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Biomedical subjects

T Naito

Publications and source records attributed to T Naito.

At least 55 records · Page 3Linked to original sources

Magnetic response of human extrastriate cortex in the detection of coherent and incoherent motion.

Although direction selectivity is a cardinal property of neurons in the visual motion detection system, movement of numerous elements without global direction (incoherent motion) has been shown to activate human and monkey visual systems, as does coherent motion which has global direction. We used magnetoencephalography to investigate the neural process underlying responses to these types of motions in the human extrastriate cortex. Both motions were created using a random dot kinematogram and four speeds (0, 0.6, 9.6 and 25 degrees /s). The visual stimuli were composed of two successive motions at different speeds; a coherent motion at a certain speed that changed to incoherent motion at another speed or vice versa. Magnetic responses to the change in motion consisted of a few components, the first of which was always largest. The peak latency of the first component was inversely related to the speed of the preceding motion, but for both motions it was not affected by the speed of the subsequent motion. For each subject, the estimated origin of the first component was always in the extrastriate cortex, and this changed with the speed of the preceding motion. For both motions, the location for the slower preceding motion was lateral to that for the faster preceding motion. Although the latency changes of the two motions differed, their overall response properties were markedly similar. These findings show that the speed of incoherent motion is represented in the human extrastriate cortex neurons to the same degree as coherent motion. We consider that the human visual system has a distinct neural mechanism to perceive random dots' motion even though they do not move in a specific direction as a whole.

Adult↗

Blood-brain barrier transport of 125I-labeled basic fibroblast growth factor.

PURPOSE: This study was carried out to examine the blood-brain barrier (BBB) transport of human basic fibroblast growth factor (bFGF) and investigate its mechanism. METHODS: The BBB transport of 125I-bFGF was measured by several in vivo methods including intravenous administration, in situ internal carotid artery perfusion, and intracerebral microinjection. The in vitro binding of 125I-bFGF was characterized using freshly prepared bovine brain capillaries. RESULTS: The distribution volume of 125I-bFGF in the postvascular supernatant increased with the perfusion time, and exceeded the space occupied by the brain microvasculature and its trichloroacetic acid (TCA) precipitability was more than 90%. 125I-bFGF avidly bound to isolated bovine brain capillaries with a Bmax of 206 +/- 48 pmol/mg protein, and a Kd of 36.5 +/- 15.7 nM. This binding was significantly inhibited by unlabeled bFGF and heparin in a concentration-dependent manner. The cationic peptides, protamine and poly-L-lysine (each 300 microM), produced over 85% inhibition of 125I-bFGF binding to brain capillaries. Furthermore, glycosaminoglycans with a sulfate residue, chondroitin sulfate B and C (each 10 microg/mL) also inhibited the binding of 125I-bFGF The in vivo transcytosis of 125I-bFGF from the luminal side to the brain was also inhibited by the presence of heparin (10 microg/mL) and poly-L-lysine (300 microM), whereas neither hyaruronic acid (10 microg/mL) nor insulin (10 microM) had any effect. In addition to these results, the brain efflux index method was used to confirm that the transcytosis of 125I-bFGF from brain to blood across the BBB was negligible. CONCLUSIONS: These results suggest that 125I-bFGF is transported across the BBB, possibly by an adsorptive-mediated transcytosis mechanism that is triggered by binding to negatively charged species on the luminal membrane surface of the brain microvasculature, such as heparan sulfate proteoglycans.

Animals↗

Disparate effect of beige mutation on cytotoxic function between natural killer and natural killer T cells.

Beige mice lack natural killer (NK) cytotoxicity, although NK cells are normally present. In recent studies, NK T cells have been newly identified. We therefore examined the number and function of NK T cells in beige mice. The number of NK T cells was at a normal level in the liver of beige mice. NK cytotoxicity was decreased in the liver of these mice, whereas NK T cytotoxicity was intact. When immunochemical staining for perforin was conducted, the majority of NK cells and the minority of NK T cells in beige mice carried a giant granule, containing perforin, in the cytoplasm. In the case of control B6 mice, the majority of NK cells and the minority of NK T cells had multiple, dispersed granules containing perforin. These results suggest that NK T cytotoxicity is unaffected by the beige mutation, owing to their cytotoxicity being mediated without the secretion system of perforin.

Animals↗

Up-regulation of monocyte chemoattractant protein-1 in tubulointerstitial lesions of human diabetic nephropathy.

BACKGROUND: We previously described that monocyte chemoattractant protein-1 (MCP-1) plays an important role in progressive glomerular and interstitial damage in inflammatory renal diseases. However, the expression of MCP-1 in diabetic nephropathy remains to be investigated. METHODS: We examined whether locally expressed MCP-1 participates in human diabetic nephropathy via recruiting and activating monocytes/macrophages (Mphi). Urinary and serum MCP-1 levels were measured by enzyme-linked immunosorbent assay in 45 patients with diabetic nephropathy. The presence of MCP-1 in diseased kidneys was determined by immunohistochemical and in situ hybridization analyses. RESULTS: Urinary MCP-1 levels were significantly elevated in patients with diabetic nephrotic syndrome and advanced tubulointerstitial lesions. Moreover, urinary levels of MCP-1 were well correlated with the number of CD68-positive infiltrating cells in the interstitium. In contrast, serum MCP-1 levels remained similar to those of healthy volunteers. Furthermore, we detected the MCP-1-positive cells in the interstitium of diabetic nephropathy via both immunohistochemical and in situ hybridization analyses. CONCLUSION: These observations suggest that locally produced MCP-1 may be involved in the development of advanced diabetic nephropathy, especially in the formation of tubulointerstitial lesions possibly through Mphi recruitment and activation. Moreover, up-regulation of MCP-1 may be a common pathway involved in the progressive tubulointerstitial damage in diabetic nephropathy as well as inflammatory renal diseases.

Adolescent↗

7-Hydroperoxycholesterol as a marker of oxidative stress in rat kidney induced by paraquat.

The in vivo paraquat-induced oxidative stress in rat tissue was studied by analyzing cholesterol-derived hydroperoxide as an index of lipid peroxidation. Paraquat (10 mg/kg) was administered i.p. to rats. Rats were sacrificed and lung, liver, and kidney were collected 2, 24 h, and 5 d after paraquat injection. Lipids were extracted and analyzed by HPLC with post-column chemiluminescence. We found that two cholesterol-derived hydroperoxides, 7alpha-hydroperoxycholest-5-en-3beta-ol (7alpha-OOH) and 7beta-hydroperoxycholest-5-en-3beta-ol (7beta-OOH) were present in lungs of control animals (0.06 and 0.06 nmol/g, respectively), in livers (6.5 and 15.8 nmol/g, respectively) and in kidneys (3.7 and 8.9 nmol/g, respectively). In liver paraquat increased lipid peroxidation approximately by 60% over the levels of control animals only at 2 h after paraquat treatment. In kidney, augmented lipid peroxidation, 7alpha-OOH and 7beta-OOH (by 70% and 147%, respectively) above levels was found at 2 h after paraquat treatment. Interestingly, these increase remained in kidney of rats 5 d after a single dose of paraquat. In contrast, cholesterol-derived hydroperoxides were not affected in lung of paraquat dosed rats. This is the first report on 7alpha-OOH and 7beta-OOH accumulations in rat liver and kidney, and it seems to reflect greater oxidative stress in the pathology of kidney of rats treated with acute paraquat at low dose.

Animals↗

[Comparison between cytomegalovirus hepatitis and Epstein-Barr virus hepatitis in healthy adults].

In order to determine the factors responsible for the differentiation of cytomegalovirus (CMV) hepatitis and Epstein-Barr virus (EBV) hepatitis in previously healthy adults, the clinical features and laboratory data of both types of hepatitis were retrospectively analyzed. CMV hepatitis showed a tendency to increase in our department. In comparison with EBV hepatitis, CMV hepatitis occurred in significantly older hosts than EBV hepatitis. We found that lymphadenopathy, cough and sore throat was more common in EBV hepatitis than in CMV hepatitis. The number of peripheral white blood cell count and atypical lymphocytes, and serum GOT, GPT, LDH and CRP levels of CMV and EBV hepatitis showed no significant differences.

Adolescent↗

Left ventricular mass and global function in essential hypertension after antihypertensive therapy.

This study compares left ventricular global function in 55 patients (25 with hypertrophy and 30 without hypertrophy) with essential hypertension, whose blood pressure had been stable for longer than 1 year, with that in 35 healthy subjects. Left ventricular global function was calculated using the echocardiographic Doppler index as described by Tei et al. (Tei index). No significant differences were observed in echocardiographic left ventricular systolic function between the three groups. Left ventricular global function differed significantly between the three groups, however, suggesting impaired left ventricular global function even in the absence of left ventricular hypertrophy. Similar changes were observed in the ratio of peak velocity of atrial systole to peak velocity of early diastole during left ventricular inflow waveform (A/E), indicating that this disorder mainly reflects impaired left ventricular diastolic function. Unlike A/E, the Tei index is not affected by increasing age, and, therefore, is appropriate for evaluating left ventricular global function in hypertensive patients, most of whom are middle-aged or older. This index may be useful for determining treatment strategy and evaluating treatment effects.

Adrenergic beta-Antagonists↗

Type II citrullinemia in an elderly patient treated with living related partial liver transplantation.

A 60-year-old woman was admitted to our hospital for repeated consciousness disturbance. Blood examination showed hyperammonemia, and plasma amino acid analysis revealed a marked increase in the citrulline level. To establish a diagnosis, a percutaneous needle biopsy of the liver was performed. The determination of the urea cycle enzyme activities revealed a selective marked decrease in argininosuccinate synthetase activity, indicating the final diagnosis of type II citrullinemia. The mean survival period of this disease after the appearance of symptoms has been reported as 26.4 months, and most conservative treatments are not effective. We performed a living related partial liver transplantation. Over the subsequent 13-month follow-up, the patient's condition has remained fairly good.

Biopsy, Needle↗

Improved brain delivery of a nonsteroidal anti-inflammatory drug with a synthetic glyceride ester: a preliminary attempt at a CNS drug delivery system for the therapy of Alzheimer's disease.

1,3-Diacetyl-2-ketoprofen glyceride (DAKG), a prodrug of ketoprofen, was synthesized as a model compound in our attempt to develop a central nervous system (CNS) drug delivery system to treat Alzheimer's disease. The primary purpose of the present study is to test whether DAKG improves the delivery of ketoprofen to the brain and to quantitatively evaluate several factors that influence the brain distribution of this prodrug. ddY mice were injected with either ketoprofen or DAKG at a dose of 40 micromol/kg and then the plasma and brain pharmacokinetics of these agents were assessed. The brain uptake clearance of ketoprofen and DAKG across the BBB was measured by in situ mouse brain perfusion. In addition, the efflux permeability of ketoprofen through the BBB was evaluated using the in vivo mouse brain microdialysis technique. The in vivo metabolism of DAKG in the brain was assessed by a short infusion into the internal carotid artery coupled with the brain metabolism index (BMI) method. Administration of DAKG produced an approximately 3-fold increase in the area under the brain concentration - time curve of ketoprofen, compared with administration of ketoprofen itself. The brain uptake clearance (CL(in) ) of ketoprofen across the BBB was 0.0308 +/- 0.0046 mL/min/g whereas the CL(in) of DAKG was 1.60 +/- 0.16 mL/min/g, suggesting a marked increase in BBB permeability following lipidization of ketoprofen. The BMI method confirmed that DAKG is taken up by the brain to rapidly release ketoprofen in a dose-dependent manner. The in vitro metabolism studies revealed that isolated bovine brain capillaries as well as whole brain homogenate have the hydrolysis activity to DAKG. In addition, the brain concentration of ketoprofen after DAKG administration was maintained for a significant period following co-administration of probenecid. These results suggest that DAKG improves the delivery of ketoprofen to the brain, and this improved delivery is due to avid uptake of DAKG across the BBB followed by rapid hydrolysis to ketoprofen within the brain. The ketoprofen produced in the brain was probably cleared by the active efflux system operating in the BBB. Significant inhibition of this efflux system by co-administration of probenecid could result in a sustained concentration of ketoprofen in the brain following DAKG administration.

Alzheimer Disease↗

Cardiac function in dialysis patients evaluated by Doppler echocardiography and its relation to intradialytic hypotension: a new index combining systolic and diastolic function.

AIM, PATIENTS AND METHODS: Cardiac function of 40 patients on maintenance dialysis was examined using a new Doppler index combining systolic and diastolic function. Immediately before dialysis, ultrasonic pulsed Doppler was used to measure right and left ventricular inflow and outflow waveforms. The sum of the isovolumetric contraction time (ICT) and isovolumetric relaxation time (IRT) was calculated by subtracting the ejection time from the interval between the end of an inflow waveform and the start of the next inflow waveform. The new index was obtained by dividing the sum of the two isovolumetric times by the ejection time. Cardiac function was evaluated in dialysis patients and healthy controls using new indices of the right and left heart systems. RESULT: Indices of the right and left heart systems in dialysis patients were significantly higher than those in healthy controls. With respect to hypotension during dialysis, patients were divided into two groups, a group with decreased blood pressure (group A: 27 patients) and a group with normal blood pressure (group B: 13 patients). Only the left heart system index in group A was significantly higher. There were no significant differences in other M-mode Doppler indices between the two groups. CONCLUSION: The new index was a more sensitive evaluator of cardiac function and predictor of hypotension during dialysis compared to standard echocardiographic indices.

Adult↗

Identification of 7-hydroperoxycholesterol in human liver by liquid chromatography-mass spectrometry.

BACKGROUND: A liquid chromatography-mass spectrometry with an atmospheric chemical ionization interface has been developed to identify simultaneously various oxygenated cholesterols in lipid extracts from alcoholic fatty liver. METHODS: We collected human liver tissues from alcoholic and control subjects at autopsy. We purified the lipid extracts with solid phase extraction and injected them onto a spherisorb ODS column, by using methanol that contained 10 mM ammonium acetate as a mobile phase and a flow rate of 0.7 ml/min. RESULTS: We found the presence of 7-hydroperoxycholesterol and other oxysterols (5-cholesten-3beta-ol-7-one, cholest-5-ene-3beta, 7-diol, and 5, 6beta-epoxy-5beta-cholestan-3beta-ol) in alcoholic fatty liver tissues. CONCLUSIONS: We assume that long-term ethanol ingestion leads to excessive oxidative stress and to the accumulation of cholesterol-derived hydroperoxides and oxysterols in alcoholic fatty liver.

Adult↗

A case of CREST syndrome and myeloperoxidase-specific anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis.

We report the first case of myeloperoxidase-specific anti-neutrophil cytoplasmic autoantibody (MPO-ANCA)-associated glomerulonephritis in a patient with CREST syndrome. A 74-year-old Japanese man with CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia) developed rapidly progressive renal failure without elevation of blood pressure. Renal biopsy revealed glomerular sclerosis and fibrous crescents. The MPO-ANCA titer was elevated to 145 EU/ml. When patients with collagen diseases develop rapidly progressive glomerulonephritis, the possibility of MPO-ANCA-associated glomerulonephritis should be kept in mind.

Aged↗

[Cytokines in the vitreous fluid of patients with proliferative diabetic retinopathy--vascular endothelial growth factor and platelet-derived growth factor are elevated in proliferative diabetic retinopathy].

PURPOSE: To determine the relation between vascular endothelial growth factor (VEGF) and platlet-derived growth factor (PDGF) in the vitreous fluids from patients with proliferative diabetic retinopathy (PDR). SUBJECTS AND METHOD: Concentrations of VEGF and PDGF in the vitreous fluids from 53 eyes, 31 eyes in 30 PDR patients and 22 eyes in 22 non diabetes mellitus(DM) patients serving as controls, were measured by enzyme-linked immunosolvent assay. The levels of VEGF and PDGF were compared between PDR and non DM patients. The relationship between these factors and clinical characteristics such as age, sex, protein concentration in the aqueous humor, HbA1c and duration of diabetes were investigated. RESULTS: Levels of both VEGF and PDGF in the PDR group were significantly higher than in non DM group (p < 0.01). A positive correlation was observed between the levels of VEGF and protein concentration in the aqueous humor (p < 0.01). However, levels of both VEGF and PDGF did not correlate with age, sex, or HbA1c. CONCLUSION: Both VEGF and PDGF were shown to be correlated with the pathogenesis of PDR.

Diabetic Retinopathy↗

Sequence analysis of RNA-2 of different isolates of broad bean wilt virus confirms the existence of two distinct species.

The complete nucleotide sequence of RNA-2 from a Japanese isolate IP of broad bean wilt virus (BBWV) was determined. The sequence encodes a single large polyprotein, which contains a putative movement protein and two coat proteins (CPs). The 3'-terminal sequences of RNA-2 were also determined for three other Japanese isolates and two ATCC isolates (PV132 and PV176) of BBWV. The CPs of the four Japanese isolates share 86.8-98.0% amino acid sequences homology with one another and 88.3-96.5% with those reported for the isolate PV131 (BBWV-2). However, they have only 57.9-66.2% homology with those of PV132 and PV176 (BBWV-1).

3' Untranslated Regions↗