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Biomedical subjects

M Ikeda

Publications and source records attributed to M Ikeda.

At least 541 records · Page 30Linked to original sources
PubMed1998

Non-occupational exposure of adult women in Manila, the Philippines, to lead and cadmium.

In total, 45 adult women in Manila, the Philippines, volunteered to participate in the study by offering peripheral blood samples and 24-h total food duplicate samples. In addition, they offered raw (uncooked) rice as well as wheat flour and maize starch from the kitchen. Lead (Pb) and cadmium (Cd) in food duplicates and blood samples were measured by inductively coupled plasma mass spectrometry after homogenization (when necessary) and wet-ashing. The consumption of rice, wheat and maize was calculated by weighing each food item in the duplicates taking advantage of the food composition tables. The dietary exposure level of the women was 11 micrograms Pb/day and 14 micrograms Cd/day, and the levels of Pb and Cd in their blood were 37 ng Pb/ml and 0.47 ng Cd/ml. There is a subtle age-dependent increase in the dietary burden of Pb and Cd and also in blood levels of Pb and Cd. Rice accounted for 18 and 21% of dietary Pb and Cd intake, respectively and cereals (i.e. rice, wheat and maize in combination) accounted for 24% both for Pb and Cd. The calculation from the published data on air quality in Manila suggested that another and yet a greater source of Pb burden was Pb in atmospheric air which may account for 85% of total Pb uptake, whereas the amount of Cd in air was quite small (i.e. < 10% of the total uptake).

Adult↗
PubMed1998

Lactoferrin markedly inhibits hepatitis C virus infection in cultured human hepatocytes.

We found that bovine lactoferrin (bLF), a milk protein belonging to the iron transporter family, effectively prevented hepatitis C virus (HCV) infection in cultured human hepatocytes (PH5CH8), a cell line susceptible to HCV infection and supportive of HCV replication. Because preincubation of HCV with bLF was required to prevent the infection of HCV to the cells, and preincubation of bLF with the cells showed no inhibitory effect on HCV infection, we demonstrated that the anti-HCV activity of bLF was due to the interaction of bLF with HCV, but not due to the interaction of bLF with the cells. We further found that human lactoferrin also had anti-HCV activity, but bovine transferrin, the other member of the iron transporter family, did not have anti-HCV activity. Our findings suggest that lactoferrin is one of candidates for an anti-HCV reagent that will be well-tolerated and effective in the treatment of patients with chronic hepatitis.

Animals↗
PubMed1998

Increased expression of the sodium/iodide symporter in papillary thyroid carcinomas.

Iodide is concentrated to a much lesser extent by papillary thyroid carcinoma as compared with the normal gland. The Na+/I- symporter (NIS) is primarily responsible for the uptake of iodide into thyroid cells. Our objective was to compare NIS mRNA and protein expression in papillary carcinomas with those in specimens with normal thyroid. Northern blot analysis revealed a 2.8-fold increase in the level of NIS mRNA in specimens with papillary carcinoma versus specimens with normal thyroid. Immunoblot analysis using anti-human NIS antibody that was produced with a glutathione S-transferase fusion protein containing NIS protein (amino acids 466-522) showed the NIS protein at 77 kD. The NIS protein level was elevated in 7 of 17 cases of papillary carcinoma but was not elevated in the normal thyroid. Immunohistochemical staining revealed abundant NIS in 8 of 12 carcinomas, whereas NIS protein was barely detected in specimens with normal thyroid. Although considerable patient-to-patient variation was observed, our results indicate that NIS mRNA is elevated, and its protein tends to be more abundant, in a subset of papillary thyroid carcinomas than in normal thyroid tissue.

Carcinoma, Papillary↗
PubMed1998

Protection against blood-brain barrier disruption in focal cerebral ischemia by the type IV phosphodiesterase inhibitor BBB022: a quantitative study.

We examined the effect of BBB022, a type IV phosphodiesterase inhibitor, on blood-brain barrier (BBB) integrity after transient middle cerebral artery occlusion (MCAo) in rats. Male Sprague-Dawley rats were anesthetized with halothane and subjected to 120 min of temporary MCAo by retrograde intraluminal insertion of a nylon suture coated with poly-L-lysine. The drug (BBB022 in saline, 1 mg kg-1 h-1, i.v.) or vehicle (0.9% saline, 1-2 ml kg-1 h-1) was administered by infusion after the onset of MCAo. Four animal groups were studied: Groups A and B were treated by infusion of vehicle or drug over 5 h, and groups C and D over 48 h. Damage to the BBB was judged by extravasation of Evans blue (EB) dye, which was administered i.v. at 3 h after the onset of MCAo in groups A and B; and at 46 h in groups C and D. Fluorometric quantitation of EB was performed 1 or 2 h later in six brain regions. In the 5-h infusion series (group B), BBB022 decreased dye extravasation in the ipsilateral cortex, striatum and hemisphere (hemisphere mean+/-S.E.M. : 41.2+/-5.4 vs. 82.4+/-9.2 microg/g, p=0.005) compared to the vehicle-treated group (A). The 48-h infusion of BBB022 (group D) also decreased dye extravasation in the ipsilateral cortex (7.4+/-2. 5 vs. 29.0+/-8.3 microg/g, p=0.05), striatum (17.2+/-2.2 vs. 50. 8+/-12.1 microg/g, p=0.03) and hemisphere (30.7+/-4.0 vs. 93.2+/-18 microg/g, p=0.01) compared to the vehicle-treated group (C). BBB022 also significantly improved the neurological score at 3 and 5 h after MCAo (in the 5-h infusion group) and at 60 min, 24 h and 48 h (in the 48-h infusion group) compared to the vehicle groups. These data indicate that BBB022 prevents ischemic damage to the BBB after focal cerebral ischemia in rats.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

Inhibition by imipramine of ATP-evoked responses in rat pheochromocytoma cells.

The effect of imipramine on the ATP-evoked release of dopamine was analyzed in parallel with its effects on the rise in the intracellular Ca2+ concentration ([Ca2+]i) and current induced by ATP in rat pheochromocytoma PC12 cells. Imipramine (10-300 microM) inhibited the ATP-evoked release of dopamine and rise in [Ca2+]i in a concentration-dependent fashion though the effect of imipramine on the release was slightly more obvious. Imipramine also inhibited the ATP-activated inward current at a similar concentration range. These results show a new pharmacological profile of imipramine, namely the inhibition of P2X2 receptors.

Adenosine Triphosphate↗
PubMed1998

The inhibitory effect of novel triterpenoid compounds, fomitellic acids, on DNA polymerase beta.

We previously found new triterpenoid compounds, designated fomitellic acid A and B, which selectively inhibit the activities of mammalian DNA polymerase alpha and beta in vitro. On DNA polymerase beta, the fomitellic acids acted by competing with both the substrate and the template primer, but on DNA polymerase alpha, they acted non-competitively. At least on DNA polymerase beta, the evidence suggests that each of the fomitellic acids bind to the active region competing with the substrate and/or template primer, and subsequently inhibits the catalytic activity. We therefore further investigated the enzyme-binding properties by using DNA polymerase beta and its proteolytic fragments. The 39 kDa enzyme was proteolytically separated into two fragments of the template-primer-binding domain (8 kDa) and the catalytic domain (31 kDa). The fomitellic acids bound tightly to the 8 kDa fragment, but not to the 31 kDa fragment. The immuno-precipitation by antibodies against the enzyme or each of the fragments also proved the binding. These results suggest that the fomitellic acid molecule competes with the template-primer molecule on its 8 kDa binding site, binds to the site, and the fomitellic acid molecule simultaneously disturbs the substrate incorporation into the template primer.

Animals↗
PubMed1998

Interleukin-18 activates the IRAK-TRAF6 pathway in mouse EL-4 cells.

The pleiotropic biological activities of interleukin-18 (IL-18) are mediated by IL-18 receptor (IL-18R). When the ligand binds to the IL-18R, IL-18R initiates a signaling cascade that results in the activation of nuclear factor kappa B (NF-kappa B). When mouse EL-4 cells were exposed to IL-18, IL-1 receptor-associated kinase (IRAK) was recruited to IL-18R and was phosphorylated. In addition, tumor necrosis factor receptor-associated factor-6 (TRAF6) was associated with IRAK. Therefore, we concluded that IL-18/IL-18R-mediated signaling may share the IRAK/TRAF6 pathway through NF-kappa B activation with the IL-1/IL-1 receptor system.

Animals↗
PubMed1998

Molecular cloning of extremely thermostable esterase gene from hyperthermophilic archaeon Pyrococcus furiosus in Escherichia coli.

A genomic library of the hyperthermophilic archaeon Pyrococcus furiosus was constructed in Escherichia coli using pBluescript II SK(+) as a cloning vector. One positive clone exhibiting thermophilic ester-hydrolyzing activity was directly detected by an in situ plate assay using the chromogenic substrate 5-bromo-4-chloro-3-indolyl-acetate. The plasmid isolated from the clone contained a 3.8 kb HindIII fragment from P. furiosus. Expression of active thermostable esterase in E. coli was independent of isopropyl-beta-D-thiogalactopyranoside, suggesting that the archaeal esterase gene was heterologously controlled by its own promoter sequence, not by the vector-located lac promoter. Assays of esterase activity in heat-treated extract of the recombinant E. coli showed the highest temperature optimum (100 degrees C) and thermostability (a half-life of 50 min at 126 degrees C) among esterases reported to date.

Cloning, Molecular↗
PubMed1998

Close correlation between mutations of E2F4 and hMSH3 genes in colorectal cancers with microsatellite instability.

Defects in mismatch repair function can lead to the microsatellite instability (MI+; replication error) phenotype in certain human cancers. We previously reported that MI+ tumor-specific repeat number alteration at 13 consecutive trinucleotide (CAG) repeats within a coding exon of the E2F4 gene is a possible target of the defective repair pathway. Additional investigations revealed that E2F4 mutations are common (11 of 17 cases, 65%, mostly deletions) in a subset of human colorectal cancers with extensive MI+ phenotype, with respect to the proportion of loci affected and that most of these E2F4-mutated tumors (9 of 11, 82%) were accompanied by frameshift mutations in a polyadenine stretch within the seventh exon of the hMSH3 gene, a known mismatch repair gene that is responsible for repair of mismatch loops of two to four nucleotides. However, neither of these mutations was detected in 15 tumors with a lower incidence of MI+ loci. Similar repeat number alterations were less frequent in CAG repeats from other genes in all of the MI+ tumors we examined. These results indicate the presence of a novel cascade of mutational events that may be involved in acquisition of the malignant phenotype of human colorectal cancers with genetic instability.

Colorectal Neoplasms↗
PubMed1998

Identification of a novel apoptosis-inducing factor derived from leukemic cells: endothelial interleukin-8, but not monocyte-derived, induces apoptosis in leukemic cells.

The human myelogenous leukemia cell line HL-60, treated with phorbol 12, 13-dibutyrate (PDBu), produces apoptosis-inducing factors (AIFs) in leukemic cells. We have purified AIF against leukemic cell line K562 as target cells, and N-terminal amino acid sequencing analysis revealed that this purified protein is identical to endothelial cell-derived interleukin-8 ([(Ala)-IL-8]77). In Western blot analysis of supernatants of PDBu-treated HL-60 cells, only [(Ala)-IL-8]77 was detected. Moreover, recombinant human [(Ala)-IL-8]77 induced apoptosis in leukemic cell lines such as K562, HL-60, KG-1, U937, THP-1 and Jurkat, but monocyte-derived IL-8 ([(Ser)-IL-8]72) did not. Therefore [(Ala)-IL-8]77 plays an important role in inducing apoptosis against leukemic cells and may lead to a new therapy for leukemia.

Apoptosis↗
PubMed1998

Ligand-inducible retinoid X receptor-mediated protein: DNA interactions in the retinoic acid receptor beta2 gene promoter in vivo.

Retinoid X receptors (RXRs) are recently characterized transcription factors that are members of the nuclear hormone receptor superfamily. However, it is not known whether the endogenous RXR complex requires its ligand for access to its hormone response element (HRE) of a target gene in vivo. Hence, dimethyl sulfate-based genomic footprinting was carried out to examine occupancy of HREs in the retinoic acid (RA) receptor beta2 (RARbeta2) gene promoter in the murine melanoma cell line S91 cultured in the absence or presence of T3, all-trans-RA (atRA), or CD2624, an RXR-selective retinoid. No footprint was observed at the RA-response element (betaRARE) in the absence of ligands. However, a footprint was detected at the betaRARE and other cis-acting elements after a 6 h incubation with CD2624 and atRA. Interestingly, only the betaRARE was footprinted after 60 min incubation with CD2624. These results suggest that the endogenous RXR complex can interact with an HRE of a target gene in the presence of ligand, and subsequently may initiate additional interactions between DNA and other transcription factors.

Animals↗
PubMed1998

Identification and characterization of a novel protein interacting with Ral-binding protein 1, a putative effector protein of Ral.

Ral-binding protein 1 (RalBP1) is a putative effector protein of Ral and exhibits a GTPase activating activity for Rac and CDC42. To clarify the function of RalBP1, we isolated a novel protein that interacts with RalBP1 by yeast two-hybrid screening and designated it POB1 (partner of RalBP1). POB1 consists of 521 amino acids, shares a homology with Eps15, which has been identified as an epidermal growth factor (EGF) receptor substrate, and has two proline-rich motifs. The POB1 mRNA was expressed in cerebrum, cerebellum, lung, kidney, and testis. POB1 interacted with RalBP1 in COS cells and the C-terminal region of POB1 was responsible for this interaction. The binding domain of RalBP1 to POB1 was distinct from its binding domain to Ral. Ral and POB1 simultaneously interacted with RalBP1 in COS cells. The binding of POB1 to RalBP1 did not affect the GTPase activating activity of RalBP1. Furthermore, POB1 bound to Grb2 but not to Nck or Crk. POB1 was tyrosine-phosphorylated in COS cells upon stimulation with EGF and made a complex with EGF receptor. These results suggest that RalBP1 makes a complex with POB1 and that this complex may provide a link between tyrosine kinase, Src homology 3 (SH3)-containing protein, and Ral.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Primary structure and functional expression of a novel non-selective cation channel.

A non-selective cation channel is believed to play important roles in various tissues. A novel complementary DNA encoding non-selective cation channel was isolated from MIN6, a mouse insulin secreting beta-cell line. This channel (mNSC1) conducts predominantly monovalent cations in Xenopus oocytes and is selective for cations over anions (PK/PCl = 10). The current was completely blocked by lanthanum and niflumate. The mNSC1 of 423 amino acids contains a characteristic leucine repeat and unique membrane topology. The messenger RNA of this channel are abundant in the brain, heart, and lung. We may therefore conclude that studies with this channel will provide important information for understanding physiological functions of the excitable cells as well as non-excitable epithelia.

Amino Acid Sequence↗
PubMed1998

Expression of arthritis-causing HLA-B27 on Hela cells promotes induction of c-fos in response to in vitro invasion by Salmonella typhimurium.

HLA-B27 confers a very strong genetic predisposition to development of a reactive arthritis after infection by bacteria such as Salmonella typhimurium. This study examines the role of HLA-B27 in the initiation of the earliest host activities after exposure to Salmonella, namely activation of the immediate early genes in the epithelial cells. Our major finding is that in Hela cells, the expression of c-fos was induced by Salmonella invasion only when the cells expressed the transfected HLA-B27 gene, but not the HLA-A1 gene or a truncated HLA-B27 gene lacking the exons encoding the cytoplasmic domain. C-fos is potentially capable of complexing with members of the c-jun family to become the AP-1 transcription complex. Parallel to c-fos expression, we found that only with the HLA-B27 transfectant was there expression of AP-1. AP-1 potentially controls the expression of a large number of genes. On screening a panel of proinflammatory molecules, we found that Salmonella invasion induced expression of monocyte chemoattractant protein-1 in the HLA-B27 cells. Since each of these separate positive findings belong to the same cascade of events after cell activation, together they reinforce the hypothesis that HLA-B27 plays a modulatory role in the early signal transduction events induced by Salmonella invasion. This hypothesis adds another item to the list of allele-specific activities carried out by HLA class I molecules. If similar activation also occurs in the joints, it may play a major role in arthritis.

Arthritis↗
PubMed1998

Renal hemodynamics in rats with cadmium-induced nephropathy.

Glomerular filtration rate (GFR) is known to decline in patients with cadmium (Cd)-induced nephropathy. However renal hemodynamics in Cd-induced nephropathy remain unknown. We investigated renal hemodynamics in experimental Cd-induced nephropathy. Male Sprague-Dawley rats were given 0.18 mg/rat of cadmium chloride i.p. three times a week for 3 and 16 months. Age-matched control rats were given physiological saline. Mean arterial pressures after 3 and 16 months were identical among the groups. In comparison with age-matched control rats, significant decreases in GFR associated with a significantly lower filtration fraction (FF) were demonstrated in both groups of Cd-treated rats, but the changes were more prominent in the 16-month Cd-treated rats. Renal plasma flow was significantly decreased in the 3-month Cd-treated rats whereas it was preserved in the 16-month Cd-treated rats because of anemia. Urinary sodium excretions in both groups of Cd-treated rats were significantly greater than those in the respective control rats. On light microscopic examination, only mild degeneration of tubular cells and interstitial edema in limited areas of the proximal tubules were observed in the 3-month Cd-treated rats. In the 16-month Cd-treated rats multifocal tubular atrophy and interstitial fibrosis in the outer cortex were noted. Electron microscopic examinations revealed conspicuous degenerative changes in the proximal tubular epithelial cells, diffuse thickening of glomerular basement membranes, and foot process fusions in 16-month Cd-treated rats. These data suggested that the decline in GFR in the Cd-treated rats resulted mainly from the decline in FF, which might be functional rather than structural in origin and might be associated with proximal tubular dysfunctions.

Animals↗
PubMed1998

Safe pleural contraction employing a new tip for electrosurgical units. An ex vivo experiment.

BACKGROUND: Certain pulmonary lesions are treated by lung tissue contraction induced by heat administered by laser or electrosurgical unit (ES). ESs are comparatively less expensive, less complicated and more ubiquitous than a lasers but with their conventional tip carries the a risk of damaging the pleura. We developed a large ball tip (M-tip) for ES and evaluated its effect on the pleura in comparison with that of Nd:YAG laser in ex vivo lung. METHOD: We employed lobes obtained through surgical resection. Using the Nd:YAG laser, the lung was irradiated for 2 seconds at levels of 5, 10 and 20 watts (10, 20 and 40 Joules). Using the M-tip ES, the pleura received treatment at levels of 10, 20 and 40 watts for 2 seconds (20, 40 and 80 Joules) in spray coagulation mode. Upon completion of these procedures, 144 tissue specimens obtained from 24 lobes were examined under light microscopy. RESULTS: Upon the application of Nd:YAG at 20 Joules, 22 (92%) of 24 visceral pleura demonstrated amorphous degeneration. With the application of ES at 40 Joules watts, 24 (100%) samples examined demonstrated amorphous degeneration (P = 0.47). Of the samples where pleural destruction was evident (Nd:YAG; 40 Joules, ES; 80 Joules), an accompanying air leak pattern (pleural destruction associated with slight parenchymal contraction) was observed in 5 (21%) of the samples treated with Nd:YAG and in 10 (42%) of those treated with the M-tip ES (p = 0.12). CONCLUSION: The M-tip ES induced proper contraction of the pleura with relatively little destructive damage to the pleura at 40 Joules. Accordingly, it may be possible to induce pleural contraction using this new device with the same degree of safely that the Nd:YAG laser provides.

Aged↗
PubMed1998

Variation in the ratio of respirable particulates over inhalable particulates by type of dust workplace.

OBJECTIVE: The aim of the present study was to clarify the quantitative relationship between respirable particulates and inhalable particulates in various dust workplaces. METHODS: Both respirable particulate and inhalable particulate concentrations were measured in 1644 dust workplaces by means of elutriation, and the ratio of respirable particulate mass over that of inhalable particulate (R/I ratio) was calculated for each workplace. RESULTS: Statistical analyses showed that the R/I ratio varied substantially, depending on the type of dust work. The ratio was highest in welding workplaces (mean +/- SD: 53 +/- 19%) and lowest in foundries (23 +/- 16%); the former value suggests that respirable particulate exposure may be underestimated in substantial parts of welding work when only the occupational exposure limit for inhalable particulates is taken for compliance testing. CONCLUSIONS: Simple compliance with the limit for inhalable particulates is not sufficient, and the limit for respirable particulates should also be simultaneously cleared.

Dust↗