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Biomedical subjects

A Yoshida

Publications and source records attributed to A Yoshida.

At least 577 records · Page 32Linked to original sources
PubMed1993

Increased mechanical extraction of T-tubule/junctional SR from cardiomyopathic hamster heart.

We determined the contents of L-type calcium channels (LCC) and other membrane proteins in ventricular homogenates and microsomes prepared from hearts of 30- to 70-day-old Syrian cardiomyopathic (Bio 14.6) and normal hamsters. Quantitative immunoblot assay revealed that myopathic microsomes, as compared with normal controls, were enriched about twofold with the alpha 1-subunit of LCC, the ryanodine receptor calsequestrin, and Na(+)-K(+)-adenosinetriphosphatase (ATPase), whereas the contents of these proteins in ventricular homogenates were not different. In contrast, Na(+)-H+ antiporter and sarcoplasmic reticulum (SR) Ca(2+)-ATPase showed no difference in their contents in both homogenates and microsomes. Radioligand binding assay further showed no significant difference in the number of binding sites for [3H]prazosin, [125I]iodocyanopindolol, and [3H]saxitoxin between myopathic and normal microsomes. These result suggest that whereas membrane densities of LCC and the other proteins examined are not increased in myopathic cardiomyocytes, T-tubule/junctional SR membranes are more easily extracted from them by mechanical disruption. This, together with 1.5-fold higher yield of microsomal fractions from myopathic heart muscle, shows that abnormality exists in the mechanical property of cell membrane in the myopathic heart.

Animals↗
PubMed1993

Renal hypouricemia with both drug-insensitive secretion and defective reabsorption of urate: a novel type of renal hypouricemia.

Renal handling of urate in the hypouricemic patient with increase in both urate clearance (Cur) and Cur/creatinine clearance (Ccr) and normal urinary excretion of urate was studied according to the pharmacological evaluation. In the present case there was no response of urate excretion to either pyrazinamide or probenecid. Both furosemide and prednisolone could not alter Cur and Cur/Ccr. Administration of inosine could have increased Cur, which was greater than Ccr. These results suggest that the present case had the defect of both pre- and postsecretory reabsorption of urate, accompanied by the existence of drug-insensitive secretion of urate, which is different from hitherto known types of renal hypouricemia, i.e. a novel type of renal hypouricemia.

Adult↗
PubMed1993

Renal hypouricemia due to enhanced tubular secretion of urate associated with urolithiasis: successful treatment of urolithiasis by alkalization of urine K+, Na(+)-citrate.

We encountered a case of hypouricemia with increases both in urate clearance (Cur) and in the ratio of Cur to creatinine clearance (Cur/Ccr), the normal daily urinary excretion of urate, and urolithiasis. Pyrazinamide markedly decreased Cur and Cur/Ccr, and both probenecid and benzbromarone markedly increased Cur and Cur/Ccr, however, benzbromarone did not increase either Cur or Cur/Ccr under pretreatment with pyrazinamide in the patient. Thus, the diagnosis was made of renal hypouricemia due to enhanced tubular secretion of urate. The urinary pH of the patient tended to be acidic. Three months after the start of alkalization of the patient's urine by K+, Na(+)-citrate, both urolithiasis and the symptoms related to urolithiasis disappeared. These results suggest that renal hypouricemia due to enhanced tubular secretion of urate can result in urolithiasis and the alkalization of urine may be an effective treatment for uric acid stones.

Benzbromarone↗
PubMed1993

Erythromycin inhibits the production of elastase by Pseudomonas aeruginosa without affecting its proliferation in vitro.

Extracellular proteases from Pseudomonas aeruginosa play important roles in infections in the respiratory tract. The effect of erythromycin (EM), a macrolide antibiotic, on the production of elastase by P. aeruginosa was investigated in vitro and compared with the effect of other antibiotics. Thirty-four (94.4%) of thirty-six different strains produced detectable amounts of elastase determined by the gel diffusion method. The elastase production was inhibited completely by EM in 27 (79.4%) of 34 strains at some concentrations between 0.125 and 64 micrograms/ml. At 4 micrograms/ml or less, the elastase production was inhibited completely in four (11.8%) strains and more than 50% in the other 10 (29.4%). At 8 micrograms/ml or less, the elastase production was inhibited completely in 11 (32.4%) strains and more than 50% in the other nine (26.5%). The proliferation was partially inhibited at 32 and 64 micrograms/ml. Roxithromycin inhibited the elastase production at higher concentrations than EM without inhibiting the proliferation. Midecamycin and ampicillin did not inhibit the elastase production or the proliferation. Doxycycline and ticarcillin inhibited the elastase production and/or the proliferation at concentrations greater than 16 micrograms/ml. Although ofloxacin (OFLX) inhibited both the proliferation and the elastase production in parallel at low concentrations, there were six (16.7%) strains resistant to OFLX. Among them the elastase production was inhibited in five strains by EM. These results suggest that EM acts on P. aeruginosa to inhibit extracellular production of elastase without affecting the proliferation of the bacteria.

Cell Division↗
PubMed1993

Tumor induction by concurrent oral administration of ethylenethiourea and sodium nitrite in mice.

Carcinogenic potential of ethylenethiourea (ETU) in combination with sodium nitrite was investigated in ICR mice of both sexes. Groups of 30 males and 30 females each were given 10 weekly oral administrations of ETU and sodium nitrite with the following combinations of dosing (ETU vs sodium nitrite, mg/kg/wk): 0 vs 0, 100 vs 0, 0 vs 70, 25 vs 17.5, 50 vs 35, and 100 vs 70. Thereafter, the animals were allowed to live without treatment up to 18 mo after the first administration. Concurrent administration of ETU and sodium nitrite caused earlier development of tumors and/or dose-dependent increases in the incidences of tumors in the lymphatic tissue, lung, forestomach, Harderian gland, and uterus, whereas treatment with either ETU or sodium nitrite failed to show carcinogenic activity. In addition, carcinomas in the forestomach and uterine horn were limited to mice receiving concurrent administrations of ETU and sodium nitrite. These results indicate that ETU is most probably converted in vivo into N-nitroso ETU and that the N-nitroso ETU has a greater carcinogenic potential in mice than ETU alone.

Animals↗
PubMed1993

Effect of bredinin on early embryonic development in mice.

Bredinin, an immunosuppressive agent, had a teratogenic effect and a decreasing effect in litter size in mice and in rats. We investigated the direct effect of bredinin on the development of mouse preimplantation embryos in vitro. Bredinin strongly inhibited the first differentiation step from the morula to the blastocyst stage, whereas the steps from the two-cell embryo to the morula stage were not inhibited. At 10(-6) or 10(-5) M of bredinin, only one or none of the morula embryos developed to a blastocyst after a 48 h culture; while approximately 90% of the embryos developed to blastocysts in the absence of bredinin. To determine whether the bredinin inhibition was reversible, the morula embryos were cultured with 10(-5) M of bredinin for 48 h. The embryos were transferred to bredinin-free culture conditions, and their development was observed. The inhibitory effect of bredinin was reversible. The expansion of zona-free blastocyst was also inhibited by bredinin. When blastocyst embryos were cultured in the presence of bredinin (10(-6) M), the mean size of the embryos was reduced to half the initial size. In addition, the steps of hatching from the zona pellucida and attaching to the substratum were significantly inhibited by bredinin. Trophoblast outgrowth was completely inhibited by 10(-6) M bredinin; however, the area of trophoblast outgrowth was expanded to 18-fold the initial size after a 96 h culture in the absence of bredinin. Thus, the decrease in the number of offspring is due to the direct effect of bredinin on mice embryos.

Animals↗
PubMed1993

Regulation of cholesterol metabolism in adrenal cortex: effects of apoproteins on cholesterol esterase in rat adrenal glands.

We have investigated the effects of apoproteins on cholesterol esterase (CEase) in rat adrenal glands in order to clarify the mechanism of synthesis of free cholesterol which is the most important substrate for steroidogenesis. We prepared lipid mixtures containing cholesteryl oleate plus apoproteins with and without phosphatidylcholine as a substrate for CEase in order to investigate the effect of the substrate state on CEase. The substrate containing only cholesteryl oleate and apo-HDL increased both acid and alkaline CEase activities. Both acid and alkaline CEase activities were also increased by a substrate containing apo-HDL plus cholesteryl oleate and phosphatidylcholine more than by a substrate containing cholesteryl oleate plus apo-LDL with phosphatidylcholine or cholesteryl oleate with phosphatidylcholine. We have already reported that phosphatidylcholine is an important factor for the regulation of adrenal CEase. Therefore, the present studies show that apoproteins as well as phosphatidylcholine may be important factors for the regulation of adrenal CEase.

Adrenal Cortex↗
PubMed1993

Regulation of cholesterol metabolism in adrenal cortex: comparative studies on cholesterol esterase in human adrenal glands.

We have studied the nature and characteristics of cholesterol esterase (CEase) in human adrenal adenoma and hyperplasia tissues showing Cushing's syndrome, comparing with those in normal tissue. Each tissue demonstrated that two pH optima were found at around 4.5 and 8.0. The results of a subcellular distribution study show that acid and alkaline CEase are mainly located in lysosomes and microsomes, respectively. Our previous data suggested that phosphatidylcholine which was sonicated with cholesteryl oleate as a substrate may play a crucial role in the regulation of CEase in rat adrenal. The effect of phosphatidylcholine was therefore investigated in the present study. Acid CEase in normal tissue was increased in a dose-dependent manner by phosphatidylcholine, but not in the adenoma or hyperplasia tissues. None of those tissues showed any enhancement in alkaline CEase activity when phosphatidylcholine was added to the substrates. It is therefore suggested that the mechanism of regulation of CEase among three different kinds of human adrenals may be different from the data for the effect of phosphatidylcholine. Basal activity of acid CEase in adenoma and hyperplasia was significantly higher than that in normal tissue, and also that of alkaline CEase in hyperplasia tissue was significantly higher than that in normal tissue. Thus it is suggested that such an adrenocortical disorder as Cushing's syndrome due to adenoma and diffuse hyperplasia of the adrenal cortex may possess the nature and characteristics of autonomy of steroidogenesis which seems to be induced by the active metabolism of cholesterol, when compared with normal tissue.

Adenoma↗
PubMed1993

The signal-averaged electrocardiogram of P wave in patients with documented atrial fibrillation or flutter and in patients with left or right atrial overload without atrial fibrillation.

To evaluate the significance of the signal-averaged P wave in various pathological conditions of the atrium, signal-averaged electrocardiograms and echocardiograms were studied in the following 4 groups: (1) 10 normal subjects (control group), (2) 24 patients with paroxysmal atrial fibrillation or flutter (AF) (AF group), (3) 12 patients with left atrial overload without AF (LA group), and (4) 10 patients with right atrial overload without AF (RA group). Original P wave durations showed no significant difference among the 4 groups. Filtered P wave durations (F-PDs) in the AF and LA groups were significantly longer than that in the control group. F-PD correlated significantly with left atrial dimension (LAD). F-PD in AF patients with LAD shorter than 40 mm was significantly longer than that in the control group, but there was no significant difference in F-PD between AF patients with LAD longer than 40 mm and the LA group. Root mean square voltages of original P waves were significantly higher in the LA and RA groups than that in the control group, but in AF patients it did not differ from that in the control group. In conclusion, the signal-averaged P wave is useful to predict atrial fibrillation, but prolongation of F-PD is seen not only in patients with AF but also in patients with LA overload.

Atrial Fibrillation↗
PubMed1993

The central projections of the monkey tooth pulp afferent neurons.

Transganglionic transport of horseradish peroxidase conjugated to wheatgerm agglutinin (HRP:WGA) entrapped in hypoallergenic polyacrylamide gel was used to study the patterns of termination of primary afferents that innervate the upper and lower tooth pulps within the trigeminal sensory nuclear complex (TSNC) of the monkey. HRP:WGA injections were also made into the lower incisors and molars, in order to examine the topographic arrangement of pulpal afferent projections. HRP-labeled pulpal afferents innervating lower and upper teeth projected ipsilaterally to the rostral subnucleus dorsalis (Vpd) and caudal subnucleus ventralis (Vpv) of the nucleus principalis (Vp); the rostrodorsomedial (Vo.r) and dorsomedial (Vo.dm) subdivisions of the nucleus oralis (Vo); the dorsomedial subdivision of the nucleus interpolaris (Vi); and laminae I-II and/or V of the nucleus caudalis (Vc) at its rostralmost level. The HRP-labeled terminals from upper and lower pulpal afferents formed a rostrocaudal column from the midlevel of Vp to the rostral tip of Vc. The label in Vp and Vo was considerably dense, but the column of terminals was interrupted at the Vpd-Vpv transition. The label in Vi and Vc was much less dense compared to that in the rostral nuclei, and the column of terminals was interrupted frequently. The representation of the upper and lower teeth in TSNC was organized in a somatotopic fashion that varied from one subdivision to the next, though their terminal zones overlapped within Vpd. The upper and lower teeth were represented in Vpv, Vo.r, Vo.dm, Vi, and Vc in a ventrodorsal, dorsoventral, lateromedial, lateromedial, and lateromedial sequence, respectively. Topographic arrangement was also noticed for the projections of pulpal afferents from the lower incisors and molars: The representations of the lower incisors and molars in Vpv, Vo.r, Vo.dm, Vi, and Vc were organized in a lateromedial, dorsoventral, ventrodorsal, ventrodorsal, and lateromedial sequence, respectively. The present results indicating sparse projections from pulpal afferents in the monkey's Vc are in good correspondence with a clinical report that trigeminal tractotomy just rostral to the obex has no significant effect on dental pain perception in patients. Furthermore, the present study indicates that projection patterns of pulpal afferents--which include the termination sites, the density of terminations between nuclei, and topographic arrangement--differ among animal species.

Afferent Pathways↗
PubMed1993

L-gulono-gamma-lactone oxidase is not induced in rats by xenobiotics stimulating L-ascorbic acid biosynthesis.

L-Ascorbic acid (AsA) is synthesized from D-glucose in rats; the terminal step of this synthetic pathway is catalyzed by L-gulono-gamma-lactone oxidase (GLO). In this study, we examined the effects of phenobarbital (PB) and 3-methylcholanthrene (MC), both of which are known to stimulate AsA biosynthesis in rats, on the hepatic levels of GLO activity, GLO mRNA, and AsA. Firstly, the existence of GLO mRNA was examined in the liver, kidney, lung, small intestine, spleen, testis, and prostate from a male rat; and GLO mRNA was found to be present only in the liver, in which GLO activity was also detected. The intraperitoneal injection with PB (100 mg/day/kg body weight, once a day for 2 days) or MC (20 mg/day/kg body weight, once) significantly elevated the hepatic level of AsA and the urinary excretion of AsA in rats (5-week-old males). The hepatic levels of cytochrome P-450IIB1 mRNA and cytochrome P-450IIB2 mRNA and those of cytochrome P-450IA1 mRNA and cytochrome P-450IA2 mRNA were also elevated in the rats treated with PB and MC, respectively, indicating a normal response of these animals to these compounds. However, the level of GLO mRNA and the activity of GLO in the liver tended to be slightly decreased by the administration of PB or MC, though the differences were not significant. Thus it is clear that the treatment with PB or MC stimulates the biosynthesis of AsA by increasing the activity of some enzyme(s) participating in the synthesis prior to GLO.

Animals↗
PubMed1993

Ascorbic acid deficiency reduces the level of mRNA for cytochrome P-450 on the induction by polychlorinated biphenyls.

Ascorbic acid (AsA) deficiency causes a decrease in hepatic concentration of cytochrome P-450 and a decrease in hepatic activity of drug-metabolizing enzymes in rats unable to synthesize AsA (ODS rats). To study the mechanism of the decrease in hepatic concentration of cytochrome P-450 isozymes by AsA deficiency, we chose the xenobiotics-inducible cytochrome P-450 and performed the experiments indicated below. AsA-deficient rats were fed polychlorinated biphenyls (PCB) which markedly induce both CYP1A subfamily and several isozymes in CYP2B subfamily. First, we assayed the activities of two drug-metabolizing enzymes so that one could be functionally distinguished from another. AsA deficiency significantly reduced the hepatic activity of aminopyrine-N-demethylase in ODS rats with and without dietary PCB, but had no effect on benzo(a)pyrene hydroxylase activity. Secondly, quantitative immunoblot analyses demonstrated that the levels of CYP2B1/2B2 and CYP1A1 in the AsA-deficiency rats fed PCB were approximately 60 and 80% lower than those found in rats fed AsA-supplemented diet. The degree of reduction in CYP2B1/2B2 was greater than CYP1A1. Thirdly, AsA deficiency caused a decrease in hepatic abundance of CYP2B1/2B2 mRNA, whereas it had no effect on the levels of CYP1A1 and 1A2 mRNA. These results indicated that dietary AsA selectively affects the levels of CYP2B1/2B2 mRNA among cytochrome P-450 induced by PCB and plays important roles for optimum induction of drug-inducible cytochrome P-450. We concluded that AsA deficiency decreases specific froms of drug-inducible cytochrome P-450, especially CYP2B1/2B2 and that the reduction of CYP2B1/2B2 mRNA level in AsA-deficient rats caused a decrease in cytochrome P-450 concentration and hepatic activity of drug-metabolizing enzymes.

Aminopyrine N-Demethylase↗
PubMed1993

Differential sensitivity of rat cardiac sarcolemma and mitochondria to damage induced by lipid peroxidation.

It is well known that the sarcolemma is the organelle most susceptible to lipid peroxidative attack in the isolated membrane preparations. To determine whether this also occurs in the intact heart, we studied the effect of cumene hydroperoxide, an agent capable of initiating lipid peroxidation, on the ultrastructure and lanthanum (La) staining of isolated rat hearts perfused with HEPES buffer (pH 7.4) containing: 140 mM NaCl, 5 mM KCl, 1 mM MgCl2, 3 mM HEPES, 1.5 mM CaCl2 and 11 mM glucose. No ultrastructural alterations or intracellular deposits of La were observed in myocytes of rats perfused with HEPES buffer. Perfusion with cumene hydroperoxide (0.5 mM) for 30 min induced a release of malondialdehyde-like substance in the perfusate and a spectrum of myocardial ultrastructural alterations. La was always observed only outside the sarcolemma in myocytes with moderate damage consisting of clearing of the mitochondrial matrix and slight margination of chromatin in the nuclei. Intracellular La was found in myocytes with severe and irreversible damages consisting of fragmentation of cristae and electron-dense amorphous particles in mitochondria. La was deposited on the outer surface of the mitochondrial membranes, lipid droplets and myofilaments. These data suggest that mitochondria are more susceptible than is the sarcolemma to lipid peroxidation induced by cumene hydroperoxide in the beating rat heart.

Animals↗
PubMed1993

Sequential promotion of normal and leukemic hemopoiesis by recombinant human granulocyte colony-stimulating factor during the course of myelodysplastic syndrome.

A 48-year-old man developed refractory anemia with excess of blasts in transformation. Complete response was achieved by low-dose ara-C therapy, but he relapsed 15 months later, with pancytopenia and 13.0% myeloblasts in normocellular marrow. He was treated unsuccessfully with prednisolone, metenolone, and 1-alpha-hydroxyvitamin D3 for 8 weeks. He then developed life-threatening pneumonia and was treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF Filgrastim; 125 micrograms/day s.c.). The pneumonia resolved and, interestingly, he achieved a partial response, with normal blood cell counts and only a few dysmyelopoietic cells in the marrow. However, thrombocytopenia progressed when rhG-CSF administration was tapered. When the dose was increased again, leukemic blasts were found to proliferate. When rhG-CSF was discontinued, blasts rapidly decreased in the peripheral blood. Chromosomal analysis revealed a complex abnormality during the first relapse, a normal 46,XY karyotype during the partial response, and recurrence of the same complex abnormality during leukemic transformation. The stimulation index of marrow mononuclear cells cultured with rhG-CSF increased with disease progression. These findings suggest that rhG-CSF initially stimulated the selective proliferation of normal hemopoietic cells, but the evolution or selection of a leukemic clone responsive to rhG-CSF appears to have occurred subsequently.

Follow-Up Studies↗
PubMed1993

Activities of some regulatory enzymes of carbohydrate metabolism in the liver of rats fed a histidine-excess diet.

1. Glycogen is accumulated in the liver of rats given a histidine-excess diet. 2. In order to know the regulatory point, the activities of eight hepatic key enzymes in the carbohydrate metabolism were measured after feeding either a basal or a histidine-excess diet for 0, 3 and 7 days. 3. The active glycogen synthase level was about 2.6- and 3.0-fold higher after feeding for 3 and 7 days, respectively, but the total activity of this enzyme was not affected after feeding for 3 days and was increased after feeding for 7 days. 4. The active glycogen phosphorylase, glucose 6-phosphatase and pyruvate kinase activities were significantly decreased, and fructose 1,6-bisphosphatase activity was increased on a histidine-excess diet for 3 days. 5. Thus, of these enzymatic changes, mainly the enhancement of active glycogen synthase might lead to the substantial accumulation of hepatic glycogen. 6. The in vivo incorporation of radioactive glucose into liver glycogen was stimulated in rats given a histidine-excess diet.

Animals↗