Biomedical subjects

H Shinoda

Publications and source records attributed to H Shinoda.

At least 73 records · Page 4Linked to original sources

PubMed1994

Role of endogenous PGE2 in osteoblastic functions of a clonal osteoblast-like cell, MC3T3-E1.

MC3T3-E1 cells actively synthesized and released prostaglandin E2 (PGE2) during culture. PGE2 release was minimal on day 9 and gradually increased with culture up to day 27. DNA content gradually increased until day 27. Alkaline phosphatase (ALP) activity increased up to day 15 and decreased thereafter. In contrast to the decrease in ALP activity, calcium accumulation increased rapidly after day 21, possibly due to mineralization by the cells. Indomethacin, a cyclooxygenase inhibitor, blocked PGE2 production completely at concentrations higher than 0.3 mumol/L. In the presence of indomethacin (3 mumol/L), DNA content was slightly decreased on day 27. Furthermore, ALP activity on day 15 was greater than that of the control and this high activity was maintained until day 27. However, calcium accumulation was not affected by the addition of indomethacin. These results suggest that endogenous PGE2 down-regulates ALP activity and slightly stimulates the proliferation of MC3T3-E1 cells as an autocrine mediator, although it does not directly influence the cells' mineralizing activity.

Alkaline Phosphatase↗

PubMed1994

Anchorage and retentive effects of a bisphosphonate (AHBuBP) on tooth movements in rats.

The purpose of this study was to examine the effect of 4-amino-1-hydroxybutylidene-1,1-bisphosphonate (AHBuBP), a potent blocker of bone resorption, on orthodontic tooth movements in rats. In the first experiment, the right and left upper first molars were moved buccally for 3 weeks with a uniform standardized expansion spring under systemic administration of AHBuBP every other day. The total tooth movement during the 3-week experimental period was 40% of that in the control at a dose of 0.5 mg P/kg. In the second experiment, the right and left upper first molars were first moved buccally for 3 weeks without AHBuBP. The spring was then removed and administration of AHBuBP was initiated. The total relapse movement during the 3-week experimental period was 50% of that in the control at a dose of 0.5 mg P/kg. Results of the first and second experiments were both dose dependent. Histologic examination showed that in the experimental animals fewer osteoclasts appeared on the alveolar bone surface, and both bone resorption and root resorption were inhibited. Inhibition of tooth movement was also observed when AHBuBP was applied topically. These results suggest that AHBuBP could be useful in enhancing anchorage or retaining teeth in orthodontic treatment.

Alendronate↗

PubMed1994

Effects of topical administration of a bisphosphonate (risedronate) on orthodontic tooth movements in rats.

In orthodontics, undesirable movement of anchor teeth during tooth movement and relapse of moved teeth after treatment are the main causes of unsuccessful results. If these tooth movements could be prevented with pharmacological agents, a less complex orthodontic force system and less extensive retention would be required. The purpose of this study was to examine the effect of topical administration of a bisphosphonate (risedronate), a potent blocker of bone resorption, on orthodontic tooth movements in rats. In the first experiment, both the right and left upper first molars were moved buccally with a standardized expansion spring under administration of risedronate. Risedronate solution was injected into the subperiosteum area adjacent to the left upper first molar. The right first molar served as a control with an injection of 0.9% NaCl solution. The topical administration of risedronate caused a significant and dose-dependent reduction of tooth movement after the orthodontic force was applied. In the second experiment, the right and left upper molars were first moved buccally for three weeks. The spring was then removed, and administration of risedronate was begun. The topical administration of risedronate inhibited relapse of the tooth in a dose-dependent manner. The administration of risedronate did not affect either overall growth of the animals or longitudinal growth of tibiae. These results suggest that topical application of risedronate may be helpful in anchoring and retaining teeth under orthodontic treatment.

Administration, Topical↗

PubMed1994

[Establishment and characterization of strain KE-39 derived from human gastric cancer].

We succeeded in establishing a human gastric carcinoma cell line (KE-39) from oncocytes obtained from the primary focus of a 77-year-old male stomach cancer patient. From a histopathological point of view the gastric carcinoma was a poorly differentiated adenocarcinoma exhibiting a funicular from and a structure with a solid vesicular focus. The oncocytes adhered to glass and proliferated in cell clusters, with a doubling time of about 38.4 hours. Upon transplantation of the cancer cells into nude mice, no visible tumors were found, but from a histological point of view poorly differentiated adenocarcinoma similar to the primary focus was found in all cases. With immunological staining they were found to be positive for anti-CEA antibody and anti-CA19-9 antibody, but negative for anti-ICAM-1 antibody. KE-39 is a cell line which was established from the primary focus, and it was reported in the belief that it is a useful cell line, upon the investigation of its cancer metastasis mechanism and cytological characteristics.

Adenocarcinoma↗

PubMed1994

Effects of intracerebroventricular administration of N-acetylhistamine on body temperature in mice.

The purpose of this study was to examine the effects of intracerebroventricular (i.c.v.) administration of N-acetylhistamine on rectal temperature, histamine level, histidine decarboxylase (HDC) activity, and the turnover rate of monoamines in mice. More than 60 micrograms of N-acetylhistamine induced hypothermia. The maximum effect of hypothermia was observed 20 min after administration of N-acetylhistamine (60-120 micrograms/mouse). A significant drop in rectal temperature of 3 degrees C was induced by 120 micrograms of N-acetylhistamine. Concurrent with the appearance of hypothermia, the histamine levels were increased. However, both histamine H1 and H2 antagonists did not prevent hypothermia. The i.c.v. administration of N-acetylhistamine inhibited HDC activity, but had no effect on the turnover rates of monoamines. These data confirmed that endogenous N-acetylhistamine may be a metabolite which lacks significant physiological roles, and demonstrated that exogenous N-acetylhistamine is not a good pharmacological tool for the study of the functions of the brain histaminergic system in mammals.

Animals↗

PubMed1993

Activin enhances osteoclast-like cell formation in vitro.

The effect of activin (activin A/EDF) on osteoclast formation was investigated. In mouse bone marrow cell cultures, activin enhanced the formation of tartrate-resistant acid phosphatase (TRACP)-positive multinucleated cells (MNC) in a dose-dependent manner, either in the presence or absence of 1,25-(OH)2D3 or PTH. In organ cultures of neonatal mouse calvaria, activin also enhanced the generation of TRACP-positive giant cells in the endosteal periosteum and increased the TRACP staining of whole calvaria, but did not exhibit bone resorbing activity. These results indicate that activin stimulates the formation of osteoclasts, but not osteoclast activation. Activin is produced by bone marrow cells and might be involved in the local process of osteoclast differentiation.

Acid Phosphatase↗

PubMed1993

Aminoalkylbisphosphonates, potent inhibitors of bone resorption, induce a prolonged stimulation of histamine synthesis and increase macrophages, granulocytes, and osteoclasts in vivo.

Aminoalkyl derivatives of bisphosphonates are potent inhibitors of bone resorption. A single I.P. injection of 4-amino-1-hydroxybutylidene-1,1-bis-phosphonate (AHBuBP) induced a prolonged enhancement of histidine decarboxylase (HDC) activity in the bone marrow, spleen, lung, and liver of mice and resulted in an increase in histamine. The induction of HDC by the agent was dose dependent (16-80 mumol/kg) and peaked 3-4 days after its injection (40 mumol/kg). Repeated S.C. injections of smaller doses of AHBuBP (0.32 or 1.6 mumol/kg/day) for 4 days also enhanced HDC activity. However, the minimum dose capable of inhibiting bone resorption (0.064 mumol/kg/day) was lower than that inducing HDC. Unexpectedly, AHBuBP, at the doses inducing HDC, increased macrophages, granulocytes, and even osteoclasts. The size of osteoclasts was also enlarged by the agent. Another aminobisphosphonate, 3-amino-1-hydroxypropylidene-1,1-bisphosphonate, but none of non-amino derivatives, also exhibited essentially the same effects as those of AHBuBP. These results indicate that in spite of increase in osteoclasts and their enlargement, bone resorption is still inhibited by amino bisphosphonates. As granulocyte and granulocyte-macrophage colony-stimulating factors and interleukin-3 induce HDC in hematopoietic organs, and histamine has a hematopoietic activity, the HDC induction by aminobisphosphonates may be relevant to the proliferation of progenitor cells of macrophages, granulocytes, and osteoclasts.

Alendronate↗

PubMed1993

Roles of prostacyclin, EDRF and active oxygens in leukocyte-dependent platelet adhesion to endothelial cells induced by platelet-activating factor in vitro.

1. The mechanism of polymorphonuclear leukocyte (PMN)-dependent platelet adhesion to cultured endothelial cells induced by platelet-activating factor (PAF) was investigated to determine whether PMNs release or generate any factor(s) capable of inducing platelet adhesion, and the roles of prostacyclin and endothelium-derived relaxing factor (EDRF). 2. Cell-free supernatants, sonicates or rapid filtrates of PAF-stimulated PMN suspensions did not induce platelet adhesion to endothelial cells, but the PMN sonicates induced platelet adhesion when endothelial cells were pretreated with both aspirin and NG-nitro-L-arginine (L-NOARG). Its microphotograph showed that mainly platelet aggregates adhered to the endothelial cell surface. 3. Platelet adhesion induced by the PMN sonicates to aspirin- and L-NOARG-pretreated endothelial cells was dose-dependently prevented by OP-41483 (1-100 nM), and slightly by L-arginine (1 mM). The inhibition of platelet adhesion by OP-41483 and L-arginine was potentiated by their combination. 4. WEB 2170 (3 microM), a PAF antagonist, inhibited platelet adhesion induced by the PMN sonicates. However, PAF alone did not induce significant platelet adhesion to aspirin- and L-NOARG-treated endothelial cells. 5. Platelet adhesion induced by the PMN sonicates was not suppressed by AA-861 and indomethacin. However, both superoxide dismutase and catalase significantly inhibited platelet adhesion, and, in combination, their inhibitory effect was synergistically potentiated. Mannitol had no effect. It was also significantly inhibited by alpha 1-antitrypsin, whereas chymostatin and elastatinal had no effect. 6. PAF-induced platelet adhesion to endothelial cells in the presence of intact PMNs was not suppressed by indomethacin and AA-861, or by protease inhibitors. SOD alone, and in combination with catalase, caused a slight but significant inhibition, while catalase and mannitol by themselves had no effect.7. PMN-induced platelet adhesion was slightly inhibited by OP-41483 (100 nM). L-Arginine (1 mM)alone had no effect, but slightly potentiated the effect of OP-41483. This platelet adhesion was not accompanied by suppression of prostacyclin synthesis.8. The results with the PMN sonicates show that prostacyclin, EDRF and active oxygens are important modulators of intercellular interactions between platelets and endothelial cells. These results further suggest that the mechanism of intact PMN-dependent platelet adhesion is primarily through platelet endothelial cell interactions in which leukocyte-derived active oxygens play a role, but does not involve platelet-platelet interactions inhibitable by prostacyclin.

Animals↗

PubMed1992

Developmental expression of the proenkephalin and prosomatostatin genes in cultured cortical and cerebellar astrocytes.

Astrocytes were prepared from rats of 4 ages, embryonic day 20, postnatal days 3 and 8, and adult, in order to study the developmental time course of expression of enkephalin and somatostatin (SS). Glial fibrillary acidic protein (GFAP) content was constant in both cortical and cerebellar astrocytes prepared from all ages. SS mRNA and peptide decreased over this developmental time course in cerebellar astrocytes; the time course of changes in SS mRNA paralleled that for rat cerebellum. Proenkephalin (PE) mRNA increased about 3-fold in cerebellar astrocytes from embryonic day 20 to adult but remained constant in cortical astrocytes; in contrast, PE mRNA showed a 10- to 12-fold increase in rat cerebellum and cortex developmentally. For both cerebellar and cortical astrocytes, free met-enkephalin decreased from embryonic day 20 to adult, whereas total met-enkephalin (measured following trypsin-carboxypeptidase B digestion of the extracts) increased. These results suggest (1) that there is a developmental regulation of the expression of both enkephalin and SS peptides in astrocytes, and (2) that the regulation occurs at the level of transcription for SS but at the level of precursor processing for PE. Possible trophic functions for astrocyte-derived peptides early in CNS development are discussed.

Aging↗

PubMed1992

Determination of histamine and polyamines in calcified tissues of mice: contribution of mast cells and histidine decarboxylase to the amount of histamine in the bone.

A simple method for determining histamine and polyamines in various tissues was devised. The method, however, could not be applied to calcified tissues, because the high concentration of Ca2+ in the extract interferes with the chromatographic separation of these amines. By treating the extracts from calcified tissues with K2CO3, we succeeded in removing the Ca2+, and the method could then be applied to determine the amines in bone tissues of mice. By using this method, we examined the contribution of mast cells and histidine decarboxylase (HDC) to the amount of histamine in the bone. The results indicate that (1) the HDC activity in the bone is the highest among the tissues of normal mice, and the histamine produced by the HDC in the bone is metabolized rapidly; (2) a major part of HDC in the bone is present in the bone marrow cells other than mast cells, and most of histamine in the bone is attributable to the histamine pooled in mast cells; (3) mast cells in the diaphysis are located largely along the endosteal lining; and (4) the method devised in this study may be useful for studying the roles of histamine (or mast cells) and polyamines in calcified tissues.

Animals↗

PubMed1992

Therapeutic efficacy of combination of antitumor agent with AHC-52 against multidrug-resistant cells in the intravenously inoculated P388 leukemia model.

To predict the clinical effect on leukemic disease of a combination regimen developed to circumvent multidrug resistance (MDR), we tested various antitumor agents in the presence and absence of AHC-52, a sensitizing agent for multidrug-resistant cells, in the i.v.-i.v. model of murine leukemia. In this model system, sensitive and resistant P388 murine leukemia cells are inoculated i.v. into mice, and each antitumor agent is injected via the i.v. route. Vincristine (VCR) had no effect on the survival of mice bearing VCR-resistant P388, a relatively poorly resistant subline, when given either as a single agent or in combination with AHC-52. In contrast, adriamycin (ADR) alone had no effect on these mice, but its combination with AHC-52 resulted in significant survival, the maximal value achieved being 196% (treated mice/control animals, T/C). Etoposide (VP-16) strongly enhanced survival, even when used alone, and this effect was markedly potentiated by AHC-52. Combination of any antitumor drug with AHC-52 was ineffective in mice bearing ADR-resistant P388, a highly resistant subline. On the other hand, AHC-52 strongly augmented the therapeutic efficacy of these antitumor agents in mice bearing the sensitive parent P388 leukemia, producing some curative effects. On the basis of these results, the feasibility of this type of combination therapy is discussed.

Animals↗

PubMed1992

Diurnal rhythms in Ca transfer into bone, Ca release from bone, and bone resorbing activity in serum of rats.

To characterize diurnal rhythms in calcium transfer in and out of bone, rats were adapted to a 12:12 h light-dark illumination program (with light from 0600 to 1800 h). For studies of deposition, rats were injected with 45CaCl2 at 0300, 0700, 1100, 1500, 1900 or 2300 h and killed with chloroform inhalation 60 min later, and radioactivity was determined in tibia and mandibular incisor. Peak deposition occurred at 2400 h, with a nadir at 1200 h. For studies of radionuclide release, rats were prelabeled with 45CaCl2 for 6 days and serum obtained from the tail at 4-h intervals. 45Ca and specific activity were maximal around 1200-1600 h and lowest late in the dark period. To determine the role of humoral factor(s), fetal rat limb bones were cultured in media prepared with sera from light-dark-adapted rats. Activity was maximal in serum collected at 0800 h and minimal at 1600 h. Heat inactivation at 100 degrees C for 5 min eliminated the difference between the peak and nadir. The results suggest that a heat-sensitive humoral factor(s) regulates diurnal rhythms in calcium metabolism.

Animals↗

PubMed1992

Antagonism of platelet-activating factor-induced increase in cytosolic free calcium concentration in human endothelial cells.

The effects of platelet-activating factor (PAF) antagonists on the agonist-induced increase in cytosolic free calcium concentration, [Ca2+]i, in human vascular endothelial cells grown in monolayer were investigated by a continuous superfusion technique using a calcium fluorescent probe, fura-2. PAF caused a small but dose-dependent increase in [Ca2+]i. Seven structurally dissimilar PAF antagonists dose-dependently suppressed the peak response, among which WEB 2086 was the most potent, followed by WEB 2170 greater than FR 900452 not equal to ONO 6240 greater than BN 52021 not equal to kadsurenone not equal to CV 3988. These antagonists except for CV 3988 were specific for PAF, since they had no effects on calcium mobilization induced by thrombin or histamine, while CV 3988 had a non-specific effect. PAF in the same range of concentration increased prostacyclin release from human endothelial cells. WEB 2086 also inhibited the PAF-induced prostacyclin release, while it had not effect on the release induced by histamine and thrombin. These results demonstrate the specificity and dose-response characteristics of PAF antagonists in cultured human endothelial cells and suggest that a PAF antagonist could be a valuable therapeutic agent in certain human diseases where PAF activation of endothelial cells may have a critical role.

Calcium↗

PubMed1991

Pharmacological characteristics of catalepsy induced by intracerebroventricular administration of histamine in mice: the importance of muscarinic step in central cholinergic neurons.

Histamine-induced catalepsy was antagonized potently by scopolamine, an antimuscarinic drug, and partially blocked by sparteine. Neither methylatropine nor antinicotinic drugs could reverse histamine-induced catalepsy. These results indicate the greater importance of muscarinic receptors rather than their nicotinic counterparts in histamine-induced catalepsy. Various antiparkinson drugs, i.e. biperiden and trihexyphenidyl, which have antimuscarinic activity or dopamine agonists, i.e. L-dopa, amantadine and bromocriptine, could antagonize the histamine-induced catalepsy to various degrees. Thus, catalepsy induced by icv histamine can be evoked not only by an activation of the histamine receptor, but also indirectly due to cholinergic and dopaminergic imbalance.

Amantadine↗

PubMed1991

Alterations in somatostatin and proenkephalin mRNA in response to a single amygdaloid stimulation versus kindling.

Previous studies have shown changes in both somatostatin (SS)- and proenkephalin(PE)-derived peptides in the brains of amygdaloid-kindled rats, suggesting possible roles for the peptides in the kindling process. In this study, we have extended this analysis by looking at the time course of changes in SS and PE mRNAs at various times after kindling, in comparison with a single non-convulsive stimulation. Blot analysis of total RNA showed increases in SS mRNA in striatum, frontal cortex and hippocampus of animals receiving only a single stimulation as well as kindled animals--the increase occurred 1-3 days following stimulation and levels were back to basal by 1 week. PE mRNA did not change. In situ hybridization analysis, one day after the last kindling stimulation, showed significant elevations of SS mRNA in CA1, CA2 and dentate gyrus of hippocampus and of PE mRNA in olfactory cortex that were specific to kindling. However, both a single stimulation and kindling increased PE mRNA in olfactory tubercle and arcuate nucleus. In contrast, a single electrical stimulus increased PE mRNA in ventral striatum and SS mRNA in cingulate cortex and olfactory tubercle. These data support the idea that changes of SS mRNA in hippocampus and of PE mRNA in olfactory cortex may be related to kindling, and point out the importance of using animals which receive a single electrical stimulus, rather than sham-operated animals, as controls.

Amygdala↗

PubMed1991

Platelet-leukocyte interaction in adhesion to endothelial cells induced by platelet-activating factor in vitro.

1. Platelet-activating factor (PAF, 10 nM) did not induce platelet adhesion to endothelial cells cultured in monolayer but it induced their adhesion to protein-coated plastic. However, PAF induced a marked platelet adhesion to endothelial cells when polymorphonuclear leukocytes (PMNs) were present. Lyso-PAF had no effect. 2. Phase-contrast microscopic examination showed that single platelets rather than their aggregates adhered to the endothelial cell surface around aggregating and adhering PMNs. 3. Significant platelet adhesion was induced by PAF at concentrations higher that 0.01 nM with the maximal response at 10 nM. Platelet adhesion occurred within minutes after PAF addition, reaching a maximum approximately after 30 min. Platelet adhesion also occurred significantly at a PMN:platelet ratio of 1:800, and linearly up to 1:50. 4. The PAF-induced platelet adhesion was suppressed by three structurally unrelated PAF antagonists, WEB 2086, ONO 6240 and BN 52021, in a concentration-dependent manner. 5. PAF also increased PMN adhesion to endothelial cell monolayers, which was further augmented by the presence of platelets. 6. The present study demonstrates that PAF induces platelet adhesion to endothelial cells in vitro when PMNs are present and that there is a close interaction between platelets and PMNs in their adhesion to endothelial cells. The present study further suggests that PMNs could play a central role in platelet adhesion to vascular endothlium in certain pathological conditions.

Adenine↗

PubMed1991

Effect of HEBP (1-hydroxyethylidene-1,1-bisphosphonate) on experimental osteoporosis induced by ovariectomy in rats.

The present study was undertaken to test whether long term administration of HEBP could prevent the progress of bone loss induced by ovariectomy in rats. Administration of HEBP was started from day 111 after ovariectomy. The animals received subcutaneous injections of HEBP, at a dose of 0, 2, 4, or 8 mg/kg, every other day for 92 days. Tibiae, femora and incisor teeth were investigated by chemical analyses and by contact microradiography. Effects on calcium, phosphorus, and alkaline phosphatase activity in the plasma were also examined. Progress in the loss of bone density and ash content caused by ovariectomy was prevented by the administration of 2 mg/kg HEBP for 92 days and was partially prevented by the administration of 4 mg/kg. At a dose of 8 mg/kg, however, HEBP did not prevent the bone loss but, rather, potentiated it. These chemical findings were qualitatively confirmed by contact microradiography. A dose-dependent inhibition was observed in the mineralization of incisor dentin. These results suggest that HEBP, at least at low dose levels in which the inhibition of mineralization is not predominant, has a potency to prevent the progress of bone loss induced by ovariectomy. At higher doses, however, this compound seems not to be effective, because of the severe inhibition of mineralization.

Animals↗

PubMed1991

PAF-mediated platelet adhesion to endothelial cells induced by FMLP-stimulated leukocytes.

N-formyl-methionyl-leucyl-phenylalanine (FMLP), but not leukotriene B4 (LTB4), induced a significant platelet adhesion to endothelial cell monolayer when polymorphonuclear leukocytes (PMNs) were present in vitro. Neither of FMLP and LTB4 had an effect on the platelet adhesion in the absence of PMNs. An antagonist of platelet-activating factor (PAF), WEB 2086 completely inhibited the platelet adhesion induced by FMLP, while indomethacin and AA-861 had no effect. These results suggest that PMN-dependent platelet adhesion to endothelial cells induced by FMLP is mediated by PAF, and that PAF plays an important role during cell-cell interactions among platelets, PMNs and endothelial cells.

Azepines↗