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M Kinoshita

Publications and source records attributed to M Kinoshita.

At least 19 recordsLinked to original sources
PubMed2006

Optical mapping of spatiotemporal emergence of functional synaptic connections in the embryonic chick olfactory pathway.

In order to understand the functional maturation of the CNS, it is essential to first describe the functional maturation of sensory processing. We have approached this topic by following the ontogenetic patterning of neural circuit formation related to cranial and spinal sensory input using voltage-sensitive dye imaging. In previous studies, we have described the functional maturation of synapses in brainstem/midbrain neural circuits. Here, we elucidate the functional maturation of forebrain circuits by investigating neural networks related to the olfactory nerve (N. I) of chicken embryo. In the isolated N. I-olfactory bulb-forebrain preparation, application of electrical stimulation to N. I elicited excitatory postsynaptic potential (EPSP)-related slow optical signals in the olfactory bulb. The slow signal was mainly mediated by glutamate, and was easily fatigued with repetitive stimuli because of the immaturity of synapses in the embryonic CNS. Ontogenetically, the slow signal was detected from the 6-day embryonic stage, suggesting that functional synaptic connections between N. I and olfactory bulb emerge around this stage. In addition, from the 8-day embryonic stage, another response area was discriminated within the forebrain, which corresponded to the higher-ordered nucleus of the olfactory pathway. In comparison with our previous studies concerning the functional development of other cranial nerve-related sensory nuclei in the embryonic brainstem and midbrain, these results suggest that the olfactory pathway is functionally generated in the early stages of development when neural networks related to other visceral and somatic sensory inputs are also in the process of developing.

Aging↗
PubMed2006

Beneficial effect of interferon-beta treatment in patients with multiple sclerosis is associated with transient increase in serum IL-6 level in response to interferon-beta injection.

In order to predict the clinical benefit of interferon-beta (IFN-beta) to patients with multiple sclerosis (MS), the following markers were investigated; (1) chronological change of cytokines (IFN-gamma, TNF-alpha, IL-6, IL-10, and TGF-beta) after administration of IFN-beta, (2) untoward effects of IFN-beta such as headache and arthralgia, (3) backgrounds of the patients such as age and relapse rate, (4) efficacy of IFN-beta therapy assessed by the change of relapse rate and progression of disability. Chronological blood sampling was performed 0, 10, and 24 h after injection of IFN-beta. The increase of serum IL-6 level in response to IFN-beta administration was associated with headache, arthralgia, relapse rate before treatment, and disability score at the initiation of the therapy. Significant association of change of serum TNF-alpha with age and headache was also observed. The important finding in this study was that patients with a transient increase in IL-6 in response to IFN-beta showed a slow disease progression. This result suggests that this transient increase in the serum IL-6 predicts favorable response to IFN-beta treatment.

Adult↗
PubMed2006

Multiple interleukin-18 injections promote both mouse Th1 and Th2 responses after sublethal Escherichia coli infection.

Interleukin (IL)-18 is considered to induce exclusively the Th1 immune response but not the Th2 response in the presence of adequate IL-12 stimulation in bacterial infections. However, we demonstrate herein that multiple IL-18 injections to the mice not only enhance the early Th1 response but also stimulate the Th2 response later after viable Escherichia coli infection. Multiple IL-18 injections (three alternate-day injections) raised the serum interferon (IFN)-gamma level at 6 h and serum Th2 cytokine levels, such as IL-4, IL-10 and IL-13, at 48 h after infection, while a single IL-18 injection increased only the serum IFN-gamma level. Depletion of mouse CD4+ cells suppressed the IL-18-induced Th2 cytokines, IL-4, IL-10 and IL-13. In contrast, depletion of natural killer (NK)1.1+ cells reduced the IFN-gamma and IL-13 levels. Moreover, multiple IL-18 injections up-regulated the serum IgM level at 72 h after infection while a single IL-18 injection did not. Interestingly, neutralization of IL-4 but not IFN-gamma partially suppressed the increased serum IgM. Liver mononuclear cells (MNCs) from the mice treated with multiple IL-18 injections significantly increased more production of not only IFN-gamma but also Th2 cytokines and IgM by in vitro lipopolysaccharide (LPS) stimulation than those from the phosphate-buffered saline (PBS)-treated mice, while liver MNCs from the single IL-18-injected mice also increased IFN-gamma production but significantly suppressed IL-4 and IgM production compared to those from the PBS-treated mice. Our findings suggest that multiple injections of IL-18 up-regulate both the cellular and humoral innate immunities, thereby enhancing host defence against bacterial infections.

Animals↗
PubMed2006

2'-,5'-Oligoadenylate synthetase response ratio predicting virological response to PEG-interferon-alpha2b plus ribavirin therapy in patients with chronic hepatitis C.

OBJECTIVE: Although all the mechanisms of elimination of hepatitis C virus (HCV) by Interferon (IFN) have not been fully elucidated, the 2'-5'-oligoadenylate (2-5A) system is one of the mechanisms of the antiviral effect of IFN. Consequently, the measurement of 2'-5'-oligoadenylate synthetase (2-5AS) activity could be useful for the evaluation of IFN treatment. This retrospective study was aimed at assessing whether 2-5AS activity functions as a clinical marker of virological response to PEG-interferon-alpha2b (PEG-IFN) plus ribavirin therapy of chronic hepatitis C. METHODS: The 32 patients included in this study had high viral loads of serum HCV-RNA of genotype 1b with chronic hepatitis C. All the patients received a regimen of PEG-IFN plus ribavirin for 48 weeks, and were then divided into two groups: one group (effective group) with undetectable serum HCV-RNA levels at 24 weeks (n = 22) of therapy, the other group (ineffective group) with persistent presence of HCV-RNA in serum at 24 weeks (n = 10). The 2-5AS activity in serum was measured 2, 8 and 12 weeks before initial administration. RESULTS: The 2-5AS response ratio (measured value/measured value of baseline 2-5AS) at 2, 8 and 12 weeks after the administration in the effective group was significantly higher than that in the ineffective group. CONCLUSIONS: These results suggest that the ratio of 2-5AS is closely related to the antiviral effect, and that the measurement of 2-5AS response ratio may be a useful clinical parameter of virological response to PEG-IFN plus ribavirin therapy of chronic hepatitis C.

2',5'-Oligoadenylate Synthetase↗
PubMed2005

Thermolabile phenotype of carnitine palmitoyltransferase II variations as a predisposing factor for influenza-associated encephalopathy.

To assess the etiology of influenza-associated encephalopathy (IAE), a surveillance effort was conducted during 2000-2003 in South-West Japan. All fatal and handicapped patients except one (4/34 patients) exhibited a disorder of mitochondrial beta-oxidation evoked by the inactivated carnitine palmitoyltransferase II (CPT II) with transiently elevated serum acylcarnitine ratios (C(16:0) + C(18:1))/C(2) > 0.09 during high-grade fever. Analyses of genotypes and allele compositions of CPT II revealed a thermolabile phenotype of compound heterozygotes for [1055T > G/F352C] and [1102G > A/V368I], which shows a higher frequency in IAE patients than healthy volunteers (P < 0.025). The thermolabile phenotype of CPT II variations may be a principal genetic background of IAE in Japanese.

Adolescent↗
PubMed2005

Radiofrequency thermal ablation for recurrent meningioma extending extracranially.

BACKGROUND: Image-guided and temperature-controlled radiofrequency thermal ablation techniques were applied to reduce tumor volume and relieve the symptoms caused by extracranial extension of recurrent meningioma. METHOD: We treated two patients with recurrent meningioma, an 81-year-old woman presenting with bulging of the temple and a 68-year-old woman presenting with visual disturbance, facial disfigurement, and sensory disturbance. Neuroimaging in both patients, revealed a large tumor extending extracranially and involving the infratemporal fossa. To avoid injury to important anatomical structures either compressed or entrapped by the tumor, the spatial relation between the planned ablation volume and these structures was confirmed by 3-D reconstruction of the ablation target. During the ablation procedure, local temperatures over the tissue being cauterized were continuously monitored to limit the ablation area to that within the planned volume adjusting RF power. FINDING: Radiofrequency ablation produced tumor necrosis as planned without adverse effects and resulted in swift relief of symptoms and signs with shrinkage of the tumor. CONCLUSION: This technique may be an effective alternative for recurrent meningiomas extending extracranially and for which radical surgical procedures are not indicated.

Aged↗
PubMed2005

A defective Th1 response of the spleen in the initial phase may explain why splenectomy helps prevent a Listeria infection.

Listeria monocytogenes (Listeria) are known to grow and proliferate in the liver while a splenectomy induces host resistance against a Listeria infection despite the fact that a splenectomy inhibits the Th1 response. Therefore, the mechanism by which a splenectomy helps to prevent the growth of Listeria still remains to be elucidated. After an i.v. challenge of Listeria (1 x 10(6) CFU) in C57BL/6 mice, Listeria rapidly increased in the spleen but not in the liver until 48 h. However, after this initial phase, Listeria remarkably grew in the liver. In contrast, when the mice received a splenectomy beforehand, no remarkable growth of Listeria in the liver was observed after Listeria challenge despite the fact that serum IFN-gamma and IL-12 levels at 24 h after Listeria challenge were significantly lower than those in the sham mice. However, the liver leucocytes from mice by 6 h after infection produced a substantial amount of IFN-gamma while spleen MNC did not, whereas spleen leucocytes at 24 h after Listeria challenge did. Consistently, the IFN-gamma and IL-12 levels in the tissue homogenates of the spleen were significantly lower than in those of the liver until 6 h after infection. This defective spleen Th1 response in the early phase of Listeria infection was corrected by an IL-18 i.p. injection just after the Listeria challenge. Our findings suggest that Listeria exploit the defective Th1 environment of the spleen in the initial phase and afterwards overcome the host defense mechanism of the liver.

Animals↗
PubMed2004

Functional anatomy of the lateral collateral ligament complex of the elbow: morphology and strain.

The anatomy of the lateral ulnar collateral ligament (LUCL) of the elbow was investigated in 26 fresh frozen cadavers. Two types of insertion of the LUCL were originally described but we found another type which is characterized by a broad single expansion along with a thin membranous fibre. Strain on the LUCL was measured in situ during extension and flexion with the forearm in supination, pronation and neutral. Strain in the proximal fibres started to occur at around 32 degrees flexion and peaked at between 50 degrees and 60 degrees flexion. Strains measured in the distal fibres were smaller in magnitude. Forearm rotation had little effect on strain during extension to flexion. Based on these results, we conclude that the LUCL functions in unison with the annular ligament.

Adult↗
PubMed2004

Examination of a smallest CELSS (microcosm) through an individual-based model simulation.

Research of the effect of space environment on an ecosystem consisting of plants and animals is essential when they are to be positively used in space. Although there have been experiments on various organisms under space environment in the past, they mainly studied the effect of space environment on an individual organism or a single species. Microcosm is drawing attention as an experimental material of an ecosystem consisting of multiple species. The object in this research is to understand the nature of this network system called ecosystem. Thus, a mixed microorganism culturing system consisting of three types of microorganisms which form a minimum food chain system as a closed ecosystem (chlorella as the producer, bacteria as the decomposer, and rotifer as the consumer) was taken for the subject, on which to research the universal characteristics of ecosystems. From the results of experiments under the terrestrial environment, formation of colonies, which is an ecological structure, has been observed at its mature stage. The organisms form an optimal substance circulation system. Therefore, formation of colonies in simulation models is important. Many attempts have been made to create ecosystem models. For example, the Lotka-Volterra model forms a simultaneous equation with the differential equation expressing predator and prey relationship and many numerical calculations have been conducted on various ecosystems based on expanded L-V models. Conventionally, these top-down methods have been used. However, since this method only describes the average concentration of organisms that are distributed uniformly throughout the system and cannot express the spatial structure of the system, it was difficult to express ecosystem structures like colonies and density distributions. In actual ecosystems, there is heterogeneity in the number of individuals and in substance density, and this is thought to have great significance in ecosystems. Consequently, an individual-based model was used that applies rules to predator-prey relationship, suppression, production, self suppression, etc., of each species. It enabled the emergence of the overall system only by its local rules, and it was possible to reproduce colony generation. In addition, the transition and the ratio of populations for each species match well with experimental results.

Animals↗
PubMed2004

Polymorphisms of NS5B protein relates to early clearance of hepatitis C virus by interferon plus ribavirin: a pilot study.

Although randomized trials have shown enhancement of efficacy for combination therapy with interferon (IFN) alpha-2b and ribavirin compared with IFN monotherapy as first-line treatment for chronic hepatitis C, infection with genotype 1b and high viremia are still associated with significantly low response rates compared with non-1 genotypes and low viremia. We analysed amino acid sequences of the viral RNA-dependent RNA polymerase (RdRP) or nonstructural protein 5B (NS5B), responsible for ribavirin misincorporation into RNA products in patients with genotype 1b-related chronic hepatitis C and high viremia, and examined the relationship between such RdRp polymorphisms, and the initial decline in viral load induced by combination therapy with IFN-alpha and ribavirin. Substitution of glutamic acid to lysine at the 124th position (E124K) and of isoleucine to valine at the 85th position (I85V) were found to be closely associated with a potent decline of viral load and viral clearance at 8 weeks of treatment (five of five patients, coincidence rate 100%). In conclusion, our results suggest that the polymorphisms of E124K and I85V identified in NS5B protein are crucial for early viral clearance in patients with genotype 1b and high viremia by combination therapy with IFN and ribavirin, and that detection of amino acid sequence motifs might enable prediction of clinical efficacy.

Aged↗
PubMed2003

Chronic cerebral hypoperfusion induces white matter lesions and loss of oligodendroglia with DNA fragmentation in the rat.

Cerebrovascular white matter lesions represent an age-related neurodegenerative condition that appears as a hyperintense signal on magnetic resonance images. These lesions are frequently observed in aging, hypertension and cerebrovascular disease, and are responsible for cognitive decline and gait disorders in the elderly population. In humans, cerebrovascular white matter lesions are accompanied by apoptosis of oligodendroglia, and have been thought to be caused by chronic cerebral ischemia. In the present study, we tested whether chronic cerebral hypoperfusion induces white matter lesions and apoptosis of oligodendroglia in the rat. Doppler flow meter analysis revealed an immediate reduction of cerebral blood flow ranging from 30% to 40% of that before operation; this remained at 52-64% between 7 and 30 days after operation. Transferrin-immunoreactive oligodendroglia decreased in number and the myelin became degenerated in the medial corpus callosum at 7 days and thereafter. Using the TUNEL method, the number of cells showing DNA fragmentation increased three- to eightfold between 3 and 30 days post-surgery compared to sham-operated animals. Double labeling with TUNEL and immunohistochemistry for markers of either astroglia or oligodendroglia showed that DNA fragmentation occurred in both of these glia. Messenger RNA for caspase-3 increased approximately twofold versus the sham-operated rats between 1 and 30 days post-surgery. Immunohistochemistry revealed up-regulation of caspase-3 in the oligodendroglia of the white matter, and also in the astroglia and neurons of the gray matter. Molecules involved in apoptotic signaling such as TNF-alpha and Bax were also up-regulated in glial cells. These results indicate that chronic cerebral hypoperfusion induces white matter degeneration in association with DNA fragmentation in oligodendroglia.

Animals↗
PubMed2003

Neural-cadherin expression associated with angiogenesis in non-small-cell lung cancer patients.

An immunohistochemical analysis for E(epithelial)-cadherin and N(neural)-cadherin expression in relation to tumour angiogenesis was performed in 150 patients with nonsmall cell lung cancer (NSCLC). In all, 71 carcinomas (47.3%) were E-cadherin-negative. Epithelial-cadherin-negative tumours had lymph node metastases significantly more frequently than E-cadherin-positive tumours (P=0.0100). On the other hand, 46 carcinomas (30.7%) were N-cadherin-positive. Regarding tumour vascularity, there was no significant correlation between E-cadherin expression and tumour vascular. In contrast, the frequency of hypervascular tumours was significantly higher for N-cadherin-positive carcinomas than for N-cadherin-negative carcinomas (P=0.0373). Regarding prognosis, the 5-year survival rate of patients with E-cadherin-negative NSCLCs was significantly lower than that of patients with E-cadherin-positive NSCLCs (P=0.0146). In contrast, of the patients with large cell carcinomas, the 5-year survival rate of patients with N-cadherin-positive tumours was significantly lower than that of patients with N-cadherin-negative tumours (P=0.0013). A multivariate analysis demonstrated that E-cadherin status (P=0.0339) and tumour vascularity (P=0.0295) were significant indicators for survival. In conclusion, E-cadherin expression and tumour vascularity are significant prognostic factors of NSCLC patients. Furthermore, N-cadherin expression is associated with tumour angiogenesis, and its expression is one of prognostic factors of patients with large cell carcinomas. Thus, N-cadherin also might play a specific role in undifferentiated large cell carcinomas.

Antigens, CD34↗
PubMed2003

Relationship between transcardiac gradient of endothelin-1 and left ventricular remodelling in patients with first anterior myocardial infarction.

Aims To evaluate whether plasma endothelin-1 (ET-1) is extracted or produced through the heart in patients with acute myocardial infarction (AMI), and the relationship between transcardiac extraction of plasma ET-1 and left ventricular (LV) remodelling. Methods and results We measured the plasma level of ET-1 in the aortic root (Ao) and coronary sinus (CS) in 48 consecutive patients, who received successful revascularization and enalapril, for a first anterior AMI. In the acute phase the plasma ET-1 level was significantly higher both in the Ao and the CS compared to the control subjects. However, the plasma ET-1 level was significantly lower in the CS than in the Ao in the acute phase and after 1 month. There were significant correlations between transcardiac extraction of ET-1 in the acute phase and LV ejection fraction and LV end-diastolic volume index (LVEDVI) after 1 month. Stepwise multivariate analysis showed that maximal creatine phosphokinase and transcardiac extraction of plasma ET-1 during the acute phase were independently and positively correlated with the absolute change in LVEDVI after 1 month. Conclusions These results indicate that elevated circulating ET-1 is extracted through the heart in patients with a first anterior AMI and that the extracted ET-1 plays a significant role in modulating post-infarct LV remodelling.

Atrial Natriuretic Factor↗
PubMed2003

A rat model for the energetic regulation of gonadotropin secretion: role of the glucose-sensing mechanism in the brain.

Energy availability has been considered to regulate gonadal activity by modulating the release of gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) at various reproductive phases, such as lactation and puberty in domestic as well as wild animals. Experimental models with rats and sheep have demonstrated that fasting or glucoprivation suppresses pulsatile LH release. From those experiments, the information on energy deficiency is considered to be detected by specific central sensors and conveyed to the hypothalamus to regulate LH release as well as food intake. Noradrenergic neurons, originating in the medulla oblongata and projecting to the hypothalamic paraventricular nucleus (PVN), is reported to be one of the pathways mediating the response of LH release to energy deficiency. The other component is considered to be an energy-sensing mechanism in the brain. Glucose or other oxidizable fuels may function as a metabolic signal to regulate LH release. Previous studies suggest the presence of a glucose-sensing mechanism in the rat hindbrain. From our previous results in the rat, the ependymocytes lining the wall of the cerebroventricle could possibly serve as a glucose sensor to regulate GnRH/LH release. Greater understanding of the nature of the energy-sensing mechanism in the brain will contribute to the nutritional manipulation of reproductive performance in domestic animals in various conditions.

Animals↗
PubMed2003

MRI in ALS patients.

Explore the source record for details and available documents.

Amyotrophic Lateral Sclerosis↗
PubMed2003

Improvement of central motor conduction after bone marrow transplantation in adrenoleukodystrophy.

The case is described of a 20-year-old man with adrenoleukodystrophy who showed right spastic hemiparesis and gait disturbance. Brain magnetic resonance imaging disclosed predominant involvement of the left corticospinal pathway. The clinical symptoms improved after bone marrow transplantation. Transcranial magnetic stimulation disclosed significant improvement in various parameters of central motor conduction.

Adrenoleukodystrophy↗