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Biomedical subjects

M Akamatsu

Publications and source records attributed to M Akamatsu.

At least 19 recordsLinked to original sources
PubMed2002

"A system biology" approach to bioinformatics and functional genomics in complex human diseases: arthritis.

Human and other annotated genome sequences have facilitated generation of vast amounts of correlative data, from human/animal genetics, normal and disease-affected tissues from complex diseases such as arthritis using gene/protein chips and SNP analysis. These data sets include genes/proteins whose functions are partially known at the cellular level or may be completely unknown (e.g. ESTs). Thus, genomic research has transformed molecular biology from "data poor" to "data rich" science, allowing further division into subpopulations of subcellular fractions, which are often given an "-omic" suffix. These disciplines have to converge at a systemic level to examine the structure and dynamics of cellular and organismal function. The challenge of characterizing ESTs linked to complex diseases is like interpreting sharp images on a blurred background and therefore requires a multidimensional screen for functional genomics ("functionomics") in tissues, mice and zebra fish model, which intertwines various approaches and readouts to study development and homeostasis of a system. In summary, the post-genomic era of functionomics will facilitate to narrow the bridge between correlative data and causative data by quaint hypothesis-driven research using a system approach integrating "intercoms" of interacting and interdependent disciplines forming a unified whole as described in this review for Arthritis.

Animals↗
PubMed2001

Non-competitive GABA antagonists: probing the mechanisms of their selectivity for insect versus mammalian receptors.

A great variety of non-competitive antagonists of ionotropic gamma-aminobutyric acid (GABA) receptors have been reported. While they are structurally diverse, there are common features in their structures. Thus, it was hypothesized that they bind to an identical site in different or overlapping orientations, and this hypothesis was validated by three-dimensional structure-activity relationship (3D-QSAR) analysis using receptor-binding data. Meanwhile, although most antagonists are highly toxic to both vertebrates and invertebrates, several classes of antagonists, such as nor-diterpene lactone picrodendrins, phenyl heterocyclic compounds and disubstituted bicyclophosphorothionates, were found to exhibit selectivity for housefly versus rat GABA receptors. To probe their selectivity mechanisms, the 3D-QSAR method was applied to the three classes of antagonists. This revealed several important differences that might be related to the selectivity of antagonists between the structures of the non-competitive antagonist-binding sites of housefly and rat GABA receptors.

Animals↗
PubMed2001

Neurofibromatosis type 1 with basilar artery fusiform aneurysm manifesting Wallenberg's syndrome.

A case of neurofibromatosis type 1 (NF1) manifesting Wallenberg's syndrome and fusiform aneurysm of the basilar artery is reported. The patient suddenly developed dysarthria, walking difficulty and sensory disturbance. Neurological examination suggested Wallenberg's syndrome and MR imaging confirmed an ischemic lesion at the left lateral medulla oblongata. Cerebral angiography revealed a fusiform aneurysm at the middle portion of the basilar artery. However, there was no occlusive change in either the posterior inferior cerebellar artery or the vertebral artery. The clinical and radiological features are discussed together with a review of NF1 cases with intracranial aneurysms in the literature.

Diagnosis, Differential↗
PubMed2001

An electromyographic investigation of the effect of stimulus-response mapping on choice reaction time.

The activity of the agonist muscles was recorded during the performance of a two-choice visual reaction time (RT) task in which the compatibility of the stimulus-response mapping was manipulated. Correct trials were distinguished according to whether or not the activation of the agonist of the required response was preceded by an activation of the agonist of the nonrequired response. Double activation trials were more numerous for the incompatible than for the compatible mapping. Furthermore, these trials yielded longer RTs than the single muscular activation trials. These results suggest that initial activations of nonrequired responses are more frequently aborted and corrected when the mapping is incompatible than when it is compatible. This finding supports the dimensional overlap model of stimulus-response compatibility (S. Kornblum, T. Hasbroucq, & A. Osman, 1990).

Adolescent↗
PubMed2000

Changes in spinal excitability during choice reaction time: the H reflex as a probe of information transmission.

The aim of the present study was to investigate the modulations in amplitude of H reflexes elicited in a hand muscle, the flexor pollicis brevis, during the performance of a choice reaction time (RT) task in which this muscle was directly involved. Ten subjects were to choose between a left- or a right-thumb key-press according to the lateral location of a flash of light. The stimulus-response mapping was either compatible or incompatible. Hoffman reflexes were elicited at different times during the RT by stimulation of the median nerve. Twenty-five milliseconds before the voluntary response, the amplitude of the H reflex suddenly increased when the muscle was involved in the response and decreased symmetrically when the muscle was not involved in the response. Mapping compatibility exerted no detectable influence on the changes in spinal excitability. The latter result supports the assumptions that are at the core of Sternberg's additive factor method.

Adult↗
PubMed2000

[Percutaneous tumor ablation therapy for the advanced stage of HCC].

We have performed percutaneous tumor ablation (PTA) including percutaneous ethanol injection therapy (PEIT) for 90% of the patients with hepatocellular carcinoma. Until December 1998, the 793 patients received PTA, 5 years survival rate reached 39.8%. Excluding the patients with Child C whose hepatic function were extremely low, 5 years survival rate reached to the level of 41.2%. Since 5 years survival rate in stage IV-A reached 24.4%, the patients of stage IV-A may be considered to have an indication for PTA. We have confirmed the effectiveness of the local treatment including radiotherapy for advanced hepatocellular carcinoma with portal vein invasion. We are attempting to perform PTA for the extra-hepatic lesions that had no indication of other treatment. However the indication of PTA is limited by the presence of diffuse nodules, exacerbation of the hepatic function, or tumor invasion to portal vein, bile duct, inferior vena cava.

Carcinoma, Hepatocellular↗
PubMed1999

Vinexin forms a signaling complex with Sos and modulates epidermal growth factor-induced c-Jun N-terminal kinase/stress-activated protein kinase activities.

Vinexin, a novel protein that plays a key role in cell spreading and cytoskeletal organization, contains three SH3 domains and binds to vinculin through its first and second SH3 domains. We show here that the third SH3 domain binds to Sos, a guanine nucleotide exchange factor for Ras and Rac, both in vitro and in vivo. Point mutations in the third SH3 domain abolished the vinexin-Sos interaction. Stimulation of NIH/3T3 cells with serum, epidermal growth factor (EGF), or platelet-derived growth factor (PDGF) decreased the electrophoretic mobility of Sos and concomitantly inhibited formation of the vinexin-Sos complex. Phosphatase treatment of lysates restored the binding of Sos to vinexin, suggesting that signaling from serum, EGF, or PDGF regulates the vinexin-Sos complex through the Sos phosphorylation. To evaluate the function of vinexin downstream of growth factors, we examined the effects of wild-type and mutant vinexin expression on extracellular signal-regulated kinase (Erk) and c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) activation in response to EGF. Exogenous expression of vinexin beta in NIH/3T3 cells enhanced JNK/SAPK activation but did not affect Erk activation. Moreover mutations in the third SH3 domain abolished EGF activation of JNK/SAPK in a dominant-negative fashion, whereas they slightly stimulated Erk. Together these results suggest that vinexin can selectively modulate EGF-induced signal transduction pathways leading to JNK/SAPK kinase activation.

3T3 Cells↗
PubMed1999

Sensorimotor polyneuropathy associated with chronic lymphocytic leukemia, IgM antigangliosides antibody and human T-cell leukemia virus I infection.

A 65-year-old man presented with a sensorimotor polyneuropathy associated with B-cell chronic lymphocytic leukemia (CLL) and immunoglobulin M (IgM) antibody to various gangliosides. Electrophysiological studies denoted significant abnormalities of motor and sensory nerve conduction. Although the pathology of sural nerve biopsy looked minimally affected, immunohistochemical studies showed specific binding of IgM to the human peripheral nerve. Our patient also had high titer of antibody to human T-cell leukemia virus I (HTLV-I) in both serum and cerebrospinal fluid (CSF), which might activate B-cell-mediated immunity and facilitate the production of IgM antibody. The other unique feature is the reactivity of antibody to gangliosides. The patient had IgM antibody reactivities to gangliosides with disialosyl residue such as GT1b, GQ1b and GD3, but not to GD1b. IgM antibody to gangliosides with disialosyl residue has been reported in ataxic symptoms, but our patient failed to demonstrate ataxia. Without reactivity to GD1b, sensory ataxic neuropathy might not develop even in the presence of antibody reactive to other gangliosides with disialosyl residue.

Aged↗
PubMed1999

The time-course of preparatory spinal and cortico-spinal inhibition: an H-reflex and transcranial magnetic stimulation study in man.

In a previous study where reaction-time methods were combined with transcranial magnetic stimulation (TMS) of the motor cortex, cortico-spinal excitability was shown to reflect time preparation. Provided that subjects can accurately estimate time, the amplitude of motor-evoked potentials (MEPs) diminish progressively during the interval separating the warning signal from the response signal (i.e., the foreperiod). On the other hand, several experiments have demonstrated that the amplitude of the Hoffman (H) reflex elicited in prime movers diminishes during the foreperiod of reaction-time tasks. The aim of the present study was to compare the time course of the respective decrements of H-reflex and MEP amplitude during a constant 500-ms foreperiod. The subjects (n=8) participated in two experimental sessions. In one session, H-reflexes were induced in a tonically activated, responding hand muscle, the flexor pollicis brevis, at different times during the foreperiod of a visual-choice reaction-time task. In the other session, motor potentials were evoked in the same muscle by TMS of the motor cortex delivered in the same behavioral conditions and at the same times as in the first session. The results show that both H-reflexes and MEPs diminish in amplitude during the foreperiod, which replicates and extends previous findings. Interestingly, the time constants of the two decrements differed. There was a facilitatory effect of both electrical and magnetic stimulations on the subject's performance: reaction time was shorter for the trials during which a stimulation was delivered than for the no-stimulation trials. This facilitation was maximal when the stimulations were delivered simultaneously with the warning signal and vanished progressively with stimulation time.

Adult↗
PubMed1999

Multineuronal spike classification based on multisite electrode recording, whole-waveform analysis, and hierarchical clustering.

We proposed here a method of multineuronal spike classification based on multisite electrode recording, whole-waveform analysis, and hierarchical clustering for studying correlated activities of adjacent neurons in nervous systems. Multineuronal spikes were recorded with a multisite electrode placed in the hippocampal pyramidal cell layer of anesthetized rats. If the impedance of each electrode site is relatively low and the distance between electrode sites is sufficiently small, a spike generated by a neuron is simultaneously recorded at multielectrode sites with different amplitudes. The covariance between the spike waveform at each electrode site and a template was calculated as a damping factor due to the volume conduction of the spike from the neuron to the electrode site. Calculated damping factors were vectorized and analyzed by hierarchical clustering using a multidimensional statistical test. Since a cluster of damping vectors was shown to correspond to an antidromically identified neuron, spikes of different neurons are classified by referring to the distributions of damping vectors. Errors in damping vector calculation due to partially overlapping spikes were minimized by successively subtracting preceding spikes from raw data. Clustering errors due to complex spike bursts (i.e., spikes with variable amplitudes) were avoided by detecting such bursts and then using only the first spike of a burst for clustering. These special procedures produced better cluster separation than conventional methods, and enabled multiple neuronal spikes to be classified automatically. Waveforms of classified spikes were well superimposed. We concluded that this method is particularly useful for separating the activities of adjacent neurons that fire partially overlapping spikes and/or complex spike bursts.

Action Potentials↗
PubMed1999

Structure-activity relationships of RGD mimetics as fibrinogen-receptor antagonists.

The activities of a series of RGD mimetics, which contained a variety of cationic structures, for the inhibition of platelet aggregation and fibrinogen-receptor binding were measured. The stability of the coulombic ion-pairing complex of the model compounds with the acetate anion as a model for the receptor was calculated in terms of the ionic interaction energy. The results suggest that stability is one of the significant factors which govern the inhibitory potency of fibrinogen-receptor binding. The distance between cationic and anionic groups might also affect the potency. A compound which contained an amidinophenyl structure as the cationic moiety showed exceptionally high inhibitory activity, suggesting that some other factors, in addition to coulombic interaction and the distance, affect the potency.

Blood Platelets↗
PubMed1998

[Granulomatous slack skin].

A 48-year-old woman developed granulomatous slack skin (GSS), one of the special forms of cutaneous T-cell lymphoma. The lesional skin slack with an atrophic, poikilodermic surface and granulomatous induration. Histopathological findings included epidermotropism, diffuse lymphoid cell infiltration and foreign body giant cells as well as granulomatous reactions from superficial to deep dermis, including part the subcutis. The diagnosis was established by positive results for rearrangement of the T-cell receptor gene. The therapeutic possibilities, especially with corticosteroids and monitoring the disease course by following serum angiotensin converting enzyme activity are discussed.

Breast↗