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Biomedical subjects

Y Kikuchi

Publications and source records attributed to Y Kikuchi.

At least 109 records · Page 6Linked to original sources
PubMed2000

Clinical characteristics of clear cell carcinoma of the ovary: a distinct histologic type with poor prognosis and resistance to platinum-based chemotherapy.

BACKGROUND: A retrospective review of treatment results comparing women with clear cell carcinoma of the ovary (CCC) with a group with serous adenocarcinoma of the ovary (SAC) was conducted. METHODS: Between 1988-1998, 662 patients with epithelial ovarian carcinoma were identified through the medical records department and the tumor registry at 4 institutions. After the central pathologic review, 101 patients with pure or dominant (>/= 90%) CCC (15.3%) were entered into the current study. Two hundred thirty five patients with pure SAC were selected as a group for comparison. All patients underwent staging laparotomy followed by platinum-based chemotherapy. Distribution of the International Federation of Gynecology and Obstetrics (FIGO) disease stage, response to chemotherapy, and prognosis for patients with CCC were compared with the same values in patients with SAC. RESULTS: Patients with CCC were significantly more likely to have FIGO Stage I disease than were patients with SAC (48.5% vs. 16.6%). A high recurrence rate was noted in those patients with Stage IC CCC (37%). In those patients with Stage IC disease, the survival rates for patients with CCC were lower than those for patients with SAC. The 3-year and 5-year survival rates for Stage III CCC patients were significantly lower compared with Stage III SAC patients. The response rate to platinum-based chemotherapy in patients with CCC was significantly lower than that in patients with SAC. CONCLUSIONS: CCC is an intriguing histologic type of epithelial ovarian cancer that demonstrates a clinical behavior distinctly different from that of SAC.

Adenocarcinoma, Clear Cell↗
PubMed2000

The zebrafish bonnie and clyde gene encodes a Mix family homeodomain protein that regulates the generation of endodermal precursors.

Vertebrate endoderm development has recently become the focus of intense investigation. In this report, we first show that the zebrafish bonnie and clyde (bon) gene plays a critical early role in endoderm formation. bon mutants exhibit a profound reduction in the number of sox17-expressing endodermal precursors formed during gastrulation, and, consequently, a profound reduction in gut tissue at later stages. The endodermal precursors that do form in bon mutants, however, appear to differentiate normally indicating that bon is not required at later steps of endoderm development. We further demonstrate that bon encodes a paired-class homeodomain protein of the Mix family that is expressed transiently before and during early gastrulation in both mesodermal and endodermal progenitors. Overexpression of bon can rescue endodermal gene expression and the formation of a gut tube in bon mutants. Analysis of a newly identified mutant allele reveals that a single amino acid substitution in the DNA recognition helix of the homeodomain creates a dominant interfering form of Bon when overexpressed. We also show through loss- and gain-of-function analyses that Bon functions exclusively downstream of cyclops and squint signaling. Together, our data demonstrate that Bon is a critical transcriptional regulator of early endoderm formation.

Amino Acid Sequence↗
PubMed2000

The catalytic RNA of RNase P from Escherichia coli cleaves Drosophila 2S ribosomal RNA in vitro: a new type of naturally occurring substrate for the ribozyme.

We have found that the catalytic RNA of RNase P of Escherichia coli (M1 RNA) can cleave 2S ribosomal RNA (2S rRNA) of Drosophila melanogaster at specific positions in vitro. The cleavage mainly occurred at two sites between nucleotides 11 and 12, and between 16 and 17 of 2S rRNA. Kinetic analyses of the reaction revealed that a dimer caused by intermolecular interaction of 2S rRNA may be the substrate for the cleavage between 11 and 12, while a simple monomer is the substrate for the cleavage between 16 and 17. Substrate recognition by M1 RNA is also discussed.

Animals↗
PubMed2000

Telomere shortening by cisplatin in yeast nucleotide excision repair mutant.

Telomeres are unique DNA tandem repeats that form the ends of eukaryotic chromosomes to protect the chromosomes from degradation and illegitimate recombination. In yeast, loss of telomere may be compensated for through the acquisition of new telomere by RAD52-mediated or RAD52-independent recombinational repair. In this report, the effects of cis-dichlorodiammine-platinum (II) (cisplatin) on telomere length and the role of nucleotide excision repair in telomere maintenance were examined in the yeast Saccharomyces cerevisiae. We showed that the SSL2 (RAD25) DNA repair yeast mutant exhibited a gradual shortening of the telomere in the presence of cisplatin. Further telomere shortening was prevented upon the withdrawal of cisplatin. Complementation of the mutant with the wild-type SSL2 (RAD25) gene abolished the cisplatin-induced telomere degradation. These results suggest that telomeres are susceptible to cisplatin-induced intrastrand crosslinks and that Ssl2 (Rad25) or the nucleotide excision repair pathway may play a critical role in the repair and the maintenance of telomere integrity.

Cell Survival↗
PubMed2000

Two zebrafish (Danio rerio) antizymes with different expression and activities.

Cellular polyamines are regulated by a unique feedback mechanism involving ornithine decarboxylase (ODC) antizyme. The synthesis of mammalian antizyme requires a programmed translational frameshift event induced by polyamines. Antizyme represses ODC, a key enzyme for polyamine synthesis, through accelerating enzyme degradation by the 26 S proteasome. Antizyme also inhibits the cellular uptake of polyamines. In the present study we isolated two distinct zebrafish (Danio rerio) antizyme cDNA clones (AZS and AZL) from an embryonic library. Their sequences revealed that both clones required translational frameshifting for expression. Taking account of +1 frameshifting, AZS and AZL products were 214 and 218 residues long respectively and shared 51.8% amino acid identity. In rabbit reticulocyte lysates, both mRNA species were translated through spermidine-induced frameshifting. The presence of the two antizyme mRNA species in embryos, adult fish and a cultured cell line was confirmed by Northern blot analysis. The ratio of AZS mRNA to AZL mRNA in the adult fish was 1.8-fold higher than in the embryos. Whole-mount hybridization in situ demonstrated that both mRNA species are expressed in every tissue in embryo, but predominantly in the central nervous system and the eyes. Bacterial expression products of both cDNA species inhibited ODC activity, but only the AZS product accelerated ODC degradation in vitro. These results show that both zebrafish antizymes are induced by polyamines but their mRNA species are expressed differently during development. The difference in activities on ODC degradation suggests their functional divergence.

Amino Acid Sequence↗
PubMed2000

Color Doppler sonographic findings in splenic hamartoma.

We present the gray-scale and color Doppler sonographic findings in a case of a splenic hamartoma in a 40-year-old man. Gray-scale sonograms showed a 2 x 2 cm, hypoechoic splenic mass that was homogeneous without evidence of cystic change or calcification. Color Doppler sonograms showed multiple radial blood-flow signals inside the mass, and spectral analysis confirmed arterial and venous flow. Arteriograms showed multiple small, hypervascular masses with fine tumor vessels and tumor stains within the spleen. Histologic analysis following a splenectomy showed dilated vessels and congestion consistent with the color Doppler sonographic findings.

Adult↗
PubMed2000

Response of the radial artery to three vasodilatory agents.

We examined the response of the radial artery to vasoactive agents (isosorbide dinitrate, ISDN, 1 mg, 3 mg, and 5 mg; verapamil, 1 mg, 3 mg, and 5 mg; and lidocaine, 10 mg, 30 mg, and 50 mg) in 100 consecutive patients admitted for elective coronary angiography. The drug solutions were directly injected into the radial artery from the puncture site. As a result, 5 mg of ISDN increased the diameter of the radial artery by 31% and 28.8% at the proximal and distal sites, respectively. Similarly, 5 mg of verapamil increased it by 9% and 10.8% at the proximal and distal site, respectively. But 10 mg of lidocaine decreased it by -15.6% and -12.1% at the proximal and distal site, respectively. At the doses utilized, ISDN was the most potent vasodilator for the radial artery and lidocaine caused paradoxical vasoconstriction.

Adult↗
PubMed2000

Distinct expression of CDX2 and GATA4/5, development-related genes, in human gastric cancer cell lines.

CDX2 is a tumor-suppressor homeobox gene involved in colon carcinogenesis, but its role in gastric cancer is unknown. Although GATA4, -5 and, -6 transcription factors have distinct functions in the regulation of gastrointestinal epithelial cell differentiation, there have been no reports regarding GATA4/5/6 alterations in gastrointestinal carcinomas. By using a semiquantitative reverse transcription-polymerase chain reaction assay, we studied the expression of gut development-related genes CDX2/1 and GATA4/5/6 in 11 human gastric cancer cell lines. The expression of CDX2 appeared to progressively decrease with the transition from well differentiated to poorly differentiated cancer cell lines. CDX1 was below detectable levels in all cell lines. The expression of GATA4 and GATA5 was undetectable in four and six cell lines, respectively, whereas the majority of the cell lines expressed GATA6 abundantly. These results suggest that CDX2 and GATA4/5 may be associated with the carcinogenesis of the stomach. Mol. Carcinog. 28:184-188, 2000.

Adenocarcinoma↗
PubMed2000

Use of confocal microscopy to detect Salmonella typhimurium within host cells associated with Spv-mediated intracellular proliferation.

The major limitation in histological examination of orally inoculated mice of Salmonella typhimurium has been the difficulty of attaining high enough levels for immunochemical detection. This problem has been solved by the use of confocal laser scanning microscopy (CLSM) analysis, which allows detection of bacteria in the immunostained sections of mouse spleens at a minimum rate of approximately 1000 colony-forming units (cfu)/spleen. Here, we demonstrate that over 80% of salmonellae of the wild type of S. typhimurium were detected intracellularly within Mac-1 positive cells by the CLSM analysis of immunostained sections from spleens in orally or subcutaneously inoculated mice. Only 40% of salmonellae of the spv -deleted strain were detected inside Mac-1 positive cells. These data suggest that the spv genes play a key role in intracellular proliferation within phagocytes in the mouse spleen.

Animals↗
PubMed2000

Extragenic suppressors that rescue defects in the heat stress response of the budding yeast mutant tom1.

The TOM1 gene codes for a so-called HECT protein, a putative ubiquitin ligase, in Saccharomyces cerevisiae. Deletion of the entire gene (tom1-10) or the sequence encoding the HECT domain (tom1-2) causes temperature sensitivity for growth. Here we report the isolation of extragenic, recessive suppressors of tom1-2, which were designated tmr (for tom1 revertant) mutations. These were classified into eight complementation groups and six of the genes were identified: tmr1/cyr1, tmnr2/sch9, tmr3/zuo1, tmr4, tmr5/mot1, tmr6/sse1, tmr7 and tmr8/kre6. These results suggested that the tom1 phenotype can be rescued by down-regulating the cAMP/PKA pathway. It was found that the temperature sensitivity of the tom1-2 mutant is indeed suppressed by multiple copies of PDE2 or BCY1, which encode negative regulators of the cAMP/PKA pathway. The MSN2 gene, which encodes a zinc-finger transcription factor involved in the general stress response is also a multicopy suppressor of tom1. It was found that induction levels of both STRE-mediated (general stress response) and HSE-mediated gene expression (heat shock response) upon shift to high temperature are reduced by more than half in the tom1 mutant. Most of the isolated tmr mutations rescued one of the defects seen in both types of heat stress response in the tom1 mutant.

Cyclic AMP↗
PubMed2000

Modulation of cisplatin sensitivity by taxol in cisplatin-sensitive and -resistant human ovarian carcinoma cell lines.

PURPOSE: The aim of this study was to determine whether taxol can circumvent cisplatin resistance, using a KF28 cell line derived from human ovarian carcinoma and a cisplatin-resistant line, KFr13, derived from the parental cell line, KF28, and taxol-resistant cell lines, KF28TX and KFr13TX, derived from the respective parental counterpart. METHODS: KF28 is a single-cell clone of the human ovarian carcinoma cell line KF. The cisplatin-resistant KFr13 subline was established by repeated exposure of the parent KF28 cell line to escalating doses of cisplatin. Similarly, KF28TX and KFr13TX were established by repeated exposure of the KF28 and KFr13 cell lines to escalating doses of taxol. A cytotoxicity assay was performed using a crystal violet staining method. Platinum and taxol accumulation were assayed by atomic absorption and reverse-phase high-performance liquid chromatography. The quantitative assay of MDR1 mRNA used polymerase chain reaction. RESULTS: KFr13 cells were about 4.8-fold more resistant to cisplatin and about 1.8-fold more sensitive to taxol than were KF28 cells. When taxol resistance was induced in KF28 and KFr13 cells, sensitivity to cisplatin rose about 1.3- and 1.6-fold respectively. Elevation of sensitivity was correlated with platinum uptake by both KF28TX and KFr13TX cells. Expression of multidrug resistance (MDR1) mRNA, which was not observed in KF28 and KFr13 cells, was observed after induction of taxol resistance. CONCLUSIONS: These results may suggest rational therapeutic strategies for patients with cisplatin-resistant or refractory ovarian carcinoma.

Antineoplastic Agents↗
PubMed2000

Fertilizability and developmental capacity of individually cultured bovine oocytes.

Culture of single oocytes throughout in vitro maturation (IVM), fertilization (IVF) and culture (IVC) provides detailed information on maturity, fertilizability and developmental capacity of individual bovine oocytes and embryos. In the present study, effects of sperm concentration (Experiment 1), microdrop size (Experiment 2), and the addition of hypotaurine (HT) or glutathione (GSH; Experiment 3) during IVF were investigated. In Experiment 4, in vitro maturity and developmental capacity of bovine oocytes cultured for IVM in a medium supplemented with fetal calf serum (FCS), bovine serum albumin (BSA) or polyvinyl alcohol (PVA) during IVM were investigated. In Experiments 1 to 3, the percentages of normal (2 pronuclei with a spermtail) and polyspermic fertilization in singly cultured oocytes were similar to those of group IVF culture (5 oocytes/drop). The addition of GSH during single oocyte IVF significantly increased the proportion of normal fertilization and decreased the polyspermic fertilization compared with addition of HT or of the control. The rates of mature oocytes (62.4 and 67.7%) and blastocyst development (12.9 and 15.2%) for single oocyte IVM cultures (Experiment 4) were also similar compared with the group culture; PVA supplementation significantly increased the matured oocyte rate, but decreased blastocyst development significantly (7.1%) as compared with FCS (19.5%) or BSA (15.6%). These results indicate that a single oocyte culture system throughout in vitro production of bovine embryos provides similar maturity, fertilizability and developmental capacity to oocytes cultured in groups.

Animals↗
PubMed2000

Effects of a pectic polysaccharide from a medicinal herb, the roots of Bupleurum falcatum L. on interleukin 6 production of murine B cells and B cell lines.

The effect of T-cell-independent B cell mitogen, a pectic polysaccharide, bupleuran 2IIc, from a medicinal herb, the roots of Bupleurum falcatum L. on interleukin 6 (IL-6) production of murine B cells and B cell lines was investigated in order to clarify the mechanism of enhanced immunoglobulin (Ig) secretion from B cells. Bupleuran 2IIc enhanced IgM secretion from highly purified murine normal B cells. When normal B cells from murine spleen were cultured with bupleuran 2IIc in the presence of anti-IL-6 neutralizing antibody, the enhanced IgM secretion by bupleuran 2IIc was reduced. When B cells were stimulated with bupleuran 2IIc, their IL-6 secretion and the transcription of IL-6 mRNA were enhanced. The enhanced IL-6 secretion by bupleuran 2IIc was also observed in B cell line, Y16 cell. When bupleuran 2IIc was digested with endo-alpha-(1-->4)-D-polygalacturonase, the resulting enzyme resistant carbohydrate portion, "ramified" region (PG-1) composed of rhamnogalacturonan core containing neutral sugar side chains showed potent IL-6 secretion-enhancing activity. These results suggest that the "ramified" region of bupleuran 2IIc stimulates the secretion of IL-6 as the active site, and the resulting IL-6 may partially contribute the enhancement of IgM secretion as an autocrine and/or paracrine mechanism.

Adjuvants, Immunologic↗
PubMed2000

Local treatment of AIDS-associated bulky Kaposi's sarcoma in the head and neck region.

Kaposi's sarcoma (KS) is frequently seen in the head and neck regions of HIV-infected patients. We report two cases of patients with AIDS who consulted the ENT clinic. One patient came to our clinic complaining of abnormal sensations in the pharynx, and dysphasia due to a gross KS in the oropharynx. The excision of the tumor improved the difficulty of swallowing. The other patient complained of masticatory problems and tongue pain due to a bulky KS on the dorsal side of the tongue. We treated the tongue lesion with intralesional chemotherapy. The administration of intralesional vinblastine resulted in a partial response. Unless systemic chemotherapy is effective enough to improve a functional disorder, it is thought that local therapy employing excision or intralesional chemotherapy is one of the common therapeutic option of the otolaryngologist, because this treatment avoids severe side effects caused by systemic chemotherapy or radiotherapy.

Acquired Immunodeficiency Syndrome↗
PubMed2000

A 5-day course of oral desensitization to trimethoprim/sulfamethoxazole (T/S) in patients with human immunodeficiency virus type-1 infection who were previously intolerant to T/S.

BACKGROUND: Trimethoprim/sulfamethoxazole (T/S) is an essential drug in patients with human immunodeficiency virus type-1 (HIV-1) infection to prevent opportunistic infections. About 40% to 60% of them develop skin rash which leads to discontinue the medication. A precise mechanism of the reaction is not known. OBJECTIVE: To make the patients more tolerable to the medication and to make clear whether or not the reaction is caused by serum sulfamethoxazole-specific IgE. METHODS: We established a 5-day protocol, in which T/S was administered orally as a granular form in increasing doses beginning with 0.005 g (it contains trimethoprim 0.4 mg and sulfamethoxazole 2 mg) and doubled every 12 hours until the therapeutic dose was achieved. We tried to desensitize T/S in 17 patients with HIV-1 infection who were previously intolerant to T/S and measured the specific IgE in sera. RESULTS: Desensitization was successfully completed in 15 (88.2%) of the patients. In two patients who failed the desensitization, one was due to fever and the other was gastric irritation. During followup in a mean period of 16.6 months (range, 8 to 23 months) as of May, 1999, none has had Pneumocystis carinii pneumonia (PCP) while receiving T/S after desensitization. Sulfamethoxazole-specific IgE did not increase, indicating that it was not the major cause of skin rash due to T/S in our cases. CONCLUSION: These preliminary results show that most patients who were thought to be intolerant to T/S and had no sulfamethoxazole-specific IgE can be safely desensitized and received the drug subsequently as an effective prophylaxis for PCP.

Administration, Oral↗
PubMed2000

Transactivation mechanisms of mouse clock transcription factors, mClock and mArnt3.

BACKGROUND: The Arnt3 (also termed as BMAL1 or MOP3)/Clock heterodimer is a positive regulator of circadian rhythm and activates the transcription of target genes such as per1 and vasopressin. RESULTS: We investigated the transcriptional mechanism of mArnt3/mClock heterodimer. While mClock did not possess any distinct activation domain, mArnt3 contained a transcriptional activation domain at the most C-terminal end, the activity of which was not expressed, even in the one hybrid system, until it was bound by mClock. It has been suggested that mClock plays a regulatory or structural role in exerting a transcription enhancing effect of the mArnt3/mClock heterodimer. Deletion proceeding from amino acids 559-492 of mClock markedly reduced the transactivation activity of mArnt3/mClock heterodimer, in consistence with the results of the Clock-delta 19 mutant. Yeast and mammalian two-hybrid systems revealed that CBP and p300 interacted with mArnt3 via the CREB binding domain. The In vivo interaction between mArnt3 and CBP was confirmed by the GST pull down assay. CONCLUSION: Taken together, these results suggest that the mArnt3/mClock heterodimer exerted its transactivation activity via CBP or p300 interacting with mArnt3 in the heterodimer with mClock playing a structural or regulatory role in the transactivation process.

ARNTL Transcription Factors↗
PubMed2000

In vitro hyperprocessing of Drosophila tRNAs by the catalytic RNA of RNase P the cloverleaf structure of tRNA is not always stable?

We have previously reported that the catalytic RNA subunit of RNase P of Escherichia coli (M1 RNA) cleaves Drosophila initiator methionine tRNA (tRNA(Met)i) within the mature tRNA sequence to produce specific fragments. This cleavage was dependent on the occurrence of an altered conformation of the tRNA substrate. We call this further cleavage hyperprocessing. In the present paper, to search for another tRNA that can be hyperprocessed in vitro, we used total mature tRNAs from Drosophila as substrates for the in vitro M1 RNA reaction. We found that some tRNAs can be hyperprocessed by M1 RNA and that two such tRNAs are an alanine tRNA and a histidine tRNA. Using mutant substrates of these tRNAs, we also show that the hyperprocessing by M1 RNA is dependent on the occurrence of altered conformations of these tRNAs. The altered conformations were very similar to that of tRNA(Met)i. We show here that M1 RNA can be used as a powerful tool to detect the alternative conformation of tRNAs. The relationship between these hyperprocessing reactions and stability of the tRNA structure will also be discussed.

Alanine↗