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Biomedical subjects

Y Nagano

Publications and source records attributed to Y Nagano.

At least 109 records · Page 6Linked to original sources
PubMed1991

Rational design and synthesis of a novel class of active site-targeted HIV protease inhibitors containing a hydroxymethylcarbonyl isostere. Use of phenylnorstatine or allophenylnorstatine as a transition-state mimic.

A novel class of HIV-1 protease inhibitors containing a hydroxymethylcarbonyl (HMC) isostere were designed from the substrate transition state and synthesized. Phenylnorstatine [Pns; (2R,3S)-3-amino-2-hydroxy-4-phenylbutyric acid] and the 2S diastereomer, (2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid, named allophenylnorstatine (Apns) were effective transition-state mimics, and incorporation of Pns-Pro or Apns-Pro at the P1-P1' site gave potent and specific HIV-1 protease inhibitors. In the inhibitory assays, the chemically synthesized [Ala67,95] HIV-1 protease was used.

Amino Acid Sequence↗
PubMed1991

[Cytoplasmic staining pattern characteristic for anti Jo-1 antibody in HEp-2 cells].

We wished to confirm the staining pattern of HEp-2 cells by the anti Jo-1 antibody, because we found antibodies in serum with positive anti Jo-1 antibody which showed either a fibrilar cytoplasmic staining or a nuclear speckled staining pattern in indirect immuno fluorescence+ examinations using HEp-2 cells. Sera available from eight patients with PM DM (polymyositis and/or dermatomyositis) showed positive anti Jo-1 antibody in the double immuno-diffusion technique but had various staining patterns of HEp-2 cells in the immunofluorescent examination. We examined these eight sera with the immuno-blotting method utilizing whole cell extract of HeLa cells, and found the 50 kDa band from all sera tested, to which Jo-1 antigen had been reported to move. We eluted the antibody which formed the 50 kDa band from the nitrocellulose membrane and applied it on HEp-2 cells. This maneuver gave us the fine granular cytoplasmic staining of anti Jo-1 antibody on HEp-2 cells. We therefore concluded that the anti Jo-1 antibody should have cytoplasmic staining on HEp-2 cells although observers might miss it due to other types of associated antinuclear antibodies.

Antibodies, Antinuclear↗
PubMed1991

Interaction of sodium and potassium ions with Na+,K(+)-ATPase. IV. Affinity change for K+ and Na+ of Na+,K(+)-ATPase in the cycle of the ATP hydrolysis reaction.

The Kd for ouabain-sensitive K+ or Rb+ binding to Na+,K(+)-ATPase was determined by the centrifugation method with radioactive K+ and Rb+ in the presence of various combinations of Na+, ATP, adenylylimidodiphosphate (AMPPNP), adenylyl-(beta,gamma-methylene)diphosphonate (AMPPCP), Pi, and Mg2+. From the results of the K+ binding experiments, Kd for Na+ was estimated by using an equation describing the competitive inhibition between the K+ and Na+ binding. 1) The Kd for K+ binding was 1.9 microM when no ligand was present. Addition of 2 mM Mg2+ increased the Kd to 15-17 microM. In the presence of 2 mM Mg2+, addition of 3 mM AMPPCP with or without 3 mM Na+ increased the Kd to 1,000 or 26 microM, respectively. These Kds correspond to those for K+ of Na.E1.AMPPCPMg or E1.AMPPCPMg, respectively. 2) Addition of 4 mM ATP with or without 3 mM Na+ decreased the Kd from 15-17 microM to 5 or 0.8 microM, respectively. Because the phosphorylated intermediate was observed but ATPase activity was scarcely observed in the K+ binding medium containing 3 mM ATP and 2 mM Mg2+ in the absence of Na+ as well as in the presence of Na+ at 0 degrees C, it is suggested that K+ binds to E2-P.Mg under these ligand conditions. 3) The Kd for Na+ of the enzyme in the presence of 3 mM AMPPCP or 4 mM ATP with Mg2+ was estimated to be 80 or 570 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1991

Renal failure with nephrotic syndrome: reversal with large doses of furosemide.

The present study documents the occurrence of renal failure in 4 nephrotic patients including 3 with minor glomerular lesions and one with membranoproliferative glomerulonephritis. One patient died of sepsis at 3 months after onset of the acute renal failure. In the remaining 3, forced diuresis employing albumin plus furosemide in increasing doses to 600 mg/day reversed the renal failure independent of corticosteroid therapy. All of the 4 patients showed characteristic findings consisting of a remarkably low fractional excretion of sodium and an unexpectedly low urine osmolality at the onset of acute renal failure, although they were rather hypervolemic. Our findings suggest that the occurrence of a low fractional excretion of sodium and low osmolality may provide a good index of an absolute indication for intensive weight reduction therapy such as high-dose furosemide in nephrotic patients with acute renal failure in order to reverse the acute renal failure.

Acute Kidney Injury↗
PubMed1990

Effects of cytokines from virus-induced human lymphoblasts on the growth and viability of the promyelocytic leukemia cell line HL-60.

Cells of the human B-cell lymphoblastic leukemia line, BALL-1, were stimulated with Sendai virus. It is shown that the crude culture supernatants contain not only interferon-alpha (IFN-alpha) and tumor necrosis factor-alpha (TNF-alpha) but also other cytokines, here collectively termed 'X' cytokines. The latter did not affect the cytostatic or differentiation-inducing effect of IFN-alpha but synergistically increased the cytotoxicity of TNF-alpha.

Burkitt Lymphoma↗
PubMed1990

Effects of prolonged exposure to interferon-alpha on the viability, proliferation, differentiation, and tumorigenicity of HL-60 promyelocytic leukemia cells.

HL-60 promyelocytic leukemia cells were cultured continuously in the presence of 22,000 IU/ml of purified interferon-alpha (IFN-alpha) for up to 469 days. Study of the properties of the cells at various times during this period showed some changes in their expression of IgG Fc receptors, and in the maturation of the cells as indicated by their esterase content. The differences from control cells cultured in parallel were most marked after exposure to IFN-alpha for some 40-300 days, but were no longer seen after 400-470 days. The difference in tumorigenicity was significant after 150 days, but no longer after 300 days.

Animals↗
PubMed1990

The role of oxidized low density lipoprotein in the pathogenesis of atherosclerosis.

Recently, it has been suggested that oxidized low density lipoprotein (LDL) plays an important role in atherogenesis by facilitating the accumulation of lipids in macrophages. In vitro studies from our laboratory have shown that oxidized LDL is recognized not only by a specific receptor, but also by a receptor which recognizes both oxidized LDL and acetyl LDL. Probucol, originally developed as an antioxidant, prevents the oxidative modification of LDL in vitro. Our recent studies show that probucol prevents the progression of atherosclerosis in homozygous WHHL rabbits in vivo without any changes in plasma LDL cholesterol levels. These results strongly suggest that oxidative modification of LDL could occur in vivo and probucol could slow the progression of atherosclerosis, especially the foam cell-rich fatty streak lesions, without changing plasma cholesterol levels.

Animals↗
PubMed1990

Scanning electron microscope study of neuromuscular junctions in different muscle fiber types in the zebra finch and rat.

Examination by scanning electron microscopy revealed differences between neuromuscular junctions in the muscle fibers of the zebra finch (bird) and rat. The neuromuscular junctions between the anterior and posterior latissimus dorsi muscles of the zebra finch were compared. The junctions of the former, exclusively slow tonic fibers, were small and numerous along the long axis of a single muscle fiber. The synaptic depressions per junction were few. The junctions of the latter, exclusively fast twitch fibers, were large and consisted of more synaptic depressions than the former. Junctional folds were occasionally found in some depressions. The neuromuscular junctions between the extensor digitorum longus and soleus muscles of the rat were also compared. The former consisted almost entirely of fast twitch muscle fibers, whereas the latter consisted of both slow twitch fibers (75%) and fast twitch fibers (25%). The junctions in the extensor digitorum longus muscle were almost all labyrinthine gutters containing exclusively slit-like junctional folds. In the soleus muscle, two types of junctions were observed. One type was similar to that of the extensor digitorum longus muscle; the other was characterized by labyrinthine gutters containing sparse, narrow slit-like and pit-like junctional folds. We suggest from these structural differences of the subneural apparatuses that the junction of the fast twitch muscle is characterized by the subneural apparatus containing numerous slit-like junctional folds, and that of the slow twitch muscle fiber characterized by the apparatus containing sparse, narrow slit-like and pit-like junctional folds.

Animals↗
PubMed1990

[Magnetic resonance angiography using a magnetic resonance flow tagging technique].

A direct bolus imaging method, which was developed for flow quantitation, was applied to the cervical regions of four normal volunteers to perform magnetic resonance angiography. A transverse section of 10 mm thickness was selectively excited to tag blood flow in the supraclavicular region and a projected image of the tagged bolus viewed in terms of anteroposterior direction was obtained after the echo time (TE). Like cine magnetic resonance imaging, multiple images representing four to 16 cardiac phases were obtained with repeated excitations. With a relatively long TE, ranging from 50 to 200 msec, we advanced tagged blood farther downstream, so as to elongate the visualized bolus along the vessel. Within the visualized bolus, the outer layer close to the vessel wall, where the blood flow velocity was slow, stretched like long tails behind the central part of the bolus producing arrow-head shapes, and the tails were assumed to represent the vascular structure. Bilateral common carotid and vertebral arteries were visualized in each image size approximately 5 cm obtained at the systolic phase. Since prolonged TE yielded less signal intensity, the bolus was not clearly visualized when TE was longer than 100 msec. The cine display of images with multiple cardiac phases produced good evaluations of dynamic changes of pulsatile flow, and this method is expected to be a useful diagnostic tool which combines the capability of flow quantitation with non-invasive angiography. The accuracy of this method in delineating a stenotic lesion was also evaluated using phantom with steady flow, since it is one of the most important capabilities of a clinically used angiographic method.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗
PubMed1989

A chloroplast gene encoding a protein with one zinc finger.

We have sequenced a pea chloroplast gene encoding a protein with a zinc finger (zfp A). The putative protein is conserved in chloroplast DNA and shows sequence homology to the E. coli protein controlling fol C expression. Exposure of etiolated pea leaves to light leads to the accumulation of zfp A transcripts. The accumulation of these transcripts does not require de novo protein synthesis in the chloroplast, although the expression of highly inducible genes such as rbc L requires it. These properties suggest that zfp A encodes a protein involved in the regulation of chloroplast gene expression.

Amino Acid Sequence↗
PubMed1989

Hypercoagulable state in the Watanabe heritable hyperlipidemic rabbit, an animal model for the progression of atherosclerosis. Effect of probucol on coagulation.

Blood coagulation in a strain of rabbits designated as Watanabe heritable hyperlipidemic (WHHL) rabbits was examined. The activities of vitamin K-dependent clotting factors, contact factors and clotting factor VIII (F VIII) and the fibrinogen level were significantly higher in WHHL rabbits than in normolipidemic rabbits (all age groups). Values for vitamin K-dependent clotting factor were already higher at 2 months of age. Contact factors and fibrinogen levels increased age after 5 to 8 months. F VIII increased between 5 and 8 months and then decreased. At 2 months of age, WHHL rabbits were divided into two groups. Group A was fed standard rabbit chow and group B standard rabbit chow containing 1% probucol. Probucol prevented the progression of atherosclerosis in group B in the absence of a significant reduction in plasma cholesterol level. F VIII and fibrinogen levels were statistically decreased in all rabbits at all ages in group B (P less than 0.05). These differences in clotting factors between the two groups were most obvious at 8 months (P less than 0.02). We conclude that vitamin K-dependent clotting factors may increase with hyperlipemia and that increases in F VIII and fibrinogen may be closely related to the progression of thromboatherosclerosis.

Aging↗
PubMed1989

Avian spinal cord chimeras. Further studies on the neurological syndrome affecting the chimeras after birth.

These experiments bring new information concerning the immunological status after birth of quail----chick spinal cord chimeras. Such birds have been produced using recipient flocks of chickens different from those in our previous experiments. The breakdown of tolerance after hatching has been recorded and found to vary with the origin of the embryos. Chickens of broiler JA 657 strain and of a white leghorn strain raised in Japan started to exhibit signs of neural graft rejection later in life than the white leghorn chickens from a French breeder used in our previous studies. As previously described, in two animals, long-term tolerance was observed only for allogeneic chick----chick neural tube grafts. In one chimera the neurological syndrome resulting from rejection was reversible, and no signs of immune attack of the grafted central nervous tissue could be detected at sacrifice. This and other observations reported in this article strongly support the contention that the host immune response to foreign neural tissues starts in peripheral nerves and ganglia where no blood-brain barrier exists rather than in the spinal cord. A humoral response of the host against non-polymorphic quail antigens present on fibroblasts was observed in all birds at the time of rejection.

Animals↗
PubMed1989

Sialic acid levels and lag time of growth in chemically defined medium containing 200 mM phosphate among strains of various serotypes of Streptococcus agalactiae.

The type-specific capsular polysaccharide antigen of Streptococcus agalactiae has in previous experimental studies been considered a significant antiphagocytic factor, whereas the lipoteichoic acid moiety has been suggested to be a factor in adherence to human fetal cell lines. Since epidemiological data concerning these cell constituents in strains from the genital tract are lacking, we attempted serotyping and analysis of these constituents of 100 vaginal isolates. The capsular polysaccharide level was shown to be the amount of sialic acid that occupied the terminal side chains of the polysaccharide. We carried out a study to ascertain whether strains exhibited a lag time of growth in a chemically defined medium containing 200 mM phosphate, which has been suggested to be characteristic of strains with high lipoteichoic acid levels. Strains were classified, on the basis of the results of distribution of sialic acid levels, into three categories: (i) strains with a low sialic acid content of equal to or less than 9 micrograms/mg of cell dry weight; (ii) strains with a moderate sialic acid content of more than 9 but less than 12 micrograms/mg of cell dry weight; and (iii) strains with a high sialic acid content of equal to or more than 12 micrograms/mg of cell dry weight. Strains that belonged to the last category, which, as previous experimental data indicate, are potentially virulent strains, were significantly distributed among isolates of types Ia (P less than 0.001) and III (P less than 0.05). On the other hand, strains exhibiting a lag time of growth in the above-mentioned medium were detected to a significant extent in type III isolates (P <0.02). These results may be related to the epidemiological finding that isolates from neonates with late-onset infection were more frequently serotype Ia and III isolates.

Adult↗
PubMed1989

Screening of type Ia and Ib Streptococcus agalactiae strains with high sialic acid levels by determination of susceptibility to tetracyclines.

The type-specific capsular polysaccharide antigen of Streptococcus agalactiae is recognized to be an antiphagocytic factor in strains having large amounts of it. In the present study, it was indicated that vaginal isolates of types Ia and Ib could be classified into two groups on the basis of both their levels of the sialic acid, which occupies the terminal side chains of the polysaccharide, and their susceptibility to tetracyclines: one group comprised strains with low sialic acid levels (less than 9 micrograms/mg of cell dry weight) as well as with susceptibility to tetracyclines (MIC, less than or equal to 0.5 micrograms/ml), and the other comprised strains with higher sialic acid levels (greater than or equal to 9 micrograms/mg) and resistance to tetracyclines (MIC, greater than or equal to 8 micrograms/ml). A few isolates were found to have low levels of sialic acid and to be resistant to tetracyclines, but no isolates that were both relatively high in sialic acid and susceptible to tetracyclines were ever detected. Among strains of those serotypes, the MICs of tetracyclines were not in proportion to the sialic acid levels and were not affected when the sialic acid levels of each strain were altered by using Todd-Hewitt broth with various concentrations of Na2HPO4 and glucose. It was, therefore, apparent that the correlation of sialic acid levels with susceptibility to tetracyclines was not related directly to the sialic acid content or to the amount of the capsular polysaccharide. Since no plasmid DNAs were detected among representative strains that were tetracycline resistant, it was apparent that at least for the strains tested, resistance was chromosomal gene associated. In strains of S. agalactiae of types of Ia and Ib, the determination of susceptibility to tetracyclines was considered to be useful for screening strains with higher sialic acid levels.

Culture Media↗