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Biomedical subjects

K Honda

Publications and source records attributed to K Honda.

At least 343 records · Page 19Linked to original sources

[The possibilities and problems of a home setting hospice service for a patient living alone].

We provided home care service for a patient in the terminal stage of lung cancer. This patient had some difficulties, such as living by himself, having little financial means, and unable to use welfare programs because of the age restrictions of certain institutions. We, however, arranged the home care the patient wanted by carefully making contact with the health and welfare institutions involved. Through this case, we reported the possibilities and problems of a home setting hospice service for a patient living alone.

Home Care Services, Hospital-Based↗

Anemia-inducing substance from plasma of patients with advanced malignant neoplasms.

Patients with advanced malignant neoplasms develop anemia and immunosuppression. During an attempt to identify the causes, we have found that plasma from such patients makes RBCs more fragile in hypotonic buffer, according to results obtained with a coil planet centrifuge. Plasma from these patients suppresses mitogen-stimulated lymphocyte proliferation. In this study, we identified the substance with these effects as a protein. During two-dimensional gel electrophoresis, two isomers with M(r) 50,000 and slightly different isoelectric points near 6.0 were found. Cell fractionation showed that these proteins were in both the cytosol and the nuclear fraction of cells in neoplasms. Another protein with the same antigenicity and a M(r) 100,000 found in the nuclear fraction of cells in neoplasms.

Anemia↗

Safety of the donor in living-related liver transplantation--an analysis of 100 parental donors.

The safety and lack of undue operative stress on the donor are documented from an analysis of 100 parental donors, whose children (3 months to 17 years old), received LRLTx at our institution between June 1992 and May 1994. Survival rate of recipients was 86%. No primary nonfunctioning liver was observed. The donors were 56 mothers and 44 fathers. Their ages ranged from 19 to 51 years and their weight ranged from 44 to 80 kg. They received partial liver resections to harvest the grafts. With regard to the liver graft, the left lobe was used in 24 cases (group L) and the left lateral segment was used in 75 cases (group S). The right lobe was used in one case. In the two groups, blood losses were 242 +/- 5 (S) and 312 +/- 14 ml (L); operation times were 6.22 +/- 0.11 (S) and 7.15 +/- 0.21 hr (L), respectively; in both groups, the postoperative hospital stay was 11 days (S, L). No significant differences between the two groups were observed in peripheral RBC and WBC count or serum AST. An increase in total bilirubin was not observed. In the exceptional case using the right lobe, blood loss of 2300 ml necessitated a blood transfusion of 1000 ml, and the total bilirubin increased up to 4.0 mg/dl on the third postoperative day, which prolonged the postoperative hospital stay to 17 days. These results conclusively suggest that safety is guaranteed when the left lobe or the left lateral segment is used as the liver graft for LRLTx.

Adolescent↗

On the mechanism of preferential incorporation of dAMP at abasic sites in translesional DNA synthesis. Role of proofreading activity of DNA polymerase and thermodynamic characterization of model template-primers containing an abasic site.

DNA polymerase preferentially incorporate dAMP opposite abasic sites (A-rule). The mechanism of the A-rule can be studied by analyzing three dissected stages of the reaction including (i) initial nucleotide insertion, (ii) proofreading excision of the inserted nucleotide and (iii) extension of the nascent primer terminus. To assess the role of the stage (ii) in the A-rule, kinetic parameters of the proofreading excision of primer terminus nucleotides opposite abasic sites were determined using E.coli DNA polymerase I Klenow fragment. The relative efficiency of the excision (Vmax/Km) revealed that removal of A was the least favored of the four nucleotides, but the differences in the efficiencies between excision of A and the other nucleotides was less than 2-fold. In addition, in an attempt to reconcile kinetic data associated with the stage (i) or (ii), the differences in free energy changes (delta delta G degrees) for the formation of model template-primer termini containing XN pairs (X = abasic site, N = A, G, C or T) were determined by temperature dependent UV-melting measurements. The order of delta delta G degrees was XG > XA = XC > or = XT, with delta delta G degrees being 0.5 kcal/mol for the most stable XG and the least stable XT. Based on these data, the role of the stage (ii) and energetic aspects of the A-rule are discussed.

Base Sequence↗

Differentiation of vertebral osteomyelitis and tuberculous spondylitis by magnetic resonance imaging.

Twenty patients with vertebral osteomyelitis and 18 with tuberculous spondylitis were investigated by magnetic resonance imaging to identify the distinguishing features. The number of vertebral bodies involved was less in vertebral osteomyelitis than in tuberculous spondylitis, and the paravertebral abscesses were smaller. The magnetic resonance intensity of the involved vertebral bodies was more homogeneous in vertebral osteomyelitis than in tuberculous spondylitis. Rim enhancement with Gadolinium-DTPA was less frequent in vertebral osteomyelitis. The differentiation of the two conditions by MRI was helpful in establishing the correct diagnosis of the infection.

Adult↗

Amplification and detection of the VNTR locus D4S95 in a Japanese population.

The D4S95-VNTR locus was amplified and the polymorphism analysed in a population sample of 169 randomly selected Japanese individuals. A total of 14 alleles containing 850-1360 base pairs were distinguished by agarose gel electrophoresis. The distribution of alleles was symmetrical with respect to one peak at 1030 bp. The mean exclusion chance and discrimination power were calculated as 0.604 and 0.876 respectively.

Alleles↗

HLA-A and -DRB4 genes in controlling the susceptibility to Hashimoto's thyroiditis.

HLA-linked genetic factors involved in the pathogenesis of HT were studied in 71 patients with HT by serologic typing for HLA-A, -B, -C, -DR, and -DQ specificities and by DNA typing for HLA-DRB1, -DRB3, -DRB4, -DRB5, -DQA1, -DQB1, AND -DPB1 genes using the PCR-SSOP method. Typing results demonstrated significant positive associations of HT with HLA-A2 and -DRB4*0101 (DR53) (p < 0.01, RR = 2.03, EF = 0.61 and p < 0.0001, RR = 4.48, EF = 0.69, respectively). Although HLA-DR8, -DRB1*0403, -DQA*03, and -DQB1*0303 were statistically more prevalent in the patient group than in the controls, these associations were presumably due to the strong linkage disequilibria of these alleles with HLA-A2 or -DRB4*0101 in the Japanese population. Ninety-seven percent of the patients (69 out of 71) were positive for HLA-A2 or -DRB4*0101 compared to 79% in controls (RR = 8.7, p < 0.0005). The combination of HLA-A2 and -DRB4*0101 showed higher OR of risk for HT (OR = 12.8) than HLA-A2 (OR = 7.3) or DRB4*0101 (OR = 7.5) alone. These observations suggest that at least two loci, HLA-A and HLA-DRB4 together, may control the susceptibility to HT. On the other hand, the frequency of DQA1*0102 was significantly decreased in the patient group, suggesting that DQA1*0102 might confer resistance to HT.

Genetic Predisposition to Disease↗

srb: a Bacillus subtilis gene encoding a homologue of the alpha-subunit of the mammalian signal recognition particle receptor.

We cloned a Bacillus subtilis gene (srb) encoding a homologue of the mammalian signal recognition particle receptor alpha-subunit (SR alpha). The gene is 987 bp in length and encodes a 329-amino acid protein. The deduced amino acid sequence of the protein shared 26.6, 36.2 and 49.7% identity with those of mammalian SR alpha, archaebacterial DP alpha and Escherichia coli FtsY, respectively. The protein contains three conserved GTP-binding elements like the other three SRP receptor proteins, though the N-terminal portion of the putative B. subtilis protein was shorter than the others. Secondary structure prediction showed than an amphipathic alpha-helix is positioned in the N-terminal region. A defect in srb inhibited cell growth and protein translocation.

Amino Acid Sequence↗

Nitric oxide is a mediator of tachykinin NK3 receptor-induced relaxation in rat mesenteric artery.

1. The mechanism of vasodilatation induced by tachykinin peptides was studied in isolated mesenteric arteries of rats. 2. Senktide, a selective NK3 agonist, elicited potent endothelium-dependent relaxation of arteries precontracted with phenylephrine (10(-5) M), but an NK1 agonist did not. 3. A non-peptide NK3 antagonist, SR 142801, inhibited senktide-induced relaxation. However, a non-peptide NK1 antagonist, CP-96,345, and a peptide-based NK2 antagonist, L-659,877, had no effect on senktide-induced relaxation. 4. N omega-nitro-L-arginine (L-NOARG), a nitric oxide synthesis inhibitor, markedly attenuated the relaxant response to senktide. 5. These results suggest that the endothelium of rat mesenteric arteries possesses tachykinin NK3 receptors, and that NK3 agonist-induced vasodilatation is mediated by release of nitric oxide (NO) from the endothelium.

Amino Acid Sequence↗

[Discovery and development of tamsulosin hydrochloride, a new alpha 1-adrenoceptor antagonist].

Benign prostatic hyperplasia (BPH) is an age-related disorder characterized by urinary outlet obstruction. This obstruction is due to both mechanical compression of the urethra by the hypertrophied prostate and to functional contraction of the prostate and urethra by sympathetic stimulation. We invented a novel compound tamsulosin hydrochloride, a sulphamoylphenethylamine derivative which possesses potent and selective alpha a-antagonism, and showed that this compound selectively reduced the intra-urethral pressure in the prostatic segment of the urethra in vivo. We also found that the alpha 1-adrenoceptor plays an important functional role in the prostate and urethra. For clinical use, a control release formulation was developed. This formulation did not induce orthostatic hypotension and could be administered at a fixed dose. A placebo-controlled double-blind dose finding study resulted in 0.2 mg/d as the optimal dose. This formulation significantly improved urinary outlet obstruction without affecting blood pressure as compared with placebo in P-III study, and was approved in 1993 for use in the treatment of bladder outlet obstruction associated with BPH. Tamsulosin hydrochloride is the first alpha 1-antagonist which improves bladder outlet obstruction associated with BPH without affecting blood pressure, and the treatment can be initiated and maintained at a fixed dose. Recently, the alpha 1-adrenoceptor subtypes alpha 1A, alpha 1B and alpha 1C were identified. The alpha 1C subtype is predominant and plays an important role in the human prostate. Tamsulosin hydrochloride shows high selectivity for this subtype, further supporting the clinical findings that tamsulosin hydrochloride improves bladder outlet obstruction associated with BPH with no effect on the cardiovascular system.

Adrenergic alpha-Antagonists↗

[Gastrin/CCK-B receptor antagonists for a novel antiulcer agent].

Gastrin plays an important role in gastrointestinal functions such as gastric secretion and mucosal growth. The hypergastrinemia that results from long-term treatment with proton pump inhibitors and histamine H2-receptor antagonists induces hyperplasia of enterochromaffin-like (ECL) cells and increases the secretory response to pentagastrin (acid rebound). Recently, potent and selective gastrin/CCK-B-receptor antagonists, L-365,260, PD136450 and YM022, have been developed. These compounds inhibit basal and meal-stimulated acid secretion as well as pentagastrin-stimulated acid secretion in rats and dogs. Long-term treatment with gastrin/CCK-B-receptor antagonists does not cause hyperplasia of ECL cells and acid rebound at all. Moreover, they prevent hyperplasia and acid rebound induced by proton pump inhibitors and histamine H2-receptor antagonists. Therefore, gastrin/CCK-B-receptor antagonists are suggested to be novel antiulcer and antisecretory agents without potential for acid rebound, hyperplasia and carcinoid.

Animals↗

Studies on serotonin (5-HT)3-receptor antagonist effects of enantiomers of 4,5,6,7-tetrahydro-1H-benzimidazole derivatives.

We assessed the 5-HT3-receptor antagonist effects of 4,5,6,7-1H-benzimidazole compounds which are derivatives of YM060, a potent and selective 5-HT3-receptor antagonist, in isolated guinea pig colon. YM114 (KAE-393), YM-26103-2, YM-26308-2 (3 x 10(-9) to 3 x 10(-8) M) produced concentration-dependent shifts to the right of the dose-response curves for both 5-HT and 2-methyl-5-HT (2-Me-5-HT). YM114 (pA2 = 9.08 against 5-HT, pA2 = 8.88 against 2-Me-5-HT), YM-26103-2 (pA2 = 8.27 against 5-HT, pA2 = 8.19 against 2-Me-5-HT), and YM-26308-2 (pA2 = 8.58 against 5-HT, pA2 = 8.4 against 2-Me-5-HT) showed similar pA2 values irrespective of the agonist used, suggesting that they have 5-HT3-receptor blocking activity irrespective of the N-position at the aromatic ring. Since these compounds have an asymmetric center, their enantiomers exist. The S-isomers were one to three orders of magnitude less potent than the respective R-isomer compounds, indicating that the stereochemical configuration of 4,5,6,7-tetrahydro-1H-benzimidazoles is an important determinant of their affinity for 5-HT3 receptors. These results suggest that the highly potent 5-HT3 receptor antagonism and high selectivity for 5-HT3 receptors of 4,5,6,7-tetrahydro-1H-benzimidazole derivatives are conserved irrespective of the position of the nitrogen atom in the aromatic ring and that 5-HT3 receptors favor the R-isometric conformation of these compounds.

Adrenergic alpha-Antagonists↗

Changes in 3H-quinuclidinyl benzilate binding and protein synthesis in the striatum following chronic administrations of muscarinic agonist.

Injection of the muscarinic agonist oxotremorine into rat striatum for seven consecutive days resulted in a 44% reduction in 3H-quinuclidinyl benzilate (3H-QNB) binding, and it caused decreases in binding affinity to agonists. Furthermore, it eliminated the shift from the high affinity site to the low affinity site that occurs in the presence of 5'-guanylyl imidodiphosphate (Gpp (NH)p). In addition, oxotremorine caused a 1.5-fold increase in the incorporation of 3H-leucine into the striatum, suggesting that it increased the syntheses of proteins other than the muscarinic receptor protein. The present results show that chronic treatment of the striatum with oxotremorine causes alterations in not only the quantity, but also the sensitivity of muscarinic receptors to guanine nucleotide.

Animals↗

Optimum pH control mechanism for porcine pancreatic alpha-amylase.

We studied the substrate-dependence of pH activity of porcine pancreatic alpha-amylase by using a series of p-nitrophenyl maltooligosaccharides. The mechanism controlling the optimum pH of mammalian alpha-amylase involved the reception and recognition of a substrate component at some other substrate binding sites, in addition to those at subsite 5 that were reported previously [K. Ishikawa et al., Biochemistry, 32, 6259-6265 (1993)].

Animals↗

Dopamine tonically modulates natriuresis in the saline-expanded dogs.

Dopamine (DA) has been shown to be an endogenous catecholamine that promotes natriuresis by activating tubular DA receptors, but its role on natriuresis appears to be equivocal, and the precise mechanisms and signaling pathway of multiple DA's receptor subtypes are not yet clarified. We used low dose of DA intravenously in saline (S) volume-expanded dogs to see the alterations in natriuresis. The results showed that there is a critical dose that induces no enhancement of natriuresis of volume expansion, and that the lower and higher doses of DA produced relatively larger natriuresis. Pretreatment of metoclopramide (MCP) in this settings caused even higher and significant increases of natriuresis. In conclusion, DA seems to determine tonically the level of natriuresis in saline-expanded dogs. DA may exert a dual effect on signal transduction pathways such that one leading to antinatriuresis with high affinity and the other to natriuresis with low affinity signaling cascades for DA. MCP may block the antinatriuretic limb of the signaling pathway.

Animals↗

Effects of hemitransection of the midbrain on milk-ejection burst of oxytocin neurones in lactating rat.

Unilateral knife cuts were performed in the midbrain of lactating rats and the activities of oxytocin neurones were recorded extracellularly from the supraoptic nuclei (SON) in order to investigate the location of the neural mechanism responsible for the synchronization of milk-ejection bursts of oxytocin neurones in different magnocellular nuclei of the hypothalamus. The lesions involved the mesencephalic lateral tegmentum, the intermedial tegmentum and the central grey. Ninety-six SON neurones were antidromically activated by neurohypophyseal stimulation and were also identified as oxytocin neurones, which included 17 pair-recorded neurones. First, the response of oxytocin neurones recorded from the unilateral SON to bilateral or unilateral suckling was tested. During bilateral suckling, not only the oxytocin neurones recorded from the SON on the intact side (n = 34) but also those recorded from the SON on the lesioned side (n = 58) displayed milk-ejection bursts. When only the nipples ipsilateral to the lesion were suckled (ipsilateral suckling), bursts were induced in most of the oxytocin neurones on the intact (83.3%, n = 12) and lesioned side (88.9%, n = 27). In contrast, none of the oxytocin neurones (n = 37) produced bursts and none of the rats tested (n = 23) showed milk ejections during contralateral suckling. Secondly, some characteristics of the bursts of pair-recorded neurones during bilateral suckling and their response to different modes of suckling were investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗