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Biomedical subjects

K Tsuzuki

Publications and source records attributed to K Tsuzuki.

At least 127 records · Page 7Linked to original sources
PubMed1989

Ion channels activated by quinolinic acid in cultured rat hippocampal neurons.

The membrane responses to quinolinic acid, an excitotoxic brain metabolite, were studied in cultured rat hippocampal neurons with the patch-clamp technique. In the whole-cell recording mode, pressure applications of quinolinic acid elicited inwardly directed membrane currents over a membrane potential range of -60 to -5 mV. The current response reversed at about 0 mV. The current-voltage (I-V) relation of the response had a negative slope conductance at membrane potentials more negative than -40 mV. On removal of Mg2+ from the extracellular solution, the current response showed no region of negative slope conductance at potentials more positive than -60 mV. In Mg2+-free solution applications of quinolinic acid elicited discrete pulse-like current flows through the outside-out membrane patch. The single channel conductance was 40-46 pS over a membrane potential range of -40 to -80 mV, and 50-55 pS at membrane potentials more positive than +30 mV, showing an outward rectification. These values of the single channel conductance were similar to those of the main conducting state of the channels activated by N-methyl-D-aspartate (NMDA). The responses to quinolinic acid were completely suppressed by the NMDA receptor antagonist (+/-)-2-amino-5-phosphonovaleric acid. The results indicate that quinolinic acid selectively activates NMDA receptors in the cultured rat hippocampal neurons.

2-Amino-5-phosphonovalerate↗
PubMed1989

Surgical correction of Stahl's ear using the cartilage turnover and rotation method.

Various operative methods for the correction of Stahl's ear exist. We, however, have devised an alternative "turnover and rotation" procedure. In this procedure, the deformed cartilage itself is used in its original contour to form a new scaphoid fossa, thus simplifying the corrective procedure and establishing a reliable operative method in which reversion to the original state is thought to be highly unlikely.

Adolescent↗
PubMed1989

The influence of congestion and ischemia on survival of an experimental vascular pedicle island flap.

We investigated the relationship between the survival rate of experimental rat pedicle island flaps and mild vascular insufficiency, using a flap designed to induce constant distant necrosis. To eliminate individual variation, the vasculature of each flap was evaluated by injecting dye prior to ligating either or both of the pedicle vessels. Seventy-five male Wistar rats divided into four groups were used. Six of the rats died, so 69 rats were evaluated. Statistically, the dye distance of each group was the same. In the control group of 29 rats, survival length was directly proportional to dye distance. Although the mean values of the survival length minus the dye distance of each flap (delta S.L.) in the venous inadequacy group were not different from those of the control group, there was significant difference between the mean values of the arterial insufficiency and the venous inadequacy plus arterial insufficiency groups and those of the control group. In the pedicle island flap, mild venous inadequacy was less responsible for necrosis when the arterial inflow was sufficient. However, when the arterial inflow was impaired, even mild venous inadequacy affected flap survival.

Animals↗
PubMed1989

Binding of Clostridium botulinum type C neurotoxin to different neuroblastoma cell lines.

Binding of type C neurotoxin (C1 toxin) from Clostridium botulinum (strain Stockholm) to neuroblastoma cell lines was studied by using biotinylated anti-toxin antibody and avidin-biotinylated peroxidase complex. The neurotoxin bound with high efficiency to mouse neuroblastoma (NS-20Y and NIE-115) cells and to hybridomas of rat glioblastoma and mouse neuroblastoma (NG108-C15) cells. The toxin bound little to human neuroblastoma, rat astrocytoma, and nonneural cell lines. Binding of the neurotoxin to NG108-C15 cells was inhibited by gangliosides (GT1b and GM1) and by monoclonal antibodies (CA-12 and C-9), although inhibition was not complete. Sequential preincubation of C1 toxin with GT1b and CA-12 caused complete inhibition. A Scatchard plot of binding of 125I-labeled C1 toxin to NG108-C15 cells showed a hyperbolic curve. Monoclonal antibody CA-12 but not C-9 neutralized the lethal activity of the toxin toward mice. Only C-9 clearly inhibited toxin binding to GT1b. These results suggest that NG108-C15 cells have at least two kinds of receptors for C1 toxin. From the results of binding tests with neuraminidase-, pronase-, and trypsin-treated NG108-C15 cells, the chemical nature of the high-affinity site was presumed to be a glycoprotein containing sialic acid. GT1b may have an important role in low-affinity sites.

Animals↗
PubMed1989

Motilides, macrolides with gastrointestinal motor stimulating activity. I. O-substituted and tertiary N-substituted derivatives of 8,9-anhydroerythromycin A 6,9-hemiacetal.

Chemical modifications of 8,9-anhydroerythromycin A 6,9-hemiacetal (1), which showed gastrointestinal motor stimulating (GMS) activity 10 times more potent than that of erythromycin A (EM-A), were undertaken to search for derivatives having stronger GMS activity and no antimicrobial activity; details are described in this and a subsequent paper. Displacement of a methyl group of the dimethylamino group of 1 with an ethyl group and an isopropyl group provided de(N-methyl-N-ethyl-8,9-anhydroerythromycin A 6,9-hemiacetal (55) and de(N-methyl)-N-isopropyl-8,9-anhydroerythromycin A 6,9-hemiacetal (58), respectively. They showed significant GMS activity and no antibacterial activity. In particular, the GMS activity of 58 was increased to 248 times that of EM-A. EM-A and the derivatives obtained in this study mimic exogenous motilin in the dog. The name "motilide", meaning a motilin-like macrolide, is proposed for this new family of macrolide compounds.

Anti-Bacterial Agents↗
PubMed1989

Motilides, macrolides with gastrointestinal motor stimulating activity. II. Quaternary N-substituted derivatives of 8,9-anhydroerythromycin A 6,9-hemiacetal and 9,9-dihydroerythromycin A 6,9-epoxide.

A series of quaternary ammonium derivatives of 8,9-anhydroerythromycin A 6,9-hemiacetal (1) and 9,9-dihydroerythromycin A 6,9-epoxide (2) has been prepared and tested for antimicrobial activity and gastrointestinal motor stimulating (GMS) activity in the dog (in vivo). The GMS activity is enhanced markedly when small alkyl halides and unsaturated alkyl halides such as allyl bromide and propargyl bromide are added to the dimethylamino group of 1. Among them, N-propargyl-8,9-anhydroerythromycin A 6,9-hemiacetal bromide (3) exhibits GMS activity 2890 times stronger than that of erythromycin A and is completely devoid of antimicrobial activity. The potency of 3 is comparable to that of synthetic motilin both in vitro and in vivo.

Animals↗
PubMed1989

Synthesis and biological activity of analogues of diazaquinomycin A, a new thymidylate synthase inhibitor.

Diazaquinomycin A (1), a new thymidylate (TMP) synthase inhibitor, is poorly soluble in various solvents and exhibits no antitumor activity, while a series of the analogues prepared from 1 are more soluble in water and chloroform than 1, and some of them exhibit antitumor activity in mice. Some analogues in which the lactam rings are replaced by pyridine rings did not inhibit TMP synthase. The diethoxy analogue 25 is a 10-fold more potent inhibitor of TMP synthase than 1. The diacetoxy analogue 23 exhibits significant antitumor activity (T/C: 175%) against Meth-A fibrosarcoma in mice.

Animals↗
PubMed1989

The effect of bispecific monoclonal antibody recognizing both hepatoma-specific membrane glycoprotein and anthracycline drugs on the metastatic growth of hepatoma AH66.

A monoclonal mouse antibody (MoHG) was produced using in vitro cultured AH66R tumor cells treated with cholesteryl hemisuccinate as an immunogen. The antibody identified a 90 kd membrane glycoprotein (HG-90) which is expressed on in vitro cultured hepatoma cell lines AH66 and AH66R. A monoclonal antibody was prepared to the anthracycline drug daunomycin, and it also reacted with adriamycin. A fusion was made of the hybridoma HG-90 with the hybridoma which recognized daunomycin/adriamycin. This bispecific hybridoma A8C recognized both determinants. We studied the therapeutic effect of the A8C bispecific antibody with adriamycin treatment and compared it to the effect of the bispecific antibody to which adriamycin had been conjugated via an albumin (Alb) bridge. The therapy model used was the tumor AH66R in Donryu rats. Tumor bearing rats had their subcutaneous tumors resected on day 10, a time when distant metastases were present. After the surgical resection of the tumor the rats were injected intravenously for two cycles with the bispecific antibodies, followed by the administration of adriamycin (ADR) or MoHG.Alb.ADR conjugates. A slight therapeutic effect occurred with either MoHG or ADR alone but treatment with the bispecific antibody followed by the administration of ADR or with the MoHG.Alb.ADR conjugates significantly prolonged survival, with 60% of the treated animals being "tumor free" when sacrificed on day 80. Lower serum concentrations of alphafetoprotein were observed with the bispecific antibody and drug treatment. This suggests that the bispecific antibody/drug treatment is potentially more beneficial in the suppression of distant metastases than the MoHG.Alb.ADR conjugate. This may be due to an increase in the local drug concentration of unmodified adriamycin.

Animals↗
PubMed1988

Our method of correcting cryptotia.

Our technique for the correction of cryptotia using both Z-plasty and the advancement flap is described. The main advantages are the simple design of the skin incision and the possibility of its application to cryptotia other than severe cartilage deformity and extreme lack of skin.

Child↗
PubMed1988

Characterization of bacteriophage nucleic acids obtained from Clostridium botulinum types C and D.

Nontoxigenic strains of Clostridium botulinum types C and D are converted to toxigenic strains by infection with specific Tox+ bacteriophages. The nucleic acids were extracted from five converting phages, c-st, c-468, c-203, c-d6f, and d-1873, and one nonconverting phage, c-n71, and treated with nucleases. The nucleic acids isolated were not digested by RNase A, but were digested by DNase I and exonuclease III, indicating that they were double-stranded DNA. On the basis of the restriction endonuclease digestion patterns on 0.8% agarose gel electrophoresis, the length of c-st, c-n71, c-468, and c-d6f phage DNAs was estimated to be about 110 kilobase pairs and that of c-203 and d-1873 was about 150 kilobase pairs. The digestion patterns of c-st, c-468, and c-n71 phage DNAs by PstI and HindIII were very similar. High homology was observed in the dot hybridization test. For other phages and nucleases, a good similarity was not observed. Only a little similarity was observed between c-203 and c-d6f phages. The existence of the structural genes for the toxin in both c-st and c-n71 phages was confirmed by the hybridization test with these phage DNAs and the oligonucleotide probe which represented the DNA sequence predicted for the N-terminal amino acids (2 to 17) of C. botulinum type C toxin. The loss of the converting ability of c-n71 phage may be caused not by the deletion of the tox+ gene but rather by the base mutation in c-st phage DNA.

Amino Acid Sequence↗
PubMed1988

Establishment of a monoclonal antibody recognizing an antigenic site common to Clostridium botulinum type B, C1, D, and E toxins and tetanus toxin.

The partial amino acid sequence of the light-chain (Lc) component of Clostridium botulinum type C1 toxin was determined. The sequence was quite similar to those of the other types of botulinum and tetanus toxins. Nine monoclonal antibodies against botulinum type E toxin were established by immunizing BALB/c mice with type E toxoid or its Lc component. Six antibodies reacted with the heavy-chain component and three reacted with the Lc component of the toxin. One of the latter three antibodies reacted with botulinum type B, C1, and D toxins and tetanus toxin, as well as botulinum type E toxin. This antibody recognized the Lc components of these toxins, indicating that there exists one common antigenic determinant on the Lc regions of these toxins.

Amino Acid Sequence↗
PubMed1988

Combination-sensitive neurons in the ventroanterior area of the auditory cortex of the mustached bat.

1. Because the ventroanterior (VA) area is one of the target areas of the FM-FM area in the auditory cortex of the mustached bat, Pteronotus parnellii parnellii, response properties of combination-sensitive neurons in this area were studied with constant-frequency (CF) tones, frequency-modulated (FM) sounds, and sounds similar to the bat's biosonar signal (pulse), which consisted of long CF components (CF1-4) and short FM components (FM1-4). CF1-4 and FM1-4 are the components in the four harmonics (H1-4) of the pulse. 2. Combination-sensitive neurons are clustered in a small area immediately anteroventral to the Doppler-shifted CF processing (DSCF) area and posteroventral to the anterior division of the primary auditory cortex. Because this cluster in the VA area is small, it was difficult to record a sufficient number of combination-sensitive neurons to explore the functional organization of the cluster, but it was found that the response properties of these VA neurons were unique. 3. Combination-sensitive neurons in the VA area are tuned to particular combinations of signal elements similar to the first and second harmonics of the pulse and/or echo. Unlike neurons in the FM-FM, dorsal fringe (DF), and CF/CF areas, no neurons in the VA area are tuned to the signal elements in the first and third or fourth harmonics. 4. The great majority of combination-sensitive neurons in the VA area can not be easily classified into either FM-FM or CF/CF neurons, because they show facilitative responses to combinations of CF1/CF2, FM1-FM2, and FM1-CF2. Therefore, they are called H1-H2 neurons. In the FM-FM and CF/CF areas, all the neurons could be easily classified as FM-FM or CF/CF. This uniqueness of H1-H2 neurons is related to the fact that their best frequencies for facilitation are predominantly between 61.0 and 62.0 kHz, i.e., within the frequency range of stabilized Doppler-shifted echo CF2. 5. In addition to 27 H1-H2 neurons, 7 FM1-FM2 neurons were also recorded in the VA area. The best delays of these H1-H2 and FM1-FM2 neurons measured with FM1-FM2 pairs are between 1 and 10 ms. Unlike neurons in the FM-FM and DF areas, their delay-tuning curves are very broad, even if their best delays are short, and extend beyond zero delay to several millisecond "negative" delays of the FM2 from the FM1, i.e., several millisecond delays of the FM1 from the FM2.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗