Biomedical subjects

Naoko Sato

Publications and source records attributed to Naoko Sato.

At least 19 recordsLinked to original sources

PubMed2007

Expression of organic cation transporter SLC22A16 in human endometria.

SLC22A16 is one of newly isolated organic cation transporters, which is responsible for uptake and transport of adriamycin into cells. Adriamycin is one of the key drugs for treatment of endometrial cancer. Therefore, we examined expression of SLC22A16 in human endometrium and its disorders. Protein and mRNA expression levels of SLC22A16 were examined in 124 endometrial cancer specimens, 25 normal endometrial tissue samples (15 in proliferative phase, 10 in secretory phase), and 7 endometrial cancer cell lines using immunohistochemical analysis and reverse transcription-polymerase chain reaction. Changes in SLC22A16 mRNA expression level after progesterone exposure were also examined. Immunohistochemical analysis showed that SLC22A16 protein was highly expressed in endometrium during the normal secretory phase, but its level was significantly reduced in the proliferative phase. SLC22A16 protein was detected in 59 of 124 (48%) endometrial cancer specimens and 3 of 7 (43%) endometrial cancer cell lines. The mRNA levels measured by quantitative reverse transcription-polymerase chain reaction were comparable with levels of protein expression. Furthermore, SLC22A16 mRNA levels were increased in endometrial cancer cell lines in the presence of progesterone. In conclusion, SLC22A16 is expressed in various endometrial tissues. Its expression level is high during the secretory phase and may be regulated by progesterone. Our findings also suggest that it may be possible to use progestins to increase the response of endometrioid endometrial carcinoma with SLC22A16 expression to adriamycin-based chemotherapeutic regimens.

Cell Line, Tumor↗

PubMed2006

Kallmann syndrome phenotype in a female patient with CHARGE syndrome and CHD7 mutation.

We report on a 14 7/12-year-old Japanese female patient with CHARGE syndrome and CHD7 mutation who also exhibited Kallmann syndrome (KS) phenotype. She had poor pubertal development and apparently impaired sense of smell. A GnRH test showed severely compromised responses of LH (<0.5 --> <0.5 IU/L) and FSH (<0.5 --> 1.2 IU/L), and magnetic resonance imaging delineated hypoplastic olfactory bulbs. Mutation analysis revealed a heterozygous nonsense mutation at exon 33 of CHD7 (7027C>T, Q2343X). The results provide further support for the notion that KS phenotype can be included in the phenotypic spectrum of CHARGE syndrome, and indicate that CHARGE syndrome with KS phenotype is caused by a CHD7 mutation.

Abnormalities, Multiple↗

PubMed2006

Long-range negative correlation of glucose dynamics in humans and its breakdown in diabetes mellitus.

Diurnal fluctuations in glucose levels continuously monitored during normal daily life are investigated using an extended random walk analysis, referred to as detrended fluctuation analysis (DFA), in 12 nondiabetic subjects and 15 diabetic patients. The DFA exponent alpha = 1.25 +/- 0.29 for healthy individuals in the "long-range" (>2 h) regime is shown to be significantly (P < 0.01) smaller than the reference "uncorrelated" value of alpha = 1.5, suggesting that the instantaneous net effects of the dynamical balance of glucose flux and reflux, causing temporal changes in glucose concentration, are long-range negatively correlated. By contrast, in diabetic patients, the DFA exponent alpha = 1.65 +/- 0.30 is significantly (P < 0.05) higher than that in nondiabetic subjects, evidencing a breakdown of the long-range negative correlation. It is suggested that the emergence of such positive long-range glucose correlations in diabetic patients-indicating that the net effects of the flux and reflux persist for many hours-likely reflects pathogenic mechanisms of diabetes, i.e., the lack of long-term stability of blood glucose and that the long-range negatively correlated glucose dynamics are functional in maintaining normal glucose homeostasis.

Adaptation, Physiological↗

PubMed2006

[Kallmann syndrome].

Explore the source record for details and available documents.

Chorionic Gonadotropin↗

PubMed2006

Kallmann syndrome: somatic and germline mutations of the fibroblast growth factor receptor 1 gene in a mother and the son.

CONTEXT: Although Kallmann syndrome (KS) caused by heterozygous loss of function mutations of the fibroblast growth factor receptor 1 gene (FGFR1) is occasionally associated with characteristic features, such as dental agenesis and cleft palate, FGFR1 mutations remain unidentified in several KS patients with such characteristic features. SUBJECTS AND METHODS: We examined a 14-yr-old Japanese boy with hypogonadotropic hypogonadism, olfactory dysfunction, and dental agenesis and his fertile mother with olfactory dysfunction and dental agenesis. Direct sequencing was performed for FGFR1 using leukocyte genomic DNA from the proband and leukocyte and nail genomic DNA from the mother. To examine a possible somatic mutation, a specific forward primer was designed to introduce a BstXI site into the normal allele only, and nested PCR amplification, followed by BstXI digestion, was carried out three times with different reverse primers. RESULTS: After standard PCR amplifications, a heterozygous 2-bp deletion at exon 10 (1317_1318delTG), which is predicted to cause a frameshift at the 439th codon for serine and resultant termination at the 461st codon (S439fsX461), was identified in the proband, but was not found in the mother. After selective amplification of the mutant allele, this deletion was detected in nail DNA, but not in leukocyte DNA, from the mother. CONCLUSION: The results suggest that the 2-bp deletion took place as a somatic mutation in the mother and was transmitted to the boy because of germline mosaicism. Such a somatic mutation occurs in some apparently FGFR1 mutation-negative KS patients with dental agenesis.

Adolescent↗

PubMed2006

Contribution of the cyclic nucleotide phosphodiesterases PdeA and PdeB to adaptation of Myxococcus xanthus cells to osmotic or high-temperature stress.

A tBLASTn search of the Myxococcus xanthus genome database at The Institute for Genomic Research (TIGR) identified three genes (pdeA, pdeB, and pdeC) that encode proteins homologous to 3',5'-cyclic nucleotide phosphodiesterase. pdeA, pdeB, and pdeC mutants, constructed by replacing a part of the gene with the kanamycin or tetracycline resistance gene, showed normal growth, development, and germination under nonstress conditions. However, the spores of mutants, especially the pdeA and pdeB mutants, placed under osmotic stress germinated earlier than the wild-type spores. The phenotype was the opposite of that of the receptor-type adenylyl cyclase (cyaA or cyaB) mutant. Also, pdeA and pdeB mutants were found to have impaired growth under the condition of high-temperature stress. Intracellular cyclic AMP (cAMP) levels of pdeA or pdeB mutant cells under these stressful conditions were about 1.3-fold to 2.0-fold higher than those of wild-type cells. These results suggest that PdeA and PdeB may be involved in osmotic adaptation during spore germination and temperature adaptation during vegetative growth through the regulation of cAMP levels.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2005

Gonadotrophin therapy in Kallmann syndrome caused by heterozygous mutations of the gene for fibroblast growth factor receptor 1: report of three families: case report.

Gonadotrophin therapy (GT) is frequently used to induce fertility in Kallmann syndrome (KS). We studied the effects and the consequences of GT in autosomal dominant KS caused by heterozygous FGFR1 mutations. Three Japanese families were examined. In family A, an adult male received GT and had two sons. In family B, an adult female received GT and gave birth to dizygotic male and female twins. In family C, an adult female received GT and produced a son and a daughter. Direct sequencing was performed for FGFR1, and clinical assessment was carried out for KS features. The father and the elder son of family A had P745S mutation, the mother and the female twin of family B had G687R mutation, and the mother and the two children of family C had S107X mutation. KS phenotype was detected for the mutation-positive subjects, except for the elder son of family A who had apparently normal phenotype. GT in FGFR1 mutations is effective in acquiring fertility but has a risk of transmitting the mutation and the disease phenotype to the next generation.

Adult↗

PubMed2005

The involvement of polyamines as substrates of transglutaminase in zonal different hepatocyte proliferation after partial hepatectomy.

We have recently demonstrated the inverse correlation between transglutaminase (TGase) activity and DNA synthesis in periportal hepatocytes (PPH) and perivenous hepatocytes (PVH) at 1 d after partial hepatectomy. In order to elucidate a role of polyamines as substrates of TGase in the differential growth capacities between PPH and PVH from regenerating liver, we investigated the zonal differences in alteration of ornithine decarboxylase (ODC) activity and polyamines. In two subpopulations, the inverse correlation between DNA synthesis and epsilon-(gamma-glutamyl) lysine (Gln-Lys) cross-linking catalyzed by TGase was demonstrated at 1 d after partial hepatectomy. ODC activity in PPH significantly increased with a peak at 1 d after partial hepatectomy, whereas did not in PVH. Protein-binding SPD in PPH also transiently increased with a peak at 1 d after partial hepatectomy, but did not in PVH. These results suggest that at 1 d after partial hepatectomy, in PPH, the inhibition of Gln-Lys cross-linking by the formation of N-gamma-glutamyl SPD leads to the increase of DNA synthesis, whereas in PVH, enhanced formation of Gln-Lys cross-linking leads to the lower DNA synthesis.

Animals↗

PubMed2005

Characterization of a metal-chelating substance in coffee.

A metal-chelating substance in brewed coffee was separated and characterized by its chemical structure. This substance was a brown polymer. The contents of sugars, amino acids and phenolics in the substance were evaluated. This polymer contained small amounts of sugars and amino acids in its partial structure. After being decomposed by alkaline fusion, the decomposition products were identified by HPLC and GC-MS. Several phenolics were detected in the decomposed products. To characterize this substance, various types of model compounds were prepared by roasting chlorogenic acid, sucrose, and (or) protein with cellulose powder. Among these model compounds, the polymer-forming ability was highest in the model prepared from all four of materials, but the metal-chelating ability was the highest in the model prepared from chlorogenic acid and cellulose. These results suggest that this metal-chelating substance was a melanoidin-like polymer formed by the decomposition and polymerization of sugars, amino acids and phenolics.

Chelating Agents↗

PubMed2004

Cytochrome P450 oxidoreductase gene mutations and Antley-Bixler syndrome with abnormal genitalia and/or impaired steroidogenesis: molecular and clinical studies in 10 patients.

We report on molecular and clinical findings in 10 Japanese patients (four males and six females) from eight families (two pairs of siblings and six isolated cases) with Antley-Bixler syndrome accompanied by abnormal genitalia and/or impaired steroidogenesis. Direct sequencing was performed for all the 15 exons of cytochrome P450 oxidoreductase gene (POR), showing two missense mutations (R457H and Y578C), a 24-bp deletion mutation resulting in loss of nine amino acids and creation of one amino acid (L612_W620delinsR), a single bp insertion mutation leading to frameshift (I444fsX449), and a silent mutation (G5G). R457H has previously been shown to be a pathologic mutation, and computerized modeling analyses indicated that the 15A>G for G5G could disturb an exonic splicing enhancer motif, and the remaining three mutations should affect protein conformations. Six patients were compound heterozygotes, and three patients were R457H homozygotes; no mutation was identified on one allele of the remaining one patient. Clinical findings included various degrees of skeletal features, such as brachycephaly, radiohumeral synostosis, and digital joint contractures in patients of both sexes, normal-to-poor masculinization during fetal and pubertal periods in male patients, virilization during fetal life and poor pubertal development without worsening of virilization in female patients, and relatively large height gain and delayed bone age from the pubertal period in patients of both sexes, together with maternal virilization during pregnancy. Blood cholesterol was grossly normal, and endocrine studies revealed defective CYP17A1 and CYP21A2 activities. The results suggest that Antley-Bixler syndrome with abnormal genitalia and/or impaired steroidogenesis is caused by POR mutations, and that clinical features are variable and primarily explained by impaired activities of POR-dependent CYP51A1, CYP17A1, CYP21A2, and CYP19A1.

Abnormalities, Multiple↗

PubMed2004

Simultaneous expression of CD13, CD22 and CD25 is related to the expression of Fc epsilon R1 in non-lymphoid leukemia.

Like CD19 or CD56, CD22 in non-lymphoid leukemia has been considered an aberrantly expressed antigen. CD22 had been believed to be restricted to B lymphoid, however, it was also found to be expressed in human basophils. Mature basophils are unique granulocytes expressing CD13, CD22 and CD25. To estimate whether the expression of CD22 in non-lymphoid leukemia is aberrant or related to basophilic character, we analyzed 108 patients with primary and secondary leukemia. Among non-lymphoid leukemias, surface CD22 expression was more frequently observed in peroxidase-negative AML and secondary leukemia, and was usually observed simultaneously with CD13 and CD25. Samples obtained from 17 cases were further analyzed, and all the Fc epsilon R1-positive cases were observed in peroxidase-negative AML and secondary non-lymphoid leukemia, and mostly expressed CD13, CD22 and CD25. Therefore, surface CD22 expression in non-lymphoid leukemia was thought to relate to basophilic phenotype in some cases. Like CD22, some of the so-called aberrantly expressed antigens may not actually be aberrant, but are expressed in a stage of differentiation and maturation of progenitors. Moreover, CD22 may be one of target molecules for treatment of CD22-positive, poorly prognostic leukemia.

Adolescent↗

PubMed2004

Clinical assessment and mutation analysis of Kallmann syndrome 1 (KAL1) and fibroblast growth factor receptor 1 (FGFR1, or KAL2) in five families and 18 sporadic patients.

We report on the clinical and molecular findings in 25 males and three females with Kallmann syndrome (KS) aged 10-53 yr. Ten males were from five families, and the remaining 15 males and three females were apparently sporadic cases. Molecular studies were performed for Kallmann syndrome 1 (KAL1) and fibroblast growth factor receptor 1 (FGFR1, also known as KAL2) by sequence analysis for all the coding exons, by PCR-based deletion analysis, and by fluorescence in situ hybridization (FISH) analysis, showing six novel and two recurrent intragenic KAL1 mutations in seven familial and four sporadic male cases and two novel intragenic FGFR1 mutations in two sporadic male cases. In addition, submicroscopic deletions at Xp22.3 involving VCX-A, STS, KAL1, and OA1 were identified in three familial cases and one sporadic male case affected by a contiguous gene syndrome. Clinical assessment in the 15 males with KAL1 mutations showed normal and borderline olfactory function in two males and right-side dominant renal lesion in seven males, in addition to variable degrees of hypogonadotropic hypogonadism (HH) in all the 15 males and olfactory dysfunction in 13 males. The two males with FGFR1 mutations had HH and anosmia and lacked other features. Clinical features in the remaining 11 cases with no demonstrable KAL1 or FGFR1 mutations included right renal aplasia in one female, cleft palate in one male, cleft palate and perceptive deafness in one male, and dental agenesis and perceptive deafness in one male, in addition to a variable extent of HH and olfactory dysfunction. The results suggest the following: 1) KAL1 mutations might be more prevalent in the Japanese patients than previously estimated in the Caucasian patients and can be associated with apparently normal olfactory function; 2) FGFR1 mutations account for approximately 10% of KS patients, as previously reported in the Caucasian patients, and can result in HH and olfactory dysfunction-only phenotype; and 3) renal aplasia, which is characteristic of KAL1 mutations, and cleft palate and dental agenesis, which are characteristic of FGFR1 mutations, can occur in patients without KAL1 and FGFR1 mutations.

Adolescent↗

PubMed2004

Testicular dysgenesis without adrenal insufficiency in a 46,XY patient with a heterozygous inactive mutation of steroidogenic factor-1.

Steroidogenic factor-1 (SF-1) regulates multiple genes involved in the adrenal and gonadal development and in the biosynthesis of a variety of hormones, including adrenal and gonadal steroids, anti-Mullerian hormone (AMH), and gonadotropins. We identified a novel SF-1 mutation in a 27-yr-old Japanese patient with a 46,XY karyotype. Sequence analysis was performed for all the seven exons of SF-1, revealing a heterozygous single base pair deletion at exon 2 (18delC) that is predicted to cause a frameshift at the sixth codon and resultant termination at the 74th codon. Functional studies showed that the mutation produced no demonstrable protein and had no transcription activity or dominant negative effect. Clinical features included small dysgenetic testes with vasa deferentia and epididymides, absent uterus, blind-ending vagina, clitoromegaly, and psychosexual disturbance. Endocrine studies showed normal adrenal function (cortisol response to ACTH stimulation, 13.4-->25.3 microg/dl) and primary hypogonadism (testosterone response to hCG stimulation, 0.57-->0.76 ng/ml; gonadotropin responses to GnRH stimulation: LH, 10-->59 mIU/ml; FSH, 36-->69 mIU/ml), and urinary steroid hormone profile analysis indicated grossly normal steroidogenic enzyme activities. The results suggest that SF-1 haploinsufficiency can selectively impair testicular development and permit the biosynthesis of AMH and testosterone in dysgenetic testes and the production of gonadotropins in pituitary gonadotropes.

Adult↗

PubMed2004

The entering of indium-111 and iron-59 into the hepatocytes from partially hepatectomized rats differ from that of gallium-67.

We recently suggested that the transferrin (Tf)-gallium-67 (67Ga) complex dissociated on the surface of the hepatocytes after partial hepatectomy and free 67Ga bound to heparan sulfate in the extracellular matrix. In the present study, we investigated whether the entering of indium-111 (111In) and iron-59 (59Fe) with high affinity to transferrin differed from the entering of 67Ga by the hepatocytes after partial hepatectomy. 111In was almost taken by the plasma and little taken by the red blood cell. On the other hand, the uptake of 59Fe by the red blood cell was higher than plasma. The uptake of 59Fe by the bone marrow was significantly higher than that of 111In. The uptake of 111In and 59Fe by the liver tissue was reached a maximum 2 d after partial hepatectomy but the uptake ratio of 111In was lower than that of 59Fe. We suspected that the uptake of 59Fe by the liver tissue was the highest because of the high binding affinity of Tf-59Fe to Tf-receptor. The entering of 111In and 59Fe into the hepatocytes was also reached a maximum 2 d after partial hepatectomy but the ratio of 59Fe was slightly lower than that of 111In. These results suggested that the binding affinity to Tf could have played a crucial role in the differences of the entering of 111In, 59Fe and 67Ga into the hepatocytes of partially hepatectomized rats.

Animals↗

PubMed2004

Zonal differences in DNA synthesis and in transglutaminase activity between perivenous versus periportal regions of regenerating rat liver.

We investigated a relationship within zonal differences in DNA synthesis and in transglutaminase (TGase) activity between perivenous versus periportal regions of regenerating rat liver. Using the digitonin/collagenase perfusion technique, hepatocyte subpopulations were isolated from each region at various time points after partial hepatectomy. The amounts of DNA synthesis as well as the levels of TGase mRNA and activity in each subpopulation were measured. Although increased DNA synthesis was observed in both subpopulations with a peak at 24 h after partial hepatectomy, the amount of DNA synthesis in periportal hepatocytes (PPH) was twice as much as that in perivenous hepatocytes (PVH). In PVH, TGase activity peaked at 24 h after partial hepatectomy with a preceding increase in its mRNA expression at 12 h, whereas TGase activity in PPH at 24 h was one-half of that in PVH. As TGase is known to have a growth-arresting activity, our data indicate that relatively higher TGase activity in PVH at 24 h after partial hepatectomy might correlate with relatively lower DNA synthesis in this region compared to periportal region.

Animals↗

PubMed2004

Uptake of gallium-67 by the hepatocytes during liver regeneration in carbon tetrachloride-treated mice.

Gallium-67 (67Ga) has been used as a tumor or inflammation-imaging agent in nuclear medicine. We recently reported that the peak of serum alanine aminotransferase (ALT) level was 1 d after carbon tetrachloride (CCl4) treatment in rats. However, the peak of 67Ga uptake by the liver tissue and hepatocytes was 2 d after the treatment. If 67Ga is taken in the hepatic disorder phase, the pattern of 67Ga uptake by the hepatocytes should be consistent with that of the ALT level. In order to answer why it was not, we carried out a detailed examination. The lipid peroxidation of hepatocytes from CCl4-treated mice was greatly increased 1 d after CCl4 treatment; serum ALT was also increased 1 d after the treatment. The uptake of 67Ga by the liver tissue reached a maximum 1 and 2 d after the treatment, while maximum by the hepatocytes was achieved after 2 d. The incorporation of bromodeoxyuridine into the hepatocytes also reached maximum 2 d after the treatment. These results suggest that the uptake of 67Ga by the hepatocytes is carried out during liver regeneration rather than during hepatic disorder by CCl4 treatment.

Animals↗

PubMed2004

Relationship between liver injury and transglutaminase activities in guinea pigs and rats.

We investigated the effect of transglutaminase (TGase) on in guinea pigs and rats. Serum alanine aminotransferase (ALT) level increased 1 d after CCl(4) treatment of both in guinea pigs and rats since TGaese activity was greatly higher in guinea pigs than rats. However, serum ALT level in guinea pigs was very much lower than that in rats. Liver TGase activities decreased after CCl(4) treatment in both guinea pigs and rats. However, TGase activities in the liver from guinea pigs were higher than that from rats. Decreased TGase activities by CCl(4) in the liver from guinea pigs and rats were significantly recovered by retinoic acid treatment that was reported to increase TGase. Degree of recovery of serum ALT level by retinoic acid in rats was larger than in guinea pigs. These results suggested that the distinction of the effect of retinoic acid on serum ALT level in CCl(4)-treated animals was due to the different TGase activity that increased membrane stability.

Alanine Transaminase↗

PubMed2004

Development of an experimental system for evaluation of stress effect on ethyl alcohol metabolism using radiorespirometric analysis in rat.

We attempted to develop an experimental system for evaluation of stress effect on ethyl alcohol metabolism by the radiorespirometric analysis using [(14)C]ethyl alcohol. Each rat was immobilized in an adjustable restraint device for 3 h. The excretion of (14)CO(2) in the breath was significantly decreased by restraint stress. The liver alcohol dehydrogenase activity was also decreased by restraint stress. We think that radiorespirometric analysis may be useful for the evaluation of stress effect on real metabolism of ethyl alcohol in the liver.

Alcohol Dehydrogenase↗