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N Shinomiya

Publications and source records attributed to N Shinomiya.

At least 37 records · Page 2Linked to original sources
PubMed1999

Incomplete Sjögren-Larsson syndrome in two Japanese siblings.

Sjögren-Larsson syndrome (SLS) is a rare, autosomal recessive disorder characterized by ichthyosis, spastic diplegia and mental retardation. Biochemical studies have pinpointed the pathogenesis resulting in the deficiency of the fatty aldehyde dehydrogenase (FALDH) component of the fatty alcohol NAD+ oxidoreductase complex. Histochemical analysis revealed a reduction in alcohol dehydrogenase (AD) activity in the skin. SLS patients have been categorized biochemically into two groups: complete and incomplete reduction according to the degree of FALDH deficiency. Our patients demonstrated incomplete clinical features, including a 1/3 reduction in FALDH activity, and decreased AD activity in the ichthyotic lesion. The phenotypical differences between our cases and classic SLS are probably due to the partial FALDH deficiency.

Aldehyde Oxidoreductases↗
PubMed1999

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Journal Article↗
PubMed1998

Osteoclastogenesis inhibitory factor suppresses osteoclast survival by interfering in the interaction of stromal cells with osteoclast.

Osteoclastogenesis inhibitory factor (OCIF) was originally identified as a factor inhibiting osteoclast (OC) formation. The number of OC in rats treated with OCIF decreased, suggesting that OCIF inhibits OC formation in vivo; however, it is also possible that OCIF affects the number of OC by promoting apoptosis of OC. To address this issue, the effects of OCIF on the survival of OC were examined using well established mouse culture systems. OCIF dose-dependently inhibited OC formation in mouse marrow cultures. Addition of OCIF during day 0-3 did not alter the peak levels of OC formation on day 7 and 8. However, the addition of OCIF during day 5 and thereafter resulted in the rapid decrease of the number of OC. OCIF inhibited the survival of OC formed in mouse marrow cultures in dose- and time-dependent manners. The involvement of stromal cells in OC survival was examined using crude and stromal cell-depleted OC populations. OCIF dramatically inhibited the survival of crude OC populations rich with stromal cells. However, in stromal cell-depleted OC populations, OC spontaneously decreased in the absence of OCIF and OCIF did not enhance the decrease further at least up to 48 h. Apoptotic OC were detected in detached cell populations treated with OCIF in mouse marrow cultures and a specific inhibitor for caspase-3 rescued the death of OC. OCIF mutant lacking the death domain homologous regions inhibited OC survival, though the potency was much less than native OCIF. Taken together, OCIF inhibited not only OC recruitment but also OC survival. OCIF inhibited OC survival by interfering the interaction of stromal cells with OC.

Animals↗
PubMed1998

Expression of cyclooxygenase-2 protein in gastric adenocarcinoma.

BACKGROUND AND OBJECTIVES: Epidemiological studies have suggested that the regular use of nonsteroidal antiinflammatory drugs, which inhibit cyclooxygenase (COX), reduces the risk of colon cancer. The inducible COX-2 isoform has been reported to be upregulated in colorectal carcinomas and may play a role in colorectal carcinogenesis. The purpose of this study was to investigate the expression of COX-2 protein in human gastric adenocarcinomas. METHODS: COX-2 protein expression was examined in 23 patients with gastric adenocarcinoma by immunoblotting and immunohistochemistry. RESULTS: There was an increase in COX-2 protein levels in 19 of the 23 carcinomas (83%) compared with the paired normal gastric mucosa by an immunoblot analysis. There was no correlation between tumor histology and COX-2 protein expression. An immunohistochemical study in the 19 cases showed diffuse COX-2 staining in the cytoplasm of cancer cells. Mononuclear cells or fibroblasts of the cancer stroma were not stained with COX-2. Sporadic staining for COX-2 was observed in the normal fundic or metaplastic glandular cells in all cases. CONCLUSIONS: COX-2 protein expression was elevated in most human gastric adenocarcinomas in comparison to the normal mucosa. COX-2 may therefore play an important role in gastric carcinogenesis.

Adenocarcinoma↗
PubMed1998

Carbonic anhydrase I and II as a differentiation marker of human and rat colonic enterocytes.

Carbonic anhydrase (CA) is an enzyme that is expressed in the intestine and catalyzes the reversible hydration of CO2 in the following reaction: CO2 + H2O<==>H2CO3<==>H(+)+HCO3-. To elucidate the association of CA expression with the differentiation of colonic enterocytes, we investigated the expression and localization of CA using a Northern blotting analysis, Western blotting analysis, and immunohistochemical staining. A Northern blotting analysis revealed an abundant expression of CA I and II mRNA in the colonic epithelial cells. However, the expression of CA III mRNA was not detected. According to the results of immunohistochemical staining of the human colonic mucosa using antisera against CA I and II, both CA I and II were localized on the cytoplasm of non-goblet columnar cells in the upper half of the crypts where more differentiated cells are located. According to the results of immunohistochemical staining of the rat colonic mucosa, neither CA I and II were detected at the new-born stage. The expression of CAs in the upper half of the crypts began to rise from 1 week after birth, and thereafter increased according to the growth of the rats. At 3 weeks after birth, the expression of CAs was almost the same as that of the adult rats. The amount of CA proteins evaluated by a Western blotting analysis revealed that the expression of CAs increased gradually until reaching a maximum level at 6 or 8 weeks. These results therefore suggest that CA I and II appear to be good markers for the differentiation of enterocytes in the colonic mucosa.

Animals↗
PubMed1998

Inhibitory effects of ginsenoside Rh2 on tumor growth in nude mice bearing human ovarian cancer cells.

Ginsenoside Rh2 (Rh2), isolated from an ethanol extract of the processed root of Panax ginseng CA Meyer, inhibits the growth of B16 melanoma cells. This study was designed to evaluate the ability of Rh2 to inhibit growth of human ovarian cancer cells (HRA) in vitro and in nude mouse. Rh2 inhibited proliferations of various established human ovarian cancer cell lines in a dose-dependent manner between 10 and 60 microM in vitro and induced apoptosis at around the IC50 dose. When HRA cells were inoculated s.c. into the right flank of nude mice, all mice formed a palpable tumor within 14 days. Although i.p. administration of Rh2 alone hardly inhibited the tumor growth, when Rh2 was combined with cis-diamminedichloroplatinum(II) (CDDP) the tumor growth was significantly inhibited, compared to treatment with CDDP alone. When mice were treated p.o. with Rh2 daily (but not weekly), the tumor growth was significantly (P<0.01) inhibited, compared to CDDP treatment alone. When Rh2 was combined with CDDP, the degree of tumor growth retardation was not potentiated. The survival time was significantly (P<0.05) longer than that of medium alone-treated controls or the group treated with CDDP alone. Then, we examined whether p.o. administration of Rh2 has a dose-dependent inhibitory effect on the tumor growth. I.p. and weekly administration of CDDP had more potent antitumor activity in the order of 1 mg/kg, 2 mg/kg and 4 mg/kg, whereas p.o. and daily administration of Rh, (0.4 to 1.6 mg/kg) not only had antitumor activity comparable to that of 4 mg/kg CDDP, but also resulted in a significant increase of the survival. Doses of Rh2 used in this study did not result in any adverse side-effects as confirmed by monitoring hematocrit values and body weight, unlike 4 mg/kg CDDP, which had severe side-effects. It is noteworthy that p.o. but not i.p. treatment with Rh2 resulted in induction of apoptotic cells in the tumor in addition to augmentation of the natural killer activity in spleen cells from tumor-hearing nude mice. Thus, particularly in view of the toxicity of CDDP, Rh2 alone would seem to warrant further evaluation for treatment of recurrent or refractory ovarian tumor.

Animals↗
PubMed1998

Effect of hyperbaric oxygen on intercellular adhesion molecule-1 (ICAM-1) expression in murine lung.

BACKGROUND: The lung is one of the most susceptible organs to the toxic effect of high pressure oxygen. However, the contribution of the cellular adhesion molecules and inflammatory leukocytes in the pulmonary oxygen toxicity, especially in an acute exudative phase, is not well understood. In the present study we have investigated the toxic effect of hyperbaric oxygen (HBO) expressed by the analysis of the intercellular adhesion molecule-1 (ICAM-1) on the pulmonary vascular endothelial cells and leukocyte function. METHODS: Mice were exposed to HBO at 3 ATA of PO2 for 3, 4, or 6 h. Expression of ICAM-1 was serially observed by immunohistochemical analysis. The oxidative metabolic activity of the leukocytes was measured after HBO exposure. RESULTS: After HBO exposure an increase in the number of pulmonary interstitial leukocytes (PIL) and bronchoalveolar lavage (BAL) was observed at 72 h and 48 h, respectively. The expression of ICAM-1 was strongly enhanced immediately after HBO exposure and this enhancement lasted for 24 h. This suggests the importance of enhanced expression of adhesion molecules in the generation of pulmonary oxygen toxicity. However, we could not detect increased chemiluminescence activity in the early phase in the BAL cells and PIL. CONCLUSION: Expression of ICAM-1 was enhanced from the very early stage after HBO, but neither accumulation of leukocytes in the lung nor increase in the chemiluminescence activity were observed in this phase. Therefore, activation of inflammatory leukocytes in the pulmonary oxygen toxicity may occur only after prolonged (more than 4 h) or repetitive exposures to HBO.

Animals↗
PubMed1997

Caffeine induces S-phase apoptosis in cis-diamminedichloroplatinum-treated cells, whereas cis-diamminedichloroplatinum induces a block in G2/M.

Caffeine overrides checkpoints in the G2 phase of the cell cycle by inhibiting DNA repair at this phase and increases the cytotoxicity of antitumor drugs, such as cis-diamminedichloroplatinum (CDDP). The enhanced cell death induced by caffeine is characterized by apoptosis. In this paper, we demonstrate that this apoptotic event occurs in S phase of the cell cycle, whereas CDDP induces a block in G2/M. DNA histogram analysis revealed that caffeine reduced G2 arrest in CDDP-treated EL-4 cells. In a synchronous population, the ratio of cyclin B:p34cdc2 was upregulated just before the cells went into the apoptotic pathway. A rapid increase in DNA fragmentation was detected at 12-24 h, when marked regression of G2/M phase was observed. Moreover, the degree of DNA fragmentation in CDDP + caffeine-treated cells was not reduced when the cell cycle was arrested at metaphase by exposure to the spindle-inhibitor nocodazole. It is possible that execution of the apoptotic program after treatment with caffeine did not require the EL-4 cells to reenter G1 phase. The apoptotic cell fraction in the group of CDDP + caffeine was recognized as an S population by bivariate analysis of apoptosis and DNA content. These results suggest that enhancement of the apoptotic activity of CDDP-treated cells by caffeine is not a G1-phase event but an S-phase-specific event, whereas cells were arrested in G2/M phase, and that it is regulated by G2 checkpoint-related proteins.

Animals↗
PubMed1996

MRI in the mild type of mucopolysaccharidosis II (Hunter's syndrome).

We report imaging findings in a 3-year-old boy with the typical mild type of Hunter's disease. MRI revealed multifocal large cyst- or spindle-like areas of increased and decreased signal in the white matter, including the corpus callosum on T1- and T2-weighted images. The white matter showed high signal on T2-weighted images, isointense with cerebrospinal fluid on all other pulse sequences. To our knowledge, these appearances have not been reported in this disorder. Deposition of mucopolysaccharide and/or glycolipid and increase in fluid content seem to be responsible.

Brain↗
PubMed1996

Common acute lymphoblastic leukemia preceded by hypercalcemia in an infant.

A case of common acute lymphoblastic leukemia (ALL) preceded by hypercalcemia was observed in an infant. A high blood level of parathyroid hormone related protein (PTH-rP) was detected during the first examination at Ohashi Hospital. Treatment with antineoplastic agents led to complete remission. The blood PTH-rP level decreased as a result of treatment. PTH-rP produced by leukemic cells was though to be the cause of the hypercalcemia.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

An upregulation of interleukin-2 receptor, transferrin receptor expression and cytokine production mediated by hemin in human peripheral blood mononuclear cells.

BACKGROUND: We previously reported that hemin-induced mitogenicity in mouse splenocytes was potentiated up to two-fold by interleukin (IL)-2, and the combination of hemin and IL-2 was also effective in inducing cytotoxicity for NK-resistant target cells. The purpose of this study was to investigate the effects of hemin both on expression of membrane surface receptors and on production of cytokine in human peripheral blood mononuclear cells (PBMC). METHODS: Human PBMC were obtained from 16 healthy volunteers. We analyzed hemin-mediated surface phenotypes of cells using flow cytometry, and levels of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma in the culture-supernatant of cells by ELISA system. RESULTS: Hemin induced increased expression of both transferrin receptor and IL-2 receptor (CD25) on PBMC in a dose-dependent manner. When the combination of hemin (30 mumol/L) and IL-2 (100 U/mL) was added to the culture of PBMC, the population of double positive cells was increased up to 70.4%. These effects of hemin were enhanced by the addition of catalase in the culture. Treatment with hemin plus IL-2 effectively enhanced the production of TNF-alpha and IFN-gamma in PBMC. CONCLUSION: Hemin upregulated both IL-2 receptor and transferrin receptor expression, and stimulated TNF-alpha and IFN-gamma production in PBMC. IL-2 cooperated with hemin in eliciting these effects.

Adult↗
PubMed1995

A distinct mRNA encoding a soluble form of ICAM-1 molecule expressed in human tissues.

A soluble form of ICAM-1 (sICAM-1) have been observed in normal human serum (Rothlein et al., J. Immunol. 147, 3788-3793) and at elevated levels in inflammatory and tumor bearing status (Seth et al., Lancet, 338, 83-84; Giavazzi et al., Canc. Res. 52, 2628-2630; Harning et al., Canc. Res., 51, 5003-5005). However, the mechanism to produce the sICAM-1 has been still unknown. In this report we presented evidence for the presence of the mRNA specifically encoding sICAM-1, which is probably generated by alternative splice donor site selection. A 19-base deletion occurred right upstream of the transmembrane region gave rise to reading frameshift and eliminate the entire transmembrane and cytoplasmic domains, resulting in incapability of ICAM-1 molecules to reside in the membrane. A reverse transcription-polymerase chain reaction (RT-PCR) using a primer pair specific to sICAM-1 revealed a positive expression in all tissues analyzed, though the amount and the ratio to the conventional species varied slightly from tissue to tissue. Inflammatory cytokines displayed a complex pattern in the ICAM-1 mRNA expression depending on the combination of cytokines and the cultured cell lines used.

Alternative Splicing↗
PubMed1994

Proliferating cell nuclear antigen and Ki-67 in lung carcinoma. Correlation with DNA flow cytometric analysis.

BACKGROUND: To study the prognosis of patients with lung carcinomas, the efficacy of proliferating cell nuclear antigen (PCNA) in ensuring both the proliferative activity defined using Ki-67 labeling and the cell cycle data obtained using flow cytometry was determined. METHODS: The authors used immunostaining to study frozen and paraffin embedded sections of 165 surgically resected lung carcinomas [squamous cell carcinoma, n = 84; adenocarcinoma, n = 62; large cell carcinoma, n = 15; small cell carcinoma, n = 4] for the presence of PCNA and Ki-67 antibodies. Also studied were two parameter flow cytometric analysis of fluorescein isothiocyanate conjugated PCNA/propidium iodide for 165 fresh frozen tissues. Clinicopathologic data (sex, age, tumor stage, survival period, histologic type, degree of cell differentiation, and cellularity) were evaluated using the Statistical Analysis System. RESULTS: The percentages of PCNA positive cells per 1000 nuclei were 52% of squamous cell carcinoma; 49% in adenocarcinomas; 76% of large cell carcinoma; and 63% of small cell carcinoma. Positive PCNA staining was significantly correlated with stage, cellularity, and DNA index. Calculation of logistic regression coefficients indicated an association between overall survivals and tumor cellularity (P < 0.0003), percentage of cells stained with PCNA antibody (P < 0.02), DNA pattern (aneuploid versus diploid) (P < 0.009), DNA index (P < 0.009), and percentage of cells in S-phase (P < 0.04). Both cellularity (P = 0.03) and DNA (P = 0.08) retained its independent level of significance by multivariate analysis. CONCLUSIONS: In addition to clinical stage and histologic differentiation, both cellularity and DNA content may help predict the course of lung carcinomas.

Adenocarcinoma↗
PubMed1994

Enhancement of CDDP cytotoxicity by caffeine is characterized by apoptotic cell death.

The ability of caffeine, an agent that suppresses cell replication by inhibiting deoxyribonucleic acids (DNA) repair, to modulate the cytotoxicity of cis-diamminedichloroplatinum (CDDP) was investigated in murine lymphoma cell line EL-4. EL-4 cells were precultured with or without 20 micrograms/ml CDDP for 1 h and then cultured in the presence of 5 mM caffeine up to 48 h after reseeding. In CDDP-pretreated cells, suppression of cell growth and decrease in cell viability from 24 h were observed. Cell cycle arrest in G2 + M phase and a concomitant increase in both rhodamine 123 (R123) uptake and cell size (forward scatter) were observed in these cells. Treatment with caffeine alone suppressed growth rate, R123 uptake, cell size, and frequency of S phase fraction in the cell cycle. Combination of the two agents, CDDP+caffeine, strongly suppressed not only cell viability but also R123 uptake and cell size, compared with CDDP pretreatment alone. DNA histogram analysis by flow cytometry revealed that cultivation with caffeine hastened G2 + M arrest in CDDP-pretreated cells by reduction in the time of passing through S phase. DNA fragmentation was observed following incubation of CDDP-pretreated cells with caffeine for 16 h when marked accumulation in G2 + M phase was observed. The intensity of these ladder fragments increased in a time-related manner. These results demonstrate that enhancement of cytotoxic activity against CDDP-treated cells by caffeine is characterized by an acceleration of DNA degradation in G2 + M phase, namely apoptotic cell death. The fact that induction of DNA fragmentation during G2 + M phase by caffeine modulates the cytotoxicity of CDDP may give rise to a new combination regime of chemotherapy against malignant tumor cells.

Animals↗
PubMed1994

Effects of deep saturation diving on the lymphocyte subsets of healthy divers.

We examined the effect of deep saturation diving on the host defense mechanisms of five healthy volunteers using fluorescein-dye-conjugated monoclonal antibodies. Six divers engaged in a 440-m saturation diving simulation with total hyperbaric exposure of 30 days; five served as subjects. Change in the expression of surface molecules on the lymphocytes was analyzed during that period. Blood samples were serially taken on Days 4, 6, 8, 15, 22, 29, and after surfacing. The total number of lymphocytes showed no remarkable change. However, the fraction of T (CD3+) cells decreased from 68.0 +/- 3.3% to 55.8 +/- 5.8% (Day 8), and B cells increased reciprocally. In these T cells, the CD4:CD8 ratio (normally > 1.0) became less than 1.0 during compression and thereafter. In spite of the prophylactic use of anti-external otitis agents, one of the divers revealed a remarkable growth of Pseudomonas in the external auditory meatus, showing a high level of blood endotoxin (10.2 pg/ml). These results suggest that decrease in CD4+ fraction of T lymphocytes might explain in part the decreased resistance of divers to infective microorganisms in deep saturation diving.

Adult↗
PubMed1993

Granulocyte colony-stimulating factor enhances the extracellular emission of reactive oxygen from neutrophils stimulated with formylmethionylleucylphenylalanine.

Pretreatment of neutrophils with granulocyte colony-stimulating factor (G-CSF) enhanced luminol-dependent chemiluminescence emission by the stimulation of formylmethionylleucylphenylalanine (FMLP), opsonized zymosan, and zymosan. The intensity of the priming effects was in the following order: FMLP > zymosan > opsonized zymosan. However, the priming effect of G-CSF was not detected by the stimulation of phorbol myristate acetate. The reaction curve with the stimulation of FMLP showed a bimodal shape, and the elevation of the first peak by the priming effect was further prominent in comparison with the elevation of the second peak. This indicates that G-CSF mainly enhances the extracellular release of oxygen radicals in response to the stimulation with FMLP. This is the first report investigating intra- and extracellular events in chemiluminescence reaction of neutrophils primed with G-CSF.

Cytochalasin B↗
PubMed1993

Detection of specific IgE-secreting cells with an enzyme-linked immunospot assay.

BACKGROUND: An in vitro assay system for monitoring the induction of human allergen-specific IgE synthesis with an enzyme-linked immunospot assay is described. METHODS: IgE-secreting cells, responding specifically to short ragweed pollen allergens. Amb a V and Amb a VI, were directly enumerated after the coculture of high-density, resting B cells with either autologous T cells or allergen-specific T-cell clones from the peripheral blood of two ragweed-allergic individuals. Both T-cell clones were type 2-like T helper cells (TH2) as determined by reverse transcription polymerase chain reaction. The IgE-producing cells were detected on a nitrocellulose-based paper disc coated with antigen after treatment with biotinylated, anti-human IgE and avidin-peroxidase conjugate. RESULTS: We demonstrated the induction of Amb a V- or Amb a VI-specific IgE synthesis from either peripheral blood B cells or purified resting B cells. Specific IgE-secreting B cells could be detected only when T cells were present in the culture, providing that they were not separated by a membrane. The addition of interleukin-4 had an enhancing effect on the overall numbers of IgE-secreting cells and allergen-specific T cells and a synergistic effect in the coculture of B cells and an autoreactive T-cell line. CONCLUSIONS: These results suggest that cognate interaction T and B cells is required for the de novo induction of IgE responses. This in vitro system could thus provide a useful model for analysis of the molecular and cellular mechanisms that regulate the allergen-specific IgE responses in human beings.

B-Lymphocytes↗