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Biomedical subjects

S Ozawa

Publications and source records attributed to S Ozawa.

At least 19 recordsLinked to original sources

Reverse redistribution on Tl-201 SPECT images after reperfusion therapy for acute myocardial infarction: possible mechanism and prognostic implications.

So-called reverse redistribution on stress Tl-201 imaging has been reported previously, but its significance and clinical implications are not well understood. In patients who received reperfusion therapy for acute myocardial infarction, we frequently observed reverse redistribution on stress Tl-201 images. To investigate the significance of reverse redistribution, 61 patients who underwent reperfusion within 4 h of the onset of chest pain underwent submaximal exercise Tl-201 imaging 3 weeks later. We performed simultaneous coronary arteriography and left ventriculography. We divided these 61 patients into three groups based on the pattern of Tl-201 images. Reverse redistribution was found in 19 patients (Group A), 12 patients had redistribution (Group B), and 30 patients had nonreversible defects (Group C). All patients in Group A had less residual stenosis than those in the other groups, and showed significant improvement of left ventricular function. Furthermore, 12 patients (Group A) demonstrated reverse redistribution or a normal pattern in a follow-up study performed 12 months later. However, in the delayed images the defect was smaller than that shown in the previous study. None of the patients had any symptoms and all returned to their previous occupations. In conclusion, reverse redistribution was common in patients undergoing reperfusion therapy for acute myocardial infarction, especially those with little residual stenosis. Reverse redistribution appears to indicate improved regional wall function in such patients.

Aged

Agonist- and subunit-dependent potentiation of glutamate receptors by a nootropic drug aniracetam.

GluR1 and GluR2 cDNAs encoding non-NMDA subtypes of glutamate receptor were isolated from a rat brain cDNA library by Boulter et al. (Science, 249 (1990) 1033-1037). Functional receptors activated by kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and glutamate were expressed in Xenopus oocytes injected with GluR1, GluR2 or a mixture of GluR1 and GluR2 RNAs. In GluR1-expressed oocytes, 1 mM aniracetam potentiated AMPA-induced currents by 99 +/- 10% (mean +/- S.E.M., n = 5) and glutamate-induced currents by 140 +/- 8% (n = 4), but little affected kainate-induced currents. Aniracetam was effective from a concentration of 0.1 mM, and it exhibited more conspicuous effects with the increase of the dose. In oocytes injected with GluR1 plus GluR2 RNAs, aniracetam more markedly potentiated current responses to AMPA and glutamate than those in oocytes injected with GluR1 RNA alone. For example, 1 mM aniracetam potentiated AMPA-induced currents by 396 +/- 76% (n = 4) and glutamate-induced currents by 970 +/- 65% (n = 5) in oocytes injected with 10% GluR1 and 90% GluR2 RNAs. In these oocytes, however, the potentiation of kainate-induced currents by 1 mM aniracetam was only 8 +/- 5% (n = 4). Thus, we conclude that the potentiation of the AMPA/kainate receptor by aniracetam depends on both species of agonists and subunit composition of the receptor.

Animals

Inhibition of mite protease (Df-protease) with protease inhibitors.

A protease from house dust mite(Dermatophagoides farinae) having high specificity towards a substrate of blood coagulation factor XIIa catalyzes the activation of kallikrein-kinin system in plasma (Takahashi et al., 1990). To prevent the formation of kinin by the mite-protease, inhibition of the protease with its inhibitors was tested in vitro and in vivo. Its kinetic studies revealed that Ki values are 3.9 x 10(-10) M for aprotinin, 3.0 x 10(-9) M for soybean trypsin inhibitor (Kunitz) and 2.5 x 10(-8) M for gabexate mesylate. Enhancement of blood permeability in guinea pigs caused by the protease was markedly suppressed by these inhibitors.

Animals

Effect of repeated oral doses of a novel immunosuppressive macrolide lactone on hepatic mixed-function oxidase system in the rat. Comparative study with ciclosporin.

Effect of pretreatment of rats with FK506((-)-(1R,9S,12S,13R,14S,17R,18E,21S,23S,24R,25S,27R)-17-allyl-1,14- dihydroxy-12-[(E)-2-[(1R,3R,4R)-4-hydroxy-3methoxycyclohexyl]-1- methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4- azatricyclo-[22.3.1.0(4.9)]octacos-18-ene-2,3,10,16-tetrone hydrate, CAS 104987-11-3) on microsomal cytochrome P-450 system and oxidations of the administered drug and other model substrates were studied and compared with those of a pharmacologically related drug, ciclosporin (cyclosporin A). Oral treatment of male Sprague-Dawley rats with FK506 (0.4, 2 or 10 mg/kg/d) for 7 days did not decrease microsomal content of total cytochrome P-450 in livers, but rather increased the content in groups with the dose of 0.4 or 10 mg/kg to the levels of 126-130% of the control. Microsomal NADPH-cytochrome c reductase activities were decreased up to 67% of the control with the increasing dose of FK506 and to 62% in a group treated orally with cyclosporin A (25 mg/kg/d for 7 days), although another microsomal electron-transport component, cytochrome b5, was rather increased in all the treated groups. Treatment with FK506 or cyclosporin A did not reduce but slightly increased microsomal activities of aniline hydroxylation, p-nitroanisole O-demethylation and O-ethoxyresorufin O-deethylation. Microsomal depropylation of 7-propoxycoumarin, a typical P-450IIIA-substrate, was also not reduced in all dose groups of FK506, while it was decreased by the treatment with 25 mg/kg cyclosporin A.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Postnatal vaginal nodules induced by prenatal diethylstilbestrol treatment correlate with later development of ovary-independent vaginal and uterine changes in mice.

Pregnant ICR/JCL mice were given 4 daily subcutaneous injections of 0.2-2000 micrograms diethylstilbestrol (DES) starting on day 15 of gestation. Offspring of mothers given DES were killed at 1-10 days of age and examined for nodules of enlarged polygonal cells under the epithelium of the Müllerian (upper) vagina. Some offspring were ovariectomised at 30 days and killed at 120 days. The nodules which appeared in the prenatally DES-exposed mice (2-2000 micrograms/day) at 3-7 days were not connected with the epithelium of the sinus vagina and reacted positively to an antibody to epidermal growth factor. Nodule formation may prove to be prodromic of later ovary-independent vaginal changes in the DES-exposed mice. Epithelial stratification (2-2000 micrograms/day) and downgrowths and/or pegs (20-2000 micrograms/day) occurred in vaginae of ovariectomized mice exposed prenatally to DES; however, adenosis-like lesions occurred only in the offspring of mothers given the highest prenatal injections of 2000 micrograms DES. Wolffian remnants and hypospadias (2-2000 micrograms/day) were also encountered in the DES-exposed mice. Ovary-independent stratification of the uterine epithelium (20-2000 micrograms/day) and disorganization of the circular musculature (2-2000 micrograms/day) were also observed in the DES-exposed mice. None of these changes was found in ovariectomised 0.2 micrograms DES-exposed and control mice.

Animals

An arylamine acetyltransferase (AT-I) from Syrian golden hamster liver: cloning, complete nucleotide sequence, and expression in mammalian cells.

A cDNA clone (designated hamAT101) encoding an arylamine acetyltransferase, AT-1, was isolated from a hamster liver lambda gt11 cDNA library using a specific polyclonal antibody raised against AT-1. The cloned cDNA insert consisted of 1181 nucleotides, including an open reading frame of 870 nucleotides encoding 290 amino acid (Mr 33,503). The isolated cDNA displayed high sequence similarity to those of chicken, rabbit, and human acetyltransferases. In Northern blots, the hamAT101 cDNA probe hybridized to an RNA band of 18S in the livers of both slow and rapid acetylator phenotypes. To confirm that hamAT101 cDNA encodes the monomorphic but not the polymorphic protein, the isolated cDNA was expressed in monkey kidney cells (COS-1 cells) using the vector p91023(B). A protein with a molecular weight similar to that of AT-1 was detected upon Western blotting in the 9000 x g supernatant from the transfected cells. The activity toward four different substrates of the 9000 x g supernatant was also examined. In agreement with the results of purified AT-1, the cDNA-expressed protein exhibited a high capacity for N-acetylation of 4-aminoazobenzene and 2-aminofluorene, and O-acetylation of 2-hydroxyamino-6-methyldipyrido [1,2-a:3',2'-d] imidazole, whereas no activity was found for the N-acetylation of p-aminobenzoic acid. These results, in addition to the RNA blot hybridization, indicate that hamAT101 encodes the hamster acetyltransferase AT-1.

Amino Acid Sequence

Excitatory synapse in the rat hippocampus in tissue culture and effects of aniracetam.

Excitatory synaptic connections between rat hippocampal neurons were established in tissue culture. The electrophysiological and pharmacological properties of these synapses were studied with the use of the tight-seal whole-cell recording technique. The excitatory postsynaptic current (EPSC) in a dissociated CA1 neuron evoked by stimulation of an explant from the CA3/CA4 region of the hippocampus had two distinct components in Mg(2+)-free medium. The fast component was abolished by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (2 microM), whereas the slow component was abolished by the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonovalerate (D-APV) (50 microM). In solution containing 1 mM Mg2+, the peak amplitude of the fast component was almost linearly related to the membrane potential. In contrast, the conductance change underlying the slow component of the EPSC was voltage-dependent with a region of negative-slope conductance in the range of -80 to -20 mV. A nootropic drug, aniracetam, increased both the amplitude and duration of the fast component of the EPSC in a concentration-dependent manner in the range of 0.1-5 mM, whereas it had no potentiating effect on the slow component. Aniracetam (0.1-5 mM) similarly increased current responses of the postsynaptic neuron to alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA). Current responses to quisqualate and glutamate in the presence of D-APV were also potentiated by aniracetam. However, neither NMDA- nor kainate-induced current was potentiated by 1 mM aniracetam.

2-Amino-5-phosphonovalerate

Purification of hepatic N-hydroxyarylamine sulfotransferases and their regulation by growth hormone and thyroid hormone in rats.

From liver cytosols of male Sprague-Dawley rats, two N-hydroxyarylamine sulfotransferases (HASTs) which sulfate N-hydroxy-2-acetylaminofluorene and a phenolsulfotransferase (PST-I) have been purified about 290-, 690-, and 210-fold, respectively, by the use of DEAE-anion exchange, Blue-Sepharose CL-6B, DEAE-HPLC, and ATP-agarose affinity chromatography. All three enzymes showed almost the same molecular weight of 33 kDa on SDS-polyacrylamide gel electrophoresis. In Western blots using antibody raised against HAST I, the two HASTs, but not PST-I, were detected. The content of total HAST in male rats was estimated as 4-5 micrograms/mg cytosolic protein, about 4 times higher than that in female rats. Direct comparison of the DEAE-HPLC elution profiles of cytosol showed that HAST I and HAST II were male-dominant and male-specific, respectively, in their expression in the livers. Hypophysectomy decreased the level of HAST by 60% in male rats, but had no obvious effect in female rats. Intermittent injection of growth hormone to mimic the male secretory pattern raised the content in hypophysectomized rats of both sexes close to that in intact male rats, while the continuous infusion of growth hormone to mimic the female secretory pattern showed limited effects. In addition, the administration of triiodothyronine stimulated HAST in hypophysectomized rats of both sexes, and the extent of stimulation was nearly the same as observed in the male-type growth hormone treatment. PST-I, in contrast to HAST, showed no clear sex-related difference in hepatic content, and was not apparently affected by growth hormone or triiodothyronine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Two types of kainate response in cultured rat hippocampal neurons.

1. Two different types of kainate response were recorded in cultured rat hippocampal neurons with the use of the whole-cell and outside-out configurations of the patch-clamp technique. 2. There was an outward rectification in the current-voltage (I-V) plot of the kainate-induced current (type I response) in relatively large neurons bearing a morphological resemblance to young pyramidal cells. In smaller neurons with elliptical somata and fine neurites, the kainate response was characterized by a remarkable inward rectification in the I-V plot of the kainate-induced current and a significant permeability to Ca2+ (type II response). 3. Both type I and type II responses were negligible below 2 microM and almost saturated at 500 microM kainate. The concentrations producing half-maximal responses and the Hill coefficients were 68 microM and 1.76 and 56 microM and 1.21 for type I and type II responses, respectively. Both responses were suppressed similarly by the non-N-methyl-D-aspartate (NMDA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). 4. The mean single-channel conductance (gamma) of the type II kainate response was estimated, from the relation between the whole-cell mean currents and current variances, to be 8.7 pS. The power spectrum for the current noise was fitted with the sum of two Lorentzians with cutoff frequencies (fc) of 61.1 +/- 1.4 and 327.8 +/- 10.5 Hz (n = 12).(ABSTRACT TRUNCATED AT 250 WORDS)

6-Cyano-7-nitroquinoxaline-2,3-dione

Thyroxine increases epidermal growth factor levels in the mouse thyroid in vivo.

Immunoreactive epidermal growth factor (EGF) has been detected in the thyroid, which raises questions concerning the source of thyroidal EGF and what affects its levels. We therefore have examined the effects of manipulating thyroid function on the immunoreactive EGF levels in plasma, thyroid, submaxillary gland (SMG), and kidney of adult male BALB/c mice, and we also analyzed the prepro-EGF messenger RNA in these tissues. Groups of six mice received daily injection of T4 (1 microgram, 5 micrograms, or 25 micrograms) or bovine TSH (1 mU) for up to 14 days. The plasma EGF concentration was 0.31 +/- 0.01 ng/ml in control animals, and T4 (5 micrograms) decreased the plasma levels by about one-half within 1 week. The thyroidal EGF was 0.50 +/- 0.14 ng/mg protein in control animals, and T4 (5 micrograms) increased the thyroidal EGF 8-fold within 1 week. There was a negative correlation between plasma and thyroidal EGF concentration (r = -0.93, P less than 0.01). Increasing doses of T4 also increased the SMG EGF content, while plasma levels fell (r = -0.88, P less than 0.01). The TSH treatment did not significantly alter the plasma or tissue EGF levels. Studies on mRNA prepared from these three tissues, using the reverse transcription and the polymerase chain reaction, indicated that the prepro-EGF mRNA was present in thyroid, SMG, and kidney. In conclusion, it appears that at least some thyroidal EGF is synthesized in the thyroid. Our observations that T4 increases the level of intrathyroidal EGF in a dose- and time-dependent fashion, while plasma levels fall, suggest the possibility that intrathyroidal EGF represents a shortloop feedback for the autocrine and/or paracrine regulation of thyroid function.

Animals

Effect of oral administration of a prostacyclin analog (OP-41483) on pulmonary function and bronchial responsiveness in stable asthmatic subjects.

To examine whether prostacyclin has an attenuating effect on nonspecific bronchial responsiveness in asthma, we measured provocative concentration of methacholine producing a 20% fall in forced expiratory volume in 1 second (PC20-FEV1) before and after oral administration of a chemically stable prostacyclin analog (OP-41483) (200 micrograms 4 times a day for 4 days) in 8 patients with stable asthma. Neither baseline pulmonary function nor PC20-FEV1 significantly improved after the treatment. These results suggest that prostacyclin may have no direct effect on bronchial responsiveness in asthmatics. Further studies using more potent and long-lasting prostacyclin mimetic will be needed to confirm the conclusion.

Acetylcholine

Effect of certain growth factors on proliferation in serum-free collagen gel culture of vaginal epithelial cells from prepuberal mice exposed neonatally to diethylstilbestrol.

Neonatal treatment with diethylstilbestrol (DES) induces ovary-independent vaginal epithelial changes in mice. The response of vaginal epithelial cells from intact prepuberal BALB/cCrgl mice treated neonatally with 2 micrograms of DES for 5 days to growth-stimulatory and -inhibitory factors was studied using a serum-free collagen gel culture system that sustains the growth of normal vaginal epithelial cells. Cells from control and DES-exposed mice at 21 days of age showed about a 5-fold increase in number during 10 days in a serum-free medium supplemented with transferrin, bovine serum albumin fraction V, insulin, and epidermal growth factor. Epidermal growth factor and insulin stimulated dose-related proliferation of vaginal epithelial cells from both control and DES-exposed mice; however, cells from DES-exposed mice showed a reduced growth response to epidermal growth factor and an increased growth response to insulin, compared with control cells. Insulin-like growth factor I (1-100 ng/ml) tested in the absence of insulin failed to stimulate cell growth. Transforming growth factor-beta (0.05-5 ng/ml) consistently inhibited cell growth in a dose-dependent manner.

Animals

[Development of pancreatic exocrine function including intestinal negative feedback regulation using oral trypsin inhibitor in rats].

To investigate the development of pancreatic exocrine function and intestinal negative feedback regulation with aging in rats, we measured pancreas weight, content of amylase and trypsinogen in the rat pancreas and plasma CCK concentrations, activity of amylase and trypsin in the small intestine at an hour after oral administration of trypsin inhibitor (TI), and also examined amylase secretory response to CCK-8 in the rat pancreatic acini at various ages in vitro. As a result, amylase content per pancreas weight increased with the age and amylase activity in the small intestine at al ages showed a significant increase in TI group compared to controls. Plasma CCK concentrations were elevated after administration of TI at all ages. Amylase release from pancreatic acini stimulated by CCK-8 responded poorly on days 7, then gradually increased with age, showing a biphasic dose response curve with maximal response of 10(-10) M of CCK-8 from 14-day-old to 66-day-old. The results indicated that the mechanism of pancreatic secretory response to TI already might exist at the stage of sucking rat and secretory response to CCK-8 in vitro showed a low response, and developed with age.

Administration, Oral

[Serum and ascitic phospholipase A2 activities and their heat stabilities in taurocholate induced rat acute pancreatitis].

Serum and ascitic phospholipase A2 (PLA2) activities in rat acute pancreatitis induced by sodium taurocholate (TCA) were investigated with special reference to their heat stabilities and were compared to those in serum of carrageenan induced granuloma in rats. PLA2 activity was measured by previously reported radiochemical method and was separated into two forms, heat stable and labile PLA2, based on the stability to preincubation at 55 degrees C for 5 minutes. While a heat stable PLA2 predominantly increased in ascitic fluid, the elevations of both heat stable and labile PLA2 activities in serum were observed in TCA induced pancreatitis. On the other hand, serum PLA2, which was mainly composed of heat labile form, elevated with the increase of leukocyte count in carrageenan induced granuloma rats. These facts suggested that serum PLA2 activity might increase in acute inflammatory changes other than in pancreatic diseases. And it is assumed that PLA2 derived from extrapancreatic origins as well as pancreatic secretory PLA2 may also contribute to high PLA2 level in acute pancreatitis, because pancreatic secretory PLA2 was generally accepted to be heat stable.

Acute Disease

[Therapeutic effect of ofloxacin on intractable pulmonary tuberculosis and ofloxacin resistance of tubercle bacilli isolated from the patients. Chest DIsease Cooperative Study Unit of National Sanatoriums in Kinki District].

Ofloxacin, a synthetic antibacterial pyridone-carboxylic acid derivative, was used in the treatment of intractable pulmonary tuberculosis. In this study, the therapeutic effect of Ofloxacin on pulmonary tuberculosis and Ofloxacin resistance were analyzed. All patients had been hospitalized in eight national sanatoria in Kinki district, and were excreting tubercle bacilli resistant to various anti-tuberculosis drugs agents. Ofloxacin was given to 118 patients orally at a daily dose of 300 mg to 600 mg for more than 3 months. A few anti-tuberculosis drugs, which had failed in the negative conversion of bacilli previously, were used in combination. By Ofloxacin, 23 patients (19.5%) showed negative conversion of tubercle bacilli in sputum culture within 5 months, and they remained culture-negative for at least 6 months after conversion. Side-effects were observed in 2 patients. One complained of arthralgia and the other felt abdominal fullness. But both were not serious. From these results, it was concluded that Ofloxacin was effective for intractable pulmonary tuberculosis. The resistance of tubercle bacilli to Ofloxacin increased significantly after it was used.

Adult

[Study on the pulmonary tuberculosis in the elderly].

A study was made for 13 cases of patients over 80 years of age who received medical treatment for tuberculosis. Four factors of onset of tuberculosis at old age were indicated. 1. No opportunity for examination of X-ray for old generation. 2. Atypical shadows on the chest X-ray film. 3. Low stress tolerance. 4. Exacerbation of old tuberculosis during the treatment of other diseases. The results suggest the possibility of increasing pulmonary tuberculosis among the elderly persons in the near future.

Aged