Biomedical subjects

M Ohsawa

Publications and source records attributed to M Ohsawa.

At least 91 records · Page 5Linked to original sources

PubMed1998

The long-term effect of menopause on postmenopausal bone loss in Japanese women: results from a prospective study.

The aim of this study was to elucidate perimenopausal bone loss in relation to menstrual conditions and to investigate the long-term effect of menopause on bone loss in aged women. The rate of change in bone mineral density (BMD) was measured twice at an exact interval of 12 months by dual-energy X-ray absorptiometry (DXA) at the lumbar spine in 176 pre- and postmenopausal healthy women 41-65 years of age. Serum follicle-stimulating hormone, intact and N-fragment osteocalcin (OC), three types of vitamin D3, parathyroid hormone (PTH), and calcitonin were also determined. Women who exercised regularly or had anatomical changes at the lumbar spine were excluded from this study. The subjects were divided into eight groups based on their menstrual status and years since menopause. Annual bone loss at the lumbar spine of premenopausal women with regular menstruation was -0.2+/-1.9% (95% confidence interval, -0.9 approximately -0.4%) and was not statistically different from zero, while that of women with irregular menstruation or at menopausal transition was -2.1+/-3.4% (-3.4 approximately -0.8%), and -3.3+/-2.3% (-5.2 approximately -0.3%), respectively, and was significantly different from zero. Serum OC levels of women at menopausal transition were significantly higher than those of women with regular menstruation, suggesting that bone loss had commenced in these women. The rate of annual change in BMD of women who were menopausal for 1-3, 4-6, 10-12, and more than 13 years was -3.1+/-4.0% (-4.7 approximately -1.5%), -1.2+/-2.6% (-2.2 approximately -0.2%), -1.0+/-3.0% (-2.3 approximately -0.3%), and -2.3+/-2.1% (-3.7 approximately -1.0%), respectively, and was significantly less than zero. But the annual bone loss of women who were menopausal for 7-9 years was -1.5+/-2.6% (-3.0 approximately -0.1%) and was not statistically significant from zero. These results indicate that postmenopausal women lose BMD in two phases. The early bone loss is rapid and commences during irregular menstruation, then is attenuated within 6 years after the onset of menopause. The second bone loss commences after the attenuation of the first bone loss. Among bone metabolic hormones, intact PTH alone showed an age-related increase and was suggested as being a causal factor of bone loss in women who were menopausal for 13 years or more.

Absorptiometry, Photon↗

PubMed1998

Epstein-Barr virus and gastrointestinal lymphomas in Korea.

To analyze the association of Epstein-Barr virus (EBV) with gastrointestinal non-Hodgkin's lymphomas arising in immunocompetent patients, 56 consecutive cases of gastrointestinal lymphomas (B-cell: 52-cases, T-cell: 3 cases, T/NK-cell: 1 case) occurring in the stomach (33 cases), intestine (22 cases) and esophagus (1 case) were investigated for the presence of EBV using polymerase chain reaction analysis as a screening method followed by EBER-1 RNA and DNA in situ hybridization (ISH) and immunohistochemistry for the expression of latent membrane protein 1 (LMP-1). Forty-seven cases demonstrated extractable DNA and EBV DNA was detected only in 4 cases. Among the, RNA (EBER-1) and DNA ISH analysis confirmed the presence of the EBV genome in tumor cells in 3 cases (T/NK-cell lymphoma of ileum, gastric high-grade B-cell lymphoma of mucosa-associated lymphoid tissue, gastric diffuse large B-cell lymphoma). Only the T/NK cell lymphoma showed diffuse positivity of tumor cells while 2 gastric B-cell lymphomas demonstrated a scattered positive reaction and no cases expressed LMP-1. Nine cases without extractable DNA by the PCR method showed no nuclear signal by EBER-1 ISH. These findings suggest that most sporadic primary gastrointestinal lymphomas in Korea are not associated with EBV.

Gastrointestinal Neoplasms↗

PubMed1998

Dimensional changes of MOD mold cavity corresponding to the degree of setting expansion.

The correlation between the degree of linear setting expansion and the dimensional changes in a mold space was examined. The dimensional changes in the mold were determined by investing the MOD-type wax pattern using a die-investing material of which the degree of the setting expansion was controlled by diluting a concentration of colloidal silica solution. The wax was eliminated in an electric furnace at 130 degrees C and a fusible alloy, m.p. 48 degrees C, was cast into the mold space at room temperature. The dimensions of the wax pattern and the casting were compared. The degree of linear setting expansion was measured in a paper ring by means of a dial gauge. A high correlation was found between the dimensional changes of the mold space and the degree of the linear setting expansion. The expansion was highest at the axiogingival portion while those at both the axial dimension and the occlusal dimension were smallest. Linear regression lines (Y = AX + B) revealed the differences in the expansion mode at both the external and internal portions to show a discrepancy in value B.

Dental Casting Investment↗

PubMed1998

Hepatitis C viral genome in a subset of primary hepatic lymphomas.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are not only hepatotropic but possibly hematotropic. Recent studies showed the presence of HBV in lymphoma cells of extrahepatic origin. In the current study, we examined the presence of HBV DNA and HCV RNA in the tumor tissues of nine patients with primary hepatic lymphoma (PHL). Immunohistochemical study using polyclonal anti-HCV antibody was possible in four cases. The age of the patients ranged from 45 to 78 years (median, 58 yr), with a male-to-female ratio of 2:1. A history of chronic hepatitis was found in three patients and of cirrhosis in one. Histologically, all of the cases were non-Hodgkin's lymphoma of B-cell phenotype, with a diffuse large cell type being the most common. Polymerase chain reaction using both the S and X region primers failed to detect HBV DNA in the lymphoma tissues. The HCV genome was detected by in situ hybridization in the tumor cells but not in the surrounding hepatocytes in the one case of cirrhosis, which probably resulted from a blood transfusion more than 20 years previous; immunohistochemical analysis revealed positive staining for anti-HCV antibody in the cytoplasm of lymphoma cells in this case. In two cases, positive signals were found only in the hepatocytes surrounding the lymphoma. This is the first report showing the presence of the HCV genome in the lymphoma cells of PHL. HCV could be involved in development of PHL directly or via exogenic antigenic stimulus from HCV-infected hepatocytes.

Aged↗

PubMed1998

Role of intracellular calcium in modification of mu and delta opioid receptor-mediated antinociception by diabetes in mice.

We examined the effects of calcium modulators on mu and delta opioid receptor agonist-induced antinociception in both diabetic and nondiabetic mice. In nondiabetic mice, intracerebroventricular (i.c. v.) pretreatment with calcium and thapsigargin, which increase intracellular calcium, reduced [D-Ala2,N-MePhe4,Gly-ol5]-enkephalin (DAMGO)-induced antinociception by shifting its dose-response curve to the right. However, in diabetic mice i.c.v. pretreatment with calcium and thapsigargin did not affect DAMGO-induced antinociception. In contrast i.c.v. administration of agents that decrease intracellular calcium, such as EGTA and ryanodine, enhanced DAMGO-induced antinociception in both diabetic and nondiabetic mice. In contrast with DAMGO i.c.v. pretreatment with calcium and thapsigargin enhanced (-)-TAN67-induced antinociception in nondiabetic mice by shifting its dose-response curve to the left. However, (-)-TAN67-induced antinociception in diabetic mice was not affected by pretreatment with calcium or thapsigargin. Moreover i.c. v. pretreatment with EGTA, but not with ryanodine, reduced (-)-TAN67-induced antinociception in nondiabetic mice. In diabetic mice i.c.v. pretreatment with both EGTA and ryanodine reduced (-)-TAN67-induced antinociception. These results suggest that cytosolic calcium has different effects on mu and delta opioid receptor agonist-induced antinociception. Further, these results suggest that the modification of mu and delta opioid receptor agonist-induced antinociception by diabetes in mice may be due to increased levels of intracellular calcium.

Analgesics↗

PubMed1998

Diesel exhaust particles block induction of oral tolerance in mice.

We investigated the effect of diesel exhaust particles (DEP) on oral tolerance. Oral tolerance was induced by feeding mice with 10 mg of hen egg lysozyme (HEL) daily over a period of 5 days before immunization with the antigen. Varying doses of DEP were orally administered immediately before each feeding of HEL. The results showed that oral administration of HEL significantly suppressed production of anti-HEL IgG, IgG1 and IgG2a antibodies, delayed-type hypersensitivity and proliferative responses of lymph node cells to the antigen. The suppression of these immune responses to HEL by the oral antigen was associated with a marked decrease in secretion of interferon-gamma and interleukin-4 from the lymphoid cells. Administration of DEP dose-dependently blocked suppression by oral HEL of antigen-specific IgG, IgG1 and IgG2a antibody production, delayed-type hypersensitivity and lymphoid cell proliferation. The suppression by the fed antigen of secretion of interferon-gamma and interleukin-4 was also markedly diminished by the particles. Thus, DEP appear to be effective in blocking induction of oral tolerance.

Adjuvants, Immunologic↗

PubMed1997

Possible involvement of protein kinase C in the attenuation of [D-Ala2, NMePhe4, Gly-ol5]enkephalin-induced antinociception in diabetic mice.

The effects of pretreatment with a highly selective protein kinase C inhibitor, calphostin C, on the antinociception induced by the intracerebroventricular (i.c.v.) administration of the mu-opioid receptor agonist [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAMGO) were studied in diabetic and non-diabetic mice. The antinociceptive potency of i.c.v. DAMGO in diabetic mice was lower than that in non-diabetic mice. I.c.v. pretreatment with phorbol 12,13-dibutyrate (50 pmol), a protein kinase C activator, for 60 min attenuated the antinociception induced by i.c.v. DAMGO in non-diabetic mice, but not in diabetic mice. I.c.v. pretreatment with calphostin C (3 pmol) for 60, 120 and 240 min, but not 10 min, increased the antinociceptive effect of DAMGO (10 ng) in diabetic mice, but not in non-diabetic mice. The dose-response curve for DAMGO-induced antinociception in diabetic mice, but not in non-diabetic mice, was shifted to the left by i.c.v. pretreatment with calphostin C (3 pmol) for 60 min. In non-diabetic mice, i.c.v. pretreatment with a high dose of calphostin C (10 pmol) for 60 and 120 min potentiated DAMGO-induced antinociception. These results indicate that protein kinase C may be involved in DAMGO-induced antinociception in mice. Furthermore, these results suggest that the attenuation of DAMGO-induced antinociception in diabetic mice may be due in part to increased protein kinase C activity.

Analgesics, Opioid↗

PubMed1997

Antinociceptive effects of (+)-matrine in mice.

The antinociceptive potency of matridin-15-one ((+)-matrine) was examined using the acetic acid-induced abdominal contraction test and the tail-flick test in mice. (+)-Matrine, at doses of 1 to 10 mg/kg, s.c., produced a marked and dose-dependent inhibition of the number of acetic acid-induced abdominal contractions in mice. The antinociceptive effect of (+)-matrine in the acetic acid-induced abdominal contraction test in mice was identical to that of pentazocine. Indeed, there was no significant difference in the ED50 (mg/kg with 95% confidence limits) values for the inhibition of acetic acid-induced abdominal contractions between (+)-matrine (4.7 (4.1-5.3)) and pentazocine (3.3 (2.2-5.0)). Furthermore, in the tail-flick assay, (+)-matrine at doses of 10 and 30 mg/kg, s.c., again produced a dose-dependent antinociceptive effect. When nor-binaltorphimine (20 mg/kg, s.c.), a selective kappa-opioid receptor antagonist, was administered 3 h before treatment with (+)-matrine, the antinociceptive effect of (+)-matrine was markedly antagonized. Furthermore, the antinociceptive effect of (+)-matrine was partially antagonized by pretreatment with beta-funaltrexamine, a selective mu-opioid receptor antagonist. Naltrindole, a selective delta-opioid receptor antagonist, had no effect on the antinociceptive effect of (+)-matrine. In conclusion, (+)-matrine produced an antinociceptive effect mainly through the activation of kappa-opioid receptors and partially through mu-opioid receptors.

Abdomen↗

PubMed1997

Modification of morphine-induced place preference by diabetes.

The effects of diabetes on morphine-induced place preference in mice were examined. Morphine caused dose-related place preference in both diabetic and non-diabetic mice. This morphine-induced place preference in diabetic mice was greater than that in non-diabetic mice. The morphine (5 mg/kg)-induced place preference in both diabetic and non-diabetic mice was significantly antagonized by pretreatment with beta-funaltrexamine, a selective mu-opioid receptor antagonist, but not with naloxonazine, a selective mu1-opioid receptor antagonist. The morphine (5 mg/kg)-induced place preference in non-diabetic mice was attenuated by pretreatment with either naltriben, a selective delta2-opioid receptor antagonist, or 7-benzylidenenaltrexone. a selective delta1-opioid receptor antagonist. Moreover, the morphine (10 mg/kg)-induced place preference in non-diabetic mice was antagonized by pretreatment with 7-benzylidenenaltrexone (0.7 mg/kg). Although 7-benzylidenenaltrexone had no effect on the place preference induced by 5 mg/kg morphine in diabetic mice, it reduced the place preference induced by 3 mg/kg morphine. Furthermore, the morphine (5 mg/kg)-induced place preference in diabetic mice was significantly antagonized by co-pretreatment with beta-funaltrexamine (10 mg/kg) and 7-benzylidenenaltrexone (0.7 mg/kg). 2-Methyl-4a alpha-(3-hydroxyphenyl)- 1,2,3,4,4a,5,12,12a alpha-octahydroquinolino[2,3,3-g]isoquinoline (TAN-67), a non-peptide delta-opioid receptor agonist, produced place preference in diabetic, but not in non-diabetic mice. These results support the hypothesis that the morphine-induced place preference is mainly mediated through the activation of the mu2-opioid receptor. Furthermore, the enhancement of the morphine-induced place preference in diabetic mice may be due to the up-regulation of delta-opioid receptor-mediated functions.

Animals↗

PubMed1997

Effect of a monoclonal antibody against interleukin-4 on the induction of oral tolerance in mice.

The present study was undertaken to investigate the effect of a monoclonal antibody against interleukin-4 on the induction of oral tolerance. Oral tolerance was induced by feeding mice with low and high doses (0.1, 1 and 10 mg) of hen egg lysozyme once a day for 5 days before immunization with the antigen. An anti-interleukin-4 monoclonal antibody was i.p. injected 30 min before each oral administration of hen egg lysozyme. The results showed that the oral administration of hen egg lysozyme suppressed immune responses to the antigen including delayed type hypersensitivity, production of both isotypes of immunoglobulin (Ig) G1 and IgG2a antibodies and proliferation of lymph node cells in a dose-dependent manner. The suppression of these responses by the oral antigen was associated with a marked reduction of interferon-gamma secretion and a moderate decrease in interleukin-4 production by lymphoid cells. The treatment with the anti-interleukin-4 monoclonal antibody blocked dose-dependently the suppression of the delayed type hypersensitivity response to hen egg lysozyme, anti-hen egg lysozyme IgG2a antibody production and interferon-gamma secretion. In contrast, the anti-interleukin-4 antibody facilitated the suppression of anti-hen egg lysozyme IgG1 antibody production and interleukin-4 secretion. Thus, the neutralization of interleukin-4 by anti-interleukin-4 antibodies appears to be effective in modulating the induction of oral tolerance.

Animals↗

PubMed1997

Pretreatment with the protein kinase C activator phorbol 12,13-dibutyrate attenuates the ethanol-induced loss of the righting reflex in mice: modification by diabetes.

The effects of the protein kinase C (PKC) activator phorbol 12,13-dibutyrate (PDBu) on the ethanol-induced loss of the righting reflex were studied in diabetic and non-diabetic mice. The ethanol-induced loss of the righting reflex was significantly less in diabetic mice than in non-diabetic mice. Intracerebroventricular (i.c.v.) pretreatment with PDBu dose- and time-dependently reduced the ethanol-induced loss of the righting reflex in non-diabetic mice. The reduction of the ethanol-induced loss of the righting reflex caused by PDBu was reversed by concomitant i.c.v. pretreatment with calphostin C, a selective PKC inhibitor. On the other hand, PDBu had no effect on the ethanol-induced loss of the righting reflex in diabetic mice. I.c.v. pretreatment with calphostin C (10 pmol) increased the ethanol-induced loss of the righting reflex in diabetic mice but not in non-diabetic mice. These results suggest that the activation of PKC reduces the ethanol-induced loss of the righting reflex in mice. Furthermore, it is possible that this attenuation of the ethanol-induced loss of the righting reflex in diabetic mice may be due in part to increased PKC activity.

Animals↗

PubMed1997

Epstein-Barr virus in gastric carcinoma in Suzhou, China and Osaka, Japan: association with clinico-pathologic factors and HLA-subtype.

Information on geographic differences of Epstein-Barr virus (EBV) positivity and association with HLA in gastric carcinoma are limited. Therefore, the association of gastric carcinoma with EBV was examined in 118 patients from Suzhou, China, where the incidence of nasopharyngeal carcinoma (NPC) is high, and in 216 patients from Osaka, Japan, where the incidence of NPC is low, NPC being one of the EBV-associated carcinomas. Expression of HLA-A2 was also examined in some of these cases. The EBV genome was evidenced by PCR and in the tumor cells by in situ hybridization in 7/90 and 9/151 of cases from Suzhou and Osaka, respectively. Immunohistochemistry revealed that cancer cells in all cases with EBV did not express latent membrane protein-I. Type A was found in all cases positive for EBV. Among several histologic and clinical factors, only age of patients showed a correlation with EBV positivity: patients over 60 showed a higher frequency than patients below 60 years of age (p < 0.05). Typing of the HLA-A locus was possible in 16 cases positive for the EBV genome: 3 of 4 cases from Suzhou and 4 of 7 from Osaka were positive for HLA-A2 products. Severe lymphoid cell infiltration was found in 2 of 7 cases and 1 of 4 cases with and without the HLA-A2 type, respectively. The reported frequency of EBV positivity in Chinese living in Taiwan and in Japanese living in Hawaii is higher than in Suzhou, China, and Osaka, Japan, respectively. Our findings suggest that EBV association with gastric carcinoma is influenced by environmental and cultural factors.

Adenocarcinoma↗

PubMed1997

Epstein-Barr virus in lymphoproliferative diseases in the sino-nasal region: close association with CD56+ immunophenotype and polymorphic-reticulosis morphology.

Association between Epstein-Barr virus (EBV) and nasal T-cell lymphoma (NTL) has been demonstrated. NTL has 2 types of histologic figures: one is ordinary non-Hodgkin's lymphoma (NHL) with monomorphous proliferation, and the other is polymorphic-reticulosis (PR) morphology. The presence of the EBV genome and its sub-types (A and B) were examined on paraffin-embedded specimens from 36 cases of sino-nasal lymphomas (SNL) collected from Seoul, Republic of Korea, where the frequency of NTL is high. Patients' ages ranged from 2 to 74 years (median 54 years) with a male-to-female ratio of 2.5:1. Immunophenotypically, 8 cases were B-cell type, 11 were T-cell type with CD56-, 14 were CD56+ type, and 3 were null-cell type. Five of 11 cases with ordinary NHL of T-cell type and 9 of 14 cases with PR were CD56+. The EBV genome was found by polymerase chain reaction (PCR) and in the tumor cells by in situ hybridization (ISH) in 1 of 4 B-cell type (25%), 5 of 10 T-cell type (50%), 11 of 13 CD56+ type (85%), and in both of null-cell type (100%). Of 16 cases with PR morphology, 15 (94%) were positive for the EBV genome. All of the 5 NTLs of ordinary NHL with CD56- were negative for EBV. Concerning the sub-type of EBV, 16 cases had type A, while none had type-B EBV. These findings suggest that NTL comprises 2 groups: EBV-positive NTLs are CD56+ and/or histologically PR, and EBV-negative NTLs are CD56- and histologically ordinary NHL. The current results on Korean patients, together with earlier studies on Japanese and Malaysian patients, have shown the predominance of type-A EBV in sino-nasal lymphoma in Asia.

Adolescent↗

PubMed1997

Tumor size as a prognostic indicator of histologic grade of soft tissue sarcoma.

BACKGROUND AND OBJECTIVES: Tumor size is one of the independent factors affecting prognosis of patients with soft tissue sarcoma (STS). We evaluated the significance of tumor size in combination with tumor depth in each histologic grade. METHODS: A total of 162 adult patients with localized STS in the extremities and trunk were selected. Patient ages ranged from 15 to 84 (median 46.5) years with a male-to-female ratio of 1.19. Histologic grade of tumors was low in 53 cases, intermediate in 51, and high in 58. Two types of categorization were set, and their significance in predicting the prognosis of patients in each grade was evaluated. In the first category (intermediate grade), tumors were dichotomized at 10 cm: Group A comprised patients with deeply seated tumors measuring > 10 cm; Group B comprised patients other than those in Group A. In the second category (high grade), tumors were dichotomized at 5 cm: Group C comprised patients with deeply seated tumors measuring > 5 cm; Group D comprised patients other than those in Group C. RESULTS: Categorization was not useful in the prognosis of low grade tumors. In the intermediate grade group, the 5-year-survival rate of Group B patients (78%) was higher than in Group A patients (59%) (P < 0.05), showing that dichotomization at 10 cm was useful. In the high grade group, the 5-year survival rate in Group C patients (32%) was lower than in Group D patients (56%), showing that dichotomization at 5 cm was useful. CONCLUSIONS: These findings show that tumor size for the prognosis of patients with STS differs according to each histologic grade.

Adolescent↗

PubMed1997

Epstein-Barr virus in malignancies in renal transplant recipients in Japan.

A role for Epstein-Barr virus (EBV) in the development of malignancies including lymphomas, and carcinoma of the stomach, nasopharynx, thymus and salivary gland is suggested. It is indicated that EBV evokes polyclonal-B-cell-proliferative diseases in immunocompromised hosts, such as transplant patients, which results in monoclonal malignant lymphomas. The suppression of immune functions in these patients is thought to lead to incomplete elimination of the cells expressing EBV latent infection genes. To examine the etiological role of EBV in the development of malignancies following renal transplant in Japan, 42 malignancies in 1744 cases of renal transplant were studied for the presence and type of EBV. The polymerase chain reaction revealed that 5 malignancies were positive for EBV, all type A: 2 of 2 cases of non-Hodgkin's lymphoma (NHL), 2 of 8 cases of gastric adenocarcinoma of the common type, and 1 of 2 cases of gastric plasmacytoma. In situ hybridization revealed positive signals in the nucleus of tumor cells in 2 cases of NHL and 1 of plasmacytoma. Positive signals were found in the small lymphoid cells but not in the tumor cells in 2 cases of gastric carcinoma. On the basis of these findings, a role for EBV in the development of malignancies in renal transplant patients is unlikely except for lymphoid neoplasias.

Adolescent↗

PubMed1997

Role of noradrenergic functions in the modification of naloxone-precipitated withdrawal jumping in morphine-dependent mice by diabetes.

The role of noradrenergic functions in the modulation of naloxone-precipitated withdrawal jumping in morphine-dependent mice by diabetes were examined. Both diabetic and non-diabetic mice were chronically treated with morphine (8 - 45 mg/kg, s.c.) for 5 days. During this treatment, neither diabetic nor non-diabetic mice showed any signs of toxicity. After morphine treatment, withdrawal was precipitated by injection of naloxone (0.3 mg/kg, s.c.). The number of naloxone-precipitated withdrawal jumps within 5 min after injection of naloxone was significantly less in morphine-dependent diabetic mice than in morphine-dependent non-diabetic mice. However, there was no significant difference in the number of naloxone-precipitated withdrawal jumps from 5 to 15 min after injection of naloxone between diabetic and non-diabetic mice. The turnover rate of noradrenaline 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. These results suggest that the functional changes in central noradrenergic systems may be involved in the reduction of naloxone-precipitated jumping in morphine-dependent diabetic mice.

Analgesics, Opioid↗

PubMed1997

Pretreatment with protein kinase C activator phorbol 12,13-dibutyrate attenuates the antinociception induced by mu- but not epsilon-opioid receptor agonist in the mouse.

The effects of pretreatment with a protein kinase C activator, phorbol 12,13-dibutyrate, on antinociception induced by i.c.v.-administered mu-opioid receptor agonist (D-Ala2, NMePhe4, Gly(ol)5) enkephalin (DAMGO) or morphine and epsilon-opioid receptor agonist beta-endorphin were studied in male ICR mice. The tail-flick responses were used for antinociceptive tests. I.c.v. pretreatment with phorbol 12,13-dibutyrate (50 pmol) for 30 or 60 but not 10 min attenuated antinociception induced by i.c.v.-administered DAMGO. I.c.v. pretreatment with phorbol 12,13-dibutyrate (10 and 50 pmol) for 60 min caused a dose-dependent attenuation of DAMGO (19.5 pmol)- or morphine (6.0 nmol)-induced antinociception. The dose-response curve for DAMGO-induced antinociception was shifted to the right by 7.3-fold by i.c.v. pretreatment with phorbol 12,13-dibutyrate (50 pmol) for 60 min. However, the i.c.v.-administered beta-endorphin-induced antinociception was not affected by the same pretreatment with phorbol 12,13-dibutyrate. The attenuation of i.c.v.-administered DAMGO- and morphine-induced antinociception by phorbol 12,13-dibutyrate was reversed by concomitant i.c.v. pretreatment with a selective protein kinase C inhibitor calphostin C. These results suggest that activation of protein kinase C by phorbol 12,13-dibutyrate leads to the desensitization of mu-, but not epsilon-opioid receptor-mediated antinociception. These findings also provide additional evidence for differential intracellular modulation on antinociceptive action of mu- and epsilon-opioid receptor agonists.

Analgesics↗

PubMed1997

Biomarkers for responses to heavy metals.

Biomarkers for pathophysiological responses to heavy metals are described with special reference to immunotoxic responses to them. Autoantibody induction in animals by exposure to cadmium is exemplified and discussed on its relevance to pathogenesis of cadmium-induced renal disease. The availability of autoantibodies as a mechanism-oriented biomarker is discussed further in association with cases of autoantibody induction in heavy metal workers.

Animals↗