[Acute myocarditis with erythema nodosum].
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Biomedical subjects
Publications and source records attributed to Y Noda.
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Magnetic fields (MF) may affect biological systems by increasing free radical concentrations. To test this, we have investigated whether low frequency (60 Hz) low intensity (0.1 mT) MF can modulate the phorbol 12-myristate 13- acetate (PMA) induced respiratory burst in primed rat peritoneal neutrophils, followed in real time using the dye 2',7'-dichlorofluorescin (DCFH), which reacts with free radical-derived oxidants such as H2O2 (which is formed from the dismutation of superoxide) to become 2',7'-dichlorofluorecein (DCF), a highly fluorescent compound. In the presence of the MF, a 12.4% increase in the fluorescence signal was observed in PMA-stimulated neutrophils (n = 5, P < 0.02, 18 pairs of measurements). We believe this represents the first experimental observation of MF influencing events involving free radical species generated during signal transduction in living cells.
The present study was undertaken to investigate the involvement of nitric oxide (NO) in the behaviors induced by 1-(1-phenylcyclohexyl) piperidine (phencyclidine; PCP) in mice, using N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase. PCP (1, 3, and 10 mg/kg s.c.) dose dependently induced hyperlocomotion and stereotyped behaviors, including sniffing, head movement, and ataxia, in mice. PCP also caused a marked deficit of motor coordination in mice, the effect being exerted in a dose-dependent manner. Although pretreatment with L-NAME (50 mg/kg i.p.) slightly enhanced the ataxia induced by PCP (3 mg/kg), it failed to modify other stereotyped behaviors and the lack of motor coordination induced by PCP (2 mg/kg). The hyperlocomotion induced by PCP (3 mg/kg) was significantly enhanced by L-NAME (5 and 50 mg/kg) and 7-nitro indazole (25 mg/kg), but not by D-NAME (50 mg/kg), a less active enantiomer of L-NAME. However, the behavioral changes induced by PCP, at the high dose, 10 mg/kg, were not enhanced by L-NAME and D-NAME. The enhancing effects of L-NAME on the PCP (3 mg/kg)-induced hyperlocomotion were significantly prevented by L-arginine (1 g/kg i.p.). However, D-arginine (1 g/kg i.p.) and L-lysine (1 g/kg i.p.) had no effect in this regard. These results suggested the involvement of central NO production in the mediation of PCP-induced behaviors, hyperlocomotion in particular, in mice.
PURPOSE: To examine the possibility of freezing human embryos at late cleaved stages (morula or blastocyst stage), we cryopreserved human embryos 5 days (day 5) or 6 days (day 6) after insemination and investigated their developmental potential after thawing. MATERIALS AND METHODS: One hundred nineteen morphologically good-quality human embryos from 43 women undergoing in vitro fertilization treatment between 1991 and 1992 were frozen using dimethylsulfoxide as a cryoprotectant. The embryos were cryopreserved for 5 to 30 months. After thawing they were then cultured in vitro for 24 hr to investigate their developmental potential. Survival rates and developmental rates were morphologically assessed after 24 hr of in vitro culture. RESULTS: Developmental rates were significantly (P < 0.01 or P < 0.05) lower than survival rates at every developmental stage. There was no difference in total survival rates between embryos frozen 5 days after insemination (78.2%; 54/69) and embryos frozen 6 days after insemination (70.0%; 35/54). However, the developmental rates after 24 hr of culture was significantly (P < 0.05) lower for embryos frozen 6 days after insemination (6.0%; 3/50) than for embryos frozen 5 days after insemination (18.8%; 13/69). Only two embryos developed into fetuses after transfer into the uterus (1.7%; 2/119). CONCLUSIONS: From the results, the developmental potential of frozen-thawed human blastocysts was found to be significantly reduced, even though the blastocysts were of morphologically good quality. Longer in vitro exposure of embryos appears to reduce their developmental potential.
The purpose of this study was to determine whether encapsulation of vasoactive intestinal peptide (VIP) into liposomes potentiated its vasorelaxant effects in vivo. Using intravital microscopy, we measured the diameter of second-order arterioles (53 +/- 1 microns) in the hamster cheek pouch before, during and after suffusion of VIP, liposomes and VIP encapsulated into liposomes for 7 min. We found that VIP (0.05, 0.1 & 1.0 nmol) induced significant, time- and concentration-dependent vasodilation (9 +/- 1%, 13 +/- 3% and 14 +/- 1% increase from baseline values, respectively; mean +/- SEM; n = 12; p < 0.05). Arteriolar diameter returned to baseline values within 1-4 min after suffusion was stopped. These effects were significantly potentiated when VIP (0.05, 0.1 & 1.0 nmol) was encapsulated into liposomes (26 +/- 6%, 38 +/- 7% and 34 +/- 3% increase from baseline values, respectively; n = 12; p < 0.05). In addition, arteriolar diameter returned to baseline values 5-13 min after suffusion was stopped. Suffusion of liposomes alone had no significant effects on arteriolar diameter (n = 12; p > 0.5). We conclude that encapsulation of VIP into liposomes potentiates and prolongs of its vasorelaxant effects in the peripheral microcirculation in vivo.
We investigated the effects of RGH-2202 (posatirelin, (-)-(2S)-N-[(1S)-1-[[(2S)-2-carbamoyl-1-pyrrolidinyl[carbonyl]-3- methylbutyl]-6-oxopipecolamide), a thyrotropin-releasing hormone (TRH) analog, on behavioral changes during a chronic phase of focal ischemia in rats in comparison with the parent peptide. The left middle cerebral artery (MCA) was occluded under halothane anesthesia, and the subsequent behavioral changes were observed for 35 days. RGH-2202 (1, 3, and 10 mg/kg) and TRH (10 mg/kg) were given IP just after the operation and afterward once a day for 14 days. MCA-occluded rats exhibited neurologic symptoms including hemiplegia and abnormal posture and disturbance of passive avoidance learning during the entire 35-day observation period. The repeated treatment with either peptides improved the neurologic and cognitive deficits. In addition, a recovery from deficits was still advanced after discontinuation of the drug treatment. In these effects, RGH-2202 was about three times more potent than TRH. Neural tissue damage in drug-treated groups, measured by omega 3 binding site densities 35 days after MCA occlusion, was included to be less than that in the vehicle-treated group. These results suggest that appropriate treatment with RGH-2202 may be useful in the treatment of functional disturbances after focal cerebral ischemia.
A computer-assisted method of estimating the distribution of muscle fiber conduction velocities is described. An electrode array composed of 2 stimulating and 4 recording electrodes is used to record surface muscle action potentials (MAPs) in response to direct muscle stimulation. The velocity distribution and the single muscle fiber action potential (SFAP) are calculated from the recorded MAPs by an iterative method of estimation. The estimation is based on the assumption that the spatial orientation of each muscle fiber viewed from the recording electrodes is the same along the muscle fibers and a MAP is recorded as a linear summation of all SFAPs. The accuracy of this estimation is demonstrated using simulated MAPs. The method is also tested on MAPs containing simulated amplifier noise, stimulus artifact, and errors in distance between electrodes. Finally we applied this method to MAP recordings of the biceps brachii in 23 healthy subjects. The velocity distribution was successfully estimated in 20 cases. The average of the estimated distributions was smaller than that described by previous workers. The reasons for the difference are discussed.
Kinesin is known as a representative cytoskeletal motor protein that is engaged in cell division and axonal transport. In addition to the mutant assay, recent advances using the PCR cloning technique have elucidated the existence of many kinds of kinesin-related proteins in yeast, Drosophila, and mice. We previously cloned five different members of kinesin superfamily proteins (KIFs) in mouse brain (Aizawa, H., Y. Sekine, R. Takemura, Z. Zhang, M. Nangaku, and N. Hirokawa. 1992. J. Cell Biol. 119:1287-1296) and demonstrated that one of them, KIF3A, is an anterograde motor (Kondo, S., R. Sato-Yashitake, Y. Noda, H. Aizawa, T. Nakata, Y. Matsuura, and N. Hirokawa. J. Cell Biol. 1994. 125:1095-1107). We have now characterized another axonal transport motor, KIF2. Different from other KIFs, KIF2 is a central type motor, since its motor domain is located in the center of the molecule. Recombinant KIF2 exists as a dimer with a bigger head and plus-end directionally moves microtubules at a velocity of 0.47 +/- 0.11 microns/s, which is two thirds that of kinesin's. Immunocytological examination showed that native KIF2 is abundant in developing axons and that it accumulates in the proximal region of the ligated nerves after a 20-h ligation. Soluble KIF2 exists without a light chain, and KIF2's associated-vesicles, immunoprecipitated by anti-KIF2 antibody, are different from those carried by existing motors such as kinesin and KIF3A. They are also distinct from synaptic vesicles, although KIF2 is accumulated in so-called synaptic vesicle fractions and embryonal growth cone particles. Our results strongly suggest that KIF2 functions as a new anterograde motor, being specialized for a particular group of membranous organelles involved in fast axonal transport.
It has been demonstrated previously that pregnancy can be achieved by the direct insertion of embryos into the endometrial stroma (intra-endometrial embryo transfer) of mice. In this study we evaluated whether intra-endometrial transfer resulted in a higher pregnancy rate than conventional embryo transfer. Mouse blastocysts (ICR strain), recovered on day 4 of pregnancy, were transferred into pseudopregnant day 2, day 3 and day 4 mice of the same strain; 1-, 2- and 8-cell embryos were also transferred into pseudopregnant day 4 mice. In intra-endometrial embryo transfer, a 27 gauge injection needle was inserted near the utero-tubal junction into the endometrial stroma and then removed; one blastocyst was transferred into each uterine horn with a glass micropipette. Conventional transfers were performed simultaneously as controls. The pregnancy rates and embryonic viability rates were evaluated 9 days after embryo transfer. Furthermore, the rates of live birth for intra-endometrial and conventional embryo transfers were compared when blastocysts were transferred into pseudopregnant day 4 uteri by both methods. In the transfer to pseudopregnant day 2 recipients, the pregnancy and embryonic viability rates were significantly higher (P < 0.01) in intra-endometrial [23.4 (11/47) versus 15.9% (15/94)] than in conventional embryo transfer [4.3 (2/46) versus 2.2% (2/92)]. In the transfer to pseudopregnant day 3 recipients, both rates were also higher (P < 0.01) in intra-endometrial [90.9 (40/44) versus 87.5% (77/88)] than in conventional transfer [67.4 (31/46) versus 64.1% (59/92)].(ABSTRACT TRUNCATED AT 250 WORDS)
1. We investigated the effects of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthase, on the performance of rats in a radial arm maze and in habituation tasks, and on monoamine metabolism in the brain. 2. Daily administration of L-NAME (10-60 mg kg-1) resulted in a dose-dependent impairment of performance during the acquisition of the radial arm maze task, while it failed to affect performance in those rats that had previously acquired the task. 3. The rate of decrease in locomotor activity in the habituation task in the L-NAME-treated rats was significantly less than that in control rats. 4. NG-nitro-D-arginine methyl ester (D-NAME, a less active inhibitor of NO synthase) showed no effects in the above behavioural tasks. 5. NO synthase activity was significantly decreased in both the L-NAME and D-NAME-treated rats, with the magnitude of inhibition being greater in the L-NAME-treated animals. 6. The content of 5-hydroxyindoleacetic acid (5-HIAA) in the hippocampus and the 5-HIAA/5-hydroxytryptamine ratio in the hippocampus and cortex were significantly decreased in the L-NAME (60 mg kg-1)-treated rats compared with these values in the controls. 7. Striatal 3,4-dihydroxyphenylacetic acid (DOPAC) content was significantly increased in the L-NAME (60 mg kg-1)-treated rats compared with the values in the controls, while the DOPAC/dopamine ratio was not changed. 8. These results suggest that: (i) NO may play an important role in performance during the acquisition,but not retention, of the radial arm maze task, and (ii) that endogenous NO may be involved in the regulation of monoamine metabolism.
1. Immobility induced by forced swimming is well known as an animal model of depression. To develop an animal model for the negative symptoms of schizophrenia, in particular the depressive symptoms, the effect of phencyclidine (PCP) on immobility in the forced swimming test was investigated in mice, since PCP produces such negative symptoms in humans. 2. Repeated treatment with PCP (10 mg kg-1 day-1, s.c., once a day for 14 days) prolonged the immobility time in the forced swimming test 24 h after the final injection compared with saline treatment; the effect was not obtained by single or 5 treatments with PCP (10 mg kg-1, s.c.), or by repeated treatment with methamphetamine (0.5 and 1 mg kg-1 day-1, s.c., once a day for 14 days). 3. The enhancing effect of PCP (10 mg kg-1 day-1, s.c.) on the immobility persisted for at least 21 days after the withdrawal of the drug. 4. Haloperidol (0.3 and 1 mg kg-1, p.o.), ritanserin (3 and 10 mg kg-1, p.o.), risperidone (0.1-1 mg kg-1, p.o.), and clozapine (3 and 10 mg kg-1, p.o.) failed to attenuate the immobility induced by the forced swimming in mice repeatedly treated with saline when the drugs were administered 1 h before the forced swimming test. However, ritanserin (30 mg kg-1) and clozapine (30 mg kg-1) did attenuate this immobility. 5. The enhancing effect of PCP on the immobility was attenuated by ritanserin (3 and 10 mg kg-1, p.o.), risperidone (0.3 mg kg-1, p.o.), and clozapine (3 and 10 mg kg-1, p.o.), whereas haloperidol (0.3 and 1 mg kg-1, p.o.) had no effect. 6. These results suggest that the enhancement of immobility in the forced swimming test brought about by repeated PCP treatment could be used as a model of the negative symptoms, particularly the depression, of schizophrenia. This effect of PCP appeared to be mediated, at least in part, via 5-HT2A receptors.
Overproduction of TmrB protein, a 22.5-kDa protein with an N-terminal ATP-binding region and a C-terminal amphiphilic alpha-helix, confers resistance to tunicamycin on Bacillus subtilis. TmrB protein was found to bind Sepharose 6B to which tunicamycin was covalently linked. Experiments with mutant proteins found that the C-terminal region of TmrB protein might be involved in the binding to tunicamycin.
A clinico-pathological study was done to elucidate characteristic features of subacute interstitial pneumonia. The patients were four men and mine women, with a mean age of 60 years. In ten patients, the disease was idiopathic, three had collagen vascular disease, (and one was undergoing gold therapy for rheumatoid arthritis). The time interval between onset of symptoms and open lung biopsy was 80 +/- 40 days. Eleven patients had progressive dyspnea, seven had coughing, and only one complained of fever. Fine crakles were heard in ten patients. Mild increases in CRP were observed in all cases. Mild increases in total serum IgG concentration were observed in five of eight cases. Multiple patchy infiltration or diffuse interstitial shadows, located predominantly in the lower fields of both lungs were the characteristic chest roentgenographic findings. The average %VC was 62.7 +/- 17% and the average PaO2 was 68.3 +/- 10 Torr. Bronchoalveolar lavage was done in nine patients, and the mean total cell count was 16.5 +/- 10.2 x 10(4)/ml. A moderate increase in lymphocytes (30.8 +/- 18.6%) with a low CD4/8 ratio (0.48 +/- 0.57), a mild increase in neutrophils (6.2 +/- 9.1%), and a mild increase in eosinophils (2.3 +/- 3.7%) were observed. Pathologically, interstitial cellulo-fibrous changes associated with alveolar space closure due to organization of exudate were the main features. Patients were given steroid pulse therapy or oral steroids. The results were mild to marked improvements in chest roentgenographic findings and lung function.(ABSTRACT TRUNCATED AT 250 WORDS)
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Forty-two patients with head and neck cancer were treated with tegafur suppository for 7 days preoperatively and clinical value of this treatment was assessed. In a group which indicated tumor tissue concentrations of 5-FU were more than 0.5 micrograms/g, local recurrence decreased in the period of postoperative observation for 42 months. A survival rate of this group was better than others. From these results, preoperative tegafur suppository treatment seemed to have a role in expectation of improvement of local control in head and neck cancer therapy.
BACKGROUND: Association between Epstein-Barr virus (EBV) and human malignancies, including sino-nasal lymphoma (SNL), has been suggested. EBV-associated malignancies have been reported to show distinct geographic distribution. EXPERIMENTAL DESIGN: In the present study, the presence of an EBV genome and its subtypes (type A and B) were examined in 52 cases of sino-nasal lymphomas of B and T cell type collected from two areas of Japan: Osaka, situated on the mainland, and Okinawa, islands situated in a southwest part of Japan with a subtropical climate. Our previous epidemiologic study showed that the frequency of nasal T cell lymphoma was 3.5 times higher in Okinawa than in Osaka. RESULTS: There were no prominent differences in age distribution or sex ratio between these two areas: age ranged 8 to 85 (median 54) years, with a male to female ratio of 1.26:1. Immunophenotypically, 27 cases were B cell type (20 Osaka, 7 Okinawa), 20 were T cell type (9 Osaka, 11 Okinawa), and 5 were undefined. By PCR, EBV positivity in throat washings of normal individuals in Osaka and Okinawa was 52 and 53%, respectively, with marked preponderance of subtype A in both areas. EBV genome was found in 6 of 15 cases (40%) and 4 of 5 cases (80%) of nasal B and T cell lymphomas in Osaka and in 3 of 7 cases (43%) and 7 of 7 cases (100%) in Okinawa, showing the different frequencies of positivity by immunophenotype but not by district. All but one patient had type A EBV. The in situ hybridization confirmed the results of PCR as positive signals in the nucleus of proliferating cells. Latent membrane protein-1 was expressed in 13 of 22 cases (59%). CONCLUSIONS: These findings suggest that EBV, exclusively type A, might be a causative factor in sino-nasal lymphoma of not only T cell but also B cell type in Japan.
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