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Biomedical subjects

Kenji Nakai

Publications and source records attributed to Kenji Nakai.

13 recordsLinked to original sources

Condition known as "dark rings under the eyes" in the Japanese population is a kind of dermal melanocytosis which can be successfully treated by Q-switched ruby laser.

BACKGROUND: In general, dark rings under the eyes are believed to be a phenomenon caused mainly by physiological change because of their daily fluctuation. Medically speaking, the precise cause or pathogenesis of dark rings is unknown, and this condition has not been clearly defined. In our experience, the dark rings associated with conventional nevus of Ota can be successfully treated with Q-switched ruby laser (QSRL). OBJECTIVE: This study was conducted to clarify the nature of dark rings under the eyes and to determine the efficacy of QSRL. PATIENTS AND METHODS: Fifty-four patients who received a biopsy for pigment macules of the face were retrieved, and of that number 12 patients with bilateral homogeneous pigment macule on suborbital regions were selected for study of the dark rings. Of those patients, the histology and the efficacy of QSRL were evaluated retrospectively. RESULTS: Histologically, all 12 patients indicated dermal melanocytosis, which was confirmed by the Masson-Fontana silver stain and staining against S100. In five patients who received QSRL therapy two times or more, the clinical improvement of two patients was scored as good (40-69%), and two other patients as excellent (>70% clearance). CONCLUSIONS: We speculate that so-called dark rings under the eyes in the Japanese population is a kind of dermal melanocytosis which can be successfully treated by QSRL.

Biopsy↗

Risk factors for development of pre-diabetic state from normal glucose regulation.

As a strategy to prevent the progression of diabetes mellitus, it is important to screen out the subjects who will develop a pre-diabetic state (PDS) in the future. To find out the potential risk factors for PDS, we employed the values of fasting plasma glucose and hemoglobin A1c (HbA1c), which are routinely measured in our health checkup. We selected 3,879 individuals who had normal glucose regulation at both fasting plasma glucose < 6.1 mmol/l and HbA1c < 5.5% in 1997 and investigated whether they would develop PDS in the next 5 years. PDS is defined at fasting plasma glucose >or= 6.1 mmol/l and HbA1c >or= 5.5%. Among 3,879 individuals, 21 developed PDS and 2,128 maintained normal glucose regulation in 2001. The remaining 1,730 subjects fit one of the two criteria for PDS. The parameters measured in 1997, including fasting plasma glucose, HbA1c, triglyceride, alanine aminotransferase, gamma-glutamyltranspeptidas, cholinesterase, uric acid, red blood cells, hemoglobin, percent body fat and diastolic blood pressure, were significantly higher in the individuals who developed PDS than in those who maintained normal glucose regulation. On the other hand, hematocrit was significantly lower in PDS than in normal glucose regulation. Logistic regression analysis identified alanine aminotransferase >or= 40 U/l, triglyceride >or= 1.69 mmol/l, low-density lipoprotein cholesterol >or= 3.62 mmol/l and hematocrit < 38% as valuable factors for predicting the development of PDS. The present study demonstrates that the subjects with high risks for PDS could be identified from several clinical parameters and that they should be encouraged to improve their living habits not to develop diabetes mellitus.

Alanine Transaminase↗

[Development of 64-channel magnetocardiography and clinical application].

A magnetocardiogram (MCG) can detect three-dimensional electric phenomena of the heart, because MCG does not influence the lung and torso form of the internal organs. In this symposium, we report the application of 64-channel MCG for the measurement of various arrhythmias (atrial flutter, atrial fibrillation), myocardial injury, and fetus arrhythmia. We composed function images of the conduction wave front and injured myocardium superimposed on a three-dimensional heart outline from the magnetic field. The injured myocardium was determined by a three-dimensional RT dispersion map. This algorithm allows the non-invasive determination of the space location of signal source and injured myocardium. In addition, 64-channel MCG can detect the fetal arrhythmias and autonomic nervous activity, which allows the diagnosis of fetus arrhythmia in detail before birth. Thus, MCG measurement is a useful non-invasive diagnostics procedure. However, there are several problems such as sealed room installation and the use of liquid helium. In the future, a newer technology that does not require liquid helium and a sealed room will be necessory.

Arrhythmias, Cardiac↗

Three-dimensional recovery time dispersion map by 64-channel magnetocardiography may demonstrate the location of a myocardial injury and heterogeneity of repolarization.

BACKGROUND: QT dispersion reveals heterogeneities in the repolarization time in the three-dimensional (3D) structure of the ventricular myocardium. In this study, we report on a 3D function map of recovery time (RT) dispersions as measured by 64-channel magnetocardiography (MCG). METHODS: MCG were simultaneously recorded in 29 controls and 21 patients with previous myocardial infarction (MI). The 3D current density was calculated from 64-channel MCG data in the Bz component using a space filter. The heart outline, reconstructed from the integrated the current density, revealed both the atrium and ventricle. The RT for the intervals between QRS onset and the time of the maximum dT/dt of T wave, and the peak to the end of the T wave (T(peak)-negative dT/dt) were automatically measured by means of a computer from 3D MCG data. The corrected RT (RTc) and corrected T(peak)-negative dT/dt were then calculated using Bazett's formula. The 3D RTc and the corrected T(peak)-negative dT/dt dispersion map were superimposed on the heart outline generated by MCG. RESULTS: The RTc was significantly longer for the MI group than in the control group (67+/-25 ms1/2 vs. 16+/-6 ms1/2) (p<0.0001). The corrected T(peak)-negative dT/dt dispersions in each patient was also significantly longer for the MI group than in the control group (35+/-27 ms1/2 vs. 10+/-5 ms1/2) (p<0.0001). Furthermore, the 3D RTc and T(peak)-negative dT/dt dispersion maps corresponded with the space location of MI, as defined by Tc-99m tetrofosmin myocardial imaging CONCLUSIONS: 3D RTc and T(peak)-negative dT/dt dispersion maps in the ST segment, obtained by 64-channel MCG may be used demonstrate the location of a myocardial injury and heterogeneities of repolarization.

Adult↗

Ethnic differences in CYP2C9*2 (Arg144Cys) and CYP2C9*3 (Ile359Leu) genotypes in Japanese and Israeli populations.

CYP2C9 is a major P450 2C enzyme, which hydroxylates about 16% of drugs that are in current clinical use and contributes to the metabolism of a number of clinically important substrate drugs such as warfarin. Ethnic differences in the genetic variation of CYP2C9 have been reported, and might be related to the frequencies of adverse reactions to drugs metabolized by CYP2C9 in different ethnic groups. In the present study, ethnic differences in the CYP2C9*2 and CYP2C9*3 allele distribution in Japanese and Israeli populations were evaluated using a newly developed oligonucleotide based DNA array (OligoArray(R)). The population studied consisted of 147 Japanese and 388 Israeli donors (100 Ashkenazi Jews, 99 Yemenite Jews, 100 Moroccan Jews and 89 Libyan Jews). The CYP2C9*2 [Arg144Cys (416 C>T), exon 3] and CYP2C9*3 [Ile359Leu (1061 A>C), exon 7] genotypes were determined using an OligoArray(R). The accuracy of genotyping by the OligoArray(R) was verified by the fluorescent dye-terminator cycle sequencing method. A Hardy-Weinberg test indicated equilibrium (chi(2)<3.84 is Hardy-Weinberg) in all populations. The CYP2C9*2 genotype (CC/CT+TT) was absent in Japanese (1/0) (OR 0.02), and its frequency was significant in Libyan Jews (0.697/0.303) (OR 2.13; 95% CI 1.07-4.24) compared with Ashkenazi Jews (0.83/0.17), Yemenite Jews (0.899/0.101), and Moroccan Jews (0.81/0.19). The frequencies of CYP2C9*3 genotype (AA/AC+CC) was significantly lower in Japanese (0.986/0.014) (OR 0.08), and was higher in Libyan Jews (0.652/0.348) (OR 3.03; 95% CI 1.5-6.1) and Moroccan Jews (0.77/0.23) (OR 1.69; 95% CI 0.62-3.48) compared with those in Ashkenazi Jews (0.85/0.15) and Yemenite Jews (0.849/0.151). Thus, the CYP2C9*2 (Arg144Cys) and CYP2C9*3 (Ile359Leu) variants were rare in the Japanese population, and showed different frequencies in the four Jewish ethnic groups examined.

Adult↗

Construction of a three-dimensional outline of the heart and conduction pathway by means of a 64-channel magnetocardiogram in patients with atrial flutter and fibrillation.

BACKGROUND: Magnetocardiography (MCG) has the potential for collecting three-dimensional (3D) intracardiac electric information, because the magnetic field is unaffected by the shape of the lungs and torso. In the present study, we report on the generation of a 3D heart outline and conduction pathway by means of a current density map using a 64-channel SQUID system, and an evaluation of its significance in patients with atrial flutter (AFL) and atrial fibrillation (AFIB). METHODS: The subjects consisted of 20 healthy volunteers, and 3 patients with AFL and 4 patients with AFIB. A 64-channel MCG was recorded after digitization at 500 Hz, and a 3D current density was reconstructed from the magnetic fields using a space filter in conjunction with the minimum normalization method of Tikhonov. A 3D heart outline was generated from the integrated current density by the space filter. The conduction pathway was superimposed on a heart outline generated by a magnetic field. The heart outline was verified by the silhouette on the magnetic resonance (MR) images. An MCG was recorded pre- and post interventional therapy, and therapeutic efficacy was evaluated. RESULTS: The 3D heart outline of the atrium and ventricle corresponded to the silhouette of the right atrium and left ventricle, respectively, on an MR image. The serial conduction pathway of the QRS segment superimposed on the 3D heart outline map demonstrated the conduction pattern generated within the heart. The MCG revealed a counter-clockwise rotation in patients with AFL, and random micro-reentry in the case of AFIB. After interventional therapy, restoration of the sinus rhythm was verified in patients with both AFL and AFIB. CONCLUSIONS: A 64-channel MCG was used to evaluate the 3D heart outline and conduction pathway in patients with AFL and AFIB without the need for MR images. Condensed Abstract A 64-channel MCG was used to evaluate the 3D heart out line and conduction pathway in patients with AFL and AFIB.

Aged↗

Ethnic differences of coronary artery disease-associated SNPs in two Israeli healthy populations using MALDI-TOF mass spectrometry.

Differences in prevalence and mortality from coronary artery disease (CAD) were observed among the different Israeli ethnic groups. The incidence of CAD in Israel is highest among Ashkenazi Jews and is much lower among Yemenite Jews. In this present study, we selected 15 single nucleotide polymorphisms (SNPs) from 14 candidate genes involved in (1) the renin-angiotensin system, (2) lipid metabolism, (3) cytokines and adhesion molecules, and (4) growth factors, and (5) the coagulation-fibrinolysis system. We analyzed the 15 SNPs in 94 Israeli healthy populations (47 Ashkenazi Jews and 47 Yemenite Jews) obtained from the National Laboratory for the Genetics of Israeli Populations. We applied chip-based MALDI-TOF mass spectrometry as a method for screening multiplexed genotyping of SNPs for ethnic difference in these healthy populations. Among the 15 candidate SNPs, significant differences in allelic frequency were observed in the 1166A>C of the AGTR1 gene, R158C of the Apo E gene, W64R of the ADRB3 gene, S101S of the TIMP 2 gene, and A222V of the MTHFR gene with respect to allele frequency. The incidence of A/C allele of the AGTR1 gene were 0.638/0.362 vs 0.765/0.235, C/T allele in the apo E gene was 0.915/0.085 vs 0.989/0.011, T/C allele of the ADRB3 gene was 0.989/0.0011 vs 0.926/0.074, G/A allele of the TIMP2 gene was 0.974/0.054 vs 0.830/0.170, and C/T allele in the MTHFR gene was 0.521/0.479 vs 0.819/0.181 for Ashkenazi Jews and Yemenite Jews, respectively. We demonstrated an ethnic difference of CAD-associated SNPs in two Israeli healthy populations using MALDI-TOF mass spectrometry. Further study is necessary to prove causal relation with CAD-associated SNPs and the prevalence of CAD.

Apolipoproteins E↗

Serum levels of cardiac troponin I and other marker proteins in patients with chronic renal failure.

BACKGROUND: Serum levels ob biochemical markers for acute myocardial infarction (AMI) can be increased in patients with chronic renal failure (CRF) or skeletal muscle injury, creating diagnostic confusion. We evaluated the clinical utility of cardiac troponin I (cTnI) as a marker of AMI, particularly in patients with CRF. METHODS: Subjects consisted of 59 healthy volunteers and 102 patients: 61 with CRF undergoing hemodialysis (CRF-HD), 10 with CRF under conservative therapy (CRF-CT), 21 with renal disease (RD), and 10 with muscle disease (MD). Patients with RD, CRF, and MD were evaluated to verify the absence of myocardial injury. We developed an immunoradiometric assay to measure serum cTnI using monoclonal antibodies. The lower limit of detection was 0.33 micro g/l. Serum cTnI, creatine kinase (CK), CK-MB, cardiac troponin T (first-, second-, and third-generation assay: cTnT-I, cTnT-II, and cTnT-III), and cardiac myosin light chain 1 (cMLC1) were measured. RESULTS: cTnI was not detected in healthy volunteers or patients with CRF, RD, or MD. In patients with CRF-HD, elevated levels occurred in 4.9% (3/61) for CK, 0% (0/61) for CK-MB, 39.5% (15/38) for cTnT-I, 7.3% (3/41) for cTnT-II, 13.0% (3/23) for cTnT-III, and 77.0% (47/61) for cMLC1; and in patients with MD the levels were increased in 70% (7/10) for CK, 50% (5/10) for CK-MB, 44.4% (4/9) for cTnT-I, 20% (2/10) for cTnT-II, and 50% (5/10) for cMLC1. CONCLUSIONS: cTnI is a highly specific marker for AMI and is particularly useful for detecting AMI in patients with CRF or MD. Serum levels of biochemical markers for acute myocardial infarction (AMI) can be increased in patients with chronic renal failure (CRF) or skeletal muscle injury, creating diagnostic confusion. We evaluated the clinical utility of cardiac troponin I (cTnI) as a marker of AMI, particularly in patients with CRF.

Biomarkers↗

[Educational program of clinical laboratory medicine to develop the ability to use proper laboratory examinations in medical practice].

A model core curriculum for medical education was proposed in 2001 as a guideline to standardize and improve the educational program in Japanese medical schools. Many subjects involved in clinical laboratory medicine were listed in this model core curriculum. Original and characteristic educational curricula in each medical school were also required in this guideline. In our university, we constructed the educational program of clinical laboratory medicine with lectures, clinical practice, and small group seminars including reversed CPC, according to the guideline. We need further trials to achieve the goal, i.e. education to develop the ability to use proper laboratory examinations in medical practice, as a good clinical doctor.

Clinical Laboratory Techniques↗

Highly multiplexed genotyping of coronary artery disease-associated SNPs using MALDI-TOF mass spectrometry.

Highly multiplexed genotyping methods are needed to support a comprehensive analysis of single nucleotide polymorphisms (SNPs) in coronary artery disease (CAD)-related genes. In this study we evaluated chip-based MALDI-TOF mass spectrometry for multiplexed genotyping of SNPs associated with CAD. Our analysis included 14 healthy Japanese individuals and 19 Japanese patients with myocardial infarction whose first attack occurred before age 50. We selected 29 candidate genes involved in 1) the renin-angiotensin system, 2) lipid metabolism, 3) cytokines and adhesion molecules, 4) growth factors, and 5) the coagulation-fibrinolysis system. Genotyping of candidate SNPs was performed by MALDI-TOF MS using a MassARRAY system, and 4-plex analysis was achieved at a maximum. All 39 SNPs determined by the fluorescent dye-terminator cycle sequencing method from four randomly selected patients were found to be in complete agreement with the results obtained from MassARRAY system. Significant differences were observed in the -1965delG of PAI1 (SERPINE1) with respect to allelic frequency, the G>A in the promoter region SNP in SM22 (TAGLN) for dominant genotype, and in two other SNPs (C>T in intron 1 of HGF, and -1965delG of PAI1) for recessive genotype. Three SNPs (803T>C of AGT, 677CT of MTHFR, 190T>C of ADRB3) showed weak differences in allelic frequency. MALDI-TOF-MS provided high performance with a multiplex assay design for analysis of CAD-related SNPs by increasing the throughput while maintaining a high level of accuracy.

Cell Adhesion Molecules↗

[Biochemical marker for myocardial injury].

Recently, the general idea of the acute coronary syndrome (ACS) that includes acute myocardial infarction and unstable angina has been established. ACC/AHA guidelines in 1996 and 1999 had emphasized the importance of the initial diagnosis and the early treatment in acute myocardial infarction. We presented about the recent advances in "injured myocardial marker" around the ACS in this paper. The sensitivity and specificity for detecting myocardial injury by troponin T and I(TnT and TnI) were superior compared with those in creatinine kinase (CK) and CK-MB. Easy rapid detection system by using whole blood was useful in the diagnosis a high risk cases in ACS. Measurement of TnT and TnI are recommended the use in the emergency room. A guideline for a diagnosis of acute myocardial infarction had a revision (ACC/ESC) on 2000. Biochemical markers of TnT & TnI were recommended as the first step for defining the myocardial injury. Unstable angina pectoris with a minimal myocardial injury (rise in CK under two times) was defined acute myocardial infarction. As for the measurement of the myocardial injury, rapid detection and accuracy & specificity may enhance the value of modality. In future, inflammation marker such as the high sensitivity CRP and an activated platelet may be thought to become important.

Acute Disease↗