[Physiologic study of optokinetic after nystagmus].
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Electronystagmography↗
Biomedical subjects
S Kojima
Publications and source records attributed to S Kojima.
Comparative effects of chelating agents on pulmonary toxicity of systemic nickel in mice.
N-Benzyl-D-glucaminedithiocarbamate (BGD), diethyldithiocarbamate (DDTC), dihydroxyethyldithiocarbamate (DHED), trans-1,2-cyclohexanediamine N,N,N',N'-tetraacetic acid (CDTA) and meso-2,3-dimercaptosuccinic acid (DMSA) were studied for their protective effects against the pulmonary toxicity in mice induced by acute exposure to nickel. Nickel injection increased lipid peroxidation, lactate dehydrogenase (LDH) activity and the concentrations of protein, phospholipids (PL) and essential metals such as Ca, Fe and Zn and decreased the reduced glutathione (GSH) concentration and alkaline phosphatase (ALP) activity in the lungs. At 30 min after Ni treatment, DMSA, BGD and DDTC effectively depressed Ni concentration in the lungs. At 24 h after Ni treatment, DMSA and BGD were effective in mobilizing Ni from the lungs. Both DMSA and BGD significantly prevented increases in lipid peroxidation and in the concentrations of PL, Ca, Fe and Zn, and decreases in GSH concentration and ALP activity in the lungs of mice caused by Ni injection. Treatment with DMSA or BGD was more effective than that with other chelating agents in decreasing the pulmonary Ni concentration and preventing other changes caused by acute exposure to Ni, resulting in effective protection against Ni-induced pulmonary damage.
Alkaline Phosphatase↗
Immunohistologic distribution of basement membrane in oral squamous cell carcinoma.
The distribution pattern of the basement membrane (BM) around tumor cells was determined in 72 oral squamous cell carcinomas by immunohistochemical staining with antibodies against human type IV collagen, laminin, and heparan sulfate proteoglycan. An intact continuous BM was found in 29 cases, whereas partial or widespread loss of the BM was detected in the other 43 cases (59.7%). Statistical analysis showed that the degree of BM loss was correlated with the degree of differentiation of tumor cells, but not with tumor size, and, most significantly, with the mode of cancer invasion and the incidence of lymph node metastasis. Carcinoma with a well-defined tumor-stromal boundary generally expressed an intact continuous BM. In contrast, the majority of diffusely invasive carcinomas lacked a continuous BM. Carcinomas with a widespread loss of BM structures showed a high frequency of regional lymph node metastasis (16 of 18 cases, 88.9%).
Basement Membrane↗
Comparative effects of diethyldithiocarbamate and N-benzyl-D-glucamine dithiocarbamate on cis-diamminedichloroplatinum-induced toxicity in kidney and gastrointestinal tract in rats.
Sodium diethyldithiocarbamate (DDTC) and sodium N-benzyl-D-glucamine dithiocarbamate (BGD) were compared for their protective effects against cis-diamminedichloroplatinum (DDP)-induced toxicity in kidney and gastrointestinal tract in rats. Rats were injected i.p. with the dithiocarbamates (2.0 mmol kg-1) immediately or 1 h after i.v. injection of DDP (20 mumol kg1). Treatment with BGD immediately or at 1 h after DDP injection effectively prevented the nephrotoxicity of DDP, but administration of DDTC immediately or 1 h after DDP afforded little protection. N-Benzyl-D-glucamine dithiocarbamte significantly reversed the reduction in maltase, sucrase and aminopeptidase activities of jejunal mucosa of rats treated with DDP, whereas treatment with DDTC concurrent with DDP could not reverse the reduction in disaccharidase activity following DDP injection. The platinum concentrations in liver and kidney were significantly decreased by treatment with BGD and DDTC. The treatment with DDTC at 1 h after DDP was more effective on the reduction of platinum concentrations in these tissues than that immediately after DDP. There was no difference between the renal and hepatic concentrations of platinum in two time intervals of BGD. The pharmacokinetic studies indicated that DDTC is more rapidly metabolized than BGD, resulting in larger total clearance and elimination rate constant values. These results reveal that the administration of BGD immediately and at 1 h after DDP can protect against the renal and gastrointestinal toxicities caused by DDP, whereas DDTC afforded little protection, and that the time interval between administration of DDP and DDTC greatly influences its protective effect on DDP-induced toxicity, indicating that the chelation therapy of BGD for DDP is superior to that of DDTC.
Animals↗
Solution synthesis of human midkine, a novel heparin-binding neurotrophic factor consisting of 121 amino acid residues with five disulphide bonds.
Human midkine (hMK), a novel heparin-binding neurotrophic factor consisting of 121 amino acid residues with five intramolecular disulphide bonds, was synthesized by solution procedure in order to demonstrate the usefulness of our newly developed solvent system, a mixture of dichloromethane or chloroform and trifluoroethanol. The final protected 121-residue peptide was assembled from two large fully protected intermediates, Boc-(1-59)-OH and H-(60-121)-OBzl, in CHL/TFE(3:1, v/v) using water-soluble carbodiimide in the presence of HOOBt as coupling reagents. After removal of the protecting groups by HF followed by treatment with Hg(OAc)2 in 50% acetic acid, the fully deprotected peptide was subjected to the oxidative folding reaction. The final product was confirmed to have the correct disulphide structure from its tryptic peptide mapping and to possess the same biological activities as those of the natural product. In order to clarify the active region of the hMK molecule, the N-terminal half domains [(1-59) and (60-121)] were also synthesized by the same procedure used for the hMK synthesis. The C-half domain was confirmed to show the full pattern of bioactivities except for the neuronal cell survival activity, while the N-half one showed much less activity in general.
Amino Acid Sequence↗
Identification and determination of urinary metabolites of 2-isopropylnaphthalene in rabbits.
Four unconjugated metabolites, which were produced through the oxidation of the isopropyl chain of 2-isopropylnaphthalene (2-IPN), were isolated from the urine of rabbits receiving 2-IPN orally and identified: 2-(2-naphthyl)propionic acid, 2-(2-naphthyl)-2-propanol, 2-(2-naphthyl)-1,2-propanediol, and 2-(2-naphthyl)-2-hydroxypropionic acid, together with a small amount of the unchanged compound. Further, the unconjugated metabolites, which were produced through the oxidation of the naphthalene ring, were isolated and identified: 2-isopropylnaphthols and 2-isopropyl-5,6 (or 7,8)-dihydronaphthalene-5,6 (or 7,8)-diol. The identification of these metabolites was made by means of TLC, GLC, MS, IR, GC/MS, and FT-NMR. The presence of glucuronides of metabolites B, C, D, F, and H was also suggested by TLC and GLC of the extract obtained after hydrolysis by beta-glucuronidase. In addition, quantitative determination of the metabolites indicated that the total urinary excretion of the metabolites except 2-isopropylnaphthols in 24 hr after administration was about 29% of the dose.
Administration, Oral↗
Galectins-1 and -3 and their ligands in tumor biology. Non-uniform properties in cell-surface presentation and modulation of adhesion to matrix glycoproteins for various tumor cell lines, in biodistribution of free and liposome-bound galectins and in their expression by breast and colorectal carcinomas with/without metastatic propensity.
Protein (lectin)-carbohydrate (cellular glycoconjugate) recognition is operative in biochemical information transfer. Galectins constitute a family of endogenous galactoside-binding lectins with conserved features in the binding site. The members of this lectin category are assumed to be involved in cell adhesion and growth regulation. To assess to what extent the different modes of binding-site presentation and/or carbohydrate fine-specificities will affect aspects of galectin behavior, homodimeric cross-linking galectin-1 and monomeric chimeric galectin-3, with its collagenase-sensitive stalk linked to the carbohydrate-recognition domain, were investigated. Cell-surface expression of the two galectins and accessible galectin-binding sites on various tumor cell lines was ascertained by FACScan analysis. In particular, ligand accessibility for the two galectins differed for the tested cell line types. Binding of tumor cells to laminin and plasma or placental fibronectin was generally reduced by treatment of cells or matrix with galectins. Galectin-3 was more efficient than galectin 1 at impairing laminin's potency as matrix. Cell binding of galectin-1, on the other hand, proved on average more effective for blocking cell association to fibronectins after its preincubation with cell suspensions. Differences were also apparent in the biodistribution of the galectins, where an avian homolog of galectin- served as the control to distinguish effects of spatial and sugar-binding features. Histopathological analysis of lymph-node-negative and -positive breast and colorectal carcinomas (n = 180 including 60 metastatic lesions) indicated a correlation of either increased galectin-1 binding and reduced galectin-3 expression or reduced binding of both galectins with the occurrence of lymph node lesions. Together with data on the heparin-binding lectin, revealing reduced expression to be associated with a positive lymph-node status in the breast cancer group, these results can be interpreted to reflect cell-type-dependent requirements of galectin ligand presentation during the metastatic cascade. By introducing mammalian lectins to lectin-histochemical studies, the detection of quantitative differences in glycosylation brings an understanding of its cell biological significance one step closer.
Adenocarcinoma↗
Diagnosis of malaria using a plate hybridization method for the detection of polymerase chain reaction products.
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Animals↗
cDNA cloning for mitochondrial cytochrome c and its adult-specific isoform from Ascaris suum.
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Amino Acid Sequence↗
Quantitative analysis of interleukin-6 in vitreous from patients with proliferative vitreoretinal diseases.
PURPOSE: To explore immunological mechanisms in the pathogenesis of proliferative vitreoretinal diseases, we measured the concentration of interleukin-6 in the vitreous body and serum from patients with proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), and premacular fibrosis. To evaluate immunological etiology, interleukin-6 levels in each disease were compared with disease severity. METHODS: Clinical samples were obtained at the beginning of pars plana vitrectomy from 30 eyes of 26 patients with PDR, 12 eyes of 12 patients with PVR, and 10 eyes of 10 patients with premacular fibrosis. Interleukin-6 was quantitated with an enzyme-linked immunosorbent assay. RESULTS: The levels of detectable interleukin-6 in the vitreous specimens ranged from 22.8 to 666.4 pg/mL in the PDR patients and from 28.2 to 416.3 pg/mL in the PVR patients. No interleukin-6 was detected in the vitreous specimens from patients with premacular fibrosis or in any serum samples from patients. Interleukin-6 levels of vitreous specimens from PDR patients were higher than those from PVR patients (P <.02, Mann-Whitney U-test). There was no correlation between clinical severity and interleukin-6 levels in vitreous specimens from either PDR or PVR patients. CONCLUSION: Our results indicated that cell-mediated immunity is involved in the pathogenesis of proliferative vitreoretinal diseases.
Adolescent↗
Monitoring of Plasmodium vivax sensitivity to chloroquine in vitro in Thailand.
The sensitivity of Plasmodium vivax to chloroquine in vitro was investigated in patients admitted to the Bangkok Hospital for Tropical Diseases, Thailand, between September 2001 and May 2002. Of 42 isolates, 34 were successfully tested for parasite sensitivity to chloroquine in vitro; the results showed a significant decrease in sensitivity compared with data published in 1989 and 1995: the IC50 and IC90 were 187.2 and 1217.9 ng/mL blood, respectively, an approximate 4-fold decrease in sensitivity in comparison with other data from the past 2 decades. A number of in vitro tests were performed simultaneously using both WHO microplates and our own laboratory-prepared pre-dosed microplates under the same conditions and there was no significant difference between the results.
Animals↗
Nested polymerase chain reaction for detection of Plasmodium falciparum infection in Malaysia.
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Base Sequence↗
A monoclonal antibody-based dipstick assay for diagnosis of urinary schistosomiasis.
A Schistosoma haematobium species-specific mouse immunoglobulin (Ig) G1 monoclonal antibody (mab) Sh2/15.F that bound a 29 kDa peptide was utilized to develop a membrane-based dipstick enzyme-linked immunosorbent assay for specific diagnosis of urinary schistosomiasis. Strips of polyvinylidene difluoride membrane were wetted with methanol and stored in distilled water. The strips were used to capture urinary antigens which were then revealed by incubation in a mixture of specific mab and peroxidase-conjugated goat anti-mouse IgG. The assay correctly identified 26/30 (87%) of egg-negative control individuals and 53/54 (98%) of parasitologically confirmed cases including all of 6 individuals treated with praziquantel (40 mg/kg) but not cured. Also, the assay detected S. haematobium antigens in the urine of 3 individuals from whom 2 specimens had to be examined microscopically to confirm infection, thus suggesting that the mab detection method may have greater sensitivity than microscopy.
Adolescent↗
Neoglycoproteins with the synthetic complex biantennary nonasaccharide or its alpha 2,3/alpha 2,6-sialylated derivatives: their preparation, assessment of their ligand properties for purified lectins, for tumor cells in vitro, and in tissue sections, and their biodistribution in tumor-bearing mice.
Neoglycoproteins were prepared with chemoenzymatically synthesized complex biantennary N-glycan derivatives the nonreducing ends of which bear typical sequences found in glycoproteins. A chemically obtained biantennary heptasaccharide-azide was reduced and acylated with a 6-aminohexanoyl spacer. Elongation of the deprotected heptasaccharide using glycosyltransferases yielded a biantennary nonasaccharide with terminal galactose residues and two undecasaccharides terminating with alpha 2,6- or alpha 2,3-linked sialic acid. The free amino group of the spacer of these oligosaccharides was converted into an isothiocyanate. Its subsequent coupling to bovine serum albumin gave neoglycoproteins with a yield of 2.4-3.6 glycan chains per carrier molecule. This versatile synthetic pathway allows employment of a wide variety of complex-type glycans, which can be introduced to various test systems in vitro and in vivo to evaluate potential biomedical applications. Solid-phase assays with biotinylated sugar receptors revealed discriminatory binding properties of the three neoglycoproteins, especially for the mistletoe lectin. This direct assay system is preferable to the measurement of inhibitory capacities with respect to model ligands. Ligand type- and cell type-dependent quantitative differences in the binding properties of the probes were detected by FACScan analyses with a panel of tumor cell lines and by monitoring of staining in tissue sections for small cell and non-small-cell lung cancer and mesotheliomas. Biodistribution of iodinated neoglycoproteins in mice gave a prolonged presence of the sialylated probes in serum. Relative to the nonasaccharide, the uptake, especially of the iodinated neoglycoprotein with alpha 2,3-sialylated ligand chains, was clearly elevated in mice for kidneys and Ehrlich tumors. On the basis of the documented feasibility of these applications, it is concluded that the further elaboration of glycan chain variants by the described synthetic approach in combination with the given test panel is warranted to evaluate the potential of complex glycan chain-carrying neoglycoproteins for diagnostic and therapeutic purposes.
Animals↗
131I in milk and rain after Chernobyl.
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Accidents↗
Evaluation of albumin loss during low-density lipoprotein apheresis.
Because the reduced plasma oncotic pressure from hypoproteinemia causes hyperlipidemia, serum albumin levels should be maintained during low-density lipoprotein (LDL) apheresis. The amount of albumin loss was evaluated in seven patients with familial hypercholesterolemia during LDL apheresis in which columns packed with dextran sulfate-cellulose beads were used as a selective adsorbent of LDL. Serum albumin level significantly decreased from 4.3 +/- 0.3 (mean +/- SD) g/dl to 3.6 +/- 0.2 g/dl. The albumin loss was assessed by two different methods: 1) radioimmunoassay of microalbumin content in the discarded fluid, and 2) measurement of changes in plasma albumin reserve. The albumin losses during one apheresis session were 3.7 +/- 2.9 g and 8.3 +/- 5.7 g, respectively, depending upon which of two different methods was used. There was a significant correlation between these two methods (r = 0.84, p less than 0.02). The amount of albumin loss during apheresis was estimated to be between 4.1% and 9.1% of total plasma albumin reserve, and more than half of the decreased serum albumin level appeared to be attributable to dilution due to the electrolyte solution used for priming of the extracorporeal circuit.
Adult↗
Prognostic significance of TEL/AML1 fusion transcript in childhood B-precursor acute lymphoblastic leukemia.
PURPOSE: A retrospective study was conducted to investigate the prognostic significance of TEL/AML1 fusion resulting from a cryptic t(12;21) in Japanese patients with childhood B-precursor acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: Leukemic samples from 144 children with newly diagnosed ALL (104 with CD10-positive B-precursor ALL, 11 with CD10-negative B-precursor ALL, 5 with B-ALL, and 24 with T-ALL) were analyzed by reverse-transcription polymerase chain reaction. RESULTS: The frequency of patients with TEL/AML1 was 16% (23 of 144) and all patients with TEL/AML1 also had CD10-positive B-precursor ALL. TEL/AML1 was not found in any samples from the patients with T-ALL, B-ALL, or CD10-negative B-precursor ALL. Among patients with CD10-positive B-precursor ALL, age, initial white blood cell count, and immunophenotype did not differ with TEL/AML1 positivity, although the patients were predominantly male (p < 0.01). Clinical outcomes of 94 patients treated with recent protocols were analyzed. Five of the 21 (23.8%) patients with TEL/AML1 relapsed and 4 of these relapsed > 24 months after diagnosis. Although the overall 5-year survival rate was better among patients with TEL/AML1 fusion transcript than among those without it (87.3 +/- 8.7% versus 75.9 +/- 5.8%, respectively), the 5-year disease-free survival (DFS) rates of patients with TEL/AML1 fusion transcript and those without it were similar (64.0 +/- 13.5% versus 69.1 +/- 6.3%, respectively). However, for 57 patients treated with the latest intensive protocol, the 4-year DFS rate was much higher for the patients with TEL/AML1 fusion transcript than for those without it (100.0% v.s. 69.6 +/- 8.4%, respectively, p = 0.1472). CONCLUSIONS: This study confirmed that TEL/AML1 gene fusion is the most common genetic event in pediatric ALL in Japan and is restricted to CD10-positive B-precursor ALL. Moreover, it was associated with an improved survival rate among patients treated with intensive therapy. Therefore, these data suggest that the patients with TEL/AML1 may not necessarily be candidates for less aggressive treatment.
Adolescent↗
Clinical significance of "cannibalism" in urinary cytology of bladder cancer.
OBJECTIVE: To investigate the cytologic characteristics and clinical significance of "cannibalism" (cytophagocytosis), a characteristic histologic finding associated with malignancy, found in urinary cytology samples during the diagnosis of bladder cancer. STUDY DESIGN: The subjects were 252 patients with bladder cancer initially treated from 1981 to 1991. For their pretreatment urine samples, membrane filtration was performed to determine the presence and amount of cannibalism, a tumor cell within a tumor cell. The urinary cytologic findings were then correlated with the histologic findings of primary bladder cancer. RESULTS: Only cells from urinary cytology-positive specimens demonstrated cannibalism. The positive rate of cannibalism was significantly higher in grade 3 (25%) than grade 1 (0%) or 2 (8%) superficial papillary cancer (P < .01) and also higher in muscle-invading bladder cancer (57%) than grade 3 superficial papillary cancer (P < .01). The rate did not differ significantly between muscle-invading cancer and superficial nonpapillary cancer (44%). In 198 patients with superficial bladder cancer, progression was observed in 19 (10%) during a mean follow-up of 72 months. All of them showed positive urinary cytology results in pretreatment samples, and among the patients with positive urinary cytology, the progression rate was significantly higher when cannibalism was present than when it was absent (38% vs. 17%, P < .05). Moreover, in high grade cases, cannibalism had significant predictive value for progression. By multivariate analysis, cannibalism was an independent factor for prediction of progression, as were tumor grade and stage. CONCLUSION: Cannibalism in urinary cytology appears to be an indicator of both the anaplastic grade and invasiveness of transitional cell carcinoma of the bladder. Furthermore, cannibalism may provide a reliable predictor of progression of superficial bladder cancer.
Biopsy↗