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Biomedical subjects

M Nishikawa

Publications and source records attributed to M Nishikawa.

At least 559 records · Page 31Linked to original sources

Effects of atrial natriuretic peptide infusion and its metabolism in patients with chronic renal failure.

Synthetic alpha-human atrial natriuretic peptide (hANP) was infused continuously at a rate of 80 ng/kg/min for 20 min into normal volunteers and patients with chronic renal failure (CRF) receiving hemodialysis. Blood pressure (BP) decreased significantly both in normals and in patients with CRF. The magnitude and the duration of the decrease, however, were greater in patients with CRF. The plasma aldosterone concentration (PAC) decreased significantly in normals and only minimally in patients with CRF. The half time (T1/2) of plasma hANP in patients with CRF (M +/- SE: 4.5 +/- 0.5 min) was longer than that in normals (1.8 +/- 0.2 min). Moreover, the metabolic clearance rate in patients with CRF (64 +/- 7 ml/kg/min) was less than in normals (150 +/- 20 ml/kg/min). Thus, the T1/2 in plasma of hANP in patients with CRF was noticeably longer than in a normal control group. These findings suggest that hANP suppresses PAC regardless of electrocyte imbalances and/or volume change induced by kidney dysfunction and that the kidney may be important in degrading hANP.

Adrenal Glands↗

Mechanism of thyroid stimulation by human chorionic gonadotropin in sera of normal pregnant women.

To elucidate the mechanism of thyrotropic activity of human chorionic gonadotropin in sera of normal pregnant women, we examined the effect of blockade of the TSH receptor on the serum-induced cAMP accumulation and the effect of hCG on the TSH binding to FRTL-5 cells. In the presence of crude immunoglobulin fractions in sera from patients with primary hypothyroidism, cAMP accumulation induced by both crude and purified hCG, and normal pregnant women serum were significantly inhibited compared with that in the presence of normal IgGs. The mode of inhibition of these IgGs on the cAMP accumulation was similar for TSH and hCG when analysed by Lineweaver-Burk plots. Moreover, binding of [125I]bTSH to the TSH receptor in porcine thyroid cell membrane was apparently inhibited by adding 4 x 10(6) IU/l of purified hCG. Binding studies of TSH in FRTL-5 cells also indicated the dose-dependent displacements of [125I]TSH by hCG. Although half-maximal inhibitory concentration of hCG was about 20 times as high as that of TSH on a molar basis, displacement of [125I]TSH was observed at a concentration of hCG of 10(5)IU/l or more, which could be a physiological concentration of hCG in sera of normal pregnant women. These results suggest that thyrotropic activity of hCG in sera of normal pregnant women is, at least in a part, mediated by TSH receptors.

Animals↗

Regulation of atrial natriuretic hormone production by triiodothyronine in cultured rat atrial myocytes.

Since thyroid hormones have been reported to increase the synthesis of rat atrial natriuretic hormone and its mRNA accumulation, we further investigated the mechanism of stimulation of rANH synthesis by T3 using cultured rat atrial myocytes. T3 (10(-9)-10(-7) mol/l) increased cellular content and secretion into the medium of immunoreactive rANH in a dose-dependent manner. However, the ratio of secreted/cellular rANH was not altered by the addition of T3. Furthermore, in both cellular and secreted rANH, the larger molecular form (gamma-rANH) apparently predominated over the smaller one (alpha-rANH), and this profile was not influenced by T3 (10(-7) mol/l). Although T3 (10(-9)-10(-7) mol/l) also increased cellular rANH mRNA accumulation, the ratio of cellular rANH/rANH mRNA was not changed. Moreover, using actinomycin D, we found that T3 (10(-7) mol/l) did not affect the degradation of rANH mRNA. From these findings, we suggest that T3 has no specific effects on the translational and posttranslational processes and the release of rANH, but that T3 stimulates rANH synthesis in the pretranslational levels, probably in the transcriptional level of rANH gene.

Animals↗

[Ventricular dilation during the treatment of subdural hygromas].

Fifty-one cases with subdural hygroma experienced in the past 20 years were retrospectively reviewed. Eight patients showed definite ventricular dilation differing from simple restoration of the ventricles following disappearance of the cavity. The mean age was 72.4 years. Six patients presented with mental change as the initial symptom. On the initial computed tomography (CT), 75% of the cases had bilateral lesions, all were low density, and 88% were crescent shaped. Trepanation performed on six patients yielded watery clear or xanthochromic fluid. Nine to 61 days (mean 4 weeks) after admission, definite ventricular dilation was observed. Cisternography performed in four patients was all abnormal, although cerebrospinal fluid (CSF) pressure was within normal range. Cerebral blood flow images using 123I-iodoamphetamine and single photon emission CT in four patients revealed periventricular low uptake which was disproportionately large compared with the ventricular span on CT. A ventriculoperitoneal shunt was placed in four patients. The final outcome, however, was poor irrespective of treatment. These findings indicate that an impairment of the CSF circulation was not the sole cause of the ventricular dilation. Low CSF pressure and the disproportionately large periventricular low perfusion, compared with the ventricular span on CT scan, suggest a pre-existing periventricular parenchymal damage, which had been subsequently compromised by the presence of subdural mass lesion. Therefore, attention should be paid in aged patients with bilateral low dense, crescent-shaped subdural hygroma, presenting with mental change, for the risk of subsequent ventricular dilation which may affect the functional outcome.

Aged↗

Evidence for a direct adverse reaction of neuroleptics in self-induced water intoxication of psychiatric patients.

A mentally retarded patient who developed polydipsia and hyponatremia following the long-term use of neuroleptics is described. Before the investigation, he was treated with a combination of five drugs: diazepam, propericiazine, carbamazepine, lithium carbonate and trihexyphenidyl. The treatment was switched to diazepam alone; to propericiazine, trihexyphenidyl and diazepam; to carbamazepine and diazepam; and finally to lithium carbonate with diazepam. Under the five drug treatment protocols, his weight gains during the day were monitored, every day as an index of the water he drank in the day time. The combination of the five drugs caused the greatest weight differences per day and the other drug regimens, except diazepam alone, seemed to increase the weight differences to some extent. These findings indicate that a drug combination such as the neuroleptics, lithium and carbamazepine used for emotional stabilization must be carefully monitored to avoid the induction of compulsive drinking.

Adult↗

WF-2421, a new aldose reductase inhibitor produced from a fungus, Humicola grisea.

WF-2421 is a novel aldose reductase inhibitor produced by Humicola grisea. WF-2421 was purified from the culture filtrate by successive ion exchange chromatography and the chemical structure was assigned to be alpha-formamido-5'-(2-formamido-1-hydroxyethyl)- beta,2',6-trihydroxy-3-biphenylpropanoic acid (1) on the basis of spectroscopic evidence. The IC50 value of WF-2421 was 3 x 10(-8) M against partially purified aldose reductase of rabbit lens.

Aldehyde Reductase↗

Studies on WF-3681, a novel aldose reductase inhibitor. IV. Effect of FR-62765, a derivative of WF-3681, on the diabetic neuropathy in rats.

Pharmacokinetic properties of WF-3681 and FR-62765 in rats were examined. FR-62765 showed higher peak concentrations in the plasma and higher concentrations in the sciatic nerve than WF-3681 when each compound was administered orally to rats. We therefore evaluated FR-62765 in rats with diabetic neuropathy. As a result, FR-62765 at 32 mg/kg/day administered for 3 weeks to streptozotocin-induced diabetic rats significantly prevented the accumulation of sorbitol in the sciatic nerve and the reduction of motor nerve conduction velocity in the tail. From these results it was concluded that the aldose reductase inhibitor FR-62765 might be a useful drug for diabetic neuropathy.

Aldehyde Reductase↗

Diagnostic value of Lipiodol injection in focal nodular hyperplasia of the liver.

We encountered a case of small focal nodular hyperplasia (FNH) of the liver. It was difficult to distinguish FNH from hepatocellular carcinoma by means of sonography, computed tomography (CT), and angiography. After the injection of Lipiodol, it accumulated densely on FNH, but was washed away after a short time, as observed on the follow-up CT. This progress was different from that in hepatocellular carcinoma.

Adult↗

Urinary excretion of glycated protein determined with a specific radioimmunoassay.

We developed a simple and highly sensitive RIA for glycated protein (GP), and used it to measure GP in serum and urine from 15 normal controls and 30 diabetics (14 with urinary excretion rate of albumin, Ualb less than 15 micrograms/min, group A; nine with 15 less than or equal to Ualb less than or equal to 150 micrograms/min, group B; and seven with Ualb greater than 150 micrograms/min, group C). The mean serum concentration of GP was above normal in all groups of diabetics, and the mean glycation ratios of serum protein (SGP) were higher in groups B and C than in normal subjects. Urinary concentrations of GP also were increased in groups B and C, although the glycation ratio of urinary protein (UGP) was decreased in group C. Consequently, the selectivity of urinary excretion of GP (UGP/SGP) was significantly decreased in group C. Moreover, there was a significant difference in the mean values of selectivity between groups of patients with various degrees of retinopathy. We suggest that measurements of serum and urinary GP are useful to evaluate the progression of diabetic complications.

Blood Proteins↗

[Association of an epidermoid tumor with a cerebral aneurysm on the contralateral internal carotid artery].

A 71-year-old female was evaluated for a sudden loss of consciousness. Initial computed tomography and cerebral angiography revealed a severe subarachnoid hemorrhage, a large cystic lesion in the left occipital region, and an aneurysm at the bifurcation of the internal carotid and the posterior communicating artery on the right side. As the subarachnoid hemorrhage was thought to be due to rupture of the aneurysm, we attempted to clip the aneurysmal neck at first, and 2 weeks later the cystic tumor was removed for the purpose of internal decompression. The extirpated specimen proved to be an epidermoid tumor. Association of a brain tumor and an cerebral aneurysm is very rare, especially a combination of an epidermoid tumor and a cerebral aneurysm, and until now only 2 cases have been reported to the best of our knowledge. Moreover, the epidermoid tumor of our case was located intracerebrally. The phenomenon that the internal carotid aneurysm was on the left side and the tumor on the right side may suggest that these 2 lesions originated quite coincidentally. It is controversial to decide which lesion and when to treat first in a case of association of a tumor and an aneurysm, and we discussed as to the surgical therapy reviewing literature.

Aged↗

[Aggressive natural killer cell lymphoproliferative disease of large granular lymphocytes with leukemia-like clinical course in the terminalstage].

A 20-year-old man was admitted to our clinic with fever elevation up to 39 degrees C for two months, generalized lymphadenopathy and hepatosplenomegaly. Histological examination of right scalene lymph node with HE staining showed T cell lymphoma-like finding. The patient was given vindesine and prednisolone, and there was almost no clinical improvement. Abnormal large granular lymphocyte appeared in peripheral blood and increased up to 17,000/microliters in the terminal stage of clinical course. These lymphocytes had abundant pale cytoplasm with rich large azurophilic granules and a large nucleus with a few nucleoli. The phenotype of these cells were as follows: Fc gamma R+, CD2+, CD5-, CD7-, CD3-, CD4-, CD1-, CD8-, sIg-, CD20-, CD11-, CD13-, OKIa+, CD25-, CD16+, Leu7-. These cells did not have the activity of antibody dependent cellular cytotoxicity but had natural killer activity. The gene of T cell receptor (beta and gamma chain) did not rearranged in these cells. We concluded that the abnormal cells were derived from natural killer cells, which caused aggressive clinical course.

Adult↗

[Studies on C1 inactivator resistant fibrinolytic activity].

The fibrin lysis activity in the presence of enough quantity of C1 inactivator (C1.INA) is called C1.INA resistant fibrinolytic activity (C1.IRFA). C1.INA inhibits the activation of intrinsic fibrinolysis, therefore C1.IRFA is considered to reflect the extrinsic fibrinolytic activity mainly. We studied the effect of C1.INA using fibrin plate assay on fibrin lysis activity (FLA) and C1.IRFA in normal individuals and pregnant women, and studied the fluctuation of FLA and C1.IRFA during venous occlusion test (VO) or 1-deamino-8-D-arginine vasopressin (DDAVP) administration. After VO or DDAVP administration, the euglobulin lysis time (ELT) was reduced, FLA increased and C1.IRFA also increased. The increase in C1.IRFA accounted for most of the increase in FLA. Therefore, the increased fibrinolytic activity during VO or DDAVP administration is due to extrinsic fibrinolytic activity. In the pregnant women, the fibrinolytic activity was decreased during pregnancy and the low fibrinolytic activity is suggested to be involved in the low extrinsic fibrinolytic activity. The measurement of C1.IRFA is considered to be useful.

Complement C1 Inactivator Proteins↗

[Dynamic MRI of liver tumors--evaluation by inversion recovery snap shot FLASH MR imaging].

We have studied 20 patients with liver tumor (hepatoma 12, hemangioma 6, metastatic tumor 2) using inversion recovery snap shot FLASH dynamic MR imaging. After intravenous injection of Gd-DTPA, serial 17 images were obtained during 7 minutes. Hepatoma showed central enhancement on early phase (0-20 sec) in 11 patients and absent or less enhancement than surrounding liver parenchyma on late phase (1-3 min) in 12 patients. Hemangioma showed peripheral enhancement on early phase in 6 patients, and slight to moderate enhancement on late phase in 5 patients. Peripheral slight enhancement were seen on late and delayed (5-7 min) phase in two patients with metastatic liver tumor. These characteristic enhancement patterns should facilitate differential diagnosis of liver tumors.

Aged↗

A role for calmodulin in the growth of human hematopoietic progenitor cells.

A possible role for calmodulin in the colony growth of human hematopoietic progenitor cells was investigated using pharmacologic approaches. We obtained evidence for a dose-dependent inhibition of colony formation of myeloid progenitor cells (CFU-C) stimulated by interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), or granulocyte CSF (G-CSF) by three calmodulin antagonists, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7), N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide hydrochloride (W-13), and trifluoperazine. Chlorine-deficient analogs of W-7 and W-13, with a lower affinity for calmodulin, did not inhibit the growth of CFU-C colonies. W-7, W-13, and trifluoperazine inhibited the colony formation of immature erythroid progenitor cells (BFU-E) stimulated by IL-3 plus erythropoietin (Ep) or GM-CSF plus Ep, in a dose-dependent manner, while they did not affect the colony formation of mature erythroid progenitor cells (CFU-E) induced by Ep. W-7, W-13, and trifluoperazine also led to a dose-dependent inhibition of GM-CSF-induced colony formation of KG-1 cells. Calmodulin-dependent kinase activity derived from the KG-1 cells was inhibited by these three calmodulin antagonists in a dose-dependent manner. These data suggest that calmodulin may play an important regulatory role via a common process in the growth of hematopoietic progenitor cells stimulated by IL-3, GM-CSF, and G-CSF. Mechanisms related to the growth signal of Ep apparently are not associated with calmodulin-mediated systems.

Bone Marrow Cells↗

Decreased expression of type II protein kinase C in HL-60 variant cells resistant to induction of cell differentiation by phorbol diester.

To evaluate the molecular basis for susceptibility of the cell differentiation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), we examined biochemical activities and expression of subspecies of protein kinase C from HL-60 cells that are susceptible to differentiation induced by TPA and HL-60R cells, HL-60 variant cells that are resistant to such induction. Analysis of the subcellular distribution of protein kinase C revealed that the activity of this kinase in the cytosol from HL-60R cells was 30% of that from parental HL-60 cells but that the enzyme activities in the membrane showed similar values in these cells. Treatment of HL-60 cells with 100 nM TPA for 30 min resulted in a 75% decrease in protein kinase C activity in the cytosol and a 300% increase in this activity in the membrane. A minor subcellular redistribution of the enzyme activity was found in HL-60R cells after TPA treatment. Based on analysis of protein kinase C isozymes by hydroxyapatite column chromatography, the relative activities of types I, II, and III in the cytosol of HL-60 cells were 11, 80, and 9%, whereas those in HL-60R cells were 27, 36, and 37%, respectively. Type II isozyme was a major protein kinase C in the cytosol of HL-60 cells, but type II was less in the HL-60R cells. Among the three isozymes, type II enzyme was most sensitive to TPA with histone H1 as the substrate, although all three isozymes were activated Ca2+-dependently in the presence of phosphatidylserine. We suggest that the acquired resistance of HL-60R cells toward induction of cell differentiation by TPA may be associated with a decrease in the expression of the type II isozyme of protein kinase C.

Blotting, Western↗

Concentrations of essential elements after repeated administrations of tin and selenium.

To study effects of simultaneous administration of tin (Sn) and selenium (Se) on concentrations of several essential elements, mice were injected with either SnCl2 (ip) or Na2SeO3 (sc), alone or both compounds at a daily dose of 5 mumol/kg each for 12 consecutive days. Mice were sacrificed at 20 h after the last injection and concentrations of Sn, Se, Na, Ca, Zn, P, Fe, K, and Mg in the liver, kidney, spleen, pancreas, testis, seminal vesicle, lung, femoral muscle, and femoral bone were determined. In the control mice, Sn and Se concentrations were the highest in bone (0.69 micrograms Sn and 6.93 micrograms Se/g dry wt). Administered Sn was found to accumulate in all organs except the testis. Among the essential elements determined, Na was the most affected in terms of concentration in the organs and Mg was the least affected element in these organs. Among the organs tested, each elemental concentration in the pancreas was most affected. Simultaneous injections of Sn and Se appeared to keep the correlation coefficients between elements similar to those found in the control mice.

Animals↗

Effects of leptomycin B on the cell cycle of fibroblasts and fission yeast cells.

An antifungal antibiotic, leptomycin B (LMB), which induced cell elongation of fission yeast, Schizosaccharomyces pombe, was found to be a unique inhibitor of the cell cycle of mammalian and fission yeast cells. Proliferation of rat 3Y1 fibroblasts was reversibly blocked by LMB in both the G1 and G2 phases and the treated cells were presumably introduced into the resting state (GO). After removal of LMB, proliferative tetraploid cells were produced from the cells which had been arrested by LMB at the G2 phase, as a result of DNA replication without passage through the M phase. LMB also inhibited the proliferation of S. pombe in both the G1 and G2 phases. These results suggest that the molecular target of LMB is one of the components necessary for progression of both G1 and G2 in the eukaryotic cell cycle.

Animals↗