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Biomedical subjects

K Kashima

Publications and source records attributed to K Kashima.

At least 145 records · Page 8Linked to original sources
PubMed1997

Induction of various cytokines and development of severe mucosal inflammation by cagA gene positive Helicobacter pylori strains.

BACKGROUND: Helicobacter pylori strains possessing the cagA gene are thought to induce interleukin 8 (IL-8) in gastric mucosa. However, it is still unclear whether a relation exists between the cagA gene and the expression patterns of cytokines other than IL-8. AIMS: To investigate the relation between the cagA gene and the production of various cytokine proteins using an enzyme linked immunosorbent assay (ELISA). PATIENTS AND METHODS: In 184 patients, the cagA gene was detected by polymerase chain reaction (PCR), and levels of production of IL-1 beta, IL-6, IL-7, IL-8, IL-10, and tumour necrosis factor alpha (TNF-alpha) in antral biopsy specimens were measured by ELISA. RESULTS: Mucosal levels of IL-1 beta, IL-6, IL-8, and TNF-alpha were significantly higher in H pylori positive than in H pylori negative patients. Furthermore, the mucosal levels of IL-1 beta and IL-8 were significantly higher in specimens infected with cagA positive strains than in those infected with cagA negative strains. In H pylori positive patients, the mucosal level of IL-8 was closely correlated with that of IL-1 beta (p < 0.0001), and the mucosal level of IL-6 was closely correlated with that of TNF-alpha (p < 0.0001). CONCLUSION: These findings suggest that the ability to induce cytokines differs among the strains; cagA+ strains induce various kinds of cytokines and may cause severe inflammation, whereas cagA- strains induce IL-8 and IL-1 beta only weakly and may cause only mild inflammation. However, as most patients infected with the cagA+ strains have gastritis, these strains may not be equivalent to ulcerogenic strains.

Adult↗
PubMed1997

Effect of granulocyte-colony stimulating factor on generation of oxygen-derived free radicals and myeloperoxidase activity in neutrophils from poorly controlled NIDDM patients.

To evaluate whether granulocyte-colony stimulating factor (G-CSF) improves an impaired production of oxygen-derived free radicals by neutrophils from poorly controlled NIDDM patients, we studied the effect of G-CSF on myeloperoxidase (MPO) activity and chemiluminescence amplified by a Cypridina luciferin analog (CLA-DCL), which is dependent on O2 generation, and luminol (L-DCL), which is dependent on OCl(-) generation, in response to formyl-methonyl-leucyl-phenylalanine. Both CLA-DCL and L-DCL by neutrophils from the diabetic group (n = 15, HbA(1c) >10%) were significantly decreased (26 and 37%, respectively: P < 0.01) compared with the age-matched normal control group (n = 15), and L-DCL was more sensitive to this inhibition than CLA-DCL (P < 0.05). In both control and diabetic neutrophils, G-CSF significantly enhanced both CLA-DCL (175% in control and 156% in diabetic) and L-DCL (283% in control and 346% in diabetic). In diabetic neutrophils, the enhancing effect of G-CSF on L-DCL was more sensitive than on CLA-DCL (P < 0.001). There was a positive correlation between HbA(1c) and the enhancing effect of G-CSF on L-DCL in diabetic patients (P < 0.05), but not on CLA-DCL. MPO activity was also decreased in the diabetic group (63%, P < 0.05), and G-CSF improved this impaired MPO activity (184%, P < 0.01). Furthermore, there was a positive correlation between HbA(1c) and the improving effect of G-CSF on MPO activity (P < 0.05). Because bacterial infection still accounts for an important cause of morbidity and mortality in diabetic patients, these data suggest that G-CSF may be useful as a drug to prevent the aggravation of bacterial infection by improving neutrophil function, especially through H2O2-MPO-OCl(-) mechanism, in poorly controlled diabetic patients.

Adult↗
PubMed1997

Epalrestat, an aldose reductase inhibitor, improves an impaired generation of oxygen-derived free radicals by neutrophils from poorly controlled NIDDM patients.

OBJECTIVE: To study the in vivo effect of epalrestat (Epa), an aldose reductase inhibitor, on the generation of oxygen-derived free radicals by neutrophils from poorly controlled NIDDM patients (HbA1c > 10%). RESEARCH DESIGN AND METHODS: A total of 31 diabetic patients were randomly divided into two groups: an Epa(+) group of 16 patients treated with 150 mg/day epalrestat and an Epa(-) group of 15 patients treated without epalrestat. A control group of 20 age- and sex-matched normal healthy subjects also participated. HbA1c, postprandial plasma glucose (PPG), and neutrophil bactericidal function were measured before and at the end of the drug treatment period (4 weeks). Neutrophil bactericidal function was measured as chemilu-minescence amplified by a Cypridina luciferin analog (CLA), which is dependent on O2- generation, and by luminol (L), which is highly dependent on OCl- generation, in response to formyl-methonyl-leucyl-phenylalanine (fMLP). RESULTS: At the start of the experiment, both CLA-dependent chemiluminescence (CLA-DCL) and L-dependent chemiluminescence (L-DCL) were clearly decreased in diabetic subjects (64 and 54%, respectively; P < 0.05) compared with control subjects (2,182 +/- 144 and 3,221 +/- 173 kc.min-1.10(-6) cells, respectively). At the end of the experiment, CLA-DCL and L-DCL in the Epa(+) group were significantly improved by 44 and 46%, respectively; however, these values were still lower than the corresponding results in the control group. HbA1c and PPG in both the Epa(+) and Epa (-) groups were significantly higher than in the control group, and treatment had no effect on either HbA1c or PPG. CONCLUSIONS: These data suggest that epalrestat may be a useful drug to prevent infection by improving the impaired O2- and OCl- generation by neutrophils from poorly controlled NIDDM patients.

Aldehyde Reductase↗
PubMed1997

Expression of fibroblast growth factor 2 mRNA in early and advanced gastric cancer.

We examined the expression of FGF-2 mRNA in 16 early and 14 advanced gastric cancer by in situ hybridisation to elucidate its role in cancer progression. Anti-sense RNA probes were synthesized by transcribing the subcloned vector with T7 RNA polymerase in the presence of digoxigenin-labeled UTP. FGF-2 mRNA was located mainly in the cytoplasm around the nuclei of endothelial cells, fibroblasts and carcinoma cells. The expression was more frequently in the diffuse type carcinomas (4/7, 57%) than in the intestinal type tumours (5/23, 22%). The survival rates of advanced gastric cancers with FGF-2 mRNA expression were significantly lower than those without FGF-2 mRNA expression (p < 0.01). No significant correlation was seen with other clinicopathological factors. These results suggest that FGF-2 may play an important role for the growth of diffuse type gastric cancers, particularly at their advanced stage.

Aged↗
PubMed1997

Hepatic damage influences the decay of nitroxide radicals in mice--an in vivo ESR study.

To determine the role of the liver in the elimination of free radicals from the body, the clearance rate (K) of nitroxide radicals (Tempol) at the hepatic domain was compared with that at the pelvic domain of live mice, using L-band ESR spectroscopy. The reduction of Tempol in biopsy specimens (liver tissue and femoral muscle) and blood obtained from Tempol-treated mice was also monitored using X-band ESR spectroscopy. Results indicated that the reduction of nitroxide radicals was delayed in both the liver and peripheral tissues when the liver was damaged. The decrease in both blood supply and reductants in the damaged liver might be involved in delaying the reduction in the whole body, because the liver can reduce the radicals supplied via the blood from the peripheral tissues, and the reductants such as reduced, glutathione in the peripheral tissues are supplied from the liver.

Animals↗
PubMed1997

Deletion of chromosome 11 and development of colorectal carcinoma.

The deletion of chromosome 11q is observed frequently in tumors of the large intestine. To investigate the relationship between aberrations of chromosome 11 and histopathological features of colorectal carcinoma, we examined the frequency of chromosome aberrations using fluorescence in situ hybridization to 29 short-term cultured cells from surgical specimens. Numerical aberrations were not related to any factors. The deletion of chromosome 11 was frequently observed in larger (> or = 5 cm) and more invasive tumors (> or = T3 category) (p < 0.05). Furthermore, the incidence of aberrations tended to increase in Dukes' B. Although translocation of chromosome 11 was also found in 17% of cases, it was not associated with histopathological features. Our findings indicate that the deletion of chromosome 11 is closely related to the progression of colorectal carcinoma.

Chromosome Aberrations↗
PubMed1997

Cytoplasmic biotin-like activity interferes with immunohistochemical analysis of thyroid lesions: a comparison of antigen retrieval methods.

Cytoplasmic biotin-like activity was identified in formalin-fixed and paraffin-embedded human thyroid lesions by immunostaining for biotin by use of the peroxidase-antiperoxidase method or by peroxidase-labeled streptavidin alone. The reactivity of cytoplasmic biotin-like activity was markedly enhanced both by pretreatment with trypsin and after heating by autoclaving. Of 208 thyroid lesions, 93 showed positive immunostaining for biotin with use of trypsin pretreatment. The positive incidence of cases and positive cell ratio were highest in papillary carcinoma, followed by follicular carcinoma but lowest in the lethal types of thyroid carcinoma: anaplastic carcinoma, squamous cell carcinoma and poorly differentiated insular carcinoma. We conclude that cytoplasmic biotin-like activity in the common thyroid neoplasms should be considered as an interfering factor for immunostaining with avidin-biotin combined with selected antigen retrieval methods and with in situ hybridization with biotinylated probes.

Bacterial Proteins↗
PubMed1997

Rapid detection of lymphoma-specific translocations in interphase nuclei of non-Hodgkin's lymphoma by fluorescence in situ hybridization.

We have recently developed a method to detect tumor-specific rearrangement of the IgH gene in interphase nuclei by fluorescence in situ hybridization. Tumor-specific IgH gene rearrangement is equivalent to 14q32.33 translocation. Using this approach, we detected 14q32.33 translocation in 29 of 70 patients with B-cell non-Hodgkin's lymphoma (NHL). Chromosome t(3;14) was found in 10 of these 29 patients, and were demonstrated as a fusion signal of BCL6 and VH gene probes in interphase nuclei. Furthermore, in another series of 11 patients and a NHL cell line, we demonstrated t(14;18) and t(11;14) in interphase and metaphase cells with a combination of BCL2 (or PRAD1) with IgH gene probes. Interphase FISH with lymphoma-associated gene probes is a rapid procedure for cytogenetic diagnosis of B-cell NHL.

Cell Nucleus↗
PubMed1997

Genetic aberrations in the development and subsequent progression of myelodysplastic syndrome.

We performed longitudinal analyses of chromosomes and studied the configuration of NRAS, TP53, NF1, and cFMS genes in 70 patients with myelodysplastic syndrome(MDS). The NRAS mutations were detected in 6 patients(9%) at codons 12 or 13. The TP53 mutations were found in 10 patients(14%) in exons 4 through 8. Longitudinal studies revealed that the NRAS mutation was a late-appearing event, while the TP53 mutations were detectable at the presentation of MDS. No patients had both NRAS and TP53 mutations, simultaneously. NF1 and cFMS genes showed any mutational event among these 70 patients. Patients with a TP53 mutation had a significantly shorter survival time than those with an NRAS mutation or those without NRAS or TP53 mutation. However, patients who showed an NRAS mutation had a shorter survival time once the mutation emerged, similar to that of patients with a TP53 mutation.

Adolescent↗
PubMed1997

[Analysis of microsatellite regions and DNA ploidy pattern in signet ring cell carcinomas of the stomach].

We examined microsatellite instability (MSI) and loss of heterozygosity (LOH) in regions of several important genes in 25 signet-ring cell carcinomas of the stomach. The relationship between microsatellite analysis and DNA ploidy pattern was also investigated. MSI was observed in 15% (2/13) of early carcinomas and in 17% (2/12) of advanced carcinomas. Although LOH in the region of APC gene was found in 16% (4/25) and LOH of p53 was found in 12% (3/25), 15% (2/13) of early carcinomas and 33% (4/12) of advanced carcinomas showed LOH in regions of E-cadherin gene. Cyto-fluorometrical study revealed that 85% (11/13) of early carcinomas were diploid pattern, and aneuploid components were demonstrated in 50% (6/12) of advanced carcinomas. However, no MSI-positive cases contained aneuploid components, and in contrast, all p53-LOH cases contained aneuploid components. Our results suggest that gene abnormalities which have been frequently reported in differentiated adenocarcinomas are rare events in signet-ring cell carcinomas other than those associated with cell adhesion, and that MSI is not related to the occurrence of aneuploid cells.

Adult↗
PubMed1996

Quantitative age-related changes in apical dendrites and dendritic spines of CA1 pyramidal neurons among senescence accelerated mice (SAMP1TA/Ngs).

SAMP1TA/Ngs, a substrain of senescence accelerated mouse, is a useful animal model for research on brain dysfunction due to senescence. In a previous study it was reported that the age-related changes in basal dendrites and spines of CA1 pyramidal neurons coincide with the behavioral characteristics found in SAMP1TA/Ngs. The goal of the present study was to investigate morphological changes in apical dendrites and dendritic spines of CA1 pyramidal neurons among 3-, 5-, 7-month-old SAMP1TA/Ngs. Pyramidal neurons of the hippocampus were stained by the rapid Golgi method, and the number of apical dendrites, the number of their spines and the density of the dendritic spines were evaluated. The number and density of the spines of apical dendrites were significantly higher at 5 months than at 3 or 7 months of age. We propose that the low number of dendritic spines in 3-month-old animals was caused by immaturity, while the changes in the density and number of dendritic spines in 7-month-old mice were due to accelerated aging. The data on the morphology of apical dendrites are a useful complement to the results reported previously. The findings of the present study also support the hypothesis that this model mouse demonstrates changes in respective developmental stages, i.e. immaturity, adulthood and senescence. This pattern of postnatal growth has special meaning because it indicates the usefulness of the strain in the study of geriatric disorders in humans.

Aging↗
PubMed1996

Evidence of a direct action of taurine and calcium on biological membranes. A combined study of 31P-nuclear magnetic resonance and electron spin resonance.

To determine the actions of taurine and calcium on biological membranes, the effects of these compounds on the mobility of phospholipids of resealed and sonicated ghosts of human erythrocytes were investigated, using 31P-NMR spectroscopy. In addition, the effects of taurine and calcium on lipid fluidity were investigated by ESR spectroscopy, using a spin-labeling method with 5-doxyl stearic acid. The mobility of the membranes decreased following treatment with 10 mM taurine, but coadministration of 2.5 mM calcium blocked this effect. The fluidity of the membranes was not changed following treatment with 10 mM taurine, but decreased following coadministration of 2.5 mM calcium. These actions of taurine and calcium on the dynamics of biological membranes might explain, in part, the observation that most of the pharmacological effects of taurine on mammalian organs occur in the presence of calcium ions.

Calcium↗
PubMed1996

Cytogenetic analyses of hepatocellular carcinoma by in situ hybridization with a chromosome-specific DNA probe.

BACKGROUND: Numerical chromosome analysis has been established in solid tumors by using in situ hybridization (ISH) with a chromosome-specific probe. We analyzed human hepatocellular carcinoma (HCC) by ISH for chromosome 17 and investigated the correlation of its copy number with histologic malignancy, proliferative activity, p53 mutation, and DNA ploidy. METHODS: Chromosome 17 was hybridized with a pericentromere-specific DNA probe directly on the tumor cells isolated from paraffin blocks of 25 surgically resected HCCs. Proliferative activity was measured by Ki-67 immunohistochemistry, p53 mutation was analyzed by p53 immunohistochemistry, and DNA ploidy was estimated by cytofluorometry. RESULTS: Forty-four percent of the 25 HCCs showed numerical abnormality of chromosome 17. Many disomic cases had a less malignant histology, whereas many polysomic cases had a more malignant histology. The Ki-67 positive index of polysomic cases was higher than that of disomic cases. In 22 cases (88.0%), the copy number of chromosome 17 was well matched with DNA ploidy. However, the numerical abnormality of chromosome 17 did not show a significant correlation with p53 mutation. Two of four HCCs that showed histologic heterogeneity were also heterogenous on ploidy pattern and the copy number of chromosome 17. Conversely, there was one case in which only ISH could demonstrate heterogeneity, although the other features exhibited homogeneity. CONCLUSIONS: Numerical chromosome abnormalities correlated with the increase of histologic malignancy proliferative activity, and DNA ploidy. Moreover, ISH analysis was useful in assessing the intratumoral heterogeneity in HCC, especially when current methods failed to detect it. Thus, ISH provides information on important biologic features, such as malignant potential and intratumoral heterogeneity, in HCC.

Adult↗