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Biomedical subjects

M Naito

Publications and source records attributed to M Naito.

At least 109 records · Page 6Linked to original sources
PubMed2000

Acute effects of endothelin-1 and TAK-044 (ET(A) and ET(B) receptor antagonist) in rats with dilated cardiomyopathy.

The hemodynamic effects of endothelin (ET)-1 and TAK-044 (ET(A) and ET(B) receptor antagonist) were studied in a rat model of dilated cardiomyopathy after autoimmune myocarditis. Six weeks after immunization, survived Lewis rats (30/43 = 70%) were randomly allocated into five groups to be given 0, 0.3, 3, 30 and 60 mg/kg/day (groups F0, F0.3, F3, F30 and F60; each group, n = 4) of TAK-044 using an osmotic pump subcutaneously. Age-matched normal Lewis rats (n = 26) were also randomly divided into four groups to be given 0, 0.3, 3 and 30 mg/kg/day (groups N0, N0.3, N3 and N30; each group, n = 4). ET-1 concentrations in plasma and myocardium were measured, and immunohistochemical detection of ET-1 in the left ventricle from the remaining rats (groups F and N) was performed. After administration of TAK-044 for 7 days, 2, 4, 11, 21 and 42 ng/min ET-1 every 20 min was infused using a pump, and the change in mean arterial pressure of each group during the infusion was examined. The plasma and myocardial ET-1 concentrations were significantly higher in group F than group N (12.3 +/- 1.5 vs. 5.4 +/- 0.2 pg/ml and 426 +/- 31 vs. 98 +/- 6 pg/g tissue; both p < 0.01). Strong positive signals for ET-1 were found to be widely distributed in the left ventricular myocardium of both groups of rats. Although the ET-1-induced increase in the mean arterial pressure was abolished in group N30, the maximal dose of ET-1 produced a 34% increase in the mean arterial pressure in group F30. Even in group F60, ET-1-induced hypertension was blocked incompletely. These results indicate that the heart may be a major ET-1-producing organ, and a higher dose of ET-1 antagonist is needed to block the effect of ET-1 in rats with dilated cardiomyopathy.

Animals↗
PubMed2000

Analysis of novel metastasis-associated gene TI-227.

TI-227 is a cancer metastasis-associated gene isolated from the B16-F10 mouse melanoma subline that preferentially metastasizes to the lung following intravenous injection. TI-227 is more highly expressed in the B16-F10 and colon26-nl17 sublines, which preferentially metastasize to the lung following intravenous injection, than in the B16-BL6 and colon26-nl22 sublines, which preferentially metastasize to the lung following subcutaneous injection. Since TI-227 could not be detected in normal tissues, there is a possibility that it is expressed specifically in tumors that preferentially metastasize to the lung following intravenous inoculation. Although the 5' end of TI-227 was analyzed, its total sequence contained no obvious open reading frame. However comparison with the isolated human counterpart, TI-227H gene, revealed a highly homologous region near the 3' end, which was expected to contain a very short open reading frame.

Adenocarcinoma↗
PubMed2000

Multidrug resistance reversal activity of taxoids from Taxus cuspidata in KB-C2 and 2780AD cells.

Some non-taxol-type taxoids having neither an oxetane ring at C-4 and C-5 nor an N-acylphenyl-isoserine group at C-13, such as taxuspine C, 2'-desacetoxyaustrospicatine, and 2-desacetoxytaxinine J, which were isolated from the Japanese yew Taxus cuspidata, increased cellular accu-mulation of vincristine (VCR) in multidrug-resistant 2780AD cells as potently as verapamil, and efficiently inhibited [(3)H]azidopine photolabeling of P-glycoprotein (P-gp). Taxuspine C, 2'-desacetoxyaustrospicatine, and 2-desacetoxytaxinine J at 10 microM completely reversed the resistance to colchicine, VCR, and taxol in KB-C2 cells, which overexpress P-gp, while taxinine and taxinine M showed no effect. Taxuspine C, 2'-desacetoxyaustrospicatine, and 2-desacetoxytaxinine J may be candidate pharmaceuticals for reversing multidrug resistance (MDR) and also may be good modifiers of MDR in cancer chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Inhibitory effect of ATF3 antisense oligonucleotide on ectopic growth of HT29 human colon cancer cells.

ATF3 is a transcription factor belonging to the Jun / Fos family whose mouse homologue (TI-241) was isolated, using the differential screening method, from B16 mouse melanoma cells as a blood-borne metastasis-associated gene. Here we show the tumorigenicity-inhibiting effect of an antisense oligonucleotide designed to reduce the expression of ATF3 in HT29 colon cancer cells. HT29 cells were reported to metastasize to the skin after intravenous inoculation. The antisense oligonucleotide inhibited cell attachment to the collagen-coated floor of the plates and invasion of HT29 cells in vitro, which are thought to be two important factors in the process of cancer metastasis and ectopic tumor growth. While the antisense oligonucleotide had no effect on cell growth of HT29 cells in vitro, mice that were inoculated subcutaneously with HT29 cells and treated with the antisense oligonucleotide survived longer than the control mice due to the inhibition of tumor growth in vivo. These show that ATF3 plays an important role in the ectopic growth / metastasis of HT29 colon cancer cells.

Activating Transcription Factor 3↗
PubMed2000

Isolation of chicken vasa homolog gene and tracing the origin of primordial germ cells.

To obtain a reliable molecular probe to trace the origin of germ cell lineages in birds, we isolated a chicken homolog (Cvh) to vasa gene (vas), which plays an essential role in germline formation in Drosophila. We demonstrate the germline-specific expression of CVH protein throughout all stages of development. Immunohistochemical analyses using specific antibody raised against CVH protein indicated that CVH protein was localized in cytoplasm of germ cells ranging from presumptive primordial germ cells (PGCs) in uterine-stage embryos to spermatids and oocytes in adult gonads. During the early cleavages, CVH protein was restrictively localized in the basal portion of the cleavage furrow. About 30 CVH-expressing cells were scattered in the central zone of the area pellucida at stage X, later 45-60 cells were found in the hypoblast layer and subsequently 200-250 positive cells were found anteriorly in the germinal crescent due to morphogenetic movement. Furthermore, in the oocytes, CVH protein was predominantly localized in granulofibrillar structures surrounding the mitochondrial cloud and spectrin protein-enriched structure, indicating that the CVH-containing cytoplasmic structure is the precursory germ plasm in the chicken. These results strongly suggest that the chicken germline is determined by maternally inherited factors in the germ plasm.

Amino Acid Sequence↗
PubMed2000

Efficient introduction of macromolecules and oligonucleotides into brain capillary endothelial cells using HVJ-liposomes.

In this study, we examined the feasibility of introducing macromolecules into cultured mouse brain capillary endothelial cells (MBEC4 cells) by utilizing the hemagglutating virus of Japan (HVJ)-liposomes with fusogenic activity. We used fluorescein isothiocyanate dextran (FITC-Dextran) and FITC-labeled oligodeoxynucleotide (FITC-ODN) as models of a macromolecule and an ODN, respectively. Intracellular fluorescence appeared rapidly after the exposure of MBEC4 cells to FITC-Dextran-containing HVJ-liposomes, and remained detectable for at least 3 days. Only a control level of intracellular fluorescence was seen after treatment with FITC-Dextran alone, FITC-Dextran with empty HVJ-liposomes or FITC-Dextran-containing liposomes without fusogenic activity. In the early phase after administration (0-30 min), the introduction of FITC-Dextran into MBEC4 cells by the HVJ-liposome method resulted in a rapid and time-dependent increase of intracellular fluorescence intensity. Moreover, FITC-ODN was also introduced into MBEC4 cells by the HVJ-liposome method, although FITC-ODN alone was not introduced. These results indicate that the HVJ-liposome method is useful for the efficient introduction of macromolecules, including ODN, into brain capillary endothelial cells.

Animals↗
PubMed2000

[Effects of fibrinogen, fibrin and their degradation products on the behaviour of vascular smooth muscle cells].

The transition of fibrinogen to fibrin and to their degradation products within the arterial wall has been reported to be accompanied by atherosclerotic progression. A major step in the pathogenesis of atherosclerosis is the vectorial migration of vascular smooth muscle cells (SMCs) from the arterial media through the internal elastic lamina into the intima and their subsequent proliferation in the intima. I have been studying the effects of fibrinogen, fibrin and their degradation products on the behaviour, particularly migration, of SMCs. Fibrinogen/fibrin stimulates the adhesion and migration of SMCs and their effects are mediated by both the RGD-containing region of the alpha chain of fibrinogen/fibrin and integrin alpha v beta 3 on the cell surface. SMCs migrate into fibrin gel even with no other chemotactic stimuli. SMCs displayed two-fold increase in migration into crosslinked fibrin gels compared to non-crosslinked gels, suggesting the importance of fibrin crosslinking by factor XIIIa on its three-dimensional structure for the migration of SMCs. Fibrin gels prepared with batroxobin, which cleaves only fibrinopeptide A, with ACTE, which cleaves only fibrinopeptide B, and with protamine sulfate, which cleaves nothing, but forms a fibrin-like gel, induce migration of SMCs in a manner similar to the gel prepared with thrombin, suggesting that the cleavage of fibrinopeptides is not involved in the migration of SMCs. Both anti-fibrinogen fragment D and E antibodies inhibit the migration of SMCs into fibrin gel, suggesting that both D and E regions of fibrin are involved in the migration of SMCs into fibrin gel. The migration of SMCs into fibrin gel also depends on the RGD-containing region and integrin alpha v beta 3. Both fibrinogen fragments D and E inhibit the migration of SMCs into fibrin gels, suggesting that these fragments may be involved in the regulation of SMC migration into fibrin gel as the result of fibrinolysis. Although subcultured SMCs usually show a synthetic phenotype, the behaviour of contractile SMCs may be crucial for the subsequent migration of the cells. We employed an in vitro assay system to evaluate the effects of fibrin gels on the migration of SMCs from explants taken from rabbit aorta. alpha v beta 3 integrin and the RGD-containing region are involved in the migration of SMCs into the fibrin gels. SMCs which migrated from the explants showed positive staining with monoclonal antibodies against SMC myosin heavy chain isoforms, SMemb, SM1 and SM2, suggesting that they are in an intermediate state changing from a contractile to synthetic state. These findings show that fibrin (ogen) itself induces adhesion and migration of SMCs without other chemotactic or chemokinetic substances, suggesting a crucial role for fibrin (ogen) in the development and progression of such vascular diseases as atherosclerosis, thrombosis and restenosis following balloon angioplasty.

Animals↗
PubMed2000

[Why do medical students not have a geriatrics textbook?].

To study the opinions of medical students on textbooks of geriatrics, we made a questionnaire for 5th-year medical students. All students had their own textbook (s) of internal medicine, and nearly half of the students had textbook (s) of physical examination. However, only 3.6% of students had their own textbook of geriatrics. The reasons for not having a textbook of geriatrics were as follows: 1) no understanding which textbook is better (59.1%), 2) no need to have a textbook (15.5%), 3) no appropriate textbooks (4.1%), and 4) others (17.6%). The most important point for choosing a textbook was as follows: 1) information from friends or seniors (38.9%), 2) looking by oneself (47.7%), 3) recommendation of a teacher (9.8%), and 4) others (3.6%).

Adult↗
PubMed2000

In vitro model of atherosclerosis using coculture of arterial wall cells and macrophage.

In order to determine the precise mechanism of the interactions between different types of cells, which are common phenomena in tissues and organs, the importance of coculture techniques are becoming increasingly important. In the area of cardiology, artificial arteries have been developed, based on the understanding of physiological communication of the arterial smooth muscle cells (SMC), endothelial cells (EC), and the extracellular matrix (ECM). In the study of atherosclerosis, the modification of low-density lipoprotein (LDL), which result in the recruitment and accumulation of white blood cells, especially, monocytes/macrophages, and foam cell formation, are hypothesized. Although there are well known animal models, an in vitro model of atherogenesis with a precisely known atherogenesis mechanism has not yet been developed. In this paper, an arterial wall reconstruction model using rabbit primary cultivated aortic SMCs and ECs, was shown. In addition, human peripheral monocytes were used and the transmigration of monocytes was observed by scanning electron and laser confocal microscopy. Monocyte differentiation into macrophages was shown by immunohistochemistry and comprehensive gene expression analysis. With the modified form of LDL, the macrophages were observed to accumulate lipids with a foamy appearance and differentiate into the foam cells in the ECM between the ECs and SMCs in the area of our coculture model.

Animals↗
PubMed2000

Effects of gliclazide on low-density lipoprotein oxidizability and atherosclerosis in cholesterol-fed rabbits.

We studied the effects of a widely-used sulfonylurea, gliclazide, on the oxidizability of low density lipoprotein (LDL) and the development of experimental atherosclerosis in cholesterol-fed rabbits. Daily oral administration of gliclazide (20 mg/kg/day) tended to inhibit the aortic atherosclerosis induced by feeding a 1% cholesterol diet for 10 weeks, although it did not affect diet-induced hyperlipidemia. The administration of gliclazide tended to inhibit the increase of serum thiobarbituric acid-reacting substances (TBARS) by cholesterol feeding and to increase the lag time of the conjugated-diene formation of LDL subjected to in vitro oxidation by copper ion, although without significance. The present study suggests that gliclazide may have antioxidative properties in vivo, and have further beneficial effects for the treatment of diabetes mellitus by inhibiting the oxidation of LDL.

Animals↗
PubMed2000

Japanese sisters associated with pseudohomozygous familial hypercholesterolemia and sitosterolemia.

Pseudohomozygous familial hypercholesterolemia is a rare condition of unknown etiology. Sitosterolemia is a rare autosomal recessively inherited disorder that is characterized by premature coronary artery disease, cutaneous xanthomas, and increased plasma plant sterols and 5alpha-stanols. Only a few cases of both sitosterolemia and pseudohomozygous familial hypercholesterolemia have been reported. In this study, we report two sisters with both conditions. With a low-cholesterol diet (< 250 mg/day), serum cholesterol concentration decreased rapidly to an almost normal level and cutaneous xanthomas gradually regressed and finally disappeared; however, plant sterol levels did not change during the period. Plant sterols should be measured in patients considered to have pseudohomozygous familial hypercholesterolemia. The two conditions in this family may have been the results of a single gene mutation. The findings also indicate that low cholesterol diet therapy is effective for the treatment of hypercholesterolemia but not of sitosterolemia in this family.

Child↗
PubMed2000

New cytotoxic agents, BE-52440A and B, produced by a streptomycete.

New cytotoxic substances, designated BE-52440A and B, were isolated from the mycelium of Streptomyces sp. A52440. The active principles were extracted from the mycelium by methanol and purified by silica gel column chromatography. BE-52440A and B exhibited cytotoxic activity against murine and human tumor cell lines.

Animals↗
PubMed2000

Evaluation of portosystemic collaterals by SPECT imaging after endoscopic variceal sclerotherapy: usefulness for predicting recurrence.

UNLABELLED: Bleeding from esophageal varices is a major cause of morbidity and mortality in cirrhotic patients. Identification of patients at high risk for bleeding is particularly important. The aim of this study was to determine whether detection of portosystemic collaterals by SPECT could predict the outcome of endoscopic injection sclerotherapy of esophageal varices and be useful for selecting appropriate therapy. METHODS: Sixty-two patients with liver cirrhosis who were considered at high risk of bleeding were treated with endoscopic injection sclerotherapy. Endoscopy was performed every 3 mo after therapy or until bleeding occurred. Before and within 2 wk after therapy, tomographic images of intra-abdominal blood pool were constructed by SPECT. RESULTS: Before therapy, the following portosystemic collateral routes were observed: coronary veins in 53 (85.5%) of 62 patients, short gastric veins in 8 patients (12.9%), splenorenal shunts in 10 patients (16.1%), and paraumbilical veins in 6 patients (9.7%). Patients positive for imaging of coronary veins were divided into 3 groups on the basis of changes in images after therapy: complete responders (n = 17), whose coronary vein images disappeared completely; partial responders (n = 18), whose images became smaller; and nonresponders (n = 18), whose images did not change significantly before or after therapy. The rates of recurrence after endoscopic injection sclerotherapy until 6 mo in complete responders (4/17, 23.5%) and partial responders (7/18, 38.9%) were significantly less (P < 0.05) than that in nonresponders (11/13, 84.6%). The rate of recurrence of esophageal varices until 6 mo in nonresponders treated with additional submucosal injection sclerotherapy (1/5, 20.0%) was significantly less (P < 0.05) than that in nonresponders without additional submucosal injection sclerotherapy (11/13, 84.6%). CONCLUSION: Abdominal blood-pool SPECT, a noninvasive method, is useful for evaluating the therapeutic effectiveness of endoscopic sclerotherapy, for predicting the recurrence of varices, and for selecting appropriate management after sclerotherapy.

Collateral Circulation↗
PubMed2000

Impaired splenic erythropoiesis in phlebotomized mice injected with CL2MDP-liposome: an experimental model for studying the role of stromal macrophages in erythropoiesis.

Erythropoiesis occurs in the presence of erythropoietin (EPO) without macrophages in vitro. In hematopoietic tissues, however, erythroid cells associate closely with stromal macrophages, forming erythroblastic islands via interactions with adhesion molecules. To elucidate the role of macrophages in erythropoiesis, we selectively abrogated stromal macrophages of splenic red pulp of phlebotomized mice by injection with dichloromethylene diphosphonate encapsulated in multilamellar liposomes (CL2MDP-liposome). In the spleen, no erythropoietic activity occurred until 5 days after the treatment. Colony assay revealed that the erythropoiesis was suppressed at the level of CFU-E. The splenic erythropoietic activity gradually developed from day 6 after the treatment, when F4/80+ macrophages began to appear in the red pulp. EPO mRNA was expressed in kidney but not in liver or spleen of phlebotomized mice injected with CL2MDP-liposome, and the serum EPO concentration in these mice was higher than that in phlebotomized mice. These findings suggest that abrogation of stromal macrophages by injection with CL2MDP-liposome impairs the splenic microenvironment for erythropoiesis induced by hypoxic stress, and this may be an excellent experimental model for further characterization of the in vivo role of splenic macrophages in erythropoiesis.

Anemia↗
PubMed2000

Defective macrophage recruitment and clearance of apoptotic cells in the uterus of osteopetrotic mutant mice lacking macrophage colony-stimulating factor (M-CSF).

There are large numbers of macrophages in the uterus of normal mice. During estrus and metestrus endometrial epithelial cells express macrophage colony-stimulating factor (M-CSF). Numbers of uterine macrophages showed cyclic changes and accumulated beneath the endometrial epithelial cells at estrus and metestrus. However, numbers of uterine macrophages in osteopetrotic (op/op) mice were reduced tenfold compared with normal littermate mice and op/op mouse macrophages were ultrastructurally immature throughout the estrous cycle. Several macrophage chemokines were produced in the uterus. However, administration of antibody against the macrophage colony stimulating factor receptor (c-fms) severely diminished the number of uterine macrophages in normal littermate mice, implying that M-CSF plays a major role in macrophage recruitment in the uterus. Endometrial epithelial cells underwent apoptosis at estrus and metestrus and were disposed into the uterine lumen in op/op mice and littermate mice. In littermate mice a large number of macrophages accumulated beneath the endometrial epithelial cells and actively removed apoptotic cells. In contrast, there were few macrophages in op/op mice and clearance of apoptotic cells by macrophages was defective in the uterus of these mice. Thus M-CSF plays important roles in the recruitment and differentiation of macrophages and in scavenging effete epithelial cells in the uterus.

Animals↗
PubMed2000

[Concentration of isepamicin sulfate in bone marrow blood].

Fifteen patients who were performed a rotator cuff repair were subjected for the determination of a concentration of isepamicin sulfate (ISP), which was infused intravenously, in venous blood and bone marrow blood. The concentrations were measured at 0, 30, 60 minutes after the injection. There was no statistically significance between ISP concentrations in venous and bone marrow blood. This study revealed that the transference of ISP to the bone marrow was excellent.

Adult↗