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Biomedical subjects

T Shimada

Publications and source records attributed to T Shimada.

At least 811 records · Page 45Linked to original sources
PubMed1988

Thyroid functions in patients with various chronic liver diseases.

In order to clarify an alteration in thyroid functions in patients with chronic liver diseases, serum total and free thyroxine (T4, FT4), total and free triiodothyronine (T3, FT3), total reverse T3 (rT3), thyrotropin (TSH), thyroxine-binding globulin (TBG) concentrations, and T3 uptake (T3U) were measured by radioimmunoassays in 53 patients with chronic hepatitis (CH), 24 patients with compensated liver cirrhosis (LC), 17 patients with hepatocellular carcinoma associated with LC (HCC), and 40 normal subjects. Serum T4, T3, and rT3 in CH, and serum rT3 in HCC were significantly increased, while serum T4 in LC and serum T3 in HCC were significantly decreased. Serum TBG was increased and T3U was decreased in these patients. Serum TBG in CH and LC correlated positively with transaminase, and inversely with prothrombin time. FT4 and T4/TBG ratios in CH and LC and FT3 and T3/TBG ratios in LC and HCC were significantly decreased. Although T4/TBG ratios in HCC and T3/TBG ratios in CH were significantly decreased, FT4 in HCC and FT3 in CH were not decreased. The ratio of rT3/T3 in CH and LC correlated with various liver function tests. FT3 in LC and HCC correlated inversely with BSP (45') and positively with KICG. No differences in serum TSH values were found between chronic liver diseases and normal subjects. From these results, it was concluded that the thyroid functions in patients with chronic liver diseases were affected by the decrease in serum thyroxine, elevated serum TBG, the degree of which is in proportion to that of the liver cell damage, and impaired peripheral conversion of T4 to T3, the degree of which is in proportion to that of the hepatic dysfunction.

Adolescent↗
PubMed1988

The distribution and structure of the lymphatic system in dog atrioventricular valves.

A morphological study of the lymphatic system in atrioventricular (AV) valves of adult dogs and puppies was carried out using a series of techniques including India ink injection, a hydrogen peroxide technique, light microscopy, and electron microscopy. Lymphatic capillaries were found in all cusps of the AV valves, and were shown to extend delicate networks in the subendocardium of the atrial side of the valves. The extent of their development varied among cusps, being most prominent in the anterior cusp of the mitral valve. Marked differences were noted in the intravalvar distribution between lymphatic capillaries and blood microvessels. The ultrastructures of the lymphatic capillaries in the AV valves were also demonstrated.

Animals↗
PubMed1988

Effects of mechanical stretch on the membrane potential of guinea pig ventricular muscles.

We studied the effect of stretch on the membrane potentials and ultrastructure of isolated ventricular papillary muscles of guinea pigs. The muscles were stimulated at 0.5 Hz and stretched stepwise from slack length (90% of Lmax) to 100% (mild stretch), 110-120% (moderate stretch), and 130-140% of Lmax (severe stretch), under microscopic control. In control Tyrode solution (K+ = 5.4 mM, Ca2+ = 1.8 mM, Mg2+ = 0.5 mM), the mild to moderate stretch significantly depolarized the resting potential (RP) by about 6 mV as compared to that in slack length, whereas the severe stretch hyperpolarized the membrane by about 5 mV. The latter finding was new and was focused on in later experiments. Both the hyperpolarization and depolarization became more marked when [K+]o was decreased to 1.35-2.7 mM, and became less with elevated [K+]o to 10.8-21.6 mM, thereby suggesting the participation of altered K+ conductance (gK) with these changes in the RP. Perfusion with low [Ca2+]o (0.45 mM) enhanced the depolarization but eliminated the hyperpolarization; high [Ca2+]o (7.2 mM) inhibited the depolarization without effect on the hyperpolarization. D-600 (1 microM), caffeine (10 mM), and ryanodine (1 microM), all of which may produce decreases in [Ca2+]i, abolished the hyperpolarization with inconsistent effects on the depolarization. Moderate to severe stretches decreased the maximum rate of rise of action potential (Vmax), by shifting the Vmax-RP relationship toward hyperpolarizing direction. The shift could be reversed partially after increasing [Mg2+]o to 8.0 mM. Electron microscopic examination revealed that the sarcoplasmic reticulum (SR) remained intact with mild to moderate stretches with significant lengthening of sarcomere length, while with a severe stretch, the SR showed a structural disarrangement with a non-uniform lengthening of sarcomere length. Our observations suggest that stretch-induced hyperpolarization is probably mediated by the increase in gK, presumably secondary to the increase in [Ca2+]i. Ca2+ may be released from the SR upon mechanical stretch of the organelle.

Action Potentials↗
PubMed1988

Effect of oleic acid on mitochondrial oxidative phosphorylation in rat brain slices.

We tested the effect of oleic acid on oxidative phosphorylation and free fatty acid composition in rat brain slices simultaneously to investigate the relationship between the change in respiratory control ratio and the uptake of oleic acid in the brain mitochondria. The uncoupling of mitochondria was observed when the ratio of oleic acid to stearic acid in the free fatty acid fraction was nearly doubled, but was not recovered even by the addition of fatty acid-free bovine serum albumin. The data suggest that the intactness of oxidative phosphorylation of brain mitochondria is maintained by the precise control of the free fatty acid composition in the mitochondrial membranes.

Animals↗
PubMed1988

[Infarct size related to the distribution and site of coronary artery lesions studied by the unfolded map technique using single photon emission computed tomography].

To assess the relative importance of the anatomical characteristics of the coronary artery distribution and the sites of the arterial stenoses in relation to infarct size, 21 patients with old myocardial infarction and angiographically-proven 90% or greater stenoses (AHA classification) of one of the major coronary arteries were studied. The infarct size was evaluated by a new quantitative method, the unfolded map, derived from single photon emission computed tomography (SPECT). Eleven patients had right coronary artery disease (Group RCA: segment 1; five patients and segment 2; six patients). Seven patients who had the large left anterior descending artery (LAD) which was distributed to the inferior portion of the apical area were defined as Small R, and four patients with large RCA as Large R. Ten patients each had a significant stenosis in the LAD (Group LAD: segment 6; six patients and segment 7; four patients). Four patients with significant stenosis proximal to segment 9 were defined as Pre-9, and seven patients with stenosis distal to the segment, as Post-9. Stress T1-201 scintigraphy with SPECT was performed and the unfolded map was obtained with data of the maximal count circumferential profiles in the redistribution image. Infarction was defined as a defect below 55% of the standard value. The necrotic area ratio expressed as percentage of the defect area to the entire map area was calculated and used as the indicator of infarct size. Although there was no significant difference in the necrotic area ratio between segment 1 and 2 lesions. Large R had the significantly larger necrotic area ratios (24.9 +- 4.6%) than did Small R (9.7 +- 4.4%; p less than 0.01). In the Group LAD, there was no significant difference in the necrotic area ratio between segment 6 and 7 lesions, but Pre-9 had the larger ratio (30.4 +- 3.3%) than did Post-9 (15.4 +- 7.7%; p less than 0.01). These data suggest that the factors related to infarct size are either the distribution of the coronary arteries in the apical area in the Group RCA or the sites of the stenotic lesions relative to the branching portion of the first diagonal branch in the Group LAD.

Adult↗
PubMed1987

Role of Na+/H+ antiport in intracellular pH regulation by rabbit enterocytes.

The steady-state intracellular pH (pHi) of isolated rabbit enterocytes was determined using 9-aminoacridine, a fluorescent weak base, and the null-point method with digitonin. When cells are incubated in a Na+-containing solution, the estimated value of pHi was in the range of 7.10-7.20, whereas it was 6.60-6.70 when cells were incubated in a Na+-free solution, indicating an important role of external Na+ in maintaining pHi at a slightly alkaline level. Pulse injection of Na+ into a Na+-free cell suspension induced a slowly developing alkalinization of pHi. The time course of the alkalinization was found to be dependent on the Na+ concentration. Li+ had the same effect as Na+, while K+ had a slight effect. Amiloride inhibited the effects of Na+ dose-dependently. These results indicate that the Na+/H+ antiport plays an important role in maintaining the pHi at a neutral or slightly alkaline level in the intact enterocytes.

Amiloride↗
PubMed1987

Cytochrome P-450-mediated activation of procarcinogens and promutagens to DNA-damaging products by measuring expression of umu gene in Salmonella typhimurium TA1535/pSK1002.

A simple and sensitive procedure for the determination of cytochrome P-450 (P-450)-mediated activation of chemical procarcinogens and promutagens to DNA-damaging products has been developed using a method measuring the expression of the umu gene in Salmonella typhimurium TA1535/pSK1002, which is based upon the initial procedures as described by Oda et al. [Mutation Res. 147, 219 (1985)]. The chemicals examined were a variety of potent carcinogenic and mutagenic compounds including heterocyclic aromatic amines, aromatic amines, polycyclic aromatic hydrocarbons and aflatoxin B1. These chemicals were incubated with rat liver microsomes or a reconstituted monooxygenase system containing three forms of purified P-450 in the presence of a bacterial tester strain, and the induced-umu gene expression was determined by measuring the beta-galactosidase activity produced by fusion gene in the cells. The activity was increased linearly for at least 2 hr with an initial lag time of 30 min and was dependent on the concentrations of P-450 in the reaction mixture. Thus, the metabolic activation of these compounds by P-450 could be compared on a basis of the specific beta-galactosidase activity/min/nmol P-450. Among three forms of P-450, two isozymes induced by 3-methylcholanthrene were found to be more active in catalyzing the metabolic activation of most of the chemicals examined than a form of P-450 which is induced by phenobarbital. Data also showed that a high spin form of P-450 isolated from 3-methylcholanthrene-treated rats had a profound role in the activation of procarcinogens and promutagens. This conclusion was based on the results of catalytic activities by three forms of P-450 in a reconstituted monooxygenase system, and on the effects of specific antibodies against these P-450s on the reactions catalyzed by liver microsomes.

Animals↗
PubMed1987

Lifespan extension of basal cell nevus syndrome fibroblasts by transfection with mouse pro or v-myc genes.

Dermal fibroblasts from patients with the autosomal dominant cancer-prone disease Basal Cell Nevus Syndrome (BCNS) exhibit a serum dependence, anchorage dependence and in vitro lifespan (about 20 population doublings or less) similar to those of fibroblasts from normal age-, race- and sex-matched controls. Transfection with v-myc or with an activated mouse pro-I gene (which specifies sensitivity to promotion of neoplastic transformation in JB6 mouse epidermal cells) specifically conferred partial immortality on the BCNS fibroblasts by substantially extending their population doubling levels by more than 19 population doublings. This suggests that either v-myc or pro-I gene can cooperate with BCNS gene(s) to produce an extension of lifespan or partial immortality. However, the transfected BCNS fibroblasts that escaped senescence were anchorage-dependent even after exposure to the tumor promoters 12-O-tetradecanoyl-phorbol-13-acetate (TPA), epidermal growth factor (EGF) or platelet-derived growth factor (PDGF). These observations indicate that BCNS fibroblasts differ from their normal counterparts in susceptibility to extended growth and may therefore be pre-neoplastic. It is clear that they require more than an activated pro or myc gene for progression to the tumor cell phenotype.

Adult↗
PubMed1987

Enhancement by a synthetic isoprenoid of the toxicity of conjugates of epidermal growth factor with Pseudomonas exotoxin.

A newly synthesized isoprenoid, N-solanesyl-N,N'-bis(3,4-dimethoxybenzyl)ethylenediamine, has a verapamil-like structure but no calcium channel blocking activity. The isoprenoid enhanced the cytotoxic effect of a conjugate of epidermal growth factor coupled with Pseudomonas exotoxin in human KB cells. By using iodinated epidermal growth factor ([125I]EGF), the effect of the isoprenoid on intracellular transport of EGF was examined. The isoprenoid did not affect the binding and uptake of [125I]EGF by KB cells. The release of radioactivity associated with [125I]EGF into medium was slow in the presence of the isoprenoid. Density gradient fractionation studies using cell homogenates suggest that [125I]EGF accumulates in an undegraded form in lysosomes when cells are treated with the isoprenoid. The pH value in lysosomes of KB cells was 5.5, and SDB did not affect significantly the pH value at the concentrations used to potentiate the cytotoxicity of chimeric toxins. Electron microscopy showed an increased number of electron-dense bodies in KB cells grown for 24 hr with 17-51 micrograms/ml isoprenoid. The potentiating action of chimeric toxins by the isoprenoid is discussed in relation to the altered lysosomal function in treated cells.

ADP Ribose Transferases↗
PubMed1987

Lipid composition of the plasma membrane isolated from normal and precancerous rat bladder epithelium.

Four-week-old Wistar strain rats were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) solution for 12 weeks and used as a precancerous model. Sixteen-week-old rats of the same strain were used as controls. Plasma membranes (PMs) were prepared from normal and precancerous bladder epithelium. The lipid content and the fatty acid compositions of total lipids, phospholipids, and their subclasses were analysed. The following observations were made: 1) Precancerous PMs had longer chains composed of more unsaturated fatty acids than the normal ones. 2) There were high amounts of arachidonic acid in rat bladder epithelium, and it accounted for more than fifty percent of phosphatidylethanolamine. PMs of precancerous epithelium had more arachidonic acid than those of the normal epithelium. These findings may be useful for the early detection of precancerous epithelium.

Animals↗
PubMed1987

Lack of correlation between formation of reactive metabolites and thymic atrophy caused by 3, 4, 3', 4'-tetrachlorobiphenyl in C57BL/6N mice.

The possible role of active metabolites of 3, 4, 3', 4'-tetrachlorobiphenyl (TCB) in causing thymic atrophy was investigated using inbred strains of mice. The generation of reactive species which bind covalently to cellular proteins was used to monitor the formation of active TCB metabolites. The amount of in vitro covalent binding of TCB to proteins by liver microsomes was increased markedly by pretreatment of AHH-responsive C57BL/6N mice with either 3-methylcholanthrene (MC) or TCB itself, although these two inducers were not effective in AHH-nonresponsive DBA/2N mice. MC treatment also caused an induction of microsomal TCB-binding activity in all of the (C57BL/6N X DBA/2N) F1 mice. Moreover, among 38 individuals of [(C57BL/6N) (DBA/2N) F1 X DBA/2N] backcross, 23 mice responded to MC with respect to microsomal TCB-binding activity while others did not. These results suggest that the conversion of TCB to protein-bound metabolites is mediated by particular form(s) of cytochrome P-450 which is (are) induced by an Ah receptor mechanism. In order to ascertain whether the active TCB metabolites play a role in causing thymic atrophy, 14C-labeled TCB was administered IP to C57BL/6N mice and the amount of covalent binding of radioactive metabolites to tissue proteins was determined. The in vivo binding was evident in the liver, particularly in the microsomal fraction, on the basis of protein content. In contrast, the thymic proteins contained no measurable amounts of bound radioactivity even when the mice showed marked thymic atrophy. These data suggest that thymic atrophy caused by TCB is not likely to result from the generation of reactive metabolites.

Animals↗