Publications by authors named "Kazutaka Suzuki"

25 Publications

  • Page 1 of 1

Sézary Syndrome with CD4/CD8 Double-Negative Neoplastic T Cells in Peripheral Blood.

Case Rep Hematol 2021 1;2021:5527725. Epub 2021 Jun 1.

Department of Hematology, Yokkaichi Municipal Hospital, 2-2-37 Shibata, Yokkaichi 510-8567, Japan.

Sézary syndrome is a rare leukemic type of cutaneous T-cell lymphoma characterized by the presence of neoplastic T cells with cerebriform nuclei (Sézary cells) in the skin, lymph nodes, and peripheral blood. Typical Sézary cells have a CD3CD4CD8 phenotype; however, in cases of the aberrant loss of antigens on Sézary cells, especially the loss of critically important T-cell antigens such as CD4, there is a possibility of misdiagnosing the disease or underestimating the tumor burden of the disease. Here, we report a rare case of Sézary syndrome with CD4/CD8 double-negative Sézary cells in the peripheral blood. Most of the Sézary cells in the peripheral blood had lost CD4 expression, and we diagnosed the disease and evaluated the tumor burden by multicolor flow cytometry. Intriguingly, the Sézary cells showed a typical CD4CD8CD7 phenotype in the skin even though the cells in the peripheral blood lacked CD4. The patient responded well to treatment with bexarotene and narrow-band ultraviolet B therapy. Analysis by multicolor flow cytometry is essential to diagnose this rare type of Sézary syndrome and evaluate the tumor burden.
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http://dx.doi.org/10.1155/2021/5527725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189774PMC
June 2021

Organophosphate Agent Induces ADHD-Like Behaviors via Inhibition of Brain Endocannabinoid-Hydrolyzing Enzyme(s) in Adolescent Male Rats.

J Agric Food Chem 2020 Feb 13;68(8):2547-2553. Epub 2020 Feb 13.

Department of Occupational and Environmental Health , Nagoya City University Graduate School of Medical Sciences , Nagoya 467-8601 , Japan.

Anticholinergic organophosphate (OP) agents act on the diverse serine hydrolases, thereby revealing unexpected biological effects. Epidemiological studies indicate a relationship between the OP exposure and development of attention-deficit/hyperactivity disorder (ADHD)-like symptoms, whereas no plausible mechanism for the OP-induced ADHD has been established. The present investigation employs ethyl octylphosphonofluoridate (EOPF) as an OP-probe, which is an extremely potent inhibitor of endocannabinoid (EC, anandamide and 2-arachidonoylglycerol)-hydrolyzing enzymes: that is, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). An ex vivo experiment shows that EOPF treatment decreases FAAH and MAGL activities and conversely increases EC levels in the rat brain. Subsequently, EOPF (treated intraperitoneally once at 0, 1, 2, or 3 mg/kg) clearly induces ADHD-like behaviors (in elevated plus-maze test) in both Wistar and spontaneously hypertensive rats. The EOPF-induced behaviors are reduced by a concomitant administration of cannabinoid receptor inverse agonist SLV-319. Accordingly, the EC system is a feasible target for OP-caused ADHD-like behaviors in adolescent rats.
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http://dx.doi.org/10.1021/acs.jafc.9b08195DOI Listing
February 2020

Influence of Percutaneous Occlusion of Atrial Septal Defect on Left Atrial Function Evaluated Using 2D Speckle Tracking Echocardiography.

Int Heart J 2020 Jan 17;61(1):83-88. Epub 2020 Jan 17.

Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences.

Percutaneous occlusion of atrial septal defect (ASD) has recently become a standard therapeutic strategy, but little is known about left atrial (LA) function thereafter. The present study aimed to determine LA function in 43 children with ASD and 13 controls based on LA strain measured by two-dimensional echocardiographic speckle tracking (2DE-ST). Among these children, 12 underwent surgery (ASD-S), 31 had device closure (ASD-D), and 13 were included as controls. LA strain was significantly decreased after ASD-D but was not significantly altered after ASD-S, indicating that percutaneous occlusion of an ASD might decrease LA function. Furthermore, the size of the ASD device negatively correlated with LA strain. These results imply that ASD occlusion devices negatively influence LA function and might be important when decided therapeutic strategies for ASD. LA strain measured by 2DE-ST should become a good indicator of LA function after ASD treatment in children.
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http://dx.doi.org/10.1536/ihj.19-173DOI Listing
January 2020

Prediction of postnatal clinical course in primary congenital dilated cardiomyopathy.

Pediatr Int 2019 Dec;61(12):1196-1201

Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Background: The aim of this study was to investigate the prediction of postnatal prognosis using fetal and perinatal data in patients with primary congenital dilated cardiomyopathy (PCDCM), and to estimate the incidence of this disease.

Methods: We examined correlations between fetal or perinatal data and postnatal clinical course in a multicenter retrospective study of eight patients with PCDCM. Incidence was calculated in a population-based study.

Results: All patients developed heart failure at a median of 8 days (range, 0-43 days), and six patients died or required extracorporeal artificial heart therapy at a median of 67 days (range, 0-92 days). The cardiothoracic area ratio from fetal echocardiography, the Apgar score, and the standard deviation of birth weight correlated significantly with the date at onset of heart failure. However, no data correlated with survival. Cumulative incidence of PCDCM was calculated as 1.21 per 100 000 total births (95% confidence interval, 0.37 to 2.06).

Conclusions: Primary congenital dilated cardiomyopathy has a poor prognosis, but cardiothoracic area ratio from fetal echocardiography, body weight at birth, and Apgar score correlate with the timing of the onset of heart failure, and these indicators might therefore be useful for peri- and postnatal management.
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http://dx.doi.org/10.1111/ped.14029DOI Listing
December 2019

Prognostic Risk Analyses for Postcardiotomy Extracorporeal Membrane Oxygenation in Children: A Review of Early and Intermediate Outcomes.

Pediatr Cardiol 2019 Jan 21;40(1):89-100. Epub 2018 Aug 21.

Department of Cardiovascular Surgery, Nagoya City University, Nagoya, Japan.

We evaluated the morbidity and mortality of children requiring postcardiotomy extracorporeal membrane oxygenation (ECMO) to determine independent factors affecting early and intermediate outcomes. Between January 2002 and December 2015, 79 instances of ECMO after cardiac surgery in 73 children were retrospectively reviewed. Follow-up was completed in December 2016. Predictive risk analyses were employed concerning weaning of ECMO, hospital discharge, and mortality after discharge. Age and weight were 14.9 ± 25.6 months and 7.0 ± 5.3 kg, respectively. Median support time was 8.3 ± 4.4 days. Sixty-seven (85%) were successfully weaned off ECMO and 48 (61%) survived to hospital discharge. Multi-variate logistic regression analysis identified the first day to obtain negative fluid balance after initiation of support (adjusted odds ratio = 0.42), high serum lactate levels (0.97), and high total bilirubin (0.84) during support as significant independent factors associated with successful separation from ECMO. The first day of negative fluid balance (0.65) after successful decannulation was an independent risk factor for survival to hospital discharge. After hospital discharge, actuarial 1-year, 5-year, and 10-year survival rates were 94%, 78%, and 78%, respectively. Low weight increased the risk of death after hospital discharge by a multi-variate Cox hazard model. High serum lactate, high serum bilirubin, and unable to obtain early negative fluid balance during support impacted mortality of decannulation. Obtaining a late negative fluid balance in post-ECMO were independent risk factors for death after successful weaning. Low weight affected intermediate outcomes.
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http://dx.doi.org/10.1007/s00246-018-1964-yDOI Listing
January 2019

Measurement of spontaneous blinks in patients with Parkinson's disease using a new high-speed blink analysis system.

J Neurol Sci 2017 Sep 29;380:200-204. Epub 2017 Jul 29.

Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Introduction: Parkinson's disease (PD) patients often have a blinking abnormality. In this study, we examined the kinematic features of spontaneous blinking in 65 PD patients and 62 healthy controls by a new research method utilizing an intelligent vision sensor camera prototype with a 1kHz sampling rate.

Methods: Spontaneous blinks were measured by use of a non-stress 'intelligent vision sensor' camera prototype.

Results: The mean spontaneous blink rate was 17.9 (blinks/min) in the PD patients and 15.6 in the controls (no correlation). However, there were extremely low and extremely high blink-rate groups among the PD patients. The amplitude of the closing and opening phase in the PD patients were significantly smaller than those in the controls. Small blink waves (100-200msec) prior to blink onset existed in 60% of the PD patients and in 18% of the controls.

Conclusion: During spontaneous blinking the blink amplitude is decreased, and the pause between the closing and opening phase is prolonged in patients with PD. Small blink waves prior to blink onset were also characteristically found in the PD patients.
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http://dx.doi.org/10.1016/j.jns.2017.07.035DOI Listing
September 2017

Fipronil application on rice paddy fields reduces densities of common skimmer and scarlet skimmer.

Sci Rep 2016 Mar 16;6:23055. Epub 2016 Mar 16.

National Institute for Environmental Studies, Onogawa 16-2, Tsukuba, Ibaraki 305-8506, Japan.

Several reports suggested that rice seedling nursery-box application of some systemic insecticides (neonicotinoids and fipronil) is the cause of the decline in dragonfly species noted since the 1990s in Japan. We conducted paddy mesocosm experiments to investigate the effect of the systemic insecticides clothianidin, fipronil and chlorantraniliprole on rice paddy field biological communities. Concentrations of all insecticides in the paddy water were reduced to the limit of detection within 3 months after application. However, residuals of these insecticides in the paddy soil were detected throughout the experimental period. Plankton species were affected by clothianidin and chlorantraniliprole right after the applications, but they recovered after the concentrations decreased. On the other hand, the effects of fipronil treatment, especially on Odonata, were larger than those of any other treatment. The number of adult dragonflies completing eclosion was severely decreased in the fipronil treatment. These results suggest that the accumulation of these insecticides in paddy soil reduces biodiversity by eliminating dragonfly nymphs, which occupy a high trophic level in paddy fields.
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http://dx.doi.org/10.1038/srep23055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4793285PMC
March 2016

Effects of tolvaptan on congestive heart failure complicated with chylothorax in a neonate.

Pediatr Int 2015 Oct 10;57(5):1020-2. Epub 2015 Sep 10.

Department of Pediatrics and Neonatology, Graduate School of Medical Sciences Nagoya City University, Nagoya, Japan.

Tolvaptan is an oral vasopressin type 2 receptor antagonist that can be used for heart failure patients with hyponatremia or symptomatic congestion. Although the effects of tolvaptan in adults have been well documented, only limited information is available in children. The case of a neonate with congestive heart failure complicated with chylothorax after palliative surgery for transposition of the great arteries treated with tolvaptan is reported. Slow up-titration to 0.1 mg/kg successfully increased urine output and improved refractory congestive heart failure without hypernatremia. Subsequently, bodyweight and chylothorax decreased gradually. Moreover, the use of tolvaptan reduced the dosage of furosemide. Tolvaptan could be an alternative drug for neonates with congestive heart failure. Further large studies are needed to confirm the efficacy and identify the appropriate dose of tolvaptan in neonates.
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http://dx.doi.org/10.1111/ped.12697DOI Listing
October 2015

Implicit Memory in Monkeys: Development of a Delay Eyeblink Conditioning System with Parallel Electromyographic and High-Speed Video Measurements.

PLoS One 2015 12;10(6):e0129828. Epub 2015 Jun 12.

Department of Neurobiophysics, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Sanuki, Kagawa, Japan.

Delay eyeblink conditioning, a cerebellum-dependent learning paradigm, has been applied to various mammalian species but not yet to monkeys. We therefore developed an accurate measuring system that we believe is the first system suitable for delay eyeblink conditioning in a monkey species (Macaca mulatta). Monkey eyeblinking was simultaneously monitored by orbicularis oculi electromyographic (OO-EMG) measurements and a high-speed camera-based tracking system built around a 1-kHz CMOS image sensor. A 1-kHz tone was the conditioned stimulus (CS), while an air puff (0.02 MPa) was the unconditioned stimulus. EMG analysis showed that the monkeys exhibited a conditioned response (CR) incidence of more than 60% of trials during the 5-day acquisition phase and an extinguished CR during the 2-day extinction phase. The camera system yielded similar results. Hence, we conclude that both methods are effective in evaluating monkey eyeblink conditioning. This system incorporating two different measuring principles enabled us to elucidate the relationship between the actual presence of eyelid closure and OO-EMG activity. An interesting finding permitted by the new system was that the monkeys frequently exhibited obvious CRs even when they produced visible facial signs of drowsiness or microsleep. Indeed, the probability of observing a CR in a given trial was not influenced by whether the monkeys closed their eyelids just before CS onset, suggesting that this memory could be expressed independently of wakefulness. This work presents a novel system for cognitive assessment in monkeys that will be useful for elucidating the neural mechanisms of implicit learning in nonhuman primates.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0129828PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4466547PMC
April 2016

Predicting the potential distribution of the amphibian pathogen Batrachochytrium dendrobatidis in East and Southeast Asia.

Dis Aquat Organ 2015 Apr;113(3):177-85

Invasive Alien Species Research Team, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506, Japan.

Batrachochytrium dendrobatidis (Bd) is the pathogen responsible for chytridiomycosis, a disease that is associated with a worldwide amphibian population decline. In this study, we predicted the potential distribution of Bd in East and Southeast Asia based on limited occurrence data. Our goal was to design an effective survey area where efforts to detect the pathogen can be focused. We generated ecological niche models using the maximum-entropy approach, with alleviation of multicollinearity and spatial autocorrelation. We applied eigenvector-based spatial filters as independent variables, in addition to environmental variables, to resolve spatial autocorrelation, and compared the model's accuracy and the degree of spatial autocorrelation with those of a model estimated using only environmental variables. We were able to identify areas of high suitability for Bd with accuracy. Among the environmental variables, factors related to temperature and precipitation were more effective in predicting the potential distribution of Bd than factors related to land use and cover type. Our study successfully predicted the potential distribution of Bd in East and Southeast Asia. This information should now be used to prioritize survey areas and generate a surveillance program to detect the pathogen.
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http://dx.doi.org/10.3354/dao02838DOI Listing
April 2015

Batrachochytrium dendrobatidis prevalence and haplotypes in domestic and imported pet amphibians in Japan.

Dis Aquat Organ 2014 May;109(2):165-75

Den-en-chofu Animal Hospital, 2-1-3 Denenchofu, Ota-ku, Tokyo 145-0071, Japan.

The international trade in amphibians is believed to have increased the spread of Batrachochytrium dendrobatidis (Bd), the fungal pathogen responsible for chytridiomycosis, which has caused a rapid decline in amphibian populations worldwide. We surveyed amphibians imported into Japan and those held in captivity for a long period or bred in Japan to clarify the Bd infection status. Samples were taken from 820 individuals of 109 amphibian species between 2008 and 2011 and were analyzed by a nested-PCR assay. Bd prevalence in imported amphibians was 10.3% (58/561), while it was 6.9% (18/259) in those in private collections and commercially bred amphibians in Japan. We identified the genotypes of this fungus using partial DNA sequences of the internal transcribed spacer (ITS) region. Sequencing of PCR products of all 76 Bd-positive samples revealed 11 haplotypes of the Bd ITS region. Haplotype A (DNA Data Bank of Japan accession number AB435211) was found in 90% (52/58) of imported amphibians. The results show that Bd is currently entering Japan via the international trade in exotic amphibians as pets, suggesting that the trade has indeed played a major role in the spread of Bd.
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http://dx.doi.org/10.3354/dao02732DOI Listing
May 2014

Batrachochytrium dendrobatidis haplotypes on the hellbender Cryptobranchus alleganiensis are identical to global strains.

Dis Aquat Organ 2013 Feb;102(3):181-6

Department of Natural Sciences, University of the Ryukyus, Nishihara, Okinawa, Japan.

To determine whether the chytrid fungus Batrachochytrium dendrobatidis (Bd) found on the hellbender Cryptobranchus alleganiensis in the southern US is endemic or exotic, we identified the genetic type of this fungus using partial DNA sequences of the internal transcribed spacer (ITS) region. We identified 3 genetic types, which are found on Japanese amphibians other than the Japanese giant salamander Andrias japonicus, a species that belongs to the same family (Cryptobranchidae) as hellbenders. The fungus collected from hellbenders exhibited low genetic diversity and matched the common Bd genetic types which have been detected from around the world. These results support that the chytrid fungus on the hellbender is a novel pathogen, as proposed by previous studies. Although we have not observed disease symptoms directly linked to this fungus on this endangered salamander, further evaluation of the influence of this exotic fungus on this species is warranted.
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http://dx.doi.org/10.3354/dao02561DOI Listing
February 2013

[Measurement of age-related changes in human blinks using a high-speed blink analysis system].

Nippon Ganka Gakkai Zasshi 2012 Sep;116(9):862-8

Department of Ophthalmology, Kyoto Prefectural University Graduate School of Medicine, Japan.

Purpose: To measure the spontaneous and voluntary blinks of both younger and older people using a new device that simplifies the detailed recording of eye blinking.

Methods: Fifty healthy volunteers (10 women and 15 men under 40 years of age, range: 22-38 years, and 20 women and 5 men above 60 years of age, range: 63-85 years) were examined after obtaining informed consent from each subject. Eyelid movements of all subjects were recorded using a high-speed blink analysis system. The spontaneous eye-blinks of the subjects were recorded during sessions consisting of a 40 seconds' period following which the subjects were instructed to blink as rapidly as possible for 5 seconds in which the blinks were again recorded. The upper lid position and movement data were plotted every millisecond by processing the recorded images.

Results: The frequency of the spontaneous blinks did not differ between the younger and older subjects. The women tended to blink more frequently in both age groups. The average amplitude and duration time of the spontaneous blinks in the younger subjects were greater than those in the older subjects. Voluntary blinks in the younger subjects were more frequent than in the older subjects. Women tended to make deeper and faster voluntary blinks.

Conclusion: Whereas the frequency of the voluntary blinks differed between the younger and older subjects, that of the spontaneous blinks did not differ. The findings of this study also revealed the gender-related differences in spontaneous and voluntary blinks.
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September 2012

Differences in susceptibility of five cladoceran species to two systemic insecticides, imidacloprid and fipronil.

Ecotoxicology 2012 Mar 5;21(2):421-7. Epub 2011 Oct 5.

National Institute for Environmental Studies (NIES), Tsukuba, Ibaraki, Japan.

Differences in susceptibility of five cladocerans to the neonicotinoid imidacloprid and the phenyl-pyrazole fipronil, which have been dominantly used in rice fields of Japan in recent years, were examined based on short-term (48-h), semi-static acute immobilization exposure tests. Additionally, we compared the species sensitivity distribution (SSD) patterns of both insecticides between two sets of species: the five tested cladocerans and all other aquatic organisms tested so far, using data from the ECOTOX database of U.S. Environmental Protection Agency (USEPA). The sensitivity of the test species to either imidacloprid or fipronil was consistent, spanning similar orders of magnitude (100 times). At the genus level, sensitivities to both insecticides were in the following descending order: Ceriodaphnia > Moina > Daphnia. A positive relationship was found between body lengths of each species and the acute toxicity (EC(50)) of the insecticides, in particular fipronil. Differences in SSD patterns of imidacloprid were found between the species groups compared, indicating that test cladocerans are much less susceptible than other aquatic species including amphibians, crustaceans, fish, insects, mollusks and worms. However, the SSD patterns for fipronil indicate no difference in sensitivity between cladocerans tested and other aquatic organisms despite the greater exposure, which overestimates the results, of our semi-static tests. From these results, Ceriodaphnia sp. should be considered as more sensitive bioindicators (instead of the standard Daphnia magna) for ecotoxicological assessments of aquatic ecosystems. In addition, we propose that ecotoxicity data associated with differences in susceptibility among species should be investigated whenever pesticides have different physicochemical properties and mode of action.
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http://dx.doi.org/10.1007/s10646-011-0802-2DOI Listing
March 2012

Treatment of spontaneous chytridiomycosis in captive amphibians using itraconazole.

J Vet Med Sci 2011 Feb 14;73(2):155-9. Epub 2010 Sep 14.

Den-en-chofu Animal Hospital, Otaku, Tokyo.

We performed this study in order to establish an effective, simple and safe treatment for chytridiomycosis. The subjects were 12 amphibians (11 anurans of 4 different species and 1 urodela) diagnosed with chytridiomycosis by clinical signs and a PCR test. A 0.01% aqueous solution of the antifungal agent itraconazole was used to treat the subjects, and we evaluated the efficacy of treatment by 3 methods: clinical signs, direct microscopy and a nested PCR test. A 10-min immersion in a 0.01% aqueous solution of itraconazole every other day for a total of 7 treatments resulted in an improvement of clinical signs in 11 of the 12 cases. Specifically, we observed an abatement of increased sloughing and disappearance of zoosporangia by direct microscopy. DNA fragments of Batrachochytrium dendrobatidis were not detected by a PCR test at the end of treatment, nor were they detected after treatment (20-57 days following treatment; average, 34.4 days). No recurrence was observed 12 months after the end of treatment, nor did we observe any obvious side effects from itraconazole. Therefore, we recommend this as a treatment method for chytridiomycosis and as an elimination technique for use in captive amphibians.
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http://dx.doi.org/10.1292/jvms.10-0261DOI Listing
February 2011

Amphibian chytridiomycosis in Japan: distribution, haplotypes and possible route of entry into Japan.

Mol Ecol 2009 Dec 13;18(23):4757-74. Epub 2009 Oct 13.

National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506, Japan.

A serious disease of amphibians caused by the chytrid fungus Batrachochytrium dendrobatidis was first found in Japan in December 2006 in imported pet frogs. This was the first report of chytridiomycosis in Asia. To assess the risk of pandemic chytridiomycosis to Japanese frogs, we surveyed the distribution of the fungus among captive and wild frog populations. We established a nested PCR assay that uses two pairs of PCR primers to amplify the internal transcribed spacer (ITS) region of a ribosomal RNA cassette to detect mild fungal infections from as little as 0.001 pg (1 fg) of B. dendrobatidis DNA. We collected swab samples from 265 amphibians sold at pet shops, 294 bred at institutes and 2103 collected at field sites from northern to southwestern Japan. We detected infections in native and exotic species, both in captivity and in the field. Sequencing of PCR products revealed 26 haplotypes of the B. dendrobatidis ITS region. Phylogenetic analysis showed that three of these haplotypes were specific to the Japanese giant salamander (Andrias japonicus) and appeared to have established a commensal relationship with this native amphibian. Many other haplotypes were carried by alien amphibians. The highest genetic diversity of B. dendrobatidis was found in the American bullfrog (Rana catesbeiana). Some strains of B. dendrobatidis appeared to be endemic to Japanese native amphibians, but many alien strains are being introduced into Japan via imported amphibians. To improve chytridiomycosis risk management, we must consider the risk of B. dendrobatidis changing hosts as a result of anthropogenic disturbance of the host-specific distribution of the fungus.
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http://dx.doi.org/10.1111/j.1365-294X.2009.04384.xDOI Listing
December 2009

[Measurement of spontaneous blinks with a high-speed blink analyzing system].

Nippon Ganka Gakkai Zasshi 2008 Dec;112(12):1059-67

NTT Kansai Health Administration Center, 2-6-40, Karasugatuji, Tennnouji-ku, Osaka 543-0042, Japan.

Purpose: In order to analyze spontaneous blink kinematics easily and circumstantially, we developed a new method using an intelligent vision system (IVS) camera with a 1 KHz sampling rate, and evaluated the efficacy of this system.

Method: Eleven healthy male volunteers were examined after obtaining informed consent. Eyelid movements in the primary eye position were recorded with an IVS camera twice, for 30 seconds each. Data of upper lid position and lid movement were plotted every 1 msec by image processing of the recorded images. Thereafter blink duration and maximum blink velocity in every spontaneous blink were calculated.

Results: Thirty-nine instances of complete lid-closure type and seventy of incomplete lid-closure type of spontaneous blinks were observed. The average duration of the down-phase, the up-phase, and the total blink were the same for both types; about 100 msec., 220 msec., and 320 msec. respectively. The average down-phase maximum velocity was about 180 mm/sec. in complete lid-closures and 120 mm/sec. in incomplete lid-closures. The average up-phase maximum velocity was about 60 mm/sec. in complete lid-closures and 45 mm/sec. in incomplete lid-closures. Blink amplitude and the maximum velocity achieved during lid closing and opening were strongly correlated and exhibited a linear relationship (r = 0.85, r = 0.73 p < 0.0001).

Conclusion: This new, non-invasive system is an easy to use measuring method for blink kinematics and is highly reliable and very useful.
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December 2008

Alcohol produces imbalance of adrenal and neuronal sympathetic activity in patients with alcohol-induced neurocardiogenic syncope.

Circ J 2008 Jun;72(6):979-85

Department of Cardiology, Surugadai Nihon University Hospital, Tokyo, Japan.

Background: The mechanism of alcohol-induced syncope is unknown.

Methods And Results: Head-up tilt tests (HUT: upright at 80 degrees for 30 min) were performed before and after alcohol consumption in 25 patients with unexplained syncope after drinking alcohol. Plasma levels of epinephrine (P-E) and norepinephrine (P-NE) were measured in a supine position and during HUT (at 15 min). Before drinking alcohol, HUT did not provoke neurocardiogenic syncope (NCS) in any of the 25 patients. After drinking alcohol, HUT provoked NCS in 11 patients (alcohol-positive or AP group) but not in 14 patients (alcohol-negative or AN group). Prior to alcohol consumption, P-E and P-NE increased during HUT in both groups, and did not differ significantly between the 2 groups. After alcohol consumption, P-E and P-NE increased during HUT in both group. During HUT, P-NE did not differ between the 2 groups, but P-E was significantly higher in the AP group than in the AN group during HUT (258.0+/-179.2 vs 70.9+/-35.1 pg/ml, p<0.05).

Conclusion: These results suggest that an imbalance in the increases of adrenomedullar sympathetic nerve activity (as expressed by the P-E level) and peripheral sympathetic nerve activity (as expressed by the P-NE level) both induced by alcohol, may play a crucial role in alcohol-induced NCS.
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http://dx.doi.org/10.1253/circj.72.979DOI Listing
June 2008

Basic autonomic nervous function in patients with neurocardiogenic syncope.

Clin Exp Hypertens 2007 Apr;29(3):165-73

Department of Cardiology, Surugadai Nihon University Hospital, Tokyo, Japan.

Basic autonomic nervous function was evaluated in patients with neurocardiogenic syncope (NCS). Atropine, isoproterenol, propranolol, phenylephrine, and phentolamine were administered successively, and parasympathetic nerve activity and beta- (and alpha-) activity, sensitivity, and secretion of the sympathetic nerve were determined in patients with NCS and control subjects. In patients with NCS, beta- and alpha- sensitivity were higher and beta-activity and beta- and alpha-secretion lower than in control subjects. In patients with NCS, the increased basic beta-sensitivity may contribute to induce strong cardiac contractions and augment ventricular mechanoreceptor response, and a compensatory state against diminished neuronal sympathetic activity is suggested by the increased alpha-sensitivity.
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http://dx.doi.org/10.1080/10641960701361569DOI Listing
April 2007

Pioglitazone-induced insulin sensitization improves vascular endothelial function in nondiabetic patients with essential hypertension.

Am J Hypertens 2005 Dec;18(12 Pt 1):1626-30

Division of Hypertension and Nephrology, Department of Medicine, National Cardiovascular Center, Suita, Japan.

Background: It has been suggested that insulin resistance is involved in the impaired vascular endothelial function not only in diabetic patients but also in hypertensive patients. The present study assessed the hypothesis that primary treatment of insulin resistance may reverse endothelial dysfunction in hypertensive subjects.

Methods: Fifteen nondiabetic patients with essential hypertension were enrolled in this study. An oral glucose tolerance test (OGTT) and insulin sensitivity test were performed. Insulin sensitivity was determined with the steady-state plasma glucose (SSPG) method. Only subjects with insulin resistance (SSPG > or =8.3 mmol/L) were included. Endothelium-dependent vasodilation during reactive hyperemia (flow-mediated dilation) was evaluated using ultrasonography. Six months after treatment with the insulin-sensitizing agent pioglitazone (30 mg/day), these examinations were repeated in all subjects.

Results: Pioglitazone did not decrease fasting plasma glucose and hemoglobin A1c (HbA1c) in the nondiabetic subjects, although the area under the curve for glucose and insulin on OGTT significantly decreased. A marked decrease in SSPG was observed after pioglitazone treatment (10.7 +/- 1.4 to 7.9 +/- 2.1 mmol/L, P < .001). Endothelium-dependent vasodilation evaluated by flow-mediated dilation was also improved by pioglitazone (5.0% +/- 2.2% to 6.3% +/- 2.4%, P = .023). Furthermore, the increase in flow-mediated dilation was closely correlated with the decrease in SSPG (r = 0.72, P = .002) but not with the decrease in area under the curve for glucose or insulin on OGTT. Endothelium-independent dilation induced by glyceryl trinitrate was not altered by pioglitazone.

Conclusions: The present findings demonstrate that pioglitazone improves endothelial function in nondiabetic hypertensive individuals with insulin resistance, and that the improvement is associated with the amelioration of insulin resistance itself rather than that of hyperglycemia or hyperinsulinemia.
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http://dx.doi.org/10.1016/j.amjhyper.2005.05.035DOI Listing
December 2005

Elevated aldosterone in amniotic fluid and maternal blood has diagnostic potential in pregnancies complicated with a fetus of Bartter syndrome.

Fetal Diagn Ther 2005 Nov-Dec;20(6):481-4

Department of Obstetrics and Gynecology, Nagoya City University Graduate School of Medicine, Nagoya, Japan.

Pregnancies with fetuses affected with the Bartter syndrome, an autosomal recessive disorder of hyperreninism and hyperaldosteronism, are complicated by early onset of polyhydramnios which results in preterm deliveries. We have assessed biochemical changes in amniotic fluid and the mother's blood with a view to early diagnosis. Aldosterone levels of both amniotic fluid and the mother's blood were found to be increased at 27 weeks of gestation, while electrolyte levels did not differ significantly from those reported earlier for controls. After birth the baby suffered from polyuria with hyponatremia, hypomagnesemia and hypercalciuria which could be controlled by treatment with sodium chloride and magnesium. Elevated aldosterone thus might be a useful marker for early diagnostic purposes.
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http://dx.doi.org/10.1159/000088035DOI Listing
January 2006

Pioglitazone improves left ventricular diastolic function in patients with essential hypertension.

Am J Hypertens 2005 Jul;18(7):949-57

Division of Hypertension and Nephrology, Department of Medicine, National Cardiovascular Center, Suita, Japan.

Background: Left ventricular (LV) hypertrophy and diastolic dysfunction, which are common cardiac consequences of hypertension, are modified by insulin resistance. The present study assessed the hypothesis that primary treatment of insulin resistance may reverse such cardiac changes in hypertensive patients.

Methods: A total of 30 patients with essential hypertension were enrolled in this study. In echocardiographic examinations, LV mass index, the peak velocity ratio of early diastolic to atrial filling (E/A), and the E-wave deceleration time (DcT) were determined. Insulin sensitivity test with steady-state plasma glucose (SSPG) method, oral glucose tolerance test, and blood samplings for measurement of adiponectin and matrix metalloproteinase (MMP)-2 were also performed. Six months after treatment with pioglitazone (30 mg/day), an insulin sensitizer, these examinations were repeated.

Results: Pioglitazone significantly increased E/A and decreased DcT, without a change in LV mass index. These improvements in diastolic properties were much greater in subjects with a marked (>or==3.3 mmol/L) decrease in SSPG (n=11) than the others (n=19), although the decrease in glucose levels did not differ between the two groups. In addition, the changes in E/A and DcT were closely correlated with the decrease in SSPG. Pioglitazone treatment significantly elevated plasma adiponectin and MMP-2 levels, and the increase in MMP-2 was positively correlated with the increase in adiponectin.

Conclusions: The present findings demonstrate that pioglitazone improves LV diastolic function without LV mass regression in hypertensive patients in proportion to the amelioration of insulin resistance. These findings suggest that increased adiponectin and MMP may be involved in the beneficial effect of pioglitazone on diastolic function.
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http://dx.doi.org/10.1016/j.amjhyper.2005.02.003DOI Listing
July 2005

Close association of endothelial dysfunction with insulin resistance and carotid wall thickening in hypertension.

Am J Hypertens 2004 Mar;17(3):228-32

Department of Gastroenterology and Metabolic Diseases, Osaka Prefectural General Hospital, 3-1-56 Mandai-higashi, Sumiyoshi-ku, Osaka 558-8558, Japan.

Background: Endothelial dysfunction has been regarded as an early stage in the atherosclerotic process. Endothelial dysfunction and insulin resistance were observed in hypertensive subjects and were associated with carotid wall thickening.

Methods: We examined the determinants of endothelial dysfunction including insulin sensitivity and carotid wall thickening. A total of 41 subjects with nondiabetic essential hypertension were studied. Endothelial function of brachial artery and carotid wall thickening were assessed noninvasively using ultrasound technique. In brachial artery, we measured flow-mediated endothelium-dependent vasodilation (FMD) and glyceryl trinitrate-induced endothelium-independent vasodilation (GTN). We estimated intima-media thickness of the common carotid artery (IMT). Insulin sensitivity was measured according to the steady-state plasma glucose (SSPG) method. High SSPG levels indicated insulin resistance.

Results: On univariate analysis, there were significant negative correlations between FMD and SSPG (r = -0.695, P <.0001) or IMT (r = -0.449, P <.004). The FMD was negatively correlated significantly with age and with systolic and diastolic blood pressures (BP). A significant negative correlation was observed between GTN and SSPG. There was a significant positive relation between SSPG and IMT. On multiple regression analysis including systolic BP, SSPG, and age as independent variables and FMD as a dependent variable, FMD was independently related to SSPG (P <.03) and systolic BP (P <.02). If the presence of SSPG, diastolic BP, and age were entered as independent variables against FMD, FMD was independently related to SSPG (P <.002).

Conclusions: One of the major determinants of endothelial function was insulin resistance. Our findings suggest that endothelial dysfunction and early structural vascular changes were related to insulin resistance.
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http://dx.doi.org/10.1016/j.amjhyper.2003.11.013DOI Listing
March 2004

Removal of estrogenic activities of 17beta-estradiol and ethinylestradiol by ligninolytic enzymes from white rot fungi.

Water Res 2003 Apr;37(8):1972-5

Department of Forest Resources Science, Faculty of Agriculture, Shizuoka University, Ohya 836, Japan.

We investigated whether manganese peroxidase (MnP) and the laccase-mediator system with 1-hydroxybenzotriazole (HBT) as mediator can remove the estrogenic activities of the steroidal hormones 17beta-estradiol (E(2)) and ethinylestradiol (EE(2)). Using the yeast two-hybrid assay system, we confirmed that the estrogenic activities of E(2) and EE(2) are much higher than those of bisphenol A and nonylphenol. Greater than 80% of the estrogenic activities of E(2) and EE(2) were removed following 1-h treatment with MnP or the laccase-HBT system; extending the treatment time to 8h removed the remaining estrogenic activity of both steroidal hormones. HPLC analysis demonstrated that E(2) and EE(2) had disappeared almost completely in the reaction mixture after a 1-h treatment. These results strongly suggest that these ligninolytic enzymes are effective in removing the estrogenic activities of E(2) and EE(2).
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http://dx.doi.org/10.1016/S0043-1354(02)00533-XDOI Listing
April 2003

Multifactorial insulin resistance and clinical impact in hypertension and cardiovascular diseases.

J Diabetes Complications 2002 Jan-Feb;16(1):19-23

Koshien University College of Nutrition, 10-1, Momijigaoka, Hyogo, Takarazuka, Japan.

Insulin resistance and hyperinsulinemia have been observed in over 70% of the nonobese, nondiabetic subjects with essential hypertension (HT). Alpha-1 blockers, ACE-antagonists, long-acting Ca blockers including nifedipine CR, some form of beta-blockers, tilisolor, which is reported to increase blood flow, improve insulin sensitivity when blood pressure is better controlled. Decrease of serum potassium during insulin sensitivity test and intraplatelet free Ca2+ concentration is positively and negatively correlated with insulin sensitivity, respectively. Blood pressure is correlated with insulin resistance, which is also observed in secondary HT. The resistance is correlated with salt sensitivity as well as impaired nocturnal fall of blood pressure. These suggest the possible association of insulin resistance with altered intracellular cation metabolism. Insulin resistance and associated hyperinsulinemia have been observed in effort as well as vasospastic angina pectoris (VSAP), atherothrombotic cerebral infarction, and in ASO without obesity, HT, or diabetes, suggesting the resistance resulting from endothelial dysfunction. Insulin resistance has been observed in heart failure and is correlated with angiotensin II. Resistance is also observed in hypertrophic cardiomyopathy and is partially correlated with TNF-alpha. These results indicate that insulin resistance seem to be multifactorial. An effort to normalize insulin sensitivity is crucial to eliminate multiple risk factors as well as to prevent the progression of atherosclerotic vascular lesions.
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http://dx.doi.org/10.1016/s1056-8727(01)00192-1DOI Listing
May 2002
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