Search PubMed⌕ Search

Biomedical subjects

M Fujiwara

Publications and source records attributed to M Fujiwara.

At least 181 records · Page 10Linked to original sources
PubMed1998

A synthetic ceramide analog (L-PDMP) up-regulates neuronal function.

To address the role of brain gangliosides in synaptic activity, the ceramide analogs, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP) and its enantiomer, L-PDMP, were used to inhibit and stimulate ganglioside biosynthesis in cultured cortical neurons. Prolonged treatment with both PDMP isomers exhibited opposite effects on functional synapse formation measured by spontaneous synchronized oscillatory activity of intracellular Ca2+ between the neurons: suppression by D-PDMP and facilitation by L-PDMP. Up-regulation of synaptic activity by L-PDMP could be correlated with the slow but robust activation of p42 mitogen-activated protein kinase. Treatment with L-PDMP after transient forebrain ischemia in rats ameliorated the deficit of a well-learned spatial memory by an 8-arm maze task, suggesting a new potential therapeutic approach for neurodegenerative disorders.

Animals↗
PubMed1998

p53 and p21(WAF1) expression in lymphocytic thyroiditis and thyroid tumors.

To clarify the roles of increased apoptosis and cell proliferation in chronic autoimmune lymphocytic thyroiditis and thyroid tumorigenesis, expression of p53 and p21(WAF1) proteins was immunohistochemically investigated in a series of 158 cases. Positive epithelial cells were quantified to give numbers per unit square and to score for distribution. They were found scattered in nontumorous thyroid tissue, their numbers increasing with the severity of thyroiditis and the correlation between expression of the two proteins, regardless of the presence or absence of thyroid neoplasms. Simultaneous expression of both proteins was occasionally found in the same cells by analysis of serial histologic sections. In thyroid tumors, increased expression was found to be diffuse, focal, or scattered for the distribution of p53- or p21(WAF1)-immunopositive cells in accordance with tumor cell dedifferentiation, showing significant correlation between expression of the two proteins. Correlated with these findings, enhanced apoptosis along with decreased Bcl-2 expression and increased Ki-67 labeling in lymphocytic thyroiditis and thyroid tumors was also confirmed in the same series, using in situ DNA nick-end labeling and immunohistochemical methods. Increased expression of p53 and/or p21(WAF1) proteins was thus suggestive of possible DNA damage and increased apoptosis in autoimmune thyroiditis. In addition, a significant correlation between protein overexpression and dedifferentiation of thyroid tumor cells was apparent.

Antibodies↗
PubMed1998

Dual-isotope SPECT diagnosis of a skull-base metastasis causing isolated unilateral hypoglossal nerve palsy.

We describe a 48-year-old female with an isolated unilateral hypoglossal nerve palsy caused by a skull base metastasis from breast cancer. The patient had a medical history of conservative breast therapy for breast cancer. Although the cause of such a neurological deficit includes various pathologies, the reports focusing on metastatic tumor have been limited in number. Radiologic investigation showed a mass involving both the right hypoglossal canal and the clival edge. Swelling of the hypoglossal nerve was observed in views including its canal. Three-dimensional CT images demonstrated the tumor protruding from the enlarged external orifice of the hypoglossal canal. In the present report we mentioned a nuclear medicine procedure to visualize and characterize the small, abnormal tissue in the skull base. Dual-isotope SPECT confirmed an abnormal uptake of 99mTc-HMDP around the hypoglossal canal and a 201Tl-positive elongated lesion running along the hypoglossal nerve.

Cranial Nerve Diseases↗
PubMed1998

Age-related changes in dividing cells of the olfactory epithelium of the maturing guinea pig.

Changes in dividing cells of the olfactory epithelium from guinea pigs of different ages were examined by immunohistochemical staining using anti-proliferating cell nuclear antigen antibody. Numerous dividing cells were scattered diffusely in the basal layer of the olfactory epithelium at 1 and 2 months following birth and then gradually decreased with maturation until 4 months. Findings then remained constant between 4 and 24 months. Subsequently, cell numbers were found to decrease as animals became older. The number of olfactory receptor cells did not vary significantly between 1 and 30 months. Although no correlation could be found between the numbers of dividing cells and olfactory receptor cells, it is still possible that the longevity of the olfactory receptor cells changes to maintain the overall size of the neuronal population.

Aging↗
PubMed1998

Expression of bone morphogenetic proteins in salivary pleomorphic adenomas.

Salivary pleomorphic adenomas are often associated with chondroid tissue formation. We investigated the relationship between chondroid tissue formation and the expression of bone morphogenetic proteins (BMPs), which are strong inducers of ectopic bone and cartilage formation. Fifteen pleomorphic adenomas and seven normal salivary glands were examined genetically and immunohistochemically. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that BMP-1, BMP-2, BMP-3, BMP-4, and BMP-7 mRNAs were overexpressed in 10 (66.7%), 9 (60.0%), 1 (6.7%), 8 (53.3%), and 12 (80.0%), respectively, of the 15 pleomorphic adenomas. Overexpression of BMP-2 mRNA was observed in pleomorphic adenomas. Marked chondroid formation or expression of type II collagen was frequently observed in pleomorphic adenomas that overexpressed BMP-2 mRNA. Immunohistochemically, BMP-2 was detected in modified myoepithelial cells aroud chondroid tissue and basement membranes. These results suggest that BMPs, and expecially BMP-2, have a role in chondroid formation in pleomorphic adenomas.

Adenoma, Pleomorphic↗
PubMed1998

Telomerase activity significantly correlates with cell differentiation, proliferation and lymph node metastasis in colorectal carcinomas.

Telomerase activity was examined by the telomeric repeat amplification protocol assay, in a total of 37 colorectal adenocarcinomas, including stages A, B and C according to the Astler and Collier classification, and correlated with clinicopathological features. Of 17 stage C lesions, 13 were positive (76.5%; P<0.01), demonstrating a significant correlation with lymph node metastasis. In contrast, only 6 of 20 stage A and B carcinomas were positive (30.0%), this being significantly lower (P < 0.05). Moderately or poorly differentiated subtypes were more predominant in the telomerase-positive than in the telomerase-negative groups (P< 0.05) with greater elevation of mitotic and Ki-67 labeling indices (P < 0.0001). No significant relation was found between telomerase activity and p53 protein accumulation or Bcl-2 protein expression. The good correlation with tumor staging, lymph node metastasis, differentiation, and mitotic and Ki-67 labeling indices suggests that this parameter might have potential application in estimation of prognosis.

Adenocarcinoma↗
PubMed1998

Upregulation of HIV-1 replication in chronically infected cells by ingenol derivatives.

We have previously reported that ingenol derivatives are highly potent inhibitors of human immunodeficiency virus type 1 (HIV-1) replication in acutely infected cells. In this study, however, we have found that some ingenol derivatives strongly enhance the replication of HIV-1 in chronically infected cells at nanomolar concentrations. One of the derivatives could activate nuclear factor kappa B (NF-kappa B), a potent inducer of HIV-1 replication, through the activation of protein kinase C (PKC). Whereas another derivative, which affected neither PKC nor NF-kappa B, significantly enhanced HIV-1 replication, suggesting that a PKC-independent mechanism may also exist in ingenol derivative-induced HIV-1 upregulation.

Butyrates↗
PubMed1998

Role of nerve terminal L-type Ca2+ channel in the brain.

The microinjection of Bay K 8644 (BAYK), an L-type Ca2+ channel stimulant, into rat caudate putamen dose-dependently potentiated locomotor activity. DA receptor antagonists significantly blocked BAYK-induced hyperactivity. Striatal DA levels as detected by microdialysis increased 140 fold above steady state levels 20 min after BAYK administration into caudate putamen. This increase was not influenced by a Na+ channel blocker. Pretreatment with 1,4-dihydropyridine (DHP) L-type Ca2+ channel antagonists, but not nifedipine, into caudate putamen significantly blocked the BAYK induced-hyperactivity and DA efflux. The lowest level of intracellular DA detected by fluorohistochemistry coincided with the highest level of extracellular DA. These results indicate that the extraordinary DA release is regulated by a subtype of L-type Ca2+ channel that is present in the nerve terminal.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1998

Extracellular presence of IL-8 in the astrocyte-rich cultured cerebellar granule cells under acidosis.

In order to evaluate the functional role of chemotactic cytokines in the regulation of brain function, we examined the effects of acidosis on the production of IL-8 in cultured neurons and/or astrocyte-rich cerebellar granule cells as assessed by the ELISA method. A time-dependent and significant production of IL-8 was detected in the extracellular fluid of astrocyte-rich cultured cells at 2, 3 and 6 hrs after treatment with acidified Krebs-HEPES buffer (pH 6.9), although such production did not appear in the fluid of neuron-rich cells. Additionally, microglia were detected by microscopic examination in both cultured cells under acidotic conditions. Only astrocyte-containing cultured cells produced a marked increase in intracellular IL-8 under acidotic conditions, although this production was much less than that seen in the extracellular fluid at 6 hrs under acidosis. The increase of IL-8 in astrocyte-rich cultures induced by acidosis was potentiated by treatment with glutamate, which enhanced the increase of cytosolic Ca2+ levels under acidosis, and was affected by extracellular Ca2+ conditions, by cyclosporine A, an inhibitor of calcineurin, and by trifluoperazine, an inhibitor of phospholipase A2. Significant inhibition of IL-8 production was detected after 6 hrs of pretreatment with trifluoperazine. Furthermore, the production of IL-8 under acidosis was associated with the appearance of astrocyte damage. These results suggest that Ca2+-dependent IL-8 is produced by astrocytes, but not neuronal cells, under acidosis, and that this production may be related to the process of cell dysfunction resulting from membrane destruction induced by acidosis.

Acidosis↗
PubMed1998

SKW 6.4 cell differentiation induced by interleukin 6 is stimulated by butyrate.

We investigated if sodium butyrate (NaBu), an inhibitor of histone deacetylase, and its analogs modulate cytokine-induced differentiation of the human B cell line SKW 6.4 transformed by the Epstein-Barr virus. NaBu markedly enhanced interleukin (IL)-6-induced IgM production with an accompanying increase in the level of histone H4 acetylation and augmented IgM production induced by IL-4 and phorbol 12-myristate 13-acetate. From both the enhancing effect of cell differentiation and the effect of inducing histone hyperacetylation in SKW 6.4 cells, other histone deacetylase inhibitors and NaBu analogs were divided into three groups: those that increased both IL-6-induced antibody production and histone acetylation, those that caused histone hyperacetylation, but failed to induce the differentiation, and those that were ineffective at inducing either activity. No agent that enhanced IgM production without inducing histone hyperacetylation was found among the inhibitors and analogs we tested. These results suggest that the increase in the histone acetylation is necessary, but it is insufficient to augment differentiation of SKW 6.4 cells. Thus another activity of NaBu in addition to the inhibition of histone deacetylase may be involved in promoting IL-6-induced differentiation. Our results also suggest that fatty acids that have a straight chain of four carbon atoms or are branched with four and five carbon atoms, which contain no hydrophilic substituents, or those with similar structures, show this other activity.

Acetylation↗
PubMed1998

RD6-2198, a novel betain-type fluoroalkylated oligomer, inhibits the replications of human immunodeficiency virus type 1 and other enveloped viruses.

We have examined a novel betain-type fluoroalkylated oligomer, RD6-2198, for its inhibitory effects on the replication of human immunodeficiency virus type 1 (HIV-1) and other enveloped viruses, including herpes simplex virus types 1 and 2 (HSV-1 and HSV-2, respectively) and respiratory syncytial virus (RSV) in cell cultures. We have found that the compound is a potent and selective inhibitor of these viruses. RD6-2198 inhibited the replication of HIV-1IIIB at a concentration of 0.85 microg/ml with a selectivity index greater than 59 in MT-4 cells. Furthermore, its 50% effective concentration (EC50) values for HSV-1, HSV-2 and RSV, were 0.51, 0.94 and 3.0 microg/ml, respectively. We found that the RD6-2198 suppressed the gp120-CD4 interaction (as monitored by an enzyme-linked immunosorbent assay (ELISA) method). RD6-2198 also inhibited the binding of anti-gp120 monoclonal antibody to gp120 expressed on MOLT-4/IIIB cells (MOLT-4 cells chronically infected with HIV-1IIIB). However, the compound did not inhibit the interaction of anti-CD4 antibody with CD4. These results suggest that RD6-2198 interacts with the viral envelope glycoprotein and thereby inhibits the viral adsorption process. In addition, RD6-2198 was also found to suppress the proliferation of MOLT-4/IIIB cells. When applied topically, RD6-2198 at a concentration of 10 mg/ml completely protected mice from an intravaginal HSV-2 infection.

Animals↗
PubMed1998

Angiocytotoxic therapy in human non-small cell lung cancer cell lines--advantage of combined effects of TNP-470 and SN-38.

The combined effects of TNP-470, a promising antiangiogenic agent, and SN-38, a camptothecin derivative, were evaluated in four human cultured cell lines derived from non-small cell lung cancer (NSCLC). Cytotoxicity experiments were determined by using a tetrazolium salt (MTT) assay. The inhibitory effects of TNP-470 on cell proliferation were dose related and the 50% inhibitory concentrations on these cell lines were 47.3-139.8 microM. Evaluation of drug interactions with isobologram and the combination index values showed that sequential exposure to SN-38 followed by TNP-470 produced synergistic effects in the four cell lines tested. Our findings suggest that such an angiocytotoxic chemotherapy might be promising for the treatment of NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Pulmonary blastoma in an adult. A case with rapid progression.

A case of biphasic type pulmonary blastoma in a 59-year-old man is reported. Although the tumour was radically resected, there was rapid metastasization to the neck, mediastinum, liver and multiple bones. Despite radiotherapy, the patient died about 14 months postoperatively. Close follow-up and aggressive chemotherapy should be considered for such tumours.

Combined Modality Therapy↗
PubMed1998

[Expression of angiotensin type-2 receptors in rat brain during the cell injury].

The present study examined changes in angiotensin type-2(AT2) receptor mRNA level after global brain ischemia or during glutamate neurotoxicity in cultured cortical cells in rats. The AT2 mRNA level increased by three-fold in both the cortex and hippocampus, which are known to be sensitive to ischemic injury, 3 hr after ischemia. The day 10-14 cortical neurons were exposed to glutamate at a toxic concentration of 100 microM for 15 min. AT2 receptor mRNA was then increased 2-fold after exposure to glutamate, while the maximum increase was observed in a dose-dependent manner 3 hr after glutamate stimulation. AT2 receptor binding also increased 3-12 hr after glutamate exposure. The increase in the mRNA level was antagonized by N-nitro L-arginine methyl-ester, a nitric oxide synthase inhibitor. The hemoglobin, a nitric oxide trap, also inhibited the increase in the mRNA level. These results suggest that the increase in the mRNA level is associated with the nitric oxide synthesis by glutamate exposure. The viability of cortical cells after glutamate stimulation was partially restored by the antisense oligonucleotide for the AT2 receptor. The present results thus suggest the AT2 receptor may in some way be related to one of the processes in cell injury.

Animals↗
PubMed1998

[Apoptosis in the repeated cerebral ischemia--behavioral & histochemical study].

We have been reported that the repeated cerebral ischemia induced more severe disruption of spatial cognition than single ischemia without any other motor disturbance in 8-arm radial maze task in rats. And we have been clarified that it is corresponding with 60% of selective cell injury of the CA1 pyramidal cells in the hippocampus. Recently, characteristics of apoptosis such as internucleosomal DNA fragmentation have been found in excitotoxic neuronal death. In the present study, we investigated how necrosis and apoptosis following repeated ischemia involve to the cell death. Repeated cerebral ischemia (10 min x 2, 1 hr interval) induced significant disruption of spatial cognition not only 24 hrs but also 7 days after reperfusion. The decrease of H.E-positive neurons was found in the hippocampus CA1 area and frontal cortex within 3 days after reperfusion, while an DNA fragmentation and TUNNEL-positive neurons in the same areas were found afterward. Furthermore repeated cerebral ischemia-induced disruption of spatial cognition and apoptosis in the hippocampal CA1 area were inhibited by YM-90 K(15 mg/kg,i.p.), which is a selective AMPA/KA receptor antagonist, but not by MK-801. These results suggested that the apoptotic cell death may be occurred via non-NMDA receptor mechanism in relatively late phase of the reperfusion period and it may relate to the incidence of the disruption of spatial cognition in the rat.

Animals↗
PubMed1998

A case of microscopic polyarteritis nodosa with interstitial pneumonia successfully treated with steroid pulse therapy and immunosuppressive agents.

We report a patient with microscopic polyarteritis nodosa (mPN) and interstitial pneumonia, who was subjected to investigation by bronchoalveolar lavage (BAL), thoracic computerized tomography (CT) and gallium-67 citrate (67Ga) scintigraphy before and after administration of glucocorticoid and immunosuppressive agents. Renal function, renal histology, interstitial inflammation of the lung, and pulmonary function and histology improved cytoplasmic autoantibody (MPO-ANCA), which decreased with decreasing disease activity after starting treatment. Interstitial pneumonia may be associated with pulmonary capillaritis due to mPN. Methylprednisolone pulse therapy followed by oral prednisolone and immunosuppressive agents is considered to be an effective therapeutic strategy for combined mPN and interstitial pneumonia.

Anti-Inflammatory Agents↗