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Biomedical subjects

M Fujiwara

Publications and source records attributed to M Fujiwara.

At least 469 records · Page 26Linked to original sources
PubMed1989

Is the augmentation of K+-evoked intrasynaptosomal Ca2+ concentration due to the influx of Ca2+ in rat brain synaptosomes?

Intraterminal free Ca2+ concentration modulates the subsequent release of neurotransmitters. Depolarization of synaptosomes with 29 mM K+ augments cytosolic free Ca2+ concentration, which is triphasic, the peak times being at 10, 60, and 180 s. We examined the characteristics of each elevation of cytosolic free Ca2+ concentration in rat brain synaptosomes which had been preincubated for 3 min with a Ca2+-channel blocker, such as La3+, diltiazem, nifedipine, or verapamil, and under conditions of hypoxia or acidosis. The concentration of free Ca2+ in the quin-2-loaded rat brain synaptosomes was detected fluorometrically. All these elevations were suppressed in the presence of 200 microM EGTA or 100 microM La3+. At the first phase, the elevation of cytosolic free Ca2+ concentration with high K+ stimuli was significantly inhibited by La3+ (20 microM) or by acidosis (pH 6.7). On the other hand, diltiazem, which is a more potent blocker of the release of Ca2+ from the mitochondria, inhibited the increasing cytosolic free Ca2+ concentration at the third phase in a concentration-dependent manner. Hypoxia also showed inhibition at the third phase. These results suggest that the augmentation of high K+-evoked cytosolic free Ca2+ concentration may be due to the influx of extracellular Ca2+. The increase in cytosolic free Ca2+ concentration at the third phase is no doubt linked to the mitochondrial function.

Acidosis↗
PubMed1989

Effects of oxygen depletion on norepinephrine- and carbachol-stimulated phosphoinositide turnover in rat brain slices.

We examined the effects of in vitro anoxia and in vivo hypoxia (8% O2/92% N2) on norepinephrine (NE)- and carbachol-stimulated phosphoinositide (PI) turnover in rat brain slices. The formation of 3H-labeled polyPI in cortical slices was impaired by in vitro anoxia and fully restored by reoxygenation. Accumulation of 3H-labeled myo-inositol phosphates (3H-IPs) stimulated by 10(-5) M NE was significantly reduced by anoxia (control at 60 min, 1,217 +/- 86 cpm/mg of protein; anoxia for 60 min, 651 +/- 82 cpm/mg; mean +/- SEM; n = 5; p less than 0.01), and reoxygenation following anoxia resulted in overshooting of the accumulation (control at 120 min, 1,302 +/- 70 cpm/mg; anoxia for 50 min plus oxygenation for 70 min, 1,790 +/- 126 cpm/mg; n = 5; p less than 0.01). The underlying mechanisms for the two phenomena--the decrease caused by anoxia and the overshooting caused by reoxygenation following anoxia--seemed to be completely different because of the following observations. (a) Although the suppression of NE-stimulated accumulation at low O2 tensions was also observed in Ca2+-free medium, the overshooting in response to reoxygenation was not. (b) Carbachol-stimulated accumulation was significantly reduced by anoxia and was restored by reoxygenation only to control levels. Thus, the postanoxic overshooting in accumulation of 3H-IPs seems to be a specific response to NE. (c) The decrease observed at low O2 tensions was due to a decrease in Emax value, whereas the postanoxic overshooting was due to a decrease in EC50 value.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Effects of gallamine on the contractile response of the stomach in cats.

Stimulation of the vagal trunk in cats anesthetized with pentobarbital sodium produced a contractile response of the stomach during stimulation (initial contraction). Pretreatment with either hexamethonium (0.3 to 30 mg/kg, i.v.) or gallamine (1 to 100 mg/kg, i.v.) dose-dependently produced a delayed contraction, following the initial contraction after stimulation. After the administration of either hexamethonium or gallamine produced a maximum delayed contraction, then an additional dose of gallamine or hexamethonium was administered. The subsequent treatment further augmented the delayed contraction. The results indicate that gallamine induced the delayed contraction by a mechanism different from hexamethonium.

Animals↗
PubMed1989

Effects of nicotine on gastric contractile response to stimulation of the vagal afferent fibers in cats.

Effects of nicotine on the delayed gastric contraction due to vagal afferent stimulation were studied. Cats were pretreated with phentolamine (2 mg/kg, i.v.) and propranolol (1 mg/kg, i.v.). The delayed contraction was inhibited by nicotine (100 to 2000 micrograms/kg, i.v.) in a dose-dependent manner. The inhibition of the delayed contraction by nicotine was blocked by hexamethonium (20 mg/kg, i.v.). The results suggested that nicotine inhibits the delayed contraction by activation of hexamethonium-sensitive inhibitory neurons in the vagal pathway to the stomach.

Animals↗
PubMed1989

Immunomodulatory activity of the newly synthesized compound TOK-8801 (N-(2-phenylethyl)-3,6,6-trimethyl-5,6-dihydroimidazo[2,1-b]thiazole-2- carboxamide).

The in vitro and in vivo effects of the newly synthesized compound TOK-8801 (N-(2-phenylethyl)-3,6,6-trimethyl-5,6-dihydroimidazo[2,1-b] thiazole-2-carboxamide) on immune responses were investigated in comparison with that of levamisole (LMS). TOK-8801 enhanced the anti-sheep red blood cells (SRBC) plaque forming cells (PFC) response and mitogen-induced proliferative responses in murine splenocytes and thymocytes in vitro at concentrations of 10(-7)-10(-5) M, while LMS augmented these responses at 10(-4) M. The stimulatory effect of TOK-8801 as well as LMS on the antibody production was eliminated by the removal of T cells. TOK-8801 (0.5 mg/kg, p.o.) suppressed the in vivo generation of anti-SRBC PFC in normal mice, but the compound restored the depressed antibody production in restraint-stress mice which was mainly caused by helper T cell defects. From these results, TOK-8801 was shown to have an immunomodulatory activity in the antibody production.

Adjuvants, Immunologic↗
PubMed1989

[Treatment of hormonal refractory adenocarcinoma of the prostate with ifosfamide (IFM) and the combination of vincristine ifosfamide and peplomycin (VIP)].

Nineteen patients with hormonal refractory adenocarcinoma of the prostate were treated with ifosfamide (IFM) and the combination of vincristine, ifosfamide and peplomycin (VIP). Nine of them were treated with IFM, and nine with VIP, and one with IFM and also VIP. In the case of the IFM therapy, the over-all response rate was 0% by the Karnofsky's category of response, 20% by the response criteria of Shida et al., 50% by the National Prostatic Cancer Project (NPCP) criteria, and 0% by the response criteria of Koyama and Saito. In the case of the VIP therapy, the over-all response rate was 30% by the Karnofsky's category, 30% by the response criteria of Shida et al., 70% by the NPCP criteria and 20% by the response criteria of Koyama and Saitoh. The one-year survival rates of these patients treated with IFM and VIP were both about 20%. Only one patient treated with VIP therapy showed a partial response. Therefore, a more effective regimen for hormonal refractory adenocarcinoma of the prostate must be developed.

Adenocarcinoma↗
PubMed1989

[Red cell hypoplasia following autoimmune hemolytic anemia associated with T-CLL: report of a case and review of the literature].

A 78-year-old woman, who had axillary lymphadenopathy but no hepatosplenomegaly, was admitted because of lymphocytosis. The leukocyte count was 18.1 x 10(9)/l with 72% abnormal cells. Neither anemia nor thrombocytopenia was present. Many abnormal cells and erythroblasts were seen in the bone marrow. These abnormal cells had irregular nuclei but no granules in the cytoplasm. The surface markers of these cells were positive for E-rosette, CD 2, CD 3, and Leu 7 but negative for CD 4, CD 8, CD 11 (OKM 1), CD 16 (Leu 11), and HLA-DR. The DNA analysis revealed the rearrangement of T-cell receptor beta-chain genes. Direct Coombs test was positive and red-cell life-span (51Cr) was T 1/2 = 19.5 days. The patient was diagnosed as having T-CLL with mild autoimmune hemolysis and was followed without treatment. Seven months later, the leukemia cells of peripheral blood increased to 62.6 X 10(9)/l and the frank autoimmune hemolytic anemia developed. After prednisolone, vincristine and cyclophosphamide were administered, leukemia cells of blood decreased. Anemia with reticulocytopenia, however, persisted and direct Coombs test became negative. In the bone marrow at that time, many neutrophils and megakaryocytes besides leukemia cells were preserved, but erythroblasts were hardly seen, namely a pattern of red cell hypoplasia was observed. The patient deteriorated rapidly and died 26 months after initial recognition of lymphocytosis. When complement was added, the patient's serum obtained during red cell hypoplasia but not during autoimmune hemolysis inhibited BFU-E and CFU-GM in in vitro colony assays. This case indicates that not only B-CLL but also T-CLL is accompanied by immune hematocytopenia.

Aged↗
PubMed1989

[3H]S-145 and [125I]I-S-145-OH: new radioligands for platelet thromboxane A2 receptor with low nonspecific binding and high binding affinity for various receptor preparations.

Two new radioligands for the TXA2 receptor, [3H]S-145 (5Z-7-(3-endo-[( ring-4-3H]phenyl)sulphonylamino- [2.2.1.]bicyclohept-2-exo-yl) heptenoic acid) and [125I]I-S-145-OH (5Z-7-(3-endo[( 125I] 3-iodo-4-hydroxyphenylsulphonyl)amino- [2.2.1.] bicyclohept-2- yl)heptenoic acid) were synthesized and their binding to washed human platelets, platelet membrane and solubilized TXA2 receptor was examined. Both [3H]S-145 and [125I]I-S-145-OH bound to the above preparations in a saturable and reversible manner. In contrast to the conventional TXA2 receptor ligands, such as [3H]U-46619 and [125I]PTA-OH, nonspecific binding of these radioligands constituted less than 10% of the total binding under the standard assay conditions. Scatchard analysis revealed a single class of binding sites for all three preparations; the Kd values of the [3H]S-145 binding were 3.64, 3.14 and 8.22 nM for washed platelets, platelet membrane and the solubilized receptor, respectively, and those of [125I]I-S-145-OH binding were 5.72 and 4.09 nM for washed platelets and the solubilized receptor, respectively. Thus, [3H]S-145 and [125I]I-S-145-OH are the ligands with low nonspecific binding and the highest affinities for the TXA2 receptor, which are independent of membrane preparation and receptor solubilization. In addition, the alpha-carboxyl group of S-145 could be modified without change in the binding affinity.

Azides↗
PubMed1989

[An experimental study on internal structures in the Japanese dentulous mandible].

Measurement of the human substantia compacta and spongy bone. For the sake of a fuller understanding of the structure of the human mandible, a study was made to clarify objectively the thickness of the substantia compacta, the ratio of spongy bone to the total substantia spongiosa, and the width of the spongy bone. Subjects were 11 human mandibles from individuals ranging in age between 35 and 64. All teeth from the central incisor through the second molar remained in place. Measurement was performed with a personal-computer-based image-processing system. Results 1. Width of the substantia compacta Measurement of the width of the substantia compacta showed the thickest part (3.32-3.35 mm) to be roughly at the center of the lingual side of the incisors. The second thickest (2.85-2.90 mm) was located at the buccal-alveolar part of the molars. The thinnest (1.26-1.27 mm) part was located at the labial-alveolar part of the incisors. The next thinnest part (1.74-1.75 mm) was located at the central lingual portion of molars. In the mandible base, thicknesses at all locations fell in the range of 2.76-2.98 mm, with little location-related variation observed. In the labial(buccal)alveolar region, the substantia compacta grows thicker from the mental region toward the molars. In the central lingual region, it grows thinner from the mental region toward the molars. 2. Ratio of spongy bone to total substantia spongiosa Measurements showed the highest ratio (80.9-81.4%) of spongy bone to total substantia spongiosa to be in the lower lingual side of the incisors. This was followed by the central lingual portion of the mental region (80.36%) and the labial side and central regions of the incisors (69.71-78.36%). The ratio was lowest (29.79%) at the first and second premolars. In general, the ratio was high in the incisor region and low near the premolars. No difference was observed between the buccal and lingual sides of the incisor and premolar regions, although in the molar region, the ratio was relatively higher on the buccal than on the lingual side. 3. Width of the spongy bone within the substantia spongiosa.

Adult↗
PubMed1989

Vasorelaxing effects of prostaglandin I2 on the canine basilar and coronary arteries.

The effects of prostaglandin (PG) I2 on canine basilar and coronary arteries were studied. PGI2 caused a relaxation from the basal level more effectively in the endothelium-intact preparations of the coronary artery than in those of the basilar artery. The PGI2-induced relaxation in the basilar artery was enhanced by removal of the endothelium, and by treatment with indomethacin (10(-6) M), aspirin (5 X 10(-5) M), both cyclooxygenase inhibitors, OKY-046 (3 X 10(-5) M) and RS-5186 (10(-6) M), both thromboxane (TX) A2 synthetase inhibitors and ONO-3708 (10(-8) M), a TXA2 antagonist. The enhancing effects of removal of the endothelium and treatment with indomethacin and aspirin on the PGI2-induced relaxation were greater than those of treatment with OKY-046, RS-5186 and ONO-3708. The PGI2-induced relaxation in the coronary artery was not affected by removal of the endothelium, treatment with indomethacin (10(-6) M) or methylene blue (10(-6) M). In the endothelium-removed preparations precontracted with a TXA2 agonist, PGI2-induced relaxation was less in the basilar artery than in the coronary artery. The present experiments suggest that endothelium-derived factors (TXA2 and other cyclooxygenase products) counteract the vasorelaxing effect of PGI2 in the canine basilar artery, but not in the coronary artery.

Animals↗
PubMed1989

[4 cases of paraquat poisoning].

A clinical study was performed on 4 patients with paraquat poisoning treated between 1985 and 1987. The survival rate was 0% in our hospital.

Adult↗
PubMed1989

[An approach of in vivo measurement for ultrasonic myocardial tissue characterization].

The purpose of this study is to characterize regional myocardial alternations of reflected ultrasound throughout a cardiac cycle in normal and ischemic myocardium. Integrated ultrasonic backscatter (2-5 MHz) gated R wave of ECG was measured at the base, middle and apex in 4 dogs, and the apex before and after ischemia in other 4 dogs. Quantitative ultrasonic backscatter (IB) was reflected to a steel reflector. At the apex and middle, where a cyclic pattern of IB was discernible, maximum values were recorded near end diastole and minimum near end systole. The amplitude of the variation of IB throughout a cardiac cycle for each region increase progressively from base to middle to apex. Time-averaged IB over a cardiac cycle (averaged IB) was similar for each area of the heart (base = -50.6 +/- 0.5 dB (mean +/- SE), middle -49.4 +/- 0.5 dB, apex -49.7 +/- 0.6 dB. p = NS for comparison of any two regions). After occluding left anterior descending coronary artery for 30 minutes, the variation of IB was markedly blunted and averaged IB increased significantly (-47.5 +/- 0.5 dB. p less than 0.01 compared with preocclusion (-50.8 +/- 0.5 dB]. These results suggested that IB and averaged IB may permit assessment of intrinsic geometrical changes throughout a cardiac cycle (contractile properties) and histological changes respectively.

Animals↗
PubMed1989

Histologic studies on the hepatic lesions induced by graft-versus-host reaction in MHC class II disparate hosts compared with primary biliary cirrhosis.

By light and electron microscopic examinations, histologic changes in the liver of mice with graft-versus-host reaction (GVHR) were analyzed. To induce GVHR, C57BL/6 (B6) spleen cells were injected into (B6Xbm1)F1, (B6Xbm12)F1, and (bm1Xbm12)F1 mice. In (B6Xbm12)F1 recipient mice, bile duct changes resembling chronic non-suppurative destructive cholangitis (CNSDC) and a formation of epithelioid granulomas were observed during the course of GVHR. An epithelioid granuloma in the liver of (B6Xbm1)F1 or (bm1.Xbm12)F1 recipients was not detected. By electron microscopy, the bile duct epithelia were seen to be in close contact with infiltrating cells, and marked alterations of their cytoplasm and microvilli were demonstrated; ie, vacuolation of the cytoplasm, deterioration of microvilli, and bleb formation were frequently observed in the liver of class II-disparate hosts. Concerning the basement membrane, no marked changes characteristic of primary biliary cirrhosis (PBC), such as many-layered basement membranes containing osmium positive substance, were detected. Because the major histocompatibility complex (MHC) class II-disparate system was used in our experimental system in the GVHR, the antigen expressed on the bile duct might be a target and be associated with the formation of the initial hepatic lesions in PBC such as CNSDC and epithelioid granuloma formation. Thus, GVHR across the MHC class II antigen is believed to play an important role in the development of PBC.

Animals↗