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Biomedical subjects

M Ohsawa

Publications and source records attributed to M Ohsawa.

At least 73 records · Page 4Linked to original sources
PubMed1999

Involvement of spinal delta 1-opioid receptors in forced walking stress-induced antinociception in the tail-flick test in mice.

The purpose of this study was to elucidate the involvement of spinal delta-opioid receptor subtypes in forced walking stress-induced antinociception mice. We first confirmed that forced walking stress produced walking duration-dependent antinociception in mice as determined by the tail-flick test. Intrathecal treatment with 7-benzylidenenaltrexone, a selective delta 1-opioid receptor antagonist, significantly attenuated forced walking stress-induced antinociception. In contrast, intrathecal treatment with naltriben, a selective delta 2-opioid receptor antagonist, had no significant effect on forced walking stress-induced antinociception. Intracerebroventricular treatment with either 7-benzylidenenaltrexone or naltriben had no effect on the forced walking stress-induced antinociception. These results suggest that forced walking stress-induced antinociception is mediated by spinal delta 1-opioid receptors in mice.

Analgesics↗
PubMed1998

Successful induction of adjuvant arthritis in mice by treatment with a monoclonal antibody against IL-4.

Adjuvant arthritis (AA) is an experimental model of autoimmune disease in rats induced by immunization with Mycobacterium tuberculosis (MT). Induction of AA in other species, including mice, has been shown to be difficult. In the present study, we found that AA could be induced in mice if the animals were treated with a mAb (11B11 mAb) against IL-4. Histologically, the joints exhibited synovial edema with infiltration of many neutrophils in the early phase of inflammation. In its late phase, there were proliferation of synovium, cell infiltrate in which mononuclear cells predominated, and destruction of cartilage and subchondral bone. The joint inflammation was passively transferred to normal syngeneic recipient mice with lymphoid cells but not with sera from mice immunized with MT followed by treatment with the anti-IL-4 Ab. Delayed-type hypersensitivity (DTH) and proliferative responses of lymphoid cells to purified protein derivative were markedly augmented in 11B11 mAb-treated mice. Furthermore, the induction of arthritis was associated with a marked decrease in IL-4 secretion but a significant increase in IFN-gamma and IL-2 production. Thus, the neutralization of IL-4 by an anti-IL-4 Ab appears to be required for the induction of AA in mice.

Adoptive Transfer↗
PubMed1998

Possible involvement of protein kinase C in the attenuation of the morphine-induced Straub tail reaction in diabetic mice.

To investigate the role of protein kinase C in the attenuation of the morphine-induced Straub tail reaction in diabetic mice, we examined the effects of protein kinase C activator or inhibitor on the i.c.v. morphine-induced Straub tail reaction in mice. This reaction was less in diabetic mice than in normal mice. Intracerebroventricular pretreatment with phorbol 12,13-dibutyrate (50 pmol), a potent protein kinase C activator, attenuated the morphine-induced Straub tail reaction in normal mice, but not in diabetic mice. I.c.v. pretreatment with calphostin C (10 pmol), a selective protein kinase C inhibitor, enhanced the reaction in diabetic mice, but not in normal mice. The dose-response curve for the morphine-induced Straub tail reaction in normal mice, but not in diabetic mice, was shifted to the right by i.c.v. pretreatment with phorbol 12,13-dibutyrate (50 pmol). Furthermore, i.c.v. pretreatment with calphostin C (3 pmol) shifted the dose-response curve to the left in diabetic mice, but not in normal mice. These results indicate that activation of protein kinase C reduces the morphine-induced Straub tail reaction in normal mice. Also, the attenuation of the morphine-induced Straub tail reaction in diabetic mice may be due in part to increased protein kinase C activity.

Animals↗
PubMed1998

Modulation of the formalin-induced nociceptive response by diabetes: possible involvement of protein kinase C.

Injection of formalin into the hind paw of mice produced a biphasic nociceptive response consisting of immediate (first-phase) and tonic (second-phase) components. Although the duration of the first-phase response was significantly longer in diabetic mice than in nondiabetic mice, the second phase was significantly shorter in diabetic mice. The first-phase response was dose-dependently and significantly reduced by pretreatment with calphostin C (0.3 to 3 pmol, i.t.), a specific protein kinase C inhibitor, in diabetic mice. The second-phase response was markedly increased when diabetic mice were pretreated with calphostin C. However, calphostin C (3 nmol, i. t.) had no significant effect on either the first-phase or second-phase response in nondiabetic mice. On the other hand, pretreatment with phorbol-12,13-dibutyrate (50 pmol, i.t.), a protein kinase C activator, significantly enhanced the first-phase response in nondiabetic mice. These results suggest that the change in the formalin-induced nociceptive response in diabetic mice may be due, at least in part, to the modification of nociceptive transmission in the spinal cord by the activation of protein kinase C.

Animals↗
PubMed1998

Decreased central histamine in the amygdaloid kindling rats.

This study was conducted to elucidate the role of central histamine (HA) in seizure susceptibility. We stimulated the left amygdala of rats to produce amygdaloid kindling. We sacrificed rats 1 h, 1 week and 1 month after the last kindled seizure, and measured the histamine contents and the histidine decarboxylase (HDC) activities of various brain regions. One hour after the last kindled seizure, we found significant decreases in HA levels in the bilateral amygdala, hippocampus and diencephalon in the kindled group. The HDC activities of the bilateral amygdala and diencephalon were lower in the kindled group than in the control group. One week after the last kindled seizure, we also found a significant decrease in the HA level in the bilateral amygdala. No significant change was found in HA content or HDC activity 1 month after the last kindled seizure. These results suggest that kindling suppresses HA synthesis and that the reduced HA content is maintained until 1 week after the last kindled seizure. The reduced HA may play a role in the acquired kindled seizure susceptibility.

Amygdala↗
PubMed1998

Anticoagulant effects of 1alpha,25-dihydroxyvitamin D3 on human myelogenous leukemia cells and monocytes.

The hormonally active form of vitamin D is 1alpha, 25-dihydroxyvitamin D3 [1,25(OH)2D3], which is a principal regulator of calcium homeostasis. It also affects hormone secretion, cell differentiation, and proliferation by a mode of action that involves stereospecific interaction with an intracellular vitamin D receptor (VDR). We recently found that retinoids, which are vitamin A derivatives, exert anticoagulant effects by upregulating thrombomodulin (TM) and downregulating tissue factor (TF) expression in acute promyelocytic leukemia cells and monoblastic leukemia cells. Both the VDR and retinoid receptors belong to the same family of receptors. A heterodimer consisting of the retinoid X receptor and the VDR binds to vitamin D responsive elements on genes regulated by vitamin D. To determine whether 1,25(OH)2D3 would exhibit anticoagulant effects similar to retinoids, we measured the antigen level, activity, and mRNA level of TM and TF in human leukemic cells, vascular endothelial cells, and monocytes treated with 1,25(OH)2D3. We found that 1,25(OH)2D3 upregulates antigen expression, activity, and mRNA levels of TM and downregulates antigen expression, activity, and mRNA levels of TF in human monocytic leukemia cells, some acute myelogenous leukemia cells, and monocytes, but not in umbilical vein endothelial cells. Transient transfection studies with reporter plasmids in monocytic leukemia cells and mobility gel-shift assay showed interaction with 1,25(OH)2D3 and functional retinoic acid responsive elements present in the 5'-flanking region of the TM gene. However, auxiliary factors or other elements in the TM gene may contribute to VDR specificity and transactivation of the gene in specific target cells. These findings indicate that 1,25(OH)2D3 resembles the retinoids in its control of the transcription of the TM and TF genes in human monocytic cells. Analogs of 1,25(OH)2D3 with anticoagulant activity may serve as adjunctive antithrombotic agents in monocytic leukemia and atherosclerotic disease.

Anticoagulants↗
PubMed1998

Antitussive effect of moguisteine on allergic coughs in the guinea pig.

The effect of moguisteine, a novel peripherally acting non-narcotic antitussive drug, on allergic coughs was examined in guinea pigs. Male Hartley guinea pigs were actively sensitized to ovalbumin. The number of coughs elicited over 5 min following a 2-min exposure to ovalbumin was counted. Exposure of sensitized guinea pigs to 0.5% ovalbumin aerosol induced 22.0 +/- 3.2 coughs/5 min. Moguisteine at doses of 30 and 56 mg/kg, p.o., dose-dependently and significantly suppressed the number of allergic coughs. Dihydrocodeine at doses of 30 and 56 mg/kg, p.o., dose-dependently but not significantly reduced the number of allergic coughs. These results suggest that moguisteine may be of a therapeutic benefit in reducing allergic coughs.

Analgesics, Opioid↗
PubMed1998

Intraventricular insulin reduces the antinociceptive effect of [D-Ala2, NMePhe4, Gly-ol5]enkephalin in mice.

The effects of pretreatment with insulin on the antinociception induced by intracerebroventricular (i.c.v.) administration of the mu-opioid receptor agonist [D-Ala2, NMePhe4, Gly-ol5]enkephalin (DAMGO) were studied in mice. Intracerebroventricular pretreatment with insulin (1 and 3 mU) for 60 min dose dependently attenuated the antinociception induced by i.c.v. DAMGO (5.6 ng) in mice. Intracerebroventricular pretreatment with a highly selective tyrosine kinase inhibitor, lavendustin A, at doses of 100 and 300 ng for 10 min, dose dependently reversed the antinociceptive effect of DAMGO (5.6 ng) in insulin-treated mice. The antinociceptive effect of DAMGO (5.6 ng, i.c.v.) was significantly reduced in C57BL/KsJ-db/db diabetic mice compared with that in age-matched control (C57BL/KsJ-db/ + + ) mice. When C57BL/KsJ-db/db diabetic mice were pretreated with lavendustin A (300 ng), the antinociceptive effect of DAMGO was significantly increased. These results indicate that tyrosine kinase may be involved in the reduction of DAMGO-induced antinociception by insulin in mice. Furthermore, the attenuation of DAMGO-induced antinociception in C57BL/KsJ-db/db diabetic mice may be due in part to increased tyrosine kinase activity as a result of hyperinsulinemia.

Analgesics, Opioid↗
PubMed1998

Natural killer cell-derived large granular lymphocyte lymphoma of lung developed in a patient with hypersensitivity to mosquito bites and reactivated Epstein-Barr virus infection.

A 17-year-old female developed natural killer (NK) cell-derived large granular lymphocyte (LGL) lymphoma of the lung. She had a past history of hypersensitivity to mosquito bites (HMB). After an eight-year chronic, active Epstein-Barr virus (EBV) infection, she developed multiple lung lesions and pleural effusion. In the effusion, 60% of the cells were LGL. They were CD2+, 3-, 16+, 56+, 57+, 45RO+/RA + weak, and possessed strong NK activity. No rearrangement of T-cell-receptor genes was detected. From all these results, a diagnosis of NK-LGL lymphoma of the lung was made. EB virus DNA was detected in cells infiltrating the pleural effusion. The clonality of the LGLs was determined by Southern blot hybridization with the terminal repeat sequence of EB virus as a probe, and by chromosomal abnormalities. The patient died from respiratory failure. Necropsy of the lung revealed diffuse lymphoma composed of polymorphic cells with typical angiocentric lesions. Reportedly, lymphomas of NK lineage show predominantly extranodal involvement, and primary lung lesions are rare. In the pleural effusion of the present case, abnormally high levels of soluble Fas ligand, interleukin-10 and interferon gamma were detected. This hypercytokinemia, reflecting the microenvironment of lymphoma cells, may play a role in the progression of the lymphoma and organ injury in the lung.

Adolescent↗
PubMed1998

Large-vessel arteritis associated with chronic active Epstein-Barr virus infection.

This report describes an autopsy case of large-vessel arteritis associated with chronic active Epstein-Barr virus (EBV) infection in a 10-year-old Japanese girl. All of the 3 main coronary arteries, bilateral common carotid and subclavian arteries, abdominal aorta and its major branches, and bilateral common iliac arteries were involved, and all showed aneurysmal dilation of the lumens. Histopathologic examination revealed mesoarteritis characterized by moth-eaten-appearing destruction of the medial elastic laminae, with T lymphocyte infiltration around the vasa vasorum and severe intimal thickening. The EBV DNA genome was detected in the diseased aortic tissue by polymerase chain reaction, and in the infiltrating lymphocytes by in situ hybridization. The clinical symptoms and histopathologic manifestations of the arterial lesions in this patient were obviously different from those of Kawasaki disease and Takayasu arteritis, and the arteritis was considered to be associated with the EBV infection.

Arteries↗
PubMed1998

Hodgkin's disease of the chest wall: report of a case.

Hodgkin's disease primarily originating from the chest wall is very rare. A 48-year-old man was admitted to our hospital because of an abnormal shadow on a chest X-ray. Radiographic examinations suggested a neurogenic tumor located in the right second-intercostal space, and it was thus extirpated thoracoscopically. The tumor was thought to have arisen from the subpleural space, probably from a lymph node of the chest wall. The resected specimen measured 5.5 x 2.0 cm in size, and the pathological diagnosis was Hodgkin's disease of the diffuse lymphocyte predominant type. A clinical examination showed no other lesions in any other part of the body, including the bone marrow. Following surgery, adjuvant chemotherapy (COPP-ABVD) was given because of the possible scattering of malignant cells during surgery. To the best of our knowledge, this is the first report of Hodgkin's disease originating in the chest wall.

Chemotherapy, Adjuvant↗
PubMed1998

Modulation by serum glucose levels on morphine-induced antinociceptive effect in C57BL/KsJ-db/db mice.

The role of serum glucose levels on the sensitivity to the antinociceptive effect of morphine in streptozotocin-induced diabetic mice and C57BL/KsJ db/db mice were examined. The sensitivity to the antinociceptive effect of morphine was significantly reduced in streptozotocin-induced diabetic mice as compared with age-matched nondiabetic mice. Pretreatment with insulin (3 U/kg, s.c.) significantly reduced the serum glucose levels of streptozotocin-induced diabetic mice as compared with those of untreated diabetic mice. However, post-drug (morphine) tail-flick latency was not affected by pretreatment with insulin. The antinociceptive effect of morphine was also significantly reduced in C57BL/KsJ-db/db mice as compared with age-matched control mice. When CS-045 was administered to C57BL/KsJ-db/db mice, the serum glucose levels were significantly reduced. There was no significant difference in the antinociceptive effect of morphine between CS-045-treated C57BL/KsJ-db/db mice and C57BL/KsJ-db/++ mice. Adoptive transfer of supernatant of the spleen cell homogenate from C57BL/KsJ-db/db mice to naive ICR mice had no significant effect on the recipients' antinociceptive sensitivities to s.c. morphine. These findings support the our previous suggestion that some factor(s) derived from spleen mononuclear cells is the prime factor involving the insulin-insensitive mechanisms for the reduction of mu-opioid agonist-induced antinociception during the severe stages of diabetes.

Analgesics↗
PubMed1998

Dual action of CD30 antigen: anti-CD30 antibody induced apoptosis and interleukin-8 secretion in Ki-1 lymphoma cells.

CD30 is a member of the tumor necrosis factor superfamily. In this study, we examined the effect of four anti-CD30 (aCD30) antibodies (Abs) on CD30-positive anaplastic large cell lymphoma-derived cell line, Ki-JK. The aCD30 Abs suppressed [3H]thymidine (TdR) incorporation. With a TdT mediated dUTP-biotin nick end labeling method, apoptosis was detected in Ki-JK cells at day 5 after the addition of aCD30 Ab to the culture. Genistein, an inhibitor of protein tyrosine kinase, had no effect on aCD30 Ab-induced apoptosis. The aCD30 Ab simultaneously induced interleukin-8 (IL-8) secretion in the Ki-JK cells. In culture of the Ki-JK cells with aCD30 Ab for 5 days, the IL-8 concentration of the cell free-supernatant increased to 240 +/- 16 pg/ml, though the concentration was < 12.5 pg/ml without aCD30 Ab. In combination with aCD30 Ab, genistein decreased the concentration of IL-8 in day 5 supernatants. Although, doxorubicin and herbimycin-A suppressed [3H]TdR incorporation and induced apoptosis in the Ki-JK cells, they did not induce IL-8 secretion. Only aCD30 Ab-induced apoptosis was accompanied by IL-8 secretion. IL-8 mRNA was not detected in the Ki-JK cells by reverse transcription-polymerase chain reaction assay. IL-8 mRNA was detected 5 days after adding aCD30 Ab to the culture.

Antibodies↗
PubMed1998

Appearance of a different clone of Epstein-Barr virus genome in recurrent tumor of pyothorax-associated lymphoma (PAL) and a mini-review of PAL.

A case of pyothorax-associated lymphoma (PAL) is reported. A 76-year-old Japanese man developed a lymphoma in the pleural cavity after 46 years duration of pyothorax due to pulmonary tuberculosis. The histologic diagnosis of biopsy specimen was diffuse large cell lymphoma of B cell type. The lymphoma cells contained the monoclonal Epstein-Barr virus (EBV) determined by the analysis of terminal repeat of EBV genome and expressed EBV nuclear antigen 2 and latent membrane protein 1 (LMP1). He received antineoplastic chemotherapy and was induced to complete remission (CR). After 19 months of CR, the lymphoma developed again in the thoracic wall. Histopathology and immunohistochemical phenotypes of recurrent tumor were almost the same as those of the primary tumor with the exception of a little more frequent expression of LMP1. The EBV genome in lymphoma cells was monoclonal, however, the clone was different from that of the primary tumor. After antineoplastic chemotherapy, minor EBV-positive clones in primary lymphoma might survive and develop into recurrent tumor. These results suggest that the PAL starts as poly- or oligoclonal proliferation of B lineage cells. This poly- or oligoclonality of PAL at the initial stage may suggest underlying immunosuppressive conditions in the development of PAL.

Aged↗
PubMed1998

Changes in bone mineral density after orchidectomy and hormone replacement therapy in individuals with androgen insensitivity syndrome.

Changes in bone mineral density (BMD) after orchidectomy and after hormone replacement therapy were reported in two patients with complete androgen insensitivity syndrome (AIS). Diagnosis of AIS was made by clinical features and confirmed by the presence of 46,XY karyotype and the presence of testis component in the removed gonads. BMD at the lumbar spine and at three sites of the femur was measured by dual energy X-ray absorptiometry (DXA). The Z scores of the lumbar spine BMD before orchidectomy were -0.8 and -3.1, confirming that patients with AIS have low BMD and that androgen plays an important role in bone mineralization in 46,XY individuals. Castration reduced BMD, but treatment with daily doses of 1.25 mg of conjugated oestrogen and 10 mg of medroxyprogesterone acetate increased BMD. These results indicate that both oestrogen and androgen play an important role in balancing BMD in men.

Adult↗
PubMed1998

Site-specific localization of Epstein-Barr virus in pharyngeal carcinomas.

In this study, the correlations of factors with Epstein-Barr virus (EBV)-association were investigated in 50 patients with nasopharyngeal carcinoma (NPC), 61 with oropharyngeal carcinoma (OPC), and 55 with hypopharyngeal carcinoma (HPC) in Okinawa and Osaka prefectures in Japan. The incidence of pharyngeal carcinoma in Okinawa was previously found to be higher than that in Osaka; the incidence of OPC was approximately 6 times higher and that of HPC was two times higher. The EBV genome was detected in the tumor cells of the present patients; 83% of the Okinawa and 92% of the Osaka NPC patients. The EBV genome was not detected in OPC or HPC. A univariate analysis showed that sex, the location of the tumor, histology, and the degree of lymphocytic infiltration correlated with the EBV-positive rate. A multivariate analysis revealed that only the location of the tumor was independently correlated with the EBV-positive rate. Histology and tumor size were factors affecting the prognosis of the patients with NPC. The NPC of poorly differentiated type frequently showed the EBV genome, and NPC with lymphocytic infiltration showed a more favorable prognosis compared to the other NPC types. These findings suggest that latent genes of EBV expressed in cancer cells might trigger a cytotoxic T cell reaction against the cancer.

DNA, Viral↗