Search PubMed⌕ Search

Biomedical subjects

Naoko Kinukawa

Publications and source records attributed to Naoko Kinukawa.

At least 19 recordsLinked to original sources

Genetic structure of the dopamine receptor D4 gene (DRD4) and lack of association with schizophrenia in Japanese patients.

In order to investigate the contribution of genetic variation in the human dopamine receptor D4 gene (DRD4) to the risk of developing schizophrenia, we carried out a genetic analysis of 27 polymorphisms in 216 schizophrenic patients and 243 healthy controls from the Kyushu region of Japan. Twenty-two single nucleotide polymorphisms (SNPs) and five insertion/deletion polymorphisms were analyzed in this study, including four novel SNPs and a novel mononucleotide repeat. Linkage disequilibrium (LD) and haplotype analyses reveal weak LD across the DRD4 gene. In univariate analysis female individuals with allele -521C had a higher risk for schizophrenia. However, this finding was not significant after correction for multiple hypothesis testing. No other polymorphisms or haplotypes differed between schizophrenic patients and controls. Likewise, multivariate analyses did not reveal any statistically significant associations.

Adolescent↗

Edrophonium provocative testing for the evaluation of upper gastrointestinal hypersensitivity in patients with nonulcer dyspepsia.

The aim of this study was to examine if edrophonium provocative testing is useful for evaluating upper gastrointestinal hypersensitivity in patients with nonulcer dyspepsia (NUD). A questionnaire rating dyspeptic symptoms was done for 58 patients with NUD. The patients were then given an intravenous infusion of saline followed by 5 mg of edrophonium. Baseline esophageal manometry was also done. Patients whose usual symptoms were reproduced (48.3%) had significantly higher symptom scores (13.0 [8.5, 17.0] vs. 8.5 [6.0, 11.0]; P = 0.015) and a significantly higher number of symptoms (4.0 [2.5, 6.0] vs. 3.0 [1.0, 4.0]; P = 0.010) than patients whose usual symptoms were not reproduced. The presence of an esophageal motility disorder was not significantly different between the two groups. These findings suggest upper gastrointestinal hypersensitivity in the patients whose symptoms were reproduced. Edrophonium provocative testing might be useful for evaluating upper gastrointestinal hypersensitivity in patients with NUD.

Adolescent↗

Noninvasive measurement of isovolumetric contraction time by Doppler cardiography can be substituted for fetal cardiac contractility: evaluation of a fetal lamb study.

OBJECTIVE: The objective of this study is to clarify whether the isovolumetric contraction time obtained from Doppler cardiography (Doppler ICT) can be an index substituted for fetal cardiac contractility. MATERIALS AND METHODS: In 10 pregnant ewes, fetal hypoxemia was induced by giving a variable mixture of gases. Through experiment, the Doppler ICT, pre-ejection period (PEP), and the maximum first derivative of the left ventricular pressure waveform (Max dp/dt) were simultaneously recorded every 10min. The relationship between both the Doppler ICT and PEP, and the Max dp/dt were analyzed. RESULTS: A significant negative linear regression was founded between the Doppler ICT and the Max dp/dt. A significant negative linear regression was also shown between PEP and the Max dp/dt. Moreover, the regression of Max dp/dt on ICT had significantly less residual variance than the regression of Max dp/dt on PEP (p=0.0004). CONCLUSION: In contrast to PEP, Doppler ICT is a reliable, and non-invasive index which can be substituted for fetal cardiac contractility.

Animals↗

Sonographic diagnostic criteria for screening Sjögren's syndrome.

OBJECTIVE: The objective of this study is to establish readily applied sonographic diagnostic criteria for Sjögren's syndrome. STUDY DESIGN: Sonographic images of 79 cases of previously suspected Sjögren's syndrome (including 43 actual cases) were analyzed retrospectively for the following characteristic features: (1) multiple hypoechoic areas, (2) multiple hyperechoic lines or spots, (3) multiple hypoechoic areas surrounded with hyperechoic lines or spots, and (4) obscuration of the gland configuration. Logistic regression analysis was used to extract valuable sonographic findings. Sonographic images of 80 prospective patients (of whom 48 proved to have Sjögren's syndrome) were scored prospectively using selected features to verify the usefulness of the established criteria. RESULTS: Three sonographic findings in parotid and submandibular glands were selected by logistic regression analysis and retrospective and prospective patients compared. Experienced observers could differentiate positive cases of Sjögren's syndrome from negative controls to a highly significant degree. Findings correlated very well with sialographic grading. CONCLUSION: Sonography can be substituted for sialography when applying the selected criteria in screening for Sjögren's syndrome.

Female↗

Alteration pattern of tear cytokines during the course of a day: diurnal rhythm analyzed by multicytokine assay.

Our aim was to study the alteration pattern and interaction of inflammatory tear cytokines during the course of a day. Using a prospective, experimental design, tears were collected from 28 healthy volunteers with normal eyes during the period from April 2004 to March 2005. Tears (10 microl) were collected by capillary outflow from each eye at 9:00, 12:00, 16:00, 21:00, and 24:00 h. The concentrations of inflammatory cytokines, IL-1beta, IL-6, IL-8, IL-10, IL-12p70, and TNF-alpha were measured using cytometric bead arrays. Although the concentration of tear cytokines varied widely among eyes, the amount of cytokine had a specific alteration pattern in each eye during the course of a day. IL-1beta, IL-6, IL-10, IL-12p70, and TNF-alpha showed slight increases in the morning and the late evening. IL-8 remained low throughout the day. The alteration pattern of IL-8 was significantly different from those of TNF-alpha and IL-12p70 (P<0.01). The ratio of each pro-inflammatory cytokine to anti-inflammatory cytokine IL-10 did not significantly change throughout the day. The amount of tear cytokines changed during daytime with a specific pattern. This diurnal rhythm may influence symptoms of ocular surface diseases during the course of a day.

Adult↗

Fetal aortic distension waveforms for evaluating cardiac function and changes in blood pressure: fetal lamb validation.

AIM: To investigate which part of the fetal aortic distension waveform is mainly influenced by changes in fetal cardiac contractility and aortic blood pressure. METHODS: In acute preparation, aortic distension waveforms were recorded using an echo-tracking system, and aortic and left ventricular pressure waveforms were obtained from six late-gestation catheterized fetal lambs. Dobutamine and angiotensin II were separately infused and the correlations between the maximum value in the first derivative of left ventricle pressure waveforms (Max dP/dt) and fetal blood pressure, and the parameters obtained from aortic distension waveforms were analyzed using linear regression analysis. RESULTS: With a change in cardiac contractility, the maximum value of first derivative of the systolic rising slope in the aortic distension waveform had a positive correlation with Max dP/dt (r = 0.93, P < 0.0001). With changes in fetal blood pressure, both the amplitude and the ratio of increase from the end diastolic diameter obtained from the aortic distension waveform had a significant positive correlation with aortic blood pressure amplitude (r = 0.60, P < 0.01; r = 0.61, P < 0.01, respectively). CONCLUSION: The maximum first derivative of the systolic rising slope in the aortic distension waveform and the amplitude in the aortic distension waveform enable us to non-invasively substitute for fetal cardiac contractility and aortic blood pressure amplitude, respectively.

Animals↗

High-grade and hormone-treated prostate cancer express high levels of thymidylate synthase.

OBJECTIVE: To evaluate the expression of thymidylate synthase and dihydropyrimidine dehydrogenase in prostate tissue. MATERIALS AND METHODS: Tissue from 79 patients with localized prostate cancer was used. Thymidylate synthase and dihydropyrimidine dehydrogenase expression were determined semiquantitatively by immunohistochemistry. RESULTS: Thymidylate synthase and dihydropyrimidine dehydrogenase immunostaining grades of benign tissue were significantly higher than those of cancer tissue (both P < 0.01). Cancer tissue with a primary Gleason grade of > or = 4 expressed a higher thymidylate synthase staining grade than those with a primary Gleason grade of <4 (P < 0.01). Cancer tissue spots from patients treated with neoadjuvant therapy revealed significantly higher thymidylate synthase and dihydropyrimidine dehydrogenase grades than those with no neoadjuvant therapy (P < 0.01). CONCLUSION: High thymidylate synthase expression in localized prostate cancer might reflect an aggressive status. High expression in high-grade prostate cancers and prostate cancers after hormonal therapy suggest that thymidylate synthase could be a new therapeutic target for advanced prostate cancer.

Aged↗

Percentage of positive biopsy cores, preoperative prostate-specific antigen (PSA) level, pT and Gleason score as predictors of PSA recurrence after radical prostatectomy: a multi-institutional outcome study in Japan.

OBJECTIVE: To evaluate the clinical outcome of radical prostatectomy (RP) in Japan, by retrospectively analysing the clinicopathological data in patients with clinical T1-T2 prostate cancer treated by RP, as there can be prostate-specific antigen (PSA) recurrence after RP in substantially many patients, and its character can differ according to ethnic group and/or country. PATIENTS AND METHODS: We reviewed 1192 patients who had a RP from 1993 to 2002 with no neoadjuvant/adjuvant therapy and whose PSA level after RP decreased at least once to undetectable levels (<0.2 ng/mL). PSA recurrence was defined as > or = 0.20 ng/mL. The patient data were collected from the Urological Oncology Study Group, a subgroup of Japan Clinical Oncology Group. RESULTS: The patients' median (range) age was 67 (47-83) years and their PSA level before RP was 8.7 (1.0-153) ng/mL. During the median follow-up of 45.6 months, 302 of the 1192 patients (25.3%) developed PSA recurrence. The median time to recurrence was 369 (61-2128) days after RP. A log-rank test showed that five significant clinicopathological factors were associated with PSA recurrence after RP: the percentage of prostate needle-biopsy cores with cancer, the biopsy Gleason score, PSA level before RP, pathological stage, and the Gleason score of the RP specimen (P < 0.001 for all). In multivariate analyses, the percentage of positive biopsy cores, PSA level before RP, pT and the Gleason score of the RP specimen were all independent significant predictors of PSA recurrence after RP in Japanese men. CONCLUSIONS: The frequency of PSA recurrence after RP was 25.3% in Japan and the percentage of positive biopsy cores, PSA level before RP, pT and the Gleason score of the RP specimen were independent significant factors for PSA recurrence.

Aged↗

Serum immunoglobulin levels do not affect antibody responses to influenza HA vaccine in preterm infants.

Antibody responses to two doses of influenza hemagglutinin (HA) vaccine were evaluated in 45 previously unimmunized preterm infants aged 6-11 months before the 2003/2004 influenza season. Twenty-three (51.1%), 21 (46.6%) and 2 (4.4%) of the subjects acquired protective (>or=1:40) hemagglutination inhibition (HI) antibody titers after vaccination for A/New Caledonia (H1N1), A/Panama (H3N2) and B/Shandong, respectively. Antibody responses to A (H1N1), A (H3N2) appeared to be comparable to those reported on full-term infants of similar ages vaccinated with the identical vaccine. Serum IgG levels at vaccination had no positive association with antibody responses on univariate or multivariate analysis, indicating that prolonged hypogammaglobulinemia after 6 months of age in preterm infants was not a factor to affect antibody responses to influenza HA vaccine.

Antibodies, Viral↗

Association of HER-2 polymorphism with Japanese sporadic prostate cancer susceptibility.

BACKGROUND: Genetic polymorphisms may affect the development of prostate cancer (Pca). HER-2 is a proto-oncogene that has an important role in many human cancers, including Pca. To determine the association of the HER-2 gene with Japanese sporadic Pca, we analyzed the frequency of codon 655 (A/G, isoleucine, or valine) in case and control group. METHODS: We genotyped Ile 655 Val in Pca patients (n = 285) and in matched controls (n = 233). Statistical analyses were performed by Fisher's exact test and logistic regression analysis. RESULTS: We observed a significantly lower frequency of the Val655 allele in the Pca patients (14.7%) compared to the control group (26.2%) (P = 0.0025, odds ratio (OR) = 0.476, 95% CI = 0.306-0.740). This SNP was not found to be correlated with clinical stage, PSA level, Gleason score of biopsies or age at diagnosis. CONCLUSIONS: Our results indicate that the frequency of Val655 in HER-2 was significantly lower in Japanese Pca patients, however, it was recently reported that Val655 was significant higher in breast cancer patients. This contradictory observation in prostate and breast cancer patients is interesting considering the opposite hormonal sensitivity of these two cancers.

Aged↗

Immune response after influenza vaccination in children with cancer.

PURPOSE: To assess the immune response to inactivated trivalent split influenza vaccine in children with cancer. PROCEDURES: Forty-four children with various types of malignancies received two doses of influenza vaccine 2-4 weeks apart. Hemagglutinin-inhibition (HI) antibody titers were determined in paired sera obtained just before the first vaccination and 4 weeks after the second vaccination. RESULTS: Influenza vaccine was administered to all children without any serious adverse effects. Protective titer rates (proportion of patients achieving antibody titers > or =40 among those with pre-vaccination titers <40) and response rates (proportion of patients with fourfold or more antibody rise) were 72% and 65% for H1N1, 60% and 40% for H3N2, and 38% and 46% for influenza B, respectively. However, patients on chemotherapy showed a significantly lower immune response to influenza A than those having completed chemotherapy; protection titer rates were 42% versus 90% for H1N1 (P = 0.006) and 25% versus 83% for H3N2 (P = 0.019). For influenza B, patients with low IgG showed a lower response rate than those with high IgG (29% vs. 61%, P = 0.040). Multivariate analysis revealed that factors significantly associated with a lower immune response were low IgG (P < 0.001) and administration of chemotherapy (P = 0.003) for H1N1, administration of chemotherapy (P = 0.008) for H3N2, and low white blood cell (WBC) count (P = 0.030) and low IgG (P = 0.030) for influenza B. CONCLUSIONS: Influenza vaccination given to children with cancer was safe and induced immune reaction comparable to healthy children, although patients on chemotherapy and/or with chemotherapy-related conditions had a limited ability to produce a sufficient immune response.

Adolescent↗

Left hemisphere specialization for rapid temporal processing: a study with auditory 40 Hz steady-state responses.

OBJECTIVE: To investigate rapid temporal processing in the auditory cortex by using auditory 40 Hz steady-state responses (SSRs). METHODS: A 40 Hz tone-burst at 500 Hz spectral frequency was presented monaurally to record SSRs in 10 normal subjects. The recording electrodes were placed over C1, C2, C3, C4, C5, C6, T3, T4, Fz, Cz and Pz, referring to an electrode at the 7th cervical spinous process. For comparison, unstimulated SSRs were recorded. A total of 200 responses of 1s epoch were averaged and subjected to discrete fast Fourier transforms to yield the amplitude and phase of the 40 Hz component. The coherence (Coh) values of the 40 Hz component between homologous electrodes were also calculated. RESULTS: At the temporal electrodes contralateral to the stimulated ear, the amplitude was significantly larger and its phase was significantly smaller than those of the ipsilateral side. The interhemispheric Coh between T3 and T4 in response to right ear stimulation was significantly greater than those of left ear stimulation or the unstimulated condition. CONCLUSIONS: Our results suggest that 40 Hz auditory information is predominantly processed in the left auditory cortex, interacting with the right hemisphere. This finding is consistent with the fact that the left auditory cortex plays an important role in rapid temporal processing. SIGNIFICANCE: Auditory 40 Hz SSRs with Coh analysis are useful for investigating the left hemisphere specialization for rapid temporal processing.

Acoustic Stimulation↗

Functional characterization of mismatch negativity to a visual stimulus.

OBJECTIVE: To record mismatch negativity (MMN) to a visual stimulus fulfilling similar criteria to those of auditory MMN (A-MMN). METHODS: Twelve normal adults were instructed to simultaneously listen to a story and to pay attention to a visual target. Three windmill patterns that differed in the number of vanes (standard, deviant, or target) were used as visual stimuli, and were randomly presented. To ensure endogeneity, standard and deviant stimuli were alternated. To vary differences between frequent (standard) and infrequent (deviant) stimuli, deviants were changed by modulating the number of vanes. To examine effects of physical features of the target stimulus on changes in detection, two target conditions were used. The deviant-related component (DRC) was obtained by subtracting event-related potentials (ERPs) to the deviant stimulus from those to the standard stimulus. RESULTS: Seven subjects completed all phases of the experiment. Behavioral performances indicated that subjects' attention was directed by auditory context and identification of the target stimulus. Visual DRC appeared 150-300 ms after stimulus onset, and consisted of an early (DRN1) and a late (DRN2) component. Magnitude of deviancy from standard stimulus significantly influenced latency of DRN2 but not its magnitude, while changes in target stimulus affected latencies of both DRN1 and DRN2. CONCLUSIONS: Our DRCs satisfied criteria for A-MMN. In contrast to A-MMN, only latency of the DRC was associated with visual sensory discrimination and attentional reorienting. SIGNIFICANCE: It is possible to record valid MMN to a visual stimulus, which allows the study of preattentive visual information processing.

Adult↗

Noninvasive measurement of isovolumetric contraction time during hypoxemia and acidemia: Fetal lamb validation as an index of cardiac contractility.

OBJECTIVES: The objectives of this study are firstly to clarify how the Doppler isovolumetric contraction time (ICT) is influenced by arterial oxygen pressure (PaO2) or pH, and secondly to confirm the relationship between the Doppler ICT and myocardial contractility during hypoxemia and/or acidemia in the fetal lamb. MATERIAL AND METHODS: In 12 pregnant ewes, fetal hypoxemia and acidemia were induced by giving ewes a variable mixture of gases for 120 min. The chronological change of fetal PaO2, pH, Doppler ICT and maximum first derivative of the left ventricular pressure waveform (Max dp/dt) was recorded every 30 min. RESULTS: Doppler ICT and PaO2 had no significant regression. On the other hand, Doppler ICT and pH demonstrated a significant negative regression. Moreover, one critical given pH point was indicated with statistical significance at 7.20 and the prolongation of the Doppler ICT was found more markedly in the range below the pH of 7.20 compared with the range above 7.20. A significant negative linear regression was found between the Doppler ICT and the Max dp/dt. CONCLUSION: The measurement of Doppler ICT enables us to predict severe acidosis and a decrease of myocardial contractility in the fetus.

Acidosis↗

Overexpression of laminin-5 gamma2 chain and its prognostic significance in urothelial carcinoma of urinary bladder: association with expression of cyclooxygenase 2, epidermal growth factor receptor [corrected] and human epidermal growth factor receptor [corrected] 2.

Laminin-5 (LN-5) and cyclooxygenase 2 (COX-2) play important roles in many kinds of cancers. Recently, it has been reported that epidermal growth factor receptor [corrected] (EGFR) and/or human epidermal growth factor receptor [corrected] 2 (HER2) expressions are associated with LN-5 and/or COX-2 expressions in a few carcinoma cell lines and human tumor tissue. LN-5, COX-2, EGFR, and HER2 expressions were examined immunohistochemically in 67 patients with urothelial carcinomas (UCs), and associations among these 4 biomarkers and clinicopathologic characteristics were investigated. Patients were classified into transurethral resection group and cystectomy group based on clinical end points, and prognostic significances of increased expressions were evaluated. Overexpression of LN-5, COX-2, EGFR, and HER2 was observed in 16 (23.9%), 34 (50.7%), 42 (62.7%), and 15 (22.4%) of 67 patients, respectively. LN-5 overexpression was associated high-grade (P = .002), invasive (pTa+1 versus pT2-4, P = .011), and nonpapillary (P = .027) UCs. Concerning EGFR and HER2, high-grade (EGFR, P = .0009; HER2, P = .003) and nonpapillary (EGFR, P = .016; HER2, P = .0002) UCs had a significantly higher overexpression rate. UCs penetrating basal membrane (pT1-4) showed significantly higher overexpression rates than pTa UCs on all biomarkers. In transurethral resection group, LN-5 overexpression could be proved as an independent prognostic parameter for intravesical recurrence (P = .007), whereas in cystectomy group, nodal involvement was an independent prognostic parameter for cause-specific survival (P = .025). The current study showed that the 4 biomarkers were associated with aggressive behaviors of UCs. Above all, LN-5 overexpression was considered to play an important role in intravesical recurrence of superficial UCs.

Adult↗

Metastatic lymph node size and colorectal cancer prognosis.

BACKGROUND: Colorectal cancer patients with lymph node metastasis constitute a heterogeneous population with variable prognoses. In this study, my colleagues and I propose a simpler lymph node (LN) staging system for colorectal cancer. STUDY DESIGN: Four-hundred and twenty-three consecutive colorectal cancer patients were studied. Of these, 36 were excluded because another carcinoma was present. The remaining 387 patients entered the TNM staging analysis. In the survival analysis, 76 patients with distant metastasis were excluded and the remaining 311 patients (LN(-) = 204 and LN(+) = 107) were studied. The diameter of the largest metastatic LN (MLN) was measured on histopathological slides. After examination of various cutpoints and survival outcomes, patients with MLNs were classified into n1 (< or = 9 mm) and n2 (> or = 10 mm) groups, according to size of MLNs (n-stage). RESULTS: Using disease-free survival (DFS) and overall survival (OS) as outcomes, patients were separated into significant prognostic groups by MLN size (univariate, p < 0.0001) (5-year survival, DFS: n0 = 91.5%, n1 = 62.2%, and n2 = 34.4%; OS: n0 = 85.1%, n1 = 63.5%, and n2 = 42.5%) and International Union Against Cancer/American Joint Committee on Cancer (UICC/AJCC) (N-stage) (univariate, p < 0.0001) (5-year survival, DFS: N0 = 91.5%, N1 = 60.5%, and N2 = 36.8%; OS: N0 = 85.1%, N1 = 65.3%, and N2 = 38.0%). But in patients with fewer than 15 LNs examined (n = 31), only the new nodal stage stratified patients into significant groups (OS: p = 0.003 and DFS: p = 0.001). Only the UICC/AJCC N-stage subcategories were further split into significant prognostic groups by MLN size (UICC/AJCC N1: DFS, p = 0.048 and OS, p = 0.11; N2: DFS, p = 0.04 and OS, p = 0.04). n-stage was an independent important factor both in the DFS and OS in multivariable analysis. CONCLUSIONS: MLN size is a strong prognostic variable in colorectal carcinoma. This new metric may help clinicians treating colorectal cancer patients, but additional studies are required before clinical application.

Adult↗

Effects of volcanic ash on ocular symptoms: results of a 10-year survey on schoolchildren.

OBJECTIVE: To study the effects of volcanic ash on the ocular symptoms of schoolchildren ages 6 to 15 residing near Mt. Sakurajima, an active volcano. DESIGN: Retrospective, cross-sectional study. PARTICIPANTS: A total of 10,380 children ages 6 to 15, 1175 in a high-exposure area and 9205 in a low-exposure area, were studied. METHODS: High- and low-exposure areas for volcanic ash were selected. All subjects in both areas were examined annually each September in the decade from 1994 to 2003. MAIN OUTCOME MEASURES: The frequency of positive ocular symptoms in years with and without active volcanic eruptions was compared. The association of ocular symptoms with volcanic ash dispersal was assessed with the Mantel-Haenszel test or chi-square test. RESULTS: Subjects in the high-exposure area showed ocular symptoms more often than those in the low-exposure area (P<0.0001). Years of active volcanic eruptions (volcanic ash of 5000 g/m2/year or more) were closely related to years with a high frequency of ocular symptoms in subjects in the high-exposure area (P<0.05) but related conversely in subjects in the low-exposure area (P<0.01). Major ocular symptoms were redness, discharge, foreign body sensation, and itching, all treated effectively with eyedrops. CONCLUSIONS: Ocular symptoms in subjects were strongly influenced by volcanic eruptions in the Mt. Sakurajima area, but direct influence was limited to those living in areas very near the volcano (i.e., 4 km from the volcano's crater).

Adolescent↗