Biomedical subjects

T Kanda

Publications and source records attributed to T Kanda.

At least 307 records · Page 17Linked to original sources

PubMed1996

Optimal schedule for administering granulocyte colony-stimulating factor in chemotherapy-induced neutropenia in non-small-cell lung cancer.

A prospective randomized study was conducted to determine the optimal schedule of rhG-CSF (recombinant human granulocyte colony-stimulating factor). A group of 33 lung cancer patients treated with MVP therapy (mitomycin, vindesine, and cisplatin) were randomly assigned to three groups: an early prophylaxis group in which rhG-CSF was initiated on day 2 of the MVP cycle; a late prophylaxis group in which rhG-CSF was initiated on day 8; and a therapeutic group in which rhG-CFS was initiated after the onset of neutropenia. Ten patients who had received MVP therapy without rhG-CSF were also analyzed as a no-support group. The incidence of neutropenia was 80% (16/20 courses) in the early prophylaxis group, 44% (8/18) in the late prophylaxis group, 94% (17/18) in the therapeutic group, and 94% (16/17) in the no-support group. The incidence of neutropenia in the late prophylaxis group was less than in the early prophylaxis group (P<0.05), the therapeutic group (P<0.01), and the no-support group (P<0.01). The late prophylactic rhG-CSF schedule was therefore more effective in countering neutropenia than either the early prophylactic or therapeutic schedule.

Aged↗

PubMed1996

Changes of unmyelinated nerve fibers in sural nerve in amyotrophic lateral sclerosis, Parkinson's disease and multiple system atrophy.

Quantitative changes in unmyelinated nerve fibers (UMNFs) of sural nerves in patients of amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and multiple system atrophy (MSA) were evaluated using autopsy materials whose pathological diagnosis had been confirmed by careful postmortem examinations. Ordinary ALS cases demonstrated no involvement in cutaneous UMNFs; however, the patients with long survival due to the application of ventilatory support showed bimodality in UMNF diameter histograms, and a patient with involvement of systems other than motor pathways showed an abnormal value in two indices: a low percentage of subunits containing axon(s) and a high mean number of Schwann cell profiles per axon. A significant reduction of the mean value of UMNF density (21%) was found in PD patients. Because the density of myelinated nerve fibers did not show any significant decrease as compared with age-matched controls, the change of nerve fibers in peripheral nervous system was considered to be confined to UMNFs in PD. Elderly PD cases showed enhanced changes in the ageing process, as expressed by the two indices described above. In MSA, the mean value of UMNF density was significantly decreased (23%), and this decrease almost paralleled that of myelinated nerve fiber density. Abnormal values for the two indices described above were found and two out of four cases demonstrated bimodality in the diameter histogram of UMNFs. Unlike MSA, ALS and PD have not been included in the disorders with cutaneous UMNF involvement. Our results supply the first evidence of morphological changes in cutaneous UMNFs in PD cases. In ordinary ALS cases, the emergence of such morphological changes is suggested in cases with long survival.

Age Distribution↗

PubMed1996

Interleukin-6 secreted from human myxoma reduces murine viral myocarditis.

The effect of interleukin-6 (IL-6) secreted by a human atrial myxoma in vitro was investigated in C3H female mice with acute viral myocarditis. A culture medium containing IL-6 (100 ng/ml) and IL-8 (250 ng/ml), was prepared; viral myocarditis was induced by exposure to the encephalomyocarditis virus. Mice were assigned to four groups: 1) intraperitoneal (i.p.) injection of supernatant with IL-6 and IL-8 (0.2 ml/mice) given simultaneously with virus, 500 pfu for 4 days (Group 1); 2) i.p. injection of supernatant with IL-6 starting on Day 4 for 4 days in the same manner (Group 2); 3) i.p. injection of culture medium simultaneously with the virus (Group 3); and 4) i.p. injection of PBS in the same manner (Group 4). Uninfected control mice were administered medium only (Group 5) or supernatant with IL-6 and IL-8 (Group 6) for 4 days without virus. The survival rate on Day 14 in Group 1 was 90% significantly (p < 0.01) prolonged. The ratio of heart weight-to-day weight in the Group 1 was significantly (p < 0.01) lower. Histopathological examination revealed that cardiac necrosis and cellular infiltration in Group 1 was reduced compared with Group 3. Moreover, the radio of spleen weight/body weight in Group 1 was significantly (p < 0.01) higher than that of Group 3 and of Group 4. To confirm the effect of IL-6 or IL-8, mice were treated with recombinant IL-6 to IL-8 simultaneously with virus for 4 days. IL-6 treated mice survived significantly compared with IL-8 treated mice and untreated mice. The viral titer on day 4 of IL-6 treated mice was significantly lower than IL-8 treated or untreated mice. Thus, IL-6 derived from human myxoma improved the survival of murime viral myocarditis and reduced myocardial necrosis when the myxoma-derived IL-6 was administered simultaneously with the virus, due to eliciting cellular immunity in the spleen.

Animals↗

PubMed1996

Topiramate reduces abnormally high extracellular levels of glutamate and aspartate in the hippocampus of spontaneously epileptic rats (SER).

The spontaneously epileptic rat (SER), a double mutant, manifests both tonic and absence-like seizures. The effect of topiramate, a novel antiepileptic drug, on the extracellular levels of excitatory amino acids (EAA) in the hippocampus of SER was investigated using in vivo microdialysis. The basal levels of glutamate and aspartate in dialysates of hippocampus in SER were 2- to 3-fold higher than those in normal Wistar rats. Both the dose-response relationship and the time course of the suppression of tonic seizures by topiramate were similar to the attenuation of glutamate level in SER. Topiramate (40 mg/kg i.p.) significantly (P < 0.05) reduced both glutamate and aspartate levels in SER while showing no effect on normal Wistar rats. These findings suggest that topiramate reduces abnormally high extracellular levels of glutamate and aspartate in the hippocampus of SER. This effect may, at least in part, be related to the anticonvulsant activity of topiramate.

Animals↗

PubMed1996

A selective type V phosphodiesterase inhibitor, E4021, protects the development of right ventricular overload and medial thickening of pulmonary arteries in a rat model of pulmonary hypertension.

We evaluated the effects of oral administration of 10, 30, and 100 mg/kg/day of E4021, a type V phosphodiesterase inhibitor, on development of monocrotaline-induced right ventricular overload and medial thickening of pulmonary arteries. Right ventricular systolic pressure, mass ratio of right ventricle to left ventricle, right ventricular wall thickness, right ventricular myocardial fiber diameter, medial thickness, and smooth muscle area in pulmonary arteries were significantly less in rats that received E4021 30 and 100 mg/kg/day than in the control with monocrotaline on day 28. Myofiber diameter, medial thickness, and smooth muscle area were significantly lower in rats treated with E4021 100 mg/kg/day than in those of E4021 30 mg/kg/day. E4021 100 mg/kg/day protected development of right ventricular overload and medial thickening of pulmonary arteries.

Animals↗

PubMed1996

Nerve growth factor (NGF) induces increase in multi-ubiquitin chains and concomitant decrease in free ubiquitin in nuclei of PC12h.

Changes in Ubiquitin-immunoreactivity after nerve growth factor (NGF) treatment were investigated in PC12h cells. Ubiquitin-immunoreactivity was increased in the nucleus of NGF-treated cells. The quantitative analysis revealed that, after 7 days of NGF treatment, almost 20% of cells had ubiquitin-immunoreactive nuclei and the frequency was increased thereafter. Levels of free ubiquitin and multi-ubiquitin chains were measured by radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA), respectively. Measurements were carried out for four subcellular fractions: urea- and water-soluble extracts of nuclei and cytoplasm. Decrease in free ubiquitin was observed in water-soluble cytoplasmic extracts of NGF-treated cells, though increase in multi-ubiquitin chains in the same fraction was not observed. As for nuclei, increase in multi-ubiquitin chains and concomitant decrease in free ubiquitin were found in the water-soluble extracts after NGF treatment. Levels of multi-ubiquitin chains did not change in urea-soluble cytoplasmic extracts as well as nuclear urea-soluble ones after NGF treatment. These results indicated that multi-ubiquitination of nuclear proteins is increased during NGF-induced neuronal differentiation of PC12h cells.

Animals↗

PubMed1996

Selective capture of acentric fragments by micronuclei provides a rapid method for purifying extrachromosomally amplified DNA.

The amplification and overexpression of a number of oncogenes is strongly associated with the progression of a variety of different cancers. We now present a strategy to purify amplified DNA on double minute chromosomes (DMs) to enable analysis of their prevalence and contribution to tumourigenesis. Using cell lines derived from four different tumour types, we have developed a general and rapid method to purify micronuclei that are known to entrap extrachromosomal elements. The isolated DNA is highly enriched in DM sequences and can be used to prepare probes to localize the progenitor single copy chromosomal regions. The capture of DMs by micronuclei appears to be dependent on their lack of a centromere rather than their small size.

Cell Fractionation↗

PubMed1996

Intestinal fatty acid-binding protein is a useful diagnostic marker for mesenteric infarction in humans.

BACKGROUND & AIMS: Acute ischemic diseases of the small bowel are lethal emergencies with no reliable diagnostic biochemical tests available. Experimental studies have suggested rat intestinal fatty acid-binding protein (I-FABP) as a serum marker reflecting bowel ischemia; the present study evaluates the human homologue (human I-FABP) as a serum marker for the diagnosis of acute ischemic diseases of the bowel. METHODS: Enzyme immunoassay was applied to determine I-FABP levels in the sera of 96 subjects: 13 preoperative patients with ischemic bowel diseases (5 cases of mesenteric infarction and 8 cases of strangulated obstruction of the small bowel), 35 healthy subjects, and 48 hospitalized patients with acute abdominal pain. RESULTS: Serum I-FABP levels were < 65 ng/mL in healthy subjects. In patients with acute abdominal pain, levels ranged from < 20 to 87 ng/mL (mean, 27.4 ng/mL), not significantly different from findings in healthy subjects. However, patients with ischemic bowel disease showed significantly higher I-FABP levels, ranging from < 20 to 1496 ng/mL (mean, 265.8 ng/mL). All 5 patients with mesenteric infarction showed I-FABP levels of > 100 ng/mL. CONCLUSIONS: I-FABP is a useful biochemical marker for the accurate diagnosis of mesenteric infarction.

Adolescent↗

PubMed1996

Fine substrate specificities of four exo-type cellulases produced by Aspergillus niger, Trichoderma reesei, and Irpex lacteus on (1-->3), (1-->4)-beta-D-glucans and xyloglucan.

To investigate the fine substrate specificities of four highly purified exo-type cellulases (Exo-A from Aspergillus niger, CBHI and CBHII from Trichoderma reesei, and Ex-1 from Irpex lacteus), water-soluble substrates such as barley glucan, xyloglucan from tamarind (Tamarindus indica L.), and their oligosaccharides were employed. Four exo-type cellulases immediately hydrolyzed 3-O-beta-D-cellotriosylglucose to produce cellobiose and laminaribiose. In contrast, CBHII showed no hydrolytic activity towards 3(2)-O-beta-D-cello-biosylcellobiose, which was hydrolyzed to cellobiose by the other exo-type cellulases. These cellulases hydrolyzed the internal linkages of barley glucan and lichenan in an endo-type fashion to produce cellobiose and mix-linked oligosaccharides as main products. The DP-lowering activities of the four exo-type cellulases on barley glucan were in the order of Ex-1, CBHII, Exo-A, and CBHI. Based on gel permeation chromatography analysis of the hydrolysates, Ex-1 seemed to attack the internal cellobiosyl unit adjacent to beta-1,3-glucosidic linkages in barley glucan molecule more frequently than did the other cellulases. Xyloglucan was hydrolyzed only by CBHI and CBHII, and produced hepta-, octa-, and nona-saccharides. In addition, a xyloglucan tetradecasaccharide (XG14) was split only to heptasaccharide (XG7) by CBHI and CBHII.

Aspergillus niger↗

PubMed1996

Bone changes and mineral metabolism disorders in rats with experimental liver cirrhosis.

To investigate the pathogenesis of hepatic osteodystrophy (HOD) in parenchymal liver disease, we developed a laboratory model in animals using carbon tetrachloride (CCl4) and thioacetamide. Biochemical and histological parameters in the model were measured. In rats with both chronic non-cirrhotic liver injury and CCl4-induced cirrhosis, tibial bone volume was significantly lower than in controls. In CCl4-treated cirrhotic rats, the osteoid volume decreased while the urinary calcium/creatinine ratio increased. In all CCl4-treated rats, bone volume was significantly correlated with both the serum albumin concentration and the number of goblet cells reflecting intestinal villous atrophy. The serum concentration of vitamin D metabolites was not correlated with bone volume. Whole body retention of 47Ca was significantly lower in CCl4-treated cirrhotic rats than in controls. Furthermore, the bone volume in thioacetamide-treated cirrhotic rats was significantly lower than in controls. These data demonstrate that chronic parenchymal liver injury itself causes osteoporosis (i.e. HOD) due to a combination of low bone formation rates and high resorption rates, that HOD begins at the stage of chronic non-cirrhotic liver injury, that bone volume in HOD parallels liver damage and that the principal pathogenesis of HOD seems to be intestinal Ca malabsorption due to lower serum albumin and villous atrophy, while serum levels of vitamin D metabolites have little influence on the pathogenesis of HOD.

Animals↗

PubMed1996

KW-3902, a selective high affinity antagonist for adenosine A1 receptors.

1. We demonstrate that 8-(noradamantan-3-yl)-1,3-dipropylxanthine (KW-3902) is a very potent and selective adenosine A1 receptor antagonist, assessed by radioligand binding and cyclic AMP response in cells. 2. In rat forebrain adenosine A1 receptors labelled with [3H]-cyclohexyladenosine (CHA), KW-3902 had a Ki value of 0.19 nM, whereas it showed a Ki value of 170 nM in rat striatal A2A receptors labelled with [3H]-2-[p-(2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamidoad enosine (CGS21680), indicating 890 fold A1 receptor selectivity versus the A2A receptor. KW-3902 at 10 microM showed no effect on recombinant rat A3 receptors expressed on CHO cells. 3. Saturation studies with [3H]-KW-3902 revealed that it bound with high affinity (Kd = 77 pM) and limited capacity (Bmax = 470 fmol mg-1 of protein) to a single class of recognition sites. A high positive correlation was observed between the pharmacological profile of adenosine ligands inhibiting the binding of [3H]-KW-3902 and that of [3H]-CHA. 4. KW-3902 showed potent A1 antagonism against the inhibition of forskolin-induced cyclic AMP accumulation in DDT1 MF-2 cells by the A1-selective agonist, cyclopentyladenosine with a dissociation constant (KB value) of 0.34 nM. KW-3902 antagonized 5'-N-ethylcarboxamidoadenosine-elicited cyclic AMP accumulation via A2B receptors with a KB value of 52 nM. 5. KW-3902 exhibited marked species-dependent differences in the binding affinities. The highest affinity was for the rat A1 receptor (ki = 0.19 nM) and these values for guinea-pig and dog A1 receptors were 1.3 and 10 nM, respectively.

Adenosine↗

PubMed1996

Human endogenous retrovirus K10 encodes a functional integrase.

We cloned a human endogenous retrovirus K1O DNA fragment encoding integrase and expressed it as a fusion protein with Escherichia coli maltose-binding protein. Integrase activities were measured in vitro by using a double-stranded oligonucleotide as a substrate mimicking viral long terminal repeats (LTR). The fusion protein was highly active for both terminal cleavage and strand transfer in the presence of Mn2+ on the K1O LTR substrate. It was also active on both Rous sarcoma virus and human immunodeficiency virus type 1 LTR substrates, whereas Rous sarcoma virus and human immunodeficiency virus type 1 integrases were active only on their corresponding LTR substrates. The results strongly suggest that K1O encodes a functional integrase with relaxed substrate specificity.

Amino Acid Sequence↗

PubMed1996

Effects of superoxide dismutase and catalase on growth of retinal pigment epithelial cells in vitro following addition of linoleic acid or linoleic acid hydroperoxide.

The rod outer segments of the retina that are phagocytized by retinal pigment epithelial (RPE) cells are susceptible to lipid peroxidation because of their high content of polyunsaturated fatty acids. Linoleic hydroperoxides (LHP), synthesized by peroxidation of linoleic acids (LA), produce greater damage to retinal function than does LA. We compared the effects of LHP and LA on the growth of cultured chick embryonic RPE cells and analyzed a model of data sets using multiple linear regression for the number of cells as a function of time. The spectrum of LA had a sharp peak at 205 nm and a broad spectrum at 235 nm, while LHP had only a broad spectrum at 235 nm. Exposure to LA and LHP caused dose-dependent damage of chick embryonic RPE cells: they were significantly more affected by the addition of LHP than LA. The antioxidative enzymes catalase and superoxide dismutase minimized damage to the RPE cells caused by LHP in proportion to the enzyme concentration. However, RPE cells incubated with LA were more affected by the enzymes than when no enzymes were added.

Animals↗

PubMed1996

Modification of viral myocarditis in mice by interleukin-6.

Inflammatory cytokines play a key role in the myocardial injury produced by viral myocarditis. Although interleukin-6 (IL-6) reportedly possesses antiviral properties, its effect in viral myocarditis is unclear. To investigate the role of IL-6 in viral myocarditis induced by encephalomyocarditis virus (EMCV) in mice, we evaluated (1) the survival rate following IL-6 administration, (2) the viral titer in the heart, (3) viral replication in the heart by in situ hybridization, (4) histopathological changes using immunohistochemical staining, (5) neutralizing antibody against EMCV, (6) circulating interferon and tumor necrosis factor-alpha (TNF-alpha), (7) viral suppression in vitro by IL-6, and (8) natural killer (NK)-cell activity. Eight-week-old C3H/HeJ mice were injected intraperitoneally with EMCV (day 0) and were also injected subcutaneously twice daily for 4 consecutive days with 10 micrograms/0.1 mL of human IL-6 on day -4 (group A), day 0 (group B), or day +4 (group D) for 4 days. As a control, 0.1 mL PBS instead of IL-6 was injected on day 0 for 4 days (group C). Certain mice were killed on day 4. The myocardial virus titers, viral replication in situ, and NK-cell activity in the spleen were determined. Decreased viral titer and viral replication in the heart reduced the titer of circulating TNF-alpha, and lower NK-cell activity was observed in group B versus group C (control group). The titer of neutralizing antibodies against EMCV was significantly (P < .05) increased in group B compared with group C. The remaining mice were killed on days 10 and 30 after infection. The ratio of heart weight (HW) to body weight (BW) and myocardial injury in group B were reduced versus group C on days 10 and 30. The HW of group B on day 30 did not differ from the normal control group. The ratio of splenic weight to BW and the ratio of thymic weight to BW of group B increased on day 10, with expanded follicles observed in the spleen and enlargement of the medulla observed in the thymus. Immunohistochemical study revealed an increased percentage of macrophages in the heart and spleen of group B. In summary, IL-6 reduces myocardial damage in mice with viral myocarditis. Modification of immune responses together with reduction in viral replication appears to be the mechanism of the IL-6 effect. Although IL-6 is likely important in the process of viral antigen presentation, early activation of immune responses and attenuation of viral replication appear most significant, as reflected in the limited time window during which IL-6 is effective in myocarditis.

Animals↗

PubMed1996

Novel functional polymers: poly(dimethylsiloxane)-polyamide multiblock copolymer. V. The interaction between biomolecules and the surface of aramid-silicone resins.

Multiblock copolymers consisting of aromatic polyamide(aramid) and poly(dimethylsiloxane) (PDMS) aramid-silicone resins (PASs) were synthesized by low temperature solution polycondensation, and PAS films were prepared by casting from an N,N'-dimethylacetamide solution. In this study, we investigated bovine serum albumin (BSA) adsorption, L929 cell adhesion, and tissue reaction on the surface of PAS in order to clarify the interaction between PAS and biomolecules. It was found that the amount of adsorbed biomolecules on PAS was extremely low in contrast with those on aramid and nylon films, and it was comparable to SILASTIC 500-1 film. This suppression of adsorption of biomolecules onto PAS seemed to be due to the low surface free energy of the outermost surface of PAS, where PDMS block was condensed.

Adsorption↗

PubMed1996

Myocardial infarction in myxoma patients with normal coronary arteries. Case reports.

Three cases of patients with cardiac myxoma who had attacks of acute myocardial infarction are presented. Cineangiographic study showed normal coronary arteries. Immunohistochemical and serologic examination revealed that both interleukin-6 and interleukin-8 were secreted in cardiac myxoma. The authors discuss the relation between these cytokines and myocardial infarction with normal coronary arteries.

Adult↗

PubMed1996

MR imaging of spastic diplegia. The importance of corpus callosum.

PURPOSE: The MR findings in patients with spastic diplegia were investigated and the role of MR imaging in assessing the extent of brain injury was evaluated. MATERIAL AND METHODS: 39 male and 24 female patients (preterm/term 43/20) were imaged using a 0.5 T MR system. RESULTS: The MR findings in term patients were quite different from those in preterm patients; 55% of the term patients showed normal and minimal changes on MR, whereas 90.7% of the 43 preterm children had periventricular leucomalacia. The deep cerebral white matter was the most frequently involved site. Objective measurements revealed significant reductions of the entire sagittal area of corpus callosum in diplegic patients in comparison with normal controls. The motor palsy severity correlated well with the extent of corpus callosum involvement. CONCLUSION: The corpus callosum appears to be a sensitive marker site for the assessment of the extent of white matter injury.

Case-Control Studies↗

PubMed1996

A ubiquitin-protein ligase (E3) mutation of Saccharomyces cerevisiae suppressed by co-overexpression of two ubiquitin-specific processing proteases.

To isolate mutations related to the ubiquitin system, I constructed a plasmid carrying the YUH1 and UBP1 genes (genes of ubiquitin-specific processing proteases) whose expressions were under the control of the galactose-inducible GAL1-GAL10 promoter. Cells of a strain carrying the plasmid were mutagenized with ethyl methanesulfonate. One mutant, which showed galactose-dependent growth at a high temperature (37 degrees C), was isolated from about 380,000 mutagenized colonies. The mutation responsible for galactose-dependent growth at 37 degrees C was a single nuclear recessive mutation designated as uby1-1. UBP1 and YUH1 as well as the GAL1-GAL10 promoter are required to suppress uby1-1. At the restrictive temperature, a uby1-1 mutant did not arrest at a specific phase of the cell cycle, but still lost viability. Even at the permissive temperature (30 degrees C), the uby1-1 mutant grew somewhat slowly and showed pleiotropic phenotypes including hypersensitivity to stresses such as cadmium and canavanine, and sporulation defects. The genomic DNA fragments in a single-copy plasmid which complemented uby1-1 were isolated. Chromosomal mapping, sequencing and subcloning analyses indicated that the gene complementing uby1-1 is RSP5, which encodes a ubiquitin-protein ligase (E3) homologous to E6-AP (E6 associated protein). Deletion, complementation and linkage analyses revealed that UBY1 and RSP5 are the same gene. Therefore, the E3 protein encoded by RSP5 (UBY1) is required for vegetative growth, sporulation and stress response. The present procedure using suppression by co-overexpression of two cloned genes will be useful to isolate mutations of related genes and to analyze biochemical pathways and gene-interactions.

Base Sequence↗