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Biomedical subjects

M Takano

Publications and source records attributed to M Takano.

At least 217 records · Page 12Linked to original sources

Role of angiotensin II in the transforming growth factor-beta 1 expression of rat kidney in anti-glomerular basement membrane antiserum-induced glomerulonephritis.

Induction of acute nephritis in the rat by injecting anti-glomerular basement membrane (GBM) antiserum is accompanied by a transient increase in angiotensin II generation in blood circulation within the first 24 h and a subsequent elevation of transforming growth factor-beta 1 (TGF-beta 1) mRNA levels in kidney cortex with a peak at days 7-8. Studies were carried out to determine whether the increased generation of angiotensin II plays a role in the elevation of TGF-beta 1 mRNA. Elevation of TGF-beta 1 mRNA levels 7 d after injection of antiserum was significantly inhibited by a successive daily administration of TCV-116, angiotensin II type 1 receptor antagonist, at 1 mg/kg/d from days 0 to 2 or from days 0 to 6, while it was not influenced by a single administration of this dose on day 0. In addition, angiotensin II infusion or 24 h at a rate of 50 ng/min did not alter the level of TGF-beta1 mRNA which was measured 6 d after the infusion. These results suggest that the anti-GBM antiserum-induced increase in TGF-beta 1 expression in the kidney is not responsible for angiotensin II generated in the blood circulation during the early phase of acute nephritis, but iis probably mediated by angiotensin II generated locally in the kidney.

Angiotensin II↗

Mechanism and properties of inhibition of purified rat brain adenylate cyclase by G protein beta gamma-subunits.

The mode of the inhibition of purified rat brain adenylate cyclase by the beta gamma-subunits of G protein (beta gamma) was studied. These subunits inhibited the catalytic activity of the cyclase with the maximal inhibition of 85% and the half-maximal inhibition at about 0.7 nM beta gamma. The complex of beta gamma and adenylate cyclase isolated by density gradient centrifugation contained 1.8-2.0 mol beta gamma per mol of the cyclase when beta gamma was assayed by immunoblotting and by its inhibitory activity on adenylate cyclase. However, the beta gamma concentration-inhibition curves suggest that one of the two beta gamma molecules bound may be essential for the inhibition. The role for the second beta gamma molecule is unknown. As a tentative estimate, 70% of the adenylate cyclase activity remained inhibited by beta gamma when the complex was isolated. The inhibition was not dependent on G alpha s or calmodulin. Although purified adenylate cyclase contained a protein (0.06-0.08 mol/mol of adenylate cyclase) that reacted with anti-G alpha s antibody, this protein was not liberated from the cyclase when it formed a complex with beta gamma. In addition, guanine nucleotide analogs little affected the cyclase activity or the inhibition by beta gamma. The inhibition by beta gamma was reversed by the dilution of the complex, and the following re-addition of beta gamma suppressed the enzyme activity to about 15% of the initial activity again. These findings provide strong evidence that beta gamma inhibits adenylate cyclase directly and reversibly through the formation of the complex.

Adenylyl Cyclases↗

[Efficacy of beraprost sodium on Raynaud's phenomenon in patients with systemic sclerosis].

Raynaud's phenomenon is an important clinical manifestation in patients with systemic sclerosis (SSc). No effective therapy, however, has been established for this phenomenon. Beraprost sodium, a stable prostacycline (PGI2) analogue, has been reported to improve hemorrheological impairment in patients with rheumatic diseases. In this study, we, therefore, examined the efficacy of beraprost sodium on Raynaud's phenomenon in 30 patients with SSc. Sixty micrograms per day of beraprost sodium was found to be effective in 14 patients (47%) in the period of 15.0 +/- 12.5 weeks. Raynaud's phenomenon in patients who responded to beraprost sodium was characterized by infrequent nail fold thrombosis and narrower hand areas affected by Raynaud's phenomenon, with mild secondary symptoms such as pain. These results indicate that beraprost sodium is effective for mild forms of Raynaud's phenomenon in patients with SSc.

Adult↗

[Spinal multiple sclerosis mimicking a spinal cord tumor: a case report].

Since the advent of magnetic resonance imaging (MRI), to visualize lesions of multiple sclerosis has become easy to do. However, in some cases with primary spinal cord multiple sclerosis, it is not always easy to obtain a diagnosis in the first instance. We reported a case of primary spinal multiple sclerosis diagnosed through histological examination of a surgical specimen taken by an open biopsy. A 35-year-old woman was admitted with complaints of two-months duration of progressive weakness and sensory disturbance in the legs and buttocks. On radiological examinations including metrizamide CT myelography and MRI, enlargement of the conus medullaris was the only positive finding. Respective to her clinical course, intramedullary spinal cord tumor could not be ruled out, so an open biopsy was performed. Histological examination revealed that the cord lesion was acute demyelination with perivascular inflammation. Her neurological signs were almost completely cured with administration of corticosteroid, though new brainstem signs took place two months later and then a concrete diagnosis of her having multiple sclerosis was finally achieved. Since preoperative examinations can not differentiate spinal cord tumor from any other intramedullary cord lesions such as demyelinating foci of multiple sclerosis, surgical intervention would be approved in such atypical primary spinal cord multiple sclerosis.

Adult↗

Specificity of p-aminohippurate transport system in the OK kidney epithelial cell line.

Substrate specificity of the p-aminohippurate (PAH) transport system was investigated in the OK kidney epithelial cells. PAH uptake by OK cells from the basal side was inhibited by beta-lactam antibiotics such as benzylpenicillin (PCG) and cefazolin. The inhibition of PAH uptake by PCG was competitive and the Ki value was calculated as 108.8 microM. Transcellular transport of PCG across OK cell monolayers occurred unidirectionally from the basal to apical side, and transcellular transport and basolateral uptake were inhibited by PAH, probenecid and beta-lactam antibiotics. The basolateral uptake of cefazolin and cefotiam was also inhibited by PAH and probenecid. The basolateral uptake of PAH and PCG were not affected by aliphatic dicarboxylates with 3 or 4 carbon atoms, but were strongly inhibited by those with 5 or 6 carbon atoms. The inhibitory effect became weaker for a longer dicarboxylate with 7 carbon atoms, then increased again with increasing number of carbon atoms. Such a pattern of inhibition by dicarboxylates is essentially the same with that observed in rat renal proximal tubules in situ. These findings suggest that the PAH transport system in OK cells has a substrate specificity similar to that in rat renal proximal tubules, which is involved in the active secretion of various organic anions including drugs.

Animals↗

Patent vitelline duct in an adult deceptively appeared to be acquired umbilical urachal sinus: a case report.

Here is presented a surprisingly rare case in a 40-year-old male who had patent vitelline duct by nature. However, his congenital disease appeared deceptively to be an acquired umbilical urachal sinus on the diagnostic evaluations including fistulography before surgery. The diagnosis was definitely confirmed after the successful surgical procedure. The principal reason why these diseases were indistinguishable was reviewed. The incidence of each disease and incidence of association with umbilical fistula in each disease were discussed. With regard to these incidences, we compared urachal anomalies with vitelline duct anomalies through reference of several literatures. This is the most unique event we have ever clinically experienced.

Adult↗

Transport of oral cephalosporins by the H+/dipeptide cotransporter and distribution of the transport activity in isolated rabbit intestinal epithelial cells.

Transport of cephalosporins was studied using isolated rabbit intestinal epithelial cells. Cephradine uptake by the cells was concentrative and was inhibited by the addition of glycylsarcosine. The accumulated cephradine was effluxed from the cells by the addition of a protonophore, carbonyl cyanide 4-trifluoromethoxyphenylhydrazone (FCCP). Amiloride, an inhibitor of the Na+/H+ exchanger, reduced the steady-state uptake of cephradine, suggesting that the exchanger contributes to the maintenance of an inward H+ gradient as a driving force. Cephradine uptake by ATP-depleted intestinal cells was actively driven by the inward H+ gradient and was inhibited by FCCP and glycylsarcosine. The distribution of cephradine transport activity along the small intestine and villus-crypt axis was also examined in the isolated cells, and the transport activity was higher in the upper parts of the intestinal segments and in villus cells. These results indicate that the uptake of oral cephalosporins by intestinal epithelial cells in concentrative and reversible and that the H+/dipeptide cotransporter and the Na+/H+ exchanger play an important role for the active uptake of these drugs. The activity of the H+/dipeptide cotransporter should be higher in upper segments and in villus cells of the small intestine.

Animals↗

High-performance liquid chromatographic determination of catecholamine metabolites and 5-hydroxyindoleacetic acid in human urine using a mixed-mode column and an eight-channel electrode electrochemical detector.

An HPLC system for the simultaneous determination of acidic catecholamine metabolites, related compounds and 5-hydroxyindoleacetic acid (5-HIAA) in human urine was developed. A mixed-mode (C18/anion-exchange) column with isocratic elution using citrate buffer and an eight-channel electrochemical detector were used. Vanilmandelic acid (VMA), 3,4-dihydroxyphenylacetic acid (DOPAC), 4-hydroxy-3-methoxyphenyllactic acid (vanillactic acid, VLA), homovanillic acid (HVA), vanillic acid (VA) and 5-HIAA in urine were determined simultaneously. Detection limits and inter (n = 5) and intra-assay (n = 5) coefficients of variation were satisfactory. The mean of analytical recoveries (n = 3, +/- C.V. (%)) were between 97 +/- 3.2 (VMA) and 105 +/- 4.8 (VA). Correlations between the analytical results for VMA, HVA and 5-HIAA obtained by an established method and the present method were satisfactory. The mean +/- 2 S.D. of the excretion rates of VMA, DOPAC, VLA, HVA, 5-HIAA and VA in urine from healthy adult volunteers were 0.61-4.36, 0.13-1.02, 0-0.35, 0.67-6.55, 0.50-5.14 and 0-0.55 mg/g creatinine, respectively.

3,4-Dihydroxyphenylacetic Acid↗

Critical period for degradation of adult rat retinal ganglion cells and their regeneration capability after axotomy.

The optic nerve (ON) in adult rats was transected intraorbitally followed by retrograde labelling of retinal ganglion cells (RGCs) with fluorescence dye (DiI). A two phase reduction of axotomized RGCs was represented in the retina until 15 days after ON transection. The critical period of RGC loss is around 7 days after axotomy. In this period, the capability of neurite regeneration from RGCs in culture was strongly intensified by ON transection. These findings indicate that the 7th day after axotomy is important for both RGC survival and regeneration.

Animals↗

Differential sensitivity of organic anion transporters in rat renal brush-border membrane to diethyl pyrocarbonate.

The effect of various chemical modifiers on p-aminohippurate (PAH) uptake by a potential-sensitive system and by an anion exchanger was studied in rat renal brush-border membrane vesicles. Among various chemical modifiers, diethyl pyrocarbonate (DEPC) selectively inhibited potential-sensitive PAH uptake but not the uptake by the anion exchanger. The inhibitory effect of DEPC on potential-sensitive PAH uptake was not due to the facilitated dissipation of membrane potential, which was evidenced by the studies with a potential-sensitive fluorescence dye diS-C3(5). The potential-sensitive PAH uptake was inhibited by DEPC in a concentration-dependent manner, and kinetic analysis showed that the decreased uptake of PAH in DEPC-treated vesicles was due to the decrease of Vmax. The inhibition of the PAH uptake was protected by the presence of organic anions during the DEPC treatment. These findings indicate that PAH transport by the potential-sensitive system and by the anion exchanger is mediated by structurally distinct transporters. Amino acid residue(s) modified by DEPC, most likely a histidine residue, should play an important role in the potential-sensitive transport of PAH in rat renal brush-border membrane.

Animals↗

Cation-dependent gating of the hyperpolarization-activated cation current in the rabbit sino-atrial node cells.

1. The gating properties of the hyperpolarization-activated cation current (I(f) or Ih) were investigated in single pacemaker cells dissociated from the rabbit sino-atrial node. 2. The whole-cell I(f) was recorded in the presence of different external cations. The inward I(f) was increased when external Na+ was replaced with K+, and was decreased in Li+ or Rb+ solution. In Tris+ and Cs+ solutions, the inward I(f) was negligible. The outward tail current recorded upon depolarization was largest in Li+ solution and smaller in a sequence of Na+, Tris+ and K+ solutions. In Rb+ and Cs+ solutions, only a small tail current was recorded. 3. The outward tail current had a 'shoulder' in Na+ solution, which was much delayed by replacing Na+ with Li+. In K+ solution, the decay of the tail current was much faster, and no obvious shoulder was recorded. The tail current was slowest in Li(+)-rich and 0 mM K+ solution, and was progressively accelerated by adding K+ over the range from 0 to 3 mM. The tail current at 30 mM [K+]o showed only a small shoulder. A common binding site to modulate the I(f) deactivation was suggested for monovalent cations. 4. The shoulder of the I(f) tail became more evident as I(f) was activated to a larger extent either by prolonging the duration or by increasing the amplitude of the preceding hyperpolarization in both Na+ and Li+ solutions. 5. The I(f) was first activated by hyperpolarizing the membrane to -110 mV, and then deactivated by depolarization. The inward tail current at -50 mV showed a single exponential decay. At more positive potentials, the shoulder of the outward tail currents became more evident and the rate of the final decay was increased. 6. The time course of I(f) activation was well fitted with the sum of two exponential functions. Time constants of both components were not affected by the external cation (Na+, K+ or Li+) replacement. Likewise, the quasi-steady state activation was conserved when external Na+ was replaced with Li+. 7. Two closed and three open states were assumed in a sequential state model of the I(f) channel. The cation effects were well simulated by assuming that the deactivation rate was selectively modulated. The flow of I(f) during the spontaneous action potential was calculated. The activation of I(f) started on repolarization to the maximum diastolic potential and reached a maximum in the middle of the diastolic period. Its peak amplitude was 14% of the net inward current during the diastolic period.

Animals↗

Bestatin transport in rabbit intestinal brush-border membrane vesicles.

The effect of papain treatment on bestatin uptake by rabbit intestinal brush-border membrane vesicles (BBMVs) was studied. Papain treatment of BBMVs effectively diminished aminopeptidase activity but not bestatin uptake by a H+/dipeptide cotransporter. Bestatin uptake by BBMVs was composed of two saturable components, and after papain treatment the high-affinity component disappeared while the low-affinity component was retained. These findings suggest that high- and low-affinity components represent bestatin binding to aminopeptidase and the true uptake by the H+/dipeptide cotransporter, respectively.

Adjuvants, Immunologic↗

Effects of intracellular pH on ATP-sensitive K+ channels in mouse pancreatic beta-cells.

1. The effects of intracellular pH (pHi) on the ATP-sensitive K+ channel (K+ATP channel) from mouse pancreatic beta-cells were examined in inside-out patches exposed to symmetrical 140 mM K+ solutions. 2. The relationship between channel activity and pHi was described by the Hill equation with half-maximal inhibition (Ki) at pHi 6.25 and a Hill coefficient of 3.7. 3. Following exposure to pHi < 6.8, channel activity did not recover to its original level. Subsequent application of trypsin to the intracellular membrane surface restored channel activity to its initial level or above. 4. At -60 mV the relationship between pHi and the single-channel current amplitude was described by a modified Hill equation with a Hill coefficient of 2.1, half-maximal inhibition at pHi 6.48 and a maximum inhibition of 18.5%. 5. A decrease in pHi reduced the extent of channel inhibition by ATP: Ki was 18 microM at pH 7.2 and 33 microM at pH 6.4. The Hill coefficient was also reduced, being 1.65 at pH 7.2 and 1.17 at pH 6.4. 6. When channel activity was plotted as a function of ATP4- (rather than total ATP) there was no effect of pHi on the relationship. This suggests that ATP4- is the inhibitory ion species and that the effects of reducing pHi are due to the lowered concentration of ATP4-. 7. Changes in external pH had little effect on either single-channel or whole-cell K+ATP currents. 8. The effects of pHi do not support a role for H+ in linking glucose metabolism to K+ATP channel inhibition in pancreatic beta-cells.

Adenosine Triphosphate↗

Rainbow trout ventricular natriuretic peptide: isolation, sequencing, and determination of biological activity.

Ventricular natriuretic peptide (VNP) is a new type of cardiac natriuretic peptide initially isolated from the eel ventricle. VNP has been isolated from cardiac ventricles of the rainbow trout, Oncorhynchus mykiss, and found to consist of 35 amino acid residues carrying a C-terminal tail sequence with 14 amino acid residues. Thus, the long C-terminal sequence characteristic of VNP was also conserved in the trout VNP. A VNP with 4 amino acid residues truncated from the C-terminus was also isolated from trout ventricles and sequenced. Sequence identity of trout VNP to eel VNP was 77%; while it was 56% to eel A-type natriuretic peptide (ANP). Trout VNP caused characteristic biphasic vasopressor/depressor effects in the trout similar to those produced by rat and eel ANP. Trout VNP and human ANP were almost equipotent in their vasopressor and depressor activity in trout. Unlike eel VNP, therefore, homologous VNP did not exhibit greater activity in the trout. In the rat, however, trout VNP was more potent than eel peptide and was almost equipotent to human ANP for both vasodepressor and natriuretic effects. The high potency of trout VNP appears to be due in part to its longer-lasting effect compared to human ANP.

Amino Acid Sequence↗

Effects of internal chloride on ATP-sensitive K-channels in mouse pancreatic beta-cells.

The effect of internal Cl- on the K-ATP channel of pancreatic beta-cells was examined. Reducing Cl- from 140mM to 14mM potentiated channel activity (NPO) approximately 4.5 fold in 60% of patches but was without effect in 40% of patches. The Ki for channel inhibition by ATP was not changed. The inhibitory effect of Cl- interacted with the stimulatory action of MgGDP. In 140mM Cl-, 1mM MgGDP increased NPO in Cl(-)-sensitive patches only: when NPO was potentiated by 14mM Cl-, no further increase was produced by MgGDP. These observations suggest that MgGDP and low Cl- solution may increase channel activity via a similar mechanism.

Adenosine Triphosphate↗