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Biomedical subjects

K Nojima

Publications and source records attributed to K Nojima.

At least 37 records · Page 2Linked to original sources
PubMed2000

Induction by carbon-ion irradiation of the expression of vascular endothelial growth factor in lung carcinoma cells.

PURPOSE: To investigate the induction by carbon- ion irradiation of vascular endothelial growth factor (VEGF) mRNA and protein. MATERIALS AND METHODS: RERF-LC-AI lung squamous carcinoma cells were irradiated with carbon ions of either 13.3, 50 or 90keV/microm. Colony formation was used to determine cell survival. VEGF mRNA and protein of the irradiated cells were quantified by Northern blot analysis and ELISA assay, respectively. Genistein, Src tyrosine kinase inhibitor and H7, protein kinase C inhibitor, were used to inhibit VEGF mRNA expression. RESULTS: The relative biological effectiveness (RBE) of carbon ions (13.3, 50 and 90keV/microm) was 1.10, 1.97 and 2.30, respectively, in terms of D10 values. Single doses of 15 Gy with either X-rays or carbon ions significantly induced VEGF mRNA expression at 16-24h after irradiation with a maximum induction of 2.81-fold. A significant increase was also observed in VEGF protein levels, detected in culture supernatant 24h after irradiation with 50 and 90keV/microm carbon ions. Neither mRNA nor protein induction showed a dependence on LET. The induction of VEGF mRNA by carbon-ion irradiation was completely inhibited by pretreating cells with genistein and H7, indicating that Src tyrosine kinase and protein kinase C on cell surface membranes is involved in the induction. CONCLUSION: Irradiation of lung carcinoma cells with carbon ions induced VEGF mRNA expression and increased protein levels. The induction was dose-dependent. Radiation-induced DNA damage and/or its repair may not be a prerequisite for the induction of VEGF mRNA.

Carbon↗
PubMed1999

Association of plasma fibrinogen level and blood pressure with diabetic retinopathy, and renal complications associated with proliferative diabetic retinopathy, in Type 2 diabetes mellitus.

AIM: To clarify the association of several clinical parameters, including plasma fibrinogen level, with diabetic retinopathy in patients with Type 2 diabetes mellitus (DM). METHODS: A total of 294 Japanese patients with Type 2DM were studied; 53 patients with no diabetic retinopathy (NDR), 90 with background diabetic retinopathy (BDR), and 151 with proliferative diabetic retinopathy (PDR). Multiple logistic regression analysis was performed to assess variables independently associated with diabetic retinopathy in two settings: presence of retinopathy of any severity and presence of advanced retinopathy. RESULTS: The following parameters were identified as independent factors associated with the presence of diabetic retinopathy (NDR vs. BDR + PDR): type of therapy (P<0.0005), log-transformed plasma fibrinogen level (P < 0.05), mean blood pressure (P < 0.05), and duration of diabetes (P < 0.05). The independent variables associated with advanced retinopathy were type of therapy (P<0.00005), age (P<0.0005) and nephropathy (P<0.05). Body mass index, smoking and hypertensive status, HbA1c and total cholesterol levels were not independently associated. CONCLUSIONS: These data suggest that in patients with Type 2 DM, an increased blood viscosity due to high fibrinogen level as well as an elevated intravessel pressure play a role in the development of diabetic retinopathy, and that the progression to PDR is influenced or accompanied by the deterioration of renal status.

Aged↗
PubMed1999

Accelerated reoxygenation of a murine fibrosarcoma after carbon-ion radiation.

PURPOSE: Reoxygenation of a murine tumour after irradiation with carbon ions was investigated and compared to that after gamma-rays. MATERIALS AND METHODS: NFSa fibrosarcoma cells were transplanted into the right hind legs of syngeneic C3H male mice. Conditioning irradiation with either 290 MeV/u carbon ions or 137-Cs gamma-rays was delivered to the tumours at 8 mm diameter. At given times after irradiation the leg tumours, either clamped or not, received test doses of photons. Differences in tumour growth delay between the clamped and non-clamped tumours were interpreted in terms of reoxygenation. A lung-colony assay was used to obtain cell-survival curves. RESULTS: The oxygen enhancement ratio in the NFSa tumour for 74 keV microm(-1) carbon ions was 1.6 while that for gamma-rays was 3.4. The NFSa tumours reoxygenated 4 days after 30 Gy of gamma-ray irradiation, but reoxygenated as early as 1 day after 16 Gy of carbon ions. Reoxygenation after gamma-rays shortened to 1 day when the tumours were initially clamped for the conditioning irradiation. CONCLUSIONS: The fraction of surviving oxic cells in the NFSa tumours is larger after irradiation with carbon ions than with gamma-rays, resulting in accelerated reoxygenation.

Animals↗
PubMed1999

Calorie restriction and spontaneous hepatic tumors in C3H/He mice.

Caloric restriction started at the young adult (YA) stage and the full adult (FA) stage in mice was compared, specifically focussing on whether there would be a delay in the onset time of spontaneous hepatoma or a reduction in its frequency. Caloric restriction lengthened the life spans of both groups, the YA, and FA. Both groups showed striking reductions of spontaneous hepatomas, from 70.9 +/- 3.5% for non-restricted controls down to 35.7 +/- 5.7 and 30.4 +/- 4.0%, for mice restricted from young adult, and from full adult stages, respectively; further, the numbers of tumor-free mice in the restricted groups increased by 45.7% and 38.5%, respectively, from 11.5%, in the non-restricted control. The cumulative incidences of hepatoma in the caloric restricted groups showed a delayed and lower incidence compared with those of the non-restricted group; a parallel delay might result from a weakened activity in tumor-promotion, whereas a lower frequency, might reflect a possible reduction of target cells for hepatomata development. Both effects can be assumed to have resulted from caloric restriction. When cumulative incidences of small hepatomas were compared between the two restricted groups, restriction started at the young adult stage is assumed to have caused fewer initiation stresses, as well as to have delayed promotion, as clearly evidenced by a flatter curve of incidence with a lower total incidence. Thus, the time at which caloric restriction is started plays a critical role in its subsequent effects.

Aging↗
PubMed1998

Evidence for mRNA expression of vascular endothelial growth factor by X-ray irradiation in a lung squamous carcinoma cell line.

Vascular endothelial growth factor (VEGF) is a multipotent cytokine which plays an important role in various angiogenic conditions as well as in some tumor behaviors. Here we examined the induction of VEGF mRNA by X-ray irradiation in a lung squamous cell carcinoma cell line (RERF-LC-AI). Irradiating the cells with 15 Gy X-rays significantly increased the mRNA expression up to 2.5-fold of control at a post-irradiation time of 16-24 h. The induction of VEGF mRNA by X-ray irradiation was completely blocked by treating cells with either genistein (Src tyrosine kinase inhibitor) or H7 (protein kinase C inhibitor). This suggests that the mechanism of induction might be concerned with the pathway which triggers Src tyrosine kinase of the cell surface and the protein kinase C pathway.

Antineoplastic Agents↗
PubMed1998

Association of distal chromosome 2q with IDDM in Japanese subjects.

An insulin-dependent diabetes mellitus (IDDM)-susceptibility gene (IDDM13) has recently been mapped to a region of distal chromosome 2q, which is syntenic to the region of mouse chromosome 1 containing a murine susceptibility gene for IDDM, Idd5. To determine the contribution of this region to IDDM disease susceptibility further and to narrow the region for positional cloning of susceptibility genes, we have studied the association of distal chromosome 2q with IDDM in the genetically distinct Japanese population. A 137 mobility unit (mu) allele at D2S137 locus was significantly associated with IDDM (odds ratio 1.92, p = 0.0016). Other markers, D2S301 and D2S143, located in the same region were not associated with IDDM, indicating that IDDM13 is in linkage disequilibrium with D2S137, but not with D2S301 or D2S143. The association of D2S137 with IDDM was observed in patients lacking one of two high risk HLA alleles, DQBI*0303 and DQBI*0401, but not in patients with either of these alleles. The frequency of high risk HLA alleles was significantly lower in patients with the susceptible allele at D2S137, suggesting that IDDMI3 contributes to IDDM susceptibility in subjects without high risk genotypes at IDDM1. Demonstration of allelic association of D2S137 with IDDM localizes IDDM13 in the close vicinity (<2 centiMorgans) of D2S137, greatly facilitating fine structure mapping and positional cloning of IDDM13.

Adolescent↗
PubMed1998

Hepatocyte nuclear factor-1alpha gene and non-insulin-dependent diabetes mellitus in the Japanese population.

Recently, hepatocyte nuclear factor-1alpha(HNF-1alpha, which is encoded by the TCF1 gene) mutations were reported in a subset of patients with maturity onset diabetes of the young (MODY3). We studied the contribution of TCF1 to genetic susceptibility to common non-insulin-dependent diabetes mellitus (type 2) in Japanese subjects by investigating allelic association with type 2 diabetes use of three markers. We also studied the frequency of the G191D mutation, the only mutation of TCF1 reported so far in late-onset type 2 diabetes. A total of 356 subjects were studied. There were no significant differences in allele frequency of the three markers between patients with type 2 diabetes and control subjects. A G191D mutation was not found in the subjects studied, giving a frequency of less than 0.4% in common type 2 diabetes. The lack of association of type 2 diabetes with three markers in and near TCF1 suggests that mutations in TCF1 derived from a limited number of founders are not a major cause of common type 2 diabetes even in the genetically homogeneous Japanese population. The data also indicate that the G191D mutation in TCF1 plays little, if any, role in susceptibility to common type 2 diabetes in the Japanese.

Adult↗
PubMed1998

Mouse skin reactions following fractionated irradiation with carbon ions.

PURPOSE: Skin reactions in the mouse leg following various daily doses given with 290 MeV/u carbon ions were investigated. MATERIALS AND METHODS: Seven different LET (linear energy transfer) values ranging from 14 to 100keV/microm were selected. The fractionation schedules were 1-, 2-, 4- and 8-daily fractions. The isoeffect doses to produce moist desquamation on the dose-response curves were calculated with 95% confidence limits. RESULTS: The isoeffect doses for carbon ions of 14 and 20 keV/microm increased with an increase in the number of fractions up to 4 fractions, but became constant when the number of fractions further increased to 8 fractions. This leveling off in isoeffect dose was more prominent for 40 keV/microm. Recovered dose per fraction was largest for 2 fractions of the 14keV/microm carbon beam. The isoeffect doses for 50, 60, 80 and 100keV/microm consistently increased with an increase in the number of fractions and did not show saturation up to 8 fractions. RBE (relative biological effectiveness) increased linearly with LET for all fractionation schedules. CONCLUSIONS: These results suggest that daily fractionation with carbon ions could spare radiation damage in patients, and that changes the fractionation schedule affect clinical outcome.

Animals↗
PubMed1998

Asp905Tyr polymorphism of the gene for the skeletal muscle-specific glycogen-targeting subunit of protein phosphatase 1 in NIDDM.

OBJECTIVE: To clarify the contribution of the Asp905Tyr polymorphism of the muscle-specific glycogen-targeting subunit of protein phosphatase 1 (PP1G) to insulin resistance and related diseases. RESEARCH DESIGN AND METHODS: We investigated the Asp905Tyr polymorphism of the PPP1R3 gene, which encodes the muscle-specific glycogen-targeting subunit of PP1G, in 259 Japanese patients with NIDDM and 194 healthy control subjects. RESULTS: No significant difference was found in the genotype distribution between NIDDM patients (N = 259; Asp/Asp = 0.10, Asp/Tyr = 0.44, Tyr/Try = 0.46) and healthy control subjects (n = 194; Asp/Asp = 0.13, Asp/Tyr = 0.37, Tyr/Tyr = 0.50) or between patient groups subdivided by the mode of treatment: NIDDM patients with insulin therapy (Asp/Asp = 0.14, Asp/Tyr = 0.46, Tyr/Tyr = 0.40) and those without insulin therapy (Asp/Asp = 0.07, Asp/Tyr = 0.43, Tyr/Tyr = 0.50). However, NIDDM patients with the Tyr allele, which was previously reported to be associated with insulin resistance, tended to have lower BMIs than those without this allele (Asp/Asp: 24.5 +/- 1.1 kg/m2, Asp/Tyr: 22.6 +/- 0.4 kg/m2, Tyr/Tyr: 22.8 + 0.3 kg/m2, P = 0.06 by analysis of variance). CONCLUSIONS: These data suggest that the Asp905Tyr polymorphism of the PPP1R3 gene is not associated with NIDDM or high BMI, both of which are known to be insulin-resistant states, in the Japanese population.

Adult↗
PubMed1998

Relationships between mandibular symphysis morphology and lower incisor inclination in skeletal class III malocclusion requiring orthognathic surgery.

The purpose of this study is to clarify symphysis morphological characteristics in skeletal class III malocclusion requiring orthognathic surgery and their relationships with symphysis morphology and inclination of the long axis of the lower incisor. The materials were pretreatment lateral cephalometric radiographs from 50 subjects diagnosed as requiring orthognathic surgery. Controls were 30 adults with normal occlusion and well-balanced faces. Detailed cephalometric measurements on the mandibular symphysis (angular, linear and proportional measurements) were recorded and analyzed statistically. In the surgical group, the long axis of the lower incisor demonstrated a significant lingual inclination in relation to the mandibular plane and symphysis. Moreover, because the symphysis demonstrated lingual inclination everywhere except in the basal bone region in relation to the mandibular plane, the curvature between the alveolar and the basal bone region was significantly smaller than that of normal occlusion group. The symphysis labial external surface in the alveolar and basal bone regions demonstrated lingual inclination in relation to the mandibular plane, however, there was no difference in curvature. Small mean values were obtained for Pt.B width, Pog width, and Sym height. Significant differences were observed only in Pt.B width. In both the surgical and normal occlusion groups, a significant correlation was observed between the inclination of the long axis of the lower incisors and symphysis inclination. In the basal bone region, however, there was no significant correlation.

Adult↗
PubMed1997

Calorie restriction reduces the incidence of myeloid leukemia induced by a single whole-body radiation in C3H/He mice.

Dietary restriction, especially caloric restriction, is a major modifier in experimental carcinogenesis and is known to decrease significantly the incidence of neoplasms. Gross and Dreyfuss [Gross, L. & Dreyfuss, Y. (1984) Proc. Natl. Acad. Sci. USA 81, 7596-7598; Gross, L. & Dreyfuss, Y. (1986) Proc. Natl. Acad. Sci. USA 83, 7928-7931] reported that a 36% restriction in caloric intake dramatically decreased the radiation-induced solid tumors and/or leukemias. Their protocol predominantly produced lymphatic neoplasms. It is of interest to observe the effect of caloric restriction on radiation-induced myeloid leukemia, because the disease was observed to have been increased in the survivors of the atomic bombs in Hiroshima and Nagasaki. The spontaneous incidence of myeloid leukemia in C3H/He male mice is 1%, and the incidence increased to 23.3% when 3 Gy of whole-body x-ray irradiation was given. However, the incidence of myeloid leukemia was found to be significantly decreased by caloric restriction; it was reduced to 7.9% and 10.7% when restriction was started before (6 weeks old) and after (10 weeks old) irradiation, respectively. In addition, the onset of the myeloid leukemia in both restricted groups was prolonged to a greater extent as compared with the control diet group. Caloric restriction demonstrated a significant prolongation of the life span in the groups on a restricted diet after having been exposed to irradiation, either before or after dietary restriction, in comparison with mice that were only irradiated.

Aging↗
PubMed1994

Microheterogeneity in glycosylphosphatidylinositol anchor structures of bovine liver 5'-nucleotidase.

In our study, 5'-nucleotidase was released from bovine liver by the treatment with Bacillus thuringiensis phosphatidylinositol-specific phospholipase C and purified to a homogeneous state by concanavalin A-Sepharose and (diethylaminoethyl)-Toyopearl column chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Purified 5'-nucleotidase were then cleaved by cyanogen bromide (CNBr), and then inositol phosphoglycan-containing C-terminal peptides (IPG peptides) were separated by C18 reverse-phase liquid chromatography and analyzed by peptide sequencer, amino acid analyzer, gas chromatography (GC), and GC-mass spectrometry (MS). Ser523 of the amino acid sequence deduced from 5'-nucleotidase cDNA [Suzuki et al. (1993) J. Biochem. (Tokyo) 113, 607-613] is revealed to be the C-terminal amino acid to which a glycosylphosphatidylinositol is anchored. Separated peaks of CNBr-cleaved IPG peptides were then analyzed by electron spray ionization (ESI)-MS. Eight different molecular weight (MW) species of CNBr-cleaved IPG peptides were detected. Three fractions of CNBr-cleaved IPG peptides were separately treated by trypsin, and trypsinized IPG peptides were purified by C18 reverse-phase liquid chromatography. Finally, five different MW species of trypsinized IPG peptides (1629.4, 1752.7, 1791.8, 1832.8, and 1994.5) were detected by ESI-MS. Together with sequential exoglycosidase treatment and quantitative analysis of sugar moieties by GC and GC-MS, microheterogeneity in the structures of these five glycosylphosphatidylinositol (GPI) anchor species was determined. The common core structure was ethanolamine phosphate-mannose-mannose-mannose(-ethanolamine phosphate)-glucosamine-myoinositol phosphate. Variations observed in additional mannose, N-acetylhexosamine, and ethanolamine phosphate moieties form this heterogeneity.(ABSTRACT TRUNCATED AT 250 WORDS)

5'-Nucleotidase↗
PubMed1994

Studies on photochemical reactions of air pollutants. XII. Photochemical epoxidation of aldrin with suspended particulates in air.

Suspended particulates collected in Yokohama, Japan over various 24-h periods were found to cause the photochemical epoxidation of aldrin to dieldrin in good yield. trans-Stilbene did not undergo the epoxidation. Upon irradiation of aldrin together with the suspended particulates in quasi-air consisting of 18O2. 100% incorporation of 18O into dieldrin was obtained. Thus, the oxygen atom in dieldrin originated not from the particulates, but from oxygen in air.

Air Pollutants↗
PubMed1994

Formation of chloroamines from styrene under conditions mimicking those of water "chlorination" treatment.

The reaction of styrene with sodium hypochlorite in the presence of ammonium ion in 0.3 M phosphate buffer (pH 6.0) at room temperature afforded N-chloro-1-phenyl-2-chloroethylamine and N,N-dichloro-1-phenyl-2-chloroethylamine. 1-Phenyl-2-chloroethylamine hydrochloride, obtained as the reduction product of the two N-chloroamines, was shown to be mutagenic in the Salmonella typhimurium test.

Animals↗
PubMed1993

Responses of subfornical organ neurons projecting to the hypothalamic paraventricular nucleus to hemorrhage.

The activity of subfornical organ (SFO) neurons that were antidromically identified by electrical stimulation of the rat hypothalamic paraventricular nucleus (PVN) was tested for a response to microiontophoretic application of angiotensin II (ANG II) or hemorrhage (10 ml/kg b.w.t.). Microiontophoretically (MIPh) applied ANG II caused an increased excitability in 24 out of 28 neurons tested and the excitation was blocked by MIPh-applied saralasin (Sar), a specific ANG II antagonist. Of these neurons that responded to ANG II, 14 displayed an increase in neuronal firing in response to hemorrhage, while 10 were unresponsive. The excitatory response to hemorrhage in 5 out of 14 neurons tested was prevented by MIPh-applied Sar, whereas the response of the remaining neurons was not affected. These results show that part of SFO neurons projecting to the PVN may receive neural inputs from the peripheral baroreceptors, and suggest that the inputs may be partially attributable to the involvement of central angiotensinergic circuits.

Action Potentials↗
PubMed1993

Direct determination of opium alkaloid-bovine serum albumin conjugate by matrix-assisted laser desorption/ionization mass spectrometry.

Opium alkaloids (thebaine, codeine and morphine) have been conjugated with bovine serum albumin (BSA) to give individual antigen conjugates which are analyzed by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. It became clear that 9 molecules of thebaine were contained in a thebaine-BSA conjugate. Codeine and morphine contents in individual conjugates were determined to be 12 and 6 molecules, respectively.

Codeine↗