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Biomedical subjects

Keiko Sakuma

Publications and source records attributed to Keiko Sakuma.

8 recordsLinked to original sources
PubMed2006

Combined genotoxic effects of radiation and a tobacco-specific nitrosamine in the lung of gpt delta transgenic mice.

It is important to evaluate the health effects of low-dose-rate or low-dose radiation in combination with chemicals as humans are exposed to a variety of chemical agents. Here, we examined combined genotoxic effects of low-dose-rate radiation and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), the most carcinogenic tobacco-specific nitrosamine, in the lung of gpt delta transgenic mice. In this mouse model, base substitutions and deletions can be separately analyzed by gpt and Spi- selections, respectively. Female gpt delta mice were either treated with gamma-irradiation alone at a dose rate of 0.5, 1.0 or 1.5 mGy/h for 22 h/day for 31 days or combined with NNK treatments at a dose of 2 mg/mouse/day, i.p. for four consecutive days in the middle course of irradiation. In the gpt selection, the NNK treatments enhanced the mutation frequencies (MFs) significantly, but no obvious combined effects of gamma-irradiation were observable at any given radiation dose. In contrast, NNK treatments appeared to suppress the Spi- large deletions. In the Spi- selection, the MFs of deletions more than 1 kb in size increased in a dose-dependent manner. When NNK treatments were combined, the dose-response curve became bell-shaped where the MF at the highest radiation dose decreased substantially. These results suggest that NNK treatments may elicit an adaptive response that eliminates cells bearing radiation-induced double-strand breaks in DNA. Possible mechanisms underlying the combined genotoxicity of radiation and NNK are discussed, and the importance of evaluation of combined genotoxicity of more than one agent is emphasized.

Animals↗
PubMed2005

Serotonin transporter polymorphisms affect human blood glucose control.

We measured the effect of nutritional intervention on clinical data, including fasting blood glucose (FBG), and their association with polymorphisms of the serotonin transporter-linked polymorphic region (5-HTTLPR) which might affect adherence. Enrolled in the intervention program were 264 Japanese women not on medication for diabetes, hypercholesterolemia or hypertension. The 5-HTTLPR allele (S and L) frequencies among the subjects differed markedly from those of Caucasians: SS (n = 183), LS (n = 69), and LL (n = 12). The decrease in FBG (DeltaFBG) from the beginning to the end of the program (11 weeks; short-term study), and DeltaFBG from the beginning to a follow-up check performed between 2002 and 2004 (average of 23 years later; long-term study) was calculated. The SS homozygotes of 5-HTTLPR showed larger DeltaFBG (P = 0.01 and P < 0.0001 in the short- and long-term studies, respectively) than DeltaFBG with other genotypes.

Adult↗
PubMed2005

Expression of calbindin-D9k, VDR and Cdx-2 messenger RNA in the process by which fructooligosaccharides increase calcium absorption in rats.

We have previously shown, through evidence that the expression of calbindin-D9k protein shows a dose-dependent change in the intestine, that calbindin-D9k plays a role in the ability of a fructooligosaccharide (FOS) diet to increase calcium absorption. This study shows that the regulation of calbindin-D9k expression occurs at the transcriptional level in a segment-specific manner, decreasing in the proximal intestine and increasing in the colorectal segment. To determine the transcriptional regulation of the FOS diet on calbindin-D9k expression, two transcription factors, vitamin D receptor (VDR) and cdx-2, were analyzed during 10 d feeding of the FOS diet. The mRNA expression of VDR and cdx-2 was influenced by the FOS diet and showed a segment-specific change. In the proximal small intestine, there was a significant correlation between the changes in both mRNAs (r = 0.69, p < 0.01), while the expression of calbindin-D9k correlated neither with VDR nor with cdx-2. This means that the transcriptional change induced by the FOS diet was not regulated by VDR and cdx-2. In the colorectal segment, there were significant correlations between gene expressions of calbindin-D9k vs. VDR, r = 0.73, p < 0.01 and calbindin-D9k vs. cdx-2, r = 0.52, p < 0.05. These results suggested that both transcription factors, VDR and cdx-2, were involved in the regulation of calbindin-D9k gene expression in the colorectal segment during the process through which the FOS diet enhanced calcium absorption.

Animals↗
PubMed2004

The specific expression patterns of lactase, sucrase and calbindin-D9k in weaning rats are regulated at the transcriptional level.

During weaning, rat lactase-phlorizin hydrolase (LPH) expression decreased to the low levels found in adults, while sucrase-isomaltase (SI) sharply increased. Calbindin-D9k (CaBP) is specific to the intestine and expression peaked within a few days of weaning. The present study investigates whether these molecules are regulated at transcriptional or post-transcriptional levels and examines the effects of diet on regulation. At normal weaning on day 21, litters were separated from their dams and one group was fed with a standard laboratory diet (weaned (W) group). The other group received a diet containing lactose as the sole source of carbohydrate (lactose-fed (L) group). Mucosal cells were obtained from the proximal part of the rat small intestine and then the activity and concentration of LPH, SI and CaBP proteins and mRNAs were determined. Three parameters revealed the same changing patterns in LPH, SI and CaBP during development and there was significant (p<0.001) correlation between three parameters: LPH, r=0.97 for activity vs. protein, r=0.99 for activity vs. mRNA, r=0.96 for protein vs. mRNA, SI, r=0.99 for activity vs. protein, r=0.98 for activity vs. mRNA, r=0.96 for protein vs. mRNA, CaBP, r=0.94 for activity vs. protein, r=0.97 for activity vs. mRNA, r=0.95 for protein vs. mRNA. Expression of the three proteins did not differ between the L and W groups. Accordingly, it has been suggested that the expression of LPH, SI and CaBP during development is defined at the transcriptional level and dietary changes do not exert a primary effect on it.

Aging↗
PubMed2004

The effect of fructooligosaccharides was analyzed by cDNA expression arrays.

We have already reported that indigestible fructooligosaccharides (FOS) increased calcium absorption in rat large intestines and that calbindin-D9k (CaBP), which is an intestine-specific calcium-binding protein, is involved in that increasing effect. In this study, not only the CaBP gene, every gene that changed expression profiles as the result of FOS feeding was identified by cDNA expression arrays. Sprague-Dawley male rats were fed an experimental diet containing 10% FOS for 10 d. To compare gene expression with rats fed a control diet, total mRNA was extracted from the colorectum and analyzed using a Rat cDNA Expression Arrays filter. This arrays filter contains probes of 588 genes, and 195 of them showed detectable changes in their expression by FOS feeding. There were six genes that increased their expression more than twice that of the control. Among them, genes related to the induction of cell growth such as Map kinase 1 and Max were included. Expressions that decreased to less than half were observed in 20 genes, such as somatostatin and prohibitin, which prohibit cell growth. These results are consistent with the other observation that FOS increases cell growth in the colorectum. This approach has revealed that cDNA array technology is an effective tool for nutritional sciences that involve the regulation of a large number of genes, especially for molecular mechanisms of regulation, by nutritional constituents.

Animals↗
PubMed2003

Bisphenol A induces apoptosis in central neural cells during early development of Xenopus laevis.

Bisphenol A (BPA), known to be a xenoestrogen, is widely used in industry and dentistry. In the present study, we investigated the effects of BPA on the early development of Xenopus laevis embryos. Stage 6 embryos were exposed to 10-100 microM BPA. Developmental abnormalities were observed when the embryos were exposed to at least 20 microM BPA, with marked developmental abnormalities, such as crooked vertebrae and developmental defects of the head and abdomen, detected in all embryos up to stage 40. Interestingly, apoptosis occurred specifically in central nervous tissue cells of the brain and spinal cord, as assessed by histological analysis. BPA-induced malformations and apoptosis were not observed in embryos exposed to BPA after stage 10. When embryos were exposed to 10 microM 17beta-estradiol (E2), abnormalities were also observed until stage 40. However, the abnormalities induced by BPA and E2 were different and E2 exposure did not induce apoptosis in the central nervous system. Our results indicated that the developmental abnormalities and apoptosis induced by BPA exposure were not inhibited by the addition of E2. In conclusion, we demonstrated that BPA induced marked malformations and specific apoptosis of central nervous system cells during early development of X. laevis embryos, and that these BPA effects appeared to be due to non-estrogenic activities on developmental processes.

Air Pollutants, Occupational↗
PubMedDate not supplied

Somatic symptoms for diagnosing major depression in cancer patients.

Diagnosing depression in cancer patients has been challenging because the diagnostic criteria include somatic symptoms frequently attributed to the cancer itself or its treatment. However, few studies have explored how to appropriately deal with individual somatic symptoms. The authors used data from 220 cancer patients with major depression to examine the intercorrelations among the DSM-IV somatic and nonsomatic symptom criteria as well as whether the presence of an individual somatic symptom could discriminate the severity of major depression. Appetite changes and a diminished ability to think were positively associated with anhedonia. Sleep disturbance and fatigue were not significantly associated with nonsomatic symptoms. These associations were consistent after adjusting for physical functioning and pain. Only patients with appetite changes showed a higher severity of depression. These results suggest that individual somatic symptoms differ in nature and that appetite-related symptoms and a diminished ability to think may be useful for diagnosing depression in cancer patients, whereas sleep disturbances and fatigue may not be as useful.

Adolescent↗