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Biomedical subjects

K Honda

Publications and source records attributed to K Honda.

At least 433 records · Page 24Linked to original sources
PubMed1993

Human aortic smooth muscle cells containing angiotensin II type 1 receptors.

We characterized the angiotensin II (AII) receptor in human aortic smooth muscle cells (HASMCs). This receptor binds [125I]Sar1,Ile8-angiotensin II with a high affinity of 0.20 +/- 0.04 nM and a low capacity of 5.3 +/- 0.4 fmol/mg protein (230 +/- 17 sites/cell). Based on the Ki values, the ranking order of [125I]Sar1,Ile8-AII binding inhibition was as follows: Sar1,Ile8-AII > AII > Dup 753 > AII > AI >> PD 123319. The addition of AII to HASMCs induced a rapid, transient increase in intracellular free Ca2+ concentration followed by a lower, sustained phase. When extracellular Ca2+ was removed by adding 3 mM EGTA, this initial transient increase was not changed, but the sustained phase was abolished. These results revealed AII receptors in HASMCs to be of the type 1 receptor subtype, which induce Ca2+ mobilization mainly from intracellular Ca2+ stores.

Angiotensin II↗
PubMed1993

Pharmacological profiles of muscarinic receptors in the longitudinal smooth muscle of guinea pig ileum.

We have examined the pharmacological subtypes of muscarinic receptors mediating phosphoinositide hydrolysis and contraction in the longitudinal smooth muscle of guinea pig ileum with the use of muscarinic antagonists. Carbachol increased the formation of 3H-inositol phosphates (IPs) in a dose-dependent manner in both ileal smooth muscle and the frontal cortex of rats. The rank order of muscarinic antagonists for inhibition of IP formation induced by carbachol was 4-DAMP = atropine > pirenzepine > AF-DX 116 in guinea pig ileal smooth muscle. In ileal smooth muscle, the inhibition by the M1 antagonist pirenzepine was about 15 times less than that by atropine. However, in the rat frontal cortex, the inhibition by pirenzepine was only about 3 times less than that by atropine. The inhibitory effect of the M2 antagonist AF-DX 116 was weak in both ileal muscle and the frontal cortex. The M3 antagonist 4-DAMP strongly inhibited carbachol-induced IP formation in ileal smooth muscle. The rank order of muscarinic antagonists for inhibition of contraction induced by 10(-7) M carbachol was atropine > or = 4-DAMP > pirenzepine > AF-DX 116. These results suggest that both IP formation and the contractile response induced by muscarinic agonists are mediated through the muscarinic M3 subtype in guinea pig ileum.

Animals↗
PubMed1993

Characterization of the endothelin receptor in primary cultures of human aortic smooth muscle cells.

We characterized the endothelin receptor subtypes in primary cultures of human aortic smooth muscle cells (HASMCs) by binding studies. [125I]-Endothelin (ET)-1 saturation experiments showed the existence of a homogeneous population of binding sites with the high affinity (KD value) of 97 +/- 37 pM and maximum number of binding sites (Bmax) of 54 +/- 10 fmol/mg protein. However, almost no specific [125I]-ET-3 binding was observed. Inhibition of [125I]-ET-1 binding in the HASMCs membrane by nonlabeled compounds showed the following order of effectiveness: ET-1 = ET-2 = FR139317 >> ET-3. These results suggest that the endothelin receptor of HASMCs is of the ETA type. We also studied the effect of ET-1 on the cytosolic [Ca2+]i in HASMCs loaded with fura-2/AM. In 1.3 mM Ca2+, ET-1 produced a dose-dependent, biphasic increase in signal with a maximal effect at 10 nM. At this concentration, ET-1 produced a transient increase in [Ca2+]i that reached a peak at 1 min, which was followed by a slow but sustained increase in [Ca2+]i. This second phase was attenuated in Ca(2+)-deficient medium. Furthermore, ET-1 increased inositol 1,4,5-triphosphate in a time- and dose-dependent manner. These results suggest that the endothelin receptors of HASMCs are of the ETA type, which couple with Ca2+ channels.

Aorta↗
PubMed1993

Histamine H2-receptor plays only a minor role in histamine-induced wheal response in the squirrel monkey and guinea pig.

We examined the contribution of the histamine H2-receptor to the histamine-induced wheal response in squirrel monkeys and guinea pigs. Intradermal injection of histamine, 2-pyridylethylamine (a selective H1-agonist), and dimaprit (a selective H2-agonist) dose-dependently induced the wheal response in squirrel monkeys and guinea pigs, although the reaction to dimaprit was much weaker than that to the other agonists. Chlorpheniramine dose-dependently depressed the wheal response in squirrel monkeys and guinea pigs at doses of 0.03-1 mg/kg and 0.03-3 mg/kg, p.o., respectively. However, famotidine, ranitidine and cimetidine had no effect at doses up to 30, 100 and 300 mg/kg, p.o. in guinea pigs and up to 1, 10 and 400 mg/kg, p.o. in squirrel monkeys, respectively. Cimetidine (3-300 mg/kg, p.o.) dose-dependently potentiated the inhibitory effects of chlorpheniramine (0.1 mg/kg, p.o.) in guinea pigs, but had no effects in squirrel monkeys. Famotidine and ranitidine did not alter the response to chlorpheniramine in either animal. These results suggest that the histamine H2-receptor plays only a minor role in the histamine-induced wheal response in squirrel monkeys and guinea pigs.

Animals↗
PubMed1993

Hereditary serum cholinesterase deficiency associated with severe lipid deposition in the kidney.

A 47-year-old woman who was homozygous for a silent cholinesterase gene (hereditary serum cholinesterase deficiency) presented with nephrotic syndrome and hyperlipidemia. Renal biopsy performed in 1986 demonstrated mesangial proliferative glomerulonephritis. Four years later, a second biopsy revealed progression with mesangial interpositions and severe lipid deposition in the glomeruli, tubules and interstitium. This is the first case of hereditary serum cholinesterase deficiency accompanied by renal disease. Serum cholinesterase deficiency may be related to hyperlipidemia and abnormal lipid deposition in the kidney, which promotes the progression of renal disease.

Adolescent↗
PubMed1993

[Recent progress in the diagnosis and treatment of diabetes insipidus].

Recent progress in the diagnosis and treatment of diabetes insipidus (DI) is reviewed. Response of plasma vasopressin (AVP) to 5% hypertonic saline can be a new indicator of the capacity of AVP response to osmotic stimuli. Marked progress in the imaging analysis by computed tomography and magnetic resonance imaging (MRI) has made it possible to evaluate hypothalamic-pituitary lesions in detail. Especially, signal intensity on T1-weighted MR image of neurohypophysis is suggested to reflect its function. Sequencing analysis of genes encoding AVP-neurophysin precursor or AVP receptor is expected to be a most useful method for the diagnosis of inherited DI. Intranasal administration of DDAVP (1-deamino-8-D-AVP) is recommended as a standard therapy for DI.

Administration, Intranasal↗
PubMed1993

[Effects of air injection on hemodynamics and sympathetic nerve activity in urethane-anesthetized rabbits].

We designed this experiment to evaluate effects of intravenous bolus injection of air (0.5 ml.kg-1) on systemic blood pressure (SBP), central venous pressure (CVP), and renal nerve activity (RNA) in urethane-anesthetized rabbits. Animals were divided into the following three groups: animals with neuraxis intact (I group, N = 5), cervical vagotomized animals (V group, N = 5) and sinoaortic denervated animals (SAD group, N = 4). All animals were placed on the right-side down position to avoid effects of the posture throughout the experiments of air embolism. In the I group, air caused profound hypotension (from 95 +/- 10 to 54 +/- 15 mmHg) associated with a significant increase in CVP (from 2 +/- 2 to 7 +/- 3 mmHg) twenty seconds after the injection of air. In spite of the significant hypotension, RNA response did not show any increase for twenty seconds. This response was followed by an augmentation in RNA thirty seconds after air injection. In contrast, vagotomized animals exhibited a significant RNA increase (147 +/- 11% of the control) in response to a decrease in SBP (from 93 +/- 6 to 78 +/- 5 mmHg) and an increase in CVP ten seconds after the administration of air. In SAD group, a rapid and remarkable decline in SBP (from 85 +/- 13 to 47 +/- 12 mmHg) occurred ten seconds after the injection of air. Despite this hypotension, RNA decreased nearly to a noise level after administration of air.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1993

Orthostatic hypotension: with particular reference to experimentally-induced orthostatic hypotension in dogs.

Blood pressure (BP) and heart rate (HR) were measured while standing in a stable position for SPF beagle dogs consisting of 4 females with an average weight of 8.73 +/- 0.58 kg and average age of 7.38 +/- 0.12 months. No anesthetic was used during the procedure. These dogs were subjected to a postural change, a 90 degrees-tilt standing position, and BP and HR were measured one minute and ten minutes later. In addition, 20 mg/kg of tetraethyl-ammonium bromide (TEA) as a gangliolytic drug was administered by i.v. injection within 30 seconds, and then BP and HR were measured in the resting state for 20 minutes. When changing from the resting position to the 90 degrees-tilt standing position after administration of TEA, these were significant decreases in systolic BP, diastolic BP and mean arterial BP one minute and ten minutes later. An experimental model of orthostatic hypotension was considered to have been achieved during these methods.

Animals↗
PubMed1993

[Study on the intraneural topography of the brachial plexus].

An accurate intraneural topography of the nerve fascicules in the brachial plexus provides a correct diagnosis and proper treatment of brachial nerve injuries. Four specimens of the branchial plexus were harvested from human cadavers by careful dissection and serially cross-sectioned from the nerve root level to the peripheral nerve. A spatial relationship between each nerve fascicule was observed and traced proximo-distally with a stereoscopic microscope. The main results and conclusions are as follows: 1. Four types of normal variation were identified in the composing elements of the brachial plexus. It is special interest to note the one in which both the fifth and sixth cervical nerve roots are composed of the dorsal scapular nerve. The existence of normal variations should be taken into account when determining the level and degree of branchial plexus injuries. 2. The nerve fascicules composing each peripheral nerve are most easily discerned at the cord level of the branchial plexus where there are no definite fiber exchanges between those nerve fascicules. These results would indicate that reconstructive nerve operations can be done successfully at the cord level or, at most, at the division level.

Brachial Plexus↗
PubMed1992

Activation of paraventricular neurosecretory cells by local osmotic stimulation of the median preoptic nucleus.

Both electrical and local osmotic stimulation of the median preoptic nucleus (MnPO) predominantly produced excitation of paraventricular (PVN) neurosecretory cells in the rat. By contrast osmotic stimulation of the medial septal region was without effect, although electrical stimulation excited most cells. The results suggest that the MnPO is one of the osmosensitive sites controlling electrical activity of PVN neurosecretory cells.

Action Potentials↗
PubMed1992

A mutant alpha-amylase with enhanced activity specific for short substrates.

The 210th lysine (K210) at the active site in Saccharomycopsis fibuligera alpha-amylase was altered to arginine (R) or asparagine (N) by site-directed mutagenesis. Replacement of K210 by R strengthened the 7th and weakened the 8th subsite affinities. K210 was found to contribute to both the 8th and the 7th subsites. The catalytic activity of the K210R enzyme for the hydrolysis of maltose (G2) was three-times higher than that of the native enzyme due to an increase in the affinity of the 7th subsite adjacent to the catalytic site, whereas the activity of the K210N enzyme for G2 was decreased to 1% of that of the native enzyme by a reduction in the 7th subsite affinity.

Amylose↗
PubMed1992

Single crystal structure of a mixed-chain triacylglycerol: 1,2-dipalmitoyl-3-acetyl-sn-glycerol.

The mixed chain triacylglycerol 1,2-dipalmitoyl-3-acetyl-sn-glycerol was synthesized and its crystal structure was determined to a final reliability factor (R) of 0.11. Two molecules are present in the monoclinic unit cell: space group P2(1); a = 5.375(1), b = 8.286(2), c = 42.96(1) A; beta = 93.30(2) degrees, V = 1910 A3, rho = 1.065 g/cm3, and mu = 5.7 cm-1. The structure is a trilayer: a bilayer of palmitate chains packed in the beta mode (T parallel) and an interdigitated monolayer of acetates. The glycerol backbone and acetate extend roughly linearly from the sn-1 chain. The sn-2 chain bends around the C-2 carbon to lie next to the sn-1 chain. Analysis of the torsion angles indicate that the glycerol conformation of 1,2-dipalmitoyl-3-acetyl-sn-glycerol is markedly different from single acid triacylglycerols and from 1,2-diacyl-sn-glycerols but very similar to 1,2-dimyristoyl-sn-glycero-3-phosphocholine.

Crystallography↗
PubMed1992

Accumulation of allelic loss on arms of chromosomes 13q, 16q and 17p in the advanced stages of human hepatocellular carcinoma.

We examined loss of heterozygosity at 13 loci on 5 chromosomes in hepatocellular carcinomas (HCCs) from 56 patients. In 42 of these cases, regenerative nodules of liver cirrhosis were also analyzed. High frequencies of allelic losses were detected on chromosomes 13q (47%), 16q (40%) and 17p (64%), whereas losses on chromosome 4p and 11p were observed in less than 22% of cases in HCCs. In contrast, LOH was not detected on any loci in cirrhotic nodules. On chromosome 13q, the common region of allelic loss was mapped to the region including the retinoblastoma (RB) locus, by using 8 polymorphic probes. Furthermore, one case with 13q loss had an interstitial deletion of the RB gene, indicating the involvement of inactivation of the RB gene in hepatotumorigenesis. Losses were associated with portal-vein thrombosis or intrahepatic metastasis, increased tumor size, a poorly differentiated phenotype and clinical stage. Losses occurring together on 13q, 16q and 17p were significantly higher in patients in clinical stage IV or histologically poorly differentiated tumors, suggesting that the accumulation of allelic loss occurs in advanced tumors and that patients with multiple allelic losses may have a worse prognosis than those with a single loss.

Alleles↗
PubMed1992

Alteration of bond-cleavage pattern in the hydrolysis catalyzed by Saccharomycopsis alpha-amylase altered by site-directed mutagenesis.

The 210th lysine (K) residue in the Saccharomycopsis alpha-amylase (Sfamy) molecule was replaced by arginine (R) and asparagine (N) residues by site-directed mutagenesis. The influences of the replacements on the bond-cleavage pattern for several substrates were analyzed. Both mutant enzymes, K210R and K210N, cleave mainly the first glycosidic bond from the reducing end of maltotetraose (G4), while the native enzyme hydrolyzes mainly the second bond from the reducing end. We changed successfully the major cleavage point in the hydrolysis reaction of G4. The 8th subsite affinities of the K210R and K210N enzymes are calculated to be +2.52 and -0.01 kcal/mol, respectively, whereas that of the native enzyme is +3.32 kcal/mol as reported in the previous paper. These affinity values suggest that the K210 residue composes the 8th subsite, one of major subsites, and that a positively charged amino residue is necessary for the 8th subsite affinity. The K210N enzyme is found to be less active for short substrates like maltotetraose (G4) than for long substrates like amylose A (approximately G18). The reduced catalytic activity specifically for the short substrates is also attributable to the remarkable decrease in the affinity of the 8th subsite.

Amino Acid Sequence↗
PubMed1992

Estrogen fails to reduce tuberoinfundibular dopaminergic neuronal activity and to cause a prolactin surge in lactating, ovariectomized rats.

The activity of tuberoinfundibular dopaminergic (TIDA) neurons was estimated by measuring the concentrations of dihydroxyphenylacetic acid (DOPAC) in the median eminence of ovariectomized lactating rats, ovariectomized non-lactating female rats and castrated male rats in correlation with the estrogen-induced prolactin (PRL) surge. PRL surge with a peak at 17.00 h was observed in ovariectomized non-lactating rats but not in the other groups. DOPAC levels were significantly lower at 17.00 h than at 11.00 h in non-lactating female rats, but there was no change of DOPAC levels in lactating rats and male rats. These results indicate that TIDA neuronal activity is inhibited at the time of estrogen-induced PRL surge and that the TIDA neurons may alter their function to result in refractoriness of PRL response to estrogen in the lactating rat.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Multi-functional roles of a histidine residue in human pancreatic alpha-amylase.

Functional roles of histidine residues at the active site in human pancreatic alpha-amylase were examined by protein engineering. Three histidine residues at 101, 201, and 299 were converted to asparagine residues, respectively. It was found that His201 played multi-functional roles concerning so many functions; substrate binding, control of optimum pH, change in substrate specificity, activation by chloride ion, and inhibition by a proteinaceous inhibitor.

Binding Sites↗