Biomedical subjects

M Ohsawa

Publications and source records attributed to M Ohsawa.

At least 55 records · Page 3Linked to original sources

PubMed2000

Differential antinociceptive effects of endomorphin-1 and endomorphin-2 in the mouse.

Two highly selective mu-opioid receptor agonists, endomorphin-1 and endomorphin-2, have been identified and postulated to be endogenous mu-opioid receptor ligands. We determined the antinociceptive effects of these two ligands at the supraspinal level in mice with the tail-flick and hot-plate responses. The i.c.v. injection of endomorphin-1 and -2 inhibited the tail-flick and hot-plate responses in a dose-dependent manner. The endomorphin-1 was found to be 3.3- and 2.4-fold more potent than endomorphin-2 in inhibiting the tail-flick and hot-plate responses, respectively. The antinociception induced by endomorphin-1 was blocked by i.c.v. pretreatment with the mu-opioid receptor antagonist beta-funaltrexamine but not by the kappa-opioid receptor antagonist nor-binaltorphimine, the delta(1)-opioid antagonist 7-benzylidene naltrexamine, or the delta(2)-opioid receptor antagonist naltriben. In contrast, the antinociception induced by endomorphin-2 was blocked by i.c.v. pretreatment with beta-funaltrexamine or nor-binaltorphimine but not by 7-benzylidene naltrexamine or naltriben. The inhibition of the tail-flick response induced by endomorphin-2 was blocked by pretreatment with an antiserum against dynorphin A(1-17) but not by antisera against Met-enkephalin, Leu-enkephalin, or beta-endorphin. None of these antisera reduced the endomorphin-1-induced tail-flick inhibition. We propose that endomorphin-1 produces antinociception by stimulating one type of mu-opioid receptor, whereas endomorphin-2 initially stimulates different mu-opioid receptors, which subsequently induce the release of dynorphins that act on kappa-opioid receptors to produce antinociception.

Analgesics↗

PubMed2000

Differential mechanisms mediating descending pain controls for antinociception induced by supraspinally administered endomorphin-1 and endomorphin-2 in the mouse.

We have previously demonstrated that both endomorphin-1 and endomorphin-2 produce their antinociception by the stimulation of mu-opioid receptors. However, the antinociception induced by endomorphin-2 contains an additional component, which is mediated by the release of dynorphin A (1-17) acting on kappa-opioid receptors. These studies were done to determine whether the antinociception induced by endomorphin-1 and endomorphin-2 given supraspinally was mediated by the activation of different descending pain control pathways in the mouse. Specific receptor antagonists or antisera against endogenous opioid peptides were injected intrathecally to block the receptors or bind the released endogenous opioid peptides, and endomorphin-1 or endomorphin-2 was then administered i.c.v. to activate the descending pain control systems to produce antinociception. The tail-flick response was used as antinociceptive test. The blockade of the alpha(2)-adrenoceptors and 5-hydroxytryptamine receptors in the spinal cord by i.t. injection of yohimbine and methysergide, respectively, inhibited the antinociception induced by i.c.v.-administered endomorphin-1 and endomorphin-2. However, the antinociception induced by endomorphin-2 was inhibited by i.t. pretreatment with delta(2)-opioid receptor antagonist naltriben or kappa-opioid receptor antagonist nor-binaltorphimine, but not by the mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Try-Orn-Thr-Pen-Thr-NH(2) or the delta(1)-opioid receptor antagonist 7-benzylidene naltrexamine. Intrathecal pretreatment with antiserum against Met-enkephalin attenuated the antinociception induced by i.c.v.-administered endomorphin-2, but not endomorphin-1. Furthermore, i.t. pretreatment with antiserum against dynorphin A (1-17) also inhibited the antinociception induced by i.c.v.-administered endomorphin-2, but not endomorphin-1. Intrathecal pretreatment with antiserum against Leu-enkephalin or beta-endorphin did not inhibit i.c.v.-administered endomorphin-1- or endomorphin-2-induced antinociception. The results indicate that, like other opioid micro-receptor agonists, morphine, and [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin, endomorphin-1 and endomorphin-2 given i.c.v. produce antinociception by activating spinipetal noradrenergic and serotonergic pathways for producing antinociception. However, the antinociception induced by endomorphin-2 given i.c.v. also contains other components, which are mediated by the release of Met-enkephalin and dynorphin A (1-17) acting on opioid delta(2)- and kappa-receptors, respectively, in the spinal cord.

Adrenergic alpha-Antagonists↗

PubMed1999

The modulatory effect of (+)-TAN-67 on the antinociceptive effects of the nociceptin/orphanin FQ in mice.

To clarify the pharmacological properties of (+)2-Methyl-4aalpha-(3-hydroxyphenyl)-1, 2, 3, 4, 4a, 5, 12, 12aalpha-octahydro-quinolino[2, 3, 3-g]isoquinoline ((+)-TAN-67), the effect of (+)-TAN-67 on the antinociception induced by the intrathecal (i.t.) administration of nociceptin/orphanin FQ was studied in mice using the tail-flick test and the formalin test. I.t. administration of (+)-TAN-67, at doses of 1 to 10 ng, facilitated the tail-flick response in a dose-dependent manner in mice. In addition, i.t. administration of (+)-TAN-67 (1 to 10 ng) in mice produced a marked pain-like aversive responses. I.t. pretreatment with D-Pro(9)-[spiro-gamma-lactam]-Leu(10)-Trp(11)-physalaemin(1-11) (GR82334, 0.1-1.0 nmol), a potent and selective tachykinin NK(1) receptor antagonist, dose-dependently blocked the reduction of the tail-flick response induced by (+)-TAN-67. Furthermore, (+)-TAN-67-induced facilitation of the tail-flick response was abolished in capsaicin-treated mice. On the other hand, (+)-TAN-67-induced flinching responses were dose-dependently and significantly reduced by i.t. pretreatment with GR82334 (0.1-1.0 nmol). The duration of i.t. (+)-TAN-67-induced flinching responses was significantly reduced in capsaicin-treated mice as compared with naive mice. I.t. administration of nociceptin/orphanin FQ (1-10 nmol) dose-dependently increased the tail-flick latency. I.t. administration of nociceptin/orphanin FQ (0.1-1.0 nmol) significantly and dose-dependently reduced the first-phase nociceptive response, but not the second-phase nociceptive response. I.t. pretreatment with (+)-TAN-67 (0.3-3.0 microg) for 30 min dose-dependently attenuated the antinociception induced by i.t. nociceptin (10 nmol) in the tail-flick test. Furthermore, the antinociceptive effect of nociceptin/orphanin FQ (1 nmol, i.t.) on the first-phase response in the formalin test was dose-dependently attenuated by s.c. pretreatment with (+)-TAN-67 (0.3-3.0 microg). (+)-TAN-67 (0.3-3.0 microg, i.t.), by itself, did not facilitate the tail-flick response or produce apparent behavioral changes. It is possible that (+)-TAN-67 has an antagonistic effect on nociceptin/orphanin FQ-induced antinociception.

Analgesics↗

PubMed1999

HLA-A alleles of patients with pyothorax-associated lymphoma: anti-Epstein-Barr virus (EBV) host immune responses during the development of EBV latent antigen-positive lymphomas.

Pyothorax-associated lymphoma (PAL) is an Epstein-Barr virus (EBV) latent antigen-positive lymphoma resembling EBV-transformed lymphoblastoid cell lines (LCLs) and develops in non-immunocompromised patients. Thus, deficient anti-viral-antigen immune responses might be involved in the development of PAL. As MHC class I-restricted cytotoxic T lymphocytes (CTLs) are the major constituent of anti-viral immune responses, the HLA allele type and its expression may affect the development of PAL. Flow-cytometric analyses of PAL cell lines and LCLs using the W6/32 monoclonal antibody revealed that expression of HLA class I varied among cell lines. Although one PAL cell line, OPL-2, exhibited low expression, an LCL and another PAL cell line, OPL-1, strongly expressed HLA class I. Among the EBV latent infection genes, EBV nuclear antigens 2, 3, 4 and 6 and latent membrane proteins can induce efficient CTL responses in combination with HLA-A2 or -A11. HLA-A alleles of PAL patients were determined using low-resolution PCR-based typing with HLA-A locus sequence-specific primer combinations. The antigen frequencies of HLA-A2 and -A11 in PAL patients were not significantly different from those in the normal Japanese population. Although HLA class I antigen should be expressed during the course of lymphomagenesis, no HLA-A alleles influenced the development of overt PALs.

Aged↗

PubMed1999

Role of intracellular calcium in thermal allodynia and hyperalgesia in diabetic mice.

We examined the involvement of cytosolic calcium on thermal hyperalgesia and allodynia seen in diabetic mice. Tail-flick latencies at source voltages of a 50-W projection bulb to 35 and 50 V in diabetic mice were significantly shorter than those in non-diabetic mice. Tail-flick latencies at 35 and 50 V in diabetic mice were increased by pretreatment with ryanodine, which blocks Ca2+ release from Ca2+/caffeine-sensitive microsomal pools. On the other hand, intrathecal (i.t.) pretreatment with thapsigargin, which inhibits Ca2+ uptake into the inositol-1,4,5-trisphosphate-sensitive microsomal Ca2+ pool, decreased tail-flick latencies at 35 and 50 V in non-diabetic mice. Thus, it seems likely that thermal allodynia and hyperalgesia in diabetic mice may be due, in part, to the enhancement of intracellular calcium level in the spinal cord.

Animals↗

PubMed1999

Modification of the effect of diazepam on the propofol-induced loss of the righting reflex in mice by diabetes.

The effect of diabetes on the effect of diazepam on the propofol-induced loss of the righting reflex was investigated. There was no significant difference in the duration of the propofol-induced loss of the righting reflex between non-diabetic and diabetic mice. Diazepam increased the duration of the propofol-induced loss of the righting reflex in both diabetic and non-diabetic mice. The diazepam-induced enhancement of the effect of propofol was significantly lower in diabetic mice than that in non-diabetic mice. These effects were antagonized by the pretreatment with flumazenil. Pretreatment with FG7142, a benzodiazepine receptor inverse agonist, attenuated the duration of the propofol-induced loss of the righting reflex in non-diabetic mice, but not in diabetic mice. These results suggest that the attenuation of the diazepam-induced enhancement of the duration of the propofol-induced loss of the righting reflex in diabetic mice may be due to the dysfunction of benzodiazepine receptors.

Anesthetics, Intravenous↗

PubMed1999

Immunophenotypic and genotypic characterization of nasal lymphoma with polymorphic reticulosis morphology.

Nasal lymphoma with polymorphic reticulosis (PR) morphology is now categorized as T/natural killer (T/NK) cell lymphoma. In this study, immunophenotypes and genotypes of proliferating cells in 21 cases with PR were examined. The patients included 13 men and 8 women ranging in age from 20 to 74 (median 37) years. All patients presented with lesions in the upper respiratory tract, mostly in the nasal cavity. Histological specimens obtained from the primary lesions (19 cases) and metastatic cervical lymph nodes (2 cases) were used for analyses. Histologically, polymorphous proliferation was found in 20 cases, and these were thus diagnosed as PR. A monomorphous pattern was found in the remaining last case. Immunohistochemical analysis revealed that the proliferating cells were CD56 (123C3)+ and/or CD16 (2H7)+, TIA-1+ and frequently stained CD3 epsilon+. Tumor cells were frequently stained positively with monoclonal antibodies (mAbs) for T lymphocytes, but were negative for T-cell receptor (TCR) beta and delta chain expression. In situ hybridization analysis using an Epstein-Barr virus-encoded early RNA 1 (EBER-1) probe revealed positive signals in 13 of the 15 cases examined. Southern blotting analysis for clonality of the Epstein-Barr virus (EBV) genome in 12 positive cases confirmed the presence of monoclonal proliferation in 7 cases. The pattern of TCR gamma chain gene rearrangement was examined by PCR analysis of DNA from tumor tissues by the denaturing gradient gel electrophoresis method. The results demonstrated no clonal rearrangement in any of the 21 cases examined, including 7 cases with proven clonal proliferation of EBV-infected cells, indicating the absence of T-cell clones. Our findings strongly suggested that nasal T-cell lymphoma is in fact a NK cell lymphoma.

Adult↗

PubMed1999

Possible mechanisms for insulin-induced attenuation of the antinociceptive effect of [D-Ala2, N-MePhe4, Gly-ol5]enkephalin.

The effects of pretreatment with protein kinase C and protein kinase A inhibitors on the intraventricular insulin-induced attenuation of the antinociceptive effect of [D-Ala2, N-MePhe4, Gly-ol5]enkephalin (DAMGO) were studied in mice. Intracerebroventricular (i.c.v.) pretreatment with insulin dose- and time-dependently attenuated the antinociceptive effect of i.c.v. DAMGO (5.6 ng) in mice. Intracerebroventricular pretreatment with a highly selective tyrosine kinase inhibitor, herbimycin A, at doses of 200 and 600 ng for 70 min, dose-dependently reversed the attenuation of the antinociceptive effect of DAMGO (5.6 ng, i.c.v.) caused by insulin. Furthermore, i.c.v. pretreatment with serine/threonin kinase inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine hydrochloride (H7), at doses of 3-30 nmol for 60 min, dose-dependently reversed the attenuation of the antinociceptive effect of DAMGO (5.6 ng, i.c.v.) caused by insulin. Intracerebroventricular pretreatment with selective protein kinase C inhibitor, calphostin C, at doses of 1 and 3 pmol for 60 min, but not with a highly protein kinase A inhibitor, (8R, 9S, 11S)-(-)-9-hydroxy-9-n-hexyloxy-carbonyl-8-methyl-2, 3, 9, 20-tetrahydro-8, 11-epoxy-1H, 8H, 11H-2, 7b, 11a-triaqzadibenzo[a, g]cycloocta[c, d, e]-trinden-1-one (KT5720), at dose of 10 pmol for 60 min, reversed the attenuation of the antinociceptive effect of DAMGO (5.6 ng, i.c.v.) caused by insulin. These results suggest that the reduction of DAMGO-induced antinociception by insulin in mice may be, in part, due to the activation of protein kinase C followed by the activation of tyrosine kinase.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1999

Possible involvement of spinal protein kinase C in thermal allodynia and hyperalgesia in diabetic mice.

We examined the tail-flick response to various heat intensities in diabetic and non-diabetic mice. Heat intensities were set to one of five values by adjusting the source voltage of a 50-W projection bulb to 25, 35, 50, 65 and 80 V. These heat intensities produced surface skin heating rates of 0.1, 0.4, 0.9, 3.0 and 7.3 degrees C/s, respectively. Tail-flick latencies at source voltages of 35 and 50 V in diabetic mice were significantly shorter than those in non-diabetic mice. However, there were no significant differences in tail-flick latencies at 25, 65 and 80 V. In non-diabetic mice, tail-flick latencies were not affected by intrathecal (i.t.) pretreatment with capsaicin 24 h before testing. Tail-flick latencies at 35 and 50 V in diabetic mice were increased by pretreatment with capsaicin. Moreover, although tail-flick latencies in non-diabetic mice were not affected by i.t. pretreatment with calphostin C, a selective protein kinase C inhibitor, those at 35 and 50 V in diabetic mice were increased. However, i.t. pretreatment with (8R, 9S, 11S)-(-)-9-hydroxy-9-n-hexyloxy-carbonyl-8-methyl-2, 3, 9, 10-tetrahydro-8, 11-epoxy-1H, 8H, 11H-2, 7b, 11a-triazadibenzo [a, g]cycloocta[cde]-trinden-1-one (KT5720), a selective protein kinase A inhibitor, did not affect tail-flick latencies in either diabetic or non-diabetic mice. In non-diabetic mice, i.t. pretreatment with phorbol 12,13-dibutyrate (PDB), a protein kinase C activator, decreased tail-flick latencies at 35 and 50 V. Tail-flick latencies in diabetic mice were not affected by i.t. pretreatment with PDB 60 min before testing. Furthermore, the attenuation of tail-flick latencies induced by i.t. pretreatment with PDB in non-diabetic mice was reversed by i.t. pretreatment with capsaicin 24 h before testing. These results indicate that diabetic mice exhibit thermal allodynia and hyperalgesia. Furthermore, this thermal allodynia and hyperalgesia in diabetic mice may be due to the enhanced release of substance P followed by activation of protein kinase C in the spinal cord.

Analysis of Variance↗

PubMed1999

Antinociceptive effects of the ORL1 receptor agonist nociceptin/orphanin FQ in diabetic mice.

The antinociceptive potency of nociceptin/orphanin FQ, an opioid-like orphan receptor agonist, was examined using the tail-flick test and the formalin-induced nociception test in diabetic mice. Nociceptin/orphanin FQ, at doses of 0.1 to 10 nmol, intrathecal (i.t.), produced a marked and dose-dependent inhibition of the tail-flick response in both non-diabetic and diabetic mice. The antinociceptive effect of nociceptin/orphanin FQ in the tail-flick test in diabetic mice was greater than that in non-diabetic mice. The antinociceptive effect of nociceptin/orphanin FQ was not antagonized by pretreatment with either beta-funaltrexamine, a selective mu-opioid receptor antagonist, naltrindole, a selective delta-opioid receptor antagonist, or nor-binaltorphimine, a selective kappa-opioid receptor antagonist. The antinociceptive effects of nociceptin/orphanin FQ in diabetic, but not in non-diabetic mice, were abolished when mice were pretreated with capsaicin i.t. 24 h before testing. In the formalin test, nociceptin/orphanin FQ also produced a marked and dose-dependent antinociceptive effect on the first-phase response, but not the second phase-response, in both diabetic and non-diabetic mice. Furthermore, nociceptin/orphanin FQ significantly and dose-dependently reduced the flinching responses to i.t.-administered substance P in diabetic mice, but not in non-diabetic mice. The results of the present experiments clearly indicate that the antinociceptive potency of nociceptin/orphanin FQ is significantly greater in diabetic mice than in non-diabetic mice. Furthermore, the results of this study suggest that the reduction of substance P-mediated nociceptive transmission in the spinal cord may be responsible for the antinociceptive effect of nociceptin/orphanin FQ.

Animals↗

PubMed1999

Risk of non-Hodgkin's lymphoma in patients with hepatitis C virus infection.

Hepatitis C virus (HCV) has been suggested to play an etiological role in the development of B-cell non-Hodgkin's lymphoma (NHL) in Italy. However, another study in Scotland questioned increased risk of development of NHL in patients with chronic HCV infection. A total of 2,162 patients admitted to 3 hospitals in Osaka, where the incidence of HCV-related hepatitis is highest in Japan, during the period from 1957 to 1997 were followed up from the date of diagnosis of chronic HCV-related hepatitis until 30 October 1997. Overall, 12,404.5 person-years of observation were accrued with a follow-up period ranging from 0.25 to 40.4 (average 5.74) years. NHL of the B-cell type developed in 4 patients. The interval between onset of chronic HCV and NHL ranged from 6 to 36 (median 13) years. Expected number of cases of NHL in the sex-, age- and calendar year-matched general population was 1.90, which gave a relative risk (RR) of 2.10 (95% confidence interval 0.57-5.38; p = 0.247). Taking the much higher RR for hepatocellular carcinoma among patients with HCV infection into account, chronic HCV infection was considered to be moderately associated with increased risk of NHL.

Adolescent↗

PubMed1999

Role of intracellular calcium on the modulation of naloxone-precipitated withdrawal jumping in morphine-dependent mice by diabetes.

The role of intracellular calcium in the modifications of naloxone-precipitated withdrawal jumping in morphine-dependent mice by diabetes was examined. Naloxone-precipitated withdrawal jumping was significantly less in morphine-dependent diabetic mice than in morphine-dependent non-diabetic mice. Intracerebroventricular (i.c.v. ) pretreatment with ryanodine attenuated naloxone-precipitated withdrawal jumping in morphine-dependent non-diabetic mice. However, naloxone-precipitated withdrawal jumping in morphine-dependent diabetic mice was not affected by i.c.v. pretreatment with ryanodine. Moreover, i.c.v. pretreatment with thapsigargin, a Ca2+-ATPase inhibitor, enhanced naloxone-precipitated withdrawal jumping in morphine-dependent non-diabetic mice, but not in morphine-dependent diabetic mice. The noradrenaline (NA) turnover in the frontal cortex in morphine-dependent non-diabetic mice, but not in morphine-dependent diabetic mice, was significantly increased by naloxone injection. Naloxone-induced enhancement of NA turnover in morphine-dependent non-diabetic mice, but not in morphine-dependent diabetic mice, was blocked by i.c.v. pretreatment with ryanodine. In contrast to ryanodine, thapsigargin enhanced naloxone-induced enhancement of NA turnover in morphine-dependent non-diabetic mice. These results suggest that increased intracellular calcium augmented naloxone-precipitated withdrawal jumping and the turnover rate of NA in the frontal cortex in morphine-dependent non-diabetic mice. Furthermore, it seems likely that the attenuation of naloxone-precipitated withdrawal jumping in morphine-dependent diabetic mice may be due, in part, to the dysfunction of intracellular calcium store.

Animals↗

PubMed1999

Region-dependent G-protein activation by mu-, delta 1- and delta 2-opioid receptor agonists in the brain: comparison between the midbrain and forebrain.

The ability of selective mu- ([D-Ala2, NHPhe4, Gly-ol]enkephalin: DAMGO), delta1- ([D-Pen2, Pen5]enkephalin: DPDPE) and delta2- ([D-Ala2]deltorphin II: DELT II) opioid receptor agonists to activate G-proteins in the midbrain and forebrain of mice and rats was examined by monitoring the binding of guanosine-5'-O-(3-[35S]thio)triphosphate ([35S]GTPgammaS). The levels of [35S]GTPgammaS binding stimulated by DAMGO in the mouse and rat midbrain were significantly greater than those by DPDPE or DELT II. However, relatively lower levels of stimulation of [35S]GTPgammaS binding by all of the agonists than would have been predicted from the receptor densities were observed in either the limbic forebrain or striatum of mice and rats. The effects of DAMGO, DPDPE and DELT II in all three regions were completely reversed by selective mu-, delta1- and delta2-antagonists, respectively. The results indicate that the levels of mu-, delta1- and delta2-opioid receptor agonist-induced G-protein activation in the midbrain are in good agreement with the previously determined distribution densities of each receptor type. Furthermore, the discrepancies observed in the forebrain might reflect differential catalytic efficiencies of receptor-G-protein coupling.

Analgesics, Opioid↗

PubMed1999

Bone mineral density of epileptic patients on long-term antiepileptic drug therapy: a quantitative digital radiography study.

In order to assess the bone atrophy lesions of epileptic patients, the bone mineral densities (BMDs) of their lumbar spines and femoral necks were measured using quantitative digital radiography (QDR). The study groups were 44 patients on long-term medication for epilepsy and 62 healthy control subjects. We selected patients who had been taking phenytoin, barbiturates, and/or acetazolamide for at least 5 years. BMDs at both sites were significantly lower in the patient group than in the control group. No sex differences were found in BMDs. There were no significant correlations with the onset or the duration of illness and BMD. We compared BMD according to the type of epileptic drug being taken and theorized that phenytoin, barbiturates, and acetazolamide reduced BMD. BMDs of the 15 patients were measured again 7 years later, and were found to be significantly lower at both sites than in the previous examination. These results confirm the presence of bone atrophy lesions in epileptic patients on long-term antiepileptic drugs. Patients on antiepileptic therapy for long periods should have their BMDs checked, because they are prone to developing bone atrophy.

Absorptiometry, Photon↗

PubMed1999

kappa-Opioid receptor-mediated antinociceptive effects of stereoisomers and derivatives of (+)-matrine in mice.

The antinociceptive effects of seven matrine-type lupin alkaloids were examined using the acetic acid-induced abdominal contraction test (the writhing test) and the tail-flick test in mice. (+)-Allomatrine, the C-6 epimer of (+)-matrine, produced the antinociceptive effect at 1/3 potency of (+)-matrine or pentazocine. It was demonstrated that the antinociceptive effects of (+)-allomatrine were mediated through the activation of kappa-opioid receptors, while the antinociceptive effect of (+)-matrine was mediated by both mu- and kappa-opioid receptors. (-)-Sophoridine, the C-6 epimer of (+)-matrine, (+)-sophoranol, (-)-14 beta-hydroxymatrine and (+)-matrine N-oxide, which possess a hydrophilic group, and (-)-sophocarpine and (-)-sophoramine having a double bond(s) did not show significant antinociceptive activity.

Alkaloids↗

PubMed1999

Chronological changes in incidences of polymorphic reticulosis in Korea and Japan.

Lethal midline granuloma (LMG) is a clinical term, which describes a group of diseases histologically comprising Wegener's granulomatosis, polymorphic reticulosis (PR), and malignant lymphoma of the ordinary type (ML). PR is a variant of ML, and is considered to be a type of NK/T cell lymphoma. Our previous study revealed the clustering of patients with PR in East Asia including China, Korea and Japan. However, the frequency rate of PR varied even among these countries, with that of Korea being approximately 5 times higher than that of Japan. In the present study, we examined the incidences of each type of LMG, especially PR, in Korea (Yonsei University) and Japan (59 university hospitals) over time. A total of 102 cases and 655 cases of LMG admitted to Yonsei University, Korea from 1977 to 1996 and 59 university hospitals in Japan between 1965 and 1996, respectively, were examined. The frequency rate of PR per 100,000 outpatients of ears, nose and throat (ENT) clinics in Korea decreased from 40 to 20 between the periods of 1977-1989 and 1990-1996. However, there were no significant changes in Japan during the period studied.

Adolescent↗

PubMed1999

Modification of the expression of naloxone-precipitated withdrawal signs in morphine-dependent mice by diabetes: possible involvement of protein kinase C.

The involvement of cyclic AMP-dependent protein kinase (PKA) and protein kinase C (PKC) in the modulation of naloxone-precipitated withdrawal jumping in morphine-dependent mice by diabetes was examined. Naloxone-precipitated withdrawal jumps were significantly less in morphine-dependent diabetic mice than in morphine-dependent non-diabetic mice. I.c.v. pretreatment with either calphostin C, a PKC inhibitor, or KT-5720, a PKA inhibitor, attenuated naloxone-precipitated withdrawal jumps in morphine-dependent non-diabetic mice. However, naloxone-precipitated withdrawal jumps in morphine-dependent diabetic mice were not attenuated by i.c.v. pretreatment with either calphostin C or KT5720. Moreover, i.c.v. pretreatment with phorbol-12,13-dibutyrate (PDBu), a PKC activator, attenuated naloxone-precipitated withdrawal jumps in morphine-dependent non-diabetic mice, but not in morphine-dependent diabetic mice. The noradrenaline (NA) turnover in the frontal cortex in morphine-dependent non-diabetic mice, but not in morphine-dependent diabetic mice, was significantly increased 5 min after administration of naloxone. Naloxone-induced enhancement of NA turnover in morphine-dependent non-diabetic mice, but not in morphine-dependent diabetic mice, was blocked by i.c.v. pretreatment with either calphostin C or KT5720 1 hr before naloxone challenge and blocked by PDBu 1 hr before the last injection of morphine. These results suggest that the co-activation of PKC and PKA is needed to elicit naloxone-precipitated withdrawal jumps and enhancement of turnover rate of NA in the frontal cortex in morphine-dependent non-diabetic mice. Furthermore, the attenuation of naloxone-precipitated withdrawal jumps in morphine-dependent diabetic mice may be due, in part, to the desensitization of mu-opioid receptors by the activation of PKC.

Animals↗

PubMed1999

Effects of epinastine on the antitussive and rewarding effects of dihydrocodeine in mice.

The effects of chlorpheniramine and epinastine on dihydrocodeine were examined in mice. Orally administered dihydrocodeine (3-30 mg/kg) dose-dependently inhibited the number of capsaicin-induced coughs. The dose-dependent antitussive effects of dihydrocodeine were enhanced by each corresponding dose of chlorpheniramine or epinastine delivered at a ratio generally similar to that found in over-the-counter antitussive preparations (dihydrocodeine:histamine H1 antagonist = 3:1). The ED50 value of dihydrocodeine in combination with chlorpheniramine was nearly the same as that for dihydrocodeine in combination with epinastine. On the other hand, while combination treatment with dihydrocodeine (3 mg/kg i.p.) and chlorpheniramine (1 mg/kg s.c.) significantly potentiated place preference, no potentiation was observed with the combination of dihydrocodeine (3 mg/kg i.p.) and epinastine (1 mg/kg s.c.). These results suggest that epinastine may be a useful constituent opioid-containing antitussive preparation that would not enhance the potential for psychological dependence.

Animals↗