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Biomedical subjects

Tsutomu Nakada

Publications and source records attributed to Tsutomu Nakada.

At least 19 recordsLinked to original sources

Loss and Gain of Aqp10 Paralogs With Broad Solute Selectivity in Anguillid Eels.

Aquaporin (Aqp) 10 is a member of the aquaglyceriporin family, which transports small, uncharged solutes in addition to water. Although the solute selectivity of aquaglyceroporins varies, the mechanism of solute selectivity has not yet been fully elucidated. The common ancestor of ray-finned fish possessed two paralogous genes for aquaporin 10, aqp10.1 and aqp10.2, which produce Aqps with different solute selectivities. Most teleosts possess one or more ohnologs derived from aqp10.1 and aqp10.2; however, the common ancestor of Anguilliformes species lost all aqp10.1-derived ohnologs. Anguilliformes species, except Anguilla species, have one aqp10.2b, but recent tandem duplications in the European eel have generated three aqp10.2b paralogs (aqp10.2b1-aqp10.2b3), whose activities remain ambiguous. In this study, we found that the four sites forming the aromatic/arginine (ar/R) selectivity filter in European eel Aqp10.2b1 were identical to those in Aqp10.2b of other species. However, the Y residue at position 3 was replaced with G in the ar/R selectivity filter of Aqp10.2b2 and b3. When expressed in Xenopus oocytes, Aqp10.2b2 and b3 showed higher permeability to urea and boric acid than Aqp10.2b1, indicating that Aqp10.2b2 and b3 acquired broad solute selectivity similar to that of Aqp10.1, which was lost in the ancestral Anguilliformes species. Urea and boric acid permeabilities of Aqp10.2b1 increased when the Y residue at position 3 of the ar/R selectivity filter was replaced with G. Overall, our results outline the history of the loss and gain of Aqp10 paralogs with broad solute selectivity in anguillid eels.

Animals↗

Diffusion tensor analysis in chronic schizophrenia. A preliminary study on a high-field (3.0T) system.

The objective of this study was to delineate further the nature of diffusion anisotropy abnormalities in frontal white matter previously observed in schizophrenic patients using a high-field magnetic resonance imaging (MRI) system. Six schizophrenia patients and six healthy control subjects were examined using a highfield MRI (3.0T) system. In order to confirm previously reported abnormalities in anisotropy, data were first analyzed to determine fractional anisotropy (FA), a frequently utilized general index of anisotropy. Subsequently, the identical data set was subjected to lambda chart analysis (LCA), a newly developed algorithm for diffusion tensor analysis (DTA) that more effectively provides eigenvalue information. Frontal white matter FA was found to be significantly reduced in schizophrenic patients compared to control subjects, confirming previously reported findings. LCA revealed that the decline in FA was due to a disproportionate increase in small eigenvalue components, and not due to a decline in principal eigenvalue components.

Adult↗

Electrophysiological correlates of absolute pitch and relative pitch.

The temporal and spatial characteristics of the cortical processes responsible for absolute pitch (AP) and relative pitch (RP) were investigated by multi-channel event-related potentials (ERPs). Compared to listening, pitch-naming of tones in non-possessors of AP elicited three ERP components (P3b, parietal positive slow wave, frontal negative slow wave) over parietal and frontal scalp between 300 and 900 ms in latency, representing the cortical processes for RP. Possessors of AP elicited a unique left posterior-temporal negativity ('AP negativity') at 150 ms in both listening and pitch-naming conditions, representing the cortical processes for AP that were triggered by pitch input irrespective of the task the subjects were asked to perform. Congruency of auditory Stroop stimuli modulated the amplitudes of parietal positive slow wave (non-possessors of AP) and 'AP negativity' (possessors of AP), confirming that these components reflect the verbal labeling or pitch-to-pitch-name associative transformation that is central to pitch-naming. These results are consistent with the hypothesis that AP is subserved by neuronal processes in the left auditory association cortex that occur earlier and more automatically than the processes for RP, which involve broader areas of the cortex over longer periods of time.

Acoustic Stimulation↗

Electrophysiological correlates of grapheme-phoneme conversion.

The cortical processes underlying grapheme-phoneme conversion were investigated by event-related potentials (ERPs). The task consisted of silent reading or vowel-matching of three Japanese hiragana characters, each representing a consonant-vowel syllable. At earlier latencies, typical components of the visual ERP, namely, P1 (110 ms), N1 (170 ms) and P2 (300 ms), were elicited in the temporo-occipital area for both tasks as well as control task (observing the orthographic shapes of three Korean characters). Following these earlier components, two sustained negativities were identified. The earlier sustained negativity, referred here to as SN1, was found in both the silent-reading and vowel-matching task but not in the control task. The scalp distribution of SN1 was over the left occipito-temporal area, with maximum amplitude over O1. The amplitude of SN1 was larger in the vowel-matching task compared to the silent-reading task, consistent with previous reports that ERP amplitude correlates with task difficulty. SN2, the later sustained negativity, was only observed in the vowel-matching task. The scalp distribution of SN2 was over the midsagittal centro-parietal area with maximum amplitude over Cz. Elicitation of SN2 in the vowel-matching task suggested that the vowel-matching task requires a wider range of neural activities exceeding the established conventional area of language processing.

Adult↗

The primary motor area for voluntary diaphragmatic motion identified by high field fMRI.

In order to identify the precise location of the primary motor area for the diaphragm with respect to the classical motor homunculus, functional magnetic resonance imaging (fMRI) experiments were performed utilizing independent component-cross correlation- sequential epoch (ICS) analysis on a high-field (3.0 Tesla) system. Activations which correlated with voluntary diaphragmatic motion mapped onto the area anterolateral to that for voluntary hand motion (internal control in ICS analysis). Multiple subject analysis yielded the primary motor cortex for the diaphragm to be (+/-48, -4, 47) in the Talairach and Tournoux coordinates. The results were highly consistent with the previously reported cortical area for the diaphragm determined by transcranial electrical/magnetic stimulation.

Adult↗

Evaluation of the response of metastatic brain tumors to stereotactic radiosurgery by proton magnetic resonance spectroscopy, 201TlCl single-photon emission computerized tomography, and gadolinium-enhanced magnetic resonance imaging.

OBJECT: The goal of this study was to investigate the usefulness of proton (1H) magnetic resonance (MR) spectroscopy to evaluate the response of metastatic brain tumors to stereotactic radiosurgery (SRS) in comparison with Gd-enhanced MR imaging and single-photon emission computerized tomography with administration of thallium-201 chloride (201TlCl-SPECT). METHODS: Forty patients with a total of 47 metastatic brain tumors were evaluated. The primary lesion was identified in all cases. Stereotactic radiosurgery was effective in 37 lesions. All patients were examined using Gd-enhanced MR imaging before and after SRS. Thalium-201 chloride was administered to 27 patients with 34 tumors and SPECT images were obtained. Proton MR spectroscopy was performed in 36 patients who harbored 43 tumors. On Gd-enhanced MR images, a decrease in the volume of the Gd-enhanced lesion and a change in the enhanced effect in the lesion after treatment were recognized as showing the effectiveness of SRS between 1 and 3 months or more (mean 8.54 +/- 3.58 weeks). In 201TlCl-SPECT studies, the ratio of lesion to normal brain decreased from 2 weeks to 2 months (mean 5.03 +/- 2.77 weeks) after radiosurgery. On 1H-MR spectroscopy images a high choline (Cho) peak and a lipid-dominant (Lip) peak were observed in 25 lesions and a high Cho peak and a lactate-dominant (Lac) peak were observed in 12 lesions before SRS. A decrease in the Cho peak, a disappearance of the Lac peak, and an increase in the Lip peak were observed between 1 week and 1 month (mean 2.76 +/- 1.62 weeks) after treatment. CONCLUSIONS: Based on histopathological findings obtained at autopsy or at surgery, we assume that a high Cho peak may be observed in viable tumor tissue and a Lip peak in areas of necrosis. The results indicate that 1H-MR spectroscopy is potentially a more sensitive tool in evaluating the response to SRS than 201TlCl-SPECT or Gd-enhanced MR imaging and that it can be used earlier for this purpose than those other imaging methods.

Adult↗

Coerced training of the nondominant hand resulting in cortical reorganization: a high-field functional magnetic resonance imaging study.

OBJECT: The authors investigated brain strategies associated with hand use in an attempt to clarify genetic and nongenetic factors influencing handedness by using high-field functional magnetic resonance imaging. METHODS: Three groups of patients were studied. The first two groups comprised individuals in whom handedness developed spontaneously (right-handed and left-handed groups). The third group comprised individuals who were coercively trained to use the right hand and developed mixed handedness, referred to here as trained ambidexterity. All trained ambidextrous volunteers were certain that they were innately left-handed, but due to social pressure had modified their preferred hand use for certain tasks common to the right hand. Although right-handed and left-handed volunteers displayed virtually identical cortical activation, involving homologous cortex primarily located contralateral to the hand motion, trained ambidextrous volunteers exhibited a clearly unique activation pattern. During right-handed motion, motor areas in both hemispheres were activated in these volunteers. During left-handed motion, the right supplemental motor area and the right intermediate zone of the anterior cerebellar lobe were activated significantly more frequently than observed in naturally right-handed or left-handed volunteers. CONCLUSIONS: The results provide strong evidence that cortical organization of spontaneously developed right- and left-handedness involves homologous cortex primarily located contralateral to the hand motion, and this organization is likely to be prenatally determined. By contrast, coerced training of the nondominant hand during the early stages of an individual's development results in mixed handedness (trained ambidexterity), indicating cortical reorganization.

Cerebral Cortex↗

Cortical processing of musical consonance: an evoked potential study.

Cortical processes underlying perception of musical consonance were investigated by long-latency auditory evoked potentials (EPs). Subjects listened to a random sequence of dyadic pure tones paired at various pitch intervals (1, 4, 6, 7, or 9 semitones). Amplitudes of P2 and N2 components of auditory EPs were significantly modulated by pitch interval of the dyads, being most negative for 1 semitone (minor second) and least negative or most positive for 7 semitones (perfect fifth). The results indicate that neural processing of consonance depend not only on peripheral mechanisms in the inner ear but also on higher associative processing of pitch relationships in the cerebral cortex.

Acoustic Stimulation↗

Molecular cloning and characteristics of a novel zinc finger protein and its splice variant whose transcripts are expressed during spermatogenesis.

Testicular zinc finger protein (TZF) has a zinc finger motif of the Cys2-His2 type and its transcript is expressed predominantly in mouse spermatogenic cells. Using the fragment of TZF as a probe, we isolated the alternative splice variant form (TZF-L) from mouse testis cDNA library. Analysis of the open reading frame of each cDNA indicated that TZF and TZF-L were polypeptides of 942 and 2025 amino acid residues, respectively, and the N-terminal 902 amino acids of TZF-L were identical to those of TZF. The C-terminal region of TZF-L had more a zinc finger motif of the Cys2-His2 type and poly-Glu and poly-Pro regions. The mouse TZF/TZF-L gene spanned >20 kb and consisted of 11 exons. RT-PCR analysis of the expression level of mRNAs for mouse TZF and TZF-L showed that both transcripts are highly expressed in testis and moderately in kidney and ovary. Elevated expression of both transcripts during testicular development in mice was restricted to spermatocytes at the pachytene stage of meiotic prophase. Fusion proteins with GFP also demonstrated the nuclear localization of TZF and TZF-L. These experiments suggest that TZF and TZF-L may act to control the gene activity during spermatogenesis.

Alternative Splicing↗

Enhanced expression of B7.2 (CD86) by percutaneous sensitization with house dust mite antigen.

House dust mite antigen is a well-known allergen in the pathogenesis of atopic dermatitis (AD), a chronic relapsing inflammatory skin disease. We evaluated the AD model mice sensitized with house dust mite antigen and observed a Th2-dominant immune response. In this experiment, BALB/c mice were sensitized percutaneously with house dust mite antigen three times with 7 days interval after skin barrier disruption. A remarkable infiltration of polymorphonuclear granulocytes and monocytes in the cutis was observed in mice treated with this antigen, high serum IgE levels and IL-4 mRNA expression in local lymph node cells was also observed. CD19(+) B cell numbers overturned to CD4(+) helper T cells. In these mice, there was significant increase of B7.2 (CD86) expression on CD19(+) B cells. These results indicate that house dust mite antigen sensitizes BALB/c mice and skews their Th1/Th2 balance toward Th2.

Administration, Cutaneous↗

Absolute eigenvalue diffusion tensor analysis for human brain maturation.

The absolute eigenvalues of the diffusion tensor of white matter in sixteen normal subjects in two groups representing the early developmental stage (ages 1-10 years, n=8) and young adult stage (ages 18-34 years, n=8) were assessed using a high-field (3.0 T) magnetic resonance (MR) system. All three eigenvalues, including the largest eigenvalue, decreased significantly with brain maturation. The rate of the decline in the two small eigenvalues was, however, much higher than that of the largest eigenvalue, resulting in an actual increase in fractional anisotropy, a commonly measured relative index. The data demonstrate that an increase in anisotropy associated with brain maturation represents a significant decline in the small eigenvalue components, rather than an increase in the largest eigenvalue. The observed pattern of eigenvalue changes is best explained by the simultaneous occurrence of two of several independent phenomena within the axonal microenvironment during the myelination process, namely, (1) decline in unrestricted water content in extra-axonal space, and (2) increase in apparent diffusivity within the axon.

Adolescent↗

Feasibility study of single region lambda chart analysis for pyramidal tract physiology.

Diffusion characteristics of the pyramidal tract were assessed in nine patients who had clinical evidence of pyramidal tract dysfunction, utilizing lambda chart analysis (LCA). The underlying pathologic process of tract dysfunction was varied and included Pelizaeus-Merzbacher disease (PMD), Alexander disease, adrenoleukodystrophy (adrenomyeloneuropathy (AMD) type and cerebral type), amyotrophic lateral sclerosis (ALS), and Wallerian degeneration (WD). While pyramidal tract diffusion characteristics in WD indicated a pathological process characterized by replacement of normal fibers by smaller cellular component such as degenerated small fibers and/or gliosis, pyramidal tract diffusion characteristics in patients with PMD, Alexander disease, and adreno leukodystrophy of the cerebral type indicated a pathological process characterized by replacement of normal fibers by larger cellular components such as spheroids or edematous space. Pyramidal tract diffusion characteristics of patients with ALS or adrenoleukodystrophy of AMD type were relatively intact suggesting a pathological process characterized by relatively preserved structural architecture. These findings are highly consistent with known pathophysiological indices and indicate the feasibility of the clinical utility of LCA for assessing pyramidal tract physiology.

Adolescent↗

Dorsolateral prefrontal lobe activation declines significantly with age--functional NIRS study.

Dorsolateral prefrontal cortex (DLPF) activation in response to cognitive paradigms engaging working memory was quantitatively evaluated using functional near infrared spectroscopy (fNIRS) in cognitively normal individuals across the age spectrum (20-90 years; 8 females, 52 males). DLPF activation score (DAS) demonstrated a significant decline (r(2) = -0561, p < 0.05) as a function of age. The study indicates that blood flow response associated with DLPF activation declines as a function of age in cognitively normal individuals and that fNIRS can be used as a convenient, portable tool for assessing such activation.

Adult↗

Ear advantage and consonance of dichotic pitch intervals in absolute-pitch possessors.

Left-right asymmetry in the central processing of musical consonance was investigated by dichotic listening tasks. Two piano tones paired at various pitch intervals (1-11 semitones) were presented one note in each ear to twenty absolute-pitch possessors. As a result, a weak overall trend for left ear advantage (LEA) was found, as is characteristic of trained musicians. Second, pitches of dissonant intervals were more difficult to identify than those of consonant intervals. Finally, the LEA was greater with dissonant intervals than with consonant intervals. As the tones were dichotically presented, the results indicated that the central auditory system could distinguish between consonant and dissonant intervals without initial processing of pitch-pitch relations in the cochlea.

Adult↗

Free convection schema defines the shape of the human brain: brain and self-organization.

As a fundamental rule of nature, the shape of a functioning organ should never be considered accidental. Since the principal rules for a self-organizing neural network are not sufficient for determining the shape and anatomic features of the brain, these must be governed by other rules. Ontogeny of the global shape of the brain is guided by radial glial fibers. The rules defining the growth pattern of radial glial fibers, therefore, should be the rules for a self-organization for the shape of the brain. In this work, the overall shape and structural anatomic detail of the human brain was successfully simulated utilizing self-organization rules of heat convection represented by Boussinesq partial differential equations. The result suggests that radial glial fibers may grow in Markovian fashion, guided by gaseous substrates moving miniature distances according to a convection schema. The result also holds implication that the shape of the brain has specific physical meaning in the creation of a virtual sphere, which in turn ensures equivalence of columns within the entire cortex, the well-known vital fundamental of brain organization.

Brain↗

Clinical experience on 3.0 T systems in Niigata, 1996 to 2002.

High-field human magnetic resonance imaging (MRI) systems developed over the recent years have contributed significantly to the field of functional MRI and multinuclear spectroscopy. As more experience is gained, it has become apparent that high-field systems, especially those at 3.0 T, possess significant advantages in the clinical setting over conventional MRI systems. High-field MRI is promising as an all-in-one system for both structural and functional assessments. This review summarizes the exciting features of clinical imaging based on our cumulative 6-year experience on various 3.0 T systems.

Brain Mapping↗

Cortical reorganization in patients with subcortical hemiparesis: neural mechanisms of functional recovery and prognostic implication.

OBJECT: A systematic investigation on cortical reorganization in patients with hemiparesis of a subcortical origin, with special emphasis on functional correlates, was conducted using functional magnetic resonance (fMR) imaging performed on a 3-tesla system specifically optimized for fMR imaging investigation. METHODS: The study group included 46 patients with hemiparesis (25 with right and 21 with left hemiparesis) and 30 age-matched healthy volunteers as controls. All study participants were originally right handed. The characteristics of the lesion were putaminal hemorrhage in 19 patients, thalamic hemorrhage in 10 patients, and striatocapsular bland infarction in 17 patients. Functional recovery in subcortical hemiparesis showed two distinct phases of the recovery process involving entirely different neural mechanisms. Phase I is characterized by the process of recovery and/or reorganization of the primary system. Successful recovery of this system is typically reached within 1 month after stroke onset. Its clinical correlate is a rapid recovery course and significant recovery of function within 1 month of stroke onset. Failure of recovery of the primary system shifts the recovery process to Phase II, during which reorganization involving the ipsilateral pathway takes place. The clinical correlate of Phase II is a slow recovery course with variable functional outcome. CONCLUSIONS: Effective functional organization of the ipsilateral pathway, as identified by linked activation of the ipsilateral primary sensorimotor cortex and contralateral anterior lobe of the cerebellum, is correlated with a good prognostic outcome for patients in the slow recovery group. A high degree of connectivity between supplementary motor areas, bilaterally, appears to influence functional recovery adversely.

Aged↗

EZ-tracing: a new ready-to-use algorithm for magnetic resonance tractography.

A new algorithm for tractography based on diffusion tensor analysis (DTA) is presented. This method, called EZ-tracing, is based on a new algorithm for analyzing DTA data, lambda chart analysis (LCA), and effectively overcomes the main shortcomings of previous methods for tractography. EZ-tracing is written in MATLAB scripting language (MathWorks, Natick, MA, USA) and can be implemented on any of the common operating systems, such as Microsoft Windows, UNIX, and LINUX. The program is available in public at coe@bri.niigata-u.ac.jp.

Adult↗