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Biomedical subjects

K Muramatsu

Publications and source records attributed to K Muramatsu.

At least 19 recordsLinked to original sources
PubMed1998

Estrogen protects against while testosterone exacerbates vulnerability of the lateral striatal artery to chemical hypoxia by 3-nitropropionic acid.

Gender differences in the vulnerability of the lateral striatal artery (1STR artery) to systemic intoxication with 3-nitropropionic acid (3-NPA, succinate dehydrogenase inhibitor) were studied. Subcutaneous injection of 3-NPA (20 mg/kg once a day for 2 days) induced striatal selective lesions in half of male rats associated with motor symptoms (rolling, paddling, recumbency, etc) while female rats were resistant. Lesions were located in the lateral striata and characterized by astroglial necrotic cell death, enhanced immunoreaction to factor VIII-related antigen, edema, extravasation of IgG and sometimes bleeding. The motor and histological disturbances were highly sex-dependent and modulated by changes in hormonal levels. Males were more susceptible than females. Castration had little effect but ovariectomy enhanced the vulnerability. Replacement therapy with testosterone increased while estradiol or tamoxifen suppressed the vulnerability in ovariectomized females. Investigation of the arterial architecture of the brain often revealed rectangular and acute angled branchings in the centrolateral striatum where the ISTR artery feeds. A parallel in vitro toxicity study demonstrated that an extreme Ca++ overload and a strong cellular swelling resulted in astrocytic cell death. Data suggest that 1STR artery and astrocytes are highly vulnerable to 3-NPA intoxication in males. The greater vulnerability of the ISTR artery may contribute to the pathogenesis of neurodegenerative diseases, striatal bleeding, etc. Protective effects of estrogen and tamoxifen may mediate gender differences often observed in these disorders and suggest their potential use as therapeutic agents for these disorders.

Animals↗
PubMed1998

Simultaneous optical imaging of intracellular Cl- in neurons in different layers of rat neocortical slices: advantages and limitations.

Simultaneous recording of changes in intracellular Cl- concentration ([Cl-]i) in individual neurons situated in different layers (e.g. II/III-VI) of neocortical slices was found to be feasible by means of optical fluorescence measurements using 6-methoxy-N-ethylquinolinium iodide (MEQ). Gamma-aminobutyric acid (GABA) caused a measurable increase in [Cl-]i in adult neocortical neurons, but a decrease in immature neurons. Developmental changes in the function of the Cl- pump and cation-Cl- co-transporters were evaluated using inhibitors such as furosemide (FURO), ethacrynic acid (ETA), and bumetanide (BMT). However, it was found that these inhibitors absorb and/or emit light of the wavelength that is used for the optical imaging of MEQ. In addition, quenching of MEQ fluorescence by Cl- and leakage of loaded MEQ was significantly enhanced at a higher temperature, which will limit experimentation at > 30 degrees C. Estimation of [Cl-]i in individual neurons in slices was made possible by calibrating intracellular MEQ fluorescence signals at known Cl- concentrations ([Cl-]) in the presence of tributyltin, a Cl(-)-OH- antiporter, nigericin, a K+-H+ antiporter, and KSCN. This enables comparison of [Cl-]i between neurons in different slices. Thus, optical imaging of [Cl-]i in brain slices can provide valuable spatial information about [Cl-]i dynamics and homeostasis, although it should be emphasized that the technique does have some limitations.

Animals↗
PubMed1998

A new immunosuppressant, FTY720, prolongs limb allograft survival in rats.

A new immunosuppressant, FTY720, was applied to limb allotransplants and its effectiveness was investigated. Using inbred rats, for which the major histocompatibility complexes were completely mismatched, 31 limb transplantations were performed and FTY720 was administered at a dose of 1.5 or 3 mg per kilogram per day for 10 days postoperatively. Rejection was monitored by the appearance of the skin of the grafted hind limb, soft radiograph, microangiography, and histology. In animals receiving no immunosuppressive therapy, the mean onset of rejection was 4.2+/-1.0 days postoperatively, and the grafted limbs became acutely necrotic. The mean onset of rejection was 6.0+/-0.9 days in animals receiving FTY720 at a dose of 1.5 mg per kilogram per day and 7.9+/-1.5 days in animals receiving FTY720 at a dose of 3 mg per kilogram per day. Survival of the grafted limbs was significantly prolonged compared with that in animals without immunosuppression. The immunosuppressive effect of FTY720 appeared to be dose dependent; however, complete suppression of rejection could not be obtained with FTY720 therapy alone.

Animals↗
PubMed1998

Treatment of chronic regional pain syndrome using manipulation therapy and regional anesthesia.

In a 4-year period, 17 consecutive patients with posttraumatic chronic regional pain syndrome were treated with a new technique, Movelat manipulation therapy. At average follow-up of 8 months, satisfactory results were achieved in 15 patients (88%), but 2 patients, 1 with digital nerve injury and 1 with ulnar nerve injury, did not respond to the therapy. Factors associated with good clinical response include chronic regional pain syndrome type I, i.e., dystrophy produced by a trauma to the hand but not involving a specific nerve injury, early-stage disease (within 3 months after trauma), and involvement of the upper limbs. Complications were rare and mild (pain over the tourniquet site in 3%, temporary dizziness in 1%). This therapy is simple and safe and recommended for early treatment of chronic regional pain syndrome.

Adult↗
PubMed1998

Revascularized intercalary bone allografts with short-term immunosuppression with cyclosporine in the canine.

To study the healing process of vascularized intercalary bone allograft after withdrawal of immunosuppressive drugs, allotransplantation of the tibia diaphysis with a vascular pedicle was performed in eight adult mongrel dogs (group 2) and assessments were made both during administration and after discontinuation of cyclosporin A. As controls, similar grafts with the vascular pedicles were removed and reimplanted back to the same animals (five dogs, group 1). Allotransplantation of frozen stored bone without a vascular pedicle (10 dogs, groups 3A and 3B) were also compared. No union occurred in most cases of frozen stored bone allotransplant because the transplanted bone was resorbed, leading to loosening and subsequent failure of osteosynthesis with the plate and screws used. Under cyclosporin A immunosuppression, bony union (i.e., when trabeculae were seen crossing the graft-recipient junction with obliteration of the junction line) occurred at almost similar time intervals in all dogs of group 2 (bone allotransplant with a vascular pedicle) by 3 months postoperatively, which was similar to those of group 1. No systemic side effects of cyclosporin A were observed. Cyclosporin A was discontinued 3 months following graft implantation. The bone graft became avascular within a week following withdrawal of cyclosporin A. However, bone union was maintained, and the transplanted bone never showed bone resorption, sclerosis, or fracture on serial radiographs up to the time the animals were sacrificed, between 5 and 14 months later. Histology at sacrifice showed that the transplanted allografts were being replaced at both ends by fresh bone derived from the transplantation bed. We conclude on the basis of the results of this study that solid bony union can be obtained in allotransplanted bone with a vascular pedicle if cyclosporin A is given for a brief period. After cyclosporin A is withdrawn, although the bone becomes nonviable secondary to rejection occurring in the blood vessels, its skeletal structure remains intact, enabling it to maintain its structural support while awaiting replacement by bony ingrowth from both ends of the graft.

Animals↗
PubMed1998

NMDA receptor-mediated differential laminar susceptibility to the intracellular Ca2+ accumulation induced by oxygen-glucose deprivation in rat neocortical slices.

Slices of somatosensory cortex taken from immature rats on postnatal day (P)7-14 were labeled with fura-2. Intracellular Ca2+ concentration ([Ca2+]i) was monitored in identified pyramidal cells as the ratio of fluorescence intensities (RF340/F380) during oxygen-glucose deprivation. The RF340/F380 ([Ca2+]i) of individual pyramidal cells was monitored in each of the cortical layers II-VI simultaneously. Neurons in all neocortical layers exhibited significant increases in [Ca2+]i that varied with the duration of oxygen-glucose deprivation. Individual neurons responded to oxygen-glucose deprivation with abrupt increases in [Ca2+]i after various latencies. The ceiling level of the [Ca2+]i increase differed from cell to cell. Neurons in layer II/III showed significantly greater increases in [Ca2+]i than those in layers IV, V, or VI. Kynurenic acid, a nonselective glutamate receptor antagonist, and bicuculline, a selective gamma-aminobutyric acid (GABA)A receptor antagonist, suppressed the intracellular Ca2+ accumulation induced by oxygen-glucose deprivation in all neocortical layers examined. After kynurenic acid, but not after bicuculline, there was no longer a differential [Ca2+]i increases in layer II/III. Both 2-amino-5-phosphonopentanoic acid (AP5), a selective N-methyl-D-aspartate (NMDA) receptor antagonist, and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA receptor antagonist, strongly suppressed the intracellular Ca2+ accumulation induced by oxygen-glucose deprivation in all layers. The laminar difference in terms of the [Ca2+]i increases was abolished by AP5, but not by CNQX. These results indicate that layer II/III cells are the most prone to oxygen-glucose deprivation-induced intracellular Ca2+ accumulation, and that this is primarily mediated by NMDA receptors. Thus, layer II/III neurons would be more likely to suffer cellular Ca2+ overload and excitotoxicity during ischemia than layer IV-VI cells. Such a differential laminar vulnerability might play an important role in determining the pathological characteristics of the immature cortex and its sequelae later in life.

2-Amino-5-phosphonovalerate↗
PubMed1998

Changes in intracellular Ca2+ induced by GABAA receptor activation and reduction in Cl- gradient in neonatal rat neocortex.

We have studied the effects of gamma-aminobutyric acid (GABA) and of reducing the Cl- gradient on the [Ca2+]i in pyramidal neurons of rat somatosensory cortex. The Cl- gradient was reduced either with furosemide or by oxygen-glucose deprivation. Immature slices taken at postnatal day (P)7-14 were labeled with fura-2, and [Ca2+]i was monitored in identified pyramidal cells in layer II/III as the ratio of fluorescence intensities (RF340/F380). The magnitude of the [Ca2+]i increases induced by oxygen-glucose deprivation was significantly reduced (by 44%) by bicuculline (10 microM), a GABAA receptor antagonist. Under normal conditions, GABA generally did not raise [Ca2+]i, although in some neurons a small and transient [Ca2+]i increase was observed. These transient [Ca2+]i increases were blocked by Ni2+ (1 mM), a blocker of voltage-dependent Ca2+ channels (VDCCs). Continuous perfusion with GABA did not cause a sustained elevation of [Ca2+]i but bicuculline caused [Ca2+]i oscillations. After inhibition of Cl- extrusion with furosemide (1.5 mM), GABA induced a large [Ca2+]i increase consisting of an initial peak followed by a sustained phase. Both the initial and the sustained phases were eliminated by bicuculline (10 microM). The initial but not the sustained phase was abolished by Ni2+. In the presence of Ni2+, the remaining sustained response was inhibited by the addition of 2-amino-5-phosphonopentanoic acid (AP5, 20 microM), a selective N-methyl-D-aspartate (NMDA) receptor antagonist. Thus the initial peak and the sustained phase of the GABA-evoked [Ca2+]i increase were mediated by Ca2+ influx through VDCCs and NMDA receptor channels, respectively, and both phases were initiated via the GABAA receptor. These results indicate that, in neocortical pyramidal neurons, a reduction in the Cl- gradient converts the GABAA receptor-mediated action from nothing or virtually nothing to a large and sustained accumulation of cellular Ca2+. This accumulation is the result of Ca2+ influx mainly through the NMDA receptor channel. Thus GABA, normally an inhibitory transmitter, may play an aggravating role in excitotoxicity if a shift in the Cl- equilibrium potential occurs, as reported previously, during cerebral ischemia.

2-Amino-5-phosphonovalerate↗
PubMed1998

Fluorometric measurement of intracellular pH in vivo in feline cerebral cortex during ischemia and reperfusion.

Intracellular acidosis has been considered to play an pivotal role in the progression of neuronal damage after cerebral ischemia. However, continuous measurement of the intracellular potential of hydrogen (pH) has not been done during and after ischemia. We measured temporal changes in intracellular pH in the feline cerebral cortex in vivo during and after ischemia using a novel fluorescent pH probe, 2',7'-biscarboxyethyl carboxyfluorescein (BCECF). A closed cranial window was installed in the left temporal skull. BCECF acetoxymethyl ester was superfused over the cortex, hydrolyzed and trapped in cortical cells. Intracellular pH was measured utilizing excitation light at 507 nm and fluorescent light at 550.5 nm. Focal cerebral ischemia for 60 minutes was induced by means of middle cerebral artery occlusion. Intracellular pH in the severely ischemic group became significantly acidic (p < 0.01) during ischemia and the acidosis persisted for at least 30 minutes after recirculation. The pH change was not significant in the mildly ischemic group. The severity of ischemia was determined based on the mean transit time, which was calculated from the hemodilution curve obtained by bolus injection of saline. The extent of ischemia was further confirmed pathologically (p < 0.01). The above results suggest that intracellular acidosis resulting from severe ischemia persists even after recirculation.

Animals↗
PubMed1997

Importance of interferon-gamma in protective immunity against Hymenolepis nana cysticercoids derived from challenge infection with eggs in BALB/c mice.

The function of cytokines produced during Hymenolepis nana egg infection in mice in protective immunity against re-infection was examined. Treatment of mice with monoclonal antibody (MAb) against mouse interferon (IFN)-gamma caused suppression of protective immunity against H. nana re-infection when the MAb was injected intraperitoneally at a daily dose of 40.0 mg kg-1 during the effector phase of protective immunity. Although high levels of IFN-gamma, tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta were released into the intestinal tracts of the parasitised mice at challenge infection, there was almost no release of these cytokines in mice treated with the MAb. Daily administration of rolipram failed to suppress the protective immunity, even when 400 micrograms kg-1 of the agent was administered into mice during the effector phase of immunity. Treatment of mice with rolipram completely suppressed both TNF-alpha and IL-1 beta production in intestinal tracts, induced by H. nana challenge infection. However, endogenous IFN-gamma production in the intestine was scarcely affected by rolipram. These results strongly suggest that IFN-gamma is the most important (or essential) cytokine in protective immunity to H. nana re-infection, rather than TNF-alpha and IL-1 beta.

Animals↗
PubMed1997

Topography of hypoxic injury proved by argyrophilia in postnatal rat brain.

The argyrophil III method, a new esterification-silver staining approach, was used to elucidate regional differences in the susceptibility of developing brain to hypoxic-ischemic (H-I) injury. We created a unilateral common carotid artery-ligation model with hypoxia (8% oxygen) in postnatal day (P) 7, P14 and P21 rats. The argyrophil (i.e., deteriorated) neurons were apparent in the ipsilateral hippocampus, cortex, and striatum in each age group. Argyrophil neurons exhibited some morphological signs of the "early phase" of injury preceding the loss of structure and/or cell death in the "late phase," as indicated by hematoxylin-eosin (H-E) staining. The argyrophil neurons were apparent as early as 12 hours after the insult, whereas the histological changes revealed by H-E staining were subtle. The early phase and late phase histological changes had a stereotyped pattern of appearance in all ages studied. However, the duration of H-I situation required to produce argyrophil cells differed according to age. The most resistive age was P14 (P14 > P7 > P21) in this observation. Therefore, argyrophil III staining is feasible for H-I brain damage model in neonates. The results suggest that both the early phase and the late phase pathological processes after H-I injury have a characteristic topographical vulnerability that does not change during development but have a differing susceptibility according to age.

Animals↗
PubMed1997

Vulnerability to cerebral hypoxic-ischemic insult in neonatal but not in adult rats is in parallel with disruption of the blood-brain barrier.

BACKGROUND AND PURPOSE: Vulnerability to cerebral hypoxic-ischemic (H-I) insult and its relation to disruption of the blood-brain barrier were investigated in postnatal rats. METHODS: Pups of postnatal day (P) 7, P14, and P21 underwent ligation of a unilateral carotid artery and were exposed to hypoxic conditions. For the detection of early-phase deterioration, brains were perfusion-fixed 24 hours after H-I insult and examined by argyrophil III method. For the detection of later infarction, animals were fixed at 72 hours after the H-I insult. RESULTS: In either case, tissue damage was detected in the striatum, parietal cortex, and hippocampus. The vulnerability of P7 and P21 rats was remarkable, as compared with P14 rats. Although the developmental status of the vasculature was not significantly different at each age, the permeability of IgG after H-I injury was prominent in P7 rats and to a lesser extent in P14 rats. In P21 rats, however, there was little IgG leakage even 24 hours after the insult. Dexamethasone pretreatment blocked the extravasation of IgG and reduced the damaged tissue in P7 and P14 rats but not in P21 rats. Percentages of reduction in infarcted areas by the dexamethasone became smaller in proportion to ages. CONCLUSIONS: The results suggest that in younger rats vulnerability to H-I insult was in parallel with permeability of the blood-brain barrier, whereas in adults in might be more dependent on cellular vulnerability.

Aging↗
PubMed1997

Longer survival of rat limb allograft. Combined immunosuppression of FK-506 and 15-deoxyspergualin.

We studied the individual and synergistic effect of 3 immunosuppressive drugs, FK-506 (1 mg/kg/day), 15-deoxyspergualin (2.5 mg/kg/day) and cyclosporine (15 mg/kg/day) in a DA/Lewis rat limb allotransplantation model. 74 right hindlimb transplantations were performed. The median time for onset of rejection was 4 days in animals without immunosuppression, 37 days in animals receiving cyclosporine immunosuppression for 30 days, 61 days in animals receiving FK-506 for 30 days, 36 days in animals receiving a 30-day course of cyclosporine and, in the first 15 days, a course of 15-deoxyspergualin, and 76 days in animals receiving a 30-day course of FK-506 and 15-deoxyspergualin in the first 15 days. The combination of cyclosporine with 15-deoxyspergualin did not prolong graft survival and no synergistic effect was evident. In contrast, survival time in rat limb allografts receiving FK-506 and 15-deoxyspergualin was longer than in those receiving single FK-506 therapy. Our findings suggest a positive synergistic immunosuppressive effect with FK-506 and 15-deoxyspergualin in limb allotransplantation.

Animals↗
PubMed1996

Labeling and identification of living donor cells in brain slices of recipient hemiparkinsonian model rats for physiological recordings: methods for physiological assessments of neural transplantation.

Physiological properties of grafted neurons, such as membrane and intr acellular properties, have not been reported. To fill this lack in knowledge, physiological recordings from the identified grafted cells are required. Fluorescent latex microspheres (FLM) are non-toxic and stable, and thus seem suitable for long-term labeling of donor cells. Therefore, we tested the feasibility of labeling with FLM to identify living donor cells in the recipients' brain slices. We also tested if physiological recordings from the identified cells are possible or not. Cell suspensions were prepared from the substantia nigra (SN) of Embryonic Days 15 or 16 rats with enzymatic and mechanical trituration. Cell suspensions were then incubated with 0.5% FLM for 30 min to 2 h. The longer cells were incubated, the more FLM were taken up. The FLM-labeled SN cell suspensions were injected in the striatum of the hemiparkinsonian model rats. Eight to 13 weeks later, 150-mu m thick coronal brain slices including the graft track were prepared from the recipients. Slices were kept in vitro for several hours. Grafted cells could be clearly identified in the slice preparations by the uptake of FLM under a fluorescence microscope. Voltage-dependent currents and intracellular Ca2+ transcients were successfully recorded from the identified grafted neurons. It is suggested that labeling and identification of living donor cells with FLM is feasible and thus can provide a powerful tool to study the mechanisms underlying graft-induced amelioration of neurological deficits in parkinsonism by enabling physiological assessments of grafted cells.

Animals↗
PubMed1996

Influence of deoxyspergualin on mononuclear phagocytic system in mice.

The influence of deoxyspergualin (DSG) on mononuclear phagocytic system was examined in BALB/c mice. DSG did not influence on both the organ distribution of sheep red blood cells (SRBC) and blood clearance of colloidal carbon when the agent was administered intraperitoneally into mice at doses of 5.0 and 10.0 mg/kg for six consecutive days before antigen. Hemagglutination titers in experimental and control mice did not differ significantly when 10.0 mg/kg of DSG was given six times before SRBC injection. However, when administered during the course of the response (days 0 to 5) DSG (5.0 mg/kg/day) markedly suppressed antibody formation.

Animals↗
PubMed1996

Inhibitory action of deoxyspergualin on effector/memory T cell generation during Hymenolepis nana infection in mice.

The effects of deoxyspergualin (DSG), a newly developed immunosuppressive agent, on protective immunity to Hymenolepis nana reinfection were examined in BALB/c mice. Administration of DSG at daily doses of 10.0 mg/kg to 30.0 mg/kg (but not 5.0 mg/kg) caused suppression of protective immunity when the agent was injected intraperitoneally during the induction phase of the immunity. In contrast, daily administration of 30.0 mg/kg DSG, during effector phase, could not suppress protective immunity. DSG inhibited endogenous interferon-gamma production in mesenteric lymph nodes induced by H. nana challenge infection, when the agent was injected intraperitoneally at a daily dose of 10.0 mg/kg during the induction phase of immunity. Delayed type hypersensitivity (DTH) local transfer analysis revealed that administration of DSG at 10.0 mg/kg/day into donor mice during induction phase of immunity inhibited generation of effector/memory cells that mediate DTH to H. nana egg antigen. However, DSG could not inhibit DTH effector cell activation when cells prepared from H. nana-infected, saline-injected mice were transferred into recipient treated with 10.0 mg/kg DSG. Administration of DSG at a dose of 10.0 mg/kg daily for 5 days produced large DNA fragments in mesenteric lymph node (MLN) cells. These results strongly suggest that DSG suppresses generation of effector/memory cells by apoptotic cell death but cannot suppress lymphocyte activation in vivo.

Animals↗
PubMed1996

Comparison of OspA serotypes for Borrelia burgdorferi sensu lato from Japan, Europe and North America.

UNLABELLED: Sixty-one Borrelia burgdorferi sensu lato strains from various sources (ticks, human, and wild animals) in Japan and two strains from ticks in Far Eastern Russia were classified on the basis of reactivity with 16 monoclonal antibodies (mAb) to outer surface protein A (OspA) and by DNA-DNA hybridization assay. Eleven OspA serotypes (J1 to J11) were recognized among the Japanese and the Far East Russian isolates (serotypes J1 to J9 were identified as B. garinii, serotype J10 was identified as B. afzelii, and serotype J11 corresponded to B. japonica), whereas 7 OspA serotypes for North American and European isolates previously reported (Bettina Wilske et al, J. Clin. Microbiol. 31:340-350,1993) were not observed except for OspA serotype 2 which showed identical reactivity with OspA serotype J10. This finding provides helpful information for understanding the geographical distribution of Lyme disease borrelia and the development of vaccine and diagnostic tests. IN CONCLUSION: 1.B. burgdorferi sensu stricto has not been observed in Japan, 2. Japanese B. afzelii isolates are closely related to those from Europe, 3. B. garinii isolates from Japan are highly heterogeneous and apparently different from European B. garinii isolates.

Animals↗
PubMed1996

[Analysis of verotoxin-producing Escherichia coli (O157:H7) strains isolated in the Fukuoka area in 1994 by pulsed-field gel electrophoresis].

Nine verotoxin-producing Escherichia coli O157:H7 strains were isolated from 9 pediatric patients with sporadic enteritis between July and September 1994 at four clinics in the Fukuoka area. The patients included two families with two cases each. These strains were analyzed by pulsed-field gel electrophoresis for Xba I-digested DNA fragments. The restriction patterns were identical between each two strains within the two family outbreaks, but different among the seven strains of the distinct seven sporadic cases. It is strongly suggested that the seven sporadic cases were infected through distinct sources, and that the two family cases were due to a common source of infection or person to person infection.

Bacterial Toxins↗