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Biomedical subjects

Y Nishimura

Publications and source records attributed to Y Nishimura.

At least 847 records · Page 47Linked to original sources

In vitro and in vivo properties of human/mouse chimeric monoclonal antibody specific for common acute lymphocytic leukemia antigen.

A human/mouse chimeric monoclonal antibody specific for a common acute lymphocytic leukemia antigen was efficiently obtained by ligating human heavy-chain enhancer element to the chimeric heavy- and light-chain genes. Cell binding and competitive inhibition assays of both radioiodine and indium-111- (111In) labeled chimeric antibodies demonstrated in vitro immunoreactivity identical with that of the parental murine monoclonal antibodies. The biodistribution of the radiolabeled chimeric antibody in tumor-bearing nude mice was similar to that of the parental murine antibody. Tumor accumulation of radioiodinated parental and chimeric antibodies was lower than that of 111In-labeled antibodies, probably because of dehalogenation of the radioiodinated antibodies. Indium-111-labeled chimeric antibody clearly visualized xenografted tumor. These results suggest that a human/mouse chimeric antibody can be labeled with 111In and radioiodine without the loss of its immunoreactivity, and that chimeric antibody localizes in vivo in the same way as the parental murine antibody.

Animals↗

[A case of secondary amyloidosis complicated with ulcerative colitis].

A 54 year-old woman who had had 4 years history of ulcerative colitis (UC) was admitted to our hospital because of recently developed proteinuria and leg edema. On admission, laboratory findings disclosed massive proteinuria, hypoalbuminemia, acceleration of ESR and elevated of CRP. Her abdominal symptom was remitted. Renal biopsy showed amyloid deposition in glomeruli and arteriole. Amyloid deposition was also found on rectal biopsy. She had no evidence of familial amyloidosis and multiple myeloma. In this case, amyloid deposition might be developed after UC. Secondary amyloidosis due to UC was extremely rare, only 3 cases including ours were reported in Japan.

Amyloidosis↗

[Measurement of MICs on 16 antimicrobial agents for freshly isolated methicillin-resistant Staphylococcus aureus strains].

MICs of 16 antimicrobial agents including a newly synthesized aminoglycoside antibiotic, arbekacin (HBK), were determined against methicillin-resistant Staphylococcus aureus (MRSA) strains which had been isolated since 1988 from patients with refractory infections. 1. The proportion of highly methicillin-resistant strains was large, especially among those isolated from blood and respiratory tract. 2. All the MRSA strains were resistant to all the beta-lactam antibiotics tested. 3. Most of the strains were also resistant to aminoglycosides. However, HBK inhibited the growth of 95% of the strains at 3.13 micrograms/ml or less, showing potent activities even against highly resistant MRSA strains. 4. The MIC distribution of HBK against MRSA strains showed no change since 1986 when year to year data were compared. Based on our studies on the drug resistance pattern of MRSA since 1986, a large proportion of MRSA strains isolated from blood and respiratory tract appeared to be coagulase type II. 5. Netilmicin-resistant MRSAs have increased since 1986, and MRSA resistant to fosfomycin, minocycline, ofloxacin and norfloxacin have also increased in 1989 compared to 1988. 6. The drug resistance pattern of MRSA has been changing every year and they are acquiring multi-drug resistance. Thus, in the treatment of MRSA infections, it is very important to identify the drug susceptibility of MRSA quickly and accurately.

Aminoglycosides↗

[Bronchial atresia of additive anomalous bronchus].

A case of bronchial atresia of additive anomalous bronchus in right middle lobe was reported. A mass and emphysematous lung were found on the chest roentgenogram. CT, and MRI, and it is not difficult to diagnose.

Bronchi↗

Electrical properties of facial motoneurons in brainstem slices from guinea pig.

Electrical properties of guinea pig facial motoneurons (FMNs) were studied in a brainstem slice preparation. FMNs were identified histologically and by antidromic activation. They displayed time-varying responses and inward rectification during both subthreshold depolarization and hyperpolarization. The depolarizing rectification was caused by a persistent Na+ current (INaP); the Cs+-sensitive hyperpolarizing response had a different mechanism. Hyperpolarizing prepulses caused a 4-aminopyridine-sensitive delay of spike initiation. An evoked spike was followed by a fast- and a medium-duration hyperpolarization (the fAHP and mAHP, respectively). Blockade of Ca2+ influx abolished the mAHP without affecting spike duration, whereas spikes were prolonged and the fAHP was abolished by TEA or 4-AP. Adequate depolarization evoked tonic repetitive firing characterized by a steep F-I slope and fast adaptation. Abolition of the mAHP was associated with reduced fast adaptation and increased F-I slope, whereas the mAHP was enhanced and firing rate was slowed after TEA application. Three outward ionic currents were identified during voltage clamp: a rapidly inactivating current, a slowly inactivating current and a slow persistent Ca2+-mediated current (IK(Ca]. We conclude that spike repolarization and the fAHP are governed mainly by fast voltage-dependent currents, whereas progressive activation of IK(Ca) causes fast adaptation and, together with INaP, regulates firing rate.

Action Potentials↗

[Clinical results of hyperthermia alone in the treatment of refractory human tumors].

Retrospective analysis of patients with refractory tumors which were treated with hyperthermia alone in five institutions was performed. Hyperthermia was applied to 30 refractory tumors including 19 deep-seated tumors for a total of 427 sessions by 8 MHz or 13.56 MHz radiofrequency capacitive heating devices. Of the 30 tumors treated, 3 (10%) showed complete regression and 2 (7%) more than 50% regression. Although tumor regression was observed in small tumors, large deep-seated tumors did not respond to heat alone. Thus, response rate of hyperthermia alone was lower than expected, although subjective improvement by hyperthermia was noted in 53% patients. We consider that hyperthermia should be combined with radiation or chemotherapy whenever possible.

Adult↗

Brefeldin A inhibits the targeting of cathepsin D and cathepsin H to lysosomes in rat hepatocytes.

Effect of brefeldin A on the transport of lysosomal acid hydrolases (cathepsins D and H) was investigated in primary cultured rat hepatocytes. Both cathepsins were synthesized as proenzymes and progressively converted to mature enzymes in the control cells. However, BFA strongly inhibited the appearance of the mature enzymes in the cells in a dose dependent manner, suggesting that transport of newly synthesized lysosomal enzymes from the endoplasmic reticulum to lysosomes is blocked by the drug. The inhibitory effect by brefeldin A was reversible. Upon recovery from brefeldin A-intoxication, procathepsin D was effectively targeted into lysosomes, whereas a substantial amount of procathepsin H was found to be missorted, resulting in its secretion into the culture medium.

Animals↗

Histological analysis of the effect of hyperthermia on normal rabbit hepatic vasculature.

The effects of hyperthermia on rabbit hepatic vasculature were studied histologically. To investigate heat-induced vascular damage in the central veins, portal veins, and hepatic arterioles, the left lobes of rabbit liver were heated locally for 30 min in the range of 40-46 degrees C. Hyperthermia was induced by an 8-MHz radiofrequency current heating device using a needle type interstitial applicator. This device allowed application of heat to a central area of 10 x 10 mm no more than 1 degree C below the preset temperature. Within the area of 1 cm2, the percentage of damaged (ruptured or thrombosed) vessels was estimated for each type of hepatic vasculature. Vascular damage following hyperthermia continued up to 24 h after heating for the three types of hepatic vasculature. Central veins were the most thermosensitive followed by portal veins, whereas hepatic arterioles were the most thermoresistant. The temperature causing 50% vascular damage 24 h after heating was 41.5-42.5 degrees C, 42.5-43.5 degrees C, and 44-45 degrees C for central veins, portal veins, and arterioles, respectively. This differential thermal responsiveness of hepatic vasculature may be attributed to the histological structure of the vessels.

Animals↗

Location of phosphorylation site and DNA-binding site of a positive regulator, OmpR, involved in activation of the osmoregulatory genes of Escherichia coli.

The OmpR protein of Escherichia coli is a positive regulator involved in activation of the ompF and ompC genes which encode the major outer membrane proteins OmpF and OmpC, respectively. By employing recombinant DNA techniques, we isolated the N- and C-terminal halves of the OmpR molecule. From the results of biochemical analyses of these fragments, it was concluded that the N-terminal portion contains a site involved in phosphorylation by an OmpR-specific protein kinase EnvZ, whereas the C-terminal part possesses a DNA-binding site for the ompC and ompF promoters.

Bacterial Outer Membrane Proteins↗

Extraordinary stable structure of short single-stranded DNA fragments containing a specific base sequence: d(GCGAAAGC).

Short single-stranded DNA fragments carrying a GCGAAAGC sequence were found to move unexpectedly faster than other fragments of the same length in electrophoresis on a polyacrylamide gel containing a denaturing agent. The fragments were noted to have a stable structure even in 7M urea solution, but the stability cannot be explained simply on the basis of base pair formation alone. Physical characterization of the GCGAAAGC fragment indicated that it takes a hairpin-like structure in spite of the short chain length with only two G-C base pairs, comprised of GCG and AAAGC subsegments, each possessing a helical configuration independent of the others. Some biological implications of this unusual structure are discussed.

Base Composition↗

[Clinical results of thermoradiotherapy of locally advanced and recurrent breast cancers--comparison of results with radiotherapy alone].

From August 1979 through January 1988, 23 breast cancer patients with 25 tumors supposed to be refractory to conventional treatment were treated by thermoradiotherapy. Of the 25 tumors, 10 were locally advanced primary tumors [Group 1], 4 locally advanced recurrent tumors after operation more than 5 cm in maximum diameter [Group 2], and 11 locally recurrent tumors after radiotherapy [Group 3]. The present study was not a formal randomised-trial, but a historical-controlled study. The results were compared with tumors which were treated by radiation therapy alone between July 1962 and August 1979. The historical control groups comprised 11 tumors for Group 1, 17 for Group 2 and 19 for Group 3. Employing 4 types of heating devices (8, 13.56 MHz capacitive RF, 430, 2450 MHz microwave), hyperthermia was administered once or twice a week after irradiation, for 30-60 minutes per session, up to a total sessions of 2-9. Radiotherapy was delivered in fractions of 180 to 200 cGy per day, 5 days per week, up to 28-74.4 Gy in total, or in fraction of 400 cGy, two times per week, up to 28-60 Gy. Tumor temperatures were measured by inserting thermocouples into the tumors. The tumors that did not recur during follow-up of more than 3 months were regarded as locally controlled tumors, and the local control rate was calculated. The local control rate in Group 2 and the local response rate (CR + PRa) in Group 1 were higher than those of the historically controlled tumors. In Group 3, hyperthermia combined with lower total doses of irradiation showed a high local response rate similar to that by radiation therapy alone. Thus local hyperthermia in combination with radiation therapy seems to be more effective than radiotherapy alone for locally advanced and recurrent breast cancers.

Adult↗

Escherichia coli parA is an allele of the gyrB gene.

A thermosensitive (ts) parA mutant, MFT110, of Escherichia coli carried at least two ts mutations. The major ts defect, resulting from a mutation mapped originally at 95 min and complemented by pLC8-47, was most probably due to psd. A plasmid carrying the 1.6 kb BamHI-PvuII fragment recloned from pLC8-47 complemented the major ts mutation in MFT110 and psd(ts) in two mutants, but did not correct the Par phenotype of MFT110. The second ts mutation was salt-repairable and mapped at 83 min close to recF and tnaA. This mutation was linked with the Par phenotype as shown unambiguously by 4',6-diamidino-2-phenylindole stained nucleoids in parA mutant cells with the W3110 genetic background. Both salt-repairable ts and Par traits were corrected concomitantly by a plasmid carrying the chromosomal region solely for the gyrB gene. This strongly suggests that parA is an allele of gyrB.

Alleles↗

A case of incomplete DiGeorge syndrome associated with partial monosomy 22q11.1 due to maternal 14;22 translocation.

We report a boy with some clinical symptoms compatible with a diagnosis of incomplete DiGeorge syndrome. He had a dismorphic face, micrognathia, cleft palate, and heart anomalies similar to DiGeorge syndrome, but lacked aplasia of the thymus or hypoparathyroidism typical of the syndrome. High-resolution banding analysis revealed that his karyotype was 45,XY,-14,-22, +der(14)(14pter----14q32.32::22q11.21----22qter), the consequence of a maternal reciprocal translocation between chromosomes 14 and 22. Precise localization of the gene responsible for the present DiGeorge syndrome was assigned to subband 22q11.1.

Adult↗

Determination of cyclodextrins and branched cyclodextrins by reversed-phase chromatography with pulsed amperometric detection and a membrane reactor.

A high-performance liquid chromatographic method has been developed for the determination of cyclodextrins (CDs) and branched CDs. The method involves their separation on a reversed-phase column using a mixture of water and acetonitrile as an eluant, eluant pH modification with a cation-exchange membrane reactor surrounded by 1.5 M sodium hydroxide solutions, and pulsed amperometric detection with a gold working electrode. The calibration graphs constructed by peak height versus injected amount were linear over the ranges 50-1000 pmol. The detection limits for CDs and branched CDs were about 1-5 pmol at a signal-to-noise ratio of 3. The method was successfully applied to the assay of beta-CD in serum samples.

Chromatography, High Pressure Liquid↗

Evidence that aspartic proteinase is involved in the proteolytic processing event of procathepsin L in lysosomes.

Our recent studies have shown that cathepsin L is first synthesized as an enzymatically inactive proform in endoplasmic reticulum and is successively converted into an active form during intracellular transport and we postulated that aspartic proteinases would be responsible for the intracellular propeptide-processing step of procathepsin L accompanied by the activation of enzyme (Y. Nishimura, T. Kawabata, and K. Kato (1988) Arch. Biochem. Biophys. 261, 64-71). To better understand this proposed mechanism, we investigated the effect of pepstatin, a potent inhibitor of aspartic proteinases, on the intracellular processing kinetics of cathepsin L analyzed by pulse-chase experiments in vivo with [35S]methionine in the primary cultures of rat hepatocytes. In the pepstatin-treated cells, the proteolytic conversion of cellular procathepsin L of 39 kDa to the mature enzyme was significantly inhibited and considerable amounts of proenzyme were found in the cell after 5-h chase periods. Further, the subcellular fractionation experiments demonstrated that the intracellular processing of procathepsin L in the high density lysosomal fraction was significantly inhibited and that considerable amounts of the procathepsin L form were still observed in the light density microsomal fraction after 2 h of chase. These results suggest that pepstatin treatment caused a significant inhibitory effect on the intracellular processing and also on the intracellular movement of procathepsin L from the endoplasmic reticulum to the lysosomes. These findings provide the first evidence showing that aspartic proteinase may play an important role in the intracellular proteolytic processing and activation of lysosomal cathepsin L in vivo. Therefore, we suggest that cathepsin D, a major lysosomal aspartic proteinase, is more likely to be involved in this proposed model in the lysosomes.

Animals↗

Radiofrequency (RF) capacitive hyperthermia combined with radiotherapy in the treatment of abdominal and pelvic deep-seated tumors.

Thermal parameters and tumor response were determined in 33 abdominal and pelvic deep-seated tumors which were treated with hyperthermia in combination with radiation therapy. Hyperthermia was applied regionally for a total of 3-14 sessions (mean; 6.4 sessions), using an 8 MHz radiofrequency (RF) capacitive heating device. An average tumor temperature (Tav) of more than 42 degrees C was achieved in 17 (52%) tumors, and intratumor temperatures above 42 degrees C could be maintained for more than 20 min (effective heat session) in 103 (52%) of the 198 heat sessions. Of the 33 tumors, 4 tumors exhibited complete regression (CR), 7 PRa (80-99% regression), 7 PRb (50-79% regression) and 15 NR (less than 50% regression). Tumor response (CR + PRa) was apparently dependent on the thermal parameters. Tumors with Tav of more than 42 degrees C or those receiving more than three effective heat sessions showed a significantly higher response rate than those heated less effectively. This trend was also noted in minimum tumor temperature. As to radiation dose, most of the responders received a total of 60-70 Gy irradiation. The two characteristic features in tumor response in effectively heated tumors, were slow tumor regression and appearance of an intratumor low density area on post-treatment computed tomography.

Abdominal Neoplasms↗