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Biomedical subjects

S Nishi

Publications and source records attributed to S Nishi.

At least 37 records · Page 2Linked to original sources

Effect of mild therapeutic hypothermia on phenytoin pharmacokinetics.

The authors examined the effect of mild therapeutic hypothermia on phenytoin pharmacokinetics in 14 patients with brain damage. Each patient was given phenytoin during and after mild therapeutic hypothermia. Plasma concentrations of total phenytoin, unbound phenytoin, and 5-(p-hydroxyphenyl)-5-phenylhydantoin (5-p-HPPH), the major metabolite of phenytoin, were measured. Pharmacokinetic parameters during and after mild therapeutic hypothermia were compared. Plasma concentrations of total and unbound phenytoin were significantly higher during hypothermia than after hypothermia. The area under the plasma concentration-time curve (zero to infinity) was increased by 180% and mean residence time was prolonged by 180% during hypothermia compared with the corresponding values after hypothermia. Moreover, the elimination constant (ke) was decreased by 50% and elimination clearance of phenytoin was decreased by 67% during hypothermia compared with the corresponding values after hypothermia. The plasma concentration of 5-p-HPPH was significantly lower during hypothermia than after hypothermia. These findings suggest that phenytoin metabolism is inhibited by mild therapeutic hypothermia.

Adolescent↗

Membranoproliferative glomerulonephritis associated with hypocomplementemic urticarial vasculitis after complete remission of membranous nephropathy.

A 49-year-old-man developed proteinuria in 1978. He was diagnosed as having membranous nephropathy by renal biopsy and was treated with prednisolone. The proteinuria disappeared completely and the treatment was stopped. In 1995, after complete remission, he developed nephrotic syndrome with chronic urticaria and hypocomplementemia. Renal biopsy revealed membranoproliferative glomerulonephritis (type I) and skin biopsy showed leukocytoclastic vasculitis, which was compatible with hypocomplementemic vasculitis syndrome. Steroid therapy was very effective.

Anti-Inflammatory Agents↗

Echocardiographic diagnosis of extrapericardial tamponade due to dilated gastric roll following oesophagectomy.

A complication of lower thoracic oesophagectomy for oesophageal carcinoma is reported. Extrapericardial tamponade was caused by a dilated retrosternal gastric roll. Echocardiography was useful for diagnosis. Diagnosis, investigation and management of this unusual but life-threatening complication are discussed. Transthoracic echocardiography is a useful and practical investigation for the evaluation of complications of oesophagectomy.

Cardiac Tamponade↗

Determination of optimal blood pressure for patients with IgA nephropathy based on renal histology.

To evaluate the optimal BP control for patients with IgA nephropathy (IgAN) based on the histologic severity of the nephropathy and the degree of renal dysfunction. We analyzed 332 consecutive renal biopsy specimens and clinical data from patients with IgAN. Patients were divided into three groups based on their BP at the time of biopsy: an optimal BP (SBP<120 mmHg and DBP<80 mmHg), a hypertensive BP (SBP > or = 140 mmHg and/or DBP > or = 90 mmHg), and an intermediate BP group. Each biopsy specimen was evaluated for mesangial proliferation, degree of sclerosis and/or hyalinosis of the arterioles and the interlobular artery using a semiquantitative method. Creatinine clearance and the percentage of sclerosed glomeruli were also determined. Both the degree of renal dysfunction and the histologic changes correlated significantly with BP, even in patients with a BP <140/90 mmHg. The patients with an optimal BP at the time of biopsy had significantly less histologic damage with respect to mesangial proliferation and vessel changes than those with an intermediate or hypertensive BP. In the patients with a hypertensive BP, the percentage of sclerotic glomeruli was significantly higher and the creatinine clearance was significantly lower. The optimal BP proposed by the WHO in 1999 prevents histologic evidence of renal damage for patients with IgAN.

Adult↗

[Disorders of potassium metabolism in hemodialysis patients].

The fecal K concentration and the K-flux activity of erythrocytes were examined to investigate the role of extrarenal K excretion and K transport in peripheral tissue cells in hemodialysis patients. The fecal K concentration of hemodialysis patients was increased significantly(p < 0.01) compared to that of healthy subjects. The K-flux activity of erythrocytes and the serum K concentration correlated negatively(r = -0.482, p < 0.01) in non-diabetic hemodialysis patients, but did not correlate in diabetic hemodialysis patients. K-flux activity and Kt/V for urea correlated significantly(r = 0.412, p < 0.05). The K-flux activity of erythrocytes collected after hemodialysis therapy significantly increased (p < 0.05) compared with that of erythrocytes collected before therapy. We speculated that the K-flux activity of various cells including erythrocytes participates in the regulation of serum K in hemodialysis patients and that the inhibitory factors on K-flux activity are removed partially by hemodialysis therapy.

Adult↗

Slow induction of milrinone after coronary artery bypass grafting.

The aim of this study was to evaluate the hemodynamic effects of a slow induction of milrinone after open heart surgery. Twenty patients who underwent elective coronary artery bypass grafting were randomized into two groups, with 10 patients receiving a continuous infusion of milrinone (5 microg/kg/min) (group M), and 10 patients undergoing treatment without milrinone (group C). This is a preliminary study for evaluating the efficacy of a slow induction of milrinone, so patients in low cardiac output state were excluded. A continuous infusion without an initial loading dose was initiated in the intensive care unit. Hemodynamic parameters and the concentration of milrinone were measured 90 minutes and 3 hours after initiation of the milrinone infusion. A significant decrease in arterial pressure occurred at 3 hours in group M, and both the systemic vascular resistant indices decreased significantly (p<0.05) at 90 minutes. No significant changes occurred in group C. Cardiac index and heart rate increased significantly (p<0.05) in group M, but were unchanged in group C. No significant change in double product was observed in either group. Hypotension (systolic blood pressure less than 100 mmHg) or arrhythmia did not occur in group M. The concentration of milrinone at 90 minutes and 3 hours was 97+/-22 and 124+/-27 ng/ml, respectively. A slow induction of milrinone is safe and effective in patients following cardiac surgery.

Aged↗

Surface microarchitectural design in biomedical applications: in vivo analysis of tissue ingrowth in excimer laser-directed micropored scaffold for cardiovascular tissue engineering.

A micropatterned microporous segmented polyurethane film (20 x 12 mm in size, 30 micrometer thick) with four regions was prepared by excimer laser microprocessing to provide an in vivo model of transmural tissue ingrowth in an open cell-structured scaffold specially designed for cardiovascular tissue engineering. Three microporous regions had the same circular micropores (30 micrometer diameter) but different pore density arrangements (percentage of total pore area against unit area was 0.3%, 1.1%, and 4.5%), and the other region remained nonporous. The covered stent, prepared by wrapping the regionally different density-microporous film on an expandable metallic stent (approximately 3.1 mm in diameter), was delivered to the luminal surface of canine common carotid arteries and placed after expansion of the stent to a diameter of approximately 8 mm using a balloon catheter. At 4 weeks of implantation, all the covered stents (n = 10) were patent. The luminal surfaces of the covered stents were almost confluently endothelialized both in nonporous and microporous regions. Histological examination showed that the neointimal wall was formed by tissue ingrowth from host through micropores (transmural) and anastomotic sites. Thrombus formation occurred frequently in the lowest density porous region and nonporous region. With an increase in pore density, the thickness of the neointimal wall decreased. This study demonstrated how the micropore density of implanted devices influences tissue ingrowth in arterial implantation.

Angioplasty, Balloon↗

cDNA cloning of the mammalian sterol C5-desaturase and the expression in yeast mutant.

Sterol C5-desaturase (SC5D) cDNA is an enzyme that catalyzes the dehydrogenation to introduce C5-6 double bond into lathosterol in cholesterol biosynthesis. We have isolated and sequenced the cDNA clones encoding human and mouse SC5D. The functional complementation of a defective yeast mutant proves that the human and mouse cDNA clones encode SC5D. Mammalian SC5D was presumed as an integral membrane protein containing histidine residues conserved also in yeasts and plant.

Amino Acid Sequence↗

Molecular cloning and functional characterization of the mouse mafB gene.

The Maf family of the transcription factors plays a pivotal role in controlling development and cellular differentiation. To clarify the molecular mechanisms controlling mafB expression, a genomic clone of the mouse mafB gene was isolated and analyzed. RNase protection analysis determined the transcription initiation site at 389 bp upstream from the translation initiation site. The 3' end of the gene is located at 946 bp downstream from the termination codon. The gene lacks intron structure. Sequence analysis showed a TATA-like sequence (5'-GATAAAA-3') and an inverted CCAAT-box (5'-ATTGG-3') in the promoter region. Upstream of these sequences, there are several potential regulatory elements, including two GC-boxes (5'-GGGCGG-3'), and a palindromic sequence (5'-GTCAGCTGAC-3') which contains two Maf recognition elements (MARE, 5'-GCTGAC-3') and an E-box (5'-CAGCTG-3'). Transient transfection analysis with the 5'-flanking region of the mafB gene demonstrated that these elements are important for mafB gene expression. In addition, cotransfection analysis indicated that the MyoD activates the mouse mafB promoter and the gene is positively auto-regulated by its own product.

Animals↗

Ultrastructural characteristics of diabetic nephropathy.

Diabetic nephropathy is a major cause of chronic renal failure in Japan, and the prevalence rate has markedly increased during the past decade. Diabetic nephropathy shows various specific histological changes not only in glomeruli but also in the interstitial region. Nodular, diffuse, and exudative lesions, so-called diabetic glomerulosclerosis, are well known as glomerular lesions. At first, they were historically evaluated only by light microscopy, and thus which components of the glomeruli were modified was not sufficiently clear. Subsequent electron microscopic studies clarified that the expansion of the mesangial matrix was the true form of nodular and diffuse lesions, and that insudated serum substance was the real appearance of an exudative lesion. Interstitial lesions also exhibit specific features in diabetic nephropathy. In electron microscopic studies, it was proved that the size of mitochondria and thickness of the tubular basement membrane were increased in diabetic nephropathy. In this review, we introduce typical electron microscopic findings in diabetic nephropathy and recent opinions on the progression of diabetic nephropathy.

Diabetic Nephropathies↗

Venous blood flow measurement by determination of change in venous hemoglobin saturation.

OBJECTIVE: To evaluate a method of measuring venous blood flow in vitro by using the Fick principle and change in saturation of venous blood and to apply the method to the clinical measurement of hepatic blood flow. DESIGN: Experimental study using an in vitro model and clinical study for critically ill patients. SETTING: Department of Anesthesiology and Intensive Care Medicine in Osaka City University Medical School. MODEL: Human blood deoxygenated by bubbling of nitrogen was circulated in a closed circuit at 10-120 mL/min by a roller pump. A fiber optic sensor was attached to the circuit for continuous monitoring of hemoglobin saturation. PATIENTS: Eight critically ill patients, aged 54.3 +/- 15.1 yrs, were studied. INTERVENTIONS: Hemoglobin saturation was changed in the in vitro study by the injection of 0.2 mL of oxygenated blood. Signals from the optical fiber were analogue-digital converted and recorded in a computer. In the clinical study, an oximetry catheter was inserted into the inferior vena cava (IVC) via the femoral vein. Arterial blood (10 mL) was drawn from the radial artery, and injected into the IVC. The changes in oxygen saturation in the venous blood were recorded. MEASUREMENTS AND MAIN RESULTS: Blood flow was calculated using the Fick principle, assuming that all the injected blood passes through the sensor. In vitro estimation of blood flow was well correlated with the actual flow (r2 = .94). IVC blood flow was measured above and below the merging point of the hepatic vein. The difference of the two values was assumed to represent hepatic blood flow. IVC blood flow was calculated by the same method as for the in vitro study. The blood flows in the IVC above and below the anastomosis with the hepatic vein were 2.82 +/-0.56 (SD) Umin and 1.96 +/- 0.61 (SD) L/min. Average estimated hepatic blood flow was 0.86 L/min (range, 0.34-1.75 Umin). CONCLUSION: We examined the accuracy and reliability of this new method in the present in vitro study. This method may be clinically useful for measuring hepatic blood flow.

Adult↗

Characterization of two fly LGR (leucine-rich repeat-containing, G protein-coupled receptor) proteins homologous to vertebrate glycoprotein hormone receptors: constitutive activation of wild-type fly LGR1 but not LGR2 in transfected mammalian cells.

The receptors for lutropin (LH), FSH, and TSH belong to the large G protein-coupled receptor (GPCR) superfamily and are unique in having a large N-terminal extracellular (ecto-) domain important for interactions with the large glycoprotein hormone ligands. Recent studies indicated the evolution of a large family of the leucine-rich repeat-containing, G protein-coupled receptors (LGRs) with at least seven members in mammals. Based on the sequences of mammalian glycoprotein hormone receptors, we have identified a new LGR in Drosophila melanogaster and named it as fly LGR2 to distinguish it from the previously reported fly LH/FSH/TSH receptor (renamed as fly LGR1). Genomic analysis indicated the presence of 10 exons in fly LGR2 as compared with 16 exons in fly LGR1. The deduced fly LGR2 complementary DNA (cDNA) showed 43 and 64% similarity to the fly LGR1 in the ectodomain and transmembrane region, respectively. Comparison of 12 LGRs from diverse species indicated that these proteins can be divided into three subfamilies and fly LGR1 and LGR2 belong to different subfamilies. Potential signaling mechanisms were tested in human 293T cells overexpressing the fly receptors. Of interest, fly LGR1, but not LGR2, showed constitutive activity as reflected by elevated basal cAMP production in transfected cells. The basal activity of fly LGR1 was further augmented following point mutations of key residues in the intracellular loop 3 or transmembrane VI, similar to those found in patients with familial male precocious puberty. The present study reports the cloning of fly LGR2 and indicates that the G protein-coupling mechanism is conserved in fly LGR1 as compared with the mammalian glycoprotein hormone receptors. The characterization of fly receptors with features similar to mammalian glycoprotein hormone receptors allows a better understanding of the evolution of this unique group of GPCRs and future elucidation of their ligand signaling mechanisms.

Amino Acid Sequence↗

Treatment of membranoproliferative glomerulonephritis associated with hepatitis C virus infection. Niigata Research Group of Glomerulonephritis and Nephrotic Syndrome.

OBJECTIVE: Interferon has been used as a new therapeutic agent for glomerulonephritis since a manifest relationship between membranoproliferative glomerulonephritis (MPGN) and hepatitis C virus (HCV) infection was documented. However, several side effects and rebound phenomenon have been significant problems. We retrospectively evaluated the therapeutic effect and safety of the standard treatment with steroids and/or immunosuppressive agents for MPGN patients with an HCV infection. METHODS: Remission and renal survival rates as well as clinical and histological data were compared between MPGN groups with or without an HCV infection. In addition, the hepatic function was followed-up after the treatment. PATIENTS: The subjects were 42 biopsy proven MPGN patients. Seven were positive for an HCV infection. Secondary causes of MPGN excluding an HCV infection were omitted. Most patients were treated with steroids and/or immunosuppressive agents. RESULTS: The mean age of the MPGN patients with an HCV infection was significantly higher than that of those without an HCV infection. The renal function and the interstitial change of the former group were significantly worse than those of the latter. Nevertheless, remission and renal survival rates were not significantly different between the two groups. None in the HCV positive MPGN group showed an impairment of hepatic function during the clinical course. However, 2 subjects died from severe pneumonia during the treatment. CONCLUSION: The standard treatment with steroids and/or immunosuppressive agents did not reveal a statistical difference in the therapeutic efficacy between MPGN patients with or without an HCV infection. However, some in the former group showed a poor prognosis.

Adult↗