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Biomedical subjects

N Hirashima

Publications and source records attributed to N Hirashima.

At least 55 records · Page 3Linked to original sources

Hepatitis C virus serotype II responds more favorably to interferon-alpha therapy.

To determine whether serological typing of hepatitis C virus correlated with the response to interferon-alpha therapy, hepatitis C virus serotypes were determined by subtype-specific antibody to NS4 polypeptide by enzyme-linked immunosorbent assay in 55 Japanese patients with chronic active hepatitis C who subsequently received recombinant interferon-alpha 2a therapy. Response to interferon-alpha was defined as complete and sustained (n = 12), complete response followed by relapse (n = 26), and no response (n = 17). There was no difference in the clinical biochemical parameters between these patients groups. However, a higher proportion (50.0%) of patients with hepatitis C virus serotype II showed complete and sustained response to interferon-alpha, compared to serotype I (11.1%, p < 0.01). These data indicate that this simple hepatitis C virus serotyping assay is a useful predictor of response to interferon-alpha therapy in patients with chronic hepatitis C virus infection.

Adult↗

Chronic hepatitis C complicated by Coombs-negative hemolytic anemia during interferon treatment.

Autoimmune hemolytic anemia is an autoimmune diseases which is reported to be caused by interferon treatment. A 33-year-old male with chronic hepatitis C developed Coombs-negative hemolytic anemia, probably due to administration of interferon-alpha 2b. This is, to our knowledge, the first report of chronic hepatitis C complicated by Coombs-negative hemolytic anemia during interferon treatment.

Acute Kidney Injury↗

Action and binding of omega-conotoxin on the putative calcium channel of synaptosomal plasma membrane from electric organ of Japanese electric ray, Narke japonica.

Actions of omega-conotoxin GVIA on synaptosomes isolated from a Japanese electric ray, Narke japonica, were investigated. omega-Conotoxin inhibited, in a dose-dependent manner, both increases in free calcium concentration in, and acetylcholine release from synaptosomes depolarized with a high concentration of potassium ions. The concentrations of omega-conotoxin required for half-maximal inhibition (IC50) of increase in intrasynaptosomal Ca and acetylcholine release were 8 and 7 microM, respectively. Assay using radioiodinated toxin derivative revealed a specific binding site with a dissociation constant (KD) of 2.8 microM and a density (Bmax) of 45 pmol/mg protein of synaptosome. Binding assay with synaptosomal plasma membrane showed a KD = 7 microM and a Bmax = 200 pmol/mg protein. Autoradiography with sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis after covalent cross-linking of the toxin, using disuccinimidyl suberate, revealed the 170,000 mol. wt peptide to be an omega-conotoxin receptor. The present study has directly and clearly shown that omega-conotoxin inhibits acetylcholine release by blocking Ca influx into nerve terminals. The 170,000 mol. wt peptide identified as a receptor of the toxin exists in high density in the plasma membrane of the presynaptic nerve terminal and is likely to be a component of a voltage-dependent Ca channel responsible for the neurotransmitter release.

Acetylcholine↗

A calcium-dependent cation channel in mast cell granule membranes reconstituted into a lipid bilayer.

Secretory granules isolated from rat peritoneal mast cells were reconstituted into a lipid planar bilayer and membrane current was measured. A novel calcium- and voltage-dependent cation channel with single-channel conductances of 80 pS for fully open and 60 pS for sub-conducting states was detected. This channel opened only when potential of the cis compartment, which corresponds to the cytoplasmic side in the cell, was positive with respect to the trans compartment and only when Ca concentration of the cis compartment was higher than 10(-7) M. The open channel probability further increased, depending on the concentration of Ca. The physiological role of this channel remains to be determined.

Animals↗

Comparative electrophysiological study of reconstituted giant vesicle preparations of the rabbit skeletal muscle sarcoplasmic reticulum K+ channel.

Sarcoplasmic reticulum (SR) membranes isolated from rabbit skeletal muscle were reconstituted into two types of giant vesicles: (1) Giant proteoliposomes prepared by freeze-thawing of a mixture of SR vesicles and sonicated phospholipid vesicles without the use of detergent. (2) Giant SR vesicles prepared by fusion of SR vesicles using poly(ethylene glycol) (PEG) as a fusogen and without the addition of exogenous lipid. These giant vesicles were patch-clamped and properties of the single voltage-dependent potassium channel in the excised patch were studied. Single-channel conductance in a symmetrical solution of 0.1 M KCl and 1 mM CaCl2 was 140.0 +/- 10 pS (n = 5) for freeze-thawed vesicles and 136.4 +/- 15 pS (n = 7) for PEG vesicles. Both types of vesicles exhibited a sub-conductance state having 55% of the fully open state conductance. The voltage-dependence of open-channel probability could be expressed in terms of thermodynamic parameters of delta Gi = 0.95 kcal/mol and z = -0.77 for freeze-thawed vesicles and delta Gi = 0.92 kcal/mol and z = -0.87 for PEG vesicles. These values correlated well with previous data obtained by fusion of native SR vesicles with a planar lipid membrane. Channel orientation was found to be conserved in both types of vesicles used in the present study.

Animals↗

[Chromosomal abnormality of trisomy 4 in a patient with acute nonlymphocytic leukemia (FAB: M2)].

We report a patient with acute nonlymphocytic leukemia (FAB classification: M 2) with trisomy 4, which is the first case in our country. A 42-year-old man was admitted to our hospital because of fever and general fatigue in May, 1988. His WBC count was 8,100/microliters with 90% of leukemic cells and bone marrow smear showed 76.1% leukemic cells. The chromosomal analysis of marrow cells by G-banding revealed 47, XY, +4. In spite of administration of chemotherapy complete remission was not obtained, and he died of septic shock and severe liver damage 4 months after making the diagnosis. Chromosomal abnormality of trisomy 4 has been reported to be associated with predominantly either M 4 or M 2, and to be less than 0.1% of incidence in ANLL, according to the Second MIC Cooperative Study Group. It is suggested that trisomy 4 may be caused by exposure to some environmental factors such as toxic substances, since this chromosomal abnormality has been reported in the last 10 to 20 years.

Adult↗

Potassium channels in synaptosomal membrane examined using patch-clamp techniques and reconstituted giant proteoliposomes.

Synaptosomes isolated from the rat cerebral cortex were mixed with sonicated phospholipid vesicles and subjected to freezing-thawing to acquire giant proteoliposomes. Membranes of these giant proteoliposomes could thus be studied using patch-clamp techniques. Single-channel currents were measured with the inside-out patch of the membrane, in KCl solutions. Three different potassium channels were detected and unit conductances were 15.1, 28.6 and 91.0 pS, respectively, in a symmetrical 150 mM KCl solution. All these channels are more permeable to potassium than to sodium ions, the permeability ratio being about 2:1. Tetraethylammonium ions blocked these channels. The gating of these potassium channels is independent of the membrane potential. Presumably, these channels play a role in the resting membrane potential of presynaptic nerve terminals.

Animals↗

Giant proteoliposomes prepared by freezing-thawing without use of detergent: reconstitution of biomembranes usually inaccessible to patch-clamp pipette microelectrode.

When sarcoplasmic reticulum membrane vesicles or synaptosomes were mixed with sonicated phospholipid vesicles and subjected to freezing-thawing, giant vesicles of up to 50 microns in diameter were formed. When the biomembrane vesicles were labeled with a covalently binding fluorescent dye, the resultant giant vesicles were fluorescent, thereby suggesting that the freezing-thawing process induces fusion of phospholipid and biomembrane vesicles. When membranes of the giant proteoliposomes thus prepared were studied using the patch-clamp technique, potassium channels of the biomembranes were detectable. The present method of the giant proteoliposome preparation is simple and rapid, and provides a system suitable for the study of ion channels of various biomembranes usually inaccessible to a patch-pipette microelectrode.

Animals↗

Utilization of diethyl-beta-cyclodextrin as a sustained-release carrier for isosorbide dinitrate.

Heptakis(2,6-di-O-ethyl)-beta-cyclodextrin (2) was prepared and its physicochemical properties, such as aqueous solubility and surface activity, were compared with those of beta-cyclodextrin (1) and heptakis(2,6-di-O-methyl)-beta-cyclodextrin (3). A possible utility of 2 as a sustained-release drug carrier was examined using a water-soluble drug, isosorbide dinitrate. The dissolution and release rates of isosorbide dinitrate from capsule and tablet forms were significantly retarded by the complexation with 2. The sustained-release pattern of isosorbide dinitrate was produced for a long period after the oral administration of a single dose of capsule or tablet containing the 2 complex to rats. The results indicated that 2 may serve as a hydrophobic drug carrier for sustained-release of isosorbide dinitrate.

Animals↗

[Adjustment of urinary delta-aminolevulinic acid concentrations in workers exposed to lead and heat. Adjustments of specific gravity to 1.020 and urinary volume coefficients].

Adjustments of urinary ALA concentrations as to urinary specific gravity and creatinine were examined for workers exposed to lead and heat. Judging from our findings, we suggested that it was preferable to adopt the specific gravity (UG) at 1.020 as the adjustment value to obtain the correct urinary ALA concentration. Though corrected values thus obtained were found adequate for urine in the normal range of specific gravity, they failed to be adequate for concentrated urine samples higher than UG 1.025. Urinary volume adjustment was found to be necessary for these concentrated urine in stead of urinary specific gravity adjustment. For the practical purposes, we postulated urinary volume coefficients, which were estimated to be 0.5 for samples ranging from UG 1.026 to 1.030, 0.4 for samples from UG 1.031 to 1.035 and 0.3 for samples from UG 1.036 to 1.040, respectively.

Aminolevulinic Acid↗

[Inhibition rate of gamma-aminolevulinic acid dehydratase activity in erythrocytes as a reliable index for individual workers of low lead exposure].

As the delta-aminolevulinic acid dehydratase (ALAD) activity in erythrocytes is decreased by lead exposure, we considered that a net reduction of ALAD activity by lead in blood should be the difference between the activity fully activated with zinc (Zn2+) and dithiothreitol (DTT) and that without activation. The optimal condition of activation of ALAD was found by addition of 0.25 mM of Zn2+ and 10 mM of DTT in the reaction mixture. Judging from our previous results that the amount of inhibition of ALAD activity can be represented as the rate of inhibition and is closely correlated with the dose of lead administered to rabbits, the inhibition rate of ALAD activity and lead content in blood (Pb-B) of lead workers were measured. The scatter diagram obtained from the inhibition rate and lead content in blood has two groups being divided at 50 micrograms/ml of Pb-B. In one group less than 50 micrograms/100 ml of Pb-B, the inhibition rate has been closely related to Pb-B., the regression equation being Y = 1.82 X + 11.7, and the correlation coefficient + 0.926. In another group more than 50 micrograms/100 ml of Pb-B the inhibition rate remained constant at the 90% level. Measurement of the inhibition rate suggests to have practical validity for monitoring lead exposure in workers, and by means of a nomograph lead content in blood can be estimated from the inhibition rate.

Animals↗

[Evaluation of remission in trophoblastic disease as seen from serum hCG level (author's transl)].

The clinical course of trophoblastic diseases detected through measurement of hCG levels from 1971 to 1978 were examined. 1) Twenty out of 178 cases of hydatidiform mole developed into cases of invasive mole or choriocarcinoma after D & C. There was a decrease in hCG value to the LH level in the remaining 158 cases. 2) The hCG level fell to the LH level in 59 cases of invasive mole and choriocarcinoma after treatment, with a subsequent reoccurrence of recurrence in 3 cases in which there was no additional chemotherapy. However, there were no reoccurrences in 40 cases in which chemotherapy had been added. 3) A transient lowering of hormone secretion and cell proliferation was seen in cultures of choriocarcinoma cells, but indications of the restoration of these activities were subsequently observed. 4) A cellular effect was observed in 5.6% where hCG values decrease in LH levels. Remission is determined in hydatidiform mole when the hCG value persists at the LH level, and remission in invasive mole and choriocarcinoma when no cellular effect is detected after two courses of chemotherapy following decrease of hCG value to the LH level.

Adolescent↗