Biomedical subjects

H Okamura

Publications and source records attributed to H Okamura.

At least 289 records · Page 16Linked to original sources

PubMed1997

Loss of day-night differences in VIP mRNA levels in the suprachiasmatic nucleus of aged rats.

Age-related decreases in circadian oscillating activity are speculated to be one of the causes of psychiatric symptoms. To explore the effects of aging on vasoactive intestinal peptide (VIP) synthesis in the suprachiasmatic nucleus (SCN), we investigated the changes in VIP mRNA levels in aged rats compared with young-adult rats under a light/dark cycle using in situ hybridization combined with microcomputer-based imaging analysis. In the young-adult rats, total signals of VIP mRNA in the light-phase showed a significant decrease compared with those on the dark-phase. The VIP signal level in the aged rats was markedly lower than that in young-adults in both light and dark phases. Moreover, in the aged rats, there were no significant differences in VIP mRNA level between the light and dark phases. These results suggest that gene expression of VIP neurons, a main component of the circadian oscillating system, becomes disturbed in the aged rat brain.

Aging↗

PubMed1997

Activation of interferon-gamma inducing factor mediated by interleukin-1beta converting enzyme.

The interleukin-1beta (IL-1beta) converting enzyme (ICE) processes the inactive IL-1beta precursor to the proinflammatory cytokine. ICE was also shown to cleave the precursor of interferon-gamma inducing factor (IGIF) at the authentic processing site with high efficiency, thereby activating IGIF and facilitating its export. Lipopolysaccharide-activated ICE-deficient (ICE-/-) Kupffer cells synthesized the IGIF precursor but failed to process it into the active form. Interferon-gamma and IGIF were diminished in the sera of ICE-/- mice exposed to Propionibacterium acnes and lipopolysaccharide. The lack of multiple proinflammatory cytokines in ICE-/- mice may account for their protection from septic shock.

Animals↗

PubMed1997

Human follicular dendritic cells in vitro and follicular dendritic-cell-like cells.

Human follicular dendritic cell (FDC)-like cells (FLC) have been utilized for the in vitro analysis of germinal center reactions. However, there is no consensus whether FLC represent FDC in vitro. The purpose of the present study has therefore been to determine distinguishing features of FDC and FLC in vitro. The expression of CD40, CD54, CD49d, cytokine (gamma-IFN and IL-4)-dependent MHC-class II, and CD106 was observed to be specific for the determination of FDC in long-term culture. The cytokine-dependent emperipolesis of germinal center B cells was establised as another discriminating property for FDC in vitro. In 2 out of 72 long-term cultures of FDC, we encountered dividing cells among the non-dividing population of FDC. The dividing cells expressed accessory molecules similar to those of FDC but showed emperipolesis only for the initial few days of their growth. FDC did not enhance the CD40-dependent proliferation of germinal center B cells; in contrast, FLC augumented it. Both types of cells produced a significant amount of cytokine-dependent IL-6. Further studies are needed to determine whether FLC originate from FDC in vitro.

Cell Adhesion↗

PubMed1997

New variant groups identified from HGV isolates.

We have determined the primary sequence of the 5' noncoding region (5' NCR) and putative helicase regions (NS-3) of hepatitis G virus (HGV) and GB virus C (GBV-C) that were isolated in Japan from suspected cases of nonA-nonB and/or nonA-nonB-nonC viral hepatitis by using RT-PCR, and we compared the newly isolated sequences with three established isolates. The addition of a "G" residue was found at the 5' terminus of all 8 Japanese isolates. These isolates were more clearly distinguished from the prototype viruses by comparison with the 5' NCR sequence than by comparison with the NS-3 region. Our results suggested that at least three distinct genomic variants of HGV exist. Genotyping of HGV by using RT-PCR based on the sequence of the 5' NCR seems highly feasible.

Base Sequence↗

PubMed1997

Contribution of IL-1 beta to the enhancement of Campylobacter rectus lipopolysaccharide-stimulated PGE2 production in old gingival fibroblasts in vitro.

Campylobacter rectus is associated with adult periodontitis. We previously reported that C. rectus lipopolysaccharide (LPS)-stimulated prostaglandin E2 (PGE2) production in old cells of human gingival fibroblasts (HGFs) is higher than that in young cells. The present study examined whether an enhancement of C. rectus LPS-stimulated interleukin (IL)-1 beta production in old HGFs contributed to the increased production of PGE2. LPS was prepared from C. rectus ATCC33238. HGFs were established from healthy gingiva in three patients, aged 10-12 years. Cellular aging in culture was determined with increasing doubling. The cultured cells were treated with LPS (0.01-10 micrograms/ml), and the amount of IL-1 beta in the medium was measured after a 24 h incubation. The LPS-stimulated IL-1 beta production in each old cell (corresponding to 57-67% of complete life-span) was increased (1.6-2.6 times) compared to that in the young cells (corresponding to 17-20% of the life-span). The IL-1 beta mRNA synthesis in the presence of LPS in the old cells was higher than that in the young cells. The enhancement of LPS-stimulated PGE2 production was inhibited by anti-IL-1 beta antibody and by IL-1 receptor antagonist. These findings suggest that the greater ability of old cells to produce PGE2 in response to C. rectus LPS is due to their greater level of IL-1 beta.

Antibodies↗

PubMed1997

Effects of dopaminergic agents on reversal of reserpine-induced impairment in conditioned avoidance response in rats.

Male Slc:Wistar, Std:Wistar, and Slc:F344/N rats had good acquisition of the conditioned avoidance response (CAR), while that of the male Slc:Wistar/ST, Jcl:Wistar, and Crj:Wistar rats was bad. Reserpine-induced impairment (RII) in CAR was observed 2-72 h after administration of dopaminergic (DAergic) agents in male Slc:Wistar rats. Amitriptyline (5-80 mg/kg, P.O.), imipramine, desipramine, cis-dosulepine, and trans-dosulepine at dose of 40 mg/kg, P.O. showed no antagonism against RII in CAR 20-23 h after reserpine injection (1 mg/kg, S.C.). However, the atypical antidepressive agents sibutramine (5-10 mg/kg, P.O.), bupropion (40 mg/kg, P.O.), and nomifensine (10-40 mg/kg, P.O.) exhibited antagonism against RII in CAR. The calcium channel antagonists flunarizine, nimodipine, and KP-840 at dose of 10 and 100 mg/kg, P.O., the cerebral improving agent indeloxazine (20-80 mg/kg, P.O.), the anticholinergic agent atropine (5-40 mg/kg, P.O.), 5-hydroxy-L-tryptophan (5-HTP) (40 mg/kg, I.P.), a precursor of 5-hydroxytryptamine (5-HT), and (+/-)-threo-dihydroxyphenylserine [(+/-)-threo-DOPS] (20-200 mg/kg P.O.), a norepinephrine (NE) precursor, showed no antagonism against RII in CAR. The DAergic agents methamphetamine (5 mg/kg, P.O.) and amantadine (50-250 mg/kg, P.O.), L-DOPA (200 mg/kg, P.O.), and the DAergic D1/D2 receptor agonist apomorphine (0.1-1 mg/kg, S.C.) showed marked antagonism against RII in CAR. Although the DAergic D1-receptor agonist KF-38393 (0.3-30 mg/kg, I.P.) and the DAergic D2-receptor agonist quinpirole (0.3-10 mg/kg, I.P.) induced only a weak recovery of RII in CAR when they were administered alone, in contrast to a potent synergistic recovery of RII in CAR, which was observed when SKF-38393 (1 mg/kg, I.P.) and quinpirole (1 mg/kg, I.P.) were administered together. These results suggest that the DAergic nervous system rather than the adrenergic or 5-HT nervous system is involved in RII in CAR, and that both the DAergic D1- and D2-mediated nervous systems play important roles in this process.

Animals↗

PubMed1997

Lesion-induced neuronal nitric oxide synthase in Purkinje cells of the rat cerebellar cortex: histochemical and in situ hybridization study.

Lesion-induced induction of neuronal nitric oxide synthase (nNOS) was examined in the rat cerebellum. The stab-lesioned cerebellar cortex was examined with NADPH-diaphorase (NADPH-d) histochemistry and in situ hybridization using nNOS cRNA probe at 1, 3, 7, 14, 35 days post-lesion. NADPH-d- and nNOS mRNA-positive Purkinje cells appeared adjacent to the lesion by 3 days after the lesion. The area of distribution expanded and the number of positive cells increased at 7 days after the lesion, and at 14 days post-lesion, shrunken NADPH-d-positive Purkinje cells with irregular surface appeared. NADPH-d activity and nNOS mRNA signal could not be detected in Purkinje cells after 35 days post-lesion. Combined NADPH-d histochemistry and in situ hybridization using glutamic acid decarboxylase (GAD) cRNA probe revealed that nNOS-expressing Purkinje cells showed fewer GAD mRNA signals than those in normal Purkinje cells. The atrophic contour and the lower expression of GAD mRNA signals in NADPH-d positive Purkinje cells suggest that nNOS is expressed under a degenerating process.

Animals↗

PubMed1997

Co-localization of preprosomatostatin mRNA and preprotachykinin A mRNA in neurons of the rat suprachiasmatic nucleus.

The suprachiasmatic nucleus (SCN), a circadian oscillator, contains various peptides arranged in the compartment-specific manner. Somatostatin (SS) and substance P (SP), a peptide derived from preprotachykinin A (PPT-A), are expressed in neurons in the intermediate zone, a narrow area between the major dorsomedial and ventrolateral subdivisions. In the present study, we examined the possibility of co-localization of SS and SP in the SCN by a double-labeling in situ hybridization method using 35S-labeled and digoxigenin-labeled cRNA probes. In the SCN, most of preprosomatostatin (PPSS) mRNA-containing neurons expressed PPT-A mRNA (86%) and, in turn, almost all preprotachykinin A (PPT-A) mRNA-expressing neurons expressed PPSS mRNA signals (97%). Both PPSS and PPT-A mRNAs were also detected in the cerebral cortex and the caudate-putamen, however, their co-existence was extremely rare (< 4%) in these regions. Since the pharmacological effects of SS and SP are similar to that of the light pulses exposed on animals under constant darkness, the co-release of peptides might be an important process for entraining the circadian clock in the SCN.

Animals↗

PubMed1997

Comparative distribution of nitric oxide synthase (NOS) in pancreas of the dog and rat: immunocytochemistry of neuronal type NOS and histochemistry of NADPH-diaphorase.

We investigated the localization of nitric oxide synthase in the pancreas of the dog in comparison to the rat by the methods of immunocytochemistry using antineuronal type nitric oxide synthase serum and histochemistry using NADPH-diaphorase activity. In both species, the most intense staining was observed in neuronal cell bodies and fibers in the pancreas and nitric oxide synthase immunoreactivity was completely colocalized with NADPH-diaphorase activity. However, there were differences of the distribution between the two species. In the dog pancreas, immuno- and NADPH-diaphorase-positive nerve fibers were numerous around pancreatic ducts and moderate around the arteries and the acini but few in the islets. In contrast, in the rat pancreas, immuno- and diaphorase-positive fibers were fewer around the pancreatic ducts and acini and more abundant in the islets. The expression ratio of NADPH-diaphorase in intrapancreatic ganglion cell bodies that were scattered in the interlobular connective tissue was low to moderate (28.1% in the right lobe, 49.5% in the left lobe) in the dog, while the ratio in rat pancreas was very high in both lobes of the pancreas (about 86%). Except for neuronal staining, weak NADPH-diaphorase-positive reactions were detected in the vascular endothelial cells of the pancreas in both species. In rat islet cells, weak neuronal type nitric oxide synthase immunoreactivity was observed; however, in dog islet cells, no immunoreactivity was detected. These results suggest that nitric oxide in the pancreas is derived from vascular endothelium and neuronal tissue in both species and that the neuronal nitrergic regulation of the exocrine and endocrine pancreas is different between the species.

Animals↗

PubMed1997

Characterization of sonographically indeterminate ovarian tumors with MR imaging. A logistic regression analysis.

PURPOSE: The goal of this study was to maximize the discrimination between benign and malignant masses in patients with sonographically indeterminate ovarian lesions by means of unenhanced and contrast-enhanced MR imaging, and to develop a computer-assisted diagnosis system. MATERIAL AND METHODS: Findings in precontrast and Gd-DTPA contrast-enhanced MR images of 104 patients with 115 sonographically indeterminate ovarian masses were analyzed, and the results were correlated with histopathological findings. Of 115 lesions, 65 were benign (23 cystadenomas, 13 complex cysts, 11 teratomas, 6 fibrothecomas, 12 others) and 50 were malignant (32 ovarian carcinomas, 7 metastatic tumors of the ovary, 4 carcinomas of the fallopian tubes, 7 others). A logistic regression analysis was performed to discriminate between benign and malignant lesions, and a model of a computer-assisted diagnosis was developed. This model was prospectively tested in 75 cases of ovarian tumors found at other institutions. RESULTS: From the univariate analysis, the following parameters were selected as significant for predicting malignancy (p< or =0.05): a solid or cystic mass with a large solid component or wall thickness greater than 3 mm; complex internal architecture; ascites; and bilaterality. Based on these parameters, a model of a computer-assisted diagnosis system was developed with the logistic regression analysis. To distinguish benign from malignant lesions, the maximum cut-off point was obtained between 0.47 and 0.51. In a prospective application of this model, 87% of the lesions were accurately identified as benign or malignant. CONCLUSION: Benign and malignant ovarian lesions can be distinguished in most sonographically indeterminate lesions by means of parameters obtained from contrast-enhanced MR imaging.

Contrast Media↗

PubMed1997

Palmitoylation of p59fyn is reversible and sufficient for plasma membrane association.

Members of the Src family of protein tyrosine kinases are localized to subspecialized regions of the plasma membrane. Herein we show that the N-terminal SH4 region of the Src family member p59fyn (Fyn) is both necessary and sufficient for targeting of Fyn and heterologous proteins to the plasma membrane and detergent-insoluble subdomains. Attachment of the first 16 amino acids of Fyn to a normally cytosolic protein, beta-galactosidase, resulted in distinct plasma membrane localization of the chimeric protein. Mutation of the palmitoylation site (cysteine-3) within Fyn16-beta-galactosidase or wild-type Fyn abrogated plasma membrane localization, resulting in redistribution of the mutant proteins into intracellular membranes. Substitution of the SH4 motif within Fyn with heterologous sequences from other palmitoylated proteins (G alpha o and GAP43) revealed that the presence of palmitate is sufficient to direct plasma membrane localization independent of surrounding amino acid sequences and myristate. Palmitoylated Fyn chimeras were also enriched in the Triton X-100-resistant matrix, whereas nonpalmitoylated forms of these proteins were detected in the detergent-soluble fraction. The palmitate moiety on Fyn exhibited a half-life of 1.5-2 h. In contrast, the half-life of the polypeptide backbone was 8 h, indicating that palmitoylation is a reversible modification. These studies establish that the palmitoylated SH4 sequence of Fyn can be used to specifically target proteins to the plasma membrane in a reversible manner.

3T3 Cells↗

PubMed1997

Role of progesterone in capillary permeability in hyperstimulated rats.

The role of progesterone in capillary permeability, which may be causally related to the pathophysiology of ovarian hyperstimulation syndrome (OHSS), was investigated in immature rats. A total of 96 female Wistar rats aged 22 days were given 10 IU of equine chorionic gonadotrophin daily for 4 consecutive days, and given 30 IU of human chorionic gonadotrophin on the fifth day to produce hyperstimulated manifestations. On the sixth day, groups of 12 rats each received RU486 at a dose of 0, 1, 2.5, 5, 10, 15 or 20 mg/kg (groups 1-7), or RU486 at 5 mg/kg combined with 6alpha-methyl-17alpha-hydroxy-progesterone acetate at 10 mg/kg (group 8). On the 7th day, the ovarian weight and capillary permeability of all rats were determined. Capillary permeability was evaluated from the Evans blue dye (EB) content in the ovaries and the EB level in peritoneal irrigated fluid at 30 min after the intravenous injection of EB. The peritoneal fluid EB level was significantly lower in groups 3, 4, and 5 than in the vehicle group. However, the peritoneal EB level in group 7 was higher than in the vehicle group, although not significantly. These findings demonstrated that RU486 has two divergent effects on capillary permeability, depending on the dose administered. In group 8, on the other hand, the peritoneal EB level and ovarian EB content were significantly higher than the corresponding values in group 4, respectively, suggesting that progesterone has a role in capillary permeability and ovarian enlargement. These results imply that progesterone may contribute, at least in part, to the pathophysiology of OHSS in this experimental model.

Adrenocorticotropic Hormone↗

PubMed1997

Metabolite changes with age measured by proton magnetic resonance spectroscopy in normal subjects.

To determine whether there are metabolite changes in the left medial temporal and frontal lobes with aging, we performed proton magnetic resonance spectroscopy in 36 normal subjects. The N-acetylaspartate/creatine-phosphocreatine ratio in the medial temporal lobe tended to be decreased in subjects over 60 years of age. The ratio decrease in the frontal lobe related to aging was lower than that in the medial temporal lobe. There were no significant differences in the metabolite ratios between males and females. These findings suggest that structures in the medial temporal lobe may be more susceptible to neuronal dysfunction associated with aging than those in the frontal lobe.

Adult↗

PubMed1997

Deep venous thrombosis of the leg due to psychiatric stupor.

We report the cases of two patients with psychiatric stupor who developed venous thrombosis. A 29-year-old schizophrenic woman had been hospitalized in psychiatric institutions three times because of stupor associated with auditory hallucinations and thought blocking. These symptoms recurred and she was admitted to our hospital with deep venous thrombosis of her left leg. The other patient was a 67-year-old woman with depression. She had also suffered from insomnia. Following admission to our hospital, she developed a depressive stupor complicated by deep venous thrombosis of her left leg. Both cases were treated with sodium heparin and urokinase, and completely resolved. It is well known that dehydration, infection and decubitus ulcers are important physical complications of psychiatric stupor, but there have been few reports of deep venous thrombosis as a physical complication of stupor.

Adult↗

PubMed1997

An autopsy case of diffuse malignant mesothelioma of the pericardium.

A report is presented of an autopsy case of a 71-year-old Japanese man with a diffuse malignant epithelial mesothelioma of the pericardium with massive pericardial effusion and a thickened pericardium. He had no history of exposure to asbestos. He suffered severe heart failure and later died. Autopsy revealed that the tumor had developed over the pericardium. Microscopically, the tumor cells were arranged in an epithelial form, and histochemically, the cytoplasm of these cells contained glycogen and hyaluronic acid. The tumor tissue showed immunohistochemical positivity for cytokeratin, epithelial membrane antigen, vimentin, cancer antigen 125, thrombomodulin, mesothelial antigen, muscle actin and human milk fat globule. In contrast, all the tumor cells were negative for human carcinoembryonic antigen and epithelial antigen. Ultrastructurally, the tumor cells had long, thin microvilli, abundant intermediate filaments, intracytoplasmic lumina and long desmosomes. It is considered that the patient had a typical malignant epithelial mesothelioma of the pericardium.

Aged↗

PubMed1997

Interleukin-12 (IL-12) and IL-18 synergistically induce the fungicidal activity of murine peritoneal exudate cells against Cryptococcus neoformans through production of gamma interferon by natural killer cells.

We examined the ability of interleukin-12 (IL-12) and IL-18 to induce the production of gamma interferon (IFN-gamma) and nitric oxide (NO) by murine peritoneal exudate cells (PEC) and to stimulate the growth-inhibitory activity of these cells against Cryptococcus neoformans. PEC produced IFN-gamma and NO when stimulated with a combination of IL-12 and IL-18 but little or no IFN-gamma or NO when either cytokine was used alone. PEC anticryptococcal activity was mediated by IFN-gamma and NO production, since it was completely inhibited by a neutralizing anti-IFN-gamma monoclonal antibody (MAb) and N(G)-monomethyl-L-arginine, a competitive inhibitor of NO synthesis, respectively. To identify the IFN-gamma-producing cells among PEC stimulated with IL-12 and IL-18, we depleted NK cells, gammadelta T cells, or CD4+ T cells by treating PEC with specific Abs and complement. NK cell depletion strongly suppressed IFN-gamma production and almost completely inhibited NO production and anticryptococcal activity, while depletion of other cells had no such influence. Alternatively, purified NK cells by two cycles of glass adherence and magnetic separation with anti-CD3, -CD4, -CD8, and -B220 MAbs produced a greater amount of IFN-gamma by stimulation with IL-12 and IL-18 than unseparated non-glass-adherent PEC. Our results demonstrated that IL-12 and IL-18 synergistically induced NO-dependent anticryptococcal activity of PEC by stimulating NK cells to produce IFN-gamma.

Animals↗

PubMed1997

Adenoma malignum: MR imaging and pathologic study.

PURPOSE: To evaluate the clinical, pathologic, and magnetic resonance (MR) imaging findings in adenoma malignum, a rare variant of uterine cervical adenocarcinoma. MATERIALS AND METHODS: Medical records of all patients (n = 7) with adenoma malignum of the uterine cervix diagnosed pathologically between 1988 and 1996 were retrospectively reviewed. Unenhanced T1-weighted and T2-weighted images and gadolinium-enhanced T1-weighted MR images were evaluated, and findings were correlated with gross pathologic and microscopic features. RESULTS: In five of seven patients, enlargement of the cervix was seen. All lesions were detected as multiple cystic lesions that extended from the endocervical gland to the deep stroma of the cervix. They appeared isointense (n = 5) or slightly hyperintense (n = 2) relative to the uterus on T1-weighted images and markedly hyperintense relative to the uterus on T2-weighted images. Solid portions of variable size were seen between cystic lesions, and both the multiple cystic component and the solid portion were most apparent on the gadolinium-enhanced T1-weighted images. Microscopic parametrial invasion was seen in two patients but was not detected at MR imaging. CONCLUSION: Adenoma malignum was depicted on MR images as a multicystic mass with solid portions located in the deep cervical stroma. Gadolinium enhancement helped identify the solid portion of the tumor.

Adenocarcinoma↗

PubMed1997

Gastrointestinal submucosal tumors: evaluation with endoscopic US.

PURPOSE: To describe the endoscopic ultrasound (US) features of benign versus malignant submucosal tumors throughout the gastrointestinal tract. MATERIALS AND METHODS: One hundred nine patients aged 24-81 years suspected to have submucosal tumors (11 esophageal, 41 stomach, 24 duodenal, and 33 colorectal tumors) at barium studies or endoscopy underwent endoscopic US. The layer of origin, internal echo pattern, and lesion margin were analyzed by means of consensus and independent interpretation by three radiologists. RESULTS: Endoscopic US findings revealed several distinct patterns among various submucosal tumors. Sixteen (94%) of the 17 homogeneous lesions with histopathologic findings of malignancy were hypoechoic, although 29 (43%) of the 68 homogeneous lesions with histopathologic findings of benignity were similarly hypoechoic. Homogeneous lesions that were anechoic, of intermediate echogenicity, or hyperechoic were almost exclusively benign (39 [98%] of 40). In contrast, 23 (96%) of the 24 malignant lesions were heterogeneous (n = 7) or homogeneously hypoechoic (n = 16). The sizes of benign and malignant lesions were significantly different (P < .05). There was no significant difference in the echo pattern (i.e., homogeneous versus heterogeneous), but there was a significant difference in the proportion of hypoechoic versus nonhypoechoic lesions (anechoic, hyperechoic, or of intermediate echogenicity; P < .001). CONCLUSION: The differential diagnosis of gastrointestinal submucosal tumors is assisted with endoscopic US.

Diagnosis, Differential↗