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Biomedical subjects

M Naito

Publications and source records attributed to M Naito.

At least 271 records · Page 15Linked to original sources
PubMed1996

Modulation of multidrug resistance by SDZ PSC 833 in leukemic and solid-tumor-bearing mouse models.

P-Glycoprotein inhibitors, including the nonimmunosuppressive cyclosporin D analog SDZ PSC 833 (PSC 833), have been developed to circumvent multidrug resistance. In the present study, the potential of PSC 833 in reversing multidrug resistance was evaluated in various systemic treatment models with leukemic and solid-tumor-bearing mice. Having a relatively wide therapeutic window of daily p.o. doses from 12.5 to 75 mg/kg, PSC 833 significantly improved the antileukemic activity of the anticancer drugs adriamycin (ADM), vincristine (VCR) and etoposide (VP-16) given i.p. or i.v. against i.p.-inoculated vincristine-resistant P388 tumor (P388/VCR). PSC 833 in combination with i.p.-injected anticancer drugs in optimal schedule and dosage induced apparent cures in some leukemic mice, whereas no cures were obtained with the cyclosporin A/anticancer drug combinations. PSC 833 combined with i.v.-injected anticancer drugs was highly active, but not curative, against P388/VCR and parental P388 tumors (maximum T/C>175%) PSC 833 in combination with intravenous treatment with ADM showed prominent anti-solid-tumor activity against s.c.-inoculated colon adenocarcinoma 26 and human colorectal adenocarcinoma HCT-15. Against colon adenocarcinoma 26, the PSC 833/ADM combinations induced cure in two or three of six mice. PSC 833/ADM combinations significantly inhibited the growth of the tumor with maximum percent inhibitions of 83 and 73% in the early and advanced stages of the HCT-15 tumor models, respectively. The present study demonstrated that PSC 833 is highly active in potentiating the antitumor activity of systemically administered ADM, VCR and VP-16 against four murine and human tumors with a relatively wide therapeutic window of daily p.o. dose range of 12.5-100 mg/kg.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Crystalglobulin-induced vasculopathy accompanying ischemic intestinal lesions of a patient with myeloma.

A 37 year old man with multiple myeloma (IgG lambda) developed perforation of the small intestine and had gangrene in his feet. In the resected small intestine and below-knee amputated feet, intravascular deposition of crystals, immunohistochemically positive for IgG and a lambda light chain, were found. Although paraproteins produced in the course of plasma cell dyscrasia may crystallize and cause systemic occlusive vasculopathy, this is the first case with intestinal involvement. Because cryoglobulinemia was absent in this patient, crystals may be derived from the myeloma protein which sometimes crystallizes in the blood without the influence of low temperature.

Adult↗
PubMed1996

Development and heterogeneity of macrophages and their related cells through their differentiation pathways.

Macrophages are a heterogeneous population differing in their site of location, morphology and function. They develop from hematopoietic stem cells originating in both fetal and bone marrow hematopoiesis. In yolk sac and early hepatic hematopoiesis, primitive/fetal macrophages develop from hematopoietic stem cells, bypassing the stage of monocytic cells (monoblasts, promonocytes and monocytes), possess proliferative capacity and differentiate into resident macrophages in tissues in late ontogeny. Monocytic cells develop in hepatic hematopoiesis after the development of primitive/fetal macrophages, then move into the bone marrow in late ontogeny, forming a monocyte-derived macrophage population in tissues. Like monocytes, the monocyte-derived macrophages have no proliferative potential and are short-lived, whereas the resident macrophages are long-lived in tissue, possess proliferative capacity and can be sustained by self-renewal. In adult life, the bone marrow releases macrophage precursors (immature myeloid cells) and monocytes into peripheral blood, but normally not monoblasts or promonocyts. The myeloid precursor cells migrate into tissues and differentiate into resident macrophages or related cells in situ due to macrophage differentiation or growth factors, such as M-CSF and GM-CSF, produced in situ and/or supplied humorally. Monocytes, however, migrate into tissues in response to inflammatory stimuli and differentiate into exudate macrophages. The distinct differentiation pathways of monocyte/macrophages, resident macrophages, other macrophage subpopulations, and macrophage-related cells are reviewed together with the heterogeneity of macrophage precursor cells.

Animals↗
PubMed1996

Mechanism of nonlinear responses of taste cells to mixed tastes.

Coupling between ionic flows through different kinds of channels affects essentially the responses of multisensitive taste cells to single- and mixed-taste stimuli. The mechanism of taste transduction is studied by using a realistic model of the multisensitive cells of the rat. The transduction pathways considered are amiloride-sensitive Na+ channels for NaCl and HCl and adenosine 3',5'-cyclic monophosphate-mediating K+ channels for sucrose. Contributions of paracellular pathways and taste-insensitive ionic channels are also studied. The calculated responses of various multisensitive cells induced by single stimuli of NaCl, HCl, or sucrose reproduce experimentally observed responses as well. The two main conclusions are as follows. 1) Whether the response of a cell to a binary mixture becomes synergetic or antagonistic can be estimated from the individual responses of the cell to each component of the mixture. 2) Whether the response is enhanced or suppressed by addition of a new taste to the original taste can be determined, for most receptive cells, from a viewpoint of linear superposition of the individual responses.

Animals↗
PubMed1996

Effects of macrophage colony-stimulating factor on macrophages and their related cell populations in the osteopetrosis mouse defective in production of functional macrophage colony-stimulating factor protein.

The development of macrophage populations in osteopetrosis (op) mutant mice defective in production of functional macrophage colony-stimulating factor (M-CSF) and the response of these cell populations to exogenous M-CSF were used to classify macrophages into four groups: 1) monocytes, monocyte-derived macrophages, and osteoclasts, 2) MOMA-1-positive macrophages, 3) ER-TR9-positive macrophages, and 4) immature tissue macrophages. Monocytes, monocyte-derived macrophages, osteoclasts in bone, microglia in brain, synovial A cells, and MOMA-1- or ER-TR9-positive macrophages were deficient in op/op mice. The former three populations expanded to normal levels in op/op mice after daily M-CSF administration, indicating that they are developed and differentiated due to the effect of M-CSF supplied humorally. In contrast, the other cells did not respond or very slightly responded to M-CSF, and their development seems due to either M-CSF produced in situ or expression of receptor for M-CSF. Macrophages present in tissues of the mutant mice were immature and appear to be regulated by either granulocyte/macrophage colony-stimulating factor and/or interleukin-3 produced in situ or receptor expression. Northern blot analysis revealed different expressions of GM-CSF and IL-3 mRNA in various tissues of the op/op mice. However, granulocyte/macrophage colony-stimulating factor and interleukin-3 in serum were not detected by enzyme-linked immunosorbent assay. The immature macrophages differentiated and matured into resident macrophages after M-CSF administration, and some of these cells proliferated in response to M-CSF.

Animals↗
PubMed1996

[Cancer chemotherapy and apoptosis].

Tumor cells undergo apoptotic cell death when treated with several chemotherapeutic agents. Since these agents, acting on different cellular targets, induce a similar pattern of cell death (apoptosis), it is suggested that a common signaling pathway of apoptosis could exist and that apoptosis resistance could cause a new form of multi-drug resistance in tumor cells. Although the mechanisms of apoptosis are not fully understood, the involvement of ICE/ced-3 family proteases in chemotherapy-induced apoptosis is strongly suggested. Identification of factors directly acting on these apoptosis pathway will offer new strategies in cancer chemotherapy.

Actins↗
PubMed1996

Positive reaction of monoclonal antibody (TO73) with resistant leukemic cells.

We previously reported the characteristics of a murine monoclonal antibody (TO73) against the multidrug-resistant (MDR) human leukemic cell line. In the present study, we have studied the clinical significance of TO73 by examining its reactivity with primary and relapsed leukemic cells. Of 20 patients with primary leukemia and 15 patients with relapsed leukemia, none and four cases, respectively, reacted with TO73 (p < 0.05). Furthermore, three of the four positive cases were also positive for P-glycoprotein. These results indicate that TO73 preferentially reacts with leukemic cells resistant to chemotherapy and may be a new marker for refractory leukemia.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Physiological concentration of 17 beta-estradiol inhibits chemotaxis of human monocytes in response to monocyte chemotactic protein 1.

While estrogen is known to retard the development of atherosclerosis, the exact mechanism is unknown. The migration of monocytes into the arterial intima is important in the pathogenesis of atherosclerosis. Monocyte chemotactic protein 1 (MCP-1) is suggested to be a real chemotactic factor that is released from monocytes, endothelial cells, and smooth muscle cells. We investigated the effect of 17 beta-estradiol on the migration of human monocytes in response to MCP-1, using a modified Boyden chamber. A physiological concentration of 17 beta-estradiol (10(12) - 10(4)M) inhibited the migration of monocytes exposed to MCP-1. Two estrogen receptor antagonists, tamoxifen and clomiphene, each restored monocyte chemotaxis to MCP-1 to control level, even in the presence of 17 beta-estradiol, suggesting that estrogen receptors are related to the effect of 17 beta-estradiol. Progesterone and testosterone had no measurable effect on monocyte migration. These findings suggest that inhibition of the chemotactic response of monocytes exposed to MCP-1 may be one mechanism for the anti-atherogenic effect of 17 beta-estradiol.

Arteriosclerosis↗
PubMed1996

[Efficacy of cefditoren pivoxil in the treatment of acute otitis media due to benzylpenicillin-insensitive Streptococcus pneumoniae].

Clinical and bacteriological studies were carried out on cefditoren pivoxil (CDTR-PI) granule in infantile purulent acute otitis media treated at general practice settings and the following findings were obtained: 1. Two hundred forty eight strains were isolated from 210 patients, almost all of which (81.1%) harbored the following two strains: Streptococcus pneumoniae (42.3%) and Haemophilus influenzae (38.8%). Among S. pneumoniae, benzylpenicillin (PCG)-insensitive S. pneumoniae, (PISP) or PCG-resistant S. pneumoniae (PRSP) was 36.2%, corresponding to 15.3% of all the isolates and found in 18% of all patients. 2. The bacteria in the middle ear discharge and the nasopharyngeal swabs were correlated with conformity rate of more than 80% with regard to Streptococcus pyogenes, S. pneumoniae and H. influenzae but no Staphylococcus aureus was detected simultaneously from the two sources in any of the patients. S. aureus and coagulase-negative staphylococci (CNS) were considered to be contaminants that were originated from the external auditory meatus at the time of sampling. 3. Frequencies of isolation of S. pneumoniae from different age groups were higher in a lower age group between 0 and 4 years and those of PISP or PRSP had the similar tendency. 4. Antibacterial activities were determined for CDTR and related oral antibiotics against the strains of S. pneumoniae and H. influenzae as representative isolates. CDTR had stronger antibacterial activities against both bacteria than the reference antibiotics. CDTR was found to be transferred into the otorrhea at a mean concentration of 0.58 micrograms/ml after single administration of CDTR-PI granule formulation at 3 mg(potency)/kg. 5. As for bacterial eradication efficacies in the middle ear cavity and the nasopharynx, eradication rates were higher than 80% in the middle ear cavity in all cases without large differences among bacterial species but eradication rate of PISP was 30% in the nasopharynx, and it was significantly lower than those of PSSP and other bacteria. 6. In view of clinical effectiveness, the efficacy rate was 89.4% and bacteriological effects was 92.2%; in view of safety, adverse reactions were; observed in 9.5% and the rate of usefulness was 89.4%. 7. From above-stated results, CDTR-PI was considered as a useful oral antibiotic for infantile acute otitis media including PISP infections.

Acute Disease↗
PubMed1996

Repopulation of murine Kupffer cells after intravenous administration of liposome-encapsulated dichloromethylene diphosphonate.

Kupffer cells were selectively eliminated in mice by the intravenous administration of liposome-entrapped dichloromethylene diphosphonate. At 5 days, small peroxidase-negative and acid-phosphatase-weakly-positive macrophages appeared, increased in number, and differentiated into peroxidase- and acid-phosphatase-positive Kupffer cells. Repopulating small macrophages actively proliferated, and the number of Kupffer cells returned to the normal level by day 14. The numbers of macrophage precursors in the liver as detected by the monoclonal antibodies ER-MP20 and ER-MP58 increased after liposome-entrapped dichloromethylene diphosphonate injection. ER-MP58-positive cells proliferated and differentiated into ER-MP20-positive cells and eventually into BM8-positive Kupffer cells in the liver. Bone-marrow-derived ER-MP58-positive cells were also detectable in the liver and differentiated into ER-MP20-positive cells, but they did not become BM8-positive macrophages. Macrophage colony-stimulating factor mRNA expression was enhanced in the liver 1 day after injection. The administration of macrophage colony-stimulating factor did not shorten the period of Kupffer cell depletion but increased the number and the proliferative capacity of repopulating Kupffer cells. These findings implied that repopulating Kupffer cells are derived from a macrophage precursor pool in the liver rather than from bone-marrow-derived monocytes. Local production of macrophage colony-stimulating factor in the liver plays a crucial role in the differentiation, maturation, and proliferation of Kupffer cells.

Animals↗
PubMed1996

[Natural history of cloudy zone of pulmonary adenocarcinoma on HRCT].

Seven pulmonary adenocarcinomas with cloudy zone (CZ), which was defined as a lower density zone in the pulmonary lesion than pulmonary vessels in the surrounding normal lung on high resolution computed tomography (HRCT), were followed up for at least 3 months. There were three tumors with homogeneous CZ, one of which showed no change when rescanned after three months, the others showed enlargement with or without replacement by high density areas on rescanned images obtained after more than one year. Two tumors containing some high density areas on the initial scans showed slight decreases in size on rescanned images obtained after 1 to 3 months. However, on rescanned images obtained after more than 1 year and 9 months, these tumors also showed enlargement of CZ. Pathologically, CZs corresponded to well-differentiated adenocarcinoma of the bronchioloalveolar type with no or mild interstitial change, whereas high density areas mainly corresponded to papillary adenocarcinoma with severe interstitial fibrosis. In conclusion, long-term careful follow-up of CZ is necessary to detect enlargement or the appearance of high density. Unchanged CZ in short-term follow-up should be considered a finding suggestive of malignancy.

Adenocarcinoma, Papillary↗
PubMed1996

Neonatal changes of osteoclasts in osteopetrosis (op/op) mice defective in production of functional macrophage colony-stimulating factor (M-CSF) protein and effects of M-CSF on osteoclast development and differentiation.

In mice homozygous for the osteopetrosis (op) mutation, loss of osteoclasts in the postnatal period and their development, differentiation, and maturation following daily M-CSF administration in adult life were investigated. Histochemical, immunohistochemical, and ultrastructural approaches, as well as [3H]thymidine autoradiography, clarified the role of M-CSF on osteoclast development and differentiation. In op/op mice osteoclasts appeared normal at birth. However, osteoclast numbers were reduced within a few days after birth, and osteoclasts were undetectable by 3-4 days of age. In adult op/op mice there were no multinuclear osteoclasts; however, small numbers of mononuclear cells (so-called 'preosteoclasts') were observed on the endosteal surface of bone. These preosteoclasts expressed tartrate-resistant acid phosphatase and showed ultrastructural features of immature osteoclasts. After daily M-CSF administration in op/op mice, osteoclasts developed from the fusion of preosteoclasts and osteoclasts numbers increased to the levels of normal littermates at 3 days. Autoradiographic analysis with [3H]thymidine revealed no labeling in osteoclasts and preosteoclasts. In the mutant mice, M-CSF administration induced numerical increases of monocytes, promonocytes, and earlier precursor cells in bone marrow, ER-MP12- or, ER-MP58-positive granulocyte/macrophage colony-forming cells (GM-CFCs). Among these macrophage precursors, ER-MP58-positive cells were considered preosteoclast precursors, and possessed marked proliferative potential. These data suggest that an ER-MP58-positive cell subpopulation of GM-CFCs proliferates in response to M-CSF, differentiates into preosteoclasts which fuse with each other to develop into mature osteoclasts.

Animals↗
PubMed1996

Long-term culture of avian embryonic cells in vitro.

The pH of the embryonic blood, one of the most important environmental factors for embryonic cells, was found to range from 8.1 to 8.5 in chick embryos until 108 h after incubation. Based on these results, the culture medium adjusted to pH 8.0 was used to culture embryonic chick and quail cells. They were easily subcultured for a long period of time at pH 8.0. This pH culture condition may have wide application for manipulating embryonic cells or tissues and establishing cell lines from avian embryos.

Animals↗
PubMed1995

Identification of actin as a substrate of ICE and an ICE-like protease and involvement of an ICE-like protease but not ICE in VP-16-induced U937 apoptosis.

Human leukemia U937 cells are induced to undergo apoptosis by several chemotherapeutic agents; however, the cellular components involved in the process have not yet been identified. We found that an actin-cleavage activity (ACA) was activated in the VP-16-treated U937 cytosolic fraction and 15K- and 30K-actin fragments were produced. This ACA was inhibited by inhibitors of interleukin-1 beta-converting enzyme (ICE)/ced-3 family proteases, such as Z-Asp-CH2-DCB, YVAD-CHO, TPCK, TLCK, and iodoacetamide. Differing from ICE, the ACA could not process pro-IL-1 beta to mature IL-1 beta. Although ICE can cleave actin in vitro, ICE activity was not activated in the VP-16 treated U937 cells. These results indicate that actin is a potential substrate of ICE and ICE-like proteases, and that VP-16 preferentially activate an ICE-like protease, but not ICE itself, in U937 cells.

Actins↗
PubMed1995

Involvement of CD45 in adhesion and suppression of apoptosis of mouse malignant T-lymphoma cells.

Mouse malignant T-lymphoma CS-21 cells undergo apoptotic cell death in vitro in the absence of lymph node stromal cells but escape apoptosis and proliferate when they are attached to CA-12 stromal cells. A monoclonal antibody raised against CS-21 cell surface molecules (MCS-5) recognized a M(r) 168,000 protein, inhibited binding of CS-21 cells to CA-12 stromal cells, and suppressed apoptosis in CS-21 cells. To identify the M(r) 168,000 protein, we purified it with MCS-5 affinity chromatography and ion exchange chromatography. Partial amino acid sequences of the purified M(r) 168,000 protein were identical to those of CD45, a transmembrane tyrosine phosphatase. The purified protein possessed tyrosine phosphatase activity and was recognized by an anti-CD45 monoclonal antibody. The M(r) 168,000 protein was identified as CD45. To determine the CD45 isoform, we cloned the CD45 gene from the cDNA library of CS-21. Sixteen of 18 clones encoded CD45RO (CD45 lacking exons 4, 5, and 6), and the remainder lacked exons 4, 5, 6, and 7. Like MCS-5, an anti-CD45 monoclonal antibody, also inhibited binding of CS-21 cells to CA-12 cells and suppressed apoptosis in CS-21 cells. Our present results indicate that CD45RO expressed on CS-21 cells mediates adhesion to CA-12 cells and suppression of apoptosis.

Amino Acid Sequence↗
PubMed1995

Aspartate-based inhibitor of interleukin-1 beta-converting enzyme prevents antitumor agent-induced apoptosis in human myeloid leukemia U937 cells.

We found that a novel protease inhibitor, benzyloxycarbonyl-Asp-CH2OC(O)-2,6-dichlorobenzene (Z-Asp-CH2-DCB), which can preferentially inhibit interleukin-1 beta-converting enzyme (ICE), completely blocked the apoptotic cell death of human myeloid leukemia U937 cells caused by etoposide, camptothecin, 1-beta-D-arabinofuranosyl-cytosine and Adriamycin, as well as TNF-alpha, anti-Fas antibody and staurosporine. However, Z-Asp-CH2-DCB did not block non-apoptotic cell death of U937 cells caused by etoposide during prolonged incubation periods. These results indicate that ICE or ICE-like proteases inhibited by Z-Asp-CH2-DCB are involved in a common pathway of apoptotic cell death in U937 cells.

Antineoplastic Agents↗
PubMed1995

Protective effects of probucol against glutamate-induced cytotoxicity in neuronal cell line PC12.

The sympathetic nerve cell line PC12 is reportedly destroyed by glutamate in a concentration-dependent manner. In this study, cytotoxicity induced by 10 mM glutamate was blocked in a dose-dependent manner by incubating or pre-incubating cells with the antioxidant probucol (1-50 microM). Probucol also inhibited the increase in cellular thiobarbituric acid-reacting substances induced by glutamate exposure. These results suggest that the propagation of cellular lipid peroxidation may be related to glutamate-induced toxicity in PC12 cells.

Animals↗