PubMed Health⌕ Search

Biomedical subjects

H Yoshino

Publications and source records attributed to H Yoshino.

At least 19 recordsLinked to original sources

Ca channel currents inhibited by serum from select patients with Guillain-Barré syndrome.

We performed an electrophysiological study demonstrating inhibition of spontaneous muscle action potentials within a coculture of rat muscle and spinal cord by exposure to serum, as well as purified IgG, from patients with the acute motor axonal neuropathy (AMAN) variant of Guillain-Barré syndrome (GBS). However, exposure to serum from two patients with the acute inflammatory demyelinating polyneuropathy (AIDP) form of GBS had no effect. Using a whole-cell recording technique, we then investigated the effects of serum and purified IgG from patients with GBS on voltage-dependent calcium channel (VDCC) currents in nerve growth factor-differentiated PC12 cells. Serum from patients with GBS (AMAN) inhibited VDCC currents in PC12 cells, which was fully reversible by washing with the bath solution. Similarly, purified IgG from the serum of two patients with GBS (AMAN) also inhibited VDCC currents in PC12 cells. In contrast, sera from patients with AIDP and healthy volunteers did not affect VDCC currents in PC12 cells. These results suggest that muscle weakness in some patients with GBS might be induced by inhibition of Ca2+ channel currents within motor nerve terminals.

Action Potentials↗

Naked plasmid DNA transfer to the porcine liver using rapid injection with large volume.

The naked plasmid DNA transfer method of rapid injection with large volume has been useful for gene therapy in experimental study. However, only small animals like rodents have usually been reported on. In this study, the authors attempted to transfect naked plasmid DNA to the porcine liver by modified hydrodynamic method. We decided to transfer plasmid DNA to a part of the liver using the angio-catheter to reduce the liver damage. To discern the condition of injection, naked plasmid DNA-encoding green fluorescent protein (GFP) was transferred for use as a marker gene. The GFP gene expression was markedly observed in gene-transferred pig livers. In large animals, not only the naked gene quantity, the solution volume containing the plasmid DNA and the injection speed, but also the additional treatments of the portal vein and the hepatic artery preparation were crucial. We found that the following injection condition were needed: plasmid DNA, 3 mg; the solution volume, 150 ml and the injection speed, 5 ml/s. The portal vein and the hepatic artery were clamped during gene delivery and the blood flow of the portal vein was flushed out using normal saline. Cytotoxic T-lymphocyte antigen 4-immunoglobulin (CTLA4-Ig) gene was used to test for secretory protein. CTLA4-Ig gene was injected with a large volume of solution via the hepatic vein to the left outer lobe of the liver selectively. CTLA4-Ig was detected in the pig blood at a maximum serum level of 161.7 ng/ml 1 day after gene transfer, and the CTLA4-Ig was detected for several weeks. Our new technique of inserting a catheter into only a selected portion of the liver reduced liver toxicity and increased gene transfer efficiency. This is the first report of successful gene transfer, using a hydrodynamic method, to the segmental liver in pigs, and achieved more than enough secretory protein for the clinically therapeutic level in pigs.

Animals↗

Dopamine profoundly suppresses excitatory transmission in neonatal rat hippocampus via phosphatidylinositol-linked D1-like receptor.

Dopamine modulates synaptic transmission in various brain regions. The disorder of dopamine system may be related to neurodevelopmental dysfunction. However, the action of dopamine on synaptic transmission during development is largely unknown. We studied the effect of dopamine on GABAergic and glutamatergic transmission in neonatal rat hippocampus from the early period of synapse formation by whole-cell patch-clamp recordings from CA1 pyramidal cells. Dopamine (100 muM) profoundly decreased the amplitude of GABA(A) receptor-mediated postsynaptic currents (GABA(A)-PSCs) to 32.2+/-5.4% (mean+/-S.E.M., EC(50): 2.9 muM) in the first postnatal week, when GABA provides excitatory drive. Dopamine also decreased the amplitude of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated excitatory postsynaptic currents (EPSCs) to 29.1+/-2.7% (EC(50): 18.7 muM) in the second postnatal week, when glutamate responses first appear. The dopamine-induced inhibition declined after these periods and became only partial after postnatal day 30. Further we identified the receptor subtype involved in the dopamine-induced inhibition as phosphatidylinositol-linked D1-like receptor, since 6-chloro-2,3,4,5-tetrahydro-3-methyl-1-(3-methylphenyl)-1H-3-benzazepine-7,8-diol hydrobromide (SKF 83959), a selective agonist for phosphatidylinositol-linked D1-like receptor, clearly mimicked the action of dopamine, and 1-[6-[((17beta)-3-methoxyestra-1,3,5[10]-trien-17-yl)amino]hexyl]-1H-pyrrole-2,5-dione (U-73122), an inhibitor of phospholipase C, significantly reduced the dopamine-induced inhibition. Dopamine did not change the response to puff-applied GABA or kainic acid, nor the amplitude of miniature GABA(A)-PSCs or miniature EPSCs. These results suggest that the activation of phosphatidylinositol-linked D1-like receptor profoundly suppresses the excitatory transmission during the early period of synapse formation in the developing hippocampus by presynaptic mechanisms. This study firstly demonstrates the effect of phosphatidylinositol-linked D1-like receptor on synaptic transmission.

Aging↗

Progress in familial Parkinson's disease.

To date 11 forms of familial Parkinson's disease (PD) have been mapped to different chromosome loci, of which 6 genes have been identified as the causative genes, i.e., alpha-synuclein (SNCA), parkin, UCH-L1, PINK1, DJ-1, and LRRK2. For UCH-L1, additional families with this mutation are necessary before concluding that UCH-L1 is the definite causative gene for PARK5, as only one family so far has been reported. SNCA, UCH-L1, and LRRK2 mutations cause autosomal dominant PD and the remaining gene mutations autosomal recessive PD. Age of onset tends to be younger in familial PD compared with sporadic PD, particularly so in autosomal recessive PD. Generally familial cases respond to levodopa quite nicely and progression of the disease tends to be slower. It is an interesting question how familial PD-causing proteins are mutually related each other. In this article, we review recent progress in genetics and molecular biology of familial PD.

Age of Onset↗

Temperature chaos and bond chaos in Edwards-Anderson Ising spin glasses: domain-wall free-energy measurements.

Domain-wall free energy sigmaF, entropy sigmaS, and the correlation function C(temp) of sigmaF are measured independently in the four-dimensional +/-J Edwards-Anderson (EA) Ising spin glass. The stiffness exponent theta, the fractal dimension of domain walls d(s), and the chaos exponent zeta are extracted from the finite-size scaling analysis of sigmaF, sigmaS, and C(temp), respectively, well inside the spin-glass phase. The three exponents are confirmed to satisfy the scaling relation zeta = d(s)/2 - theta derived by the droplet theory within our numerical accuracy. We also study bond chaos induced by random variation of bonds, and find that the bond and temperature perturbations yield the universal chaos effects described by a common scaling function and the chaos exponent. These results strongly support the appropriateness of the droplet theory for the description of chaos effect in the EA Ising spin glasses.

Journal Article↗

Clinicogenetic study of PINK1 mutations in autosomal recessive early-onset parkinsonism.

The authors performed PINK1 mutation analysis of 51 families with autosomal recessive Parkinson disease (ARPD). They found two novel PINK1 mutations: one was a homozygous deletion (13516-18118del) and the other a homozygous missense mutation (C388R). Clinically, the patients with the deletion had dementia. Thus, early-onset PD with dementia may be considered PINK1-linked parkinsonism. Furthermore, patients with PINK1 mutations form 8.9% of parkin- and DJ-1-negative ARPD families.

Adolescent↗

Chronic inflammatory demyelinating polyneuropathy in a patient with hyperIgEaemia.

We herein report the case of a 46 year old man with chronic inflammatory demyelinating polyneuropathy (CIDP) with hyperIgEaemia. The patient presented with bilateral weakness, generalized hyporeflexia, and mild paresthesia of the fingers of both hands. Nerve conduction studies revealed multiple sites of motor conduction block in the absence of sensory abnormalities. Muscle strength increased, as did compound muscle action potential (CMAP) amplitude immediately after the intravenous infusion of immunoglobulin (IVIg). Serum IgE levels also fluctuated in parallel with his relapsing-remitting clinical course. We propose that pure motor CIDP may be immune mediated and suggest that IgE-mediated allergy may be one potential cause of this condition.

Action Potentials↗

Thirteen-week feeding study of thaumatin (a natural proteinaceous sweetener), sterilized by electron beam irradiation, in Sprague-Dawley rats.

This study was designed to evaluate and characterize any subchronic toxicity of thaumatin sterilized by electron beam irradiation (5.0 kGy) when administered at dietary levels of 0% (control), 0.3%, 1.0% and 3.0% to groups of 10 male and 10 female Crj: CD (SD) IGS rats for 13 weeks. Separate groups of both sexes received 3.0% non-irradiated thaumatin. There were no treatment-related clinical signs or adverse effects on the survival rate, body weight, food consumption, water consumption and urinalysis, ophthalmology, haematology, or blood biochemistry data. No treatment-related alterations in gross pathology or organ weights were found in any group. On histopathological examination, sporadic spontaneous lesions known to occur in this strain of rats were the only findings, with no specific relation to the test substance. Thus, the no-observed-adverse-effect-level (NOAEL) was judged to be a dietary level of at least 3.0% (2502 mg/kg body weight/day for males, 2889 mg/kg body weight/day for females) for electron beam irradiated thaumatin under the present experimental conditions. It was concluded that electron beam-irradiation of thaumatin does not cause changes of any toxicological significance.

Administration, Oral↗

Evaluation of intraoperative infusion solution using a complete anhepatic model in baby pigs.

Compared to cadaveric liver transplantation, living-related liver transplantation (LRLT) has the physiological advantage of avoiding hemodynamic changes due to the nonsystemic clamping of the inferior vena cava (IVC). However, metabolic changes in the level of blood glucose and lactate usually occur during the anhepatic phase in LRLT. For pediatric patients, intraoperative infusions have the potential to maintain immature homeostasis during LRLT. In the present study, a complete anhepatic model of baby pigs with nonsystemic clamping of IVC, which mimics the procedure of pediatric LRLT, was established using a heparin-coated tube as an internal shunt lactate Ringer solution (LR, Lactec), acetate Ringer solution (AR, VeenF), and a solution comprising acetate Ringer with 1% glucose (AR-G, Phisio140) were tested using piglets. Hemodynamic and metabolic (blood gas analysis, electrolytes, blood lactate, and glucose) changes were observed during the anhepatic phase. Although no major difference was observed in hemodynamic parameters, arterial blood gas data, or concentration of electrolytes among the three solution groups, significant progressive hyperlactatemia was observed in the LR group. Also, though severe hypoglycemia was found in the LR and AR groups, the AR-G group maintained blood glucose levels throughout the anhepatic phase. To conclude, using the simplified pig anhepatic model, we evaluated various solutions for pediatric LRLT.

Animals↗

Effect of continuous infusion of propofol on its concentration in blood with and without the liver in pigs.

In living donor liver transplantation, propofol, an intravenous anesthetic drug, has recently been used in both donors and recipients. Propofol is known to have intra- and extrahepatic metabolic pathways, but the effect of its continuous infusion during a long-term anhepatic state is yet to be determined. Recently, we successfully established a simplified pig model of the complete anhepatic state. In this state, we first evaluated hemodynamic parameters relating to the pharmacokinetics of continuously infused propofol (6 mg.kg(-1) x h(-1)). No significant changes in the concentration of hemoglobin or in hemodynamic parameters other than the heart rate were observed during the anhepatic phase when porpofol was continuously infused at the rate that maintains the state. Blood propofol concentrations in the mixed vein, artery, and portal vein were stable during the anhepatic phase. Finally, we confirmed the pharmacokinetics of continuously infused propofol using orthotropic liver transplantation in miniature pigs. The propofol concentration did not change markedly during the transplant procedure. In conclusion, the pharmacokinetics of continuously infused propofol was almost stable with and without the liver in pigs. Extrahepatic metabolism of propofol might help prevent changes in propofol concentrations.

Anesthetics, Intravenous↗

PARK6-linked autosomal recessive early-onset parkinsonism in Asian populations.

The authors performed linkage analysis in 39 families with autosomal recessive early-onset PD (AR-EOPD) negative for parkin and DJ-1 mutations. Eight families including three Japanese, two Taiwanese, one Turkish, one Israeli, and one Philippine showed evidence of linkage with PARK6 with multipoint log of the odds (lod) score of 9.88 at D1S2732. The results indicate worldwide distribution of PARK6-linked parkinsonism.

Age of Onset↗

Analysis of the effect of leptin on immune function in vivo using diet-induced obese mice.

Leptin can regulate several immune functions. However, the role of leptin on lymphocyte function has not been recognized in vivo. Accordingly, we have investigated the effect of leptin on starvation-induced immune dysfunction using diet-induced obese mice. To induce obesity, C57BL/6J mice were fed a high-fat diet for 14 weeks and control mice were fed a standard diet for the same period. The obese and control groups of mice were then starved for 48 h, and received intraperitoneal injections of recombinant leptin or phosphate-buffered saline four times during starvation. Other control mice in both diet groups were free fed without being starved. Although starvation of the control mice dramatically reduced the weights of the immune organs, cytokine production and increased proliferation of cultured splenocytes, these levels returned to those of the free-feeding groups with exogenous leptin administration. However, these effects of leptin were not observed in obese mice. These findings provide some evidence that leptin can regulate the immune function in vivo. It is also suggested that the action of leptin might not appear in obesity.

Animals↗

Performance analysis on hybrid ventilation system for residential buildings using a test house.

Hybrid ventilation system is a two-mode system that can automatically switch between passive and mechanical modes at different times of the day or season of the year. In this study various ventilation systems, including hybrid system, are used for the investigation. These systems are set up in a full-scale test house constructed in the Tohoku University, Japan. Case studies for evaluating the performance of these systems, by field studies and numerical simulations, are described. The results obtained from this study show that, the hybrid system can supplement the under-ventilation even under a milder weather condition and the airflow rate can be fixed at a certain high level, in comparison with passive system.

Air Movements↗

Symmetrical temperature-chaos effect with positive and negative temperature shifts in a spin glass.

Aging in a Heisenberg-like spin glass Ag(11 at. % Mn) is investigated by measurements of the zero-field-cooled magnetic relaxation at a constant temperature after small temperature shifts absolute value of Delta T/T(g) < 0.012. A crossover from fully accumulative to nonaccumulative aging is observed, and by converting time scales to length scales using the logarithmic growth law of the droplet model, we find quantitative evidence that positive and negative temperature shifts cause an equivalent restart of aging (rejuvenation) in terms of dynamical length scales. This result supports the existence of a unique overlap length between a pair of equilibrium states in the spin-glass system.

Journal Article↗

Domain growth by isothermal aging in 3D Ising and Heisenberg spin glasses.

Nonequilibrium dynamics of three-dimensional model spin glasses, the Ising system Fe0.50Mn0.50TiO3 and the Heisenberg-like system Ag(11 at % Mn), has been investigated by measurements of the isothermal time decay of the low frequency ac susceptibility after a quench from the paramagnetic to the spin-glass phase. It is found that the relaxation data measured at different temperatures can be scaled according to predictions from the droplet scaling model, provided that critical fluctuations are accounted for in the analyses.

Journal Article↗

Anti-GT1a IgG in Guillain-Barré syndrome.

OBJECTIVE: To investigate the presence of serum anti-GT1a IgG in Guillain-Barré syndrome (GBS) and its relation to clinical manifestations. BACKGROUND: Several patients with GBS and bulbar palsy have been reported to have serum anti-GT1a IgG. Most, however, also have anti-GQ1b IgG. A previous study failed to detect GT1a in human cranial nerves, but GQ1b was abundant in human ocular motor nerves. Whether anti-GT1a IgG itself determines the clinical manifestations is not yet clear. METHODS: The association of clinical manifestations with the presence of anti-GT1a IgG and with its cross reactivity was investigated. An immunochemical study was performed to determine whether GT1a is present in human cranial nerves. RESULTS: Anti-GT1a and anti-GQ1b IgG were positive in 10% and 9% respectively of 220 consecutive patients with GBS. Patients with anti-GT1a IgG often had cranial nerve palsy (ophthalmoparesis, 57%; facial palsy, 57%; bulbar palsy, 70%), and 39% needed artificial ventilation. These features were also seen in patients with anti-GQ1b IgG. There was no significant difference between the two groups with respect to the frequency of clinical findings. An enzyme-linked immunosorbent assay showed that anti-GT1a IgG cross reacted with GQ1b in 75% of the patients, GD1a in 30%, GM1 in 20%, and GD1b in 20%. All five patients who carried anti-GT1a IgG that did not cross react with GQ1b had bulbar palsy, neck weakness, absence of sensory disturbance, and positive Campylobacter jejuni serology. Thin-layer chromatography with immunostaining showed that GT1a is present in human oculomotor and lower cranial nerves. CONCLUSIONS: These findings provide further evidence that anti-GT1a IgG itself can determine clinical manifestations. The distinctive clinical features of patients with anti-GT1a IgG without anti-GQ1b activity distinguish a specific subgroup within GBS.

Adult↗

Central motor conduction in patients with anti-ganglioside antibody associated neuropathy syndromes and hyperreflexia.

OBJECTIVES: Several serum antibodies against gangliosides are diagnostically important, particularly in Guillain-Barré syndrome (GBS), Miller Fisher syndrome (MFS), and multifocal motor neuropathy (MMN). Although hyperreflexia is an atypical symptom in these disorders, it has been found in some patients with GBS, MFS, and MMN. The aim of the study was to determine whether hyperreflexia corresponds to corticospinal tract dysfunction in these patients. METHODS: The study examined central and peripheral motor conduction in patients with hyperreflexia who exhibited acute paralysis (group 1, n=5), acute ataxia and ophthalmoplegia (group 2, n=7), or chronic paralysis with conduction block (group 3, n=2). The clinical symptoms are similar to those in patients with GBS, MFS, and MMN, respectively, and serum anti-ganglioside antibodies were found to be positive in all patients. Using magnetic and electrical stimulation techniques, central and peripheral motor conduction were compared in patients in groups 1, 2, and 3 and patients with GBS (n=7), MFS (n=8), and MMN (n=6). RESULTS: Central motor conduction times (CMCTs) in patients in groups 1, 2, and 3 were significantly delayed compared with those in patients with GBS, MFS, and MMN (p<0.01, p<0.05, p<0.05, respectively), and the delayed CMCTs significantly improved in the recovery periods (p<0.01, p<0.01, p<0.05, respectively). However, motor conduction velocity, compound muscle action potential, and F wave conduction velocity were not significantly different between the patients. CONCLUSION: These findings indicate that corticospinal tract is functionally involved in patients with anti-ganglioside antibody associated neuropathy syndromes and hyperreflexia

Adolescent↗