Biomedical subjects

H Sano

Publications and source records attributed to H Sano.

At least 559 records · Page 31Linked to original sources

PubMed1989

KS-504 compounds, novel inhibitors of Ca2+ and calmodulin-dependent cyclic nucleotide phosphodiesterase from Mollisia ventosa.

Novel inhibitors of Ca2+ and calmodulin-dependent cyclic nucleotide phosphodiesterase were isolated from the culture broth of a fungus, Mollisia ventosa KAC-1148. They were designated as KS-504a, KS-504b and KS-504d. A degradative product of KS-504a, called KS-504e, was also isolated and found to inhibit the enzyme. The 50% inhibitory concentration (IC50) values of KS-504a, KS-504b, KS-504d and KS-504e for bovine brain enzyme were 122, 109, greater than 500 and 139 microM, respectively.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1989

Hydrogenation of quinone compounds during secondary ion mass spectra measurement.

Antibiotics containing a quinone group show characteristic reduced pseudo-molecular ions (M + 2)+ and (M + 3)+ during the measurements of secondary ion mass spectra using glycerol as a matrix. The ratios of peak intensities (M + 2)+ and (M + 3)+ over (M + 1)+ increase with time. As this phenomenon is not found using sulfolane as a matrix, the quinone group seems to be hydrogenated to a hydroquinone by active hydrogen which is produced from a free hydroxyl group of the glycerol by bombardment with the Xe+ beam. This hydrogenation reaction is specific for the quinone group.

Anti-Bacterial Agents↗

PubMed1989

UCN-01 and UCN-02, new selective inhibitors of protein kinase C. II. Purification, physico-chemical properties, structural determination and biological activities.

A new inhibitor of protein kinase C (PKC), UCN-01, was isolated from the culture broth of Streptomyces sp. N-126. We have found that this strain also produces UCN-02 which is a stereoisomer of UCN-01. The inhibitors have the molecular formula C28H26N4O4 and have an indolo[2,3-alpha]carbazole chromophore. Their structures have been elucidated by mass and NMR spectra. UCN-01 has been shown to inhibit PKC and protein kinase A (PKA) with IC50 values of 0.0041 and 0.042 microM, respectively, and UCN-02 has been shown to inhibit PKC and PKA with IC50 values of 0.062 and 0.25 microM, respectively. UCN-01 and UCN-02 also showed the cytotoxic effect on the growth of HeLa S3 cells.

Alkaloids↗

PubMed1989

Chemical modification of hitachimycin. II. Synthesis and antitumor activities of carbonate derivatives.

Several carbonate derivatives of hitachimycin have been synthesized and evaluated their activities including antibacterial, cytocidal against HeLa cells and in vivo antitumor against Sarcoma 180. Some of these derivatives showed higher antitumor activity than hitachimycin. Among the derivatives, 11,15-di-O-methoxycarbonylhitachimycin (2), 11,15-di-O-ethoxycarbonylhitachimycin (3) and 15-O-methoxycarbonylhitachimycin (9) were most effective in in vivo assay.

Animals↗

PubMed1989

Mechanism of polymorphonuclear leukocytes accumulation examined using inhibitors of complement and arachidonic acid cascade in rats treated with OK-432.

When the streptococcal preparation OK-432 was intraperitoneally injected for the treatment of carcinomatous peritonitis, antitumor polymorphonuclear leukocytes (PMNs) accumulated in the peritoneal cavity. We examined the mechanism of this PMN accumulation using an in vivo system in rats. FUT-175, EDTA and K76 inhibited C5a generation by OK-432 in vitro, but EGTA, prednisolone and inhibitors of arachidonic acid cascade did not. In in vivo experiments, EDTA, FUT-175, antirat C3 serum and K76 reduced the accumulation of PMNs onto filter membranes, when these reagents were reacted with OK-432 for 3 h through filter membranes placed on the turned rat peritoneum. EGTA failed to inhibit PMN accumulation. Prednisolone, indomethacin, OKY046 and AA861 inhibited PMN accumulation in a dose-dependent manner. These inhibitions of PMN accumulation were confirmed by histological examination. It was concluded that complement-derived chemotactic factor C5a generated by OK-432 induced PMN accumulation in association with chemotactic arachidonic acid metabolites.

Animals↗

PubMed1989

[Crossed cerebellar diaschisis in hydrocephalus--a case report].

A case of hydrocephalus in which a crossed cerebellar diaschisis with single photon emission CT (SPECT) using 123I-iodoamphetamine (123I-IMP) disappeared by a ventriculo-peritoneal shunting operation, was reported. A 54-year-old female had a clipping surgery for a aneurysm of the left middle cerebral artery on April 9, 1987. Post-operatively, she had a transient mild aphasia. Cerebral blood flow (CBF) study with 123I-IMP-SPECT had showed low perfusion in the left frontal and temporal lobe. But after a month, clinical symptom and CBF findings had improved. She had been doing well after the discharge until October, 1987, when she developed disorientation. CT on re-admission showed the ventricular dilatation with periventricular low density (left greater than right). 123I-IMP-SPECT study showed the crossed cerebellar diaschisis which was a low perfusion in the left frontal, temporal, parietal, thalamus, basal ganglionic area and in the opposite cerebellum. A ventriculo-peritoneal shunting operation was performed which brought the disappearance of the crossed cerebellar diaschisis and the clinical improvement. The phenomenon of crossed cerebellar diaschisis has been reported in a lot of literatures. However, those diseases were located in unilateral supratentorium. It has been speculated that crossed cerebellar diaschisis is the transneural metabolic change through the cortico-ponto-cerebellar pathway by supratentorial lesion. Crossed cerebellar diaschisis in hydrocephalus has not been reported so far.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamines↗

PubMed1989

[Evaluation of cerebral hemodynamics by 123I-IMP in cerebral AVMs before and after operation by using SPECT].

To evaluate cerebral hemodynamics by N-isopropyl-p-[123I]-iodoamphetamine (123I-IMP) preoperative and postoperative (after 1 day, and after 7-10 days) regional cerebral blood flow scan, 6 arteriovenous malformations (AVMs) which performed total removal operations were studied by using a ring type SPECT "HEADTOME". We performed the dynamic scan just after the intravenous injection of 222 MBq (6 mCi) of 123I-IMP, then the static scan 20 minutes after the intravenous injection. In preoperative dynamic scans of all cases, only the first frame image showed the increased activity on the nidus probably because of the blood pool. Preoperative static scans of all cases showed the remarkable decreased activity on the nidus, and decreased activity surrounding the nidus probably because of the peripheral steal phenomenon. In postoperative scan of the next day, 4 out of 6 cases showed the transient decreased peripheral steal, particularly 2 out of those 4 cases showed the transient hyperperfusion probably because of the normal perfusion pressure breakthrough (NPPB). And, 2 out of 6 cases showed transient peripheral low perfusion on much larger area than those of the preoperative scans probably because of the focal brain damages and edemas. We conclude that 123I-IMP SPECT on AVM is very useful to decide the indication of the removal operation, and to estimate the postoperative risk, and to evaluate the preoperative and postoperative cerebral hemodynamic changes in the peripheral area of AVM.

Adolescent↗

PubMed1989

Pancreas divisum. A predisposing factor to pancreatitis?

Cases of pancreas divisum (PD) were reviewed in our patients and 19 Japanese and 14 English series during the past 10 yr to see any significant association of PD with certain diseases. PD was diagnosed in 20 (0.64%) among our 3121 patients with successful endoscopic pancreatograms (ERP). Of 20 PD patients, acute pancreatitis in one, chronic pancreatitis in two, ampullary cancer in one, and cholelithiasis in five were diagnosed. Incidences of PD were 2.6% (1/38) in acute pancreatitis, 0.8% (2/248) in chronic pancreatitis, 0% (0/100) in pancreatic cancer, 20% (1/5) in ampullary cancer, and 0.8% (5/615) in cholelithiasis. The incidences were similar to overall incidences of ours and other Japanese series (0.69% of 36,171 patients). Higher incidences of acute pancreatitis (12.9% of 559) and pancreatic cancer (5.5% in 448) may result from the higher overall incidence (4.6% in 16,257) in English series. The relationship between pancreatitis and PD has been controversial, but our present data suggest that PD is a coincidental finding and not a predisposing factor to pancreatitis in Japan.

Adolescent↗

PubMed1989

[Binding of K-18 on the surface of tumor cells--flowcytometrical analysis in vitro].

After K-18 was contacted with various kinds of tumor cell lines in vitro, the binding pattern was examined. K-18 bound on the surface of K-562 cells showed the maximum levels 1 hr later and maintained the binding activity for 24 hrs in the analysis by flowcytometry. K-18 also bound to HeLa S3, KB, RPMI8226, P815, YAC-1 and L1210 cells. Fluorescent intensity on K-562 cells was stronger with whole molecules of K-18 than with F(ab')2 conjugated with melphalan. Normal human IgG could bind more on the surface of K-562 cells than F(ab')2 of IgG. These results suggest that K-18 might bind on tumor cells via IgG Fc receptors on their surface.

Animals↗

PubMed1988

Detection of heavy methylation in human repetitive DNA subsets by a monoclonal antibody against 5-methylcytosine.

A monoclonal antibody (IgM) against 5-methylcytosine (mC) was isolated and characterized. It showed a high specificity for mC with a cross-reactivity of less than 1% with cytosine and 0.1% with thymidine. An improved immunohybridization method, originally developed with polyclonal antibodies (Sano et al. (1980) Proc. Natl. Acad. Sci. USA 77, 3581), was applied to detect mC in immobilized DNA using the new monoclonal preparation. Human genomic DNA was cleaved with the restriction enzyme EcoRI and successively fractionated by malachite-green affinity chromatography and agarose gel electrophoresis. The fractionated DNA was transferred to nitrocellulose paper and treated with the anti-mC monoclonal antibody. Heavy methylation was observed in EcoRI-ladders of repetitive sequences of 1360, 1750, 2200 and 3400 bp, while 340, 660 and 2700 bp fragments were less methylated. The results show that methylation occurs in limited subsets of satellite II and III repetitive DNAs that contain high amounts of methylatable CpG dinucleotides, or CpG clusters.

5-Methylcytosine↗

PubMed1988

Synthesis and structural identification of four dihydroxy acids and 11,12-leukotriene C4 derived from 11,12-leukotriene A4.

Using a partially purified 12-lipoxygenase from porcine leukocytes, (5Z,8Z,10E,14Z)-12-hydroperoxy-5,8,10,14-icosate traenoic acid was synthesized from arachidonic acid with a yield of over 35%. The absolute configuration of C-12 was determined as S by chiral-phase column chromatography. It was chemically converted to at least three epoxides with the conjugated triene structure. Two were identified by proton NMR and mass spectrometry to be (5Z,7E,9E,14Z)-(11S,12S)-11,12-oxido-5,7,9,14-ic osatetraenoic acid (11,12-leukotriene A4) and (5Z,7Z,9E,14Z)-(11S,12S)-11,12-oxido-5,7,9,14-ic osatetraenoic acid (7-cis-11,12-leukotriene A4). 11,12-Leukotriene A4 underwent acid hydrolysis to yield two diastereomers of (6E,8E,10E,14Z)-(12S)-5,12-dihydroxy-6,8,10,14-i cosatetraenoic acid and two isomers of (14Z)-(12S)-11,12-dihydroxy-5,7,9,14-icosatetraenoic acid. Upon incubation with rat liver glutathione S-transferase, 11,12-leukotriene A4 was converted to 11,12-leukotriene C4, a spasmogenic compound.

Animals↗

PubMed1988

Rapid methylation of genomic DNA in proliferating T-cells from bovine thymocytes.

Two subpopulations of bovine calf thymus cells were separated by buoyant density centrifugation. The low-density cells (L-cells) showed high response to T-cell mitogens, while the high density cells (H-cells) did not. The DNA-metabolizing enzyme activities were elevated 10-fold in L-cells in comparison with those in H-cells. L-cells contained a DNA-replicating complex, DNA replitase, while H-cells did not. These observations suggested that L-cells were proliferating, mature T-cells and H-cells were dying intrathymic cells. A DNA methyltransferase was associated with DNA replitase in L-cells. In order to determine whether replitase-associated DNA methyltransferase functions at replicating regions, the methylation pattern of genomic DNA of L-cells was compared with that of H-cells. No significant difference was found in the extent of CpG dinucleotide methylation, and in the location of mC in the satellite I DNA sequence as identified by Southern hybridization and direct sequencing. Thus the majority of methylation patterns of genomic DNA did not change during T-cell development in the thymus. The results indicated that the methylation patterns were rapidly maintained in proliferating T-cells. Although methods employed in the present study might not be sensitive enough to detect transient hemimethylation, it is suggested that the rapid methylation might be catalyzed, albeit not completely, by a DNA methyltransferase associated with the DNA replitase complex.

Animals↗

PubMed1988

Thymic stroma-derived T-cell growth factor (TSTGF): II. Biochemical and functional characterization.

The culture supernatant (SN) from a cloned line of thymic stroma-derived cells in fibroblastic form (TSCF) contained a factor capable of supporting the growth of the interleukin (IL) 2-dependent, antigen-specific helper T cell (Th) clone 9-16 without requiring IL2 and antigen. This active substance, designated as thymic stroma-derived T-cell growth factor (TSTGF), was partially purified through DEAE-Sephacel chromatography and PBE 94 chromatofocusing. The original SN did not contain IL1, IL2, IL3, IL4, or interferon activities; but an appreciable magnitude of colony-stimulating factor (CSF) activity in addition to TSTGF was present, whereas the partially purified preparation of TSTGF was depleted of any type of CSF activity. The elution profile of TSTGF activity on the chromatofocusing has revealed that TSTGF has an isoelectric point (pI) of about 6.0. When a purified TSTGF sample was applied to Sephacryl S-200 column chromatography and sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis, TSTGF activity was eluted in a single peak around an apparent molecular weight of about 25,000. The activity of TSTGF also was shown to be relatively stable with heat treatment and in the wide range of pH, but it was abolished by treatment with either trypsin or dithiothreitol. These results indicate that TSTGF, a novel T-cell growth factor, is the protein that has an apparent molecular weight of about 25,000 and a pI of 6.0, and in the intact molecule, it contains the disulfide bond(s) required to maintain and/or express its biologic activity.

Biological Products↗

PubMed1988

Epstein-Barr virus-transformed B cells bearing idiotypes of anti-DNA autoantibodies.

Epstein-Barr virus (EBV)-transformed B cells obtained from healthy subjects had the same idiotypes of anti-DNA autoantibodies on their surface as those obtained from patients suffering from systemic lupus erythematosus. These clones secreted anti-single-stranded or anti-double-stranded DNA antibodies. Among them, some produced anti-DNA idiotype-positive antibodies but failed to bind DNA. This was confirmed by a competitive inhibition radioimmunoassay. It was then considered whether or not the expression of anti-DNA idiotype on B-cell clones related to the anti-DNA antibody activity in vivo. The amounts of anti-DNA antibodies were not associated with the incidence of idiotype-positive B cells in the EBV-transformed cell lines from normals. The results indicate that the clones committed to the synthesis of anti-DNA idiotype-positive antibodies commonly exist at a resting state in the circulation of healthy subjects, probably through the self-tolerance regulatory system.

Antibodies, Antinuclear↗

PubMed1988

Bilateral giant intracavernous aneurysms. Technique of unilateral operation.

We report a case of bilateral intracavernous giant aneurysms of which the right side was clipped by direct surgery. Our case was a 74-year-old woman who developed bilateral abducens palsy. Computed tomography and angiography showed bilateral intracavernous giant aneurysms. This patient was followed up in the outpatient clinic. She developed headache and right trigeminal neuralgia 2 years later. The trigeminal pain was quite severe and very disturbing to her. Repeat angiography showed an increase in the size of the aneurysms. An operation was carried out after a balloon Matus test monitoring electroencephalogram, somatosensory evoked potential, and clinical symptoms. The cavernous sinus was opened and the aneurysm was clipped. There was no postoperative complication except right ophthalmoplegia which resolved after 3 months. Headache and trigeminal neuralgia also disappeared.

Aged↗

PubMed1988

The role of chloride in the sympathetic nervous system in DOCA-salt hypertension.

Elevation in blood pressure in the deoxycorticosterone acetate (DOCA)-treated rat with a high-sodium, normal-chloride diet was less than that in the DOCA-salt rat not on such a diet. Compared with the DOCA-salt rat, there were greater sodium concentration in the carcass, and less norepinephrine turnover rates in the heart and the spleen than in the DOCA treated rat given a high sodium normal chloride diet. Extracellular fluid volumes were similar. These results suggest that not only water and sodium retention by sodium loading but also that activation in sympathetic nervous system by the combined effect of chloride and sodium are responsible for the development of DOCA-salt hypertension.

Animals↗

PubMed1988

Effects of oral magnesium on blood pressure and red cell sodium transport in patients receiving long-term thiazide diuretics for hypertension.

Twenty patients receiving long-term (1.0 to 10.3 years) thiazide diuretic treatment for essential hypertension (Th group) received magnesium supplementation as MgO (600 mg Mg/day) for 4 weeks and placebo for another 4 weeks. Before and at the end of each period, we measured blood pressure; intraerythrocyte magnesium, sodium, and potassium (R-Mg, R-Na, and R-K); and erythrocyte ouabain (10-4 M) sensitive sodium efflux rate constant (Kos). The same measurements were also performed in 21 untreated age-matched essential hypertensives (EHT group). In the Th group, R-Mg was lower, R-Na was higher, and Kos was lower than in the EHT group before magnesium supplementation. Oral magnesium resulted in a significant increase in R-Mg (p less than 0.005) and a decrease in R-Na (p less than 0.01), together with an increase in Kos (p less than 0.005) in the Th group. During magnesium supplementation, the increased Kos was correlated negatively with the lowered R-Na (r = -0.57, p less than 0.01) and positively with the increased R-Mg (r = 0.61, p less than 0.005). Systolic, diastolic, and mean blood pressures were reduced significantly during magnesium administration by a mean of 7.5, 3.0, and 4.5 mm Hg. The results indicate that long-term diuretic treatment may give rise to an intracellular magnesium deficiency and a suppression in cell membrane active transport for sodium, with a resultant increase in intracellular sodium content.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1988

Left ventricular filling characteristics in sodium-depleted and sodium-loaded patients with mild essential hypertension.

To determine left ventricular early diastolic function and transmitral blood-flow characteristics during periods of sodium depletion (50 mmol/day) and sodium loading (300 mmol/day), Doppler and standard echocardiography were performed in 13 patients with untreated mild hypertension. A high sodium intake for 7 days significantly increased (P less than 0.05) the ratio of Doppler atrial contraction phase peak velocity A to rapid filling phase peak velocity R. The isovolumic relaxation time was prolonged (P less than 0.001) and the left atrial emptying index was reduced (P less than 0.05). During sodium loading the changes in isovolumic relaxation time and the atrial emptying index were correlated with the increase in mean wall stress (r = 0.600, P less than 0.05 and r = -0.695, P less than 0.01, respectively), but not with the increase in end-diastolic volume. These results suggest that during excess salt intake, left ventricular relaxation and filling may be impaired due to a salt-induced increase in afterload in patients with mild hypertension.

Echocardiography, Doppler↗