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Y Nishimura

Publications and source records attributed to Y Nishimura.

At least 811 records · Page 45Linked to original sources
PubMed1990

[Clinical results of loco-regional hyperthermia combined with chemotherapy in the treatment of malignant tumors].

From December 1982 through January 1989, 22 patients with 25 tumors were treated by thermochemotherapy. Of the 25 tumors, 13 were locally recurrent tumors after radiotherapy, 10 distant metastases, and 2 peritoneal disseminations. Employing two types of heating devices (8MHz capacitive RF, 430MHz microwave), hyperthermia was administered once or twice weekly, for 30-60 minutes per session, up to total sessions of 2-15 (mean = 6.9). In some sessions, anticancer drugs were administered intravenously or intraarterially immediately before or simultaneously with hyperthermia. Of the 25 tumors treated, 2 (8%) showed CR, 11 (44%) PR, 7 (28%) NC, and 5 (20%) PD. The better the tumor response was, the higher local control rate was achieved. The survival rate of patients who achieved CR or PR was higher than that of patients who showed NC or PD. Tumor volume, depth of tumor, averaged maximum intratumor temperature, the number of effective heat sessions and the number of anticancer drugs used were shown to affect the tumor response by multivariate analysis. On the other hand, averaged minimum intratumor temperature and history of previous treatment did not affect the tumor response. As almost all the tumors treated were considered to be refractory to radiotherapy or chemotherapy, the tumor responses obtained with thermochemotherapy seemed very encouraging. The expanded trials are warranted to reveal the effectiveness of thermochemotherapy.

Adolescent↗
PubMed1990

The requirement of intrathymic mixed chimerism and clonal deletion for a long-lasting skin allograft tolerance in cyclophosphamide-induced tolerance.

Mechanisms of cyclophosphamide (CY)-induced tolerance were studied. When C3H/He Slc (C3H; H-2k, Mls-1b) mice were primed i.v. with 1 x 10(8) viable spleen cells from H-2-identical AKR/J Sea (AKR; H-2k, Mls-1a) mice and treated with 200 mg/kg of CY 2 days later, a long-lasting skin allograft tolerance to AKR was established. When [C57BL/6 Sea (B6; H-2b, Mls-1b) x AKR]F1 (B6AKF1) cells were used as the tolerogen, however, only a moderate, but not long-lasting, skin tolerance to AKR was observed. In the C3H mice treated with AKR cells and CY, the intrathymic clonal deletion of V beta 6+ T cells, which are strongly correlated with reactivity to Mls-1a antigens, was observed in the chimeric thymus on day 35, although neither the clonal deletion of V beta 6-bearing T cells nor the mixed chimerism was observed in the thymus on day 14. In the C3H mice treated with B6AFKF1 cells followed by CY, however, neither the clonal deletion of V beta 6+ T cells nor the mixed chimerism was observed in the thymus throughout the test period. In the lymph nodes of the C3H mice treated with AKR cells and CY, only CD4+ V beta 6+ T cells, bur not CD8+V beta 6+ T cells, had selectively decreased by day 14, and they were hardly detectable on day 35. The selective decrease of CD4+V beta 6+ T cells in the lymph nodes was also observed by day 14 when B6AKF1 cells were used as the tolerogen, although CD4+V beta 6+ T cells gradually increased on day 35, at which time almost all skin grafts from AKR had already been rejected. These results strongly support the necessity of the intrathymic mixed chimerism and clonal deletion of donor-reactive T cells for a long-lasting skin allograft tolerance in CY-induced tolerance.

Animals↗
PubMed1990

HLA-DQ molecules and the control of Mycobacterium leprae-specific T cell nonresponsiveness in lepromatous leprosy patients.

The major histocompatibility complex (MHC) controls of the outcome of the immune response to T cell-dependent antigens by dictating whether T cell responsiveness will result (MHC-immune response [Ir]genes) or alternatively T cell nonresponsiveness will occur, possibly through the activation of suppressor cells (MHC-immune suppression [Is] genes). In mice, I-A molecules typically restrict antigen-specific helper T cells. In contrast, H-2 I-E molecules have been reported to control nonresponsiveness to a variety of antigens through antigen-specific suppressor cells. In analogy, HLA-DR molecules are the dominant restriction elements for helper T cells in man. This forces the question whether DQ molecules may be involved in controlling nonresponsiveness in man, e.g. through suppression. In one system, T cell nonresponsiveness to Schistosoma japonicum, evidence has been presented supporting this notion. We have now used a second system, Mycobacterium leprae-specific T cell nonresponsiveness, that is typically found in lepromatous leprosy patients. We find positive but limited evidence for a role for HLA-DQ molecules in controlling T cell nonresponsiveness to M. leprae of the 22 nonresponder patients tested, 4 showed a proliferative T cell response to M. leprae after the addition of DQ- but not DR-specific mAb to the cell cultures. In one of the four BCG nonresponders, anti-DQ mAb had a similar effect.

Adolescent↗
PubMed1990

Immunoenzyme localization of cathepsins in the Golgi region of rat hepatocytes and renal tubule cells.

Localization of carboxyl proteinase (cathepsin D) and cysteine proteinases (cathepsins B, H, and L) in Golgi region was studied using an immunoenzyme technique. Rat livers and kidneys were used. The results obtained from the livers were similar to those from the kidneys. All cathepsins were detected in lysosomal compartments such as secondary lysosomes, multivesicular bodies (endosomes), and autophagosomes. Rough endoplasmic reticulum (rER), including nuclear envelope was focally stained. Most of Golgi cisternae were negative, but sometimes only one cisterna or the terminal portion of the cisterna were stained focally. Rarely, the trans Golgi network (TGN) was positive for the proteinases. Among numerous Golgi vesicles, only a few of them were stained. The positive vesicles were divided into two groups, one had a bristle coat and heavily stained, and other were smaller than 40 nm in diameter and weakly stained. The small vesicles seemed to bud from the ER and to fuse with the Golgi cisternae, while the large clathrin-coated vesicles seem to bud from the TGN. The results suggests that cathepsins are transported by vesicular system from the rER to lysosomes via Golgi apparatus. In addition, it is suggested that the small vesicles transport the proteinases from the ER to the Golgi cisternae and the large clathrin-coated vesicles from the Golgi cisternae to the lysosomes.

Animals↗
PubMed1990

Inhibition of intracellular sorting and processing of lysosomal cathepsins H and L at reduced temperature in primary cultures of rat hepatocytes.

Our recent studies with pulse-chase kinetic analysis in primary cultures of rat hepatocytes suggest that newly synthesized lysosomal cathepsins H and L are initially synthesized as larger proform enzymes, and then the precursor molecules are subsequently converted to the mature enzymes by limited proteolysis during the intracellular sorting process. This proteolytic maturation of procathepsins appears to proceed within an acidic environment, and these processing events are closely connected with the activation of enzymes. To further characterize the intracellular processing site for lysosomal cathepsins H and L, the pulse-chase kinetic study was carried out at 20 degrees C in cultured rat hepatocytes, because the transport of the procathepsins was expected to be blocked at the trans-Golgi compartment at 20 degrees C. We show here that the newly synthesized procathepsins are accumulated intracellularly and the processing for lysosomal cathepsins is completely arrested at 20 degrees C along the sorting pathway. The procathepsins thus accumulated in the cell are presumed to be transported to the Golgi complex, since the oligosaccharide moieties of these polypeptides appear to be phosphorylated. When the cells were shifted to 37 degrees C after an incubation for 4 h at 20 degrees C, a gradual increase of the mature forms was found. However, the processing kinetics generating the mature enzymes were slow compared to those in control cells at 37 degrees C. When the NH4Cl was present in the cells after the temperature shift to 37 degrees C, the intracellular processing of procathepsins was considerably retarded and the release of intracellular procathepsins into the extracellular medium was observed. These results indicate that NH4Cl might exert the inhibitory effect on the mannose 6-phosphate receptor-mediated intracellular targeting mechanism for the lysosomal cathepsins. Hence, the intracellular location of procathepsins accumulated at 20 degrees C is considered to be in proximity to the trans-Golgi compartment. Taken together, the present observations suggest that the propeptide-processing step for procathepsins, which is a critical step for generating the active enzymes, proceeds within the prelysosomal compartment or the lysosomes after the enzymes leave the trans-Golgi compartment.

Ammonium Chloride↗
PubMed1990

Immunocytochemical study of the surrounding envelope of autophagic vacuoles in cultured rat hepatocytes.

By the use of electron immunoperoxidase cytochemistry at the ultrastructural level, the relationship of the surrounding sac of the autophagic vacuoles to the different cytomembranes was studied. When the endoplasmic reticulum was completely stained for microsomal carboxyesterase E1, the enzyme was not found to be labeled in the developed envelopes forming autophagic vacuoles. The autophagic envelope at the formative stages was also devoid of albumin which intensely stained Golgi cisternae. However, although it was rare, the endoplasmic reticulum showed an electron-lucent region like an early autophagic envelope in its cisternae which was lacking in carboxyesterase E1. In addition, deeply curving swelled cisternae where carboxyesterase E1 was found at the edges were occasionally encountered. These observations suggest that the segregating membranes arise from an endoplasmic reticulum and the structural characteristics of the endoplasmic membranes change at very early stages of formation of autophagic vacuoles. Acid phosphatase, a lysosomal marker enzyme, began to be localized on sections of the double membranes of newly created autophagic vacuoles. The enzyme spread all along the limiting membranes of the autophagic vacuoles, while, at the same time, the double membranes were converted into a single membrane. A lysosomal membrane glycoprotein (LGP107) was also localized on the surrounding envelope of autophagic vacuoles in a fashion similar to that of acid phosphatase. Lysosomal hydrolases seem to play some role in the conversion of double limiting membranes into a single limiting membrane.

Acid Phosphatase↗
PubMed1990

Proton nuclear magnetic resonance studies of the structure of the Fc fragment of human immunoglobulin G1: comparisons of native and recombinant proteins.

The structure of the Fc fragment of human IgG1 immunoglobulin is compared for the native and recombinant proteins. A recombinant human Fc fragment was expressed by an E. coli system [Kitai K., Kudo T., Nakamura S., Masegi T., Ichikawa Y. and Horikoshi K. (1988) Appl. Microbiol. Biotechnol. 28, 52-56]. The recombinant protein, which presumably lacks oligosaccharides, was used along with the native human Fc fragment obtained by proteolytic digestion of a myeloma IgG1 protein. 1H NMR has been employed along with circular dichroism and fluorescence spectroscopy to discuss the structure of these two types of proteins. It has been concluded that (1) the overall structure of the recombinant protein is quite similar to that of the native protein, which possesses asparagine-linked oligosaccharides, but (2) a significant difference in structure exists in the neighborhood of the glycosylation site. The difference in the effector functions for the two kinds of the Fc proteins has been briefly discussed in terms of the structural change detected by 1H NMR.

Amino Acid Sequence↗
PubMed1990

Initial clinical results of a 430 MHz microwave hyperthermia system using a lens applicator.

The applicability of a 430 MHz microwave (MW) hyperthermia system using an electric field converging (lens) applicator was evaluated. Twenty-two tumors with a maximum tumor depth of less than 7 cm (10 chest wall tumors, 8 abdominal and pelvic tumors, 2 extremity tumors, and 2 neck tumors) were treated with the lens applicator heating system for a total of 72 sessions in conjunction with irradiation or chemotherapy. Of the 72 heat sessions, our treatment goal of 30 min of hyperthermia with all monitored tumor temperatures above 42 degrees C was achieved in 31 sessions (43%). The average tumor temperature was 42.5, 43.1, 42.0, and 42.0 degrees C for chest wall, abdominal and pelvic, extremity, and neck tumors, respectively; similarly 88, 83, 64 and 50% of monitored points exceeded 41 degrees C. A lens applicator heating system increased the penetration depth of MW, and tumor temperature of 41 degrees C at 5 cm from the surface was easily achieved with a four-aperture lens applicator. Of the 22 tumors, 10 tumors exhibited complete response (CR), 7 partial response (PR) and 5 no response (NR). These results suggest that the lens applicator heating system is useful for heating localized subsurface tumors with a maximum tumor depth of 5-6 cm.

Adenocarcinoma↗
PubMed1990

Synthesis and structure-activity relationships of 5-substituted 6,8-difluoroquinolones, including sparfloxacin, a new quinolone antibacterial agent with improved potency.

A series of 5,7-disubstituted 1-cyclopropyl-6,8-difluoro-4(1H)-oxoquinoline-3-carboxylic acids (10-36) were prepared; the C-5 substituent in these compounds comprised halo, hydroxy, mercapto, and amino groups and the C-7 functional group included variously substituted piperazines. In vitro antibacterial screening results indicated that the amino group was optimal among the C-5 substituents. A combination of the C-5 amino group and the C-7 3,5-dimethylpiperazinyl appendage in this series conferred the best overall antibacterial property with lack of adverse drug interactions. Compound 36k [named sparfloxacin, originally AT-4140, 5-amino-1-cyclopropyl-6,8-difluoro-7-(cis-3,5-dimethyl-1-piperazinyl)- 4(1H)-oxoquinoline-3-carboxylic acid] was superior to ciprofloxacin in both in vitro and in vivo potency and hence was selected as a promising candidate for an improved therapeutic agent.

4-Quinolones↗
PubMed1990

Comparative study on specificities of rat cathepsin L and papain: amino acid differences at substrate-binding sites are involved in their specificities.

Sixty-nine rat cathepsin L-susceptible peptide bonds were analyzed employing various peptide substrates. The proteolytic specificities of rat cathepsin L and papain were compared and the results are discussed in relation to differences in amino acid residues around their binding sites. The specificity of cathepsin L, which is characterized by a remarkable preference for hydrophobic amino acids at the P2 site of the scissile peptide bonds, was analogous to that of papain as a whole. This analogous specificity suggests that the binding sites of the two proteases are analogous, as expected from their homologous amino acid sequences. However, there is a slight difference in the preference for S3 site between them. That is, cathepsin L showed a greater preference for bulky and hydrophobic amino acids at the S3 site than did papain. Based on the computer-graphically deduced structure of the binding sites of cathepsin L, the preferences for hydrophobic amino acids at the S2 site and for bulky and hydrophobic amino acids at the S3 site of the protease are supposed to be related to the compensating amino acid substitutions at the S2 site (V133A and V157L) and the reduction in size at the S3 site (Y61Q and Y67L), respectively. The discussion of the effect of the amino acid substitutions on the proteolytic activities of cathepsin L and papain in this paper provides a basis for more advanced studies of the relationship between structure and function of proteases belonging to the papain superfamily by means of protein engineering.

Amino Acid Sequence↗
PubMed1990

Cloning and nucleotide sequence of the ispA gene responsible for farnesyl diphosphate synthase activity in Escherichia coli.

The molecular cloning and the determination of the nucleotide sequence of the ispA gene responsible for farnesyl diphosphate (FPP) synthase [EC 2.5.1.1] activity in Escherichia coli are described. E. coli ispA strains have temperature-sensitive FPP synthase, and the defective gene is located at about min 10 on the chromosome. The wild-type ispA gene was subcloned from a lambda phage clone containing the chromosomal fragment around min 10, picked up from the aligned genomic library of Kohara et al. [Kohara, Y., Akiyama, K., & Isono, K. (1987) Cell 50, 495-508]. The cloned gene was identified as the ispA gene by the recovery and amplification of FPP synthase activity in an ispA strain. A 1,452-nucleotide sequence of the cloned fragment was determined. This sequence specifies two open reading frames, ORF-1 and ORF-2, encoding proteins with the expected molecular weights of 8,951 and 32,158, respectively. A part of the deduced amino acid sequence of ORF-2 showed similarity to the sequences of eucaryotic FPP synthases and of crtE product of a photosynthetic bacterium. The plasmid carrying ORF-2 downstream of the lac promoter complemented the defect of FPP synthase activity of the ispA mutant, showing that the product encoded by ORF-2 is the ispA product. The maxicell analysis indicated that a protein of molecular weight 36,000, approximately consistent with the molecular weight of the deduced ORF-2-encoded protein, is the gene product.

Alkyl and Aryl Transferases↗
PubMed1990

Novel gelatin particle agglutination test for serodiagnosis of leprosy in the field.

We developed a novel gelatin particle agglutination test (MLPA) for the serodiagnosis of leprosy; this test is especially useful for clinical practice and epidemiological surveys of leprosy in countries in which the disease is endemic. The antigen used in the test is the chemically synthesized trisaccharide moiety of Mycobacterium leprae-specific phenolic glycolipid I. MLPA is a simple and easy technique having sensitivity and specificity comparable to those of the conventional indirect enzyme-linked immunosorbent assay. The new technique was found to be useful for monitoring of chemotherapy and predictive diagnosis of high-risk individuals in contact with persons with leprosy and may be useful for the prediction of relapse. We are now preparing to supply a quality-controlled ready-to-use MLPA kit for leprosy control in countries in which leprosy is endemic.

Agglutination Tests↗
PubMed1990

Evaluation of the susceptibility effect on the phase images of a simple gradient echo.

The phase shifts of a simple gradient echo (fast low-angle shot) were correlated with the local change in resonance frequency due to the differences in susceptibility among tissues (susceptibility effect). Susceptibility effects were considered theoretically, and the phase shifts for spherical and cylindrical configurations were calculated. A 1.5-T magnetic resonance unit and phantoms filled with solutions of copper chloride in water were used to obtain the phase images. The phase shifts of the simple gradient echo coincided with the values calculated with use of the sum of the macroscopic magnetic field and the cavity field of Lorentz. The authors conclude that the gap of the phase shifts at interfaces of tissues is useful in the evaluation of differences in magnetic susceptibility among tissues.

Cerebral Hemorrhage↗
PubMed1990

A case of pheochromocytoma producing parathyroid hormone-related protein and presenting with hypercalcemia.

A 54-yr-old man with a left adrenal pheochromocytoma showed mild hypercalcemia and elevated nephrogenous cAMP. Serum levels of PTH and 1,25-dihydroxyvitamin D3 were not elevated. Postoperatively, serum calcium and nephrogenous cAMP declined to normal ranges. Pathologically, the tumor was a benign pheochromocytoma. The clinical findings resembled those of humoral hypercalcemia of malignancy (HHM), and PTH-related protein (PTHrP) immunoreactivity was detected in the tumor extract at a concentration of 80.7 pmol/g wet wt, which is high compared to levels in malignant tumors causing HHM. Production of PTHrP was further confirmed by the demonstration of PTHrP mRNA with Northern blot hybridization analysis. Gel filtration of the extract revealed the presence of at least two different molecules with both immunological and biological activities. One of the peaks appeared close to PTHrP-(1-34), and the other between cytochrome-c and BSA. The latter showed a higher bioactivity to immunoreactivity ratio. These data indicate the multiplicity of PTHrP molecules in pheochromocytoma and support the idea that PTHrP produced by pheochromocytoma causes hypercalcemia in a similar fashion as HHM.

Adenylyl Cyclases↗
PubMed1990

Synthesis of 7-thio-substituted 4-oxoquinoline-3-carboxylic acids with antibacterial activity.

A series of C-7 thio-substituted 1-cyclopropyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acids were prepared and tested for their antibacterial activity. Structure-activity relationships associated with the C-5 and C-7 substituents were discussed. Among the C-7 substituents including alkylthio, arylthio, heteroarylthio, and cyclic aminothio groups, a 2-aminoethylthio group was the best for enhancing in vitro antibacterial activity. The C-5 variants increased activity in the order OH less than F less than H less than NH2. Of compounds prepared in this work, 5-amino-7-(2-aminoethyl)thio-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4 -oxo-quinoline-3-carboxylic acid (18) was the most active.

4-Quinolones↗
PubMed1990

Characterization of crystalline L-carnosine Zn(II) complex (Z-103), a novel anti-gastric ulcer agent: tautomeric change of imidazole moiety upon complexation.

A novel crystalline Zn(II) complex of L-carnosine was prepared and evaluated for inhibitory activity against gastric ulceration in rats. The complex was found to be much more active than various other Zn(II) compounds. It was characterized by means of infrared (IR) spectroscopy, solid-state carbon-13 (13C) and nitrogen-15 (15N) 1H-cross-polarization (CP) magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy and X-ray photoelectron spectroscopy (XPS). The spectroscopic data indicated that L-carnosine coordinates to Zn(II) as a quadridentate ligand. A comparison of the 13C-NMR signals of the imidazole carbons of the complex with those of several histidine derivatives revealed that a tautomeric change of imidazole moiety had occurred upon complexation. The binding mode of the complex was considered to be analogous to that of the corresponding Cu(II) complex.

Animals↗
PubMed1990

Conceptus uptake of the 106RuNO-nitro complex in relation to gestational stages.

106RuNO-nitro complex was administered intravenously to pregnant rats to study uptake of the radioruthenium complex by the conceptus in relation to gestational stages. Each conceptus was sampled periodically with respect to its placenta, fetal membrane, fetal fluid and fetus. Perceptible radioactivity in the fetus was detected only in the later stage of gestation and its relative concentration, defined as the ratio radioactivity per unit weight in the body tissue at sacrifice to that in the whole-body at dosing, was very low compared with other tissues. The average number of fetuses in one litter was 13 and the transfer rate of nitro complex into the fetuses 24 hr after injection to rats on the 20th day of gestation was about 1% of initial maternal dose. The relative concentration in the placenta and fetal membrane was much higher than in the fetus and decreased with time after injection. These results indicate that the placenta and fetal membrane play significant roles as barriers to the transfer of 106RuNO-nitro complex into the fetus.

Animals↗