Search PubMed⌕ Search

Biomedical subjects

K Inui

Publications and source records attributed to K Inui.

At least 235 records · Page 13Linked to original sources
PubMed1996

Expression of full-length human dystrophin cDNA in mdx mouse muscle by HVJ-liposome injection.

Duchenne muscular dystrophy (DMD) is an X-linked progressive muscle disorder which is caused by a defect of dystrophin, a 427-kDa muscle cell membrane protein. One of the possible means of DMD therapy is to express the dystrophin gene in patients' muscles. In this study, full length dystrophin cDNA was expressed in mdx (muscular dystrophy model) mouse muscle using the hemagglutinating virus of Japan (HVJ)-liposome method. With the HVJ-liposome method, the lacZ reporter genes were expressed in 50-80% of cultured mdx mouse myoblasts, which suggested its potential usefulness for an in vivo gene study. Three expression vectors containing human full length dystrophin cDNA driven by Rous sarcoma virus (RSV), mouse leukemia virus, or human dystrophin promoters, were used. HVJ-liposomes containing these plasmids were directly injected into mdx mouse quadriceps muscle. The highest efficiency of expression of dystrophin was in 26% of the muscle fibers at the injected site on day 3 after HVJ-liposome injection of the RSV-based vector. The expression was decreased on day 10. The study thus demonstrates the feasibility of full length human dystrophin cDNA transfer and dystrophin expression using HVJ-liposomes in vivo.

Animals↗
PubMed1996

[Role of apoptosis in the progression of secondary hyperparathyroidism].

In many tissues, cell proliferation is counterbalanced by apoptosis. Hyperparathyroidism is one of the most important complications in long term dialysis patients and is characterized by remarkable cell proliferation of parathyroid cells. Therefore, alteration in the regulation and clearance of excess cells by apoptosis may occur in hyperparathyroidism. In the present study, we evaluated the expression of Ki-67 (proliferative cell associated protein) and Bcl-2(apoptosis-preventing molecules), and the number of apoptotic cells in the nodular lesion of parathyroid glands with secondary hyperparathyroidism(2 degrees HPT), as compared with primary hyperparathyroidism(1 degree HPT) for clarification of the role of apoptosis in the development of 2 degrees HPT. The number of Ki-67+ cells was remarkably increased in 2 degrees HPT(12.02 +/- 10.87, mean +/- SD) compared to in 1 degree HPT(0.81 +/- 0.53) (p < 0.01). However, the number of apoptotic cells was significantly decreased in 2 degrees HPT(0.10 +/- 0.06) compared to in 1 degree HPT(0.31 +/- 0.19) (p < 0.05). To the contrary, Bcl-2+ cells were increased in 2 degrees HPT(0.35 +/- 0.23) compared to in 1 degree HPT(0.10 +/- 0.13) (p < 0.05). These results suggest that the mechanisms of parathyroid cell proliferation are different in each nodular lesion of 1 degree HPT and 2 degrees HPT. Furthermore, the remarkable proliferation of parathyroid glands may have been due to the reduction of the apoptotic process via Bcl-2 expression in 2 degrees HPT.

Adult↗
PubMed1996

Na(+)-dependent uptake of 1,5-anhydro-D-glucitol via the transport systems for D-glucose and D-mannose in the kidney epithelial cell line, LLC-PK1.

1,5-Anhydro-D-glucitol, a 1-deoxy form of D-glucose, is one of the major polyols in human and rat blood plasma, and is regarded as a sensitive marker of glycemic control in diabetic patients. Although renal tubular reabsorption of 1,5-anhydro-D-glucitol is thought to maintain the physiological plasma level of this polyol, the mechanism of its cellular uptake has not yet been established. In the present study, the transport characteristics of 1,5-anhydro-D-glucitol in a kidney epithelial cell line, LLC-PK1, were investigated. The uptake of 1,5-anhydro-D-glucitol by the LLC-PK1 cell monolayers was found to be a highly Na(+)-dependent process. The initial uptake rate of 1,5-anhydro-D-glucitol was inhibited by the presence of D-glucose, D-mannose and methyl-alpha-D-glucoside, a nonmetabolizable D-glucose analogue. D-Mannose was taken up partially by LLC-PK1 cells in a Na(+)-dependent manner. 1,5-Anhydro-D-glucitol had an inhibitory effect on the uptake of both methyl-alpha-D-glucoside and D-mannose. Phlorizin inhibited the uptake of methyl-alpha-D-glucoside and 1,5-anhydro-D-glucitol, but not of D-mannose. In contrast, phloretin inhibited the uptake of both 1,5-anhydro-D-glucitol and D-mannose, but not the uptake of methyl-alpha-D-glucoside. The apparent Michaelis-Menten constant and maximum velocity values for 1,5-anhydro-D-glucitol uptake were 29 mM and 240 pmol/mg protein/min, respectively. These findings suggest that the uptake of 1,5-anhydro-D-glucitol across the apical membranes of LLC-PK1 cells is mediated by the Na(+)/D-glucose cotransport system and probably by the Na+/D-mannose cotransport system.

Animals↗
PubMed1996

[Thoracoscopic surgery].

Recent advances in endoscopic equipment and refinement of thoracoscopic techniques and increased experience with thoracoscopy have expanded the application of this procedure for lung cancer. Thoracoscopic treatment for malignant pleural effusion, sampling of hilar and mediastinal lymph nodes, wedge resection of the lung and thoracoscopic lobectomies and pneumonectomies have been reported in many institutes. Our findings demonstrate the feasibility of performing major video-assisted thoracoscopic pulmonary resections with less postoperative morbidity. This report describes present role of video-assisted thoracoscopic surgery for early lung cancer.

Endoscopy↗
PubMed1995

Facilitation of the arterial baroreflex by the preoptic area in anaesthetized rats.

1. Activation of cell bodies in the ventrolateral part of the midbrain periaqueductal grey matter (PAG) facilitates the arterial baroreflex via the nucleus raphe magnus. The facilitatory effects of stimulation within the hypothalamus on the arterial baroreflex and their relation to the PAG and nucleus raphe magnus were studied in urethane- and chloralose-anaesthetized rats. 2. Systematic mapping experiments revealed that the preoptic area (POA) is the principal location in the hypothalamus of neuronal cell bodies that are responsible for the potentiation of the baroreflex. In addition to provoking hypotension and vagal bradycardia, both electrical and chemical stimulation of the POA produced facilitation of baroreflex vagal bradycardia (BVB) that was evoked by electrical stimulation of the aortic depressor nerve. Baroreflex hypotension was slightly augmented during activation of the POA in vagotomized rats. 3. Selective destruction of cell bodies either in the ventrolateral PAG or in the nucleus raphe magnus reduced facilitation of BVB by the POA. Hypotension and bradycardia due to POA stimulation were also markedly attenuated after such selective destruction. 4. In conclusion, the POA, the ventrolateral PAG and the nucleus raphe magnus constitute a functional complex that produces cardiovascular trophotropic effects including hypotension, vagal bradycardia and baroreflex facilitation.

Anesthesia↗
PubMed1995

'Aortic baroreceptor' neurons in the nucleus tractus solitarius in rats: convergence of cardiovascular inputs as revealed by heartbeat-locked activity.

Rat aortic depressor nerve (ADN) contains only baroreceptor afferents. We identified 'aortic baroreceptor' neurons in the nucleus tractus solitarius (NTS) as those responding to electrical stimulation of the ADN and attempted to demonstrate convergence of cardiovascular mechanoreceptor inputs in these 'baroreceptor' neurons. In chloralose-urethane-anesthetized rats, ADN stimulation evoked either short or long latency responses (SLR, LLR) in 193 neurons of the NTS. 28 (SLR, 15; LLR, 13) demonstrated ongoing activities with cardiac rhythm despite the fact that the ADN had been cut peripherally. In 12 (SLR, 5; LLR, 7) of the 28 neurons, heartbeat-locked activity was abolished by carotid occlusion (CO), and augmented by methoxamine-induced blood pressure elevation, indicating that the heartbeat-locked activity originated from carotid sinus baroreceptors (CSB). In 11 neurons (SLR, 6; LLR, 5), the heartbeat-locked activity was not affected by CO but was abolished by topical application of lidocain on the ipsilateral cervical vagus, suggesting that the heartbeat-locked activity originated mostly from cardiac mechanoreceptors. The origin of the heartbeat-locked activity of the remaining 5 neurons could not be determined. The onsets, as well as peaks of the heartbeat-locked activity of vagal origin appeared significantly earlier than those of CSB origin. In conclusion, NTS neurons receive converging projection not only from the two major arterial baroreceptors but also from the arterial baroreceptors and cardiac mechanoreceptors, thereby integrating sensory information of vascular and cardiac origins.

Animals↗
PubMed1995

Expression of the adult T-cell leukemia-derived factor, human thioredoxin, in the allotransplanted canine lung.

The relationship between the expression of adult T-cell leukemia-derived factor, human thioredoxin (ADF/TRX), and rejection in transplanted canine lungs was investigated in this study. Of a total 27 adult mongrel dogs, 24 underwent allotransplantation of the left lung with no immunosuppressant and the other three underwent autotransplantation of the left lung. Of the allotransplanted dogs, five were killed on postoperative day (POD) 1, five on POD 2, seven on POD 3, and seven on POD 5, while all three autotransplanted dogs were killed on POD 5. Histological examination was performed on the 24 allotransplanted left lungs (group A), 12 autologous right lungs (group B), and bilateral lungs of the three autotransplanted dogs (group C). The lung tissue was stained with anti-ADF antibody, and the high-ADF-producing cells (ADFh cells) in a randomly chosen field were counted as an index of ADF expression. As the signs of rejection in the group A lungs became more severe with time, the ADFh cells increased in number: 1.68 +/- 1.15, 6.08 +/- 3.44, 14.03 +/- 6.09, and 47.74 +/- 18.89, on PODs 1, 2, 3, and 5, respectively. However, the number of ADFh cells in the group B and group C lungs did not become significantly different from that on POD 1 in group A. These results suggested that ADF/TRX expression may be useful for the early diagnosis of rejection of transplanted lungs.

Animals↗
PubMed1995

Simulation for population analysis of Michaelis-Menten elimination kinetics.

A simulation study was conducted to compare the cost and performance of various models for population analysis of the steady state pharmacokinetic data arising from a one-compartment model with Michaelis-Menten elimination. The usual Michaelis-Menten model (MM) and its variants provide no estimate of the volume of distribution, and generally give poor estimates of the maximal elimination rate and the Michaelis-Menten constant. The exact solution to the Michaelis-Menten differential equation (TRUE) requires a precise analysis method designed for estimation of population pharmacokinetic parameters (the first-order conditional estimation method) and also considerable computational time to estimate population mean parameters accurately. The one-compartment model with dose-dependent clearance (DDCL), in conjunction with the first-order conditional estimation or Laplacian method, ran approximately 20-fold faster than TRUE and gave accurate population mean parameters for a drug having a long biological half-life relative to the dosing interval. These findings suggest that the well-known MM and its variants should be used carefully for the analysis of blood concentrations of a drug with Michaelis-Menten elimination kinetics, and that TRUE, in conjunction with a precise analysis method, should be considered for estimating population pharmacokinetic parameters. In addition, DDCL is a promising alternative to TRUE with respect to computation time, when the dosing interval is short relative to the biological half-life of a drug.

Computer Simulation↗