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Biomedical subjects

K Higashi

Publications and source records attributed to K Higashi.

At least 55 records · Page 3Linked to original sources
PubMed2000

FDG PET measurement of the proliferative potential of non-small cell lung cancer.

UNLABELLED: The goals of this study were to correlate FDG uptake with cell proliferation and cellular density in non-small cell lung cancer. METHODS: Thirty-one patients with 32 non-small cell lung cancers were examined with FDG PET. For semiquantitative analysis, standardized uptake values (SUVs) were calculated. All patients underwent thoracotomy within 4 wk after the FDG PET study. Cell proliferation was immunohistochemically assessed as the relative number of cells expressing the proliferating cell nuclear antigen ([PCNA] labeling index). Cellular density was also evaluated using light microscopy. RESULTS: SUVs correlated significantly with PCNA labeling index (r = 0.740; P < 0.0001) but only weakly with cellular density (r = 0.392; P = 0.0266). High FDG uptake correlated with high PCNA expression. The PCNA labeling index and SUVs were significantly lower in bronchioloalveolar carcinomas (n = 8) (12.3 +/- 9.45% and 1.45 +/- 0.76, respectively) than in nonbronchioloalveolar carcinomas (n = 19) (33.5 +/- 21.8%, P = 0.015, and 3.75 +/- 1.93, P = 0.003, respectively). However, no significant differences in cellular density were seen between bronchioloalveolar carcinomas and nonbronchioloalveolar carcinomas. CONCLUSION: FDG uptake is related to cell proliferation rather than to the cellular density of non-small cell lung cancer.

Carcinoma, Non-Small-Cell Lung↗
PubMed2000

[Multicentric Castleman's disease found by a renal sinus lesion: a case report].

A 79-year-old man complained of anorexia and weight loss. Computed tomography and magnetic resonance imaging showed a solitary mass in the left renal sinus. Left nephrectomy was carried out under a clinical diagnosis of renal pelvic tumor. The pathological diagnosis was plasma cell type of Castleman's disease. The patient suffered from lymph node swelling in the right neck at age 75 and the lymph node was resected. The pathological diagnosis was lymphadenitis but it proved to be plasma cell type of Castleman's disease. The patient also had had a lymphadenectomy in the supraclavicular fossa and in the supraorbital area at age 76. Both had been diagnosed as lymphadenitis pathologically but they proved to be plasma cell type of Castleman's disease. The final diagnosis was multicentric Castleman's disease. We reviewed multicentric Castleman's disease.

Aged↗
PubMed2000

[Assessment of functional severity on in vivo hepatic 31P-MRS in diffuse hepatic disease: comparative studies with 99mTc-GSA].

The purpose of this study was to compare the assessment of functional severity on in-vivo hepatic 31P-MRS in diffuse hepatic disease with functional severity assessed with 99mTc galactosyl serum albumin (99mTc-GSA). 31P-MRS was performed in 10 healthy control subjects and 16 patients with diffuse hepatic disease. Data were expressed as peak area ratios: PME/beta-ATP, PDE/beta-ATP, PME/PDE, Pi/beta-ATP, and PME/Pi. The functional severity of hepatic damage was evaluated visually and quantitatively (HH15, LHL15) by 99mTc-GSA in the group of patients with diffuse hepatic disease. Visual evaluation was classified into four grades based on anterior images of cardiac blood-pool and liver. We studied the correlation of spectral metabolic ratios and functional severity by 99mTc-GSA. We found statistically significant differences (ANOVA) among the classifications of Grade I, Grade II, and Grade III with both PME/beta-ATP and PME/PDE. A statistically significant direct correlation was found between HH15 and both PME/beta-ATP and PME/PDE. A significant inverse correlation was also seen between LHL15 and both PME/beta-ATP and PME/PDE. The studies comparing 31P-MRS with functional severity assessed by 99mTc-GSA showed that PME/beta-ATP and PME/PDE were useful for the assessment of functional severity in patients with diffuse hepatic disease.

Adult↗
PubMed2000

[Genetically confirmed spinal muscular atrophy type III with epilepsy, cerebral hypoperfusion, and parahippocampal gyrus atrophy].

We report a 37-year-old female with spinal muscular atrophy (SMA) type III and central nervous system (CNS) involvement. She showed gait disturbance at the age of 12 years, and difficulty of squatting at the age of 19. On examination at the age of 22, she had proximal muscle weakness and atrophy, fasciculation, normal sensory system and elevated creatine kinase in the serum. She was diagnosed as having SMA type III based on clinical, electrophysiological, and muscle biopsy findings. She suffered from subacute necrotizing lymphadenitis at the age of 23 and from epilepsy at the age of 33. Magnetic resonance imaging showed atrophy of parahippocampal gyrus with right side predominance. Single photon emission computed tomography (SPECT) using I123-IMP showed decreased accumulations of I123-IMP in the temporal lobes with left side predominance. Electroencephalogram showed theta wave without epileptic burst. SMA gene analysis revealed deletion of exon 7 and 8 in survival motor neuron (SMN) gene. A few patients with SMA and CNS involvement have been reported without genetic diagnosis. This is the first report of genetically confirmed SMA patient with CNS involvement. SMN gene is distributed not only in spinal cord but also in brain. The CNS involvement detected in this patient may be related to the loss of SMN gene function, although coincidental association of SMA and the CNS abnormalities is still considered in this atypical case.

Adult↗
PubMed2000

Correlation of Glut-1 glucose transporter expression with.

Positron emission tomography (PET) with [18F]2-fluoro-2-deoxy-D-glucose (FDG) may show negative results for bronchioloalveolar lung carcinoma. We investigated the correlation of Glut-1 glucose transporter expression with [18F]FDG uptake in non-small cell lung cancer. Thirty-two patients with 34 non-small cell lung cancers (7 bronchioloalveolar carcinomas, 23 non-bronchioloalveolar adenocarcinomas, 3 squamous cell carcinomas, and 1 adenosquamous cell carcinoma) were studied. Final diagnoses were established by histology (via thoracotomy) in all patients. [18F]FDG PET was performed 40 min after i.v. injection of 185 MBq [18F]FDG. For semi-quantitative analysis of [18F]FDG uptake, standardized uptake values (SUVs) were calculated. Glut-1 expression was studied in terms of the immunohistochemistry of paraffin sections using anti-Glut-1 antibody to determine the intensity (0-3) of Glut-1 immunoreactivity and percentage of the Glut-1-positive area. Of seven bronchioloalveolar carcinomas, six (85.7%) were negative for the expression of Glut-1, while only one (4.3%) of 23 non-bronchioloalveolar adenocarcinomas was negative (P < 0.0001). The percentages of Glut-1-positive area, as well as the SUVs, were significantly lower in bronchioloalveolar carcinomas (n = 7) (2.86% +/- 7.56% and 1.25 +/- 0.75, respectively) than in non-bronchioloalveolar adenocarcinomas (n = 23) (54.83% +/- 25.64%, P < 0.0001, and 3.94 +/- 1.93, P = 0.001, respectively). The degree of cell differentiation correlated with the percentage of Glut-1-positive area and SUVs in adenocarcinoma of the lung. Correlations between SUVs and the intensity of Glut-1 immunoreactivity were also significant (intensities 0 and 1, n = 11, SUV 1.47 +/- 0.63; intensities 2 and 3, n=23, SUV 4.78 +/- 2.13; P < 0.0001). The percentage of Glut-1-positive area correlated significantly with SUVs (n = 34, r = 0.658, P < 0.01). Overexpression of Glut-1 correlated with high [18F]FDG uptake. These findings suggest that Glut-1 expression is related to [18F]FDG uptake in non-small cell lung cancer. Glut-1 expression, as well as [18F]FDG uptake, correlated with the degree of cell differentiation in adenocarcinomas, and both Glut-1 expression and [18F]FDG uptake were significantly lower in bronchioloalveolar carcinomas than in non-bronchioloalveolar carcinomas.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1999

Inhibitory effect of tea flavonoids on the ability of cells to oxidize low density lipoprotein.

Dietary flavonoid intake has been reported to be inversely related to mortality from coronary heart disease, and the anti-atherosclerotic effect of flavonoids is considered to be due probably to their antioxidant properties. Oxidation of low density lipoprotein (LDL) has been reported to be induced by the constituent cells of the arterial wall. Accordingly, we examined the effect of pretreatment with tea flavonoids, such as theaflavin digallate, on the ability of cells to oxidize LDL. Theaflavin digallate pretreatment of macrophages or endothelial cells reduced cell-mediated LDL oxidation in a concentration- (0-400 microM) and time- (0-4 hr) dependent manner. This inhibitory effect of flavonoids on cell-mediated LDL oxidation was in the order of theaflavin digallate > theaflavin > or = epigallocatechin gallate > epigallocatechin > gallic acid. Further, we investigated the mechanisms by which flavonoids inhibited cell-mediated LDL oxidation using macrophages and theaflavin digallate. Theaflavin digallate pretreatment decreased superoxide production of macrophages and chelated iron ions significantly. These results suggest that tea flavonoids attenuate the ability of the cell to oxidize LDL, probably by reducing superoxide production in cells and chelating iron ions.

Animals↗
PubMed1999

Studies on the multidrug resistance gene expression in the livers of rats associated with different susceptibility of hepatocarcinogenesis.

Inbred carcinogen-resistant DRH rat strain developed from the closed colony Donryu rats on the basis of selective markers such as poor induction of gamma-glutamyltranspeptidase and marked reduced incidences of liver tumors during 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) administration, which took more than 10 years. Previously, we observed that the Donryu rat liver was quite sensitive to both DNA-damaging and cytotoxic effects of 3'-Me-DAB, while the DRH rat liver showed tolerance to 3'-Me-DAB under the same conditions. In the present study, we examined mRNA levels related to the cytotoxic drug resistance mechanism in the livers of DRH and Donryu rats using RT-PCR. Contrary to our expectation, we observed rather similar levels of mRNAs between the two rat strains under the following conditions: i) mdr1 mRNA induction after 3'-Me-DAB administration. ii) MLP-2 mRNA reduction by 3'-Me-DAB administration, iii) MLP-2 mRNA induction after cholestasis and iv) constitutive levels of cMOAT gene expression. On the other hand, the levels of p53 mRNA and p53 protein in the Donryu rat liver were higher than those in DRH rat liver during 3'-Me-DAB administration, suggesting that the former were more sensitive to 3'-Me-DAB than DRH rat under these conditions. In conclusion, we failed to demonstrate the difference in the cytotoxic drug resistance mechanism between DRH and Donryu rats at least under the conditions examined in this study.

Animals↗
PubMed1999

Endothelium-dependent flow-mediated vasodilation in the postprandial state in type 2 diabetes mellitus.

This study examined the effects of fat- plus sucrose-rich meals on endothelium-dependent flow-mediated vasodilation in diabetic patients. Flow-mediated vasodilation in the postprandial state decreased significantly, and the decrease correlated inversely with the magnitude of postprandial hyperglycemia, suggesting that endothelial function in diabetic patients becomes impaired postprandially.

Adult↗
PubMed1999

The occurrence of polymorphism of mannose 6-phosphate/insulin-like growth factor 2 receptor gene in laboratory and wild rats.

Carcinogen-resistant inbred DRH rat strain was established from closed colony Donryu rats in the presence of 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). Despite using 3'-Me-DAB during the stage of selection, the DRH rats developed normally and did not show any spontaneous tumor at over 1 year of age. In the present study, we examined the polymorphism in mannose 6-phosphate/insulin-like growth factor 2 receptor (M6p/Igf2r) gene and found that the DRH rat showed CCC (Proline)-type polymorphism in exon 48 and the Donryu rat had GCC (Alanine) sequence. Since the DRH rat was developed from the Donryu rat, we examined whether this polymorphism in exon 48 of M6p/Igf2r gene was due to mutation that occurred at the stage of selection in the presence of 3'-Me-DAB, using several other laboratory and wild rats. We detected the presence of polymorphism at the same site of the M6p/Igf2r gene among these rats. It is likely that the polymorphism in exon 48 of the M6p/Igf2r gene is present broadly in rats since ancient times and not due to the mutation during the course of selection unless this site is a hot spot for chemical carcinogens.

Alanine↗
PubMed1999

Attenuation by glutathione of hsp72 gene expression induced by cadmium in cisplatin-resistant human ovarian cancer cells.

Intracellular GSH has some effects on protecting cells against cadmium and is involved in the development of resistance to cisplatin (CDDP). To determine the effects of intracellular GSH on expression of the heat shock genes (hsp) induced by cadmium in CDDP-resistant cancer cells, we used two human ovarian cancer cell lines: CDDP-sensitive A2780 and its CDDP-resistant derivative A2780CP. The concentration of intracellular GSH was significantly higher in A2780CP than in A2780 cells. A2780CP cells were more resistant to CdCl2 exposure than A2780 cells. The treatment of the two cell lines with 50 microM CdCl2 induced hsp72, hsp32 and metallothionein (MT-II) mRNAs, and the induction level of each mRNA did not differ in the two cell lines. However, the treatment with 20 microM CdCl2 induced the hsp72 and hsp32 mRNAs in A2780CP cells less than in A2780 cells, while the MT-II mRNA was induced to similar levels in the two cell lines. The DNA binding activity of the heat shock factor (HSF) in response to 20 microM CdCl2 exposure was also significantly lower in A2780CP cells. The treatment of A2780 cells with N-acetyl-L-cysteine increased the intracellular GSH concentration, and profoundly suppressed hsp72 mRNA induction and HSF activation by CdCl2. These results indicate that the regulation of the hsp72 gene expression induced by CdCl2 was more suppressive in A2780CP than in A2780 cells. Our findings suggest that increased GSH biosynthesis in CDDP-resistant cancer cells may be involved in the attenuation of HSF activation by CdCl2.

Acetylcysteine↗
PubMed1999

Injection of antisense oligos to nNOS into nucleus tractus solitarii increases blood pressure.

We investigated the cardiovascular effects of bilateral microinjection of antisense oligodeoxynucleotides (oligos) into the nucleus tractus solitarii (NTS) to neuronal nitric oxide synthase (nNOS) to suppress the expression of nNOS molecular biologically. In urethane-anesthetized, paralyzed Wistar-Kyoto rats, bilateral microinjection of nNOS antisense oligos (20 pmol in a 50nl volume) into the NTS produced a significant increase in mean arterial blood pressure at 30-60min after injection, compared with rats injected with nNOS sense or scrambled oligos. Immunohistochemical study demonstrated that nNOS immunoreactivity in the rat NTS was suppressed by nNOS antisense oligos. These results indicate that suppression of the nNOS gene using antisense in the NTS increases blood pressure.

Animals↗
PubMed1999

Genetic properties for the suppression of development of putative preneoplastic glutathione S-transferase placental form-positive foci in the liver of carcinogen-resistant DRH strain rats.

The post-initiation stage of hepatocarcinogenesis was investigated in carcinogen-resistant inbred DRH rats and the parental strain, carcinogen-sensitive Donryu rats. Male rats at 5 weeks of age from both strains were treated with N-nitrosodiethylamine (200 mg/kg i.p.) followed by feeding with a diet containing 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) from 2 weeks later and were then subjected to partial hepatectomy at 1 week later. At 8 weeks after the start of treatment, the mean area occupied by glutathione S-transferase placental form (GST-P)-positive lesions was about 30% in Donryu rats but less than 4% in DRH rats despite the presence of comparable numbers of foci in the livers of both strains. These observations suggested that clonal expansion of GST-P-positive foci in DRH rat liver was significantly suppressed under these conditions. Furthermore, this genetic property was dominantly inherited in the F1 rats by crosses of DRH and carcinogen-sensitive inbred F344 rats; that is, the induction of GST-P mRNA in the livers of F344 x DRH F1 rats was dominantly suppressed after administration of 3'-Me-DAB for 8 weeks as compared with parental F344 rats under the same conditions. We compared the intrinsic properties related to growth potential of liver cells between adult DRH and Donryu rats. DRH rat liver showed retarded and/or reduced DNA synthesis after partial hepatectomy or a single i.v. injection of lead nitrate and lower activity of telomerase induced by 3'-Me-DAB administration for 1 week, as compared with the Donryu rat liver. The intrinsic properties observed in this study may be related, at least in part, to the low incidence of liver tumors induced by hepatocarcinogens in DRH rats.

Animals↗
PubMed1999

[The aged and stress response].

It is generally considered that aged people have less potential for adapting to environmental changes. In this review, an attempt is made to see whether experimental results support the above working hypothesis and how lower adaptation potential is involved in the aging process. Studies with human beings, rats and human diploid fibroblasts showed a gradual reduction of heat shock proteins (HSPs) and their mRNA and DNA binding activity of heat shock factor (HSF) during aging. Furthermore, the activation of HSF from monomer to trimer was reduced irrespective of the presence of comparative amounts of HSF in the aged cells. Cells from elder organisms or late-staged fibroblasts in culture may have altered the redox state and/or abnormal proteins. A clear interpretation of how these changes influence the activation of HSF in aged cells is impossible at present. Stress kinase JNK (Jun NH2kinase) promotes the signal transduction pathway of apoptosis. In contrast, overexpression of HSP suppresses apoptosis mediated by JNK, resulting in the increase of carcinogenic risk of aged cells. HSP as chaperone maintains unfolded intermediate protein to protect aggregation or to form native conformation of nascent protein. On the contrary, this intermediate (rich in beta-sheet) with aid from such as apoprotein E can make insoluble amyloid fibers in the brain of aged people. In certain cases, overexpression of HSP is rather toxic to the cells.

Adaptation, Physiological↗
PubMed1999

Higher induction of heat shock protein 72 by heat stress in cisplatin-resistant than in cisplatin-sensitive cancer cells.

Induction of the heat shock proteins (HSPs) is involved in the increased resistance to cancer therapies such as chemotherapy and hyperthermia. We used two human ovarian cancer cell lines; a cisplatin (CDDP)-sensitive line A2780 and its CDDP-resistant derivative, A2780CP. The concentration of intracellular glutathione (GSH) is higher (2.7-fold increase) in A2780CP cells than in A2780 cells. A mild treatment with a heat stress (42 degrees C for 30 min) induced synthesis of both the heat shock protein 72 (Hsp72) mRNA and the HSP72 protein in A2780CP cells, but not in A2780 cells. In contrast, a severe heat stress (45 degrees C for 30 min) increased synthesis of the HSP72 protein in the two cell lines. The induced level of the HSP72 protein by the severe treatment was higher in A2780CP than in A2780 cells. The gel mobility shift assay showed that DNA binding activities of the heat shock factor (HSF) in the two cell lines were induced similarly and significantly by the mild heat stress. Immunocytochemistry using an anti HSF1 antibody also indicated that mild heat stress activated the HSF1 translocation from the cytosol to the nucleus similarly in the both cell lines. Pretreatment of CDDP-sensitive A2780 cells with N-acetyl-L-cysteine, a precursor of GSH, effectively enhanced induction of the Hsp72 mRNA by the mild heat stress. The present findings demonstrate that induction of the Hsp72 mRNA by the mild heat stress was more extensive in CDDP-resistant A2780CP cells. It is likely that the higher GSH concentration in A2780CP cells plays an important role in promoting Hsp72 gene expression induced by the mild heat stress probably through processes downstream of activation of HSF-DNA binding.

Cisplatin↗
PubMed1999

Autophosphorylation of p110delta phosphoinositide 3-kinase: a new paradigm for the regulation of lipid kinases in vitro and in vivo.

Phosphoinositide 3-kinases (PI3Ks) are lipid kinases which also possess an in vitro protein kinase activity towards themselves or their adaptor proteins. The physiological relevance of these phosphorylations is unclear at present. Here, the protein kinase activity of the tyrosine kinase-linked PI3K, p110delta, is characterized and its functional impact assessed. In vitro autophosphorylation of p110delta completely down-regulates its lipid kinase activity. The single site of autophosphorylation was mapped to Ser1039 at the C-terminus of p110delta. Antisera specific for phospho-Ser1039 revealed a very low level of phosphorylation of this residue in cell lines. However, p110delta that is recruited to activated receptors (such as CD28 in T cells) shows a time-dependent increase in Ser1039 phosphorylation and a concomitant decrease in associated lipid kinase activity. Treatment of cells with okadaic acid, an inhibitor of Ser/Thr phosphatases, also dramatically increases the level of Ser1039-phosphorylated p110delta. LY294002 and wortmannin blocked these in vivo increases in Ser1039 phosphorylation, consistent with the notion that PI3Ks, and possibly p110delta itself, are involved in the in vivo phosphorylation of p110delta. In summary, we show that PI3Ks are subject to regulatory phosphorylations in vivo similar to those identified under in vitro conditions, identifying a new level of control of these signalling molecules.

Amino Acid Sequence↗
PubMed1999

Central nervous system symptoms in patients with Behçet disease receiving cyclosporine therapy.

OBJECTIVE: To investigate the association between the development of central nervous system (CNS) symptoms in patients with Behçet disease and medical therapy. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 317 patients with Behçet disease with ocular complications who visited Hokkaido University Hospital, Sapporo, Japan, between 1978 and 1994. MAIN OUTCOME MEASURES: The incidence of CNS symptoms in different medical therapies. RESULTS: Twenty-one (6.6%) of the 317 patients developed CNS symptoms, namely neuro-Behçet disease. Of the 21 patients, 12 were undergoing cyclosporine therapy. Of the 47 patients who underwent cyclosporine therapy, 12 (25.5%) developed CNS symptoms, whereas only 9 (3.3%) of 270 patients who did not undergo cyclosporine therapy developed CNS symptoms. CONCLUSIONS: Cyclosporine in the treatment of Behçet disease appears to cause neurotoxicity or to accelerate the development of CNS symptoms. Thus, neurologic complications appear to represent a major side effect of cyclosporine in the treatment of patients with Behçet disease.

Adult↗
PubMed1999

Distribution of cadmium and metallothionein in CdCl2-exposed rat kidney: relationship with apoptosis and regeneration.

Male Sprague-Dawley rats were injected subcutaneously with 0.6 mg cadmium/kg bodyweight per day for 6 weeks. In each week of exposure, rats were killed and the localization of cadmium and metallothionein in the kidney was studied by histochemical and immunohistochemical methods. Although cadmium was localized throughout the proximal tubules during exposure, apoptosis and subsequent regeneration were observed mainly in the straight portion of the proximal tubules after 4 weeks of exposure. The distribution of tubular injury may thus not necessarily coincide with that of cadmium. Expression of metallothionein was also detected in the cytoplasm and nuclei of the convoluted and the straight portion of the proximal tubules, but the latter became positive in accordance with apoptosis and regeneration. These results suggest a close relationship between metallothionein distribution and tubular cell regeneration.

Animals↗