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S Kojima

Publications and source records attributed to S Kojima.

At least 451 records · Page 25Linked to original sources
PubMed1995

Increased stabilizing effects of amphiphilic excipients on freeze-drying of lactate dehydrogenase (LDH) by dispersion into sugar matrices.

PURPOSE: The stabilizing effect of amphiphilic excipients and sugars against protein inactivation during freeze-drying was studied in relation to their physical states in freeze-dried cakes. METHODS: Physical states of amphiphilic excipients were studied by powder X-ray diffractometry and differential scanning calorimetry (DSC). Stabilizing effects of excipients were studied using lactate dehydrogenase (LDH) as a model protein. RESULTS: Although poly(ethylene glycols) (PEGs) 1000 to 2000 crystallized when freeze-dried alone, the addition of sugars decreased their crystallinity by dispersing PEG into sugar-dominant matrices. Sugars species, molecular weight of PEGs, and buffer concentration also affected the crystallinity of PEGs. Sugars also dispersed some of other amphiphilic excipients, which tended to crystallize or become "microscopically liquid" when freeze-dried without sugar. Only the amphiphilic excipients that remained amorphous solid state protected the enzyme during freeze-drying in the absence of sugars. However, combinations of sucrose and all the amphiphilic excipients studied increased the stabilizing effects markedly. The remaining activities were greater than the sum of their individual ones. CONCLUSIONS: Various amphiphilic excipients are good stabilizers for freeze-drying of proteins when dispersed into sugar-dominant matrices.

Dose-Response Relationship, Drug↗
PubMed1995

Oral solid controlled release dosage forms: role of GI-mechanical destructive forces and colonic release in drug absorption under fasted and fed conditions in humans.

PURPOSE: This study was undertaken to examine the effects of mechanical destructive forces on drug release from controlled release (CR) dosage forms in vitro and in vivo and their colonic release, using two CR tablets of acetaminophen A and B, showing slower and faster erosion rates, respectively. METHODS: In vitro release rates were determined by several official methods. Tablets were administered to healthy volunteers under fasting and fed conditions. RESULTS: Both tablets showed similar release rates under mild destructive conditions (e.g., paddle method at 10 rpm) but CR-B showed faster release under highly destructive conditions (e.g., rotating basket method at 150 rpm), where the tablet was eroded. The in vivo release from CR-B was faster than from CR-A, possibly because of enhanced erosion. The variable in vivo release from CR-B indicated large inter-subject differences in destructive GI forces. The fastest in vivo release from CR-B among individuals was approximated by the in vitro dissolution determined by destructive methods such as the rotating basket at 150 rpm. The slowest in vivo release from tablets A and B was lower than the dissolution by the paddle method at 10 rpm. The release from both tablets was markedly reduced at 3-4 hrs after dosing irrespective of feeding conditions which can be attributed to release inhibition in the colon. CONCLUSIONS: Effects of GI destructive forces on the tablet erosion and the release inhibition in the colon must be considered in the development of CR dosage forms.

Acetaminophen↗
PubMed1995

Protein kinase C phosphorylates p50 LSP1 and induces translocation of p50 LSP1 in T lymphocytes.

A lymphocyte-specific protein, p50, is phosphorylated on Ser and Thr residues in mitogen-activated T cells, suggesting that this molecule plays some role in the T cell activation cascade. p50 was identified as lymphocyte specific protein 1 (LSP1), which is a putative calcium-binding protein. In the present study, to clarify the role of p50 protein in the cascade, in vivo and in vitro phosphorylation of this molecule, and the effect of the phosphorylation on its distribution in activated T cells were examined. First, to obtain a sufficient amount of p50 as a phosphorylation substrate, p50 cDNA, which encodes a protein of 330 amino acid residues with a molecular mass of 36,728 Da, was cloned from an ICR mouse thymocyte cDNA library and expressed in Escherichia coli. When the putative coding region of p50 cDNA was expressed in E. coli, the product showed an apparent molecular mass of 50 kDa on SDS-PAGE. The recombinant p50 was phosphorylated in vitro by rabbit protein kinase C (PKC) and by murine cytosolic protein kinase, that was activated by a combination of phosphatidylserine and diacylglycerol. Furthermore, p50 was shown to be phosphorylated on the same sites in T cells upon stimulation with Con A as when phosphorylated in vitro by rabbit PKC, indicating that p50 is phosphorylated by PKC in Con A-stimulated T cells. On subcellular fractionation followed by immunoblotting analysis, membrane-bound p50 was shown to be released from the membrane following activation of PKC in T cells. These results and the recent finding that p50 binds to actin fibers raise the possibility that p50 controls the binding of actin fibers to the plasma membrane under regulation by PKC in T cells.

Amino Acid Sequence↗
PubMed1995

A subtilisin inhibitor produced by Streptomyces bikiniensis possesses a glutamine residue at reactive site P1.

We determined the complete amino acid sequence of a novel subtilisin inhibitor, SIL15, which had been isolated from the culture supernatant of Streptomyces bikiniensis and shown to be a member of the Streptomyces subtilisin inhibitor (SSI)-like (SIL) protein family, and then identified its reactive site. SIL15 is composed of 113 amino acids and exists as a dimer. Compared with other SSI-family inhibitors, SIL15 was found to be unique in that it possesses a Gln residue at the P1 site of the reactive site and has two-residue insertions in two regions, one in the alpha 1-helix and the other in the flexible loop region near the reactive site. Inhibition of subtilisin BPN' by SIL15 (inhibitor constant, 2.7 x 10(-11) M) was due to the presence of a Gln residue at the P1 site, which was well consistent with the results obtained for P1-site mutants of SSI and turkey ovomucoid domain 3.

Amino Acid Sequence↗
PubMed1995

Lymphocyte isoforms of mouse p50 LSP1, which are phosphorylated in mitogen-activated T cells, are formed through alternative splicing and phosphorylation.

p50 is phosphorylated in mitogen-stimulated T cells, and translocated from the membrane to the cytosol after activation of protein kinase C. Sequence analysis of p50 revealed that it is identical with LSP1, a putative calcium-binding and actin-binding protein. lymphocyte form of p50 exhibits heterogeneity in the apparent molecular mass on SDS-PAGE, 50 and 52 kDa (pp50 and pp52), and each isoform exhibits heterogeneity in the isoelectric point, when examined by two-dimensional PAGE. When the two molecular mass variants of p50 were dephosphorylated with alkaline phosphatase, both isoforms showed the same apparent molecular mass of 50 kDa on SDS-PAGE, but could be distinguished by their distinct isoelectric points. Dephosphorylated pp50 (p50a) has an acidic pI compared with dephosphorylated pp52 (p50b). Comparison of the peptide maps of purified p50a and p50b on HPLC revealed that the difference was limited to one peptide peak. NH2-terminal sequence and mass spectrometric analyses of these peptides showed that the peptides derived from p50a and p50b had the same NH2-terminal amino acid sequence up to eight residues, but had distinct molecular masses, 5,533.4 and 6,318.6 Da, respectively. These data suggested that pp52 (p50b) is the product of the previously cloned cDNA and the reduction in the molecular mass of the p50a-derived peptide could be explained by deletion of six amino acid residues, EHLIRH or HLIRHQ.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗
PubMed1995

An enhancing effect of 5-hydroxytryptamine on electrically evoked atropine-resistant contraction of guinea-pig proximal colon.

1. In the presence of atropine (0.2 microM) and indomethacin (2 microM), the effects of 5-hydroxytryptamine (5-HT) have been studied on electrically-evoked, neurogenic contractions of the guinea-pig proximal colon in vitro. 2. 5-HT, at higher concentrations than 1 nM, caused an increase in electrically (1 Hz, 0.3 ms, 160 mA)-evoked, atropine-resistant contractions in a concentration-dependent manner and at 30 nM produced a maximal effect (pEC50 value of 8.20 +/- 0.11, n = 6). The enhancing effects of 5-HT on the electrically evoked contractions were mimicked by alpha-methyl-5-HT (pEC50 value of 6.59 +/- 0.05, n = 6). 3. Both hexamethonium (100 microM) and spantide (10 microM), selective antagonists for nicotinic and tachykinin receptors respectively, significantly reduced the enhancement of the electrically evoked contractions by 5-HT (30 nM). 4. DAU 6285 (3 microM), a 5-HT4 receptor antagonist, abolished the enhancing action of 5-HT (30 nM), but metitepine (0.03 microM), a 5-HT1/5-HT2 receptor antagonist, ketanserin (0.01 microM), a 5-HT2 receptor antagonist, and ondansetron (1 microM), a 5-HT3 receptor antagonist, had no effect on the enhancement. The enhancing effects of alpha-methyl-5-HT (1 microM) were also abolished by DAU 6285 (3 microM). 5. Both 5-HT (30 nM) and alpha-methyl-5-HT (1 microM) had no effect on contractions to exogenous substance P (0.15-0.3 nM). 6. These results indicate that in the guinea-pig proximal colon, 5-HT produced an enhancement of atropine-resistant neurogenic contraction induced by electrical field stimulation through pre-junctional mechanisms and that the enhancement is mediated by the stimulation of 5-HT4 receptors located on intramural preganglionic cholinergic neurones and tachykininergic neurones.

Animals↗
PubMed1995

Calcitonin gene-related peptide (CGRP)-enhanced non-adrenergic non-cholinergic contraction of guinea-pig proximal colon.

1. We have investigated the effect of calcitonin gene-related peptide (CGRP) on non-adrenergic, non-cholinergic (NANC) excitatory transmission to the longitudinal muscle of the guinea-pig proximal colon. 2. In the presence of atropine (0.3 microM), guanethidine (5 microM), hexamethonium (100 microM) and indomethacin (3 microM), electrical field stimulation (EFS, 1 Hz, 0.3 ms for 10 s) produced tetrodotoxin-(300 nM)-sensitive contractions which were reduced by the combined administration of FK 888 (10 microM) and MEN 10,376 (0.3 microM), to block tachykinin NK1 and NK2 receptors, respectively. Thus, the EFS-induced NANC contractions are a tachykinin-mediated response. 3. CGRP, at concentrations higher than 0.1 nM, caused an increase in the electrically-evoked, NANC contractions in a concentration-dependent manner and at 10 nM produced a maximal effect (pEC50 = 9.20 +/- 0.17, n = 6). 4. 5-Hydroxytryptamine (5-HT, 1-100 nM) also caused an increase in the EFS-induced NANC contractions in a concentration-dependent manner and at 30 nM produced a maximal effect (pEC50 = 8.06 +/- 0.09, n = 4), but calcitonin (10-100 nM) failed to enhance the EFS-induced NANC responses. Moreover, a 5-HT4 receptor antagonist, DAU 6285 (3 microM) abolished the enhancing action of 5-HT (30 nM). 5. The combined administration of FK 888 (10 microM) plus MEN 10,376 (0.3 microM) abolished the enhancement of EFS-induced NANC contractions by CGRP (10 nM), but DAU 6285 (3 microM) had no effect on the enhancement. 6. Human CGRP8-37 (1 microM), a CGRP1 receptor antagonist had no effect on the submaximal enhancement of the electrically-evoked, NANC contractions by CGRP (1 nM).7. CGRP (30 nM) had no effect on contractions evoked by exogenous substance P (0.3-1 nM).8. These results indicate that in the guinea-pig proximal colon, CGRP produced an enhancement ofNANC contraction induced by EFS through prejunctional mechanisms and that the enhancement is mediated by the stimulation of non-CGRP1 receptors located on intramural tachykininergic neurones.Further, the possible contribution of 5-HT to the enhancing effect of CGRP appeared to be negligible.

Animals↗
PubMed1995

Effect of nafamostat mesilate on bradykinin generation and hemodynamics during LDL apheresis.

Dextran-sulfate (DS) cellulose used for low-density lipoprotein (LDL) apheresis seems to be a weak activator of the contact phase of the intrinsic coagulation pathway because the surface of this substance has negative charges. Heparin, a commonly used anticoagulant, has no effect on this process whereas the process is inhibited by a newly developed anticoagulant, nafamostat mesilate (NM). The effects on bradykinin generation were compared between heparin and NM. Five patients with severe hypercholesterolemia were treated with LDL apheresis using either heparin or NM on a different day. During apheresis with heparin, factor XII, high molecular weight kininogen, and prekallikrein were markedly decreased by passing through the DS column. A distinct generation of bradykinin was observed by passing plasma through the DS column, and this led to the rise of bradykinin levels from 12 +/- 5 (mean +/- SE) to 72 +/- 14 pg/ml after treatment of 1,000 ml of plasma. NM suppressed almost completely the rise of bradykinin levels. Although blood pressure was apt to decrease during apheresis with heparin, there was no significant difference in blood pressure between heparin and NM. Since an angiotensin-converting enzyme inhibitor may lead to a marked rise in blood levels of bradykinin by suppressing its degradation, the use of NM is recommended for apheresis in patients taking this drug.

Adolescent↗
PubMed1995

Different apheresis methods in the treatment of hypercholesterolemia in primary biliary cirrhosis: a case report.

The two different modes of low-density lipoprotein (LDL) apheresis, cascade filtration (CF) and dextran-sulfate cellulose (DSC) adsorption, were compared for efficiency of cholesterol removal in a patient with severe hypercholesterolemia due to primary biliary cirrhosis (PBC). Decrement in the total cholesterol level by the DSC method was less than that by the CF method. Apolipoprotein B was decreased to almost null by both modules whereas the decrease in albumin was much greater in the second filter of the CF method than in the DSC column. Lipoprotein X which constituted the major portion of serum cholesterol in PBC became negative by passing plasma through the second filter. The CF method was preferred to the DSC method for removal of lipoprotein X, but albumin substitution was mandatory to prevent the decrease of serum albumin in the CF method.

Adult↗
PubMed1995

[A case of Pasteurella multocida subsp. multocida septicemia due to cat bites in liver cirrhosis patient].

A 60-year-old male who had been suffering from liver cirrhosis was admitted to our hospital with high grade fever accompanied by right chest pain. Chest X-rays revealed a moderate amount of pleural fluid suggesting pleuritis. Multocida was isolated from the blood culture as well as the pleural fluid. Antibiotic therapy was initiated according to the drug susceptibility of the isolates. Ten days treatment was effective on the cessation of both septicemia and the clinical symptoms. Since the patient had been bitten several times by his own pet cats, their mouth swabs were taken for pathogenic investigations. Serotypes of the cats' isolates coincided with that of the patient's which consequently indicated the route of infection. P. multocida is a Gram negative coccobacillary organism that resides as normal flora in the oral cavity of animals, including dogs and cats. It has been originally known to be a causative agent for hemorrhagic septicemia in domestic animals. However, recently reports of P. multocida infections in man has been increasing due to the enlargement of pet populations. Although outbreaks of septicemia is rare, it occurs most often in immunologically compromised hosts, including patients with liver cirrhosis as in this case. Therefore, it is important to initiate an urgent antibiotic therapy in such cases. Overall, it is of utmost importance to instruct immunosuppressed patients to avoid excessive exposure to animals including pets.

Animals↗
PubMed1995

Streptomyces serine protease (SAM-P20): recombinant production, characterization, and interaction with endogenous protease inhibitor.

Previously, we isolated a candidate for an endogenous target enzyme(s) of the Streptomyces subtilisin inhibitor (SSI), termed SAM-P20, from a non-SSI-producing mutant strain (S. Taguchi, A. Odaka, Y. Watanabe, and H. Momose, Appl. Environ. Microbiol. 61:180-186, 1995). In this study, in order to investigate the detailed enzymatic properties of this protease, an overproduction system of recombinant SAM-P20 was established in Streptomyces coelicolor with the SSI gene promoter. The recombinant SAM-P20 was purified by salting out and by two successive ion-exchange chromatographies to give a homogeneous band by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Partial peptide mapping and amino acid composition analysis revealed that the recombinant SAM-P20 was identical to natural SAM-P20. From the results for substrate specificity and inhibitor sensitivity, SAM-P20 could be categorized as a chymotrypsin-like protease with an arginine-cleavable activity, i.e., a serine protease with broad substrate specificity. For proteolytic activity, the optimal pH was 10.0 and the optimal temperature was shifted from 50 to 80 degrees C by the addition of 10 mM calcium ion. The strong stoichiometric inhibition of SAM-P20 activity by SSI dimer protein occurred in a subunit molar ratio of these two proteins of about 1, and an inhibitor constant of SSI toward SAM-P20 was estimated to be 8.0 x 10(-10) M. The complex formation of SAM-P20 and SSI was monitored by analytical gel filtration, and a complex composed of two molecules of SAM-P20 and one dimer molecule of SSI was detected, in addition to a complex of one molecule of SAM-P20 bound to one dimer molecule of SSI. The reactive site of SSI toward SAM-P20 was identified as Met-73-Val-74 by sequence analysis of the modified form of SSI, which was produced by the acidification of the complex of SSI and SAM-P20. This reactive site is the same that toward an exogenous target enzyme, subtilisin BPN'.

Amino Acid Sequence↗
PubMed1995

Circulating erythropoietin in patients with acquired aplastic anaemia.

The plasma erythropoietin (Epo) concentration was measured by radioimmunoassay in 75 patients with acquired aplastic anaemia. Overall there was an inverse relationship between the concentration of plasma Epo and the degree of anaemia. Plasma Epo concentrations were lower in patients who were sampled soon after diagnosis as opposed to those studied at later times. Although a decrease in the plasma Epo concentration was noted in all erythroid responders following immunosuppressive (IS) therapy or bone marrow transplantation (BMT), it was lower in patients undergoing BMT than in those receiving IS therapy for any given degree of anaemia.

Adolescent↗
PubMed1995

Inhibitory effect of sodium 5,6-benzylidene ascorbate (SBA) on the elevation of melanin biosynthesis induced by ultraviolet-A (UV-A) light in cultured B-16 melanoma cells.

Sodium 5,6-benzylidene ascorbate (SBA) is a conjugate of ascorbic acid (Asc) with benzyaldehyde. It has been found that the antioxidant activity of SBA is more stable and has a longer lifetime in living cells and organs than Asc. In this study, we investigated the effect of SBA on the induction of melanin in cultured melanoma (B-16) cells irradiated by UV-A. Melanin content of B-16 cells was significantly increased by UV-A irradiation. The induction was abolished by mannitol and particularly by superoxide dismutase, suggesting the involvement of O2- in the biosynthesis of melanin in cultured melanoma cells. This was theorized by the fact that the induction was also observed in B-16 cells treated with superoxide anion radicals chemically generated in the hypoxanthine/xanthine oxidase-reaction system, instead of UV-A irradiation. The induction of melanin caused by UV-A irradiation was suppressed by SBA in a dose-dependent manner. To elucidate the mechanism of this suppressive effect, the scavenging activity against O2-, and the inhibitory effect of SBA on tyrosinase activity were examined. ESR spectrometric analysis showed that SBA strongly scavenged O2-, and the presence of SBA in the medium remarkably inhibited the tyrosinase activity in cultured B-16 melanoma cells. It can be concluded that SBA effectively inhibits the melanin biosynthesis in B-16 melanoma cells induced by reactive oxygen species (ROS) generated by UV-A irradiation via tyrosinase.

Antioxidants↗
PubMed1995

Assessment of the severity of coronary artery disease by thallium-201 washout rate after dipyridamole infusion--a coronary hemodynamic and metabolic study.

This study examined the relationship between the myocardial washout rate (WR) of thallium-201 (201Tl) in dipyridamole scintigraphy and both coronary flow reserve (CFR) and myocardial lactate extraction rate (LER) after dipyridamole infusion in 31 patients with coronary artery disease (CAD) without myocardial infarction and 16 control patients. Patients with CAD demonstrated significantly lower WR (21 +/- 17 vs 43 +/- 10%, p < 0.001), lower CFR (128 +/- 82 vs 242 +/- 89%, p < 0.001) and lower LER (-2 +/- 20 vs 10 +/- 10%, p < 0.05) than did the control patients. WR was significantly correlated with CFR (r = 0.50, p < 0.001) and LER (r = 0.41, p < 0.01) in all of the patients. CAD patients with dipyridamole-induced chest pain demonstrated significantly lower WR (14 +/- 20 vs 27 +/- 12%, p < 0.05), lower CFR (97 +/- 71 vs 162 +/- 82%, p < 0.05) and lower LER (-13 +/- 21 vs 11 +/- 9%, p < 0.001) than did CAD patients without chest pain. CAD patients with dipyridamole-induced ST depression demonstrated significantly lower WR (14 +/- 20 vs 29 +/- 8%, p < 0.05), lower CFR (105 +/- 79 vs 170 +/- 73%, p < 0.05) and lower LER (-8 +/- 21 vs 11 +/- 10%, p < 0.01) than did CAD patients without ST depression. These results suggest that the myocardial washout rate of 201Tl after dipyridamole infusion reflects the severity of coronary artery disease as assessed by coronary hemodynamics, myocardial metabolism, symptoms and electrocardiography.

Aged↗
PubMed1995

Effect of 5,6,7,8-tetrahydroneopterin on the bovine endothelial cell injury induced by cumene hydroperoxide.

Neopterin is an 2-amino-4-hydroxypteridine derivative and a precursor of biopterin, which is derived from guanosine triphosphate. Previously, we have reported that 5,6,7,8-tetrahydroneopterin (NPH4), a reduced form of neopterin, possesses an antioxidant activity in various systems. In this study, we investigated the activity in more detailed manner and discussed the possible applications of this antioxidant. Analysis by electron spin resonance spectrometry indicated that NPH4 scavenged superoxide anion radicals and hydroxyl radicals as well. Moreover, NPH4 protected the rat brain homogenate from autoxidation. Next, we examined the effect of NPH4 on the cell injury induced by cumene hydroperoxide (CHP) in cultured bovine artery endothelial cells. The activity of lactate dehydrogenase, a marker enzyme of cell injury, was elevated by CHP in a dose-dependent manner, and this elevation was dose-dependently suppressed by NPH4. The elevation of lipid peroxide content was also inhibited by NPH4 in the same fashion. These data suggest that NPH4 would be effective against various diseases whose pathogenesis is active oxygen-related.

Animals↗
PubMed1995

Comparison of first-line antihypertensive drugs by a randomized cross-over method--a preliminary report.

The present study was undertaken to compare the effects of first-line antihypertensive drugs in Japanese patients. Four antihypertensive drugs were studied: trichlormethiazide (TCT), nifedipine retard (NIF), atenolol (ATN), and enalapril malate (ENP). Thirty-eight patients (16 men and 22 women; age, 53.3 +/- 8.8 years, mean +/- SD) were enrolled in the study. After a control period of 2 to 4 weeks, the four drugs were administered according to a randomized, cross-over design, the duration of each treatment period being 8 to 12 weeks. The initial dose of each drug was increased until blood pressure (BP) fell to less than 150/90 mmHg. The maximum doses of TCT, NIF, ATN, and ENP were 4, 40, 50, and 20 mg/day, respectively. The protocol was completed in 25 of the 38 patients. The BPs (SBP/DBP) at the end of each period were 168 +/- 3 (mean +/- SEM)/105 +/- 1 (control), 149 +/- 4/ 98 +/- 2 (TCT), 138 +/- 3/89 +/- 2 (NIF), 151 +/- 4/94 +/- 2 (ATN), and 152 +/- 4/97 +/- 2 mmHg (ENP). The BP during NIF treatment was significantly lower than during the other treatments. This finding suggests that the calcium antagonist had a greater hypotensive effect than the other first-line antihypertensive drugs studied. The subjects seem to more closely resemble black rather than white populations with respect to their response to antihypertensive treatment.

Adult↗
PubMed1995

Glomerular hemodynamics during supraventricular tachycardia.

Supraventricular tachycardia (SVT) was induced in 7 patients by programmed cardiac stimulation via an esophageal lead. Blood pressure, renal function, and hormonal factors were measured before, during, and after SVT. The glomerular filtration rate increased during SVT, while renal blood flow did not change. The parameters of glomerular hemodynamics were calculated according to the method of Gomez. Glomerular pressure was 64 +/- 3 (mean +/- SE) mmHg before SVT, and rose significantly (p < 0.01) to 76 +/- 5 during SVT. This rise in glomerular pressure was associated with a decrease in afferent vascular resistance (from 3355 +/- 610 to 1770 +/- 517 dynes x sec/cm5, p < 0.05) and an increase in efferent vascular resistance (from 3726 +/- 758 to 4814 +/- 780 dynes x sec/cm5, p < 0.05). Since atrial natriuretic peptide (ANP) increased during SVT (from 40 +/- 15 to 208 +/- 72 pg/ml, p < 0.01), these changes in glomerular hemodynamics may be attributed to the physiologic action of ANP. Despite the changes in glomerular hemodynamics during SVT, natriuresis appeared after SVT and not during SVT. This suggests that natriuresis accompanying SVT could not be attributed to the changes in glomerular hemodynamics.

Adult↗