M Ohi

Kyoto Medical Center, Kioto, Kyōto, Japan

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Publications (90)250.35 Total impact

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    ABSTRACT: The significance of changes in PaCO2 during long-term noninvasive ventilation (NIV) on prognosis remains unclear. We aimed to clarify whether stabilizing PaCO2 during NIV had a favorable prognostic effect.
    Respiratory care 07/2014; · 2.03 Impact Factor
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    ABSTRACT: Objective To investigate the impact of obstructive sleep apnea syndrome (OSAS) on night-time secretion of brain natriuretic peptide (BNP) and antidiuretic hormone (ADH) in older men with nocturia accompanied by nocturnal polyuria. Methods One hundred six men with nocturia aged ≥60 years underwent full-night polysomnography to determine whether they had OSAS. Blood count, standard chemistry panel, BNP, urinary ADH, urinary creatinine (u-Cre), and urinary osmolarity were measured at 6:00 AM, and a frequency volume chart was recorded on the same day that polysomnography was performed. Results We evaluated 83 patients after excluding 18 with mild OSAS and 5 with nocturnal polyuria index <0.35. Participants with OSAS had higher apnea-hypopnea index (P <.0001) than those without OSAS. Body mass index and systolic blood pressure were higher in OSAS patients than those in the control group. BNP was higher in the OSAS patients than in the control patients (48.6 ± 41.4 vs 30.7 ± 31.5; P = .0006). On urinalysis, OSAS patients showed higher urinary sodium and u-Cre secretion than controls (24.7 ± 11.3 vs 16.2 ± 5.1; P <.0001). Urine osmolarity was also higher in OSAS patients than in the control patients (616 ± 172 vs 516 ± 174; P = .0285). There was no significant difference in urinary ADH and u-Cre (6.7 ± 10.4 vs 6.8 ± 7.8; P = .3617) between the 2 groups. Conclusion Our results indicated that older men with nocturnal polyuria and OSAS did not compensate their fluid imbalance presented with decreased secretion of ADH but increased BNP level.
    Urology 01/2014; · 2.42 Impact Factor
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    ABSTRACT: We aimed to characterize the association between jaw muscle contractions and respiratory events in patients with obstructive sleep apnea syndrome (OSAS) and to investigate the responsiveness of the contractions to respiratory events in comparison with that of leg muscles in terms of arousal types and sleep states. Polysomnographic (PSG) recordings were performed in 19 OSAS patients (F/M: 2/17; 53.1 ± 13.7 years; AHI: 31.8 ± 19.9/h) with no concomitant sleep bruxism or other sleep-related movement disorders. Muscle contractions of unilateral masseter (MAS) and anterior tibialis (AT) muscles were scored during sleep in association with graded arousals (microarousals and awakenings) related or unrelated to apneahypopnea events. Arousals were scored for 68.2% and 52.3% of respiratory events during light NREM and REM sleep, respectively. Respiratory events with arousals were associated with longer event duration and/or larger transient oxygen desaturation than those without (ANOVAs: p < 0.05). Median response rates of MAS events to respiratory events were 32.1% and 18.9% during NREM and REM sleep. During two sleep states, MAS muscle was rarely activated after respiratory events without arousals, while its response rate increased significantly in association with the duration of arousals (Friedman tests: p < 0.001). A similar response pattern was found for AT muscle. Motor responsiveness of the two muscles to arousals after respiratory events did not differ from responsiveness to spontaneous arousals in two sleep stages. In patients with OSAS, the contractions of MAS and AT muscles after respiratory events can be nonspecific motor phenomena, dependent on the duration of arousals rather than the occurrence of respiratory events. Kato T; Katase T; Yamashita S; Sugita H; Muraki H; Mikami A; Okura M; Ohi M; Masuda Y; Taniguchi M. Responsiveness of jaw motor activation to arousals during sleep in patients with obstructive sleep apnea syndrome. J Clin Sleep Med 2013;9(8):759-765.
    Journal of clinical sleep medicine: JCSM: official publication of the American Academy of Sleep Medicine 01/2013; 9(8):759-65. · 2.93 Impact Factor
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    ABSTRACT: OBJECTIVES: Prior to oral appliance therapy for snoring and obstructive sleep apnea syndrome (OSAS), patients are screened for jaw symptoms (e.g., pain). However, the presence of jaw symptoms in a large spectrum of OSAS patients remains unknown. This study aimed to assess the distribution of subjective jaw symptoms in patients with symptoms of OSAS. METHODS: Five hundred and eleven consecutive patients (66 female, 445 male; mean age 49.6 ± 12.6 years) with clinical symptoms of OSAS were enrolled for cardiorespiratory evaluation. Self-administered questionnaires were used to assess jaw symptoms, tooth grinding and clenching during sleep, morning oral dryness, morning heartburn sensation, and pain in the neck and back. RESULTS: The mean apnea-hypopnea (AHI) index was 32.5 ± 30.6 per hour of sleep. Nineteen percent of patients (n = 96) reported at least one jaw symptom. The presence of jaw symptoms was more frequently reported by patients with AHI less than 15 (25 %) than those with AHI of 15 and more (15 %, p = 0.012). In the crude analyses, jaw symptoms were associated with tooth grinding, tooth clenching, morning oral dryness, morning heartburn sensation, and neck/back pain. Multiple logistic regression analysis confirmed that jaw symptoms were associated with AHI less than 15 (odds ratio (OR) 1.99, p = 0.009), tooth clenching (OR 1.79, p = 0.006), morning oral dryness (OR 2.17, p = 0.02), and neck/back pain (OR 1.99, p = 0.005). CONCLUSIONS: Jaw symptoms can be found in 19 % of patients with symptoms of OSAS and are more frequently reported in patients with lower AHI, a patient population for whom oral appliances are often prescribed.
    Sleep And Breathing 04/2012; · 2.26 Impact Factor
  • Sleep Medicine 01/2012; 13(1):111-4. · 3.49 Impact Factor
  • Motoharu Ohi, Kazuo Chin
    Nihon Naika Gakkai Zasshi 04/2011; 100(4):966-74.
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    ABSTRACT: The appropriate target level for PaCO(2) after the introduction of long-term noninvasive positive pressure ventilation (NPPV) in patients with COPD remains uncertain, and therefore must be tested. Data on 54 patients with COPD receiving long-term domiciliary NPPV were examined retrospectively. PaCO(2) a few months after NPPV and potential confounders were analyzed with discontinuation of long-term NPPV as the primary outcome. The differences in annual hospitalization rates due to respiratory deterioration between those from 1 year before to 2 years after initiation of NPPV were compared according to the PaCO(2) measured at 6 months after NPPV (6-mo PaCO(2)). 6-mo PaCO(2) seemed to be most related to continuation of NPPV (p=0.019). Patients with 6-mo PaCO(2) of less than 60 mmHg had maintained a significantly lower PaCO(2) value 6 to 24 months after NPPV (p=0.04) and had a significantly higher continuation rate of NPPV (p=0.03) than those with a 6-mo PaCO(2) of 60 mmHg or more. Annual hospitalization rates due to respiratory deterioration were not associated with the 6-mo PaCO(2) level, but fatal hospitalization rates during the first year of NPPV were significantly correlated with relatively high 6-mo PaCO(2) (p=0.008). A relatively low 6-mo PaCO(2) value was predictive of long-term use of NPPV. The target values of 6-mo PaCO(2) may, therefore, be less than 60 mmHg in COPD patients with extremely severe hypercapnia, although more prospective studies are needed.
    Internal Medicine 01/2011; 50(6):563-70. · 0.97 Impact Factor
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    ABSTRACT: The level at which arterial carbon dioxide tension (PaCO(2)) a few months after introduction of long-term non-invasive positive pressure ventilation (NPPV) is associated with a favorable prognosis remains uncertain. Data on 184 post-tuberculosis patients with chronic restrictive ventilatory failure who were receiving long-term domiciliary NPPV were examined retrospectively. Average PaCO(2) 3-6 months after NPPV (3- to 6-mo PaCO(2)) and potential confounders were analyzed with discontinuation of long-term NPPV as the primary outcome. The effects of 3- to 6-mo PaCO(2) on annual hospitalization rates due to respiratory deterioration from 1 year before to 3 years after the initiation of NPPV were examined. The effect of the difference between the PaCO(2) value at the start of NPPV (0-mo PaCO(2)) and the PaCO(2) value 3- to 6-mo later (d-PaCO(2)) on continuation rates for NPPV was also assessed in patients who initiated NPPV while in a chronic state. Patients with relatively low 3- to 6-mo PaCO(2) values maintained a relatively low PaCO(2) 6-36 months after NPPV (p < 0.0001) and had significantly better continuation rates (p < 0.03) and lower hospitalization rates from the 1st to 3rd year of NPPV (p = 0.008, 0.049, 0.009, respectively) than those with higher levels. The 0-mo PaCO(2) (p = 0.26) or d-PaCO(2) (p = 0.86) had no predictive value. A relatively low 3- to 6-mo PaCO(2) value was predictive of long-term use of NPPV. The target values for 3- to 6-mo PaCO(2) may, therefore, be less than 60 mmHg in post-tuberculosis patients, although more studies are needed.
    Respiratory medicine 12/2010; 104(12):1850-7. · 2.33 Impact Factor
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    ABSTRACT: Exploding head syndrome (EHS) attacks are characterized by the sensation of sudden loud banging noises, and are occasionally accompanied by the sensation of a flash light. Although these attacks in themselves are usually not painful, it is reported that EHS attacks may precede migraines and may be perceived as auras. A 53-year-old woman, with a 40-year history of fulgurating migraines, experienced 2 different types of EHS attacks. During most of the attacks, which were not painful, she heard sounds like someone yelling or cars passing by. Only 1 episode was accompanied with the sensation of a flash light and of sounds similar to those of an electrical short circuit. On the video-polysomnography, video-polysomnography showed 11 EHS attacks occurred during stage N1 and stage N2; these attacks were preceded by soft snoring. She also had moderate obstructive sleep apnea syndrome (Apnea Hypopnea Index: 16.7) for which an oral appliance was prescribed; the EHS attacks did not recur after this treatment. The pathophysiology of EHS is still unclear. A detailed analysis of PSG data may help in understanding the pathophysiology of this syndrome and also in the selection of therapeutic strategies.
    Brain and nerve = Shinkei kenkyū no shinpo 01/2010; 62(1):85-8.
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    ABSTRACT: Long-term noninvasive positive pressure ventilation (NPPV) is associated with an excellent survival rate, especially in post-tuberculosis patients. Nothing is currently known on which method of ventilatory support is associated with a better continuation of long-term NPPV, which itself might lead to longer survival. One hundred and eighty four post-tuberculosis patients, who started NPPV at the Kyoto University Hospital group and the National Tokyo Hospital from June 1990 to August 2007, were examined retrospectively. Ventilator mode (an assisted mode or a pure controlled mode) and potential confounders were examined with the discontinuation of NPPV as the primary outcome. Patients treated with a pure controlled mode had significantly better continuation rates (hazard ratio, 3.09; 95% confidential interval, 1.75-5.47; p=0.0001) and better survival rates (Log-rank test; p=0.0031) than those treated with an assisted mode. Female gender and no pulmonary lesions were also associated with a significantly better probability of continuing NPPV. The five- and ten-year probabilities of continuing NPPV for 106 patients with a pure controlled mode were 68.3% and 41.4%, respectively, while those for 76 patients with an assisted mode were 46.7% and 12.7%, respectively. Patients treated with pure controlled ventilation had significantly better continuation rates and survival rates than those treated with assisted ventilation. Prospective randomized controlled trials are needed to verify the effectiveness of a pure controlled mode in patients with not only restrictive thoracic disease but also other diseases including chronic obstructive pulmonary disease.
    Respiratory medicine 09/2009; 103(12):1854-61. · 2.33 Impact Factor
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    ABSTRACT: To aid in the identification of patients with moderate-to-severe sleep-disordered breathing (SDB), we developed and validated a simple screening tool applicable to both clinical and community settings. Logistic regression analysis was used to develop an integer-based risk scoring system. The participants in this derivation study included 132 patients visiting one of 2 hospitals in Japan, and 175 residents of a rural town. The participants in the present validation study included 308 employees of a company in Japan who were undergoing a health check. The screening tool consisted of only 4 variables: sex, blood pressure level, body mass index, and self-reported snoring. This tool (screening score) gave an area under the receiver operating characteristic curve (ROC) of 0.90, sensitivity of 0.93, and specificity of 0.66, using a cutoff point of 11. Predicted and observed prevalence proportions in the validation dataset were in close agreement across the entire spectrum of risk scores. In the validation dataset, the area under the ROC for moderate-to-severe SDB and severe SDB were 0.78 and 0.85, respectively. The diagnostic performance of this tool did not significantly differ from that of previous, more complex tools. These findings suggest that our screening scoring system is a valid tool for the identification and assessment of moderate-to-severe SDB. With knowledge of only 4 easily ascertainable variables, which are routinely checked during daily clinical practice or mass health screening, moderate-to-severe SDB can be easily detected in clinical and public health settings.
    Sleep 08/2009; 32(7):939-48. · 5.10 Impact Factor
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    ABSTRACT: REM sleep behavior disorder (RBD) is characterized by loss of normal REM sleep skeletal muscle atonia, resulting in complex motor behaviors associated with dream mentation. Reports have been accumulated showing an association of RBD and neurodegenerative diseases. However, in Japan, no data has been available about demographic features of RBD in a large patient population. We describe demographic characteristics of RBD patients presenting to our sleep center with special emphasis on association of RBD and neurodegenerative diseases. The subjects were consecutive 10,745 patients who presented with sleep and/or wake problems at our sleep center from April 1998 to March 2006. Diagnosis of RBD was made based on ICSD-2 criteria. Medical and sleep histories with complementary information from family members, and findings of neurological examination were assessed retrospectively from the notes of RBD patients. Sixty-seven patients (0.6%) were diagnosed as having RBD. There was strong male predominancy (85.1%). The onset of RBD symptoms was at 61.4+/-8.8 years of age. Neurological symptoms and signs were present in twelve (17.9 % of RBD patients) when they firstly came to our sleep center: 4 patients with Parkinson disease, 4 with multiple system atrophy and 1 with probable dementia with Lewy body. Thirteen patients (43.3%) were aware of olfactory impairment when inquired (out of 30 patients). Clonazepam was administered in 29 patients, and 21 (72.4%) responded well. Our study showed the similar demographic characteristics of RBD to what was shown in the previous large case series. Although the association between RBD and neurodegenerative diseases was not so strong in our cases, it may be mainly because our sleep center was not run in the domain of neurology department and we could not vigorously detect the possible coexistence of neurodegenerative disease. The pathogenesis of RBD is still unclear; therefore, neurologists and sleep specialists need to collaborate in following up RBD patients to confirm whether they are at higher risk for developing a neurodegenerative disease.
    Brain and nerve = Shinkei kenkyū no shinpo 12/2007; 59(11):1265-71.
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    ABSTRACT: To clarify whether noninvasive positive pressure ventilation (NPPV) is effective in patients with acute exacerbations of pulmonary tuberculosis sequelae (PTS), 50 PTS patients (66 episodes) without long-term domiciliary noninvasive ventilation were studied, retrospectively. The average values (SD) of their pulmonary function tests and arterial blood gases were as follows; %predicted VC = 31.4 (8.4)%, pH = 7.29 (0.06), PaCO2 = 91.8 (19.7) mmHg, and PaO2 = 64.2 (20.3) mmHg. The probability of avoiding endotracheal intubation and recovering from an acute exacerbation with NPPV (NPPV success rate) was 92% as a whole. NPPV success rates according to the causes of deterioration were as follows; 96% in 26 episodes with only a simple right heart failure, 93% in 29 episodes with airway infectious diseases, 75% in eight episodes with pneumonia and/or acute respiratory distress syndrome. Moreover, the NPPV success rate of eight episodes in coma or semicoma was 88%. Most patients were treated in respiratory wards rather than intensive care units. Out of 46 patients who recovered from an acute exacerbation, 41 finally received domiciliary NPPV. In facilities where staff are well-trained for an acute NPPV, patients with exacerbations of PTS can be treated as successfully with NPPV as patients with COPD.
    Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 04/2006; 44(3):160-7.
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    ABSTRACT: Hypoxemia increases corrected QT dispersion (QTcD), which is the difference between the maximum and minimum QT intervals and is a strong risk factor for cardiovascular mortality. The aim of this study was to investigate the QTcD in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS), and the relationship between the QTcD and (123)I-metaiodobenzylguanidine (MIBG) cardiac imaging, which reflects cardiac sympathetic activity. A university hospital. Forty-eight OSAHS patients without cardiac diseases (mean [+/- SD] age, 45.9 +/- 10.8 years; apnea-hypopnea index [AHI] 51.9 +/- 18.5 events per hour) who underwent polysomnography before treatment and on the first night of nasal continuous positive airway pressure (nCPAP) treatment. Before and after nCPAP treatment was started, we measured the QTcD with computer software, before, during, and after sleep, as well as the washout rate of the MIBG administered for cardiac imaging. As a control, QTcD was also measured in the morning from 26 healthy subjects. Before treatment, the mean QTcD during sleep (65.0 +/- 14.6 ms) was greater than that before sleep (57.0 +/- 13.5 ms; p < 0.0001). Meanwhile, after 1 night of nCPAP therapy, the QTcD during sleep (50.6 +/- 11.4 ms) decreased from that before treatment (p < 0.0001) and was smaller than the QTcD before sleep (56.2 +/- 13.3 ms; p = 0.003). Before treatment, the QTcD during sleep correlated with the AHI (r = 0.38; p = 0.009) and the percentage of time that SaO(2) was < 90% (SaO(2) < 90% time) [r = 0.34; p = 0.018]. The QTcD did not correlate with the body mass index or the washout rate of MIBG. However, the washout rate of MIBG correlated with the AHI and the SaO(2) < 90% time. Nocturnal QTcD is increased in OSAHS patients but is decreased by nCPAP therapy independently of cardiac sympathetic function.
    Chest 06/2004; 125(6):2107-14. · 7.13 Impact Factor
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    ABSTRACT: Short-term compliance of nasal continuous airway pressure (nCPAP) therapy in elderly patients (65 years or older; n = 115) with moderate to severe obstructive sleep apnea was investigated. When nCPAP therapy was offered to elderly patients with an apnea–hypopnea index greater than 20/h, the acceptance rate of nCPAP therapy was 70%. Of those, the short-term tolerance rate of nCPAP therapy (usage over 3 months after initial trial) was 83%. The patients who refused or abandoned nCPAP therapy were less severe (in terms of the apnea–hypopnea index), less sleepy and there were a lower number with hypertension. Considering the short-term compliance of nCPAP therapy reported for middle-aged patients in the literature, it is found that acceptance and short-term tolerance of nCPAP therapy in elderly patients is high, especially in patients with hypertension and excessive daytime sleepiness.
    Sleep and Biological Rhythms 03/2004; 2(1):53 - 56. · 1.05 Impact Factor
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    ABSTRACT: Obesity has been associated with obstructive sleep apnea and hepatic steatosis. We investigated the effects of obstructive sleep apnea and treatment with nasal continuous positive airway pressure (CPAP) on serum aminotransferase levels in obese patients. We studied 40 obese men with obstructive sleep apnea syndrome. None had hepatitis B antigen or C antibody, autoimmune disease, or an excessive intake of alcohol. Serum levels of aspartate aminotransferase, alanine aminotransferase, triglyceride, glucose, insulin, and leptin were determined in the afternoon and in the morning immediately after sleep, before and after nasal CPAP treatment. Aminotransferase levels were abnormal in 35% (n = 14) of patients. Before treatment, mean (+/- SD) aspartate aminotransferase levels were higher in the morning than in the previous afternoon (presleep, 34 +/- 20 IU/L; postsleep, 39 +/- 28 IU/L; P = 0.006). The overnight mean increases in aminotransferase levels were less marked after the first night of nasal CPAP treatment (aspartate aminotransferase: from 6 +/- 11 IU/L to 2 +/- 6 IU/L, P = 0.0003; alanine aminotransferase: from 5 +/- 9 IU/L to 2 +/- 6 IU/L, P = 0.006). Leptin levels (n = 23) decreased significantly after treatment (P = 0.0002), whereas insulin resistance (calculated by the homeostasis model assessment method) and triglyceride levels were unchanged. Improvements in aspartate and alanine aminotransferase levels were maintained after 1 and 6 months of nasal CPAP treatment. Nasal CPAP therapy may have beneficial effects on serum aminotransferase abnormalities in obese patients who have obstructive sleep apnea.
    The American Journal of Medicine 05/2003; 114(5):370-6. · 5.30 Impact Factor
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    ABSTRACT: We studied the quality of life of obesity hypoventilation syndrome (OHS) by comparing it with age- and body mass index-matched patients without hypoventilation and age-matched obstructive sleep apnea (OSA) patients with body mass index (BMI) under 30, and the efficacy of nasal continuous positive airway pressure (CPAP) therapy for 3 to 6 months on the quality of life in these patients. Prospectively recruited patients from six sleep laboratories in Japan were administered assessments of the general health status by the Short-Form 36 Health Survey (SF-36) and subjective sleepiness by the Epworth Sleepiness Scale (ESS). Compared with matched healthy subjects, OHS and OSA patients not yet treated had worse results on the ESS scores and the SF-36 subscales for physical functioning, role limitations due to physical problems, general health perception, energy/vitality, role limitations due to emotional problems, and social functioning. The ESS scores of OHS patients were worse than those of the OSA groups including the age- and BMI-matched OSA patients. In the SF-36 subscales of OHS patients, only the subscale of social functioning showed worse results compared with that of BMI-matched OSA patients. After 3 to 6 months of treatment, ESS scores and these SF-36 subscales in all three patient groups improved to the normal level. These results suggested that the quality of life of OHS before nasal CPAP was significantly impaired and that nasal CPAP for OHS improved the quality of life associated with the improvement of daytime sleepiness to the level of the other OSA patients.
    Sleep And Breathing 04/2003; 7(1):3-12. · 2.26 Impact Factor
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    ABSTRACT: The control of body weight and cardiac sympathetic function in patients with obstructive sleep apnoea-hypopnoea syndrome (OSAHS) are important because both factors have significant effects on the mortality of these patients. It has recently been reported that OSAHS has a significant effect on the secretion of leptin, a hormone involved in the control of body weight and sympathetic nerve activity. In addition to the circadian rhythm of leptin secretion, the effects of one night of treatment with nasal continuous positive airway pressure (nCPAP) and the mechanism of the effects of nCPAP on nocturnal leptin secretion in patients with OSAHS has not yet been elucidated. Blood samples were obtained at 21.00 hours, 00.00 hours, 03.00 hours, and 06.30 hours from 21 subjects with OSAHS (mean apnoea and hypopnoea index 52.4/h), with and without nCPAP treatment. Iodine-123 (I(123))-meta-iodobenzylguanidine (MIBG) imaging was used to evaluate myocardial sympathetic function before nCPAP treatment. Plasma leptin reached a peak level at 00:00 hours (p<0.01) in patients with OSAHS, both with and without nCPAP treatment. The first night of nCPAP treatment significantly decreased the plasma leptin levels at 03.00 hours (without nCPAP: mean (SE) 21.6 (4.7) ng/ml; with nCPAP: 19.3 (4.1) ng/ml, p<0.02) and at 06.30 hours (without nCPAP: 17.6 (3.8) ng/ml; with nCPAP: 15.2 (3.2) ng/ml, p<0.01). The magnitude of the decrease in leptin levels after nCPAP treatment was significantly correlated with cardiac sympathetic function measured before nCPAP treatment (p<0.03). Patients with OSAHS undergo nocturnal increases in leptin levels in spite of interruption of sleep due to apnoea and hypopnoea, a trend seen in normal subjects. Plasma leptin levels in patients with OSAHS decreased significantly after the first night of nCPAP treatment. Enhanced cardiac sympathetic function in these patients may contribute to the leptin levels before nCPAP treatment and vice versa.
    Thorax 05/2002; 57(5):429-34. · 8.38 Impact Factor
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    ABSTRACT: We have previously shown that aberrant crypt foci (ACF) are the putative precursor lesions of colorectal adenomas and subsequent cancer in humans using magnifying endoscopy. The present study was designed to investigate these genetic alterations in ACF biopsy specimens from normal subjects, familial adenomatous polyposis (FAP) or sporadic patients. The non-FAP cases included 34 normal subjects, 35 colorectal adenoma patients, and 19 colorectal cancer patients; there were 4 FAP patients. Biopsies were performed on ACF by magnifying endoscopy. K-ras mutations were analyzed by 2-step polymerase chain reaction and restriction fragment length polymorphism, APC mutations by in vitro-synthesized protein assay, and beta-catenin mutations by direct sequencing. Full-length APC and beta-catenin were detected by immunofluorescence. In non-FAP cases, K-ras mutations were detected in 82% (89/106) of nondysplastic ACF and 63% (17/27) of dysplastic ACF. APC mutation and beta-catenin accumulation were not detected in non-FAP ACF, whereas in adenoma of these patients, positivity of APC mutation and beta-catenin accumulation were 78% (24/31), and that of K-ras mutation was 65% (20/31). FAP patients showed K-ras mutations in only 13% (1/8) of dysplastic ACF, which is the predominant form of ACF found in FAP. In FAP patients, somatic APC mutations were found in 100% of dysplastic ACF, as they are in adenoma. The frequency of K-ras mutations was 73% (8 of 11) in FAP adenoma. The data suggest that in sporadic colorectal carcinogenesis, assuming the biological implication of ACF as a precursor of adenomas, there is a route where K-ras mutation mainly occurs during the formation of ACF, which then become adenomas wherein APC mutation occurs. In FAP, however, somatic mutation of APC predominantly occurs during ACF formation, followed by K-ras mutation.
    Gastroenterology 10/2001; 121(3):599-611. · 12.82 Impact Factor
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    ABSTRACT: In colorectal adenoma and carcinoma, glutathione S-transferase-pi (GSTP1-1) is highly expressed. K-ras mutation is also known to occur frequently in colorectal adenoma and carcinoma, as well as in the putative precursor of adenoma, aberrant crypt foci (ACF). Further, forced expression of v-H-ras in rat liver epithelial cells has been shown to enhance rat pi-class GST expression. The aim of the present study is, therefore, to investigate the causative relationship between GSTP1-1 overexpression and K-ras mutation in these lesions. Twenty-seven specimens of colorectal carcinoma, 24 of adenoma, and 28 of ACF were examined in this study. The expression of GSTP1-1 or p21(K-ras) was examined by immunohistochemistry. The GSTP1-1 messenger RNA levels were measured by TaqMan reverse-transcription polymerase chain reaction (PCR). K-ras mutation was detected by two-step PCR restriction fragment length polymorphism. v-K-ras transfection to RPMI-4788 colon carcinoma cells was carried out by the lipofection method. Activities of GSTP1-1 promoters containing AP-1 and Sp1 responsive elements in the v-K-ras transfectants were measured by a secreted form of human placental alkaline phosphatase (SEAP) assay. Nuclear protein from these transfectants bound to the GSTP1-1 promoter was analyzed by electrophoretic mobility shift assay (EMSA). In human colorectal carcinoma, adenoma, and ACF, close association of increased expression of GSTP1-1 with K-ras mutation was observed. v-K-ras transfectants showed significantly higher SEAP activity than that of mock-transfectant activity. EMSA showed specific interaction of AP-1 with promoter of GSTP1-1. It is highly plausible that GSTP1-1 overexpression in ACF, colorectal adenoma, and carcinoma is induced by K-ras mutation via AP-1 activation.
    Gastroenterology 10/2001; 121(4):865-74. · 12.82 Impact Factor

Publication Stats

1k Citations
250.35 Total Impact Points

Institutions

  • 2011
    • Kyoto Medical Center
      Kioto, Kyōto, Japan
  • 1989–2010
    • Kyoto University
      • • Department of Respiratory Medicine
      • • Primate Research Institute
      Kyoto, Kyoto-fu, Japan
  • 2006
    • National Hospital Organization Minami Kyoto Hospital
      Kioto, Kyōto, Japan
  • 2003
    • Kobe Kaisei Hospital
      Kōbe, Hyōgo, Japan
  • 1996
    • Osaka Bioscience Institute
      Ōsaka, Ōsaka, Japan