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Biomedical subjects

Y Imai

Publications and source records attributed to Y Imai.

At least 757 records · Page 42Linked to original sources
PubMed1992

Further studies on chimeric P450 2C2/2C14 having testosterone 16 beta-hydroxylase activity which is absent in the parental P450s.

cDNAs for various chimeras between P450 2C2, P450 2C14, P450 2B5, and P450 2E1 were constructed, the chimeric P450s were expressed in yeast cells, and their catalytic activities were compared in the reconstituted system containing partially purified P450 preparations. The chimera P450(2Hc3), consisting of the 462 amino-terminal residues of P450 2C2 and the remaining 28 residues of P450 2C14, had testosterone 16 beta-hydroxylase activity, which is not seen in either of the parental P450s, in addition to higher activities of laurate (omega-1)-hydroxylation and benzphetamine N-demethylation than the parental P450s [Uno, T. et al. (1990) Biochem. Biophys. Res. Commun. 167, 498-503]. When either of the segments from P450 2C2 and P450 2C14 in this chimera was replaced with the corresponding sequences of P450 2E1 or when the 35 carboxy-terminal residues of P450(2Hc3) were replaced with those of P450 2B5, the 16 beta-hydroxylase activity disappeared. When the 262 amino-terminal residues, except for residues 90-125 (region 90-125), of P450(2Hc3) were replaced with those of P450 2C14, the resulting chimera retained both testosterone 16 beta- and laurate (omega-1)-hydroxylase activities. Further replacing the region 90-125 with that of P450 2C14 resulted in disappearance of the 16 beta-hydroxylase activity and profound decrease in the (omega-1)-hydroxylase activity. Testosterone 16 beta-hydroxylation was inhibited by laurate and laurate (omega-1)-hydroxylation by testosterone.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1992

Analysis of the mutant proBA operon from a proline-producing strain of Serratia marcescens.

The nucleotide sequence of the proBA operon from a proline-hyperproducing mutant of Serratia marcescens was determined. Two base substitutions were found: one in the proB structural gene, coding for gamma-glutamyl kinase (GK), and a second one in the promoter region of the operon. The former base substitution led to a change of the predicted amino acid at position 117 from an alanine to a valine in GK. This mutation rendered GK 700-fold less sensitive to proline-mediated feedback inhibition than the wild-type enzyme. The other base substitution, a transversion from a G-C to an A-T, was located in the spacer region between the '-35' and '-10' sequences of the promoter, and it increased the transcriptional activity of this operon fourfold. Both these two base substitutions, which were acquired at the step of selecting mutants resistant to a toxic proline analogue, 3,4-dehydroproline, confer upon cells a high proline productivity and an increased osmotolerance.

Amino Acid Sequence↗
PubMed1992

A comparison of guanfacine, bunazosin, atenolol and nadolol on blood pressure and plasma noradrenaline responses to cold pressor testing.

1. The role of the presynaptic adrenoceptor subtypes in man was investigated based on observation of the changes in blood pressure (delta BP) and plasma noradrenaline concentration (delta NA) with the cold pressor test (CPT). 2. The CPT was well reproducible for BP and NA when performed at a 2 week interval in patients with mild hypertension. 3. After administration for 4 weeks, guanfacine (Gf; alpha 2-adrenoceptor agonist) decreased the delta NA response to CPT. 4. After administration for 2 or 4 weeks, bunazosin (Bu; alpha 1-adrenoceptor antagonist) atenolol (At; beta 1-adrenoceptor antagonist) and nadolol (Nd; non-selective beta-adrenoceptor antagonist) did not affect the delta NA response to CPT. 5. Both Gf and Bu decreased the systolic blood pressure response (delta SBP) to CPT after 4 weeks of the administration. Neither At nor Nd significantly changed the delta SBP response to CPT. 6. It is likely that Gf stimulated the presynaptic alpha 2 adrenoceptors at the sympathetic nerve endings as well as the central alpha 2 adrenoceptors, inhibiting the release of noradrenaline. It is unlikely that Bu, At and Nd exerted any clearly defined action on the presynaptic adrenoceptors in human hypertensive subjects.

Adrenergic alpha-Antagonists↗
PubMed1992

Involvement of substance P present in primary afferent neurones in modulation of cutaneous blood flow in the instep of rat hind paw.

1. The participation of small-diameter afferent fibres in the microcirculatory haemodynamics of cutaneous tissue was examined by studies on the effects of antidromic stimulation of primary afferent neurones on cutaneous blood flow (CBF) and tachykinin release into the subcutaneous space in the instep of the hind paw of rats. 2. Antidromic stimulation of the sectioned sciatic nerve induced a biphasic flow response, an initial transient decrease followed by an increase, with no alteration in the blood pressure. 3. Neither phase was affected by pretreatment with phentolamine (0.1 mg kg-1, i.a.), propranolol (0.5 mg kg-1, i.a.), atropine (0.5 mg kg-1, i.a.), methysergide (0.5 mg kg-1, i.a.) or mepyramine (10 mg kg-1, i.a.) plus cimetidine (10 mg kg-1, i.a.), but both were significantly inhibited by pretreatment with capsaicin (50 mg kg-1, s.c.). 4. Spantide (1-2 mumol kg-1, i.a.), a substance P (SP) antagonist, reduced the basal CBF, and also inhibited both phases of the biphasic flow response evoked by antidromic stimulation of the sectioned sciatic nerve. 5. Intra-arterial infusion of SP (0.5 mumol kg-1, i.a.) induced a biphasic flow response similar to that elicited by antidromic stimulation of the sectioned sciatic nerve. 6. Antidromic stimulation of the sectioned sciatic nerve caused a marked increase in SP release into the subcutaneous perfusate of the instep of the rat hind paw, but no detectable increase in neurokinin A release.7. We suggest that SP and its receptors are mainly responsible for the vascular response induced by stimulation of the sectioned sciatic nerve, and that small-diameter afferent fibres containing SP tonically regulate vascular tone in cutaneous microvessels.

Animals↗
PubMed1992

Konno procedure for congenital aortic stenosis with a single coronary artery from the left coronary sinus.

A right coronary artery originating from the left coronary sinus and traversing anteriorly is thought to be one of the contraindications for a Konno aortoventriculoplasty in congenital aortic stenosis because this procedure necessitates incision of the right ventricular outflow tract. The case of a 5-year-old girl with congenital aortic stenosis associated with a single coronary artery, successfully treated surgically by the Konno procedure and right coronary artery reimplantation, is reported. Preoperatively there was a pressure gradient between the left ventricle and the ascending aorta of 109 mmHg, which disappeared postoperatively. A postoperative angiography showed a patent right coronary artery.

Abnormalities, Multiple↗
PubMed1992

Small cytoplasmic RNA of Bacillus subtilis: functional relationship with human signal recognition particle 7S RNA and Escherichia coli 4.5S RNA.

Small cytoplasmic RNA (scRNA; 271 nucleotides) is an abundant and stable RNA of the gram-positive bacterium Bacillus subtilis. To investigate the function of scRNA in B. subtilis cells, we developed a strain that is dependent on isopropyl-beta-D-thiogalactopyranoside for scRNA synthesis by fusing the chromosomal scr locus with the spac-1 promoter by homologous recombination. Depletion of the inducer leads to a loss of scRNA synthesis, defects in protein synthesis and production of alpha-amylase and beta-lactamase, and eventual cell death. The loss of the scRNA gene in B. subtilis can be complemented by the introduction of human signal recognition particle 7S RNA, which is considered to be involved in protein transport, or Escherichia coli 4.5S RNA. These results provide further evidence for a functional relationship between B. subtilis scRNA, human signal recognition particle 7S RNA, and E. coli 4.5S RNA.

Bacterial Proteins↗
PubMed1992

Schizosaccharomyces pombe sxa1+ and sxa2+ encode putative proteases involved in the mating response.

The Schizosaccharomyces pombe sxa1 and sxa2 mutants showed an exaggerated response to mating pheromones, producing excessively long conjugation tubes and exhibiting mating deficiency. This phenotype was similar to phenotypes of cells bearing an activated allele of ras1, such as ras1Val-17 or ras1Leu-66, and phenotypes of cells defective in gap1. However, genetic evidence suggested that the sxa1 and sxa2 gene products are not directly involved in the Ras1 pathway. The gene products of sxa1 and sxa2, as deduced from their nucleotide sequences, were homologous to aspartyl proteases and serine carboxypeptidases, respectively. The sxa1 gene function was required for efficient mating only in h+ cells, although even disruption of sxa1 did not completely abolish the mating ability. Conversely, the sxa2 gene function was required only in h- cells. Wild-type cells produced a diffusible substance, which may be the sxa2 gene product itself, that could confer fertility to sxa2 mutant cells placed at a distance. These observations are consistent with the possibility that the sxa gene products are involved in degradation or processing of the mating pheromones and that their loss cause a persistent response to the pheromones.

Amino Acid Sequence↗
PubMed1992

Bladder tumor staging: comparison of conventional and gadolinium-enhanced dynamic MR imaging and CT.

With computed tomography (CT) and unenhanced magnetic resonance (MR) imaging, stage pT3b extravesical extension and beyond can be diagnosed, but tumors confined to the bladder wall (stages pT1-pT3a) are poorly delineated. To determine whether visualization of such tumors could be improved with gadolinium-enhanced MR imaging, dynamic breath-hold T1-weighted MR images were obtained after intravenous infusion of 0.1 mmol/kg gadopentetate dimeglumine in 79 patients (86 tumors). Conventional MR images, CT scans, and histologic correlation were available in all cases. With dynamic gadolinium-enhanced MR imaging, the mucosa could be distinguished from the muscular layers of the bladder wall. Staging accuracy with this technique was 85% (73 of 86), which was significantly better than with CT (55%; 47 of 86) (P < .005) or conventional MR imaging (58%; 50 of 86) (P < .05). The accuracy of staging the intramural extent (pT1-pT3a) of bladder tumors was thus improved with gadolinium-enhanced dynamic MR imaging.

Adult↗
PubMed1992

Comparison of the proliferative activity and sensitivity to cytosine arabinoside of leukemic blast progenitors in acute myeloblastic leukemia at diagnosis and in relapse.

To determine whether the biological characteristics of leukemic cells change after repeated chemotherapy, we compared the proliferative activity and drug sensitivity of leukemic blast progenitors in 7 patients with acute myeloblastic leukemia at diagnosis and in relapse. The proliferative activity of leukemic blast progenitors was assessed based on primary (PE1) and secondary (PE2) colony formation in methylcellulose culture and on the recovery of clonogenic cells in suspension culture. The effect of cytosine arabinoside (Ara-C) on leukemic blast progenitors was studied both in methylcellulose and in suspension cultures. PE1 and PE2 values varied among the patients. PE2 of 4 patients out of 7 patients became significantly higher in relapse than at diagnosis. The sensitivity to Ara-C of leukemic blast progenitors deteriorated in 5 patients in relapse. The results suggest that the biological nature in terms of proliferative activity and Ara-C sensitivity of leukemic blast progenitors may change in the clinical course after chemotherapy.

Blast Crisis↗
PubMed1992

Interleukin-6 reduces the optimal growth in vitro of leukemic blast progenitors from acute myeloblastic leukemia patients.

The combined effects of five cytokines; recombinant human (rHu) granulocyte colony-stimulating factor (G-CSF), rHu granulocyte-macrophage colony-stimulating factor (GM-CSF), rHu interleukin-1 beta (IL-1 beta), rHu interleukin-3 (IL-3), and rHu interleukin-6 (IL-6) on blast colony formation in methylcellulose by leukemic blast progenitors from 10 patients with acute myeloblastic leukemia (AML) were studied. Combination of G-CSF, GM-CSF, IL-1 beta, and IL-3 stimulated maximum blast colony formation in 9 patients. Further addition of IL-6 reduced the combined effect of the four cytokines on blast colony formation. IL-6 regulates the proliferation of leukemic blast progenitors and may play an important role in the regulation of hematopoiesis.

Bone Marrow↗
PubMed1992

Pure red cell aplasia following autoimmune haemolytic anaemia. Cell-mediated suppression of erythropoiesis as a possible pathogenesis of pure red cell aplasia.

We report here a rare case of pure red cell aplasia (PRCA) following autoimmune haemolytic anaemia (AIHA). After 4 years of AIHA, the patient developed anaemia with severe erythroid hypoplasia and was diagnosed as having PRCA. At this time, Coombs' test was negative and parvovirus infection was not recognized. The patient received azathioprine, and PRCA improved. To determine the pathogenesis of PRCA, in vitro culture studies of erythropoietic and granulopoietic precursors were performed. The patient's serum or IgG did not suppress the colony formation of bone marrow colony-forming units-erythroid (CFU-E) of normal subjects and the patient. In contrast, mononuclear cells in the peripheral blood of the patient significantly suppressed CFU-E of normal subjects. Media conditioned by the patient's mononuclear cells did not significantly suppress CFU-E. The significant production of suppressive cytokine such as tumour necrosis factor or gamma-interferon by the patient's mononuclear cells was not recognized. These findings suggest that the cytotoxic mononuclear cells affected directly the erythropoietic precursors and caused PRCA in this patient. The pathogenesis of PRCA was, therefore, considered to be different from that of the preceding AIHA.

Adult↗
PubMed1992

Enhanced effect of mutant granulocyte-colony-stimulating factor (KW-2228) on the growth of normal and leukemic hemopoietic progenitor cells in comparison with recombinant human granulocyte-colony-stimulating factor (G-CSF).

We tested the in vitro effect of a novel granulocyte colony-stimulating factor (G-CSF) derivative (KW-2228) on the growth of G-CSF-dependent hemopoietic progenitor cells: granulocyte precursor cells (CFU-G), leukemic blast progenitors freshly obtained from 9 patients with acute myeloblastic leukemia (AML) and cells of a G-CSF-dependent human AML cell line (OCI/AML 1a). KW-2228 showed a higher stimulating effect than recombinant human G-CSF (rhCSF) on CFU-G; 3 out of 9 leukemic blast progenitors and OCI/AML 1a cells. The difference in biochemical stability between rhG-CSF and KW-2228 was considered to explain the superior colony-stimulating activity of KW-2228. The results show that KW-2228 will be a new granulopoietic factor.

Amino Acid Sequence↗
PubMed1992

Japanese Type A behavior pattern is associated with "typus melancholicus": a study from the sociocultural viewpoint.

An examination of the relationship between Type A behavior pattern (TABP) and "Typus Melancholicus" (TM) in 212 coronary heart disease (CHD) patients in Japan revealed that: CHD patients with TABP were significantly more likely to have a depression-prone personality, what Tellenbach calls "Typus Melancholicus"; this tendency was observed not only in CHD patients but also among healthy Type A subjects; and TM is positively correlated with Type A. The results of our studies from a comparative sociocultural viewpoint indicate that TM may be involved in Japanese TABP, suggesting the possibility that driving, self-sacrificing and obsessional traits are related to Type A behavior in a variety of different cultural contexts.

Adult↗
PubMed1992

Correlation of axenic linkage groups with the position of the microtubule-organizing center in aggregating Dictyostelium.

Positioning of the microtubule-organizing center (MTOC) in Dictyostelium discoideum was found to be genetically regulated. We examined the wild-type strain NC-4 cells independently maintained in different laboratories, freshly recovered cells from spores stocked for over 20 years, the temperature-sensitive growth mutant HU49 isolated from NC-4, as well as strain V-12 which is the opposite mating-type to NC-4. During aggregation on nonnutrient agar plates, all these strains showed similar cell polarity, as defined by the alignment of the nucleus ahead of the MTOC. By contrast, in Ax2 and Ax3, axenic strains carrying axenic mutations on linkage groups II and III, the MTOC was usually positioned ahead of the nucleus. Cells containing axenic linkage group II but not III positioned the MTOC ahead of the nucleus. Conversely cell polarity of strains including axenic linkage group III but not II was similar to that of wild-type cells. Thus axenic linkage group II, probably axeC or other linked gene(s) not yet identified, is responsible for the location of the MTOC anterior to the nucleus during aggregation. The anterior positioning of the MTOCs was prevented by growth on bacteria in cells carrying both axenic linkage groups, but not in those carrying only axenic linkage group II.

Animals↗
PubMed1992

The effects of phentolamine and nitroglycerin on right-sided hemodynamics in cardiac patients can be explained by a shift of the systemic venous return curve and right-ventricular output curve.

The present study investigated the effects of phentolamine (PH) and nitroglycerin (NG) on the hemodynamics of the right heart in patients with cardiac disease. The patients were divided into a well-functioning left heart group (W group, n = 15) and a poorly-functioning left heart group (P group, n = 15). Right cardiac hemodynamic parameters and plasma noradrenaline (NA) and adrenaline (A) concentrations were measured before and after administering PH (0.1 mg/kg, i.v.) or NG (0.6 mg, sublingual). In a parallel animal study we obtained a systemic venous return curve by measuring mean circulatory pressure (MCP), mean right atrial pressure (RAP) and cardiac output, before and after administering PH (0.1 mg/kg, i.v.) or NG (12.5 micrograms/kg, i.v.) to anesthetized open-chest dogs (n = 14). We used MCP data (W group: 7.5 mmHg, P group: 10 mmHg) obtained in a separate series of human studies in our laboratory. We constructed the venous return curve by connecting the MCP point on abscissa with the cardiac index (CI)-RAP plot obtained in the clinical study. We also constructed the right ventricular output curve by connecting the point of -2 mmHg on the abscissa with the CI-RAP plot. We obtained the following results: (1) PH shifted the CI-RAP plot to the left and upwards, while NG shifted the CI-RAP plot to the left almost horizontally on the CI-RAP plane, where CI was plotted on ordinate and RAP on abscissa. The length [formula: see text] C = control point, PH = point after PH) of the shift of CI-RAP plot due to PH was greater in the P group than in W group, while there was no difference in the length [formula: see text] C = control point, NG = point after NG) of the shift of CI-RAP plot due to NG between P and W groups. (2) Both PH and NG significantly elevated plasma NA and A concentrations in both the W and P groups. In the P group, PH increased the plasma NA concentration significantly more than did NG, but both drugs increased plasma A concentration to a similar extent. (3) Both PH and NG significantly decreased the mean pulmonary arterial pressure with NG doing so significantly more than PH.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1992

Effect of growth factors on hyaluronan and proteoglycan synthesis by retroocular tissue fibroblasts of Graves' ophthalmopathy in culture.

One of the pathological changes seen in Graves' ophthalmopathy is the deposition of glycosaminoglycans such as hyaluronan and proteoglycan in retroocular connective tissue. We analyzed glycosaminoglycans synthesized by retroocular tissue fibroblasts in culture derived from an individual not suffering from thyroid disease and from three patients with Graves' ophthalmopathy. Retroocular tissue fibroblasts synthesized both hyaluronan and proteoglycan, the latter composed mainly of chondroitin sulfate. This contrasts with the proteoglycan synthesized by adult skin fibroblasts which was composed of dermatan sulfate and heparan sulfate proteoglycan. Chondroitin sulfate proteoglycan secreted by retroocular tissue fibroblasts consisted of large and small chondroitin sulfate proteoglycans (CS-PG), their size being determined by the Sepharose CL-6B column. The effects of IGF-1 and PDGF on hyaluronan and proteoglycan synthesis were studied separately and in combination. Both IGF-1 and PDGF increased the synthesis of hyaluronan and proteoglycan in a dose-dependent manner. IGF-1 predominantly stimulated secretion of small CS-PG, while PDGF increased large CS-PG markedly when studied in retroocular tissue fibroblasts. In contrast, IGF-1 stimulated secretion of small proteoglycan while PDGF had little effect on proteoglycan synthesis in skin fibroblasts. Thus, glycosaminoglycan synthesized by retroocular tissue fibroblasts has a unique composition and each component is regulated independently, at least in part.

Blood↗
PubMed1992

Immunoglobulin G of patients with circumscribed pretibial myxedema of Graves' disease stimulates proteoglycan synthesis in human skin fibroblasts in culture.

Hyaluronic acid and proteoglycan accumulate in the affected skin of Graves' disease patients with pretibial myxedema (PTM). We aimed to determine whether an autoantibody IgG circulating in PTM patients stimulates proteoglycan synthesis in human skin fibroblasts, resulting in PTM. IgGs were purified from 14 normal subjects, 11 Graves' disease patients with PTM. 5 Graves' disease patients with active ophthalmopathy and 15 Graves' disease patients with neither PTM nor ophthalmopathy. Human skin fibroblasts were incubated with the IgGs and labeled with [35S]sulfate. The medium and cell layer were separated and the proteoglycan was extracted. The 35S radioactivity in the proteoglycan fraction was measured. Compared with normal IgGs or with those of Graves' disease without PTM or ophthalmopathy, PTM IgGs significantly increased the incorporation of the 35S into the proteoglycan. The effect of PTM IgG was dose-dependent. As PTM IgG did not alter degradation of the 35S labeled proteoglycan, an increase in 35S incorporation reflects increased synthesis. The effect was mediated through a mechanism other than adenylate cyclase activation. The present study demonstrates the presence of an autoantibody in PTM IgG that stimulates proteoglycan production through human skin fibroblasts. This is not correlated with the thyroid stimulating antibody activity. It is suggested that the activity of this antibody leads to the development of PTM.

Adult↗