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Biomedical subjects

M Fujiwara

Publications and source records attributed to M Fujiwara.

At least 505 records · Page 28Linked to original sources
PubMed1988

Histopathological characteristics of the kidney in recombinant inbred mice established from MRL/lpr x AKR crossing. Dissociation of severity of lupus nephritis from the degree of lymphadenopathy.

Recombinant inbred (RI) lines were established from (MRL/lpr x AKR) crosses in order to analyze the role of the lpr gene and the participation of background genes in the lymphoproliferation and the development of lupus glomerulonephritis (LGN). In this study, six lines were used to compare with MRL/lpr and AKR mice. Lymphadenopathy was present in four lines (A-22, A-31 b, A-31 e and C-12) but absent in the other two (A-21 and C-21). The degree of lymphoproliferation varied between individuals of the RI lines showing lymphadenopathy. On gross examinations, the most marked lymph node enlargement was seen in the A-31 b line, which resembled MRL/lpr mice in this respect; lymphadenopathy was least prominent in the C-12 line and intermediate degrees occurred in the A-22 and A-31 e lines. Like MRL/lpr mice, deaths in the RI lines were due to LGN; however, in the lines with lymphadenopathy, 50% mortalities occurred a few weeks later than in MRL/lpr mice. The kidneys were examined histologically for proliferative, exudative, extracapillary and membranous changes in the glomeruli. The glomerular lesions in the A-22, A-31 b and A-31 e lines closely resembled those in MRL/lpr mice, but in the C12 line in which lymph node enlargement was least apparent, the histological abnormalities were significantly more severe. Of the lines without lymphadenopathy, histopathological examination showed obvious renal abnormalities in the A-21 line but none in the C-21 line or in AKR mice. From these findings it appears that there are autosomal genes which affect the expression of the lpr gene and thus modify the development of LGN and lymphoproliferation.

Animals↗
PubMed1988

A nonisotopic method for determination of the in vivo activities of tyrosine hydroxylase in the rat adrenal gland.

A rapid and reliable method for determination of in vivo activities of tyrosine hydroxylase in the rat adrenal gland is presented. This method involves determining the rate of accumulation of 3,4-dihydroxyphenylalanine (Dopa) in the adrenal gland after decarboxylase inhibition by NSD 1015, using HPLC with electrochemical detection after purification of the acid-deproteinized tissue extract with Bio-Rex 70 columns followed by alumina batch method. Purification of the sample with alumina adsorption alone, a method usually used for purification of catecholamines and Dopa, was ineffective: epinephrine and norepinephrine, which are present in high concentrations, interfered with an accurate determination of Dopa, and dopamine, which is retained strongly on the reverse-phase column, interfered with a rapid analysis. Purification with Sephadex G-10 columns followed by alumina adsorption was also ineffective. After purification with columns of weak cation-exchange resins such as Bio-Rex 70 or Amberlite CG-50 followed by alumina adsorption, most of the epinephrine and norepinephrine was removed and dopamine was eliminated. Thus a rapid and accurate determination of Dopa could be made. Of the two cation exchangers, Bio-Rex 70 was more effective. Accumulation of Dopa in the adrenal gland was linear up to 30 min after administration of NSD 1015 and a plateau was reached with doses over 10 mg/kg. Using this method, we investigated the effects of immobilization stress, reserpine, and hypoxia on in vivo activities of tyrosine hydroxylase in the adrenal gland.

Adrenal Glands↗
PubMed1988

Schistosoma mansoni: induction of severe glomerulonephritis in female BXSB mice following chronic infection.

C57BL/6 (B6) and female BXSB mice were infected with 10 cercariae of Schistosoma mansoni per head in order to examine whether chronic parasite infection induced glomerulonephritis (GN) with polyclonal B-cell activation. Six months after the infection, mice were sacrificed and various immunological and histopathological examinations were performed. The following results were obtained. (1) Severe GN was induced in parasite-infected female BXSB mice. The renal changes were similar to those of male BXSB mice which spontaneously develop lupus-like GN. No substantial renal changes were observed in infected B6 mice. (2) Massive IgG and C3 deposits were found in capillary loops and also at the mesangial area of infected BXSB mice. No significant IC deposits were found in the kidney of infected B6 mice. (3) A high level of IC was detected in sera of some parasite-infected female BXSB mice, though no significant difference in the level of IC was found between infected and control mice. (4) Numbers of spleen IgG-producing cells were significantly increased in infected B6 mice. Infected female BXSB mice with splenomegaly showed higher numbers of IgGPC than uninfected mice, but there was no difference between the groups. These results suggest that genetic backgrounds played an important role in the development of lupus-like GN following the chronic infection of parasite-causing polyclonal B-cell activation.

Animals↗
PubMed1988

Regional difference in the kinetics of choline acetyltransferase in brains of neurologically normal elderly people and those with Alzheimer-type dementia.

In order to clarify the biochemical changes which occur in the brains of patients suffering from Alzheimer-type dementia (ATD), the kinetics of choline acetyltransferase (ChAT) were measured in 8 or 11 regions of post-mortem brains of 6 patients with non-neurological diseases (control subjects) and 8 patients with ATD. In the control subjects, Michaelis constants (Km) of ChAT for choline were lower in the caudate nucleus and putamen than in other regions examined, whereas Km values for acetyl-CoA in these two regions were higher. Maximal velocities (Vmax) for the control subjects were higher in the caudate nucleus and putamen than in the other regions studied. Km values for choline of ATD patients were higher than those of control subjects in all regions except the amygdala and substantia innominata (innominate); however, Km values for acetyl-CoA of ATD patients were higher than those of control subjects only in the caudate nucleus, putamen and thalamus. Vmax values of ATD patients were lower than those of control subjects in all the regions of brains with ATD. These results suggest that the binding site of ChAT for choline is sensitive to the pathological process of ATD, whereas the binding site for acetyl-CoA is resistant. Based on the presence or absence of variations of Km values, we have classified brain regions into 3 types: highly sensitive, somewhat sensitive or resistant to the pathological process of ATD.

Aged↗
PubMed1988

Endothelium-dependent contraction induced by nicotine in isolated canine basilar artery--possible involvement of a thromboxane A2 (TXA2) like substance.

The present experiments were undertaken to determine whether the response to nicotine in the isolated canine cerebral artery is endothelium-dependent. Changes in the tension of arterial strips were recorded isometrically. Removal of the endothelium was carried out by gentle rubbing, and confirmed by scanning electron microscopy. Rubbing procedure did not affect the contractile response of the strips to serotonin. Treatment of unrubbed strips with nicotine (10(-4)M) caused a transient contraction. This response was abolished by removal of endothelium and attenuated by hexamethonium (5 x 10(-6)M) and atropine (10(-6)M). The nicotine-induced contraction was attenuated also by aspirin (5 x 10(-5)M), a cyclooxygenase inhibitor, OKY-046 (5 x 10(-5)M), a thromboxane A2 (TXA2) synthetase inhibitor and ONO-3708 (5 x 10(-9)M), a TXA2 antagonist. These results indicate that the nicotine-induced contraction in canine cerebral artery is endothelium-dependent, and suggest that the endothelium-derived contracting factor (EDCF) in the nicotine-induced response is a TXA2-like substance.

Animals↗
PubMed1988

The bindings of 3H-prazosin and 3H-yohimbine to alpha adrenoceptors in the guinea-pig stomach.

Alpha adrenoceptor subtypes have been investigated by radioligand binding study in guinea-pig stomach using 3H-prazosin and 3H-yohimbine. The specific 3H-prazosin binding to guinea-pig stomach was saturable and of high affinity (KD = 1.4 nM) with a Bmax of 33 fmol/mg protein. Specific 3H-yohimbine binding to the tissue was also saturable and of high affinity (KD = 25.5 nM) with a Bmax of 150 fmol/mg protein. Adrenergic drugs competed for 3H-prazosin binding in order of prazosin greater than phentolamine greater than methoxamine greater than norepinephrine greater than clonidine greater than epinephrine greater than yohimbine. These drugs competed for 3H-yohimbine binding in order of yohimbine greater than phentolamine greater than clonidine greater than epinephrine greater than norepinephrine greater than prazosin greater than greater than prazosin greater than methoxamine. We also examined whether dopamine receptors exist in guinea-pig stomach, using radioligand binding study. Specific binding of 3H-spiperone, 3H-apomorphine, 3H-dopamine and 3H-domperidone was not detectable in the stomach. Dopaminergic drugs such as dopamine, haloperidol, domperidone and sulpiride competed for 3H-prazosin binding in order of haloperidol greater than domperidone greater than dopamine greater than sulpiride. Metoclopramide, sulpiride and dopamine competed for 3H-yohimbine binding in order of metoclopramide greater than sulpiride greater than dopamine. These results suggest that guinea-pig stomach has alpha 1 and alpha 2 adrenoceptors and has no specific dopamine receptors. It is also suggested that some dopamine receptor antagonists such as domperidone, haloperidol, sulpiride and metoclopramide have antagonistic actions on alpha adrenoceptors.

Animals↗
PubMed1988

Acetylcholine content in superior cervical ganglion following reinnervation of vagal afferent fibers in cat.

The superior cervical ganglion (SCG) was reinnervated by vagal afferent fibers by cross anastomosis between the cranial end of nodose ganglion and the caudal end of SCG in cats. Formation of functional synapses was evidenced by unilateral mydriasis and contraction of the nictitating membrane in response to inflation of the stomach with a balloon or to electrical stimulation of the afferent vagus. The acetylcholine (ACh) content in the cross-anastomosed SCG (reinnervated by vagal afferent fibers) was measured. In anastomosed SCG, the ACh content was about half of normal SCG, but significantly higher than chronically decentralized SCG. Also the ACh content in nodose ganglion (NDG) was investigated in situations in which there was anastomosis, chronic supra, infra, or supra-/infranodose vagotomy. The ACh content of anastomosed NDG was near that of supranosdose vagotomized ganglion. The ACh content of supra-/infranodose vagotomized NDG, which can be considered the NDG itself, was as much as that of normal intact NDG. It was found that the ACh content of infranodose vagotomized NDG was increased, possibly the result of vagal efferent axonal flow or transport. The ACh content of vagal trunk with or without infranodose vagotomy was also measured. The ACh content of vagal trunk with infranodose vagotomy was smaller than that of the normal trunk, but there was still a considerable quantity of ACh. There was no significant change in wet weight of the SCG and NDG before or after the operations. From these results we have concluded that the transmission of the cross-anastomosed SCG (reinnervated with vagal afferent nerve) was cholinergic; and that the vagal afferent nerve have afferent cell bodies not only in NDG but also in peripheral vagal trunks (infranodose portion). These results strongly suggest that vagal afferent fibers are in part cholinergic.

Acetylcholine↗
PubMed1988

Extraneuronal accumulation of isoproterenol in atria and ventricle of perfused rat heart.

Extraneuronal accumulation of isoproterenol in atria and ventricle of perfused rat heart was investigated. Rat hearts were perfused with various concentrations of 3H-isoproterenol for 30 min in the absence and the presence of catechol-O-methyltransferase (COMT) inhibitor (tropolone). When COMT was intact, the accumulation of 3H-isoproterenol in both atria and ventricle after perfusion with low concentration of 3H-isoproterenol (0.01 to 1 mumol/l) was less than that of perfusing concentration; the tissue/medium ratio (T/M) of isoproterenol for artia was lower than that for ventricle. The T/M of isoproterenol after perfusion with 10 and 20 mumol/l of 3H-isoproterenol were 0.94 and 1.76 for atria and 3.25 and 2.95 for ventricle, respectively. When COMT was inhibited by tropolone, the T/M increased 6.3-9.0 folds for atria and 5.1-6.7 folds for ventricle after perfusion with 3H-isoproterenol (0.01 to 1 mumol/l). From these results, it was concluded that both atria and ventricle of the rat heart have an extraneuronal O-methylating system as reported in rat whole heart, and was suggested that there might be different capacities of extraneuronal uptake and COMT between them.

Animals↗
PubMed1988

Hepatic lesions induced by graft-versus-host reaction across MHC class II antigens: an implication for animal model of primary biliary cirrhosis.

To induce graft-versus-host reaction (GVHR), C57B1/6 (B6) spleen cells were injected into (B6 x bm1)F1, (B6 x bm12)F1, and (bm1 x bm12)F1 mice. Since the strains bm1 and bm12 are mutant at the H-2Kb and I-Ab regions of major histocompatibility complex (MHC), respectively, we can assess MHC class I- or class II-different GVHR. As reported earlier, immunological perturbations assessed by the number of immunoglobulin-producing cells and immune complex deposition in renal glomeruli were demonstrated in MHC class II-different GVHR. A conspicuous finding in this report is that epithelioid granuloma formation was observed in the portal area and around the central vein of liver of (B6 x bm12)F1 mice injected with B6 spleen cells. The epithelioid granuloma formation was not observed in (B6 x bm1)F1 nor (bm1 x bm12)F1 recipient mice. Degenerative changes resembling chronic nonsuppurative destructive cholangitis in primary biliary cirrhosis were also observed in the bile duct epithelium in (B6 x bm12)F1 and (bm1 x bm12)F1 mice. These lesions were already obvious at the 2 week postinjection of donor cells and were continuously observed up to 10 weeks when immunological perturbations subsided. Thus, class II-disparate GVHR in this experimental system might provide a novel animal model of protracted disease, primary biliary cirrhosis.

Animals↗
PubMed1988

Amino acid neurotransmitters and their receptors in the brain synaptosomes of acute hepatic failure rats.

Ammonia contents in the brain stem and prosencephalon markedly increased in a rat model of acute hepatic failure induced by partial hepatectomy following CCl4 intoxication. In hepatic failure rats, synaptosomal glutamic acid (excitatory amino acid neurotransmitter) contents decreased significantly in the prosencephalon, and GABA (inhibitory amino acid neurotransmitter) contents decreased significantly in the brain stem. The molar ratio of glutamic acid to glutamine significantly diminished in the brain stem. Glutamic acid decarboxylase activity in the synaptosomes and the binding of [3H]glutamic acid and [3H]GABA to synaptosomal membrane preparations were unchanged in acute hepatic failure rats. These results indicate than an insufficiency of both excitatory and inhibitory neurotransmitter amino acids is induced by high ammonia contents in the synaptosomes of the brain stem during acute hepatic failure.

Acute Disease↗
PubMed1988

Cholesteryl ester accumulation in macrophages incubated with low density lipoprotein pretreated with cigarette smoke extract.

Although cigarette smoking is one of the major risk factors for atherosclerosis and coronary heart disease, the precise mechanisms of its adverse effects have not been fully elucidated. We incubated low density lipoprotein (LDL) with cigarette smoke (CS) extract and examined the incorporation of the lipoprotein by macrophages in vitro. When incubated with macrophages, LDL pretreated with CS extract (100 micrograms/ml) stimulated cholesteryl [14C]oleate synthesis approximately equal to 12.5-fold that with unmodified LDL and transformed macrophages to cells rich in lipid droplets positively stained with oil red O. Enhancement in cholesteryl ester synthesis was dependent on the concentration of CS-modified LDL and exhibited saturation kinetics. When subjected to electrophoreses, CS-modified LDL migrated to a more anionic position than did unmodified LDL and showed extensive fragmentation of apolipoprotein B. This LDL modification depended upon the incubation time and concentration of the CS extract. Superoxide dismutase inhibited modification of LDL by 52%, suggesting that superoxide anion is, at least in part, involved. These results suggest that CS extract alters LDL into a form recognized and incorporated by macrophages. Such modification if it occurs in vivo, could explain the increased incidence of atherosclerosis and coronary heart disease in smokers.

Animals↗
PubMed1988

Sudden infant death syndrome in Japan.

Two autopsied cases are presented, one involving a 5-month-old infant, and a 6-month-old infant both of whom died suddenly and unexpectedly. The incidence of sudden infant death syndrome in Japan is 1.2 per 1,000 babies live births. Among all cases autopsied in the departments of legal or forensic medicine in 78 universities or colleges of Japan, the incidence was 15 (0.5%) per 3,329 in 1984 and 20 (0.6%) per 3,150 in 1985.

Female↗
PubMed1988

Responsiveness of T cells to mutant major histocompatibility complex class I antigen. I. Obligatory dependence of proliferative response on the presence of stimulator type accessory cells.

Proliferative response of splenic T cells of C57BL/6 mice to mutant major histocompatibility complex (MHC) class I antigen (H-2Kbm1) was examined with regard to the role of accessory cells. T cell proliferation in mixed lymphocyte culture (MLC) was not induced when accessory cells were removed from stimulator spleen cells by passage through Sephadex G-10 or nylon-wool column. Anti-Iab antibodies did not inhibit the proliferative response to class I antigen, whereas the same antibodies completely blocked the response to class II antigen (Iabm12). Accessory cells may not be mere presenters of MHC class I antigen because stimulator cells fixed with 0.05% paraformaldehyde lost the stimulating function. The proliferative response was partially recovered by the addition of recombinant interleukin 1 (IL-1) and/or IL-2 to MLC devoid of stimulator type accessory cells. It is concluded that stimulatory type accessory cells were obligatorily involved in the T cell proliferation, and the production of IL-1 by accessory cells is thought to play a critical role in this process.

Animals↗
PubMed1988

Increased binding of [3H]muscimol and [3H]flunitrazepam in the rat brain under hypoxia.

We examined the effects of in vivo hypoxia (10% O2/90% N2) on the gamma-aminobutyric acid (GABA)/benzodiazepine receptors and on glutamic acid decarboxylase (GAD) activity in the rat brain. Male Wistar rats were exposed to a mixture of 10% O2 and 90% N2 in a chamber for various periods (3, 6, 12, and 24 h). The control rats were exposed to room air. The brain regions examined were the cerebral cortex, striatum, hippocampus, and cerebellum. GABA and benzodiazepine receptors were assessed using [3H]muscimol and [3H]flunitrazepam, respectively. Compared with control values, GAD activity was decreased significantly following a 6-h exposure to hypoxia in all four regions studied. On the other hand, the numbers of both [3H]muscimol and [3H]flunitrazepam binding sites were increased significantly. The increase in receptor number tended to return to control values after 24 h. Treatment of the membrane preparations with 0.05% Triton X-100 eliminated the increase in the binding capacity. These results may represent an up-regulation of postsynaptically located GABA/benzodiazepine receptors corresponding to the impaired presynaptic activity under hypoxia.

Animals↗
PubMed1988

Effects of naloxone and opioid agonists on gastric excitatory responses to stimulation of the vagus nerve in cats.

1. An investigation was made into the contribution of endogenous opioids to the initial and delayed excitatory response of the stomach induced by stimulation of the vagal trunk in cats. 2. Naloxone (100 to 1000 micrograms kg-1) had no effect on the initial excitatory response to stimulation of the vagal efferent fibres. However, the same treatment dose-dependently enhanced the delayed excitatory response to stimulation of the vagal afferent fibres. 3. In comparison with the mu-opioid-receptor agonist, [D-Ala2, MePhe4, Gly-ol5]enkephalin and the kappa-opioid-receptor agonist dynorphin A (1-13), lower doses of methionine enkephalin [( Met]enkephalin) markedly inhibited the excitation caused by stimulation of the vagal efferent and afferent fibres. The inhibitory effect of [Met]enkephalin was antagonized by naloxone. 4. The delta-opioid-receptor selective agonist [D-Pen2, D-Pen5]enkephalin mimicked the inhibitory effects of [Met]enkephalin and inhibition by [D-Pen2, D-Pen5]enkephalin was antagonized by the delta-opioid-receptor antagonist, ICI 174,864. 5. It is concluded that the inhibitory effects of exogenous opioids on the excitatory response of the stomach to stimulation of the vagal efferent and afferent fibres are mediated, at least in part, by delta-opioid-receptors. Naturally occurring opioids may participate in the inhibition of the delayed gastric excitation to stimulation of the vagal afferent fibres.

Animals↗