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Biomedical subjects

N Watanabe

Publications and source records attributed to N Watanabe.

At least 253 records · Page 14Linked to original sources
PubMed1999

Effect of edetate calcium disodium on yttrium-90 activity in bone of mice.

The kinetics of Yttrium-90 (Y-90) in bone of mice was investigated in combination with edetate calcium disodium (CaNa2EDTA). One group of mice were intraperitoneally administered 37.5 mg/kg CaNa2EDTA or 0.9% NaCl as a control at 1, 22, 34, 46, 58, 70, 82, 94, 154 and 166 h after injection of Y-90 acetate (post-administration), and the biodistribution was studied at 3, 24, 72, 120 and 168 h postinjection of Y-90 acetate. No difference between the post-CaNa2EDTA-treated mice and the control was demonstrated in the radioactivity in the bone. A decrease in radioactivity in the liver and kidneys was accelerated, and the radioactivity was lower than the control at 120 h postinjection. The other group of mice were also given the same dose of chelator at 12 h and 1 h preinjection of Y-90 acetate and at 1, 22, 34, 46, 58, 70, 82, 94, 154 and 166 h after injection of Y-90 acetate (pre- and post-administration), the radioactivity in bone at 3 h postinjection was significantly lower than in the control (24.4 +/- 3.92% ID/g vs. 31.7 +/- 2.26% ID/g, p < 0.05), but the decrease was not sequential. A significant reduction in radioactivity in the blood, kidneys and liver was demonstrated at 3 h, 72 h and 72 h postinjection. In conclusion, the CaNa2EDTA with the administration schedule employed here cannot chelate the Y-90 from bone but the free Y-90 before deposition into bone.

Animals↗
PubMed1999

Role of diffusion-weighted echo-planar MRI in distinguishing between brain brain abscess and tumour: a preliminary report.

Our purpose was to evaluate diffusion-weighted (DW) echo-planar MRI in differentiating between brain abscess and tumour. We examined two patients with surgically confirmed pyogenic brain abscess and 18 with metastatic brain tumours or high-grade glioma, using a 1.5 T system. The apparent diffusion coefficient (ADC) of each necrotic or solid contrast-enhancing lesion was measured with two different b values (20 and 1200 s/mm2). All capsule-stage brain abscesses (4 lesions) and zones of cerebritis (2 lesions) were identified on high-b-value DWI as markedly high-signal areas of decreased ADC (range, 0.58-0.70 [(10-3 mm2/s; mean, 0.63)]). All cystic or necrotic portions of brain tumours (14 lesions) were identified on high-b-value DWI as low-signal areas of increased ADC (range, 2.20-3.20 [(10-3 mm2/s; mean, 2.70)]). Solid, contrast-enhancing portions of brain tumours (19 lesions) were identified on high-b-value DWI as high-signal areas of sightly decreased or increased ADC (range, 0.77-1.29 [(10-3 mm2/s; mean, 0.94)]). Our preliminary results indicate that DW echo-planar MRI be used for distinguishing between brain abscess and tumour.

Aged↗
PubMed1999

Efficacy, toxicity and mode of interaction of combination radioimmunotherapy with 5-fluorouracil in colon cancer xenografts.

PURPOSE: The feasibility of radioimmunotherapy (RAIT) combined with 5-fluorouracil (5-FU) was examined in colon cancer xenografts. The mode of interaction of the two treatments was also investigated. METHODS: Mice bearing human colon cancer were treated with a combination of 4.63 MBq (L-RAIT) or 9.25 MBq (H-RAIT) (131)I-A7, an IgG1 against 45-kDa glycoprotein, and 5-FU at a dose of 30 mg kg(-1)day(-1) for 5 days. Myelotoxicity was monitored by blood cell counts and intestinal toxicity was assessed by the dosimetry. The results were compared with those of a single-modality therapy. RESULTS: The combination of 5-FU with H-RAIT enhanced the antitumor effect, improving the tumor quadrupling time from 25.3 +/- 9.59 days to 31.3 +/- 8.32 days (P < 0.05) and inducing tumor regression in 7 out of 10 mice, compared to 3 out of 9 mice treated with H-RAIT alone. The efficacy of L-RAIT was also improved by the combination. Analysis of the dose/response relationship showed an additive interaction of the two modalities. The combination of 5-FU with RAIT induced slightly more severe myelotoxicity than a single-modality treatment, but blood cell counts recovered similarly. Dose estimation suggested that RAIT does not increase the intestinal toxicity of 5-FU. CONCLUSION: The combination of two modalities would be feasible for the treatment of colon cancer, increasing antitumor effect with minor effect on toxicity.

Animals↗
PubMed1999

A method of tracking donor cells after simulated autologous transplantation: a study using synovial cells of transgenic rats.

A transgenic rat was used as a transplantation donor to simulate autologous transplantation. The sex-matched transplantation between a female transgenic and a wild-type rat can theoretically be regarded as an autologous transplantation due to the genetic agreement of these rats except for the non-protein-producing transgenes. Transgene-containing synovial cells were tracked in the joint using this autologous transplantation model. The transgenes in the donor synovial cells were detected using in situ hybridization (ISH), while mitotic activities were simultaneously examined by immunodetection of 5-bromo-2'-deoxyuridine (BrdU). A defect was generated in the knee joint capsule of a Fischer 344 (wild-type) rat. The synovium of a transgenic rat was sutured to the defect of the wild-type rat in group 1 and was allowed to free float in the joint in group 2. A large number of BrdU-labeled, transgene-containing synovial cells were detected in both groups at 3 days. The number of these cells then decreased, but they could still be identified even at 4 weeks after autologous transplantation. These results indicated that transplanted synovial cells were viable in the joint for at least 4 weeks. Furthermore, the transgenic rat was shown to be an effective animal model for distinguishing the extrinsic from the intrinsic cells in the cellular intermixed tissues in vivo. The combined method of ISH for detecting transgene-containing cells and the immunohistochemistry of BrdU for detecting proliferating cells was also shown to be effective for tracking the viability of extrinsic cells after autologous transplantation.

Animals↗
PubMed1999

Three point mutations of human butyrylcholinesterase in a Japanese family and the alterations of three-dimensional structure.

Three different mutations at codons 330 (TTA to ATA), 365 (GGA to AGA) and 515 (CGT to TGT) of human butyrylcholinesterase (hBChE) were identified in a Japanese family. We correlated alterations in in the patient's hBChE activity with possible structural alterations in the three-dimensional structure of hBChE caused by the point mutations. This study was performed using the published computer-generated three-dimensional structure of hBChE based on the structure of acetylcholinesterase. The amino acid substitution at L330I was adjacent to hydrophobic residues that form the channel domain of the active center. This side chain faced the side opposite the active center. The amino acid substitution at G365R was located at the position most remote from the active center, and this substitution site was exposed to the surface of the BChE protein. Alpha-helical structure was present to the active center, and the guanidyl residue of native Arg 515 was hydrogen-bonded to the carboxyl group of Asp 395 in the alpha-helix. These point mutations may cause steric effects on the present patient's hBChE activity. This is the first report of three-dimensional structural analysis performed on the L330I, G365R, and R515C mutations of hBChE.

Adult↗
PubMed1999

Antimony in municipal waste.

Antimony content in municipal waste was studied. Sampled municipal waste was dried, crushed and analyzed. Antimony determinations were performed by Kjeldahl decomposition--batch hydride generation spectrometry and neutron activation analysis. Overall content of antimony in waste was 40-50 g/t raw waste. It was estimated than 20% of the annual production of antimony was discarded as municipal waste in Japan. Leaching of antimony from antimony-added materials may occur, because "small tips" involved considerable amounts of antimony.

Antimony↗
PubMed1999

Experimental investigation of I-123 iodoamphetamine in the detection of lung cancer.

Experimentally we investigated the detection of lung cancer with N-isopropyl-p-I-123-iodoamphetamine (I-123 IMP). Various tumors including Lewis lung cancer were used as tumor models. Serial images were obtained. Biodistribution of Lewis lung cancer was performed. In Lewis lung cancer good visualization as in B-16 melanoma and high tumor accumulation were found with IMP. In conclusion, due to its greater accumulation almost equivalent to that in melanotic melanoma, I-123 IMP may have a role in the detection of lung cancer.

Animals↗
PubMed1999

Disappearance of hypointense multiple sclerotic lesions on FLAIR MRI.

A child is presented who displayed hypointense multiple sclerotic lesions on fluid-attenuated inversion recovery sequences by magnetic resonance imaging, with the possible pathologic tissue changes of these hypointense lesions evaluated. The magnetic resonance imaging results in this patient demonstrated the disappearance of low-signal lesions on fluid-attenuated inversion recovery in multiple sclerosis, and the improvement of this patient's condition was likely compatible with sequential magnetic resonance imaging findings. Some hypointense lesions in the supratentorial white matter that appear on fluid-attenuated inversion recovery images in multiple sclerosis patients may include reversible brain lesions, suggesting extracellular fluid collection not accompanied by axonal loss or gliosis.

Adolescent↗
PubMed1999

Labeling of phosphorothioate antisense oligonucleotides with yttrium-90.

Novel yttrium-90 (90Y)-labeled phosphorothioate antisense oligonucleotides were designed as a potential targeted radionuclide therapeutic agent for malignant tumors. A 15-mer phosphorothioate antisense oligonucleotide, which was complementary to the translation start region of the N-myc oncogene mRNA, was conjugated with isothiocyanobenzyl ethylenediamine tetraacetic acid (SCN-Bn-EDTA), via a C-5-substituted deoxyuridine that had replaced a thymine in the oligonucleotide, and was then labeled with 90Y-acetate. Following purification, the radiochemical purity of the 90-Y-Bn-EDTA-phosphorothioate antisense oligonucleotides was estimated by 2.0% agarose gel electrophoresis, and the specific hybridization of 90Y-Bn-EDTA-phosphorothioate antisense oligonucleotide to a phosphorodiester sense oligonucleotide was investigated by 20% polyacrylamide gel electrophoresis in a cell-free system. Radiochemical purity was 98.7 +/- 0.4% at 72 h after labeling and 90.3 +/- 0.9% after 72-h incubation with human normal serum. The 90Y-Bn-EDTA-phosphorothioate antisense oligonucleotide hybridized specifically to a complementary phosphorodiester sense oligonucleotide. In conclusion, phosphorothioate antisense oligonucleotides can be labeled stably with 90Y using SCN-Bn-EDTA without loss of hybridization properties.

Blood Physiological Phenomena↗
PubMed1999

Localization of indium-111 in human malignant tumor xenografts and control by chelators.

The kinetics of soluble indium-111 ((111)In) in human malignant tumor xenografts and cells was investigated in combination with chelators. Firstly, without chelator, the kinetics of (111)In-chloride was investigated in vitro and in vivo using four human malignant neuroblastoma SK-N-MC, pulmonary papillary adenocarcinoma NCI-H441, pulmonary squamous cell carcinoma PC 9, and colon adenocarcinoma LS 180 cells and xenografts. (111)In was incorporated into tumor cells in vitro to a maximum level during a 60-min incubation. A maximum level of radioactivity was demonstrated in vivo in four human malignant tumors xenografted into nude mice at 24 h postinjection of (111)In-chloride. Secondly, the effect of edetate calcium disodium (CaNa2EDTA) on radioactivity in (111)In-labeled tumors xenografts and cells was studied in vitro and in vivo. CaNa2EDTA significantly reduced (111)In-activity from the labeled tumor xenografts, whereas it had no affect on the radioactivity in the labeled cells. Thirdly, the effect of CaNa2EDTA on radioactivity in human malignant tumors xenografted into nude mice injected with (111)In-chloride was investigated. In one group of mice CaNa2EDTA administered intraperitoneally at 1, 22, 34, 46, 58, and 70 h after injection of (111)In-chloride (postadministration), the localization of (111)In at the tumors was significantly decreased at 72 h compared with the control in all four tumor types. In the other group of mice, CaNa2EDTA administered intraperitoneally at 12 and 1 h before injection of (111)In-chloride and 1, 22, 34, 46, 58, and 70 h postinjection (pre- and postadministration), the radioactivity of tumors was also significantly decreased at 72 h, and the reduction was greater than that with use of postadministration. In a comparative study, CaNa3DTPA had a more powerful effect than CaNa2EDTA. In conclusion, (111)In-activity in tumors consists of intracellular and extracellular components, and the extracellular (111)In may be cleared by chelators. Pre- and postadministration of CaNa3DTPA could remove (111)In-nonspecific localization in tumors when (111)In is released from the radiolabeled agents.

Animals↗
PubMed1999

Yttrium-90-labeled human macroaggregated albumin for internal radiotherapy: combined use with DTPA.

The aim of this study was to investigate the possibility of yttrium-90-labeled human macroaggregated albumin (90Y-MAA) as an internal radiotherapeutic agent for whole-lung irradiation in combination with diethylenetriamine pentaacetic acid (DTPA). The influence of trisodium calcium DTPA (CaNa3DTPA) on the radioactivity of 90Y-MAA in serum was investigated in vitro. The effect of CaNa3DTPA on the biodistribution of radioactivity in normal mice intraveneously injected with 90Y-MAA was examined. CaNa3DTPA could deprive in vitro radioactivity of 90Y-MAA in 48-h incubation. Most of the radioactivity (>90% injected dose per lung) was observed at murine lung after injection of 90Y-MAA. Pulmonary radioactivity was cleared within 72 h postinjection, whereas the radioactivities in the bone, liver, kidneys, and spleen increased with a peak at 48 h. CaNa3DTPA-treatment reduced the in vivo radioactivities in bone, liver, and kidneys without influence on the radioactivity of lung. In conclusion, combined use of CaNa3DTPA enables 90Y-MAA to be used as a radiopharmaceutical for internal irradiation against whole lung.

Albumins↗
PubMed1999

Analysis of genomic diversity within the Xr-region of the protein A gene in clinical isolates of Staphylococcus aureus.

Protein A of Staphylococcus aureus contains a polymorphic Xr-region characterized by a tandem repeat of eight amino acid units. In this study, the diversity of genes encoding the repeat regions and their relatedness among S. aureus strains was analyzed. Ten different protein-A types characterized by repeat numbers 4-13 were identified in a total of 293 clinical isolates. The protein-A type with 10 repeat units (10 repeats) in the Xr-region was most frequently detected in methicillin-resistant S. aureus, whereas the majority of methicillin-susceptible strains were distributed almost evenly into protein-A types with 7-11 repeats. Strains that belonged to a single coagulase type were classified into multiple protein-A types, e.g. strains with the common coagulase types II and VII were differentiated into 7 and 8 protein-A types, respectively. Nucleotide sequence analysis of the Xr-region of 42 representative strains revealed the presence of 37 different genotypes (spa types), which were constituted by a combination of several of 24 different repeat unit genotypes. Based on the similarity in arrangement of repeat unit genotypes, 34 strains with different repeat numbers were classified into 5 genetic clusters (C1-C5). The clusters C1, C2 and C3 consisted exclusively of strains with identical coagulase types II, III, and IV, respectively. These findings suggested that the protein-A gene of S. aureus has evolved from a common ancestral clone in individual clusters independently.

Amino Acid Sequence↗
PubMed1999

Mechanism of apoptosis induced by a lysosomotropic agent, L-Leucyl-L-Leucine methyl ester.

Lysosomes are fundamental for cell growth, and thus inhibition of the lysosomal function often leads to cell death. L-Leucyl-L-leucine methyl ester (LeuLeuOMe) is a lysosomotropic agent that induces apoptosis of certain immune cells. LeuLeuOMe is taken up through receptor-mediated endocytosis, and then converted into (LeuLeu)n-OMe (n>3) by dipeptidyl peptidase I (DPPI) in lysosomes, which reportedly causes rupture of the lysosomes and DNA fragmentation. In this study we examined how lysosomal damage causes DNA fragmentation in LeuLeuOMe-treated HL-60 cells. When acridine orange was employed to monitor lysosomal membrane integrity, orange or red granular fluorescence was seen in normal cells. In contrast, LeuLeuOMe-treated cells showed orange, yellow or green cellular fluorescence all over the cytoplasm, suggesting that LeuLeuOMe induced a loss of lysosomal membrane integrity. The loss was inhibited by a DPPI inhibitor, GlyPheCHN2 (GFCHN2), but not by a caspase-3 inhibitor, Ac-DEVD-CHO, indicating that a condensation product was responsible for the loss. LeuLeuOMe also induced the activation of caspase-3-like protease and DNA fragmentation, both of which were inhibited by either GFCHN2 or Ac-DEVD-CHO. Therefore, the activation of caspase-3-like protease links the loss of lysosomal membrane integrity to DNA fragmentation during apoptosis induced by LeuLeuOMe.

Journal Article↗
PubMed1999

Redox regulation of interleukin-8 expression in MKN28 cells.

Recent evidence suggests a role of reactive oxygen intermediates (ROI) in intracellular signaling and regulation of gene expression. We examined whether expression of interleukin-8 (IL-8), a key cytokine in the inflammatory responses of gastric epithelial cells, is sensitive to antioxidants and oxidative stress. IL-8 secretion was quantified by IL-8 enzyme-linked immunosorbent assay, and IL-8 mRNA expression was determined by northern blot analysis. Electrophoretic mobility shift assay was performed to detect the transcription factor, nuclear factor kappaB (NF-kappaB). N-Acetylcysteine (NAC) or dimethylsulfoxide inhibited IL-8 expression induced by tumor necrosis factor-alpha (TNF-alpha) or interleukin-1beta (IL-1beta). Externally applied H2O2 significantly up-regulated IL-8 expression. TNF-alpha-induced activation of NF-kappaB activity was suppressed by NAC, and H2O2 caused significant activation of NF-kappaB. Since ROI production is increased in the inflamed gastric mucosa, for example, in H. pylori-associated gastritis, the present results suggest that ROI may be an important modulator of IL-8 expression in gastric mucosal cells.

Acetylcysteine↗
PubMed1999

Cooperation between mDia1 and ROCK in Rho-induced actin reorganization.

The small GTPase Rho induces the formation of actin stress fibres and mediates the formation of diverse actin structures. However, it remains unclear how Rho regulates its effectors to elicit such functions. Here we show that GTP-bound Rho activates its effector mDia1 by disrupting mDia1's intramolecular interactions. Active mDia1 induces the formation of thin actin stress fibres, which are disorganized in the absence of activity of the Rho-associated kinase ROCK. Moreover, active mDia1 transforms ROCK-induced condensed actin fibres into structures reminiscent of Rho-induced stress fibres. Thus mDia1 and ROCK work concurrently during Rho-induced stress-fibre formation. Intriguingly, mDia1 and ROCK, depending on the balance of the two activities, induce actin fibres of various thicknesses and densities. Thus Rho may induce the formation of different actin structures affected by the balance between mDia1 and ROCK signalling.

Actins↗
PubMed1999

Neurological complications after stem cell transplantation in childhood.

We analyzed the incidence of neurological complications in 77 patients receiving stem cell transplantation (SCT), and 12 patients (15.8%) had the following symptoms: convulsions, intracranial hemorrhage, and leukoencephalopathy. Although statistically not significant, neurological complications were seen more frequently in patients after allogeneic transplantation, and in those with acute graft-versus-host disease (GVHD) exceeding grade II. The most significant risk factor for neurological complications was identified as unrelated donor allogenic transplantation (P = 0.016). Complications were categorized into three groups, based on time of onset and symptoms: (1) convulsions during the conditioning period, (2) intracranial hemorrhage during the period of granulocyte recovery, and (3) leukoencephalopathy at around 2 months after SCT. We propose awareness of the risks of neurological complications in each period after SCT so that immediate and effective treatment of patients can be instigated.

Adolescent↗