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Biomedical subjects

M Ichikawa

Publications and source records attributed to M Ichikawa.

At least 217 records · Page 12Linked to original sources

Immunoadsorption plasmapheresis for severe generalised myasthenia gravis.

Two patients with severe generalised myasthenia gravis of childhood were successfully treated with immunoadsorption plasmapheresis. One patient was a 5 year old girl and the other was a 12 year old girl. A dramatic improvement in bulbar symptoms and generalised muscle weakness was achieved without any side effects. Plasma exchange may also yield clinical improvement for myasthenia gravis, but the treatment is accompanied by the risk of viral infections and hypersensitivity reactions. Immunoadsorption plasmapheresis is an effective treatment for severe generalised myasthenia gravis of childhood and is superior to plasma exchange with respect to safety.

Child↗

Central and peripheral vasopressin interact differently with sympathetic nervous system and renin-angiotensin system in renal hypertensive rabbits.

This study was designed to elucidate how central and peripheral arginine vasopressin (AVP) interacts with the sympathetic nervous system and the renin-angiotensin system to maintain blood pressure in two-kidney, one-clip hypertensive rabbits. We recorded renal sympathetic nerve activity (RSNA) in the conscious state as an index of sympathetic nervous system function. The changes in mean arterial pressure, heart rate, and RSNA were recorded continuously for 60 minutes after intravenous administrations of captopril (2.5 mg/kg) and nicardipine (3.2 micrograms.kg-1.min-1) in eight identical rabbits. Despite equivalent reductions in mean arterial pressure (10 +/- 1 mm Hg), the increase in RSNA was significantly larger with captopril than that with nicardipine, and the plasma concentration of AVP was elevated (from 100% to 255 +/- 24%) with captopril. Mean arterial pressure was reduced, and RSNA was increased by intravenous infusion of AVP antagonist d(CH2)5Tyr(Me)AVP (n = 8), whereas vertebral artery infusion of the antagonist (n = 6) did not change RSNA. During central and peripheral infusions of AVP antagonist, RSNA was exaggerated by blood pressure reduction with nicardipine as well as with captopril. Increases in RSNA induced by captopril and nicardipine were larger by central infusion of AVP antagonist than by intravenous infusion. The decrease in mean arterial pressure by captopril (30 +/- 4 mm Hg) in eight sinoaortic-denervated hypertensive rabbits was larger than that in hypertensive rabbits with intact baroreflex. These data suggest that compensatory activation of RSNA was revealed by central and peripheral attenuation of AVP and that the sympathetic nervous system became the most important mechanism for blood pressure maintenance in the absence of AVP. The interaction of AVP with the sympathetic nervous system may be independent of the state of the renin-angiotensin system, since the exaggeration of RSNA by AVP antagonist was qualitatively the same with nicardipine as with captopril. In conscious renal-hypertensive rabbits, AVP in the central nervous system played a substantial role when blood pressure was reduced, although it did not contribute to blood pressure maintenance in the basal condition.

Angiotensin II↗

An acute and focal osteopenia model using ovariectomized rats: a rapid detection of the protective effect of salmon calcitonin.

A screening method for anti-osteoporotics using ovariectomized rats was designed using a compact method to monitor the bone density. It was found that ovariectomy (OVX) of Wistar female rats (11 weeks old) induced acute and focal osteopenia within 2 weeks, which responded well to intermittent salmon calcitonin (SCT: 5 and 20 U/kg, s.c., every other day) employed as the standard anti-osteoporotic and injected up to 4 weeks with or without a delay of 2 weeks after OVX.

Analgesics↗

Importance of the nucleotide loop moiety coordinated to the cobalt atom of adenosylcobalamin for coenzymic function in the diol dehydrase reaction.

Three analogs of adenosylcobalamin were synthesized and their coenzymic properties in the diol dehydrase reaction were studied. Neither adenosylcobinamide nor adenosylcobinamide phosphate was active as coenzyme and showed very low affinity for apoenzyme, irrespective of the presence of nucleotide loop fragments, such as 5,6-dimethylbenzimidazole, alpha-D-ribazole, or alpha-D-ribazole-3'-phosphate. The coordination of pyridine to the cobalt atom neither confers the coenzymic function upon adenosylcobinamide nor strengthens the inhibitory effect of cyanoaquacobinamide and methylcobinamide significantly. The analog of adenosylcobalamin in which the N-3 position of 5,6-dimethylbenz-imidazole is methylated was also not active as coenzyme and showed very low affinity for apoenzyme. Since 3,5,6-trimethylbenzimidazole in this analog is no longer coordinated to the cobalt atom, these results show that at least a part of the nucleotide loop moiety coordinated to the cobalt atom of adenosylcobalamin is essential for tight binding to the apoenzyme and therefore for manifestation of coenzymic function.

Binding Sites↗

[Detection of HIV-1 proviral DNA and RNA in serum from HIV-1 sero-positive hemophiliacs by polymerase chain reaction].

We amplified HIV-1 proviral DNA and RNA in serum by DNA-PCR and RT-RCR in 20 HIV-1 seropositive hemophiliacs asymptomatic carrier (AC): 10, AIDS-related complex (ARC):8, AIDS:2). HIV-1 DNA sequences were identified in 44 (93.6%) of 47 specimens. 23 (92.0%) of 25 samples in AC, 13 (100%) of 13 in ARC, 8 (88.8%) of 9 in AIDS had detectable bands. RNA sequences were identified in 36 (85.7%) of 42 specimens. 17 (70.8%) of 24 specimens in AC, 13 (100%) of 13 in ARC, 5 (100%) of 5 in AIDS cases had detectable bands. RNA in serum was strongly positive in two asymptomatic patients with progression to AIDS who showed no changes of other markers. Patients with almost normal CD4 cell counts had trace amounts of proviral DNA and RNA in serum. RNA in serum is the parameter most predictive of progression to AIDS and is detectable earlier than other parameters. From the results of RT-PCR before and after seroconversion, the serum of one patient was shown to be positive at 5 months before seroconversion.

Acquired Immunodeficiency Syndrome↗

[A case of systemic primary amyloidosis with BHL and M-protein in pleural effusion].

A 76-year-old man was admitted to our hospital because of productive cough and dyspnea. Chest X-ray revealed cardiomegaly, bilateral pleural effusion, mediastinal lymphadenopathy, and marked bilateral hilar lymphadenopathy (BHL). His symptoms improved after therapy including diuretic for heart failure, but BHL was unchanged. M-protein in both serum and pleural effusion, and B-J protein in urine were detected. Protein immunoelectrophoresis demonstrated a heterogeneous increase in IgA with lambda light chain predominance. Bronchoscopy disclosed some prominent mucosal lesions of the bilateral bronchi, of which biopsies demonstrated amyloid deposition. Gastric mucosal biopsy also demonstrated amyloid deposition. Therefore this case was diagnosed as systemic primary amyloidosis due to AL-protein. In systemic amyloidosis, there are only a few reports of lymph node enlargement due to amyloid deposition, and it is particularly rare with BHL. From the presence of M-protein in pleural effusion, it is suggested that not only congestive heart failure due to cardiac amyloidosis but also amyloid deposition in the pleura would be related to the fluid production.

Aged↗

The differential staining patterns of two lectins in the accessory olfactory bulb of the rat.

We examined the binding sites of Bandeiraea simplicifolia lectin I (BSL-I) and Vicia villosa agglutinin (VVA) which bind to the vomeronasal nerve of the rat. BSL-I stained the whole vomeronasal nerve and glomerular layers. VVA strongly stained the posterior 2/3, but weakly stained the anterior 1/3 of the glomerular layer. These results indicate that the glomeruli of the rat AOB have two subdivisions revealed by lectin histochemistry using BSL-I and VVA.

Animals↗

Existence of two pathways for the endocytosis of epidermal growth factor by rat liver: phenylarsine oxide-sensitive and -insensitive pathways.

The effect of phenylarsine oxide (PAO) on the internalization rate of epidermal growth factor (EGF) was investigated using perfused rat liver and isolated rat hepatocytes. In perfused liver, a tracer concentration of 125I-EGF alone or with excess unlabeled EGF (20 nM) was perfused and the internalization rate constants (kint) were measured. In the absence of PAO, kint values did not differ significantly for either dose condition. However, with the addition of PAO to the perfusate, the kint value dropped to 4% of that of the control at the low concentration of EGF, while dropping to only 40% of that of the control at the high concentration of EGF. These results suggest the existence of a PAO-insensitive internalization pathway having a kint value comparable with that of the other pathway. Similar EGF concentration-dependent inhibition of 125I-EGF internalization caused by PAO was ascertained using isolated rat hepatocytes. PAO also decreased the cellular ATP content in isolated hepatocytes. However, when we lowered the cellular ATP content with rotenone, the cell-surface binding and internalization of EGF were comparable with the control levels. We concluded that there exist dual pathways for the internalization of EGF and that excess doses of EGF lead to EGF internalization not only through a PAO-sensitive pathway but also through a PAO-insensitive pathway, whereas at a tracer dose of EGF, the internalization occurs mainly via the PAO-sensitive pathway.

Adenosine Triphosphate↗

Ultrastructural characterization of gonadotropin-releasing hormone (GnRH)-immunoreactive terminal nerve cells in the dwarf gourami.

Recently we have been studying gonadotropin-releasing hormone (GnRH) cells of the terminal nerve (TN) in the dwarf gourami, which may serve as a good model system for the study of neuromodulator functions. Here we report on the ultrastructural characterization of TN-GnRH cells using postembedding immunoelectron microscopy. The GnRH immunoreactivities could be demonstrated on dense-cored vesicles (DCVs) in cell bodies, fibers and varicosities. However, we could find no evidence of GnRH-immunoreactive synapses which are characterized by active zones. This may suggest that GnRH is released non-synaptically from DCV-containing fiber varicosities and that it exerts its modulatory action on GnRH receptors located on nearby as well as distant target neurons.

Animals↗

A novel pathway for phosphorylated oligosaccharide biosynthesis. Identification of an oligosaccharide-specific phosphate methyltransferase in dictyostelium discoideum.

The N-linked oligosaccharides on three lysosomal enzymes in Dictyostelium discoideum were found to contain mannose 6-phosphomethyl residues. We have identified and partially characterized a novel S-adenosylmethionine-dependent methyltransferase that is probably responsible for the synthesis of this unusual diester from Man-6-P. The enzyme selectively methylates the phosphate group of Man-6-P (Km 4.3 mM). Glucose-6-P and fructose-1-P are relatively poor acceptors; however, the enzyme is inactive against a broad array of other phosphorylated compounds. Using model di-, tri-, and pentasaccharide acceptors that include portions of the three different branches of high mannose-type oligosaccharides, we found that the enzyme prefers terminal alpha 1----2-linked Man-6-P residues (Km 0.15-1.25 mM) found on the known phosphorylated branches. The enzyme is membrane bound, has a neutral pH optimum and cofractionates on sucrose gradients with GlcNAc-1-P transferase, which resembles its mammalian counterpart, and is, presumably, the first enzyme in the phosphorylation pathway. Based on the substrate specificity and colocalization with GlcNAc-1-P transferase, the phosphate methyltransferase is likely to be responsible for the generation of mannose-6-phosphomethyldiester on Dictyostelium oligosaccharides.

Animals↗

Block of synapse formation between cerebral cortical neurons by a protein kinase inhibitor.

Synchronized Ca2+ transients in cultured hippocampal neurons reflect the pattern of underlying electrical activity. Here we demonstrate a similar synchronization of cerebral cortical neurons in culture, and show that this functional coupling is correlated to the appearance of morphologically identified synapses using electron microscopy. During screening of a series of drugs for inhibition of in vitro synaptogenesis, the continuous presence of a protein kinase inhibitor (K-252b) in the culture medium was found to block the synchronous firing and to decrease significantly the number of morphologically identifiable synapses. Since K-252b does not permeate the cell membrane, the results strongly suggest that phosphorylation of cell surface protein(s) by a K-252b sensitive-protein kinase is an essential process in synapse formation.

Animals↗

Steroid saponins from Polygonatum kingianum.

Four new steroid saponins, kingianosides A-D, were isolated from the rhizome of Polygonatum kingianum, together with two known steroid saponins. On the basis of chemical and spectral evidence, the structures of kingianosides A-D were established as gentrogenin 3-O-beta-D-glucopyranosyl (1-->4)-beta-D-galactopyranoside, gentrogenin 3-O-beta-D-glucopyranosyl(1-->4)-beta-D-fucopyranoside, 26-O-beta-D-glucopyranosyl-22-hydroxy-25(R)-furost-5-en-12-on-3 beta, 22-diol 3-O-beta-D-glucopyranosyl(1-->4)-beta-D-galactopyranoside and 26-O-beta-D-glucopyranosyl-22-hydroxy-25(R)-furost-5-en-12-on-3 beta,22-diol 3-O-beta-D-glucopyranosyl(1-->4)-beta-D-fucopyranoside, respectively.

Carbohydrate Sequence↗

Bandeiraea simplicifolia lectin I and Vicia villosa agglutinin bind specifically to the vomeronasal axons in the accessory olfactory bulb of the rat.

The binding of 21 lectins to the accessory olfactory bulb (AOB) of the rat was examined by histochemistry. Two lectins [Bandeiraea simplicifolia lectin I (BSL-I) and Vicia villosa agglutinin (VVA)] bound specifically to the vomeronasal (VN) axons in the AOB. Seven lectins (Datura stramonium lectin, Erythrina cristagalli lectin, Lycoperisicon esculentum lectin, Ricinus communis agglutinin I, soybean agglutinin, Solanum tuberosum lectin, and Ulex europaeus agglutinin) bound to both VN axons in AOB and olfactory axons in the main olfactory bulb. BSL-I and VVA are useful as the marker of VN axons. This selective binding of lectins indicates the presence of specific glycoconjugates on the surface of VN axons.

Animals↗

'Albumin-mediated transport phenomenon' observed for ligands with high membrane permeability. Effect of the unstirred water layer in the Disse's space of rat liver.

In this paper, we offer experimental evidence of the rate-limiting diffusion of ligands through the unstirred water layer (UWL) as an explanation for the so-called albumin-mediated transport phenomenon. The relative membrane permeability of various ligands was first evaluated using isolated rat hepatocytes. Then, the effect of albumin on the uptake of ligands of a wide range of membrane permeabilities was examined using the perfused rat liver. The results were similar to those expected from the UWL model: ligands with high membrane permeability (warfarin, diazepam and taurocholate) clearly exhibited albumin-mediated transport, those with medium membrane permeability (tolbutamide and salicylate) showed less albumin-mediated transport, and ligand with low membrane permeability (cefodizime) did not show albumin-mediated transport. These results were explained by simulation studies of two separate cases based on the UWL model; one assuming the rapid equilibrium of ligand binding with albumin, and the other considering the slow dissociation of ligands from albumin. In light of these findings, we suggest that the rate-limiting diffusion through the UWL plays an important role in the so-called albumin-mediated transport phenomenon.

Animals↗

Hepatitis E virus: cDNA cloning and expression.

Viral hepatitis E is endemic, frequently provoking epidemic outbreaks in many developing countries. We have attempted to clone the viral genome and to develop an antibody assay system. A lambda gt11 cDNA library was constructed from the bile juice containing putative causative viruses and was immunoscreened by the antisera obtained from patients and monkeys infected with hepatitis E. Three virus-specific clones were isolated and were revealed to overlap one another in sequence, with 1,459 nucleotides in total length. These clones direct the synthesis of polypeptides probably having common immunological epitope(s). Immunoplaque assay revealed the occurrence of antibodies against this epitope in the sera from experimental monkeys with the convalescent phase and from patients of Myanmar, Nepal and India. The data indicate that the cDNA fragments are useful for immunodiagnosis of hepatitis E.

Amino Acid Sequence↗

An improved cryofixation method: cryoquenching of small tissue blocks during microwave irradiation.

The metal contact method of rapid freezing is greatly improved by irradiating the specimen with microwaves at 2.45 GHz for a short period of time (50 ms), while pushing the specimen onto the surface of the copper block cooled by liquid N2. The microwave irradiation, together with two technical improvements (a light-mass plunger and a recently developed beta-gel shock absorber) for preventing bounce, produces a good freezing zone for squid retina, with high reproducibility for each experimental trial, extending from the contact surface to a depth of about 15 microns, which is comparable to the depth obtained by the metal contact method using liquid He in the absence of microwave irradiation. A good freezing zone was also experimentally demonstrated in specimens of rat liver and heart muscle. Microwave irradiation does not have appreciable effects on the ultrastructure of squid retina. The mechanism underlying the improvement in the rapid freezing under the microwave irradiation is discussed.

Animals↗