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Biomedical subjects

K Honda

Publications and source records attributed to K Honda.

At least 379 records · Page 21Linked to original sources
PubMed1994

Characterization of YM022: its CCKB/gastrin receptor binding profile and antagonism to CCK-8-induced Ca2+ mobilization.

We investigated the antagonistic activity of (R)-1-[2,3-dihydro-1-(2'- methylphenacyl)-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl]-3- (3-methylphenyl) urea (YM022), a benzodiazepine derivative, at CCKB/gastrin receptors. This compound potently inhibited [125I]CCK-8 binding to rat brain CCKB/gastrin receptors with a Ki value of 0.26 nM, but it showed weak affinity for rat pancreas CCKA receptors (Ki = 270 nM). Selectivity for CCKB/gastrin receptors was 1000-fold greater than that for CCKA receptors. Changes in intracellular free Ca2+ concentration ([Ca2+]i) in response to CCK-8 were measured in a rat anterior pituitary cell line GH3 by fura-2 fluorometry. CCK-8 (1-100 nM) dose-dependently increased [Ca2+]i in these cells, whereas YM022 had no effect on baseline [Ca2+]i even at the highest concentration of 100 nM. YM022 inhibited the mobilization of [Ca2+]i elicited by 10 nM CCK-8 in a concentration-dependent manner with an IC50 value of 4 nM. In conclusion, YM022 is an extremely potent and highly selective antagonist of CCKB/gastrin receptors. This compound is therefore useful for studying the physiological and pharmacological roles of CCKB/gastrin receptors.

Animals↗
PubMed1994

Spectral intermediate in the reaction of ferrous cytochrome P450cam with superoxide anion.

The addition of KO2 to ferrous cytochrome P450cam in the presence of d-camphor under anaerobic condition resulted in the formation of exo- and endo-5-hydroxycamphor. The product formation was inhibited by the addition of superoxide dismutase, not catalase. The ferrous form of P450cam reacts with O2- to form an intermediate species of the enzyme, of which spectrum is closely similar to that of the oxygenated form of P450cam. Subsequently, the intermediate was converted to native ferric P450cam. In contrast, ferrous form of horseradish peroxidase reacted with O2- to form Compound I of the enzyme without detection of intermediates.

Bacterial Proteins↗
PubMed1994

Vasopressin V1 receptor in rat hippocampus is regulated by adrenocortical functions.

Two subtypes of arginine vasopressin (AVP) receptors (V1 and V2) have been distinguished. In this study, we examined the characteristics of AVP binding in rat hippocampus and the effects of bilateral adrenalectomy and adrenal steroids on its [3H]AVP binding. [3H]AVP binding to rat liver and the hippocampal membranes was strongly inhibited by the V1 antagonist, OPC-21268. ADX resulted in a significant decrease in the Bmax of AVP binding in the hippocampus. Chronic treatment with aldosterone and corticosterone restored the ADX-induced reduction, but treatment with dexamethasone did not. These results suggest that the AVP V1 receptor in the hippocampus is regulated by adrenocortical neuroregulatory functions.

Adrenal Cortex↗
PubMed1994

The Bacillus subtilis SRP54 homologue, Ffh, has an intrinsic GTPase activity and forms a ribonucleoprotein complex with small cytoplasmic RNA in vivo.

B. subtilis Ffh is a homologue of SRP54, which is one component of the mammalian signal recognition particle. B. subtilis Ffh was expressed in E. coli as a derivative with a hexa histidine tag at the COOH terminus and purified to near homogeneity. The purified Ffh had intrinsic GTPase activity as predicted from its amino acid sequence. Using antiserum against Ffh, we also demonstrated that B. subtilis Ffh forms a complex with scRNA which is a B subtilis homologue of the RNA component of SRP in vivo, and that half of the resulting complex is found in the peripheral fraction of the cytoplasmic membrane where the initiation of protein translocation occurs. These findings provide evidence of a ribonucleoprotein complex in B. subtilis, reminiscent of SRP.

Animals↗
PubMed1994

Oxidized glutathione regulates physiological sleep in unrestrained rats.

Oxidized glutathione (GSSG) is an active component of sleep-promoting substance (SPS) which was originally extracted from the brainstems of 24-h sleep-deprived rats. We analyzed somnogenic and thermoregulatory activities of five doses of GSSG in unrestrained rats. A nocturnal 10-h intracerebroventricular infusion of GSSG significantly enhanced slow wave sleep (SWS) at the dosage range from 20 to 50 nmol and paradoxical sleep (PS) at 25 nmol at the expense of wakefulness during the 12-h dark period. The dose-response relations exhibited a bell shape for both SWS and PS. The administration of 25 nmol/10 h GSSG induced the maximal increase in the total time of nocturnal sleep (35% above the baseline for SWS and 86% for PS). The enhancement of sleep was mainly due to an increase in the duration of SWS episodes and in the number of PS episodes. GSSG at 25 nmol/10 h elicited significant fluctuations in brain temperature (Tbrain), biphasic hypothermal and hyperthermal reactions during the infusion period, followed by a hyperthermal state during the subsequent light period of the recovery day and then a hypothermal state during the dark period. On the basis of recent literature on the inhibitory action of GSSG on the excitatory synaptic membrane of rat brain, we speculate that the sleep-enhancing activity of GSSG was caused by its physiological modulation on the glutamatergic neurotransmission in the brain.

Animals↗
PubMed1994

Roles of the aromatic residues conserved in the active center of Saccharomycopsis alpha-amylase for transglycosylation and hydrolysis activity.

The molecular structure of Saccharomycopsis fibuligera alpha-amylase was predicted by a homology-based modeling technique, and the amino acid residues composing the active site were displayed with color codes according to their order of conservation. We noticed two highly conserved aromatic residues located in the active center, tyrosine 83 (Y83) and tryptophan 84 (W84), and examined their roles in catalytic activity by site-directed mutagenesis. The W, leucine (L), and asparagine (N) mutants at Y83 and the L mutant at W84 showed remarkable enhancement of transglycosylation activity and complementary decreases in native hydrolysis activity. The phenylalanine (F) mutant at Y83 and the F and Y mutants at W84 only decreased hydrolysis activity. Mechanistic and kinetic studies of these mutants using a reducing-end-blocked substrate and a hydrolysis-specific substrate revealed a probable transglycosylation mechanism and critical contributions of the 83rd and 84th aromatic residues to efficient hydrolysis. Given that aromatic residues stack against the faces of sugars, we assumed that Y83 and, presumably, W84 play roles in the binding of oligosaccharide substrates through the stacking interaction and in the indirect fixation of the catalytic water molecule through hydrogen bonding with the hydroxyl of the bound substrates. Mutations to nonaromatic residues could cause slight changes in the binding topology of substrates to favor transglycosylation over hydrolysis.

Amino Acid Sequence↗
PubMed1994

High-affinity specific [3H]tamsulosin binding to alpha 1-adrenoceptors in human prostates with benign prostatic hypertrophy.

The binding of a novel radioligand, [3H]tamsulosin, to human prostatic membranes with benign prostatic hypertrophy (BPH) has been characterized. [3H]Tamsulosin rapidly associated with its binding sites in human prostatic membranes with BPH, and the binding reached steady state by 30 min at 25 degrees C. The rate constants for association and dissociation of [3H]tamsulosin binding were calculated to be 0.21 +/- 0.05/nM per minute and 0.01 +/- 0.004/min, respectively. The specific binding of [3H]tamsulosin in human prostatic membranes was saturable and of high affinity (Kd = 0.04 +/- 0.01 nM). The density of [3H]tamsulosin-binding sites (Bmax) was 409 +/- 28 fmol/mg protein. The Kd and Bmax values for [3H]tamsulosin binding in human prostates were significantly lower than those for [3H]prazosin binding. [3H]tamsulosin binding was remarkable for its significantly lower degree of nonspecific binding. Six alpha-adrenoceptor antagonists competed with [3H]tamsulosin for the binding sites in the rank order: tamsulosin > WB4101 > prazosin > S-(+)-isomer > naftopidil > yohimbine. The binding affinities (pKi) of these antagonists for [3H]tamsulosin binding in human prostates closely correlated with their pharmacological potencies (pA2) in prostates. In conclusion, [3H]tamsulosin selectively labels alpha 1-adrenoceptors in human prostates, and thus may become a useful radioligand for the further analysis of these receptors.

Adrenergic alpha-Antagonists↗
PubMed1994

Non-Hodgkin's lymphoma of the gastric stump developing 9 years after a distal gastrectomy for a peptic ulcer: a case report and review of the literature.

We report herein the case of a 65-year-old man who developed non-Hodgkin's lymphoma of the gastric stump 9 years after undergoing a distal gastrectomy for a gastric ulcer. The patient presented with epigastric discomfort, and an upper gastrointestinal series and gastroscopy revealed a lymphoma lesion located close to the site of his gastroduodenal anastomosis. A total gastrectomy was performed, followed by combination chemotherapy, comprised of vincristine, Endoxan, prednisone and Adriamycin (VEPA). Histologically, the resected specimen was diagnosed as non-Hodgkin's lymphoma. The patient has remained well without any signs of recurrence for 18 months since his operation. Although there have been a number of reports of adenocarcinoma developing in the gastric stump following surgery for peptic ulcers, the development of malignant lymphoma under such conditions is rare. Following the presentation of this case, we review the available literature and discuss the possibility of malignant lymphoma developing in the gastric stump.

Aged↗
PubMed1994

Haematological improvement by long-term administration of recombinant human granulocyte-colony stimulating factor and recombinant human erythropoietin in a patient with severe aplastic anaemia.

A 6-year-old girl with post-hepatitic severe aplastic anaemia was referred to our hospital. Haematological examination showed a haemoglobin level of 5.2 g/dl, platelet count of 8,000/microliters, and white blood cell count of 130/microliters with 17% neutrophils. She was treated with recombinant human granulocyte-colony stimulating factor (15 micrograms/kg/day i.v.) and cyclosporin A (6 mg/kg/day p.o.). The absolute neutrophil count gradually increased, but Hb and platelets were not improved. The intravenous administration of recombinant human erythropoietin (100 U/kg three times a week) was started, and the reticulocyte count reached 20,000/microliters on day 12. The platelets increased to 81,000/microliters after 16 months of combined administration of recombinant human granulocyte-colony stimulating factor, recombinant human erythropoietin and cyclosporin A. After 20 months of combined administration, the haematological results were: Hb, 13.1 g/dl; platelets 80,000/microliters; WBC, 9500/microliters with 40% neutrophils. After recombinant human granulocyte-colony stimulating factor treatment, the myeloid elements of the bone marrow and the number of granulocyte-macrophage colony forming units increased. Bone marrow erythropoiesis and erythroid colonies also increased after recombinant human erythropoietin administration. The clinical course suggested a beneficial effect of haemopoietic growth factors and cyclosporin A in post-hepatitic aplastic anaemia.

Anemia, Aplastic↗
PubMed1994

Topical applications of trichloroacetic acid as therapy for nasal allergy.

A group of 22 patients (27 nostrils) with nasal allergies was treated with 80 w/v trichloroacetic acid applied to the inferior turbinates. Patients were then evaluated prospectively based on both subjective responses and clinical examinations. Allergic symptoms were reduced significantly, especially those involving nasal obstruction and watery rhinorrhea. Nasal airflow resistance also improved after treatment (P < 0.001). Nasal provocation testing revealed a significant decrease in post-treatment responses (P < 0.001). No severe side effects were noted after treatment. Findings demonstrated that local application of trichloroacetic acid is a safe, effective and simple treatment for outpatients with symptomatic nasal allergies.

Administration, Intranasal↗
PubMed1994

Segregation analysis of IgE responses to Cryptomeria japonica pollen antigen in vivo.

The IgE response to Cryptomeria japonica pollen antigen (CPAg) in vivo was determined by radioimmunoassay of the plasma of 525 members from 98 families with known nasal allergies. Based on responses, patients were classified into a non-responder or low-responder group (non/low) and a high-responder group. Segregation analysis revealed that the IgE non/low responsiveness to CPAg involved a single dominant trait. The gene frequency was calculated to be 0.44-0.60. The IgE non/low response to CPAg was found to be mediated by CPAg-specific suppressor T cells. These findings demonstrated that the phenotypic variation of IgE responsiveness to CPAg is not due the immune response gene, but rather is mediated by the immune suppression gene for CPAg, via CPAg-specific suppressor T cells.

Adolescent↗
PubMed1994

Characterization of muscarinic cholinoceptor in primary culture of smooth muscle cells from human prostate.

We obtained a primary culture of prostatic cells by an explant method from patients with benign prostatic hypertrophy (BPH). Ultrastructural morphology and growth characteristics of these cells conformed to those reported for smooth muscle cells isolated from vascular and visceral tissue sources. The cells retained their original character including the presence of androgen receptor, acid phosphatase and normal chromosomal number. [3H]-methyl-quinuclidinyl benzilate (QNB) saturation experiments showed the existence of a homogeneous population of binding sites with a high affinity and low capacity (KD = 0.17 +/- 0.05 nM., Bmax = 15,000 sites per cell). Inhibition of [3H]-methyl-QNB binding by nonlabelled compounds showed these [3H]-methyl-QNB binding sites to be M2 muscarinic cholinoceptors. cAMP formation induced by forskolin and isoproterenol was inhibited by carbamoyl choline and oxotremorine. These results suggest that prostatic smooth muscle cells contain M2 muscarinic cholinoceptors and that these cholinoceptors couple adenylate cyclase inhibition.

Cells, Cultured↗
PubMed1994

Characterization of the adrenoceptor antagonistic and antihypertensive activity of oral amosulalol, a combined alpha- and beta-adrenoceptor antagonist, in hypertensive rats.

The adrenoceptor antagonistic and antihypertensive effects of amosulalol, 5-[1-hydroxy-2-[[2-(o- methoxy)ethyl]-2-ethylbenzenesulfonamide HCl, a combined alpha- and beta-adrenoceptor antagonist, were examined in hypertensive rats. Oral administration of amosulalol (1-30 mg/kg) produced a dose-dependent antihypertensive effect without reflex tachycardia in conscious spontaneously hypertensive rats (SHR) with a duration > 10 h after the higher doses (10 and 30 mg/kg). Amosulalol was approximately threefold more potent than labetalol and arotinolol in decreasing blood pressure (BP) in conscious SHR. Oral (p.o.) administration of amosulalol 10 mg/kg produced equally potent reductions in mean arterial BP (MBP) without reflex tachycardia in deoxycorticosterone acetate-salt rats (DHR) and renal hypertensive rats (RHR) as it did in SHR. Repeated oral administration (1, 4, 8, or 12 weeks) of amosulalol 10 mg/kg elicited an antihypertensive effect without evidence of tolerance in conscious SHR and produced a rightward shift in phenylephrine (PE)-induced vasopressor and isoproterenol (ISO)-induced positive chronotropic responses with dose ratios of 3.3-12.5 and 3.7-6.4, respectively, in pithed SHR. In addition, single p.o. administration of amosulalol 10 mg/kg produced a rightward shift in these responses with dose ratios of 12.1 and 3.5, respectively, in pithed SHR. Amosulalol exerted antihypertensive activity without tachycardia through blockade of vascular alpha- and cardiac beta-adrenoceptors, and its activities were constant even after repeated p.o. administration.

Administration, Oral↗
PubMed1994

Small cytoplasmic RNA of Bacillus brevis: transcriptional and phylogenetic analysis.

Using a DNA fragment of Bacillus subtilis scRNA as a probe, a Bacillus brevis gene encoding the small cytoplasmic RNA was cloned and characterized. B. brevis scRNA consists of 273 nucleotides; the sequence has comparatively low homology (approximately 70%) with other Bacillus sequences. Phylogenetic analysis indicated that B. brevis forms a line of descent distinct from other Bacillus species. However, despite the low overall homology, both functional nucleotide sequence and secondary structural features defined among signal recognition particle (SRP) RNA family members were well conserved.

Bacillus↗
PubMed1994

Comparative study on alpha 1-adrenoceptor antagonist binding in human prostate and aorta.

1. Specific binding of [3H]-prazosin in prostatic and aortic membranes of humans was saturable and of high affinity (prostate: apparent dissociation constant, Kd = 0.35 +/- 0.03 nmol/L; aorta: Kd = 0.26 +/- 0.03 nmol/L). The density of [3H]-prazosin binding sites (Bmax) for prostate and aorta was 546 +/- 31 and 61.6 +/- 1.6 fmol/mg protein, respectively. 2. Prazosin, YM617, naftopidil and urapidil competed with [3H]-prazosin for the binding sites in a dose-dependent manner in the prostate and aorta of humans. The binding affinities of these antagonists in both tissues were compared, based on the inhibition constant, Ki. Both prazosin and urapidil showed similar affinity to [3H]-prazosin binding sites in human tissue, whereas YM617 and naftopidil showed approximately a 12 and two times higher affinity, respectively, to alpha 1-adrenoceptor sites of prostate than aorta. 3. The chloroethylclonidine treatment reduced partially the Bmax values for specific [3H]-prazosin binding in the prostate and aorta of humans with little effect on the Kd values. 4. These data suggest that YM617 is a relatively selective antagonist of human prostatic alpha 1-adrenoceptors.

Adrenergic alpha-Antagonists↗
PubMed1994

Morphological and acoustical analysis of the nasal and the paranasal cavities.

Morphological measurements of the nasal and paranasal cavities were conducted to investigate their relevance to the acoustic properties of the human nasal tract. The magnetic resonance imaging (MRI) technique was used to measure the three-dimensional geometry of the vocal tract. The area function of the nasal tract was calculated for seven subjects based on data obtained during natural breathing. The entire vocal tract was measured for five subjects during sustained production of nasal consonants. A marked morphological difference was observed between our data and previously published data [A. S. House and K. N. Stevens, J. Speech Hear. Disord. 21, 218-232 (1956); G. Fant, Acoustic Theory of Speech Production (Mouton, The Hague, 1970), 2nd ed., p. 139] particularly in the middle portion of the nasal tract. Previous data derived from cadaver specimens showed a large cavity in the middle portion possibly due to an absent or dehydrated mucous membrane, while our data showed narrow passages due to thickly layered mucosa. It has been confirmed by an additional experiment that the wide cavity is reproducible by applying an adrenergic agent to the nasal mucosa. Transfer functions of the vocal tract and the nasal tract were calculated from measured data, and compared to spectra of real speech signals recorded subsequent to the MRI experiment. The results indicate that asymmetry between the two nasal passages can cause extra pole-zero pairs, and suggest that the paranasal cavities play an important role in shaping the spectral characteristics of human nasal sounds.

Adult↗
PubMed1994

Structural requirements of Bacillus subtilis small cytoplasmic RNA for cell growth, sporulation, and extracellular enzyme production.

Bacillus subtilis small cytoplasmic RNA (scRNA; 271 nucleotides) is a member of the signal recognition particle (SRP) RNA family, which has evolutionarily conserved primary and secondary structures. The scRNA consists of three domains corresponding to domains I, II, and IV of human SRP 7S RNA. To identify the structural determinants required for its function, we constructed mutant scRNAs in which individual domains or conserved nucleotides were deleted, and their importance was assayed in vivo. The results demonstrated that domain IV of scRNA is necessary to maintain cell viability. On the other hand, domains I and II were not essential for vegetative growth but were preferentially required for the RNA to achieve its active structure, and assembled ribonucleoprotein between Ffh and scRNA is required for sporulation to proceed. This view is highly consistent with the fact that the presence of domains I and II is restricted to sporeforming B. subtilis scRNA among eubacterial SRP RNA-like RNAs.

Bacillus subtilis↗