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Biomedical subjects

K Katagiri

Publications and source records attributed to K Katagiri.

At least 19 recordsLinked to original sources
PubMed2001

Occurrence of oligosialic acids on integrin alpha 5 subunit and their involvement in cell adhesion to fibronectin.

Integrin alpha(5)beta(1), a major fibronectin receptor, functions in a wide variety of biological phenomena. We have found that alpha 2-8-linked oligosialic acids with 5 < or = degree of polymerization (DP) < or = 7 occur on integrin alpha(5) subunit of the human melanoma cell line G361. The integrin alpha(5) subunit immunoprecipitated with anti-integrin alpha(5) antibody reacted with the monoclonal antibody 12E3, which recognizes oligo/polysialic acid with DP > or = 5 but not with the polyclonal antibody H.46 recognizing oligo/polysialic acid with DP > or = 8. The occurrence of oligosialic acids was further demonstrated by fluorometric C(7)/C(9) analysis on the immunopurified integrin alpha(5) subunit. Oligosialic acids were also found in the alpha(5) subunit of several other human cells such as foreskin fibroblast and chronic erythroleukemia K562 cells. These results suggest the ubiquitous modification with unique oligosialic acids occurs on the alpha(5) subunit of integrin alpha(5)beta(1). The adhesion of human melanoma G361 cells to fibronectin was mainly mediated by integrin alpha(5)beta(1). Treatment of cells with sialidase from Arthrobacter ureafaciens cleaving alpha 2-3-, alpha 2-6-, and alpha 2-8-linked sialic acids inhibited adhesion to fibronectin. On the other hand, N-acetylneuraminidase II, which cleaves alpha 2-3 and alpha 2-6 but not alpha 2-8 linkages, showed no inhibitory activity. After the loss of oligosialic acids, integrin alpha(5)beta(1) failed to bind to fibronectin-conjugated Sepharose, indicating that the oligosialic acid on the alpha(5) subunit of integrin alpha(5)beta(1) plays important roles in cell adhesion to fibronectin.

Antibodies, Monoclonal↗
PubMed2001

Suppression of pulmonary antibacterial defenses mechanisms and lung damage in mice exposed to fluoride aerosol.

In endemic fluorosis areas in China associated with coal burning, indoor airborne fluoride pollution is severe. To determine the effects of fluoride aerosols on pulmonary antibacterial defense mechanisms and lung damage, mice were exposed to various concentrations of fluoride aerosol (2, 5, or 10 mg/m3) or filtered air (control) for 14 d, 4 h/d in an inhalation chamber. Bactericidal activity against Staphylococcus aureus in the lung and the number and profile of free pulmonary cells, protein content, and lactate dehydrogenase (LDH) activity in bronchoalveolar lavage (BAL) fluid were assessed. Urinary fluoride concentration, an indicator of fluoride exposure, increased in proportion to fluoride aerosol concentration in the chamber. Wet lung weight was significantly higher on d 14 in mice exposed to 10 mg/m3 than in controls. Pulmonary bactericidal activity against S. aureus was concentration-dependently suppressed at 5 and 10 mg/m3 fluoride. The number of alveolar macrophages (AMs) in the BAL fluid of the mice not bacterially challenged decreased significantly at 10 mg/m3 fluoride. The number of polymorphonuclear leukocytes and lymphocytes increased significantly at 10 mg/m3 fluoride exposure. The concentration of total protein (TP) and albumin in BAL supernatant increased significantly at 5 and 10 mg/m3 fluoride exposure, and LDH activity rose markedly at the higher fluoride concentration. Data indicate that fluoride inhalation produces pulmonary cellular alterations that are associated with a diminished ability to cope with infectious bacteria.

Aerosols↗
PubMed2001

CD98 induces LFA-1-mediated cell adhesion in lymphoid cells via activation of Rap1.

CD98 is a multifunctional heterodimeric membrane protein involved in the regulation of cell adhesion as well as amino acid transport. We show that CD98 cross-linking persistently activates Rap1 GTPase in a LFA-1-dependent manner and induces LFA-1/ICAM-1-mediated cell adhesion in lymphocytes. Specific phosphatidylinositol-3-kinase (PI3K) inhibitors suppressed both LFA-1 activation and Rap1GTP generation, and abrogation of Rap1GTP by retroviral over-expression of a specific Rap1 GTPase activating protein, SPA-1, totally inhibited the LFA-1/ICAM-1-mediated cell adhesion. These results suggest that CD98 cross-linking activates LFA-1 via the PI3K signaling pathway and induces accumulation of Rap1GTP in a LFA-1-dependent manner, which in turn mediates the cytoskeleton-dependent cell adhesion process.

Androstadienes↗
PubMed2001

Safety of gadolinium contrast agent in hemodialysis patients.

PURPOSE: We evaluated the safety of a gadolinium (Gd) contrast agent in hemodialysis patients. MATERIAL AND METHODS: Seventy hemodialysis patients underwent contrast-enhanced MR examination. After the examination, the patients were hemodialyzed on a usual schedule, i.e., 3 times per week at 4 h each session. The hemodialysis was performed on the same day in 16 patients, the next day in 34, 2 days later in 14 and 3 days later in 6 patients. Serum Gd concentrations before and after the first to fourth hemodialysis sessions were analyzed in 11 patients. Cardiovascular, cutaneous, respiratory, psycho-neurological and digestive side effects were evaluated in all patients. Changes in liver and kidney functions, blood counts, and electrolytes were also checked. RESULTS AND CONCLUSION: Neither side effects nor blood changes were noted in any of the patients. Average excretory rates were 78.2%, 95.6%, 98.7% and 99.5% in the first to fourth hemodialysis sessions, respectively. These results suggest that Gd contrast agents can be used in hemodialysis patients if hemodialysis is carried out promptly after the examination.

Adult↗
PubMed2001

RAPD- and actA gene-typing of Listeria monocytogenes isolates of human listeriosis, the intestinal contents of cows and beef.

Seventy-five L. monocytogenes isolates of human listeriosis, the intestinal contents of cows and beef were divided into 5 major clusters, 17 sub-clusters and 28 minor clusters by typing using random amplification of polymorphic DNA (RAPD). According to their major RAPD category, L. monocytogenes isolates serotyped as 1/2b and 4b were distinguished from L. monocytogenes isolates of serovars 1/2a and 1/2c. Moreover serovar 4b was distinguished from serovar 1/2b by a difference in the RAPD sub-cluster category. All L. monocytogenes were found to possess either actA gene Type I or II, and only one actA gene type was detected in each RAPD minor cluster. actA gene Type II was observed in 32.0%, 38.5% and 18.9% of isolates from humans, cows and beef, respectively, and was detected more frequently in serovar 4b (46.9%) than in serovars 1/2a (22.2%), 1/2b (7.7%) and 1/2c (0.0%). Twenty (80%) of 25 human isolates fell within three minor RAPD types (II-d (16%), V-p-1 (36%), V-p-2 (28%)). Two isolates from humans and beef were found to have the same RAPD type (Type IV-k-1), actA gene type (Type I) and serovar (1/2b). Our results suggest that only a few genotypes of L. monocytogenes are predominant in human listeriosis in Japan, although the human isolates were collected over a broad span of time and a wide geographical range. Our results also suggest that RAPD-, actA gene- and sero-typing can be useful for epidemiological analysis.

Animals↗
PubMed2000

Distinct mechanisms of alpha 5beta 1 integrin activation by Ha-Ras and R-Ras.

To investigate the possible roles of the Ras/Rho family members in the inside-out signals to activate integrins, we examined the ability of Ras/Rho small GTPases to stimulate avidity of alpha(5)beta(1) (VLA-5) to fibronectin in bone marrow-derived mast cells. We found that both Ha-Ras(Val-12) and R-Ras(Val-38) had strong stimulatory effects on adhesion and ligand binding activity of VLA-5 to fibronectin. However, only Ha-Ras(Val-12)-, but not R-Ras(Val-38)-induced adhesion was inhibited by wortmannin, which suggests that Ha-Ras(Val-12) is dependent on phosphatidylinositol (PI) 3-kinase on adhesion whereas R-Ras(Val-38) has another PI 3-kinase independent pathway to induce adhesion. The effector loop mutant Ha-Ras(Val-12)E37G, but not Y40C retained the ability to stimulate adhesion of mast cells to fibronectin. Consistently, PI 3-kinase p110delta, predominantly expressed in mast cells, interacted with Ha-Ras(Val-12) E37G, but not Y40C, which was also correlated with the levels of Akt phosphorylation in mast cells. Furthermore, marked adhesion was induced by a membrane-targeted version of p110delta. These results indicate that Ha-Ras(Val-12) activated VLA-5 through PI 3-kinase p110delta. The mutational effects of the R-Ras effector loop region on adhesion were not correlated with PI 3-kinase activities, consistent with our contention that R-Ras has a distinct pathway to modulate avidity of VLA-5.

Cell Adhesion↗
PubMed2000

Prediction for biodegradability of chemicals by an empirical flowchart.

A method for predicting aerobic biodegradability of chemicals was developed based on empirical knowledge. A flowchart was derived from rule of thumb relationships between the biodegradability and the number of the functional groups and substructures in a certain skeletal structure of chemicals. The flowchart classified chemicals into readily biodegradable, not readily biodegradable and not predictable. It was validated by using MITI data of 177 mono benzene derivatives and 168 acyclic compounds, resulting in correct prediction at 94% and 88% levels, respectively.

Aerobiosis↗
PubMed2000

Identification, quantitative determination, and antioxidative activities of chlorogenic acid isomers in prune (Prunus domestica L. ).

Neochlorogenic acid (3-CQA) and cryptochlorogenic acid (4-CQA), isolated from prune (Prunus domestica L.), were identified by NMR and MS analyses. In addition, the quantity of chlorogenic acid isomers in prune were measured by HPLC. These isomers, 3-CQA, 4-CQA, and chlorogenic acid (5-CQA), were contained in the ratio 78.7:18. 4:3.9, respectively. 4-CQA was identified and quantified in prune for the first time, and relatively high amounts of this isomer were characteristic. Antioxidative activities of the chlorogenic acid isomers, such as scavenging activity on superoxide anion radicals and inhibitory effect against oxidation of methyl linoleate, were also evaluated. Each isomer showed antioxidative activities which were almost the same.

Antioxidants↗
PubMed2000

Dietary docosahexaenoic acid but not eicosapentaenoic acid suppresses lipopolysaccharide-induced interleukin-1 beta mRNA induction in mouse spleen leukocytes.

Mice were fed a diet supplemented either with beef tallow (BT), BT plus ethyl eicosapentaenoate (EPA) or BT plus ethyl docosahexaenoate (DHA) for 9 weeks. EPA and DHA supplementation increased the content of the respective fatty acid in spleen leukocyte lipids, which was associated with the reduction in the arachidonate content. IL-1beta mRNA induction upon lipopolysaccharide (LPS) stimulation in spleen leukocytes in the DHA diet group was significantly lower than in the BT diet group, but the EPA diet was without any significant effect. The amount of prostaglandin E2 (PGE2) released from LPS-stimulated spleen leukocytes was significantly lower in both the EPA and DHA groups than in the BT group. Thus, dietary EPA and DHA inhibited arachidonate metabolism similarly but had different effects on IL-1beta mRNA induction in mouse spleen leukocytes.

Animals↗
PubMed2000

Rap1 is a potent activation signal for leukocyte function-associated antigen 1 distinct from protein kinase C and phosphatidylinositol-3-OH kinase.

To identify the intracellular signals which increase the adhesiveness of leukocyte function-associated antigen 1 (LFA-1), we established an assay system for activation-dependent adhesion through LFA-1/intercellular adhesion molecule 1 ICAM-1 using mouse lymphoid cells reconstituted with human LFA-1 and then introduced constitutively active forms of signaling molecules. We found that the phorbol myristate acetate (PMA)-responsive protein kinase C (PKC) isotypes (alpha, betaI, betaII, and delta) or phosphatidylinositol-3-OH kinase (PI 3-kinase) itself activated LFA-1 to bind ICAM-1. H-Ras and Rac activated LFA-1 in a PI 3-kinase-dependent manner, whereas Rho and R-Ras had little effect. Unexpectedly, Rap1 was demonstrated to function as the most potent activator of LFA-1. Distinct from H-Ras and Rac, Rap1 increased the adhesiveness independently of PI 3-kinase, indicating that Rap1 is a novel activation signal for the integrins. Rap1 induced changes in the conformation and affinity of LFA-1 and, interestingly, caused marked LFA-1/ICAM-1-mediated cell aggregation. Furthermore, a dominant negative form of Rap1 (Rap1N17) inhibited T-cell receptor-mediated LFA-1 activation in Jurkat T cells and LFA-1/ICAM-1-dependent cell aggregation upon differentiation of HL-60 cells into macrophages, suggesting that Rap1 is critically involved in physiological processes. These unique functions of Rap1 in controlling cellular adhesion through LFA-1 suggest a pivotal role as an immunological regulator.

Animals↗
PubMed2000

1Alpha-hydroxyvitamin D3 prevents the decrease of bone mineral density in lactating beagles.

We assessed the change of bone mineral density (BMD) in lactating beagles with dual energy X-ray absorptiometry (DXA) and the preventive effect of 1alpha-hydroxyvitamin D3 (1alpha(OH)D3) on the BMD. Beagles, two to five years old, were used for detecting the time course change of BMD. Since the coefficient of variation (CV(%)) on detecting lumber vertebral (L2-L4) and tibial BMD by DXA was about 0.5%, DXA was useful to detect the change of BMD in beagles. There was a marked decrease in vertebral BMD during lactational period in the control group. The BMD levels after weaning were found to reverse to the initial level at mating. The same tendency was observed in tibial BMD as vertebral BMD, though the BMD changes were not marked. Beagles were administered at a dose of 0.1 microg/kg of 1alpha(OH)D3 three times in a week, and it was found to suppress the decrease in vertebral BMD during the breast feeding period. Also, the administration of 1alpha(OH)D3 promoted the prevention of decreased BMD during lactation both in vertebrae and tibiae. Significant effects of 1alpha(OH)D3 administration on tibial BMD were not observed. No adverse effects, such as hypercalcemia and hypercalciuria, were observed during the experimental period. Therefore, DXA was useful for detecting the changes of BMD in lactating beagles and the change of BMD was marked in lumber vertebrae, which are rich in trabecular bone. The preventive effect of 1alpha(OH)D3 on the decrease of BMD during the lactation period was observed in beagles.

Absorptiometry, Photon↗
PubMed2000

Locoregional cellular immunotherapy for patients with advanced esophageal cancer.

The objectives of the present study were to determine the safety of locoregional administration of autologous lymphocytes stimulated with autologous tumor cells and interleukin (IL) 2 in vitro and to find laboratory markers to predict either clinical toxicity or clinical response. Eleven patients with advanced (n = 4) or recurrent (n = 7) esophageal cancers received the locoregional administration of these activated lymphocytes every 2 weeks for two to nine times (mean, 5.6 times), and mean numbers of the administered cells were 0.8 x 10(9) cells per treatment. The activated lymphocytes that were pretested for their surface markers and CTL activity were endoscopically injected into primary tumor sites (n = 4) or directly injected into metastatic lymph nodes (n = 2), pleural (n = 4) or ascitic (n = 1) regions. Grade 3 hypotension, grade 2 diarrhea, and grade 1 fever were observed in 1, 1, and 6 patients, respectively, and there was no adverse effect in the remaining three patients. The clinical outcome was as follows: one, complete response (CR); three, partial response (PR); two, stable response (SR); and five, progressive disease (PD). CTL activity in the administered cells was observed in 5 of the 11 patients (1 CR, 3 PR, and 1 PD) and was not observed in the remaining 6 patients (2 SR and 4 PD). Percentages of CD16+ cells in the peripheral blood of the responder group (CR+PR) significantly increased when compared with those before treatment or with those of the nonresponder group before as well as after treatment. Because the clinical toxicity was moderate and tolerable, this new method of locoregional immunotherapy will be applicable for use in treatment of patients with advanced and recurrent esophageal cancers. Both CTL activity in the administered cells and the percentages of CD16+ cells in the peripheral blood may be useful laboratory markers for predicting of clinical response.

Aged↗
PubMed1999

Laminin 5 promotes activation and apoptosis of the T cells expressing alpha3beta1 integrin.

By introducing an alpha3 gene-containing plasmid into a human T cell line Jurkat, we prepared the T cells, which express a high level of the alpha3beta1 integrin, to assess the role of laminin 5 in the skin immune system. The alpha3beta1-expressing T cells adhered to laminin 5 and exhibited spreading. These adhered T cells showed a significant tyrosine phosphorylation of intracellular proteins including p59(fyn) upon T-cell receptor (TCR) stimulation. Six hours after cross-linking TCR, these cells on laminin 5 secreted a three times higher level of IL-2 than those on a BSA-coated plate. Twenty hours after the stimulation, 48% of the alpha3beta1-expressing T cells on laminin 5 caused apoptosis. The protein level of cyclin D3 and E decreased, while that of p53 increased in these T cells. These data suggest that laminin 5 may play at least two regulatory roles for T cell functions: augmentation of IL-2 production by antigen-stimulated T cells and induction of apoptosis in these T cells.

Apoptosis↗
PubMed1999

Ubiquitin-proteasome system is involved in induction of LFA-1/ICAM-1-dependent adhesion of HL-60 cells.

Membrane-permeable proteasome inhibitors, lactacystin (LC) and N-acetyl-Leu-Leu-norleucinal (ALLN), but not calpain inhibitor Z-Leu-leucinal (ZLL), prevented LFA-1/ICAM-1-dependent cellular adhesion of TPA-stimulated HL-60 cells. These proteasome inhibitors affected neither the induction of monocytic differentiation nor the accompanying protein-tyrosine phosphorylation. They suppressed the increase in the avidity of LFA-1 to ICAM-1 without changing the expression of these molecules. Immunoblotting using monoclonal antibody FK-1, which reacts specifically with polyubiquitinated proteins, demonstrated that the proteasome inhibitors caused the drastic accumulation of the polyubiquitinated proteins in the membrane fraction of TPA-treated HL-60 cells. This indicates that accompanying activation of LFA-1, TPA induces the polyubiquitination of the membrane proteins, which are rapidly degraded by proteasomes. These data taken together show that proteolysis mediated by the ubiquitin-proteasome system is a prerequisite for the induction of LFA-1-dependent adhesion of HL-60 cells.

Acetylcysteine↗
PubMed1999

Expression of Th1 and Th2 cytokine mRNAs in freshly isolated peripheral blood mononuclear cells of a patient with cutaneous paragonimiasis.

Using semiquantitative reverse transcriptase polymerase chain reaction, we examined the levels of various cytokine mRNAs of freshly isolated peripheral blood mononuclear cells (PBMCs) from a cutaneous paragonimiasis patient in the course of successful treatment with praziquantel administration. The pre-treatment levels of Th2 cytokines such as interleukin (IL)-4, IL-5, IL-10 and IL-13 mRNAs in PBMCs of the patient were much higher than those of healthy controls. The levels of IL-4, IL-5 and IL-13 mRNAs slightly elevated on day 2 of the treatment and then declined to the control levels on day 25. The IL-10 mRNA level rapidly decreased after the chemotherapy. In contrast, the mRNA levels of interferon (IFN)-gamma, a Th1 cytokine, remained in the control levels during the course. Peripheral eosinophil counts and levels of total IgE and eosinophil cationic protein in the sera correlated well with the levels of these Th2 cytokine mRNAs. These results suggested the major role of Th2 cytokines in clinical manifestation of human helminthic infection.

Adult↗
PubMed1999

Increased levels in vivo of mRNAs for IL-8 and macrophage inflammatory protein-1 alpha (MIP-1 alpha), but not of RANTES mRNA in peripheral blood mononuclear cells of patients with atopic dermatitis (AD).

Chemokines play an important role in the selective movement of leucocytes into inflammatory areas and they also activate various cells in inflamed tissues. However, it is unclear which cells are the main sources of chemokines in actual inflammatory diseases, even though both mononuclear cells and non-inflammatory resident cells are able to produce chemokines in vitro and the former cells are also the main target of chemokines. To clarify the roles of chemokines that are produced by mononuclear cells in AD, we measured levels in vivo of mRNA for IL-8 and MIP-1 alpha, as well as the level of regulated upon activation normal T cell expressed and secreted (RANTES) mRNA in freshly isolated peripheral blood mononuclear cells from patients with AD. We compared the results with those from psoriatic patients, and patients without AD who were suffering from other cutaneous diseases and eosinophilia. Levels of mRNAs were determined by semiquantitative reverse transcriptase-polymerase chain reactions. Levels of IL-8 and MIP-1 alpha mRNA were elevated not only in atopic patients but also in non-atopic patients with inflammatory skin disease associated with eosinophilia, compared with levels in psoriatic patients and healthy controls. Levels of RANTES mRNA were similar in atopic patients but they were lower in the other two groups of patients when compared with levels in healthy controls. In atopic patients, the levels of both IL-8 and MIP-1 alpha mRNAs but not of RANTES mRNA decreased with improvements in symptom scores after therapy. These findings suggest that mononuclear cells are not only the target of chemokines but might also play an important role in the pathogenesis of AD by producing IL-8 and MIP-1 alpha.

Adolescent↗
PubMed1999

Heterogeneity in expression of cytokine mRNA in freshly isolated peripheral blood eosinophils of patients with cutaneous-disease-associated eosinophilia.

BACKGROUND: It is thought that there are subpopulations of eosinophils concerning cytokine production: some of them predominantly produce Th1 cytokines, while others produce Th2. METHODS: By semiquantitative RT-PCR, the in vivo levels of the cytokine mRNA were measured in freshly isolated eosinophils and peripheral blood mononuclear cells (PBMCs) of 19 patients with eosinophilia, including 6 with atopic dermatitis, 4 with drug eruption, 1 with chronic dermatitis, 2 with erythroderma, 3 with bullous pemphigoid, 1 each with urticaria, adult T cell lymphoma, and hypereosinophilic syndrome, and 7 healthy individuals. Eosinophils and PBMCs were isolated by centrifugation over Ficoll-Paque and magnetic cell separation using anti-CD16 antibody. RESULTS: The IL-4/IFN-gamma ratio in eosinophils as well as PBMCs was increased and correlated well with IgE levels in atopic dermatitis. In other cytokines, such as IL-8, TNF-alpha and TGF-beta1, the levels of mRNA expression were variable among each sample. CONCLUSION: Not only helper T lymphocytes but also eosinophils may take part in the pathogenesis of cutaneous diseases by virtue of heterogeneity of Th1 and Th2 cytokine production.

Adult↗