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Biomedical subjects

T Kondo

Publications and source records attributed to T Kondo.

At least 19 recordsLinked to original sources

Frontal cerebral blood flow change associated with infant-directed speech.

OBJECTIVE: To examine the auditory perception of maternal utterances by neonates using near-infrared spectroscopy (NIRS). METHODS: Twenty full-term, healthy neonates were included in this study. The neonates were tested in their cribs while they slept in a silent room. First, two probe holders were placed on the left and right sides of the forehead over the eyebrows using double-sided adhesive tape. The neonates were then exposed to auditory stimuli in the form of infant-directed speech (IDS) or adult-directed speech (ADS), sampled from each of the mothers, through an external auditory speaker. RESULTS: A 2 (stimulus: IDS and ADS) x 2 (recording site: channel 1 (right side) and channel 2 (left side)) analysis of variance for these relative oxygenated haemoglobin values showed that IDS (Mean = 0.25) increased brain function significantly (F = 3.51) more than ADS (Mean = -0.26). CONCLUSIONS: IDS significantly increased brain function compared with ADS. These results suggest that the emotional tone of maternal utterances could have a role in activating the brains of neonates to attend to the utterances, even while sleeping.

Acoustic Stimulation↗

Genome-wide profiling of promoter methylation in human.

DNA methylation in the promoter region of a gene is associated with a loss of that gene's expression and plays an important role in gene silencing. The inactivation of tumor-suppressor genes by aberrant methylation in the promoter region is well recognized in carcinogenesis. However, there has been little study in this area when it comes to genome-wide profiling of the promoter methylation. Here, we developed a genome-wide profiling method called Microarray-based Integrated Analysis of Methylation by Isoschizomers to analyse the DNA methylation of promoter regions of 8091 human genes. With this method, resistance to both the methylation-sensitive restriction enzyme HpaII and the methylation-insensitive isoschizomer MspI was compared between samples by using a microarray with promoter regions of the 8091 genes. The reliability of the difference in HpaII resistance was judged using the difference in MspI resistance. We demonstrated the utility of this method by finding epigenetic mutations in cancer. Aberrant hypermethylation is known to inactivate tumour suppressor genes. Using this method, we found that frequency of the aberrant promoter hypermethylation in cancer is higher than previously hypothesized. Aberrant hypomethylation is known to induce activation of oncogenes in cancer. Genome-wide analysis of hypomethylated promoter sequences in cancer demonstrated low CG/GC ratio of these sequences, suggesting that CpG-poor genes are sensitive to demethylation activity in cancer.

Adenocarcinoma↗

Long term smoking with age builds up excessive oxidative stress in bronchoalveolar lavage fluid.

BACKGROUND: Epithelial lining fluid plays a critical role in protecting the lung from oxidative stress, in which the oxidised status may change by ageing, smoking history, and pulmonary emphysema. METHODS: Bronchoalveolar lavage (BAL) was performed on 109 young and older subjects with various smoking histories. The protein carbonyls, total and oxidised glutathione were examined in BAL fluid. RESULTS: By Western blot analysis, the major carbonylated protein in the BAL fluid was sized at 68 kDa, corresponding to albumin. The amount of carbonylated albumin per mg total albumin in BAL fluid was four times higher in older current smokers and three times higher in older former smokers than in age matched non-smokers (p<0.0001, p=0.0003, respectively), but not in young smokers. Total glutathione in BAL fluid was significantly increased both in young (p=0.006) and older current smokers (p=0.0003) compared with age matched non-smokers. In contrast, the ratio of oxidised to total glutathione was significantly raised (72%) only in older current smokers compared with the other groups. There was no significant difference in these parameters between older smokers with and without mild emphysema. CONCLUSIONS: Oxidised glutathione associated with excessive protein carbonylation accumulates in the lung of older smokers with long term smoking histories even in the absence of lung diseases, but they are not significantly enhanced in smokers with mild emphysema.

Adult↗

Maternal smoking during pregnancy and genetic polymorphisms in the Ah receptor, CYP1A1 and GSTM1 affect infant birth size in Japanese subjects.

Genetic susceptibility to tobacco smoke might have relation to adverse pregnancy outcomes. To estimate the effects of maternal smoking and genetic polymorphisms on infant birth weight and length, we conducted a prospective cohort study of 293 women who delivered singleton live births in Sapporo, Japan. Birth weight and length were significantly lower among infants born to continuously smoking women having the aryl hydrocarbon receptor (AhR) wild type genotype (Arg/Arg; 211 g +/- 76 g; 1.2 cm +/- 0.4 cm, p < 0.01 and p < 0.01, respectively), the CYP1A1 variant genotype (m1/m2 + m2/m2; 170 g +/- 64 g, 0.8 cm +/- 0.3 cm, p < 0.01 and p < 0.05, respectively), or the GSTM1 null genotype (171 g +/- 58 g, 0.6 cm +/- 0.3 cm, p < 0.01 and p < 0.05, respectively). When combinations of these genotypes were considered, birth weight and length were significantly lower for infants of continuously smoking women in the AhR wild type + CYP1A1 variant group (315 g +/- 116 g; 1.7 cm +/- 0.6 cm, p < 0.01 and p < 0.01, respectively) and in the CYP1A1 variant + GSTM1 null group (237 g +/- 92 g; 1.3 cm +/- 0.5 cm, p < 0.05 and p < 0.01, respectively). These genotypes did not confer adverse effects among women who had never smoked; therefore, maternal smoking in combination with maternal AhR, CYP1A1 and GSTM1 genetic polymorphisms may adversely affect infant birth size.

Adult↗

Parental longevity and mortality amongst Japanese men and women: the JACC Study.

OBJECTIVES: To examine whether the risk of mortality varies according to parents' age at death. DESIGN AND SUBJECTS: A large prospective study in Japanese men and women from 45 communities across Japan. A total of 51 485 men and women aged 40-79 years completed self-administered questionnaires at baseline and followed up for 9.6 years. RESULTS: The risk of mortality from stroke, cardiovascular disease, and all causes was 20-30% lower in men and women with fathers who died at age > or = 80 years, compared with those with fathers whose age at death was <60 years. A similar reduction was found when the age at death of mothers was > or = 85 years compared with <65 years. Furthermore, the risk reduction was more evident amongst persons with both parents being long-lived parents compared with those with being short-lived parents, especially for death from cardiovascular disease. CONCLUSIONS: Our findings indicate that parental longevity could be a predictor for reduced risk of mortality from stroke, cardiovascular disease, and all causes for both Japanese men and women.

Adult↗

Evaluation of sludge reduction and phosphorus recovery efficiencies in a new advanced wastewater treatment system using denitrifying polyphosphate accumulating organisms.

A new biological nutrient removal process, anaerobic-oxic-anoxic (A/O/A) system using denitrifying polyphosphate-accumulating organisms (DNPAOs), was proposed. To attain excess sludge reduction and phosphorus recovery, the A/O/A system equipped with ozonation tank and phosphorus adsorption column was operated for 92 days, and water quality of the effluent, sludge reduction efficiency, and phosphorus recovery efficiency were evaluated. As a result, TOC, T-N and T-P removal efficiency were 85%, 70% and 85%, respectively, throughout the operating period. These slightly lower removal efficiencies than conventional anaerobic-anoxic-oxic (A/A/O) processes were due to the unexpected microbial population in this system where DNPAOs were not the dominant group but normal polyphosphate-accumulating organisms (PAOs) that could not utilize nitrate and nitrite as electron acceptor became dominant. However, it was successfully demonstrated that 34-127% of sludge reduction and around 80% of phosphorus recovery were attained. In conclusion, the A/O/A system equipped with ozonation and phosphorus adsorption systems is useful as a new advanced wastewater treatment plant (WWTP) to resolve the problems of increasing excess sludge and depleted phosphorus.

Adsorption↗

[Analysis of surgical treatment of primary lung cancer having M1 diseases].

The presence of distant metastasis is thought as systemic dissemination of disease. Patients with lung cancer in this category are not usually considered candidates for surgical resection of the primary and metastatic sites. The purpose of this study is to determine long-term survival and identify potential prognostic factors for surgical treatment to primary non-small cell lung cancer with distant metastasis. We conducted a retrospective analysis of the surgical outcome of 24 patients who were classified as having M1 disease. The 5-year survival rate was 34.6% in our facility. Among the 12 patients had N2 disease and a poor prognosis. Long-term survival can be achieved if the metastatic site is lung and there is no lymph node involvement, although differentiation of pulmonary metastasis and multiple primary lung cancer is commonly difficult.

Brain Neoplasms↗

[Bronchoplasty without lung resection for the complete transection of the left main bronchus due to blunt trauma].

Blunt bronchial injury is rare but crucial injury. A 17-year-old female was admitted due to traumatic injury. She was diagnosed with bilateral lung contusion, multiple rib fractures, spleen damage and the suspicion about the complete transection of the left main bronchus on X-ray and computed tomography (CT). She was brought to our hospital at 30 hours later from injury. Bronchoscopy revealed the complete transection and the edema of the left main bronchus. She underwent a resection of the disrupted portion and end-to-end anastomosis of left main bronchus without lung resection. We should be an immediate and accurate diagnosis of tracheobronchial disruption by X-ray, CT and bronchoscopy whenever we evaluate patients with blunt chest trauma.

Adolescent↗

Regulation of the antioncogenic Chk2 kinase by the oncogenic Wip1 phosphatase.

The antioncogenic Chk2 kinase plays a crucial role in DNA damage-induced cell-cycle checkpoint regulation. Here we show that Chk2 associates with the oncogenic protein Wip1 (wild-type p53-inducible phosphatase 1) (PPM1D), a p53-inducible protein phosphatase. Phosphorylation of Chk2 at threonine68 (Thr68), a critical event for Chk2 activation, which is normally induced by DNA damage or overexpression of Chk2, is inhibited by expression of wild-type (WT), but not a phosphatase-deficient mutant (D314A) of Wip1 in cultured cells. Furthermore, an in vitro phosphatase assay revealed that Wip1 (WT), but not Wip1 (D314A), dephosphorylates Thr68 on phosphorylated Chk2 in vitro, resulting in the inhibition of Chk2 kinase activity toward glutathione S-transferase-Cdc25C. Moreover, inhibition of Wip1 expression by RNA interference results in abnormally sustained Thr68 phosphorylation of Chk2 and increased susceptibility of cells in response to DNA damage, indicating that Wip1 acts as a negative regulator of Chk2 in response to DNA damage.

Amino Acids↗

Analysis of gene expression in apoptosis of human lymphoma U937 cells induced by heat shock and the effects of alpha-phenyl N-tert-butylnitrone (PBN) and its derivatives.

Hyperthermia, a modality of cancer therapy, has been known as a stress to induce apoptosis. However, the molecular mechanism of heat shock-induced apoptosis, especially on roles of intracellular oxidative stress, is not fully understood. First, when human lymphoma U937 cells were treated with heat shock (44 degrees C, 30 min), the fraction of apoptosis, revealed by phosphatidylserine externalization, increased gradually and peaked at 6 hr after the treatment. In contrast, intracellular superoxide formation increased early during the heat shock treatment and peaked at 30 min after the treatment. When the cells were treated with heat shock in the presence of alpha -phenyl-N-tert-butylnitrone (PBN) and its derivatives, which are potent antioxidants, the DNA fragmentation was inhibited in an order according to the agents' hydrophobicity. PBN showing the highest inhibitory effects suppressed not only intracellular superoxide formation but also various apoptosis indicators. cDNA microarray was employed to analyze gene expression associated with heat shock-induced apoptosis, and the time-course microarray analysis revealed 5 groups showing changes in their pattern of gene expression. Among these genes, c-jun mRNA expression showed more than 40 fold increase 2 hr after heat treatment. The expression level of c-jun mRNA verified by quantitative real-time PCR was about 20 fold increase, and c-jun expression was similarly suppressed by PBN and its derivatives. These results suggest that the change of c-jun expression is an excellent molecular marker for apoptosis mediated by intracellular oxidative stress induced by heat shock.

Anions↗

Nuclear localisation of glutathione S-transferase pi is an evaluation factor for drug resistance in gynaecological cancers.

AIMS: Nuclear glutathione S-transferase pi (GST7pi) has been reported to protect cancer cells against anticancer drugs. The aim of the present study was to evaluate the clinical significance of nuclear GSTpi in gynaecological cancer. MATERIALS AND METHODS: We carried out an immunohistochemical analysis of GSTpi, and examined the correlation between nuclear GSTpi: expression and prognosis in 43 epithelial ovarian cancers. We compared expression levels before and after chemotherapy in uterine cervical cancers and endometrial cancers. RESULTS: The 5-year progression-free survival rate of the nuclear GSTpi-positive group was lower than that of the cytoplasmic GSTpi-positive group, and was significantly lower than that of the negative group (14.3% vs 34.8% vs 66.7%; P = 0.041). The expression of nuclear GSTpi was compared before and after chemotherapy in uterine cervical and endometrial cancers. In eight out of 12 cases (66.7%), the expression turned positive after the chemotherapy. CONCLUSIONS: We suggest that nuclear localisation of GSTpi is associated with drug resistance. The nuclear localisation of GSTpi in tumour cells is a useful prognosticator, and may contribute to the selection of anticancer drugs for gynaecological cancers.

Adult↗

Astroglial expression of ceramide in Alzheimer's disease brains: a role during neuronal apoptosis.

Accumulating evidences indicate that ceramide is closely involved in apoptotic cell death in neurodegenerative disorders and aging. We examined ceramide levels in the cerebrospinal fluid (CSF) or brain tissues from patients with neurodegenerative disorders and the mechanism of how intra- and extracellular ceramide was regulated during neuronal apoptosis. We screened the ceramide levels in the CSF of patients with neurodegenerative disorders, and found that ceramide was significantly increased in patients with Alzheimer's disease (AD) than in patients with age-matched amyotrophic lateral sclerosis (ALS) and other neurological controls. With immunohistochemistry in AD brains, ceramide was aberrantly expressed in astroglia in the frontal cortices, but not detected in ALS and control brains. To explore for the regulation of ceramide in astroglia in Alzheimer's disease brains, we examined the metabolism of ceramide during neuronal apoptosis. In retinoic acid (RA)-induced neuronal apoptosis, RA slightly increased de novo synthesis of ceramide, but interestingly, RA dramatically inhibited conversion of [14C] ceramide to glucosylceramide (GlcCer), suggesting that the increase of ceramide mass is mainly due to inhibition of the ceramide-metabolizing enzyme GlcCer synthase. In addition, a significant increase of the [14C] ceramide level in the culture medium was detected by chasing and turnover experiments without alteration of extracellular [14C] sphingomyelin levels. A 2.5-fold increase of ceramide mass in the supernatant was also detected after 48 h of treatment with RA. These results suggest a regulatory mechanism of intracellular ceramide through inhibition of GlcCer synthase and a possible role of ceramide as an extracellular/intercellular mediator for neuronal apoptosis. The increased ceramide level in the CSF from AD patients, which may be derived from astroglia, raises a possibility of neuronal apoptosis by the response to intercellular ceramide in AD.

Aged↗

Recombinant interferon alpha treatment decreases heart rate variability indices and impairs exercise tolerance in patients with chronic hepatitis.

Complications of interferon (IFN) therapy include cardiac arrhythmias, impaired cardiac function and myocardial ischemia. Decreased heart rate variability (HRV) indices, impaired exercise tolerance and decreased left ventricular (LV) function are related to unfavorable outcome of heart disease. To investigate the effect of IFN therapy on HRV, exercise tolerance and cardiac function, 24-h ambulatory electrocardiographic monitoring (AECG), two-dimensional echocardiography, and exercise treadmill testing (ETT) was performed in 9 patients (age 56 +/- 9 years-old) with chronic hepatitis and without underlying heart disease before and after treatment with IFN (recombinant alpha 2b; 10 x 10(6) U/day for 4 weeks). HRV parameters consisted of standard deviation of RR interval (sdNN, ms), SDANN (ms), S.D. index (ms), rMSSD (ms), pNN50 (%) and frequency analysis of heart rate spectrum resulted in low (ms, 0.04-0.15 Hz), high (ms, 0.15-0.40 Hz) and total (ms, 0.01-1.00 Hz) frequency components. Ischemia was not detected by AECG or ETT, and LV function was normal after INF treatment in all patients. However, INF treatment resulted in a decrease in exercise tolerance time (449 +/- 94 s vs. 329 +/- 67 s, P < 0.05) and a decrease in several HRV parameters (S.D. index, 42 +/- 5 ms vs. 37 +/- 9 ms; rMSSD, 22 +/- 5 ms vs. 19 +/- 4 ms; pNN50, 4 +/- 3% vs. 2 +/- 1%; P < 0.05). Further, patients treated with INF tended to have a lower sdNN and total frequency spectra, although this difference did not reach the level of statistical significance. These data suggest that the arrhythmogenic effect of INF may be mediated by decreases in HRV and impairment of exercise tolerance even in patients without overt heart diseases. Further, INF therapy may be contraindicated in patients with predisposing severe cardiac disorders, including arrhythmias, ischemia and decreased LV function.

Adult↗

Familial aggregation and coaggregation of history of hypertension and stroke.

We attempted to evaluate familial aggregation and coaggregation of history of hypertension and stroke. Past and family history of hypertension and stroke for 83 089 probands and their relatives were obtained from a data set for the Japan Collaborative Cohort Study for Evaluation of Cancer Risk sponsored by the Ministry of Education (JACC Study), which was initiated from 1988 to 1990. First, evaluation was performed for familial aggregation of each of two disorders using ordinal logistic regression of the generalized estimation equations (GEE) to account for dependence of observations within families. Secondly, in order to evaluate the familial congregation of the history of hypertension and stroke, a GEE-based multivariate probed predictive model was applied. After adjusting for the proband's age, level of obesity, smoking status, drinking status, habitation area, and the gender and type of the relatives, the estimated odds ratios for the intraindividual clustering and familial aggregation of the disease history showed statistically significant relationships. In addition, the history of the two disorders showed a significant relationship in terms of familial coaggregation independently of the aggregation of each disorder itself. Our results confirmed that hypertension and stroke coaggregate strongly within families through possible effects of genetic factors, which, alone or in conjunction with environmental factors, influence susceptibility to both hypertension and stroke.

Adult↗