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Biomedical subjects

H Yamamura

Publications and source records attributed to H Yamamura.

At least 181 records · Page 10Linked to original sources
PubMed1994

Subcutaneous administration of recombinant human erythropoietin before cardiac surgery: a double-blind, multicenter trial in Japan.

BACKGROUND: Dose and injection times have not previously been determined for subcutaneously administered recombinant human erythropoietin that would allow sufficient deposition of blood for autologous use in cardiac surgery. STUDY DESIGN AND METHODS: A double-blind, multicenter trial of placebo (Group 1) and recombinant human erythropoietin at 12,000 IU (Group 2) and at 24,000 IU (Group 3) was performed on 114 patients at 26 institutions to determine the dosage that would permit an 800-g preoperative deposit of blood for autologous use. The test drug was administered subcutaneously on Days 21, 14, and 7 prior to operation, and oral iron preparations at 200 mg per day were given for 21 days. There were 28 patients in Group 1, 28 in Group 2, and 30 in Group 3, with 28 excluded for a violation of the protocol. RESULTS: Blood was safely drawn 14 and 7 days before operation from 22 patients in Group 1 (78.6%), from 26 in Group 2 (92.9%), and from all patients in Group 3 (p = 0.018). The hemoglobin level on the day before operation decreased by 1.1 +/- 1.1 g per dL (11 +/- 11 g/L) in Group 1 and by 0.9 +/- 0.9 g per dL (9 +/- 9 g/L) in Group 2 and rose by 0.1 +/- 0.8 g per dL (1 +/- 8 g/L) in Group 3, compared to initial levels. Allogeneic blood transfusion could be avoided in 62, 89, and 90 percent of Group 1, 2, and 3 patients, respectively (p = 0.013). CONCLUSION: The present study shows that subcutaneously administered recombinant human erythropoietin at a dose of 24,000 IU per week for 3 weeks is effective and sufficient to allow the safe deposition of 800 g of blood for autologous use in cardiac surgery.

Blood Donors↗
PubMed1994

Intracellular calcium dependent activation of p72syk in platelets.

We previously demonstrated that thrombin-induced activation of p72syk was independent of intracellular Ca2+ elevation in platelets. However, our previous studies also demonstrated that activation of platelets by ionophore A23187 results in a dramatic increase in tyrosine phosphorylation of several cellular proteins. In the present study, we investigated the effect of Ca2+ elevation on the activity of p72syk. When washed porcine platelets were stimulated with ionophore A23187 and the activity of p72syk was assessed by means of an immunoprecipitation kinase assay, A23187 caused a time- and dose-dependent increase in the specific activity of p72syk. In addition, pretreatment of platelets with both aspirin and ADP scavengers or chelation of extracellular Ca2+ by EGTA had no effect on the A23187-induced activation of p72syk. These results indicate that A23187-induced activation of p72syk is independent of the formation of endoperoxide/thromboxane A2, released ADP and extracellular Ca2+, suggesting the existence of a novel pathway for activation of p72syk. Furthermore, evidence is presented which indicates a synergistic effect of A23187 and thrombin on the activation of p72syk, and an inhibitory effect of pretreatment with phorbol 12-myristate 13-acetate, a protein kinase C activator, on the activation of p72syk induced by either A23187 or thrombin.

Animals↗
PubMed1994

p72syk is activated by vanadate plus H2O2 in porcine platelets and phosphorylates GTPase activating protein on tyrosine residue(s).

Protein-tyrosine kinase p72syk exists abundantly in various hematopoietic cells and is activated by physiological or non-physiological agents. In this study we used vanadate, which is well known as a protein-tyrosine phosphatase inhibitor, to investigate the activity of p72syk and a downstream substrate for p72syk. Treatment with vanadate plus H2O2 caused tyrosine phosphorylation of multiple cellular proteins and platelet activation, i.e. aggregation and secretion. During aggregation induced by this stimulant, p72syk was activated and GTPase activating protein (GAP) was phosphorylated on tyrosine residue(s). The activation of p72syk was time- and dose-dependent. Also, the time course of activation of p72syk preceded that of tyrosine phosphorylation of GAP, and GAP was actually phosphorylated on tyrosine residue(s) by p72syk in vitro. These results suggest that p72syk is activated by treatment with vanadate plus H2O2, and that GAP is one of the possible substrates for p72syk in porcine platelets.

Adenosine Triphosphatases↗
PubMed1994

Possible participation of histamine H3-receptors in the regulation of anaphylactic histamine release from isolated rat peritoneal mast cells.

Anaphylactic histamine release from isolated rat peritoneal mast cells was concentration-dependently blocked by a 5-min treatment with exogenous histamine at 0.9 and 9 microM and enhanced by a 20- to 30-min treatment with thioperamide (H3-antagonist) at 3 microM with significance, but little affected by mepyramine (H1-antagonist) and cimetidine (H2-antagonist) at the cell concentration of 10(6) mast cells/ml. At a low concentration of mast cells (10(4) mast cells/ml), (R)-alpha-methylhistamine (alpha-MH), an H3-agonist, at 0.9-90 microM also inhibited the release in a concentration-dependent fashion. Thioperamide, but neither mepyramine nor cimetidine, significantly restored the decreased release by alpha-MH. However, the complete restoration by thioperamide could not be achieved because the drug itself slightly but concentration-dependently inhibited anaphylactic histamine release. On the other hand, not only betahistine and dimaprit but also alpha-MH did not suppress histamine release from the mast cells induced by compound 48/80. In rat plasma, considerable levels of histamine were detected. From these results, it is strongly suggested that histamine H3-like receptors are largely responsible for the negative feedback regulation of the anaphylactic histamine release from rat peritoneal mast cells.

Anaphylaxis↗
PubMed1994

Two-phase increment of Ca2+ uptake, intracellular Ca2+ concentration, and histamine release following antigen stimulation in mouse bone marrow-derived mast cells (BMMC).

The relationship between the influx of Ca2+ into cells or cytosolic Ca2+ concentration ([Ca2+]i) and the histamine release following antigen stimulation in mouse bone marrow-derived mast cells (BMMC) was examined, and the results were compared with those from human lung mast cells (HLMC) and rat peritoneal mast cells (RPMC) in some experiments. Anaphylactic histamine release from BMMC as well as HLMC, but not that from RPMC, was dependent on the extracellular Ca2+. When BMMC were challenged by antigen following radioactive 45Ca2+ addition, two phases of 45Ca2+ influx into the cells were observed. The first phase, which was initiated and completed within 30 sec and 2 min, respectively, after antigen treatment, appeared to be related to anaphylactic histamine release. The second influx began 30 sec subsequent to the first one and lasted for at least 2 min, and this occurred after the completion of the histamine release; So far, it is not known how this second influx participates in the intracellular event(s). On the other hand, only one sustained elevation of [Ca2+]i occurred that reached its maximum within 2 min after antigen stimulation. Following stimulation of BMMC with antigen in the absence of Ca2+, Ca2+ addition 1 to 5 min later time-dependently enhanced the histamine release, although the release was deteriorated by further extension of Ca2+ addition. In contrast, the releasability of HLMC was rapidly decreased. These results indicate that extracellular Ca2+ not only is prerequisite for anaphylactic histamine release from BMMC, but also may modulate the release and participate in some intracellular event(s) which has yet to be focused upon.

Anaphylaxis↗
PubMed1994

Establishment of new inbred strains derived from Japanese wild rats (Rattus norvegicus).

Inbreeding of Japanese wild rats (Rattus norvegicus) resulted in five new strains. The conception rates of wild rat strains were lower than those of inbred laboratory strains, and maternal aggressiveness was observed in some wild strains. The body size of domesticated animals was larger than that of captured ancestors. Two strains have been established as inbred strains; the MITA strain has been tamed to the level of laboratory rats, while the nature of the MITD strain is wild. The MITB strain was derived from the MITA strain as a coat color variant. The MITC and MITE strains have been bred to the F15 and F11 generations, respectively. The new strains can provide new genetic variations against a wild type background and might be useful for physiological and psychological experiments.

Animals↗
PubMed1994

Body and brain development following exposure to 60Co gamma-irradiation during pregnancy in mice.

We studied the dose-response effects of gamma-irradiation on the weight gains of the body and the brain in ICR mice exposed to various doses of 60Co gamma-irradiation ranging from 0 to 1.5 Gy on day 13 of pregnancy (El3). We found that 0.5 Gy gamma-irradiation caused a significant reduction in brain weight but not in body weight among 6-week-old mice. Higher doses (1.0, 1.5 Gy) seriously inhibited body and brain development, resulting in significantly low weights at 6 weeks of age. A significantly lower brain weight among fetuses exposed to 1.5 Gy was found as early as 24 hours after exposure, while significant reductions in the body weight of these same fetuses appeared 3 days after exposure. The effects of radiation on brain and body development were similar for both males and females.

Animals↗
PubMed1994

Protein-tyrosine kinase p72syk is activated by platelet activating factor in platelets.

It has been demonstrated that activation of platelets by platelet-activating factor (PAF) results in a dramatic increase in tyrosine phosphorylation of several cellular proteins. We report here that p72syk is a potential candidate for the protein-tyrosine phosphorylation following PAF stimulation in porcine platelets. Immunoprecipitation kinase assay revealed that PAF stimulation resulted in a rapid activation of p72syk which peaked at 10 s. The level of activation was found to be dose dependent and could be completely inhibited by the PAF receptor antagonist, CV3988. Phosphorylation at the tyrosine residues of p72syk coincided with activation of p72syk. Pretreatment of platelets with aspirin and apyrase did not affect PAF induced activation of p72syk. Furthermore, genistein, a potent protein-tyrosine-kinase inhibitor, diminished PAF-induced p72syk activation and Ca2+ mobilization as well as platelet aggregation. These results suggest that p72syk may play a critical role in PAF-induced aggregation, possibly through regulation of Ca2+ mobilization.

Animals↗
PubMed1994

Effects of vanadate on prostacyclin and endothelin-1 production and protein-tyrosine phosphorylation in human endothelial cells.

The ability of vanadate, an inhibitor of protein-tyrosine phosphatases, to affect the production of prostacyclin (PGI2) and endothelin-1 (ET-1) and protein-tyrosine phosphorylation in human umbilical vein endothelial cells (HUVEC) was studied. The addition of vanadate to monolayers of cultured HUVEC caused a sustained release of PGI2 from HUVEC in a time- and dose-dependent manner. When aspirin-treated HUVEC, which have lost the ability to increase PGI2 production in response to arachidonate, were incubated with vanadate, the cells recovered their ability to increase PGI2 production in response to arachidonate. This recovery of inducible PGI2 production in aspirin-treated HUVEC was completely inhibited either by cycloheximide, a protein synthesis inhibitor, or by actinomycin D, an RNA synthesis inhibitor. In contrast, the same concentration of vanadate suppressed the basal release of ET-1 from HUVEC. Vanadate also caused an increase in protein-tyrosine phosphorylation in HUVEC. These data indicate that vanadate induces opposite effects on PGI2 and ET-1 production with a concomitant increase in protein-tyrosine phosphorylation in HUVEC.

Endothelins↗
PubMed1994

[Effects of hyperventilation upon the spinal pain modulating system (third report)].

The purpose of this study is to investigate the mechanisms of the effect of hyperventilation on the spinal pain modulating system by using phentolamine. Under enflurane anaesthesia, cats received mid-collicular decerebration and lumbar laminectomy. The spinal cord was transected at T12-L1. WDR cells, responding primarily to noxious peripheral stimuli, were sampled with a microelectrode at the depth of 2,000 microns from the cord dorsum. Following the control period, ventilation was changed to induce hypocapnia of PCO2 20-25 mmHg. After activities were well suppressed, phentolamine 0.5 mg with normal saline 1.0 ml was injected on the spinal cord. Changes of firings were investigated. When normocapnia was resumed, recovery followed. Hypocapnia of PCO2 20-25 mmHg significantly suppressed the activities of WDR cells. Phentolamine significantly antagonized the suppressive effects of hyperventilation upon the activities of WDR cells. Our results suggest that the hyperventilation has suppressive effects on single-unit activity of WDR cell and the mechanisms of those suppressive effects are related to adrenergic pain modulating system.

Action Potentials↗
PubMed1994

[A comparison between neuromuscular blocking effects of pipecuronium and vecuronium; a double blind controlled study in collaboration with 5 departments of anesthesiology].

Neuromuscular blocking effects of pipecuronium bromide 0.04 mg.kg-1 were compared those of vecuronium bromide 0.08 mg.kg-1 in a double blind study. Fifty surgical patients (ASA I or II) were allocated randomly to two groups of each 25 cases and they were anesthetized with nitrous oxide 4 l.min-1, oxygen 2 l.min-1 and isoflurane 1 MAC. Neuromuscular blockade was monitored by using mechanical twitch responses of the thumb to electrical stimulations of the ulnar nerve. Adequate neuromuscular relaxation for surgery of 85.8% to 100% block was obtained by this dose of pipecuronium. The duration of action and recovery time from 75% to 25% block were longer than those produced by twice the dosage of vecuronium (62.3 +/- 37.15 vs. 40.4 +/- 16.09 min, and 48.1 +/- 22.0 vs. 19.9 +/- 10.8 min, P < 0.05). The blocks by both drugs responded to neostigmine. Cardiovascular side effects of the both agents were not found. From these results, it is concluded that pipecuronium is a useful nondepolarizing relaxant with a long duration of action and negligible side effects.

Adult↗
PubMed1994

Displaced retinal ganglion cells in the Chinese hamster.

The size, number, distribution and dendritic morphology of displaced retinal ganglion cells (DGCs) in normal Chinese hamsters were investigated using horseradish peroxidase. The diameters of DGC soma ranged from 4 to 23 microns (mean 11.7 microns). The number of DGCs ranged from 104 to 453 (mean 249) and constituted under 1% of total retinal ganglion cells. DGCs were found in all retinal regions, but more frequently in the lower temporal periphery. Two types of DGCs were observed, one with a small to medium soma (< 18 microns in diameter) and a small dendritic field (< 100 microns in diameter), and the other with a large soma (> or = 18 microns in diameter) and a large dendritic field (> or = 100 microns in diameter). DGCs in the Chinese hamster may be developmental errors or misplaced ganglion cells.

Animals↗
PubMed1994

[The effects of hyperventilation upon the spinal pain modulating system (second report)].

The purpose of this study is to investigate the effect of hyperventilation on the spinal pain modulating system by using naloxone. Under enflurane anaesthesia, cats were prepared with midcollicular decerebration and lumbar laminectomy. The spinal cord was transected at T12-L1. WDR cells, responding primarily to noxious peripheral stimuli, were sampled with a microelectrode at the depth of 2,000 microns from the cord dorsum. Following the control period, ventilation was adjusted to produce hypocapnia of PCO2 20-25 mmHg. After activities of WDR cells were well suppressed, naloxone 0.1 mg.kg-1 was given intravenously. Changes of firings of WDR cells were investigated. Returning to normocapnia, recovery of firings was followed. Hypocapnia of PCO2 20-25 mmHg significantly suppressed the activities of WDR cells. Naloxone significantly antagonized the suppressive effects of hyperventilation upon the activity of WDR cell. Our results suggest that the hyperventilation has suppressive effects on single-unit activity of WDR cell and the mechanisms of those suppressive effects are related to pain modulating system by endogenous opiates.

Action Potentials↗
PubMed1993

Protein-tyrosine kinase p72syk is activated by thromboxane A2 mimetic U44069 in platelets.

We show that p72syk is rapidly activated following the stimulation of thromboxane A2 mimetics, U44069 and STA2 in porcine platelets. The activity of p72syk reached a maximum at 10 s and decreased to a basal level within 60 s after 1 microM U44069 stimulation. This activation was enhanced in a dose-dependent manner and completely canceled by the pretreatment of platelet suspension with ONO3708, a specific antagonist of thromboxane A2. Pretreatment of platelets with aspirin as well as apyrase did not affect the activation of p72syk. When both extra- and intra-cellular Ca2+ were depleted, the activation of p72syk was still persistent; in contrast, the deactivation process was completely abrogated even at 120 s after U44069 stimulation. These results suggest that p72syk is a responsible enzyme to the protein-tyrosine phosphorylation events, and that p72syk functions mainly before Ca2+ recruitment in thromboxane A2-stimulated platelets.

Animals↗
PubMed1993

Activation of protein-tyrosine kinase p72syk with concanavalin A in polymorphonuclear neutrophils.

We studied the abundance, subcellular distribution of a non-receptor protein-tyrosine kinase p72syk (Taniguchi, T., Kobayashi, T., Kondo, J., Takahashi, K., Nakamura, H., Suzuki, J., Nagai, K., Yamada, T., Nakamura, S., and Yamamura, H. (1991) J. Biol. Chem. 266, 15790-15796) in porcine polymorphonuclear neutrophils and the activation upon the stimulation with concanavalin A. The abundance was about 0.1% of total proteins and mainly distributed in the particulate fraction. Upon concanavalin A stimulation, the activity of p72syk increased within 30 s, attained to the maximum level at 1 min, and then returned to the basal level within 6 min. This activation was observed in a dose-dependent manner and abrogated by simultaneous addition of methyl alpha-mannopyranoside. When both extra- and intracellular Ca2+ were depleted, the activation of p72syk was still persistent; in contrast, the deactivation process was completely abrogated even at 6 min after stimulation. The replenishment of Ca2+ in the presence of A23187 resulted in a similar deactivation pattern as seen in the Ca(2+)-rich condition. In addition, genistein and herbimycin A, potent protein-tyrosine-kinase inhibitors, were capable of reducing concanavalin A-evoked p72syk activation and Ca2+ mobilization as well as the aggregation and lysozyme release. Furthermore, A23187-induced Ca2+ accumulation in inhibitor-treated cells resulted in the restoration of those cellular responses. These lines of evidence suggest that p72syk is activated with concanavalin A in a Ca(2+)-independent manner, participating in a mechanism of Ca2+ recruitment, and negatively regulated by a feedback mechanism through Ca2+ in neutrophils.

Animals↗
PubMed1993

Possible role of Na+ influx in phorbol ester-induced down-regulation of protein kinase C in HL60 cells.

Amiloride, an inhibitor of Na+/H+ exchange, inhibited down-regulation of protein kinase C in HL60 cells induced by tumor-promoting phorbol ester in dose-dependent manner judging from immunoblot analysis. This inhibition was observed with regard to type I (gamma), type II (beta), and type III (alpha) isozymes of protein kinase C. On the other hand, monensin, a Na+ ionophore, accelerated the down-regulation of protein kinase C induced by phorbol ester. When we examined 22Na+ uptake by HL60 cells, the higher uptake was observed after stimulation with phorbol ester compared to the control cells and this 22Na+ uptake was strongly inhibited by the addition of amiloride. However, monensin further stimulated the 22Na+ uptake observed in phorbol ester-treated cells. These data suggest that the increase in intracellular Na+ concentration may be one of the triggers for the induction of down regulation of protein kinase C.

Amiloride↗
PubMed1993

The lectin concanavalin A stimulates a protein-tyrosine kinase p72syk in peripheral blood lymphocytes.

We report that the activation of porcine peripheral blood lymphocytes (PBL) by lectin concanavalin A (Con A) led to the increase in tyrosine phosphorylation on 84-, 72-, 55-, 40-, and 33-kDa proteins. A non-receptor protein-tyrosine kinase (PTK), p72syk (Taniguchi et al. (1991) J. Biol. Chem. 266, 15790-15796), was detected in PBL around 0.1% of total protein and distributed in both particulate and cytosolic fractions. Furthermore, Con A induced a rapid activation of p72syk within 1 min in a manner similar to the time course of Con A-induced protein-tyrosine phosphorylation. These results suggest that p72syk plays a certain role in the activation of PBL and that p72syk may be one of the major non-receptor PTKs in T cells as well as in B cells.

Animals↗