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Biomedical subjects

M Kanda

Publications and source records attributed to M Kanda.

At least 109 records · Page 6Linked to original sources

Endothelium-dependent contraction in intrapulmonary arteries: mediation by endothelial NK1 receptors and TXA2.

1. We have examined whether three natural tachykinins, substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) induce an endothelium-dependent contraction (EDC) in the rabbit isolated intrapulmonary artery. 2. Removal of the endothelium almost abolished the contraction induced by SP (10(-8) M) while it did not attenuate the contraction induced by SP (10(-7) M), NKA (10(-9) - 10(-7) M) or NKB (10(-8) and 10(-7) M). 3. The EDC induced by SP (10(-8) M) was abolished by NK1 antagonists (FK-888, CP-96345, CP-99994 and SR-140333) but not by an NK2 antagonist (SR-48968). 4. The EDC induced by SP was attenuated by cyclo-oxygenase inhibitors (aspirin and indomethacin), thromboxane A2 (TXA2) synthetase inhibitors (OKY-046, KY-234 and KY-063) and a TXA2 antagonist (S-1452). 5. The rank order of potency causing endothelium-independent contraction (EIC) was NKA > NKB > SP. The EIC induced by SP (10(-7) M) was attenuated by an NK2 antagonist but not by NK1 antagonists, cyclo-oxygenase inhibitors, TXA2 synthetase inhibitors or a TXA2 antagonist. 6. In conclusion, SP at 10(-8) M induces EDC via endothelial NK1 receptors and TXA2 production, and SP at 10(-7) M induces EIC via NK2 receptors in the rabbit intrapulmonary artery.

Animals↗

Thromboxane A2 synthetase inhibitors with histamine H1-blocking activity: synthesis and evaluation of a new series of indole derivatives.

A novel series of N-substituted 3-(1H-imidazol-1-ylmethyl)indole carboxylic acid derivatives were prepared and evaluated for thromboxane A2 (TXA2) synthetase-inhibitory and histaminergic H1-blocking activity. Among the compounds synthesized, indole-6-carboxylic acid derivatives showed higher activities than the other positional isomers of carboxylic acid. 1-[3-(4-Benzhydryl-1-piperazinyl)propyl]-3-(1H-imidazol-1-ylmethyl )-1H-indole-6-carboxylic acid (12) had the strongest thromboxane synthetase inhibitory activity (IC50 = 5 x 10(-8) M) and H1-blocking activity (IC50 = 8 x 10(-9) M).

Animals↗

Early embryonic development in vitro and embryo transfer in the cat.

Ten female cats were given a total dose of 200 IU PMSG over 3 days to induce superovulation. One to four-cell stage embryos were collected by flushing the oviducts 48 to 54 hr after the initial 250 IU dose of hCG. Some of the normal embryos collected were examined for culture in Medium-199 supplemented with 20% FCS. After 72 hr of culture, 222/248 (89.5%) had developed to the morula stage, and by 96-168 hr, 110 (64.7%) out of 170 morulae had developed into blastocysts. Four to 12 embryos cultured in vitro per cat were transferred to one of the uterine horns of 12 recipients in which synchronous ovulation had been induced with hCG. All 4 recipients of embryos which had developed to the morula stage on culture day 3, 3 of the 5 recipients of blastocysts on culture days 4-6, and none of the 3 recipients of blastocysts on culture day 7 became pregnant. It is concluded that early feline embryos are capable of efficiently developing into transferable morulae in vitro by ordinary culture methods, but that there is partial developmental arrest from the morula to the blastocyst stage.

Animals↗

Purification and properties of branched chain amino acid aminotransferase from gramicidin S-producing Bacillus brevis.

The branched chain amino acid aminotransferase [EC 2.6.1.42] was purified to a homogeneous state from a gramicidin S-producing strain of Bacillus brevis. The enzyme had a molecular weight of about 93,000 and consisted of two identical subunits, each with a molecular weight of about 47,000. One pyridoxal phosphate is bound per subunit. In addition to branched chain amino acids, the enzyme uses L-phenylalanine and L-tryptophan as the amino donor, indicating that B. brevis branched chain amino acid aminotransferase has a broad substrate specificity for the amino donor. The enzyme utilized 2-oxoglutarate as the amino acceptor. The purified enzyme exhibits its absorption maxima at 332 and 427 nm at neutral pH.

Bacillus↗

Effects of the novel water-soluble calcium antagonist (+/-)-3-(4-allyl-1-piperazinyl)-2,2-dimethylpropyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate dihydrochloride on the responses of isolated canine arteries.

The effects of NKY-722 ((+/-)-3-(4-allyl-1-piperazinyl)-2,2-dimethylpropyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate dihydrochloride, CAS 117241-46-0), a new water soluble dihydropyridine derivative on the responses of isolated canine arteries were examined. NKY-722 (IC50: 5-16 x 10(-10) mol/l), nicardipine (IC50: 5-10 x 10(-10) mol/l) and nifedipine (IC50: 44-195 x 10(-10) mol/l) relaxed four arteries in the potency order of basilar > coronary > mesenteric > intrarenal arteries. NKY-722 was nearly equipotent to nicardipine and about 10 times more potent than nifedipine. [3H]NKY-722 was accumulated in the four arteries in the same order of amount as the vasoinhibitory effect. All three drugs inhibited the contraction induced by Ca2+ and methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylophenyl)-p yri dine-5- carboxylate (Bay K 8644) in the mesenteric arteries, indicating their Ca2+ antagonistic actions. NKY-722 and nicardipine were nearly equipotent and about 100 times more potent than nifedipine on the Ca(2+)-induced contraction and was about 4 times more potent than nicardipine and 400 times more potent than nifedipine on the Bay K 8644-induced contraction. NKY-722, nicardipine and nifedipine relaxed the mesenteric arteries precontracted with KCl by more than 90%, while they relaxed the arteries contracted with PGF2 alpha, 9,11-dideoxy-9 alpha, 11 alpha-methanoepoxy-PGF2 alpha (U-46619) and endothelin-1 only by 40-70%. The IC50 values of NKY-722 and nicardipine were similar and much smaller than that of nifedipine for all four contracting agents.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

[A case of aortic bicuspid valvular endocarditis with congenital left ventricular diverticulum].

A 29-year-old man had a prolonged fever and painful Osler's nodes on his right foot. The aortic valve was bicuspid with vegetation mass and the left ventricular diverticulum was additionally present connecting with the left ventricular outflow tract. An operation was performed after intravenous administration of antibiotics for 3 weeks. The aortic bicuspid valve and the vegetation were removed and replaced by an artificial valve (SJM-HP 19 mm). The left ventricular diverticulum was resected. The echocardiographic findings correlated well with the intraoperative observation.

Adult↗

Transfer of antibodies to kittens from mother cats chronically infected with Toxoplasma gondii.

By indirect immunofluorescence assay, anti-Toxoplasma gondii antibody levels were examined in fetuses and kittens born from chronically infected cats. Titer of anti-T. gondii IgG in sera of kittens born from infected cats was significantly high on the seventh day post-birth, and decreased to a serologically non-detectable level at 8-12 weeks post-birth under continuous suckling of maternal milk. Littermates nursed by a non-infected cat showed a faster rate of IgG antibody depletion. In sera of fetuses obtained from infected cats, anti-T. gondii IgG titer was lower than that of offspring born from infected cats. Anti-T. gondii IgM titer was non-detectable in sera of all kittens and fetuses. Kittens born from infected cats inoculated with T. gondii oocysts on Day 35 after birth shed oocysts and showed a transient increase of anti-T. gondii IgM titer. Findings in this study suggest that anti-T. gondii antibody IgG in kittens is transferred mainly via colostrum and the kittens that receive maternal anti-T. gondii antibodies develop inadequate resistance to T. gondii infection.

Animals↗

Cortical reflex negative myoclonus.

Three patients with progressive myoclonic epilepsy (PME), two of them clinically manifesting only negative myoclonus and the other manifesting both positive and negative myoclonus, were electrophysiologically investigated, and compared with two other patients with PME presenting with only positive myoclonus. Electric stimulation of the median nerve during sustained active wrist extension in the three patients with negative myoclonus often elicited a short lapse of the posture in the stimulated hand associated with a silent period in the muscle discharge with or without being preceded by an abrupt increase in the muscle discharge (C reflex). The occurrence of the stimulus-induced silent period was significantly correlated with that of the giant somatosensory evoked potentials (SEPs), and in two patients the silent period was elicited also in the opposite (non-stimulated) hand when the giant SEP was recorded at the hemisphere ipsilateral to the stimulus as well. In one patient, the duration of the silent period was positively correlated with the amplitude of the cortical SEP. Furthermore, the duration of the induced silent period was closely related to the recovery function of SEP in each individual case. In contrast, in the two patients manifesting only positive myoclonus, the silent period was not elicited by the peripheral stimulation, and the somatosensory cortex was hyperexcitable immediately after the peripheral stimulus. Thus, this stimulus-sensitive negative myoclonus is mediated by a transcortical reflex mechanism, and corresponds to the negative form of the cortical reflex myoclonus ('cortical reflex negative myoclonus').

Adult↗

Entire nucleotide sequence for Bacillus brevis Nagano Grs2 gene encoding gramicidin S synthetase 2: a multifunctional peptide synthetase.

Bacillus brevis Nagano grs2 gene, which encodes gramicidin S synthetase 2 (GS2) catalyzing activation and combination of four constituent amino acids of gramicidin S, namely, proline, valine, ornithine, and leucine, has been sequenced. The open reading frame of grs2 gene specifies a 4,450-amino acid protein with a calculated molecular weight of 508,658. There are four domains with a mean of 1,042 amino acid residues containing a repeated sequence of about 600 amino acids, which is highly homologous to the amino-terminal half of gramicidin S synthetase 1 (GS1) (about 40-50% identity). Three domains of grs2 protein, excluding the first one, show homology over the entire sequences of 1,042 amino acids, but the first domain only shows homology in the conserved 600-amino acid sequence. The last 300-amino acid sequence of grs2 protein following the fourt domain has no homology with any of the above sequences. Translation products of subcloned fragments containing the third or the fourth domain catalyzed ornithine- or leucine-dependent ATP-32Pi exchange, respectively. These results, together with a previous report on a proline-activation domain indicated that the repeated and conserved domains are the individual activation sites of the constituent amino acids; the activation sites are arranged in the order of peptide elongation on GS2. Several motifs of grs2 protein are conserved among the multiple domains of peptide synthetases and aminoacyl or acyl adenylate-forming enzymes.

Amino Acid Isomerases↗

Purification and properties of L-ornithine delta-aminotransferase from gramicidin S-producing Bacillus brevis.

In gramicidin S-producing Bacillus brevis, the addition of L-ornithine to the minimal medium with L-glutamate as the sole carbon and nitrogen source caused an 8-fold induction of L-ornithine delta-aminotransferase [EC 2.6.1.13]. The enzyme was purified to homogeneity. The native enzyme had a molecular weight of about 88,000 after gel filtration and consisted of two subunits with an identical in molecular weight of about 45,000. The enzyme was specific for L-ornithine (Km = 1.05 mM) as an amino donor and for 2-oxoglutarate (Km = 6.25 mM) as an amino acceptor, and catalyzed the conversion of L-ornithine and 2-oxoglutarate, respectively, to glutamic-gamma-semialdehyde, which is spontaneously cyclized to delta 1-pyrroline-5-carboxylate and L-glutamate. The enzyme exhibits an absorption maximum at 425 nm at neutral pH, and 1 mol of pyridoxal phosphate is bound per subunit. The enzyme activity was irreversibly inhibited by gabaculine, and L-ornithine protected the enzyme from the inhibition. The N-terminal amino acid sequence revealed a noteworthy similarity between human and yeast L-ornithine delta-aminotransferases in residues 17-28 of the B. brevis enzyme.

Amino Acid Sequence↗

Mutant genes of gramicidin S synthetase 1 defective in phenylalanine racemization have the same sequence as the wild gene.

Mutant grs1 genes were cloned and sequenced from the Bacillus brevis Nagano BI-4, C-3, E-1, and E-2 strains, which produce defective gramicidin S synthetase 1 (GS1), lacking racemase activity. Surprisingly, these mutant genes had entirely the same sequence as that of the wild type gene. These mutant strains also produce defective gramicidin S synthetase 2 (GS2), lacking 4'-phosphopantetheine, a prosthetic group of this enzyme. The participation of this group in phenylalanine racemization is suggested.

Amino Acid Isomerases↗

Generator mechanism of pain-related evoked potentials following CO2 laser stimulation of the hand: scalp topography and effect of predictive warning signal.

In order to clarify the generator mechanism of pain-related evoked potentials (pain EPs), we studied the scalp topography of the pain EPs following CO2 laser stimulation of hand dorsum by using balanced sternovertebral electrodes as the noncephalic reference in 11 normal volunteers. We also examined the effects of predictive warning signal (light-emitting diode) on the pain EPs. In both the warned and unwarned conditions, all of the 22 hand stimulations showed a large negative component (N2) at the peak latency of about 213 ms followed by a large positive component (P2) at the peak latency of about 329 ms. A preceding small negative component (N1) at the peak latency of about 148 ms was detected in 12 of the 22 hand stimulations in the warned condition and in 13 of the 22 hand stimulations in the unwarned condition. P2 was significantly larger and occurred earlier in the warned condition than in the unwarned condition, whereas other components did not differ between the two conditions, suggesting that an increased attention of the subject to the stimulus influenced the generator mechanism of the P2 component. With regards to the scalp topography, N2 was maximal at Cz and widespread transversely to both sides, whereas P2 was maximal at Cz or Pz and spread more posteriorly than N2. These findings suggest that P2 is generated by a different mechanism from N2 and is most likely associated with pain-related cognitive function. N1 was localized to the contralateral central and midtemporal areas, confirming that the nociceptive inputs are perceived in the sensory cortex in humans. The question as to whether the N1 component is generated in the hand area of the primary somatosensory cortex or in the secondary somatosensory cortex, or in both areas, remains to be solved.

Adult↗

Nuclear magnetic resonance study and secondary structure determination of the antibiotic peptide, aibellin.

Aibellin is a 20-residue peptide antibiotic that has been isolated from the fungus Verticimonosporium ellipticum. Sequence-specific assignment of the 1H- and 13C-NMR signals of aibellin in a methanol solution was achieved by using the two-dimensional NMR technique. Furthermore, its secondary structure was characterized by circular dichroism (CD) and NOESY spectra. The observed NOEs, 3JNHC alpha H coupling constants and amide hydrogen-deuterium (H-D) exchange rates show that the peptide consisted of two alpha-helices and a bent structure around a Pro-14 residue.

Amino Acid Sequence↗

Effect of aibellin, a peptide antibiotic, on propionate production in the rumen of goats.

Aibellin was administered in feed to goats (16 to 18 kg of BW) for 12 d. At 80 mg/d, the molar percentage of propionate in rumen fluid increased significantly in 8 d, and the effect lasted for as long as 10 d after administration ceased. Total VFA concentration, protozoa numbers, and NDF digestibility were not depressed significantly at this dosage but were reduced at 100 mg/d with little further increase in the molar percentage of propionate. Therefore, the optimal dosage of aibellin was 80 mg/d under our experimental conditions. In contrast, monensin (30 mg/d) and gramicidin D (60 mg/d) decreased total VFA concentration and protozoa numbers when supplemented to obtain molar percentages of propionate comparable to 80 mg/d of aibellin. From these results, aibellin may be easier and safer to use than monensin and gramicidin D to modify rumen fermentation.

Animals↗

Structural elucidation of aibellin, a new peptide antibiotic with efficiency enhancing activity on rumen fermentation.

A new peptide antibiotic, aibellin, that had the efficiency enhancing activity on rumen fermentation, was isolated from the culture broth of the fungus, Verticimonosporium ellipticum D1528, and its primary structure was elucidated from spectrometric analysis and chemical degradation. Aibellin is a 20-residue peptaibol, and it has a unique structural feature in the novel C-terminal amino alcohol. Moreover, aibellin is the first peptaibol that possesses two acidic amino acids in the C-terminal region and a Phe residue in the middle of the sequence.

Amino Acid Sequence↗

[The diagnosis of hepatocellular carcinoma determined by pattern of AFP bands separated by Con A affinity electrophoresis].

We analyzed the Con A affinity of serum AFP in patients with a serum AFP concentration greater than 50ng/ml by antibody affinity electrophoresis and Western blotting to distinguish hepatocellular carcinoma (HCC) from benign chronic liver diseases (CLD). Of 164 patients with HCC, 48 (29.3%) had a single band, while 116 (70.7%) had multiple bands. All but three of 65 patients with cirrhosis had a single band. All but one of 32 patients with chronic hepatitis had a single band. We concluded that multiple AFP bands are diagnosis of HCC. This method is a useful assay for distinguishing HCC from CLD.

Adult↗

[Current status and problems of home care for patients with terminal cancer from the viewpoint of local clinics].

On the basis of investigations of 15 patients from our clinic with terminal cancer who were treated by home hospice care, and questionnaires filled out by their caretakers, we examined the current status and problems of the home hospice care system with respect to four phases, namely, the period of preparation for home care (hospitalization period), stable period, terminal period, and the period immediately before death. [Preparation period] The following problems occurred in this phase: introduction of pain management and nutrition management was insufficient; there were only a few cases in which the patient chose home care of his or her own will; and sufficient instructions were not given to caretakers on discharge from the hospital, with respect to medical treatment at home. [Stable period] In two of the four cases in which patients complained of severe pain, the pain was not alleviated because pain management was provided only at the outpatient clinics of the hospital, and collaboration between hospitals and our clinic was insufficient. [Terminal period] Two patients could not be admitted to the hospital upon sudden exacerbation of the condition, suggesting the need to establish a system in which large hospitals can cope with sudden exacerbation of their condition of patients with terminal cancer treated at home. [Period immediately before death] Of the 14 patients who died, 7 died at home and 7 died in the hospital or during transport to the hospital. Three subjects died within a few days after admission. Two of the subjects who died in the hospital or during transport had hoped to stay home until the last moment. Further improvement of the system is necessary in order to meet the needs of terminal cancer patients who wish to die at home. On the basis of the cases taken care of at our clinic, we examined the home care system according classification into three types; hospital-outpatient clinic type; hospital-home care type; and clinic-home care type. An ideal system for the treatment of patients with terminal cancer who hope to stay at home until the last possible moment seems to be the clinic-home care type in which a primary care team that is able to dispatch physicians and nurses, and an around-the-clock support system, are supported by outside organizations and specialists.

Aged↗

Antihypertensive effect of the novel water-soluble calcium antagonist (+/-)-3-(4-allyl-1-piperazinyl)-2,2-dimethylpropyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate dihydrochloride in rats.

The antihypertensive effect of (+/-)-3-(4-allyl-1-piperazinyl)-2,2-dimethylpropyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate dihydrochloride (NKY-722, CAS 117241-46-0) was examined in conscious spontaneously hypertensive rats (SHR), normotensive Wistar rats (NWR) and anesthetized NWR, and its vasodilatory effect was investigated in the perfused NWR mesenteric vascular bed. NKY-722 and nicardipine administered intravenously (10-100 micrograms/kg) and orally (0.3-10 mg/kg) lowered blood pressure dose-dependently with an increase in heart rate in conscious SHR and NWR. The effects of NKY-722 were slower in onset and longer-lasting than those of nicardipine, and were more marked in SHR than in NWR. The effect of NKY-722 was roughly the same as that of nicardipine on intravenous administration. However, NKY-722 was 4-8 times more potent than nicardipine on oral administration. In anesthetized NWR, the hypotensive effects of NKY-722 administered via the femoral vein, portal vein and duodenum were examined in comparison with those of nicardipine. The findings suggest that NKY-722 is more efficiently absorbed from the gastro-intestinal tract and more resistant to the hepatic first pass effect than nicardipine. In the perfused NWR vascular bed, NKY-722 and nicardipine (0.01-1.0 microgram) attenuated the pressor response to KCl dose-dependently. The effect of NKY-722 was slower in onset and longer-lasting than that of nicardipine. In conclusion; NKY-722 has a potent, slow-onset and long-lasting antihypertensive activity, which is mainly attributed to its slow-onset and long-lasting vasodilatory action. NKY-722 is expected to be a useful antihypertensive drug.

Anesthesia↗