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Biomedical subjects

Yoko Yamaguchi

Publications and source records attributed to Yoko Yamaguchi.

At least 19 recordsLinked to original sources

A long-range cortical network emerging with theta oscillation in a mental task.

Human scalp EEG has demonstrated that global coherence among distant areas increases during cognitive tasks, suggesting that oscillating neural activities work to generate global neuronal assemblies for cognitive functions. The theta oscillation in a frequency range of 4-8 Hz with large amplitudes which emerges during mental tasks around the frontal midline region is called fm theta. If theta oscillation concerns the global neuronal assemblies, fm theta should be associated with regional activities that depend on task conditions. In the present study, we examine the EEG-related brain activities by developing simultaneous EEG and fMRI during a mental calculation task. EEG-related negative BOLD was dominant over anterior medial regions, suggesting a major contribution of negative BOLD to fm theta. Negative and positive BOLD were found over distant regions. Functional connectivity analyses revealed that the connectivity varied remarkably according to mental conditions. In the rest condition, the connectivity was localized, whereas in the task condition, a long-range coherent network was formed by the anterior midline, posterior cingulate and right middle temporal cortices with linking between the right middle temporal and left lateral cortices during numerical processing. Further EEG analyses indicate that the long-range coherent network executing cognitive functions is coordinated in the time window of theta oscillations.

Action Potentials↗

Optimum formulation for sustained-release insulin.

Our aim was to prepare an optimum formulation for a sustained-release preparation of insulin using biodegradable polymer composed of co-poly(D,L-lactic/glycolic) acids (PLGA)(L/G ratio: 50/50). Various kinds of PLGA microcapsules containing 3% insulin were administered subcutaneously (250 U/kg) as a single dose to rats with streptozotocin-induced diabetes, and plasma insulin levels were monitored. The following results were obtained. (1) Glycerin and water were suitable additives to prepare a reproducible injectable formulation. (2) Addition of zinc compounds was essential to diminish rapid insulin release and six-fold molar excess of ZnO to insulin was desirable. (3) The size of insulin particles showed the following order: human insulin > lyophilized human insulin > Zn-free human insulin. Zn-free insulin was similar to lyophilized insulin with respect to control of rapid release, so a smaller particle size was essential. (4) The size of the microcapsules also affected the release of insulin. With larger microcapsules (approximately 30 microm), there was gradual release and a significant second phase of insulin release, while smaller microcapsules did not allow sustained release. Some variation in microcapsule size contributed to more constant and sustained release. (5) Based on the insulin release profile in vivo, a suitable molecular weight for PLGA was around 6000. The biological activity of insulin extracted from the formulation was similar to that of normal insulin. These experiments allowed us to prepare a desirable sustained-release insulin formulation.

Animals↗

Input-dependent learning rule for the memory of spatiotemporal sequences in hippocampal network with theta phase precession.

Theta phase precession in rat hippocampal place cells is hypothesized to contribute to memory encoding of running experience in the sense that it provides the ideal timing for synaptic plasticity and enables the asymmetric associative connections under the Hebbian learning rule with asymmetric time window (Yamaguchi 2003). When the sequence of place fields is considered as the episodic memory of running experience, a given spatial route should be accurately stored in spite of differing overlap extent among place fields and varying running velocity. Using a hippocampal network model with phase precession and the Hebbian learning rule with asymmetric time window, we investigate the memory encoding of place field sequences in a single traversal experience. Computer experiments show that place fields cannot be stored correctly until an input-dependent feature is introduced into the learning rule. These experiments further indicate that there exists an optimum value for the saturation level of synaptic plasticity and the speed of synaptic plasticity in the learning rule, which are correlated with, respectively, the overlap extent of place field sequence and the running velocity of animal during traversal. A comparison of these results with biological evidences shows good agreement and suggests that behavior-dependent regulation of the learning rule is necessary for memory encoding.

Computer Simulation↗

Decomposing EEG data into space-time-frequency components using Parallel Factor Analysis.

Finding the means to efficiently summarize electroencephalographic data has been a long-standing problem in electrophysiology. A popular approach is identification of component modes on the basis of the time-varying spectrum of multichannel EEG recordings--in other words, a space/frequency/time atomic decomposition of the time-varying EEG spectrum. Previous work has been limited to only two of these dimensions. Principal Component Analysis (PCA) and Independent Component Analysis (ICA) have been used to create space/time decompositions; suffering an inherent lack of uniqueness that is overcome only by imposing constraints of orthogonality or independence of atoms. Conventional frequency/time decompositions ignore the spatial aspects of the EEG. Framing of the data being as a three-way array indexed by channel, frequency, and time allows the application of a unique decomposition that is known as Parallel Factor Analysis (PARAFAC). Each atom is the tri-linear decomposition into a spatial, spectral, and temporal signature. We applied this decomposition to the EEG recordings of five subjects during the resting state and during mental arithmetic. Common to all subjects were two atoms with spectral signatures whose peaks were in the theta and alpha range. These signatures were modulated by physiological state, increasing during the resting stage for alpha and during mental arithmetic for theta. Furthermore, we describe a new method (Source Spectra Imaging or SSI) to estimate the location of electric current sources from the EEG spectrum. The topography of the theta atom is frontal and the maximum of the corresponding SSI solution is in the anterior frontal cortex. The topography of the alpha atom is occipital with maximum of the SSI solution in the visual cortex. We show that the proposed decomposition can be used to search for activity with a given spectral and topographic profile in new recordings, and that the method may be useful for artifact recognition and removal.

Alpha Rhythm↗

Frequency measuring system using mirror gap stabilized Fabry-Perot interferometer.

The mirror gap of a Fabry-Perot interferometer was stabilized with two laser diodes; one locked to the line frequency 385,243,555.14445 MHz of the F=3<--1 in 5D(3/2)<--5S(1/2) (87Rb) and the other to the 385,284,566.3663 MHz of the F=4<--2 in 5D(5/2)<--5S(1/2) (87Rb) [Opt. Commun. 102 (1993) 432]. The length of the mirror gap was adjusted to generate the zero-cross points simultaneously at both of the two line positions. The fringe signals obtained from an interferometer thus stabilized can be used as frequency markers having accuracies of the order of 10(10) depending on the finesse of the interferometer used. Based on measurement using Cs D1 hyperfine lines reported by Udem et al. [Phys. Rev. Lett. 82 (1999) 3568], the uncertainty of markers in the region 50 THz apart from the reference lines is +/- 5 MHz.

Data Interpretation, Statistical↗

Novel heat shock protein HspQ stimulates the degradation of mutant DnaA protein in Escherichia coli.

Escherichia coli DnaA protein initiates chromosomal replication and is an important regulatory target during the replication cycle. In this study, a suppressor mutation isolated by transposon mutagenesis was found to allow growth of the temperature-sensitive dnaA508 and dnaA167 mutants at 40 degrees C. The suppressor consists of a transposon insertion in a previously annotated ORF, here termed hspQ, a novel heat shock gene whose promoter is recognized by the major heat shock sigma factor sigma32. Expression of hspQ on a pBR322 derivative inhibits growth of the dnaA508 and dnaA167 mutants at 30 degrees C, whereas growth of dnaA46 and other dnaA mutants is insensitive to changes in the level of hspQ. Cellular DnaA508 protein is degraded rapidly at elevated temperature, but hspQ disruption impedes this process. In contrast, DnaA46 protein is rapidly degraded in an hspQ-independent manner. Gel-filtration and chemical cross-linking experiments suggest that HspQ forms a stable homodimer in solution and can form homomultimers consisting of about four monomers. Heat-shock induced proteases such as Clp contain homomultimers of subunit proteins. We propose that HspQ is a new factor involved in the quality control of proteins and that it functions by excluding denatured proteins.

Alleles↗

Synchronization of neural oscillations as a possible mechanism underlying episodic memory: a study of theta rhythm in the hippocampus.

Rat hippocampal cells exhibit characteristic phase-dependent firings when oscillation in frequency range around 8Hz is present. Based on the hypothesis that theta phase coding is generated by synchronization of neural activities, an autoassociative network model of the hippocampus and the entorhinal cortex was analyzed to explore mechanisms underlying episodic memory. Phase coding in theta rhythm enables instantaneous acquisition of experienced events including temporal and spatial contents. Further comparison with electrophysiological data from both rodents and primates suggests a possible role of theta oscillations in memory encoding and online processing of episodic events.

Action Potentials↗

Cognitive map formation through sequence encoding by theta phase precession.

The rodent hippocampus has been thought to represent the spatial environment as a cognitive map. The associative connections in the hippocampus imply that a neural entity represents the map as a geometrical network of hippocampal cells in terms of a chart. According to recent experimental observations, the cells fire successively relative to the theta oscillation of the local field potential, called theta phase precession, when the animal is running. This observation suggests the learning of temporal sequences with asymmetric connections in the hippocampus, but it also gives rather inconsistent implications on the formation of the chart that should consist of symmetric connections for space coding. In this study, we hypothesize that the chart is generated with theta phase coding through the integration of asymmetric connections. Our computer experiments use a hippocampal network model to demonstrate that a geometrical network is formed through running experiences in a few minutes. Asymmetric connections are found to remain and distribute heterogeneously in the network. The obtained network exhibits the spatial localization of activities at each instance as the chart does and their propagation that represents behavioral motions with multidirectional properties. We conclude that theta phase precession and the Hebbian rule with a time delay can provide the neural principles for learning the cognitive map.

Algorithms↗

The carboxyl terminal sequence of rat transporter associated with antigen processing (TAP)-like (ABCB9) is heterogeneous due to splicing of its mRNA.

Transporter associated with antigen processing (TAP)-like (TAPL) is a half-type ATP-binding cassette (ABC) transporter with sequence similarity to TAP1 and TAP2 and is highly conserved in mammals. Tissue distribution of the TAP family (TAP1, TAP2, TAPL) in rat was investigated using the semi quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). In young male rat, greater amounts of TAPL mRNA were detected in the brain and testis than in the thymus and intestine. On the other hand, both TAP1 and TAP2 mRNAs had higher expression in the thymus. Furthermore, the expression level of TAP1 in the intestine and that of TAP2 in the brain and testis were also high. Analysis of rat TAPL cDNAs demonstrated that the carboxyl terminal sequence of the ATP-binding region was heterogeneous. At least four different isoforms (C-I, -II, -III, -IV) could be produced by alternative splicing of mRNA, as was confirmed by a genomic data search. Both C-III and C-IV types had shorter carboxyl-terminal sequences, and the C-III had the shortest sequence. The functional heterogeneity of the carboxyl-terminal splicing variants of TAPL is discussed.

ATP-Binding Cassette Transporters↗

Ovarian teratoma with a formed lens and nonsuppurative inflammation in an old dog.

A 9-year, 7-month-old female German shepherd weighing 26.6 kg was admitted to the hospital for pica and diarrhea. A large mass was found in the right ovary and removed, and cross section of the mass revealed a multilobular tumor consisting of several cystic cavities which contained tufts of dark hair in thick creamy-white sebaceous fluid. Histologically, the tumor consisted of adipose tissue, central nervous tissue, crystalline lens, cartilage and bone. In the central nervous tissue, lens and lesions like nonsuppurative inflammation comprizing of accumulation of glial cells and lymphocytic perivascular cuffing were observed. The tumor was diagnosed as a mature cystic teratoma.

Adipose Tissue↗

Interisland evolution of Trimeresurus flavoviridis venom phospholipase A(2) isozymes.

Trimeresurus flavoviridis snakes inhabit the southwestern islands of Japan. A phospholipase A(2) (PLA(2)), named PL-Y, was isolated from Okinawa T. flavoviridis venom and its amino acid sequence was determined from both protein and cDNA. PL-Y was unable to induce edema. In contrast, PLA-B, a PLA(2) from Tokunoshima T. flavoviridis venom, which is different at only three positions from PL-Y, is known to induce edema. A new PLA(2), named PLA-B', which is similar to PLA-B, was cloned from Amami-Oshima T. flavoviridis venom gland. Three T. flavoviridis venom basic [Asp(49)]PLA(2) isozymes, PL-Y (Okinawa), PLA-B (Tokunoshima), and PLA-B' (Amami-Oshima), are identical in the N-terminal half but have one to four amino acid substitutions in the beta1-sheet and its vicinity. Such interisland sequence diversities among them are due to isolation in the different environments over 1 to 2 million years and appear to have been brought about by natural selection for point mutation in their genes. Otherwise, a major PLA(2), named PLA2, ubiquitously exists in the venoms of T. flavoviridis snakes from the three islands with one to three synonymous substitutions in their cDNAs. It is assumed that the PLA2 gene is a prototype among T. flavoviridis venom PLA(2) isozyme genes and has hardly undergone nonsynonymous mutation as a principal toxic component. Phylogenetic analysis based on the amino acid sequences revealed that T. flavoviridis PLA(2) isozymes are clearly separated into three groups, PLA2 type, basic [Asp(49)]PLA(2) type, and [Lys(49)]PLA(2) type. Basic [Asp(49)]PLA(2)-type isozymes may manifest their own particular toxic functions different from those of the isozymes of the PLA2 type and [Lys(49)]PLA(2) type.

Amino Acid Sequence↗

A theory of hippocampal memory based on theta phase precession.

The neural dynamics of the hippocampal network for memory encoding of novel temporal sequences is proposed based on the theta rhythm modulated firing of place cells called theta phase precession. It is hypothesized that theta phase precession is generated at the entorhinal cortex by phase locking between local field theta oscillation and neural oscillators and that the hippocampal closed network with feedforward and backward projections employ theta phase precession to create selectivity in the associative connections needed for temporal sequence storage. Our analyses and computer experiments reveal that the phase precession generated by phase locking instantaneously endows stable phase relations among neural activities in the successively changing neural population. It is concluded that theta phase precession provides biologically plausible dynamics for the memory encoding of novel temporal sequences as episodic events.

Animals↗

Memory encoding by theta phase precession in the hippocampal network.

Recent experimental evidence on spike-timing-dependent plasticity and on phase precession (i.e., the theta rhythm dependent firing of rat hippocampal cells) associates the contribution of phase precession to episodic memory. This article aims at clarifying the role of phase precession in memory storage. Computer simulations show that the memory storage in the behavioral timescale varies in timescale of the temporal sequence from half a second to several seconds. In contrast, the memory storage caused by traditional rate coding is restricted to the temporal sequence within 40 ms. During phase precession, memory storage of a single trial experience is possible, even in the presence of noise. It is therefore concluded that encoding by phase precession is appropriate for memory storage of the temporal sequence in the behavioral timescale.

Action Potentials↗

[Fit of electroformed porcelain-fused-to-metal crown on implant abutment].

This study compared the adaptation of a conventional and an electroformed porcelain-fused-to-metal crown. A master model was selected from an ITI implant with a solid abutment (height: 4 mm). Conventional cast metal frameworks of 0.7 mm thickness were prepared with a high noble metal alloy (Degudent U, Degussa) for porcelain fusing (n = 5). Electroformed frameworks of 0.2 mm thickness were determined using pure gold deposition on the abutment using the Auro-Galva-Crown system (AGC, Wieland) (n = 5). Subsequently, a porcelain (Super Porcelain AAA, Noritake) was fused to each framework. Internal gaps between the framework and its abutment were determined using the thickness of a silicone fit checking material. The gaps were measured both before and after porcelain fusing. The thicknesses of the silicone layer of the electroformed and the conventional porcelain-fused-to-metal crown were 34.6 and 38.5 microns at the margin, 33.2 and 39.6 microns at the internal slope, 22.0 and 33.0 microns at the axial, 58.6 and 65.1 microns at the occlusal, respectively. Three-way analysis of variance revealed that the mean gaps in the electroformed porcelain-fused-to-metal crown were significantly thinner than those in the conventional porcelain-fused-to-metal crown (p < 0.05). The electroformed porcelain-fused-to-metal crown showed better adaptability than the conventional porcelain-fused-to-metal crown regardless of porcelain fusing.

Crowns↗

A novel sustained-release formulation of insulin with dramatic reduction in initial rapid release.

To ensure a strictly controlled release of insulin, a preparation method for insulin-loaded microcapsules was designed. Microcapsules were prepared with an injectable, biodegradable polymer composed of co-poly(D,L-lactic/glycolic) acids (PLGA) (mean molecular weight 6600, LA/GA ratio 50:50). Morphological examination using scanning electron microphotography demonstrated spherical particles with a main diameter of 15-30 microm. When 3% insulin-loaded PLGA microcapsules were administered subcutaneously as a single dose (250 U/kg) to streptozotocin-induced hyperglycemic rats, plasma insulin levels increased and were sustained at levels showing hypoglycemic effects. When glycerin, ethanol, or distilled water was used throughout the preparation procedure, the resultant microcapsules dramatically reduced the initial burst. The formulation in which glycerin was added to an oil phase containing PLGA, insulin, and ZnO increased plasma insulin levels to 86.7, 108.4, and 84.9 microU/ml at 1, 2, and 6 h, respectively. The levels remained at 36.2-140.7 microU/ml from day 1 to day 9. The AUC(0-24 h)/AUC(0-336 h) ratio was calculated to be 9.7%. The formulation prepared without additives gave such a rapid insulin release that animals receiving it became transiently hypoglycemic.

Animals↗

Effectiveness of acupuncture and moxibustion treatment for lymphedema following intrapelvic lymph node dissection: a preliminary report.

Although it is difficult in Western medicine to eliminate edema occurring in the lower extremities after intrapelvic lymph node dissection for malignant gynecologic tumors, we successfully treated or prevented this postoperative complication with moxibustion and acupuncture, initiated after the occurrence of lymphedema in 12 patients and as soon as possible after surgery in 12 others. An increase in deep body temperature with acupuncture or moxibustion was found to be essential for successful treatment.

Acupuncture↗

Bimodality of theta phase precession in hippocampal place cells in freely running rats.

The firing of hippocampal principal cells in freely running rats exhibits a progressive phase retardation as the animal passes through a cell's "place" field. This "phase precession" is more complex than a simple linear shift of phase with position. In the present paper, phase precession is quantitatively analyzed by fitting multiple (1-3) normal probability density functions to the phase versus position distribution of spikes in rats making repeated traversals of the place fields. The parameters were estimated by the Expectation Maximization method. Three data sets including CA1 and DG place cells were analyzed. Although the phase-position distributions vary among different cells and regions, this complexity is well described by a superposition of two normal distribution functions, suggesting that the firing behavior consists of two components. This conclusion is supported by the existence of two distinct maxima in the mean spike density in the phase versus position plane. In one component, firing phase shifts over a range of about 180 degrees. The second component, which occurs near the end of the traversal of the place field, exhibits a low correlation between phase and position and is anti-phase with the phase-shift component. The functional implications of the two components are discussed with respect to their possible contribution to learning and memory mechanisms.

Algorithms↗

A novel insulin formulation can keep providing steady levels of insulin for much longer periods in-vivo.

We have recently succeeded in preparing insulin-loaded microcapsules that release the insulin in a strictly controlled manner with little initial rapid release in-vitro or in-vivo. We show here the superiority of the best formulation prepared with co-poly(D,L-lactic/glycolic) acids (PLGA) (mean MW 5800, L/G ratio 50:50) with a main diameter of 15 approximately 30 microm in-vivo. When 3.2 % insulin-loaded PLGA microcapsules were subcutaneously given as a single dose to streptozotocin-induced hyperglycaemic rats (250 U kg(-1)), plasma insulin levels gradually increased and constant levels (30.3-94.1 microU mL(-1)) were sustained. Rats receiving the formulation once a week showed not only steady plasma insulin levels, but also gained weight at a similar speed to normal rats. Meanwhile, daily treatment with Humulin U (25 U kg(-1)) caused a transient high insulin level (2723.9 microU mL(-1) at 1 h) in plasma, but the body weight of the rats was little changed. A pharmacological study in female Cynomolgus monkeys also revealed that the microcapsular formulation provided a flat release of insulin for longer periods and showed no immunogenic activity. In the near future, therefore, this insulin formulation could become very beneficial as a provider of basal insulin levels for insulin-dependent diabetic patients.

Animals↗