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Biomedical subjects

R Sato

Publications and source records attributed to R Sato.

At least 19 recordsLinked to original sources

[Change in serum G-CSF levels in patients with Graves' disease by treatment with methimazole].

We evaluated the determination of serum G-CSF in the diagnosis of granulocytopenia due to methimazole (MMI) in 54 patients with Graves' disease, while they were being treated with MMI, by way of measuring WBC counts and serum levels of G-CSF, thyroid hormones, IgE, and interleukin-2. Serum TSH was measured by immunoradiometric assay, serum G-CSF was done by enzyme immunoassay, thyroid hormones and IgE were done by radioimmunoassay, and serum Interleukin-2 was done by enzyme-linked immunosorbent assay. The population whose G-CSF levels were higher than the minimum detectable level (30pg/ml) was 6 (30%) in normal subjects, 4 (22%) in patients with untreated Graves' disease, 2 (12%) in patients with treated euthyroid Graves' disease, 3 (23%) in patients with Graves' disease who had gone through agranulocytosis, and 2 (33%) in patients with Graves' disease complicated with granulocytopenia. There was no significant change in WBC counts for 4 weeks, but there was a significant difference between WBC counts before treatment and those at 8 weeks after treatment. We observed no significant change of serum G-CSF levels in patients with Graves' disease under treatment. However, there were significantly high levels of serum G-CSF and significantly low counts of WBC in patients with Graves' disease complicated with granulocytopenia induced by MMI, compared with those in normal subjects, patients with untreated Graves' disease, patients with treated euthyroid Graves' disease, and patients with euthyroid Graves' disease who had gone through agranulocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Tyre tread marks on the body without internal injuries.

Two cases are presented involving a 5-year-old boy with tyre tread impressions on the back and right arm and a 4-year-old girl with tread marks on the head but both had no internal injuries. These cases suggest that injuries to internal organs do not always occur when the trunk or head is run over by the wheels of a vehicle.

Accidents, Traffic

Sodium channel states control binding and unbinding behaviour of antiarrhythmic drugs in cardiac myocytes from the guinea pig.

OBJECTIVE: The aim was to investigate whether cardiac sodium channel states (rested, activated, inactivated) regulate the binding and unbinding behaviour of antiarrhythmic drugs on the receptor sites. METHODS: Single ventricular myocytes of adult guinea pig heart were obtained by an enzymatic dissociation method in the Langendorff manner. The channel state dependent blocking effects on cardiac sodium current (INa) of quinidine and disopyramide were studied under the whole cell variation of the patch clamp technique. RESULTS: 10 microM quinidine and 20 microM disopyramide produced similar levels of tonic block and use dependent block. The steady state inactivation curve (h infinity curve) was shifted parallel in the negative potential direction by quinidine (10 microM) and disopyramide (20 microM) to the same extent (-10 mV). Removal of the fast inactivation process of INa by chloramine-T did not reduce tonic and use dependent block by these drugs. Onset block study using a double pulse protocol revealed that block developments by both drugs were fitted to the sum of double exponential functions. However, time constant of fast phase of block by disopyramide was faster than that by quinidine, while slow phase was not significantly different. Definition of time courses of unbinding (recovery) at -140 mV indicated that quinidine dissociated relatively slowly as compared to disopyramide. CONCLUSIONS: Quinidine produces more potent tonic and use dependent block of INa by binding to sodium channels at both rested and inactivated states, while disopyramide has a higher affinity for activated state. Therefore, sodium channel states regulate the binding and unbinding behaviour of antiarrhythmic drugs. Furthermore, the fast inactivation process is not essential in producing tonic and use dependent block by antiarrhythmic drugs.

Action Potentials

Topological disposition of UDP-glucuronyltransferase in rat liver microsomes.

The topological disposition of a form of UDP-glucuronyltransferase (called GT-1) in rat liver microsomes was examined. Concanavalin A-Sepharose failed to bind microsomal vesicles even though GT-1 has sugar chains of "high mannose" type, indicating that mannose-containing sugar chains of microsomal glycoproteins including GT-1 are not exposed to the outer surface of microsomal vesicles. Polyclonal antibodies raised against purified GT-1 could bind to microsomal vesicles, indicating that at least part of the GT-1 polypeptide chain is extruded to the outside of the microsomal membrane. Intact microsomal vesicles were digested with carboxypeptidase Y and then subjected to immunoblot analysis using the anti-GT-1 antibodies. It was thus found that the digestion resulted in cleavage of a C-terminal, 2-kDa fragment, leaving a 52-kDa fragment of GT-1 still tightly bound to the membrane. From these results, it is concluded that GT-1 is a transmembrane protein, which extrudes its C-terminal end (at least 2 kDa) to the outside of the membrane, whereas most of its polypeptide chain together with the sugar chains are located on the luminal side of the membrane.

Animals

Immunoreactive copper-zinc superoxide dismutase in damaged human myocardium.

The myocardium in 50 autopsy cases was studied using immunostaining for copper-zinc superoxide dismutase (CuZn-SOD) and standard histochemical procedures. Mucinous degeneration observed in 42 cases showed moderately enhanced expression of immunoreactive CuZn-SOD in lesions which were stained strongly by periodic acid-Schiff but negative with Heidenhain iron-hematoxylin (HIH), von Kossa and luxol fast blue (LFB) stains, whereas coagulation necrosis in 4 cases revealed almost identical immunostaining for CuZn-SOD and HIH to that of contraction band necrosis, i.e. strongly positive HIH staining but negative immunostaining. Basophilic alteration of the myocardial cells in sections fixed with 4% formalin in 2% calcium acetate was seen in 29 cases, being identified frequently in isolated cells as well as in several foci varying considerably in size. This type of alteration demonstrated significantly enhanced expression of immunoreactive CuZn-SOD and was strongly positive with von Kossa and LFB stains. The present study indicates that the myocardium can be affected by free radicals produced in any organ of the body, and that subsequently, insoluble phospholipids react with calcium ions in the fixative and accumulate in the basophilic sarcoplasm.

Adult

Thyroid function before and after induced abortion in normal pregnant women.

We assessed thyroid function before and after induced abortion in 25 normal pregnant women. Serum TSH was significantly increased (P less than 0.02), and serum hCG-beta was significantly reduced (P less than 0.001) 1 week after induced abortion, compared with the levels before induced abortion. There was a significant negative correlation between hCG-beta and TSH, and a positive one between hCG-beta and FT4 before induced abortion (P less than 0.02). No difference was observed in thyroid hormones before and 1 week after induced abortion. The results suggest that hCG stimulates the thyroid gland, gaining an advantage over TSH, in normal pregnant women.

Abortion, Induced

Disopyramide block of cardiac sodium current after removal of the fast inactivation process in guinea pig ventricular myocytes.

To determine the necessity of sodium channel fast inactivation for the block of sodium current (INa) by disopyramide, we studied the effects of disopyramide on INa in guinea pig ventricular myocytes treated with chloramine-T, which removes the fast component of INa inactivation. After exposure to chloramine-T (2 mM), INa amplitude was reduced at all voltages and INa decay was irreversibly prevented. Disopyramide (20 microM) produced both tonic block and use-dependent block of INa in chloramine-T-treated myocytes. Before treatment with chloramine-T, the time course of both the onset of and recovery from use-dependent block by disopyramide were best fit by the sum of double exponential functions, and the time constant of the slow phase of recovery increased as the membrane was hyperpolarized. After removal of the fast component of INa inactivation by chloramine-T, the fast phase of the onset block and the fast phase of recovery from block were abolished. However, the voltage dependency of the time course of recovery from block was unchanged. Thus, although the fast sodium inactivation process is not required for tonic and use-dependent block of INa by disopyramide, it contributes to the fast phase of block development and unbinding from use-dependent block.

Animals

[Analysis of the fertility decline in Japan--focusing on the period of 1950-60 and 1975-85].

Marked fertility declines have been observed in Japan from 1950-60 and 1975-85. The dynamic structure of the fertility decline in the two periods was analyzed employing the Standardization Approach and Bongaarts Model of Proximate Determinants Analysis. The results indicate that the fertility decline in 1950-60 was mainly caused by a drop in marital fertility due to the expanding diffusion of contraception practices and increases in induced abortion. Increased age at marriage cannot be discounted as a factor also. The fertility decline in 1975-85 was mostly caused by delay of marriage as well as a reduction in proportion of the reproductive population which is composed of a cohort born in 1960 or later.

Adolescent

Characterization of phosphopeptide derived from bovine beta-casein: an inhibitor to intra-intestinal precipitation of calcium phosphate.

Casein phosphopeptide (CPP), a highly phosphorylated peptide fragment which inhibits the formation of hydroxyapatite crystal was isolated from pooled ileal contents of rats fed a semi-synthetic diet containing bovine beta-casein. The estimated amino acid sequence of the CPP was shorter than that of the trypsin-digested beta-casein but the core region consisting of consecutive bindings of phosphoserine was fully conserved. A moderate and exchangeable binding to Ca2+ of the CPP molecule well substantiates the high absorbability of calcium from milk and dairy products.

Amino Acid Sequence

Expression and characterization of a rabbit liver cytochrome P450 belonging to P450IIB subfamily with the aid of the baculovirus expression vector system.

Using baculovirus a cDNA for cytochrome P450 (P450F1) belonging to rabbit P450IIB subfamily was expressed in Spodoptera frugiperda cells, where P450F1 was located on electron-dense structures (derived from the endoplasmic reticulum) present in both the cytoplasm and nucleus. Partially purified P450F1 exhibited absorption spectra similar to those of P450(1), the major phenobarbital-inducible form in rabbit liver. Like P450(1), P450F1 could oxidize aminopyrine, benzphetamine, 7-ethoxycoumarin, 1-nitropropane, and 2-nitropropane, though its activities toward benzphetamine and 7-ethoxycoumarin were about 50 and 5%, respectively, of those of P450(1). It is concluded that the members of P450IIB subfamily can act on a variety of xenobiotics, although substrate preferences are different among them.

Animals

Aprindine blocks the sodium current in guinea-pig ventricular myocytes.

Aprindine is a class Ib antiarrhythmic agent. We studied effects of aprindine (3 mumol/l) on the Na+ current using whole cell voltage clamp (tip resistance = 0.5 M omega, [Na]i ando = 10 mmol/l at 18 degrees C). Aprindine revealed tonic block (Kdrest = 37.7 mumol/l, Kdi = 0.74 mumol/l; n = 4). Aprindine, shifted inactivation curve to hyperpolarizing direction by 11.4 +/- 3.5 mV (n = 4) without changes in slope factor. In the presence of 3 mumol/l aprindine, aprindine showed phasic block, i.e., duration-dependent block at 2 Hz (64% +/- 3% at 1.5 ms, 82% +/- 6% at 20 ms, 93% +/- 7% at 200 ms; n = 4). Short single prepulse also produced aprindine-induced phasic block (12% at 1.5 ms, 22% at 100 ms; n = 2). After removal of fast inactivation of Na+ current by 3 mmol/l tosylchloramide sodium, aprindine revealed phasic block, independent of holding potential. The recovery time constant from aprindine-induced phasic block was 4.8 s at holding potential = -100 mV and 5.0 s at holding potential = -140 mV. This use-dependent block of aprindine had pH dependency. Under acidic condition (pH 6.0), 3 mumol/l aprindine showed smaller use-dependent block (14% +/- 7% at 2 Hz; n = 4) comparing with either at pH 7.4 (68% +/- 13%; n = 4) or at pH 8.0 (90% +/- 12%; n = 4). The results suggest that aprindine could bind to the receptor via activation process through channel pore, resulting in decrease of Na+ current, and egress from the receptor through the lipid bilayer. These effects might be attenuated under acidic condition due to changes in intracellular ratio of charged to neutralized form of drug molecule.

Action Potentials

Glucose overload and hepatic energy metabolism after resection of the cirrhotic liver in rats.

The effect of glucose hyperalimentation on energy metabolism in the cirrhotic rat liver after 70% hepatectomy was studied. After resection, rats received either 30 kcal/kg per day (group I) or 200 kcal/kg per day (group II) of glucose for 48 h. In both groups, hepatic mitochondrial ATP synthesis was accelerated when palmitic acid was used as substrate and suppressed when pyruvate was used. This suggests that the energy substrate of the remnant liver was principally fatty acids rather than glucose. Hepatic energy charge was within normal limits in group I, but decreased significantly in group II after hepatectomy. An abundance of glucose in the early postoperative period, therefore, caused a hepatic energy derangement by suppressing fatty acids utilization; this suppression was corroborated by the findings of lower immunoreactive glucagon and non-esterified fatty-acid concentrations in group II. To determine optimal glucose administration, the predicted value of glucose disposal rate (GDR) was calculated after an intravenous glucose tolerance test. GDR decreased significantly after hepatectomy and did not increase appreciably even with a large dose of insulin administration. These results suggest that glucose administration should be tailored to the GDR values after resection of the cirrhotic liver.

Adenosine Triphosphate

Quinidine blocks cardiac sodium current after removal of the fast inactivation process with chloramine-T.

To determine if the fast sodium current inactivation process is necessary for sodium current (INa) blockade by quinidine, we studied the effects of quinidine on INa in guinea-pig ventricular myocytes treated with chloramine-T, which removes the fast inactivation process of INa. Following exposure to chloramine-T (2 mM), INa amplitude was reduced at all voltages and INa decay was irreversibly prevented. Quinidine (10 microM) produced resting block of INa of 36 +/- 2% (n = 5) at the peak potential of -30 mV in chloramine-T treated myocytes. Quinidine decreased INa in a dose-dependent manner. The half-blocking concentration (KD) was 1.9 +/- 0.2 x 10(-5) M (n = 4). The steady-state inactivation curve (hx) was shifted in the negative potential direction (-5.2 +/- 0.4 mV, n = 4). Even after removal of the fast inactivation process of INa, use-dependent block was observed in the presence of quinidine when various depolarizing pulse durations (5 ms approximately 200 ms) were applied repetitively at intervals of 300 ms approximately 2 s. Longer depolarizing pulses and higher frequency pulse trains produced greater use-dependent block. Use-dependent block was also enhanced at more positive holding potentials. These results suggest that quinidine produces both resting block and use-dependent block of sodium channels in the absence of the fast INa inactivation process.

Animals