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Biomedical subjects

T Mizukoshi

Publications and source records attributed to T Mizukoshi.

At least 37 records · Page 2Linked to original sources

DNA structures recognized by the human UV-DDB protein.

DNA recognition by the human UV-damaged DNA-binding (UV-DDB) protein was characterized. By circular permutation analyses, DNA duplexes containing the (6-4) photoproduct and the abasic site analog were found to be bent at angles of 54 degrees and 57 degrees, respectively, when they formed a complex with this protein. Although kinked NMR structures have been reported, fluorescence resonance energy transfer experiments revealed that these duplexes had no intrinsic bend. These results suggest that the UV-DDB protein binds DNA that can be bent easily at the above angle.

Base Sequence↗

[A trial of new protocol of rush immunotherapy with standardized mite antigen].

The objective of the present study was (1) to establish a new protocol of rush immunotherapy (IT) using a purified mite antigen for the treatment of house-dust-mite-sensitive bronchial asthma. Ten adult asthmatics were enrolled in the initial trial which was based on a 7-day protocol using a house-dust antigen, to determine the optimal maintenance dose of mite antigen. No systemic side effects were observed when the antigen dose was lower than 50 AU. Consequently, the duration of rush IT was shortened to 5 days, and the maintenance dose was determined as 50 AU in the new protocol. To confirm its safety, another ten asthmatics were enrolled in a second trial. Rush IT using the new protocol was able to be performed without any systemic side effects in all patients except one who showed urticaria at 40 AU. These results suggest that the 5-day protocol of rush IT using the mite antigen is safe in patients with house-dust-mite-sensitive asthma.

Adolescent↗

[Idiopathic pulmonary fibrosis of the upper lobe: a case report].

A 26-year-old man was admitted to our hospital complaining of exertional dyspnea. Chest x-ray films disclosed reticulonodular shadows predominantly in the upper fields of both lungs, but no apical cap. Lung biopsy specimens obtained from the upper lobe by video-assisted thoracoscopy revealed subpleural elasto-fibrosis. Also, specimens obtained from the lower lobes disclosed micro-honeycombing due to peri-lobular fibrosis resembling usual interstitial pneumonia. Although pneumothorax occurred repeatedly, the lungs reinflated on each occasion without artificial intervention. Similar radiographic findings had been obtained on the patient's father, who died of idiopathic pulmonary fibrosis at the age of 56. Idiopathic pulmonary upper lobe fibrosis was conclusively diagnosed because the patient exhibited most of the features originally described by Amitani et al.

Adult↗

[A case of protein-losing gastroenteropathy in association with mixed connective tissue disease which was successfully treated with cyclophosphamide pulse therapy].

A 47-year-old man had been given a diagnosis of mixed connective tissue disease (MCTD) on 1987 when he had presented with Raynaud's phenomenon, polyarthralgia, sclerodactyly, and a high titre of anti-RNP antibody. Once his symptoms had improved following the administration of prednisolone orally and the treatment was discontinued since 1995. He noticed dyspnea and chest pain in February 1997. The bilateral pleural effusion was pointed out in the local hospital and he was admitted to our hospital in March 1997 for further examination. In addition to pleural effusion and ascites, laboratory studies revealed hypoalbuminemia and low serum levels of complements. Renal and liver function tests were normal and the urine gave a trace test for protein. The presence of protein loss in the gut was confirmed by an elevated alpha 1-antitrypsin clearance and 99mTc-albumin scintigraphy showing abnormal radioactivity in the gastrointestinal tract. Although endoscopic examination showed no abnormal findings macroscopically and gastrointestinal biopsies revealed nonspecific inflammation only, immunofluorescent studies demonstrated deposits of C 3, C 4 and IgG in the stomach, colon, and pleura. These findings supported the pathogenesis that immune deposits in tissues caused protein-losing gastroenteropathy (PLGE) in MCTD. Intravenous administration of cyclophosphamide started since July 1997, while the high-dose corticosteroid therapy including methylprednisolone pulse therapy were not effective. Hypoalbuminemia and low serum levels of complements improved remarkably and the pleural effusion and ascites disappeared after cyclophosphamide pulse therapy four times monthly. Cyclophosphamide pulse therapy should be considered as a possibly effective treatment for PLGE in association with collagen disease resistant to corticosteroid therapy.

Cyclophosphamide↗

Structure and dynamic studies by NMR of the potent sweet protein monellin and a non-sweet analog. Evidence on the importance of residue AspB7 for sweet taste.

Monellin, an intensely sweet protein and a non-sweet analog in which the AspB7 in monellin has been replaced with AbuB7 were studied by NMR. The results of our investigations show that the 3-dimensional structure of these two proteins are very similar indicating that the lack of the beta-carboxyl group in the AbuB7 analog is responsible for the loss of sweet potency. Selectively labeled monellin was prepared by solid-phase peptide synthesis by incorporating 15N-labeled amino acids into 10 key positions including AspB7. The internal mobility of these 10 key residues in monellin was estimated by the method of model-free analyses and our NMR studies show that AspB7 is the most flexible of these 10 residues. The flexibility of the AspB7 side chain may be important for receptor binding.

Amino Acid Sequence↗

Thermal stabilization of ribonuclease T1 by carboxymethylation at Glu-58 as revealed by 1H nuclear magnetic resonance spectroscopy.

Ribonuclease T1 (RNase T1) carboxymethylated at the gamma-carboxyl group of Glu-58 with iodoacetic acid is known to be completely inactive while it retains an almost full substrate-binding ability. In order to further clarify the effects of the carboxymethylation, the thermal stabilities of intact and Glu-58-carboxymethylated (CM-) RNase T1 were compared by measuring 1H NMR spectra at various temperatures. The transition curves of unfolding were obtained by plotting, as a function of temperature, the peak areas for the alpha and delta protons of Asn-81 and Ile-90, respectively, which are well apart from each other in the three-dimensional structure of the enzyme. For each of intact and CM-RNase T1, the transition curve of the Asn-81 alpha proton was identical with that of the Ile-90 delta methyl protons, suggesting that the thermal unfolding occurred simultaneously in every part of the molecule of CM-RNase T1 as well as of intact RNase T1. The midpoint of unfolding was 52 degrees C for intact RNase T1, and was increased by 9 degrees C upon carboxymethylation at Glu-58. This marked stabilization by carboxymethylation is thought to be due to formation of a salt bridge between the introduced carboxymethyl group and the neighboring guanidium group of Arg-77.

Enzyme Stability↗

Osseous choristoma of the tongue. Report of two cases.

Osseous choristoma of the tongue is a relatively rare lesion with 53 cases previously published in the literature. In this article, two additional cases are described; one in a 53-year-old woman located close to the foramen caecum, and the other in a 18-year-old woman on the left of midline and just anterior to the circumvallate papillae that was observed over a 13-year period.

Child, Preschool↗

Chemical modification of the sugar part of methyl acarviosin: synthesis and inhibitory activities of nine analogues.

Nine analogues of methyl acarviosin (1), the core structure of acarbose and its homologues, the 6-hydroxy-(2), 6-azido-(3), 6-amino- (4), 6-acetamido-(5), 6-methoxy-(6), 6-hydroxy-2-O-methyl-(8), and 6-hydroxy-3-O-methyl derivatives (9), including the 5-methoxycarbonyl analogue (7) and 3,6-anhydro derivative (10) of 2, were synthesized by chemical modification of the sugar part of 2 derived by condensation of methyl 3,4-anhydro-alpha-D-galactopyranoside (17) and 4,7:5,6-di-O-isopropylidenevalienamine (26) or by direct coupling between 26 and the 6-substituted methyl 3,4-anhydro-alpha-D-galactopyranoside derivatives. Compounds 2 and 8 show notable inhibitory activity against yeast alpha-D-glucosidase almost comparable to that of 1. Introduction of a polar substituent at C-6 of 1 decreases the inhibitory activity. Interestingly, inversion of the conformation of the sugar part of 1 by introduction of the 3,6-anhydro bridge elicits almost no effect on the inhibitory activity.

Amino Sugars↗

[Influence of radiation doses in local radiotherapy on anti-tumor immunity and tumor metastasis].

The relationship between radiation doses and the subsequent metastasis formation after local radiotherapy against a rat transplantable fibrosarcoma was studied. KMT-17 fibrosarcoma cells were transplanted into the hind leg of syngeneic WKA rats and the leg were irradiated with various doses of 60Co gamma-rays 5 days after the tumor transplantation. 97% of the local primary tumors regressed in the rats received more than 45Gy (high dose-group), whereas only 41% of the tumors regressed in the rats received less than 40Gy (low dose-group). On the other hand, the percentage of the subsequent metastasis in the high dose-group was significantly higher than that of the low dose-group. By Winn's assay, stronger tumor-neutralizing activities were observed in the spleen cells of rats received 30Gy than those of non-irradiated rats or rats received 60Gy. The above results suggest that the low dose irradiation to the local tumor stimulates the anti-tumor immunity which results in suppression of the tumor metastasis.

Animals↗

Ion specificity of rat chorda tympani fibers to chemical and electrical tongue stimulations.

Responses of rat single chorda tympani fibers to ionic chemical stimuli and anodal tongue stimulations with ionic bathing solutions were examined. Fourteen out of 30 fibers showed the highest sensitivities to NaCl for both chemical and electrical stimulations, whereas the remaining 16 fibers showed almost no ion specificity for electrical stimulation even though most of them have the highest sensitivities to HCl for chemical stimulation. Ion specificity for electrical stimulation was significantly smaller than that for chemical stimulation.

Animals↗

[Fourteen cases of mucosal melanomas of the oral cavity].

Fourteen cases of mucosal melanomas of the oral cavity were treated from January, 1970 to April, 1986 in our department. The patients were 10 males and 4 females and in their fifth and sixth decades with the primary sites in the upper gingiva and palates in the majority. The 3 and 5 year survival rates were 21.4% and 14.3% respectively, with unfavorable prognosis in comparison with cutaneous melanoma. The clinical stages were as follows: stage Ia (1), Ib (8), II (5), which affected the prognosis. The depth of invasion, as described by Breslow et al., were beyond 1.50 mm except in one case, which might be a significant prognostic factor in the study of mucosal melanoma of the oral cavity. Seventy one percent had neck node metastases and 35% had distant metastases. The high occurrence of metastases might be related to their poor prognosis.

Adult↗

The therapeutic effects of an immunopotentiator, PS-K, on 3-methylcholanthrene-induced autochthonous tumors in C57BL/6 mice in combination with the surgical removal of primary sites.

We investigated the therapeutic effects of an immunopotentiator PS-K on recurrent or metastatic tumors observed after the surgical removal of MCA-induced primary tumors in autochthonous C57BL/6 mice and on the survival time of treated mice. The MST of mice treated with PS-K at various times (59.8-63.4 days) was prolonged as compared with that of mice treated by surgery alone (48.6 days). Local recurrence of tumors was found in 36 of 66 mice (54.6%) treated by surgery alone, whereas it was inhibited significantly (P less than 0.05) when treatment with PS-K was started 1 day after the surgery and occurred in 22 of 64 mice (34.4%) when PS-K was given for 5 days in 1 week, or in 22 of 66 mice (33.3%) when PS-K was administered twice a week for 7 weeks. The MSTs of mice with local recurrence were also found to be prolonged as compared with those of mice treated by surgery alone (54.8-67.5 days vs 49.8 days). The MSTs of mice without tumor recurrence were also prolonged significantly (P less than 0.05-0.001) by combinations of PS-K at various times, although most of the mice died of metastatic tumors even in the groups of mice where a combined treatment with PS-K had been administered. The above findings suggest that the administration of PS-K inhibits the growth of recurrent or metastatic tumor cells in autochthonous mice after the surgical removal of the primary tumors.

Adjuvants, Immunologic↗

Therapeutic effects of PS-K and busulfan on the recurrent and metastatic diseases after the surgical removal of 3-methylcholanthrene-induced autochthonous tumors in C57BL/6 mice.

The effectiveness of a protein-bound polysaccharide, PS-K, and an immunoaugmenting antileukemia agent, busulfan (BU), was investigated for the treatment of autochthonous tumors induced by 3-methylcholanthrene in C57BL/6 mice. PS-K and BU were found to be effective in dealing with recurrence and pulmonary metastasis when applied in conjunction with the surgical removal of the primary tumor. The survival time of mice to which PS-K (300 mg/kg/day X 5 or X 2/week for 7 weeks, ip) or BU (50 mg/kg X 3, po) was administered was significantly prolonged when compared with that of mice treated by surgery alone. Moreover, the incidence of the local recurrence of tumors was significantly lower in mice treated with PS-K or BU after the surgical removal of the primary tumor. The effectiveness of the treatment on metastasis was also shown by the prolongation of mean survival time in groups of mice which showed no local recurrence of tumors. The timing-dependency of the treatment with PS-K did not seem to be an important factor and no additive therapeutic effects of PS-K and BU were observed in the present study.

Adjuvants, Immunologic↗

[Radiotherapy (interstitial irradiation) of carcinoma of the tongue--an analysis of cases in the past 10 years].

A total of 82 histologically proven squamous cell carcinomas of the tongue, which were treated by interstitial irradiation (radium) at Chiba Cancer Center from 1973-1982, were reviewed. The cumulative five-year survival rate of all cases was 64%: 78% in Stage I and II group, 68% in Stage III and 47% in Stage IV. Local recurrence was noted in eight cases (10%) and later cervical node metastases in 14 cases 25% in T 1-4 N 0). The incidence of mandibular osteoradionecrosis was 18 cases (22%).

Adult↗

Qualitative discrimination of gustatory stimuli in three different strains of mice.

Qualitative similarities and differences among various taste stimuli were examined by comparing the generalization patterns of a conditioned aversion from single chemicals to other compounds in 3 different strains of mice (BALB, C3H and C57BL mice). It was observed as a common characteristic in all 3 strains of mice that generalization gradients among sugars and saccharin Na appeared in the order sucrose--saccharin Na--fructose--glucose--maltose, in which the closer stimuli generalized more strongly to each other. Strain differences were found in sensitivities to D-phenylalanine and L-proline, which generalized to sugars and saccharin Na in C57BL mice, but not in BALB and C3H mice. These strain differences correspond quite well to those previously observed in the responses of single chorda tympani fibers to these amino acids in the 3 strains of mice. A hierarchical cluster analysis and a multidimensional scaling analysis showed that 15 compounds including the 4 basic taste stimuli (sucrose, NaCl, HCl and quinine-HCl) were classified into 7 different groups according to their behavioral similarities and some amino acids were not grouped with any of the 4 basic taste stimuli in the 3 strains of mice. These results suggest the possibility that mice perceive tastes of these amino acids in a way different from human taste primaries.

Animals↗