with 0.9% saline infusion, plasma vasopressin (AVP) was not suppressed sufficiently by lowering the plasma osmolality (Posm) with an oral water load (WL), but it normally responded to a rise in Posm due to hypertonic saline infusion. Moreover, plasma AVP was normally suppressed by WL after the replenishment of saline. Plasma atrial natriuretic peptide (ANP) was low before WL, but increased normally in response to WL. However, inconsistent with the normal response in this case, decreases in plasma AVP failed to dilute urinary osmolality and to increase urine flow, irrespective of the levels of plasma ANP. These results indicate that chronic inanition due to surreptitious vomiting causes impaired renal diluting ability through decreases in GFR and RPF, irrespective of the levels of plasma AVP and ANP.

Adult↗

PubMed1992

Plasma vasopressin and atrial natriuretic hormone levels in hypopituitarism with and without hydrocortisone treatments: responses to an acute water load.

To assess whether arginine vasopressin and atrial natriuretic hormone participate in impaired urinary dilution and excretion in glucocorticoid deficiency secondary to hypopituitarism, an acute oral water load of 20 ml.kg-1 BW was undertaken in the absence and presence of an oral hydrocortisone (60 mg) treatment in patients with ACTH deficiency (N = 7) and panhypopituitarism (N = 2). Plasma arginine vasopressin and atrial natriuretic hormone and renal water handling were simultaneously determined and compared with those in similarly water-loaded normal subjects. Plasma arginine vasopressin did not fall in response to decreased blood osmolality after an acute water load in the absence of hydrocortisone; plasma atrial natriuretic hormone did not change despite blood volume expansion; and impairment in urinary dilution and excretion remained. On the other hand, in the presence of hydrocortisone, plasma arginine vasopressin fell in response to a decrease in plasma osmolality and plasma atrial natriuretic hormone increased, thereby restoring urinary dilution and excretion. These results demonstrate that the impaired arginine vasopressin response to acute water loading play an essential role in deranged renal water and electrolyte handling in the state of glucocorticoid deficiency; the impaired release of atrial natriuretic hormone also may affect these disorders.

Adult↗

PubMed1992

Mechanism of proteinuria in nephrotic syndrome.

We developed a "tissue negative staining method" to observe the molecular-level ultrastructure in situ in any portion of the ultrathin sections routinely prepared for electron microscopy. This method was used in electron microscopy of the glomerular basement membranes (GBM). The GBM in patients with nephrotic syndrome was discovered to possess a tunnel structure, designated as "nephrotic tunnel", with lumen large enough to allow free passage of protein molecules. This tunnel seemed to be involved in the etiology of nephrotic syndrome. This new method appears to be applicable to a variety of purposes in biological studies.

Animals↗

PubMed1992

Modified hemoglobin solution as possible perfusate relevant to organ transplantation.

A modified hemoglobin solution ( - conjugate solution, PHP solution) has very interesting characteristics such as oxygen-carrying property without corpuscular components. Experimental use of the PHP solution has shown promising possibilities as a perfusate relevant to organ transplantations. 1) Elongation of warm ischemic time in canine kidneys: Dogs survived even with the unilateral kidneys which had been exposed up to 4.5 hour warm ischemia and, thereafter, perfused with the PHP solution. 2) Elongation of perfusion preservation period of canine livers: Dogs survived with the transplanted livers which had been perfused for 48 hours with the PHP solution. 3) Successful perfusion of rat small intestine: Lewis rat intestines perfused and preserved for 12 hours with the PHP solution showed a higher survival rate compared with those with Collins or UW solution. 4) Removal of antibodies: By exchange transfusion with a total of 30-60 ml of the PHP solution, a Lewis rat hematocrit lowered to 5% while IgG went down to nil from 8970 mg/dl, IgA to 28 mg/dl from 118 mg/dl and IgM to 190 mg/dl from 897 mg/dl. This technique is expected to be applicable for removal of the naturally existing antibodies in xenotransplantation.

Animals↗

PubMed1992

Evaluation of a pyridoxylated hemoglobin polyoxyethylene conjugate solution as a perfusate for small intestine preservation.

A new type of artificial blood, pyridoxylated hemoglobin-polyoxyethylene conjugate (PHP) solution, (developed by PHP research group of the department of health and welfare of Japan, and produced by Ajinomoto Co., Inc. Tokyo) as an oxygen-carrying component, has been recently devised using hemoglobin obtained from hemolyzed human erythrocytes. Recently, the studies using this solution as a preservation solution were performed in some instances. To examine the mechanism of improved viability using this solution as a preservation solution, we developed a model of orthotopic small intestine transplantation (OIT) in the rat. As a baseline study, we compared parameters of viability of the grafts preserved in Collins and UW solution to those preserved in PHP solution including a survival rate, a serum level total protein and albumin, and a change in body weight after transplantation. In our study, the simple hypothermia storage together with intestinal perfusion preservation with PHP solution was performed. Animals were divided into 6, 12, and 24 hr preservation groups. All of the rats survived after 6 hr preservation following transplantation. However, in 12 hr storage, five of six rats in PHP solution preservation survived and recovery in body weight after grafting was better than those with Collins and UW solution. We conclude that the PHP solution is, therefore, considered to possibly be a more suitable perfusate for small intestine preservation than Collins and UW solution.

Adenosine↗

PubMed1992

[The distribution and localization of alpha 1-adrenoceptor agonist on the bladder and urethra of female rats].

The distribution of selective alpha 1-adrenoceptor agonist 1-(2',5'-dimethoxyphenyl)-2-glycinamidoethanol hydrochloride, midodrine, and its active metabolite 1-(2',5'-dimethoxyphenyl)-2-aminoethanol, DMAE, was evaluated on bladder and urethra of 8-weeks and 52-weeks old female rats. Prior to the intravenous injection of 14C-labeled midodrine and DMAE, bilateral ureters were ligated to prevent drug uptake from the urinary tract. In 8-weeks rats, 14C-midodrine activity was significantly (p less than 0.01) higher in the bladder than in the femoral muscle, which served as a control for drug distribution. Similarly, higher uptake of 14C-DMAE was observed in the bladder than in the femoral muscle (p less than 0.01) and the urethra (p less than 0.05). In 52-weeks rats, there was no significant difference of midodrine uptake among these tissues. However, significantly higher uptake of 14C-DMAE was observed in the urethra than in the femoral muscle (p less than 0.05). Compared with midodrine, the concentration of DMAE was significantly increased in the bladder of 8-weeks rat and in the urethra of 52-weeks rats (respectively, p less than 0.05). In autoradiogram, the grains corresponding to midodrine and DMAE were diffusely distributed on the smooth muscles of bladder (mainly bladder neck and trigone) and urethra. The grains were also recognized on the vessels and perivascular areas of these tissues. These findings support that midodrine and DMAE could be effective for stress incontinence, because these drugs are known to bind specifically to alpha 1-adrenoceptor.

Adrenergic alpha-Agonists↗