Biomedical subjects

Naoko Sato

Publications and source records attributed to Naoko Sato.

29 records · Page 2Linked to original sources

PubMed2004

Retrospective analysis of concurrent chemoradiation with the combination of bleomycin, ifosfamide and cisplatin (BIP) for uterine cervical cancer.

Combination chemotherapy consisting of bleomycin, ifosfamide, and ciplatin (BIP) is recognized as one of the most effective chemotherapies for uterine cervical cancer. However, there have been no reports that evaluate concurrent use of radiation with BIP. The objective of this study was to evaluate the toxicity and response of the combination of BIP concurrent with radiation in patients with squamous cell carcinoma of the uterine cervix. Eligibility criteria included patients who underwent radical hysterectomy (Type III hysterectomy) as a primary treatment and revealed lymph node metastases or deep myometrial invasion (stage IB and IIA) and patients who were previously untreated (stage IIB-IV). All of the patients had biopsy-proven squamous cell carcinoma of the uterine cervix. The patients received three courses of BIP chemoradiation, and the response and toxicity were evaluated. From January 2000 to December 2003, 30 patients met study eligibility criteria. All but three patients completed 3 courses of planned chemotherapy. The frequency of severe (grade 3 and 4) toxicity was as follows: anemia, 46.7%; neutrocytopenia, 73.3%; thrombocytopenia, 16.7%; and nausea and vomiting, 23.3%. Among 30 patients, 22 cases were evaluated for response. Complete response was achieved in 16 (72.7%) of patients, with a response rate of 90.9%. In conclusion, BIP chemoradiation seems to be superior to previously reported chemoradiation regimens, and has a potential as an optimal combination chemotherapy concurrent with radiation.

Adult↗

PubMed2003

The effects of STI571 on antigen presentation of dendritic cells generated from patients with chronic myelogenous leukemia.

Chronic myelogenous leukemia is caused by the acquisition of the reciprocal (9;22)(q34;q11) chromosomal translocation in hematopoietic stem cells. The fusion protein showed higher and aberrant tyrosine kinase activity. The inhibition of the tyrosine kinase activity of the protein represents a specific therapeutic strategy for bcr/abl-expressing leukemias. STI571 is a compound of the 2-phenylaminopyrimidine class that selectively inhibits the tyrosine kinase activity of the Abl protein tyrosine kinase. In this study, we evaluated the effects of STI571 on antigen presentation of dendritic cells generated from the patients with CML. The data showed that by the addition of STI571 the dendritic cells derived from CML clone showed an increased expression of CD1a, CD83, CD80 and CD86 by flow cytometry analysis and showed more intense abilities of allogeneic antigen presentation by mixed leukocyte culture, compared with the control cells without STI571. Our results suggested that STI571 not only has a direct cytotoxic effect on bcr-abl gene rearranged cells but also an indirect effect associated with increased anti-leukemic immunological function due to an intensified antigen presentation.

Antigen Presentation↗

PubMed2003

Prognostic significance of second-look laparotomy for surgically confirmed early-stage epithelial ovarian cancer: a multicenter retrospective study.

BACKGROUND: In the present study, we conducted a multicenter retrospective analysis to elucidate the prognostic significance of second-look laparotomy (SLL) in early-stage epithelial ovarian cancer that was confirmed by complete surgical exploration. METHODS: In July 2001, 12 Japanese institutions received questionnaires regarding patients with early-stage epithelial ovarian cancer and SLL. Eligibility criteria included patients with stage I or II epithelial ovarian cancer who were surgically diagnosed between January 1988 and December 1997. Data were collected regarding age, performance status, tumor histologic subtype, stage, preoperative carbohydrate antigen (CA) 125 level, results of SLL if performed, recurrence, disease-free survival, and overall survival. Survival analyses and comparisons were performed by univariate methods. RESULTS: There were 87 patients who met the eligibility criteria. There were no significant differences in the backgrounds of patients who had had SLL ( n = 30) and the non-SLL group ( n = 57). Of the 30 SLL-group patients, 28 had negative SLL findings and 2 had positive findings. Six and 5 patients in the SLL group and the non-SLL group, respectively, had recurrence ( P = 0.177), and 4 patients in the SLL group had a recurrence after "negative" SLL findings. There was no significant difference between the two groups for either overall ( P = 0.73) or disease-free survival ( P = 0.273). On univariate analysis, only clear-cell histology was associated with a poor prognosis in early-stage epithelial ovarian cancer ( P = 0.031). CONCLUSION: SLL is not beneficial for early-stage epithelial ovarian cancer. More favorable outcomes will be achieved for early-stage patients with the improvement of treatment for clear-cell adenocarcinoma.

Adult↗

PubMed2003

Masked MLL gene rearrangement was disclosed in the clinical course and sequential development of chromosome abnormality in a patient with therapy related acute myelogenous leukemia.

Therapy related acute myelogenous leukemia in a 55-year-old Japanese woman is described. She had been treated for a diagnosis of non-Hodgkin's lymphoma 2 years before the onset of the secondary leukemia. She was diagnosed as AML (FAB: M2) with monosomy 7, and successfully treated by an intensive combination chemotherapy followed by an autologous peripheral blood stem cell transplantation. The disease relapsed shortly after the treatment, and the karyotype analysis revealed a complex abnormality accompanied with t(9;11)(p22;q23), however, monosomy 7 was absent. Southern blotting analysis was performed, and MLL rearrangement was evident in both the bone marrow samples obtained at that time and the cryopreserved marrow cells obtained at the onset of the disease. The bone marrow sample stored in a Carnoy solution at the onset was further analyzed, and three karyotype panels showing 45,XX, -7, t(9;11)(p22;q23) were found. Like this situation, a masked MLL rearrangement may have existed in some cases with hematopoietic malignancies, and appear to be disclosed in the clinical course.

Cell Transformation, Neoplastic↗

PubMed2003

Free 67Ga enters into the hepatocytes of carbon tetrachloride-treated rats.

Gallium-67 (67Ga) has been used as tumor or inflammation-imaging agent in nuclear medicine for decades. Although many hypotheses concerning the mechanism of uptake of 67Ga into tumors and inflammation have been proposed, consensus has not been reached. If the mechanism of 67Ga uptake is clarified, we can improve the sensitivity of diagnostic imaging with 67Ga. We attempted to clarify the mechanism of 67Ga uptake by the liver of carbon tetrachloride (CCl(4))-treated rats. First, we investigated whether or not transferrin (Tf) is involved in 67Ga uptake by the liver tissue of CCl(4)-treated rats. It is well known that Fe(3+) can inhibit the binding of 67Ga to Tf. The administration of FeCl(3) 5 min before the injection of 67Ga slightly enhanced the uptake of 67Ga by the liver tissue of CCl(4)-treated rats. The entering of 67Ga into hepatocytes of CCl(4)-treated rats was similar to the uptake by the liver tissue. In addition, the administration of FeCl(3) slightly increased the entering of 67Ga to hepatocytes. These results suggest that free 67Ga enters into hepatocytes from the liver of CCl(4)-treated rats.

Journal Article↗

PubMed2003

Effects of polyamines on histone polymerization.

It is generally accepted that the nucleosome structure is not static, and that alternative conformations are adopted in response to several stimuli associated with the different functions. Histones are substrates for transglutaminase (TGase), and polymerized histone and polyamine binding histone have been suggested to play important roles in nucleus. We examined whether histone polymerization catalyzed by TGase was influenced by polyamines such as putrescine (PUT), spermidine (SPD), and spermine (SPM). PUT inhibited histone polymerization, and SPD slightly prevented it. However, SPM slightly enhanced histone polymerization. These results indicate that the nuclear accumulation of the polyamines may play an important role in nuclear remodeling by histone modification. We speculate that histone cross-linking by TGase may be involved in the chromatin structure. Also, we propose that histone cross-linking by TGase may be responsible for the changes in DNA function such as transcription and replication and that TGase may be involved in cell growth and differentiation.

Animals↗

PubMed2003

Effect of restraint and footshock stress and norepinephrine treatment on gastric emptying in rats.

We investigated the effects of restraint and footshock stress and norepinephrine treatment on gastric emptying. The gastric emptying was significantly inhibited by restraint stress. beta(3)-adrenergic antagonist canceled the inhibition of gastric emptying caused by restraint stress, while beta(1)-, beta(2)-, alpha(1)-, and alpha(2)-adrenergic antagonists did not affect the inhibition. Norepinephrine treatment also inhibited gastric emptying. The inhibition by norepinephrine treatment was canceled by beta(1)-, beta(2)-, and beta(3)-adrenergic antagonists, but not by alpha(1)- and alpha(2)-adrenergic antagonists. On the other hand, footshock stress did not affect gastric emptying. These results suggest that beta(3)-adrenoceptors play an important role in the inhibition of gastric emptying caused by restraint stress, while nonspecific beta-adrenoceptors are involved in that caused by norepinephrine treatment.

Adrenergic alpha-Antagonists↗

PubMed2003

Inhibitory and promotive effects of polyamines on transglutaminase-induced protein polymerization.

Transglutaminase (TGase) has been reported to be involved in the regulation of cell growth. We examined the effects of polyamines on TGase activity. The polymerization of casein was inhibited by putrescine (PUT) and spermidine (SPD). On the other hand, polymerization of N,N-dimethylcasein was increased by spermine (SPM) and SPD. These results suggested polyamines played two distinct roles as inhibitor and promoter for TGase-catalyzed protein polymerization.

Animals↗

PubMed2002

Involvement of imidazoline receptors in the centrally acting muscle-relaxant effects of tizanidine.

The centrally acting muscle relaxant tizanidine has an imidazoline structure and binds not only to alpha(2)-adrenoceptors but also to imidazoline receptors. The role of imidazoline receptors in the muscle-relaxant effect of tizanidine was studied using the alpha(2)-adrenoceptor/imidazoline receptor antagonist idazoxan and the alpha(2)-adrenoceptor antagonist yohimbine. Tizanidine decreased the spinal mono- and polysynaptic reflexes in intact rats, and the inhibitory effects were antagonized by idazoxan but not by yohimbine. After pretreatment with prazosin, tizanidine decreased the mono- and polysynaptic reflexes in spinalized rats. While yohimbine partly inhibited tizanidine-induced depression of the polysynaptic reflex, idazoxan completely abolished tizanidine-induced depression of spinal reflexes. Furthermore, tizanidine-induced muscle relaxation in the traction test was significantly inhibited by idazoxan but not by yohimbine. From these results, it is suggested that imidazoline receptors, but not alpha(2)-adrenoceptors, are involved in the supraspinal inhibitory effects of tizanidine on spinal reflexes, and at the spinal level, alpha(2)-adrenoceptors and imidazoline receptors are involved in the inhibitory effects of tizanidine.

Animals↗

PubMed2002

Contrast sensitivity of patients with severe motor and intellectual disabilities and cerebral visual impairment.

We attempt to evaluate the residual visual capacities of nine patients (seven males and two females; age range 4 to 35 years, mean 13.8 +/- 9.98) with cerebral visual impairment coupled with severe motor and intellectual disabilities by their contrast sensitivities to sine-wave gratings. Two methods were used for detecting the occurrence of ocular responses to stimuli: (1) detection of optokinetic nystagmus to drifting sinusoidal gratings by naked-eye observation and electronystagmography and (2) detection of ocular pursuit for a drifting Gabor patch by naked-eye observation. We succeeded in measuring the sensitivities of eight cases. For the remaining one case, only the Gabor method could be applied. Most cases showed low contrast sensitivity in both higher (2 and 4 cycles/degree) and lower (0.125 and 0.25 cycles/degree) spatial frequencies and relatively high contrast sensitivity in the middle (0.5 and 1 cycle/degree) range of spatial frequencies. We conclude that the residual visual capacities of patients with severe motor and intellectual disabilities and cerebral visual impairment can be measured fairly accurately by these behavioral methods.

Adolescent↗

PubMed2002

Compound heterozygous mutations in the cholesterol side-chain cleavage enzyme gene (CYP11A) cause congenital adrenal insufficiency in humans.

Cholesterol side-chain cleavage enzyme (P450scc) catalyzes the conversion of cholesterol to pregnenolone in mitochondria, which is the first step in the biosynthesis of all steroid hormones. Until now, no homozygous or compound heterozygous mutations in CYP11A have been described in humans. Here we describe novel compound heterozygous mutations in CYP11A in a patient with congenital adrenal insufficiency born to healthy parents. One mutation, a maternally inherited R353W mutation, resulted in markedly reduced P450scc activity by the single amino acid substitution, indicating that Arg(353) is a crucial amino acid residue for P450scc activity. The other mutation, a de novo A189V mutation in the paternal allele, did not affect the P450scc activity by the single amino acid substitution and turned out to be a splicing mutation, which created a novel alternative splice-donor site. It resulted in a deletion of 61 nucleotides in the open reading frame and thus partially inactivated CYP11A. These experimental data are consistent with the clinical findings indicating that the patient had partially preserved ability to synthesize adrenal steroid hormones. This is the first report of the compound heterozygote for the CYP11A mutations with congenital adrenal insufficiency and the phenotypically normal heterozygote in humans.

Adrenal Glands↗