[A case of Crohn's disease with a complication of thrombosis in the inferior vena cava].
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Adult↗
Biomedical subjects
M Niwa
Publications and source records attributed to M Niwa.
[A new strategy for the treatment of jugular foramen tumors using radiosurgery].
A new treatment strategy for jugular foramen tumors using radiosurgery is reported. Six jugular foramen tumors, including 2 glomus tumors and 4 lower cranial neurinomas, were involved. Among them only one tumor was confined in the jugular foramen, but the others extended into the posterior fossa, the upper cervical portion or both. As an initial treatment, 3 cases underwent operative resection from suboccipital or transcervical route. The tumor sizes at radiosurgery ranged from 14.3 to 36.1 mm with a mean of 22.4 mm in diameter. They were treated with a marginal dose between 13 to 16.5 Gy (mean 15.6 Gy). Follow-up MRI showed an apparent tumor shrinkage in 4 and no change in 2. Central tumor necrosis was found in 4 cases, but tumor progression was never observed in the mean follow-up period of 19 months. No complication occurred during and after the radiosurgery. These results indicate that radiosurgery is effective for the control of jugular foramen tumors with acceptable risk. Large tumors extending to the upper cervical portion and posterior fossa can be treated by operative resection combined with radiosurgery.
Adult↗
[The mu, delta and kappa properties of various opioids].
Recently, the highly selective mu, delta and kappa radiolabeled opioid ligands, such as 3H-DAGO (mu ligand), 3H-DPDPE (delta ligand) and 3H-U69593 (kappa ligand) are available. Using the kappa-homogeneous preparations from human placenta and mu-enriched gerbil cerebellum membrane preparations with these highly selective radiolabeled opioid ligands, clinically used opioids were tested for their mu, delta and kappa properties. The mu agonists such as morphine and fentanyl display a very low affinity for delta and kappa receptor. Among the agonist-antagonist, buprenorphine and butorphanol appeared to be the most highly selective agonists for mu and kappa opioid receptors, respectively. Most ligands identified as specific agonists are in fact only selective and appear to interact at more than one receptor type.
Analgesics, Opioid↗
[Opioid receptors altered binding nature in guinea-pig brain following the development of morphine dependence].
Morphine is well known to produce tolerance and dependence. The mechanisms for these phenomena are not clearly understood and there are a number of conflicting reports that chronic morphine administration decreases, increases, or leaves unchanged the number of opioid binding sites. We examined the potency of MScontin (oral controlled-release preparation of morphine) to induce morphine dependence and also determined the change of mu, delta and kappa opioid receptor types in brain homogenates obtained from morphine-dependent guinea-pigs. 1. Guinea-pigs were implanted subcutaneously with MScontin (300 mg.kg-1) and naloxone was employed to precipitate jumping behavior of withdrawal symptoms at various times. The highest degree of physical dependence was observed on the 2nd day after implantation. Therefore, this period was chosen to investigate opioid receptor binding assay. 2. Two days after implantation, the binding of 3H-DAGO (mu agonist), 3H-DPDPE (delta agonist) and 3H-U69593 (kappa agonist) to brain membranes prepared from morphine dependent and control guinea-pigs was determined. Scatchard plot of the saturation binding data revealed an increase in Bmax values (maximum specific binding) and no change in the Kd values (equilibrium dissociation constants) of 3H-opioid ligand bindings obtained from morphine-dependent animals as compared to controls. These results indicate that brain mu, delta and kappa opioid receptors are up-regulated in morphine dependent guinea-pigs.
Animals↗
Hypothermic prevention of nuclear DNA fragmentation in gerbil hippocampus following transient forebrain ischemia.
The protective effect of hypothermia on DNA fragmentation following transient forebrain ischemia in mongolian gerbils was investigated. The DNA fragmentation demonstrated in situ in gerbil hippocampal CA1 was compared between intra- and post-ischemic hypothermia. Intra-ischemic hypothermia prevented the DNA fragmentation in hippocampal CA1 completely, while severe DNA damage was observed in post-ischemic hypothermia group. the degree of DNA fragmentation of hippocampal CA1 in the post-ischemic hypothermia group was equal to that in the ischemic control group. The results suggest that hypothermia during a transient forebrain ischemia exerts a protective effect on the post-ischemic hippocampal damage by preventing the DNA fragmentation in CA1 neurons.
Animals↗
ETB receptor involvement in stimulatory and neurotoxic action of endothelin on dopamine neurones.
We examined the role of endothelin (ET) receptor subtypes in mediating the transient and sustained release of dopamine (DA) evoked by ETs and ET-1-induced dopaminergic dysfunction in rat striatal slices. Both phases of the release of DA evoked by ET-1 and ET-3 were inhibited by RES-701-1 (ETB antagonist) but not BQ-123 (ETA antagonist). The high K(+)-evoked DA release from slices remained impaired following a brief exposure to ET-1, under conditions of hypoxia/hypoglycaemia. RES-701-1 but not BQ-123 led to a recovery from ET-1-induced striatal dysfunction. Therefore, ETB receptors are involved in the stimulatory and neurotoxic actions of ETs on the striatal dopaminergic system.
Animals↗
Subunits of the Saccharomyces cerevisiae signal recognition particle required for its functional expression.
The signal recognition particle (SRP) is an evolutionarily conserved ribonucleoprotein (RNP) complex that functions in protein targeting to the endoplasmic reticulum (ER) membrane. Only two protein subunits of the SRP, Srp54p and Sec65p, and the RNA subunit, scR1, were previously known in the yeast Saccharomyces cerevisiae. Purification of yeast SRP by immunoaffinity chromatography revealed five additional proteins. Amino acid sequencing and cloning of the genes encoding four of these proteins demonstrated that the yeast SRP contains homologs (termed Srp14p, Srp68p and Srp72p) of the SRP14, SRP68 and SRP72 subunits found in mammalian SRP. The yeast SRP also contains a 21 kDa protein (termed Srp21p) that is not homologous to any protein in mammalian SRP. An additional 7 kDa protein may correspond to the mammalian SRP9. Disruption of any one of the four genes encoding the newly identified SRP proteins results in slow cell growth and inefficient protein translocation across the ER membrane. These phenotypes are indistinguishable from those resulting from the disruption of genes encoding SRP components identified previously. These data indicate that a lack of any of the analyzed SRP components results in loss of SRP function. ScR1 RNA and SRP proteins are at reduced levels in cells lacking any one of the newly identified proteins. In contrast, SRP components are present at near wild type levels and SRP subparticles are present in cells lacking either Srp54p or Sec65p. Thus Srp14p, Srp21p, Srp68p and Srp72p, but not Sec65p or Srp54p, are required for stable expression of the yeast SRP.
Amino Acid Sequence↗
Two distinct pathways are involved in the endothelin-3-evoked dopamine release from rat striatal slices.
We investigated mechanisms mediating endothelin-3-evoked dopamine release from rat striatal slices. Endothelin-3 stimulated dopamine release from the slices in a concentration-dependent manner over a range from 1 to 10 microM. Tetrodotoxin suppressed dopamine release, but left 40% of the release unaffected. Nifedipine, a voltage-gated Ca2+ channel (VGCC) antagonist, significantly inhibited dopamine release in the presence and absence of tetrodotoxin. Endothelin-3-evoked dopamine release was attenuated by D-2-amino-5-phosphnovaleric acid or Mg2+, N-methyl-D-aspartate receptor inhibitors, and this attenuation was not observed in the presence of tetrodotoxin, thereby indicating that the tetrodotoxin-sensitive component of dopamine release was partially mediated by glutamatergic pathways. This view was also supported by findings that endothelin-3 evoked glutamate release and the exogenously applied glutamate stimulated dopamine release. Based on these results, we hypothesize that endothelin-3 produces dopamine release through two distinct mechanisms; one is a direct stimulation of dopaminergic nerve terminals and the other was activation of interneurons which promoted the release of glutamate, resulting in dopamine release.
2-Amino-5-phosphonovalerate↗
Specific receptor for vasoactive intestinal contractor in myenteric cholinergic neurones.
The receptor for vasoactive intestinal contractor (VIC) involved in acetylcholine release was examined in the guinea-pig ileum. VIC (10(-9) to 10(-7) M) evoked tritium outflow from ileal strips preloaded with [3H]choline, in a concentration-dependent manner. The evoked tritium outflow was Ca(2+)-dependent and tetrodotoxin-sensitive, suggesting that VIC acts on somato-dendritic regions of the cholinergic neurones to stimulate acetylcholine release. The response to VIC did not change after desensitization to either endothelin-1, endothelin-2 or endothelin-3, hence there is probably no cross-desensitization in evoked tritium outflow between VIC and endothelins. VIC-induced contractions consisted of tetrodotoxin-sensitive and -resistant contractions, and the tetrodotoxin-resistant contraction was abolished after desensitization to either endothelin-1, endothelin-2 or endothelin-3. These results indicate that the VIC-specific receptor is located on cholinergic neurones, but not on the smooth muscle cells of guinea-pig ileum.
Acetylcholine↗
Endothelin increased [Ca2+]i in cultured neurones and slices of rat hippocampus.
We reported here the first evidence that endothelin (ET)-1 and ET-3 produced an increase in intracellular Ca2+ concentrations ([Ca2+]1), consisting of a transient and a sustained component, in cultured neurones and in slices of the rat hippocampus. In the neurones, the removal of Ca2+ or the addition of Cd2+ remarkably inhibited the ET-3-evoked sustained but not the transient response. The [Ca2+]i increased by ETs was observed in the dentate gyrus and in the vicinity of CA1 and CA3 pyramidal cell layer in the hippocampus, findings in good accord with regions where the glutamate receptor agonists have an elevated [Ca2+]i. The possible causal link between ETs and the increased [Ca2+]i in the development of hippocampal neuronal death is discussed.
Animals↗
T cell activation-associated hepatic injury: mediation by tumor necrosis factors and protection by interleukin 6.
This study investigates the molecular mechanisms underlying the induction of and protection from T cell activation-associated hepatic injury. When BALB/c mice were given a single intravenous injection of concanavalin A (Con A) (> or = 0.3 mg/mouse), they developed acute hepatic injury as assessed by a striking increase in plasma transaminase levels within 24 h. Histopathologically, only the liver was injured while moderate infiltration of T cells and polymorphonuclear cells occurred in the portal areas and around the central veins. The induction of hepatic injury was dependent on the existence as well as the activation of T cells, as untreated BALB/c nu/nu mice or BALB/c mice pretreated with a T cell-specific immunosuppressive drug, FK506, failed to develop disease. Significant increases in the levels of various cytokines in the plasma were detected before an increase in plasma transaminase levels. Within 1 h after Con A injection, tumor necrosis factor (TNF) levels peaked, this being followed by production of two other inflammatory cytokines, interleukin 6 (IL-6) and IL-1. Passive immunization with anti-TNF but not with anti-IL-1 or anti-IL-6 antibody, conferred significant levels of protection. Moreover, administration of rIL-6 before Con A injection resulted in an IL-6 dose-dependent protection. A single administration of a given dose of rIL-6 completely inhibited the release of transaminases, whereas the same regimen induced only 40-50% inhibition of TNF production. More than 80% inhibition of TNF production required four consecutive rIL-6 injections. These results indicate that: (a) TNFs are critical cytokines for inducing T cell activation-associated (Con A-induced) hepatitis; (b) the induction of hepatitis is almost completely controlled by rIL-6; and (c) rIL-6 exerts its protective effect through multiple mechanisms including the reduction of TNF production.
Animals↗
Endothelin-3 activates a voltage-gated Ca channel via a pertussis toxin sensitive mechanism leading to dopamine release from PC12 cells.
We have investigated the role of endothelin-3 (ET-3) in the stimulus-secretion coupling mechanism in rat pheochromocytoma PC12 cells. ET-3 (10-100 nM) evoked both dopamine (DA) release and an increase in intracellular Ca2+ concentration ([Ca]i). The ET-3-evoked DA release was partially inhibited by pretreatment with pertussis toxin (PTX; 2 ng/ml, 20 h). The release was also attenuated by the voltage-gated Ca channel (VGC) blockers Cd2+ (300 microM) or nicardipine (30 microM) and was completely abolished when external Ca2+ was removed. ET-3-evoked [Ca]i increase was attenuated by the application of these VGC blockers and by pretreatment with PTX, and was abolished by removal of extracellular Ca2+. Removal of external Na+ had no effect on either response. In light of these findings, we conclude that ET-3 evokes both DA release and an increase in [Ca]i by a mechanism which involves the activation of PTX-sensitive VGCs and the resultant influx of Ca2+.
Animals↗
Methylation imprinting was observed of mouse mo-2 macrosatellite on the pseudoautosomal region but not on chromosome 9.
Mouse mo-2 macrosatellites consisting of 31-bp tandem repeat units are mainly located at two loci in the C57BL/6 genome, one being at the centromere-distal telomeric region of chromosome 9 and the other at the pseudoautosomal (PA) region of chromosomes X and Y. The two clusters constitute approximately 300 kb and 150 kb, respectively. Southern analysis of a methylation-sensitive enzyme, HpaII-digested DNA showed that the mo-2 macrosatellites are detected as more than 30 polymorphic bands. Comparison of those bands between reciprocally crossed F1 mice revealed that approximately 20% of the allele-specific fragments exhibit different band intensities depending on the sex of the parent of origin. The differential methylation is observed in the mo-2 macrosatellite on the PA region but not in that on chromosome 9. Several fragments including the 3.4-kb fragment without internal HpaII site are more clearly detected when paternally derived, suggesting that the male-derived macrosatellite is undermethylated. Interestingly, the difference is much more remarkable in inter-subspecific F1 mice between C57BL/6 and MSM than F1 between C57BL/6 and C3H/He. This suggests the presence of a modifier(s) that affect(s) the methylation of mo-2 in the MSM genome.
Animals↗
Combination therapy of transcatheter chemoembolization and percutaneous ethanol injection therapy for unresectable hepatocellular carcinoma.
The therapeutic effectiveness of a combination therapy--pretreatment with transcatheter arterial chemoembolization (TACE) followed by percutaneous ethanol injection (PEI) therapy--for large (> 3 cm in diameter) unresectable hepatocellular carcinoma (HCC) was compared with that of TACE alone. PEI therapy was performed in 24 cases of unresectable HCC that had previously been treated with TACE using doxorubicin 30-60 mg or epirubicin 50-90 mg. In all, 2-10 ml of 90% ethanol mixed with carbocaine was repeatedly injected through a 21-gauge, closed-end needle (PEIT needle) for a median of 3.6 injections and 31.1 ml of ethanol. As adverse effects, transient localized pain and a burning sensation were observed in 75.0% of the cases; fever, in 66.7%; and transient hypotension, in two cases. A small unresectable tumor is a good indication for PEI therapy. In cases with a larger tumor, i.e., measuring more than 3 cm in diameter, or multiple tumors, the 1-year survival rate obtained with this combination therapy, i.e., TACE and PEI, was 87.0%, and the 2-year survival rate was 65.2%. These rates were greater than those obtained with TACE alone. Accordingly, additional PEI therapy was effective for larger tumors and multiple tumors previously treated with TACE.
Adult↗
Endothelin-3 stimulates inositol 1,4,5-trisphosphate production and Ca2+ influx to produce biphasic dopamine release from rat striatal slices.
1. Real-time monitoring of dopamine (DA) release from rat striatal slices demonstrated that endothelin (ET)-3 (0.1-10 microM) produced a biphasic DA release consisting of transient and sustained components. When extracellular Ca2+ was removed, the sustained but not transient response remarkably decreased. 2. ET-3 (1-10 microM) stimulated an increase in the intracellular Ca2+ concentration ([Ca(2+)]i), which also consisted of two components. The external Ca2+ depletion inhibited primarily the sustained component of the Ca2+ response to ET-3. 3. ET-3 increased inositol 1,4,5-trisphosphate (IP3) concentrations in striatal slices. This response peaked at 10 to 20 sec and returned to the basal level 2 min after stimulation, an event which was in good accord with a prompt and transient phase of both cytosolic Ca2+ activity and DA release evoked by ET-3. 4. Thus, ET-3 produces a transient and a sustained release of DA from striatal slices by stimulating intracellular Ca2+ mobilization via IP3 formation and extracellular Ca2+ influx, respectively.
Animals↗
A selective endothelin ETA antagonist, BQ-123, inhibits 125I-endothelin-1 (125I-ET-1) binding to human meningiomas and antagonizes ET-1-induced proliferation of meningioma cells.
1. We studied the effects of BQ-123, a selective ETA receptor antagonist, on 125I-endothelin-1 (125I-ET-1) binding to cell surface receptors in surgically exercised human meningiomas and on ET-1-induced DNA synthesis in cultured human meningioma cells in vitro, using a quantitative receptor autoradiographic technique with radioluminography and 3H-thymidine incorporation, respectively. 2. All of the human meningiomas expressed high-affinity binding sites for 125I-ET-1, regardless of differences in histological subtypes (Kd = 2.6 +/- 0.2 nM, Bmax = 374 +/- 93 fmol/mg; mean +/- SE; n = 9). 3. BQ-123 competed for 125I-ET-1 binding to sections of meningiomas with IC50S of 3.2 +/- 0.9 x 10(-7) M, and 10(-4) M BQ-123 displaced 80% of the binding. 4. ET-1 significantly stimulated DNA synthesis in cultured human meningioma cells, up to 170% of the basal level in the presence of 10(-9) M ET-1. BQ-123 inhibited ET-1 (10(-9) M)-induced DNA synthesis in meningioma cells, in a dose-dependent manner, and 10(-5) M BQ-123 reduced it to 120% of the basal level. 5. The number of meningioma cells determined after 4 days in culture was dose dependently increased in the presence of ET-1 (10(-9) and 10(-7) M). The growth rate of meningioma cells, incubated with 10(-9) M ET-1, was reduced by 50% in the presence of 10(-7) M BQ-123.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acid Sequence↗
A proposal for purification of salivary polymorphonuclear leukocytes by combination of nylon mesh filtration and density-gradient method: a validation by superoxide- and cyclic AMP-generating responses.
Isolation and purification of salivary polymorphonuclear leukocytes (SPMNs) from accompanying epithelial cells was presented by using a density-gradient method with Ficoll. SPMNs samples prepared by already established methods (nylon mesh filtration) was compared with SPMNs samples after further purification by Ficoll (d = 1.083). Microscopically, SPMNs samples after nylon mesh filtration contain higher percentage of epithelial cells than SPMNs samples after Ficoll centrifugation. In response to stimulation of superoxide generation, both samples showed the same pattern of response. However, in response to forskolin and prostaglandin E1, cyclic AMP levels in samples after nylon mesh purification were significantly higher than in samples after Ficoll purification because of the presence of contaminating epithelial cells. We can conclude that, although nylon mesh filtration is satisfactory when we need to examine superoxide generation but further purification is necessary when we want to measure factors like intracellular cyclic AMP formation.
Alprostadil↗
Characterization of opioid receptors in the Mongolian gerbil cerebellum.
Characteristics of opioid receptors binding in the Mongolian gerbil cerebellum were determined by in vitro radioligand binding technique. Homogenate of cerebellar membranes possessed a binding capacity for 3H-DAMGO, a mu-agonist, and for 3H-diprenorphine, an antagonist of mu, delta and kappa-receptors. These bindings were saturable, and characterized by high affinity (Kd values: 1.55 +/- 0.43 nM for 3H-DAMGO and 0.56 +/- 0.20 nM for 3H-diprenorphine) and high density (Bmax: 127.8 +/- 23.8 fmoles/mg protein for 3H-DAMGO and 135.8 +/- 9.03 fmoles/mg protein for 3H-diprenorphine). Autoradiographically, the binding sites were predominantly located in the molecular layer of the cerebellum. 3H-DPDPE, a delta-agonist, showed only very small binding capacity to the cerebellar membranes. The kappa-agonist, 3H-U-69593, also showed very small binding capacity to the cerebellar membranes except in the early postnatal period. Thus, the gerbil cerebellum can be considered as a tissue containing a homogeneous population of mu-opioid receptors.
Animals↗