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Biomedical subjects

A Takeda

Publications and source records attributed to A Takeda.

At least 289 records · Page 16Linked to original sources
PubMed1996

[Prognostic factors of nasopharyngeal carcinoma treated by radiotherapy].

This study was a retrospective analysis of 82 patients with histologically confirmed nasopharyngeal carcinoma, who were treated at Keio University Hospital from March 1983 to March 1993. We studied all cases(62% of them were stage IV) with regard to their prognostic factors and chronic side effects induced by radiation. All patients were received extended-field radiotherapy from the base of the skull to the supraclavicular lymph node area. The five- and ten-year overall survival rates for the entire group were 59% and 49%, respectively. Three stage I patients were alive without recurrence or metastases for more than 5 years. The ten-year survival rate stage II-III for patients (23 patients) was 78%, and for stage IV (56 patients) 37%. The five-year survival rate of patients in T2-3 group without lymph node metastasis was 88%, while it was reduced to 55% for patients with metastasis. The prognosis of T4 patients was very poor: their five-year survival rate was 37% with lymph node metastasis, and 35%, without lymph node metastasis. Patients under 46 years old showed an increased survival rate compared with patients over 46 years old. Patients who completed less than 52 days of radiation therapy found to have a better prognosis than those receiving radiation for a longer period. Our multivariate analysis indicated that age, radiation period and N-factor were statistically significant in influencing prognosis. Hearing loss occurred relatively high with 20% of cumulative incidence in our study, probably because they received radiation therapy with the extended field including bilateral middle and inner ear. Extended-field radiotherapy for patients with nasopharyngeal carcinoma might contribute to improving their cure-rate, and precise radiation planning is warranted to avoid the late complications such as hearing loss.

Adenocarcinoma↗
PubMed1995

Biological half-lives of zinc and manganese in rat brain.

The brains of rats injected intravenously with 65ZnCl2 or 54MnCl2 were subjected to high-resolution autoradiography. The distribution of 65Zn and 54Mn in each brain region gradually decreased from 6 days to 42 days for 65Zn and from 15 days to 60 days for 54Mn after the injection. The biological half-lives of Zn in each region studied were in the range of 16-43 days; the longest was observed in the amygdaloid nuclei. The regions where the long biological half-life was observed were consistent with the ones with the high density of Zn-containing neuron terminals reported previously. The biological half-lives of Mn in each region were 51-74 days; the longest were those in the hypothalamic nuclei and thalamus.

Animals↗
PubMed1995

Human cystatin A is inactivated by engineered truncation. The NH2-terminal region of the cysteine proteinase inhibitor is essential for expression of its inhibitory activity.

A series of NH2-terminal truncated forms of human cysteine proteinase inhibitor, cystatin A, was prepared by genetic engineering using Escherichia coli harboring mutated genes. Each variant of cystatin A was efficiently expressed as a fused protein with porcine adenylate kinase and released by CNBr degradation after exchange of the sole inner Met to Leu. The mutant cystatin A lacking an amino-terminal Met residue (called standard variant starting from Ile2, CystA2-98(M65L) showed the same inhibitory activity as authentic one isolated from human epidermis. Two-residue truncation scarcely influenced the activity, but further truncations deleting Pro3 and beyond conservative Gly4 and Gly5 caused a remarkable decrease of their inhibitory activity. But little effect was observed by a substitution of Pro3 with Leu. The loss of the activity by amino-terminal truncation was compensated slightly by engineered substitution of Gly75 with His on a second loop. In the two-dimensional 15N-1H HSQC NMR spectrum, four-residue truncation was found to cause changes in the chemical shifts of Val47 and Val48, which locate on a first loop and consist of a conservative QVVAG sequence. Furthermore, the truncation led to a change in fluorescence spectroscopic behavior of Trp75, which was introduced as a probe on the second loop. Fluorescence intensity of the Trp of the truncated (5-98) form was more affected by heating than the active standard variant. Conversely, fluorescence of Trp75 in 2-98 form was more quenched by acrylamide than the 5-98 variant. Thus, the amino-terminal region of cystatin A is essential for the expression of its inhibitory activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Characterization of the interaction between CD45 and CD45-AP.

CD45, a leukocyte-specific transmembrane protein tyrosine phosphatase, is required for critical signal transduction pathways in immune responses. To elucidate the molecular interactions of CD45 with other proteins involved in CD45-mediated signal transduction pathways, we have recently cloned a 30-kDa phosphorylated protein, CD45-AP, which specifically associates with CD45. Binding analysis employing several deleted or chimeric forms of CD45-AP and CD45 demonstrated that the potential transmembrane segment of CD45-AP bound to the transmembrane portion of CD45. CD45-AP was found in particulate fractions of lymphocytes along with CD45, indicating that it is likely to be a transmembrane protein. In addition, CD45-AP was resistant to proteolysis by tosylphenylalanyl chloromethyl ketone-treated trypsin applied to intact cells. This is consistent with the most likely membrane orientation of CD45-AP predicted from the amino acid sequence, that is, only a short amino-terminal segment of CD45-AP is extracellular. We propose that CD45-AP interacts with CD45 at the plasma membrane and that the bulk of CD45-AP located in the cytoplasm act as an adapter which directs the interaction between CD45 and other molecules involved in CD45-mediated signal transduction pathways.

Animals↗
PubMed1995

Characteristic induction of hepatic metallothionein in mice by tumor transplantation.

Based on the previous finding that hepatic metallothionein (MT) level was tumor-growth dependently elevated in tumor-transplanted mice, the mode of induction of hepatic MT in tumor-bearing mice was comparatively studied with inflammation-induced and stress-subjected mice. The prefeeding with zinc (Zn)-deficient diet for 1 wk suppressed both the growth of tumor and the increase of hepatic MT and Zn in tumor-bearing mice. The postfeeding with Zn-deficient diet also suppressed hepatic MT induction in the course of tumor growth. On the other hand, in the other two experimental model mice, the prefeeding with Zn-deficient diet did not suppress the increase of hepatic MT and Zn. Further, the dexamethasone treatment stimulated hepatic MT induction in tumor-bearing mice, but rather reduced that in inflammation-induced mice. These results suggest that hepatic MT was induced uniquely in tumor-bearing mice and that Zn may play a key role for the induction of hepatic MT by tumor transplantation.

Animals↗
PubMed1995

Squamous cell carcinoma antigen is a potent inhibitor of cysteine proteinase cathepsin L.

A squamous cell carcinoma antigen (SSCA), which is a member of the serpin family of proteinase inhibitors, was purified from sera of cancer patients. It did not inhibit serine proteinases. However, it non-competitively inhibited human cathepsin L with a Ki of 0.064 nM, but not cathepsins B and H among cysteine proteinases. These results indicated that SCCA is a non-functional serpin that inhibits cathepsin L in cancer cells.

Animals↗
PubMed1995

The influence of decreased left-ventricular afterload on cardiac morphology in hypertrophied rat hearts.

The influence of afterload reduction on cardiac morphology was investigated in Goldblatt rats (hypertensive Wistar rats) with left-ventricular hypertrophy. The measurements were performed on a modified heart-lung preparation in which left-ventricular afterload was reduced either 0%, 15%-30% or 35%-50%. Goldblatt rats without heart-lung preparation served as control group. The aim of this study was to investigate the effects of decreased left-ventricular afterload on the myocardial morphology. The hearts were prepared for light and electron microscopy. For ultrastructural investigations, we developed a mitochondrial alteration score and graded the myocytes according to the degree of ischemic injury. The changes ranged from score 0 (normal) to score 4 (most severe). The mean score of the group with marked afterload reduction (35%-50%) was significantly increased compared to all other groups. Our data suggest that marked afterload reduction has a negative impact on the myocardial ultrastructure in hypertension-induced left-ventricular hypertrophy. Light microscopically, we found a correlation between myocardial cell diameter and blood pressure and a significant difference in arterial wall thickness between normotensive and hypertensive rats.

Animals↗
PubMed1995

In vivo modification of GABAA receptor with a high dose of pyridoxal phosphate induces tonic-clonic convulsion in immature mice.

The biologic cofactor, pyridoxal-5'-phosphate (PLP), is responsible for tonic-clonic convulsion in immature mice. The mechanisms underlying such convulsive fits induced by administration of a single high dose of PLP were studied. The administration of PLP resulted in a 13% increase of PLP in the P2 fraction compared to control P2, and the calculated data suggested that membrane bound PLP increased over 31% (approximately 1 microM). The P2 fraction of administered mice was treated with [3H]NaBH4 and analyzed by SDS-polyacrylamide gel electrophoresis. The radioactivity was mainly incorporated into a 52 kDa protein which corresponded to a GABAA receptor subunit. The addition of PLP in vitro competitively inhibited [3H]GABA binding as well as [3H]flunitrazepam binding to synaptic membranes in a concentration-dependent manner, and 50% inhibition was achieved with 1 mM PLP. The results obtained in the present study demonstrate that PLP was rapidly permeable into the brain through the immature blood-brain barrier and then bound directly to GABAA receptor. It is probable that specific amino groups of lysine residues on the GABAA receptor react in vivo with PLP to form Schiff bases, and that the in vivo modification of the receptor produces a degeneration of GABAergic neurotransmission leading to the onset of a convulsive fit.

Animals↗
PubMed1995

Induction of heparin-binding growth-associated molecule expression in reactive astrocytes following hippocampal neuronal injury.

Heparin-binding growth-associated molecule is a potent neurotrophic factor. To obtain a better understanding of its role in the central nervous system, we studied the changes of its expression in adult rat brain after two types of neuronal injury. In the control hippocampus, expression of heparin-binding growth-associated molecule messenger RNA was confined to CA1 pyramidal neurons and some hilar cells. Following transient forebrain ischaemia, the messenger RNA expression decreased within the first two days. On day 4, however, both the messenger RNA level and the number of expression-positive cells markedly increased in the CA1 subfield, where the selective neuronal losses were seen following ischaemia. Double-staining with a heparin-binding growth-associated molecule complementary RNA probe and an anti-glial fibrillary acidic protein antibody revealed that most of the expressing cells were reactive astrocytes. Moreover, the protein induction of heparin-binding growth-associated molecule after neuronal injury was demonstrated by immunohistochemistry using the affinity-purified antibodies. This molecule was also induced after intraventricular kainate injection, which is known to cause selective pyramidal cell necrosis in the CA3 region. Four days after the insult, the number of cells expressing the messenger RNA prominently increased in the CA3 subfield ipsilateral to the injection. As observed after the ischaemic insult, most of the expression-positive cells were identified as astrocytes. The data presented here suggest that heparin-binding growth-associated molecule, produced by the reactive astrocytes, may play important roles in the repair process after neuronal injury.

Animals↗
PubMed1995

65Zn uptake by liver of rats fed 3'-methyl-dimethylaminoazobenzene.

The uptake of 65Zn, determined by gamma-counting and also by autoradiography, significantly increased with the increasing level of metallothionein in liver 4 weeks after the start of feeding a diet containing 3'-methyl-dimethylaminoazobenzene (3'-Me-DAB), at which time the serum gamma-glutamyl transpeptidase activity was not yet significantly elevated. At this time, furthermore, hepatic uptake of 67Ga-citrate did not increase and that of 99mTc-Sn-colloid decreased in 3'-Me-DAB-fed rats. These results suggest that a short-life gamma-emitting isotope such as 69mZn may be useful for the detection at the early stage of hepatic carcinogenesis.

Administration, Oral↗
PubMed1995

Differential hepatic response of 65Zn distribution between mice bearing experimental tumor and inflammation.

Discriminative detection of tumor and inflammation was tried by radio-imaging of hepatic uptake of 65Zn. This closely related to the level of metallothionein (MT) and reflected the extent of tumor growth in mice and rats transplanted with experimental tumor. The elevation of 65Zn distribution in liver of experimental tumor-bearing mice was inhibited by treatment with Zn-deficient diet, while stimulated by dexamethasone. This stimulation occurred 2 days after tumor transplantation, at which time 67Ga-citrate could not image the tumor. On the other hand, hepatic distribution of 65Zn was also elevated in mice by inducing experimental abscess, although the effect of both treatments on this elevation was different from the case of tumor; the elevation was inhibited by treatment with dexamethasone. These results suggest that radio-imaging of hepatic Zn uptake with a short-life gamma emitting isotope such as 69mZn with use of dexamethasone, if required, may be useful for a preliminary test to detect early-stage malignant disease.

Animals↗
PubMed1995

Coprevalence of bulimia with alcohol abuse and smoking among Japanese male and female high school students.

Bulimia nervosa (bulimia) is often concomitant with alcohol and other substance abuse. To investigate the coprevalence of bulimia with alcohol abuse and smoking, we surveyed 2597 male and female Japanese high school students and obtained a group of bulimic students who fulfilled four of five DSM-III-R bulimia nervosa criteria and a control group who reported no binge-eating experience. Comparison of the groups showed significantly more alcohol abuse for both male and female bulimic students than for the non-bulimic control group. The male and female adolescents with symptoms of bulimia were similar in showing a high prevalence of alcohol abuse. The incidence of smoking was significantly higher among the bulimic females than among the female controls, but there was no significant difference between the male groups' smoking experiences.

Adolescent↗
PubMed1995

Simultaneous analysis of tiaramide metabolites in horse urine and plasma by solid-phase extraction and reversed-phase ion-pair liquid chromatography.

A simple method for the simultaneous analysis of tiaramide (TRA) metabolites in the horse is described. The sample preparation method using a Bond-Elut PH cartridge and stepwise elution with ice-cold, 30% aqueous methanol followed by additional methanol is effective for recovering the metabolites with different properties. The extraction method gives good recoveries (greater than 80%) and reproducibility. Each metabolite is well separated by high-performance liquid chromatography using an octadecyl-type column of polymer-based packing with a solvent system of 20 mM phosphate buffer (pH 6.5)-acetonitrile-tetrahydrofuran (6:1:0.2) containing a quaternary ammonium salt as an ion-pairing reagent. The detection limit of each metabolite is in the range of 20-80 ng/ml. The major metabolites of TRA in equine urine and plasma are N-acetic acid (TRAA) and N-oxide. The N-oxide of TRAA is detected as a metabolite in the urine. A dealkylation product PER) is detected as a minor metabolite. Unchanged TRA is detected only at low concentrations in the urine. Several minor metabolites of DER or TRAA or both are detected in the urine.

Acetic Acid↗
PubMed1995

Purification and characterization of metallo-beta-lactamase from Serratia marcescens.

Carbapenem-hydrolyzing beta-lactamase from Serratia marcescens FHSM4055 was purified 926-fold by means of carboxylmethyl Sephadex C-50, Sephacryl S-200, and Mono S column chromatography. The molecular weight was 30,000 by SDS-PAGE and the isoelectric point was 8.7. The enzyme activity was inhibited by EDTA, and restored by adding zinc (II) or manganese (II). It was inhibited by p-chloromercuribenzoate and iodine as well as the heavy metals, Hg (II), Fe (II), Fe (III), and Cu (II). These results indicate that the enzyme is a metallo-beta-lactamase and that the SH-group of only one cysteine residue probably binds to the metal ion, thus contributing to the stability of the enzyme active center. The specific constant (kcat/Km) showed that the enzyme hydrolyzed various beta-lactam antibiotics such as carbapenems, cephalosporins, moxalactam, cephamycins, and penicillins other than monobactams. Ampicillin and piperacillin with respective amino- and imino-groups, ceftazidime with a carboxypropyloxyimino-group, and cefclidin with a carbamoylquinuclidine-group were poor substrates among the beta-lactam antibiotics other than the monobactams tested. The plots of the turnover number (kcat) against pH for the hydrolysis of cephaloridine gave an asymmetrical curve with the 'tail' on the acid side (pK1, 5.9; pK2, 9.0; pK3, 10.8), whereas those of kcat/Km gave a bell-shaped curve (pK1, 5.8; pK2, 9.8). Both results suggest that two ionic forms of an intermediate yield the same product at different rates and that the enzyme is stable under alkaline conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Endothelin-1 release from cultured endothelial cells induced by sera from patients with systemic lupus erythematosus.

OBJECTIVES: To clarify the pathophysiological role of endothelin-1 (ET-1) in the vascular injury associated with systemic lupus erythematosus (SLE) by investigating the effect of sera from patients with SLE on ET-1 release from cultured human umbilical vein endothelial cells. METHODS: Confluent monolayers of cultured human umbilical vein endothelial cells were incubated with serum samples (diluted 1:10) from 25 patients with SLE and 16 normal controls for two hours at 37 degrees C and ET-1 concentration in the culture supernatant was measured by enzyme immunoassay. RESULTS: The mean release of ET-1 from endothelial cells in the presence of serum from SLE patients was greater than in the presence of serum from normal controls (p < 0.005). ET-1 release from endothelial cells significantly correlated with the titre of IgM anti-endothelial cell antibodies (IgM-AECA) and immune complex concentration in sera from SLE patients (p < 0.05 and p < 0.01, respectively). After gel chromatography of the serum from an SLE patient, those fractions containing IgM-AECA or immune complex were shown to stimulate ET-1 release from endothelial cells. Heat aggregated IgG also stimulated ET-1 release from endothelial cells in a concentration dependent manner. CONCLUSIONS: IgM-AECA and immune complexes may stimulate ET-1 release from endothelial cells and ET-1 may play an important role in the initiation and development of vascular injury, such as pulmonary hypertension and lupus nephritis, in SLE.

Adolescent↗
PubMed1995

Comparison of 5-hydroxytryptamine-induced contraction of rat pulmonary artery to that of aorta in vitro.

We investigated the nature of the contraction produced by 5-hydroxytryptamine (5-HT) in the rat pulmonary artery, and compared it with that produced in the rat aorta. Both ketanserin and ritanserin inhibited 5-HT-induced contraction in the pulmonary artery non-competitively. In contrast, ketanserin competitively antagonized the contraction in the aorta. Bunazosin, a selective alpha 1-blocker, partially inhibited 5-HT-induced contraction in the pulmonary artery, but not in the aorta. In both the pulmonary artery and aorta, 8-OH-DPAT, a 5-HT1A selective agonist, produced a concentration-dependent contraction. In the pulmonary artery, 5-HT and 8-OH-DPAT produced contractions with similar potencies. In contrast, 8-OH-DPAT was less potent than 5-HT in the aorta. Bunazosin inhibited 8-OH-DPAT-induced contraction in both vessels. However, pindolol, a 5-HT1A antagonist, did not inhibit 8-OH-DPAT-induced contraction in the pulmonary artery. These results suggest that 5-HT produces contraction via not only 5-HT2 receptor, but also non-5-HT2 receptor (probably alpha 1-adrenoceptor) in the rat pulmonary artery. Furthermore, 8-OH-DPAT does not activate the 5-HT1A receptor to produce a contraction, but does activate other receptors which interact with alpha 1-adrenoceptor.

8-Hydroxy-2-(di-n-propylamino)tetralin↗