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Biomedical subjects

Masashi Sakai

Publications and source records attributed to Masashi Sakai.

At least 19 recordsLinked to original sources
PubMed2007

A possible relationship of nocturnal blood pressure variability with coronary artery disease in diabetic nephropathy.

Evidence suggests a relationship between short-term blood pressure (BP) variability and cardiovascular target-organ damage. Although a blunted nocturnal decrease in BP and reduced heart rate variability have been shown to be associated with cardiovascular morbidity in diabetic patients, little information is available on short-term BP variability. In this study, short-term BP variability was assessed in 36 subjects with type 2 diabetes and overt nephropathy who underwent ambulatory BP monitoring, and the factors that correlated with short-term BP variability were examined. The incidence of coronary artery disease (CAD) was significantly greater in the patients with increased 24-h systolic BP variability (67% versus 11%; p < 0.0005), while that of cerebrovascular disease was not significantly affected (61% versus 50%). Multiple stepwise regression analysis revealed that serum cholesterol (cholesterol) and plasma norepinephrine (p-NE) were significant and independent contributors to nighttime systolic BP variability (partial R2 = 0.490, p < 0.001; partial R2 = 0.470, p < 0.001) and demonstrated that body mass index and p-NE were primary determinants of nighttime diastolic BP variability (partial R2 = 0.539, p < 0.0005; partial R2 = 0.304, p < 0.05). Diabetic nephropathy patients with CAD had significantly increased daytime systolic (17.8 mmHg versus 13.1 mmHg, p < 0.0005), nighttime systolic (17.4 mmHg versus 10.5 mmHg, p < 0.0001), and nighttime diastolic (10.4 mmHg versus 7.2 mmHg, p < 0.05) BP variability. Furthermore, logistic regression analysis demonstrated that nighttime systolic BP variability was an independent risk factor for CAD (odds ratio 3.13 [95% CI 1.02-9.61]; p < 0.05). The increase in nighttime BP variability is associated with a proportional sympathetic activation in diabetic nephropathy. Elevated short-term BP variability combined with relative sympathetic prevalence during the night might represent an important risk factor for cardiovascular events in the diabetic population.

Aged↗
PubMed2006

Constraints on decay of environmental sound memory in adult rats.

When adult rats are pretreated with a 48-h-long 'repetitive nonreinforced sound exposure', performance in two-sound discriminative operant conditioning transiently improves. We have already proven that this 'sound exposure-enhanced discrimination' is dependent upon enhancement of the perceptual capacity of the auditory cortex. This study investigated principles governing decay of sound exposure-enhanced discrimination decay. Sound exposure-enhanced discrimination disappeared within approximately 72 h if animals were deprived of environmental sounds after sound exposure, and that shortened to less than approximately 60 h if they were exposed to environmental sounds in the animal room. Sound-deprivation itself exerted no clear effects. These findings suggest that the memory of a passively exposed behaviorally irrelevant sound signal does not merely pass along the intrinsic lifetime but also gets deteriorated by other incoming signals.

Acoustic Stimulation↗
PubMed2006

Constitutive expression of catABC genes in the aniline-assimilating bacterium Rhodococcus species AN-22: production, purification, characterization and gene analysis of CatA, CatB and CatC.

The aniline-assimilating bacterium Rhodococcus sp. AN-22 was found to constitutively synthesize CatB (cis,cis-muconate cycloisomerase) and CatC (muconolactone isomerase) in its cells growing on non-aromatic substrates, in addition to the previously reported CatA (catechol 1,2-dioxygenase). The bacterium maintained the specific activity of the three enzymes at an almost equal level during cultivation on succinate. CatB and CatC were purified to homogeneity and characterized. CatB was a monomer with a molecular mass of 44 kDa. The enzyme was activated by Mn2+, Co2+ and Mg2+. Native CatC was a homo-octamer with a molecular mass of 100 kDa. The enzyme was stable between pH 7.0 and 10.5 and was resistant to heating up to 90 degrees C. Genes coding for CatA, CatB and CatC were cloned and named catA, catB and catC respectively. The catABC genes were transcribed as one operon. The deduced amino acid sequences of CatA, CatB and CatC showed high identities with those from other Gram-positive micro-organisms. A regulator gene such as catR encoding a regulatory protein was not observed around the cat gene cluster of Rhodococcus sp. AN-22, but a possible relic of catR was found in the upstream region of catA. Reverse transcriptase-PCR and primer extension analyses showed that the transcriptional start site of the cat gene cluster was located 891 bp upstream of the catA initiation codon in the AN-22 strain growing on both aniline and succinate. Based on these data, we concluded that the bacterium constitutively transcribed the catABC genes and translated its mRNA into CatA, CatB and CatC.

Aniline Compounds↗
PubMed2005

Transcriptional diversity and expression of NEDD4L gene in distal nephron.

The ubiquitin ligase NEDD4L participates in plasma volume and blood pressure regulation by controlling expression of the epithelial sodium channel (ENaC). Genetic impairment of EnaC-Nedd4L-Proteasome system caused a rare mendelian hereditary human hypertension, Liddle syndrome. This finding suggested that Nedd4L is playing an important role in pathogenesis for hypertensive disorders. This prompted us to test a possible involvement of NEDD4L for the development of sodium-sensitive hypertension in Dahl salt-sensitive (DS) rats and its normotensive littermate Dahl salt-resistant (DR) rats. First, we analyzed the transcriptional diversity of rat Nedd4L gene and observed several isoforms with and without calcium-dependent membrane binding (C2) domain at the N-terminal of the protein as we found in human and mouse before. Then, we analyzed the expression of rat NEDD4L in the kidney of both DS and DR under high and low sodium regimens. NEDD4L expression examined by quantitative PCR technique revealed lower expression of NEDD4L transcripts in DS rats under either diet compared to DR animals; additionally, NEDD4L expression was significantly increased with sodium loading. Using in situ hybridization experiments, rat NEDD4L was predominantly expressed in distal nephron in a manner dependent on both sodium regimen and genetic background. A similar histological distribution pattern was observed in human kidney. The expression of NEDD4L in distal nephron and its response to chronic sodium loading suggest that it participates in the functioning of this segment in sodium reabsorption. This response was impaired in genetically sodium-sensitive animals. These findings suggested that Nedd4L gene products were involved in the development of salt-sensitive hypertension.

Adrenal Glands↗
PubMed2005

Enhanced learning of normal adult rodents by repeated oral administration of soybean transphosphatidylated phosphatidylserine.

Soybean lecithin transphosphatidylated phosphatidylserine (SB-tPS) is already known to improve the learning ability of aged or drug-induced amnesic rodents. In this study, its effect on normal adult rodents was evaluated using several learning tasks. Firstly, three behavioral tests (open-field, Y-maze, and active avoidance test) were consecutively carried out after the daily oral administration of SB-tPS (50 mg/kg per day, for 34 days). Repeated oral administration of SB-tPS did not affect either exploratory behavior in the open-field test or spontaneous alternation behavior in the Y-maze test, while mice pretreated with SB-tPS showed significant enhancement of conditioned avoidance response. Secondly, the brightness discrimination test was used to evaluate the effect of SB-tPS on learning ability. The daily oral administration of SB-tPS (50 mg/kg per day, for 27 days) to normal rats significantly increased the correct response ratio in the brightness discrimination test. Finally, to elucidate the necessity of SB-tPS pretreatment, another active avoidance test was carried out, and no enhancement of conditioned avoidance response was observed in non-pretreated mice. These results suggest that repeated administration of SB-tPS could enhance the learning ability of normal adult rodents as those of aged ones.

Acetylcholine↗
PubMed2005

The novel angiotensin II type 1 receptor (AT1R)-associated protein ATRAP downregulates AT1R and ameliorates cardiomyocyte hypertrophy.

Activation of angiotensin II (Ang II) type 1 receptor (AT1R) signaling is reported to play an important role in cardiac hypertrophy. We previously cloned a novel molecule interacting with the AT1R, which we named ATRAP (for Ang II type 1 receptor-associated protein). Here, we report that overexpression of ATRAP significantly decreases the number of AT1R on the surface of cardiomyocytes, and also decreases the degree of p38 mitogen-activated protein kinase phosphorylation, the activity of the c-fos promoter and protein synthesis upon Ang II treatment. These results indicate that ATRAP significantly promotes downregulation of the AT1R and further attenuates certain Ang II-mediated hypertrophic responses in cardiomyocytes.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Heparin recovers AT1 receptor and its intracellular signal transduction in cultured vascular smooth muscle cells.

Although vascular smooth muscle cells (VSMCs) are widely used in cardiovascular research, their phenotypic change under various culture conditions is problematic to evaluate the experimental results obtained. The levels of angiotensin (Ang) type 1/2 (AT1/AT2) receptors as well as contractile and structural proteins are degraded through culture passages. The present study demonstrated that heparin recovered Ang receptors and differentiation markers, such as desmin, SM-22 and smooth muscle alpha-actin in VSMCs at the ninth passage. Heparin also potenciated Ang II-induced activation for ERK1/2 and p38. These results suggest a potential value of heparin-treated VSMCs as the model for analysis of Ang-mediated signal transduction under physiological condition.

Actins↗
PubMed2005

Characteristics of sound discrimination enhancement after sound exposure in adult rats.

The auditory perceptual capacity of adult rats was assessed with regard to performance during 2-sound-discriminative operant conditioning. If the animals were passively exposed to a sound stimulus before the conditioning, performance was improved (sound-exposure-enhanced discrimination [SED]). SED had a stimulus specificity that could not be predicted in terms of the cochleotopy. SED was obstructed by D-2-amino-5-phosphonovaleric acid, an antagonist of N-methyl-D-aspartate receptors, infused into the auditory cortex (AC). No evidence supported the hypothesis that SED was due to a change of attention or motivation or to interference in the association process (e.g., latent inhibition). These findings suggest that passive auditory experience can enhance the perceptual capacity of an adult rat's AC.

2-Amino-5-phosphonovalerate↗
PubMed2005

[Recurrence of esophageal cancer treated by combination TS-1/CDDP therapy].

A 68-year-old man underwent subtotal esophagectomy with two fields lymphadenectomy and postoperative chemotherapy so called low dose FP therapy for advanced esophageal cancer (Stage IIIa, pT 3, pN 1, M 0) in October 1999. As he was diagnosed with a recurrence of esophageal cancer as metastatic lymph node tumors which were placed in the right anterocervical and supraclavicular region in March 2001, he underwent enucleation of metastatic lymph node tumors and postoperative chemoradiation therapy, so-called low-dose FP-R therapy. Recently, since other metastatic lymph node tumors in the neck appeared again in August 2001, he underwent radical neck lymph node dissection and postoperative chemoradiation treatment, so-called FAP-R therapy. In October 2003, a chest CT showed multiple lung tumors. He was diagnosed with multiple metastatic lung tumors originating from esophageal cancer. Then, two courses of a combined chemotherapy consisting of TS-1 and CDDP were administered at an interval of one month. We judged the effect of this chemotherapy to be a partial response (PR), because the largest metastatic lung tumor 18 mm in diameter showed a reduction rate of 81.9%, and other tumors had almost disappeared in the chest CT after the combined therapy. No severe adverse effects of more than grade 3 were observed during this combined therapy. This combined chemotherapy consisting of TS-1 and CDDP may prove effective for treating recurrent cases of esophageal cancer.

Aged↗
PubMed2004

Interaction of excitatory and inhibitory frequency-receptive fields in determining fundamental frequency sensitivity of primary auditory cortex neurons in awake cats.

Harmonic complex tones produce pitch-height perception corresponding to the fundamental frequency (F0). This study investigates how the spectral cue of F0 is processed in neurons of the primary auditory cortex (A1) with sustained-response properties. We found F0-sensitive and -insensitive cells: the former discriminated between harmonics and noise, while the latter did not. F0-sensitive cells preferred F0s corresponding to the best frequency (BF) and 0.5 x BF. The F0-sensitivity to F0=0.5 x BF was preserved for missing F0, but abolished by eliminating both F0 and the second harmonic. The inhibitory subfield of the frequency-receptive field was restricted to the spectral region between the preferred harmonics in F0-sensitive cells, while it was frequency unspecific in F0-insensitive cells. We conclude that (i) A1 is well organized for discrimination between harmonics and noise; (ii) pitch-height is represented along with the tonotopic axis; (iii) all aspects of the sustained neural responses to harmonic and noise stimuli are consequences of spectral filtering; and (iv) although the observed cell behavior explains some psychophysical pitch perception behaviors, such as pitch-chroma (helical pitch perception with frequency elevation), pitch-level tolerance and adaptive behavior, F0-encoding in A1 remains at the incomplete perceptual level (dominance of the third to fifth harmonics for pitch strength is unexplainable by the cell behavior).

Acoustic Stimulation↗
PubMed2004

Spectral-shape preference of primary auditory cortex neurons in awake cats.

The study of the influence of spectral envelopes of complex tones on cortical neuron discharges is important with respect to understanding the formant processing of vowels. That the sharpness of formants can contribute to the vowel quality has previously been shown in psychophysical experiments. However, it is unknown how this parameter is reflected by cortical neuron discharges, especially when a formant falls into different portions of the neuronal frequency receptive field (FRF). To show this is the aim of this study focusing on the sustained discharging neurons in the low frequency portion of cat primary auditory cortex (A1). The stimuli were multi-frequency tones whose spectral envelope was sinusoidally modulated with a peak fixed at a neuron's best frequency. The modulation depth, defined as damping-amplitude (DA), varied systematically. Stimulus bandwidth also varied systematically. Large DA at off-center frequencies produces a prominent spectral peak with steep slope, whereas small DA has a less well-defined spectral peak with gentle slope. Single frequency and two tone stimuli served to delineate the excitatory and inhibitory subfields of FRF. The A1 neuron preferred large DA when the sound energy fell into FRF with the relatively large inhibitory-subfield, while the same cell preferred small DA when it fell into FRF with the relatively small inhibitory-subfield. It is concluded that the A1 neuron can estimate steepness of slope of a spectral peak, and that a preference for steep slopes stems from a shift of balance toward the spectral inhibition, whereas a preference for gentle slopes, toward the spectral excitation.

Acoustic Stimulation↗
PubMed2004

Nuclear receptor LXRalpha is involved in cAMP-mediated human renin gene expression.

The cAMP-signaling pathway plays a crucial role in the regulation of the renin gene, but the mechanism involved remains poorly understood. We have focused our studies of renin gene regulation on the unique cAMP responsive element (huREN/CNRE, -135 to -107) in the human renin promoter. We have cloned a protein that binds to this unique CNRE and demonstrated that this protein is liver X receptor-alpha (LXRalpha), a transcriptional factor of the nuclear receptor family. Transient expression of LXRalpha in human renin-producing Calu-6 cells increased cAMP inducibility of human renin promoter. Similarly, LXRalpha-stably transfected Calu-6 cells exhibited increased cAMP inducibility of renin promoter as well as the endogenous renin gene. Site-directed mutation of huREN/CNRE, which disrupted LXRalpha binding, decreased cAMP-induced transcriptional activity of human renin promoter. Furthermore, we demonstrated that the binding of LXRalpha derived from human juxtaglomerular cells, the main production site of renin in the kidney, to the huREN/CNRE in vivo. These results suggest that LXRalpha plays an important role in the cAMP-mediated regulation of human renin gene transcription by binding to CNRE.

Cell Line↗
PubMed2004

Spectral-edge sensitivity of primary auditory cortex neurons in alert cats.

Although psychophysical studies have revealed involvement of spectral edges in auditory perception, little is known about neural processing. This study investigates how spectral edges are processed in neurons of alert cat primary-auditory-cortex (A1) with sustained response property. Stimuli are low-pass, high-pass and band-pass tones with sharp spectral edges whose edge-frequencies were systematically shifted, constructing edge-frequency response functions. Pure- and two-tone stimuli served to delineate excitatory and inhibitory subfields of the frequency response field (FRF). Based on the response function characteristics, cells were divided into edge-sensitive and edge-insensitive cells: the edge sensitive cells had narrow tuning to the high-edge (type-II cells) or low-edge (type-III cells) frequencies, while the edge insensitive cells were driven by any static stimuli with energy on FRF (type-I) or only very narrowband stimuli with energy confined to FRF (type-IV cells). Edge-sensitive cells showed a close correlation between the best frequencies of the single-frequency (BFSF) and edge-frequency (BFEF) response functions and between their half-height bandwidths, suggesting that the edge-frequency identification is processed along the tonotopic axis in A1. BFSF shifted (mean 0.11 octaves) into the stimulus band from the BFEF (closely corresponding to pitch shift into stimulus band from the edge frequency in human psychophysical data of edge-pitch), suggesting central mechanism of edge-pitch sensation. Type-I cells had non-significant inhibitory subfields of FRF; type-II cells had the significant inhibitory subfield on the higher frequency side; type-III cells, on the lower frequency side; and type-IV cells, on both sides, suggesting that the inhibitory mechanism characterizes the cell-type specific spectral-edge sensitivity.

Animals↗
PubMed2003

Acute renal failure due to cholesterol crystal embolism treated with LDL apheresis followed by corticosteroid and candesartan.

Cholesterol crystal embolism (CCE) is caused by the shedding of cholesterol crystals into the bloodstream, and it has been recently recognized as a serious complication after vascular procedures. Our case of CCE, which was diagnosed by skin and renal biopsies, occurred in a patient with hypertension and diabetes mellitus, 3 months after coronary angiography, with the development of renal failure and blue toes. After low-density lipoprotein apheresis (LDL-A), the skin lesions, including livedo reticularis and pain from the acrocyanotic toes, dramatically improved, with partial recovery of renal function. Following the administration of low-dose corticosteroid and candesartan--an angiotensin II type 1 receptor antagonist (ARB)--the eosinophilia disappeared and renal function improved gradually with a decrease in urinary protein excretion. Therefore, a combination therapy of LDL-A, low-dose corticosteroid, and an ARB is a possible treatment for CCE, although the possibility of spontaneous recovery of renal function cannot be eliminated for this patient.

Acute Kidney Injury↗
PubMed2002

Centripetal and centrifugal reorganizations of frequency map of auditory cortex in gerbils.

As repetitive acoustic stimulation and auditory conditioning do, electric stimulation of the primary auditory cortex (AI) evokes reorganization of the frequency map of AI, as well as of the subcortical auditory nuclei. The reorganization is caused by shifts in best frequencies (BFs) of neurons either toward (centripetal) or away from (centrifugal) the BF of stimulated cortical neurons. In AI of the Mongolian gerbil, we found that focal electrical stimulation evoked a centripetal BF shift in an elliptical area centered at the stimulated neurons and a centrifugal BF shift in a zone surrounding it. The 1.9-mm long major and 1.1-mm long minor axes of the elliptical area were parallel and orthogonal to the frequency axis, respectively. The width of the surrounding zone was 0.2-0.3 mm. Such "center-surround" reorganization has not yet been found in any sensory cortex except AI of the gerbil. The ellipse is similar to the arborization pattern of pyramidal neurons, the major source of excitatory horizontal connections in AI, whereas the surrounding zone is compatible to the arborization range of small basket cells (inhibitory neurons) in AI.

Animals↗
PubMed2002

Differential dependence of LTD on glutamate receptors in the auditory cortical synapses of cortical and thalamic inputs.

Pyramidal neurons in the auditory cortex (AC) receive glutamatergic inputs from the medial geniculate body (MGB inputs) and other pyramidal neurons (pyramidal inputs). We found that the induction of long-term depression (LTD) in supragranular layers was only partially suppressed by 50 microM D-(-)-2-amino-5-phosphonovalerate (APV), an antagonist of N-methyl-D-aspartate (NMDA) receptors (NMDARs), and 500 microM (+)-alpha-methyl-4-carboxyphenylglycine (MCPG), an antagonist of metabotropic glutamate receptors (mGluRs). However, LTD was not observed in the mixture of APV and MCPG. We hypothesized that the mixed dependence of LTD on glutamate receptors could be attributed to the heterogeneity of MGB inputs and pyramidal inputs. To test this hypothesis, the angle of slicing and other recording conditions were adjusted so that postsynaptic potentials were recorded in normal slices, but not in the slices prepared from the rats with MGB lesion. In these experiments, LTD was suppressed by MCPG alone. The conditions were adjusted to minimize the contribution of MGB inputs in field potentials. In these experiments, the induction of LTD was suppressed by APV alone. Interestingly, the induction of LTD was partially suppressed by 20 microM nifedipine, a blocker of L-type Ca(2+) channels, in the slices prepared from the rats with MGB lesions, but not in normal slices. These findings suggest that the induction of LTD requires activation of mGluRs in the synapses of MGB inputs and of NMDARs in the synapses of pyramidal inputs.

Action Potentials↗