PubMed Health⌕ Search

Biomedical subjects

M Tanikawa

Publications and source records attributed to M Tanikawa.

At least 37 records · Page 2Linked to original sources
PubMed1998

Potent prostaglandin A1 analogs that suppress tumor cell growth through induction of p21 and reduction of cyclin E.

Although the cyclopentenone prostaglandin A1 (PGA1) is known to arrest the cell cycle at the G1 phase in vitro and to suppress tumor growth in vivo, its relatively weak activity limits its usefulness in cancer chemotherapy. In an attempt to develop antitumor drugs of greater potency and conspicuous biological specificity, we synthesized novel analogs based on the structure of PGA1. Of the newly synthesized analogs, 15-epi-delta7-PGA1 methyl ester (NAG-0092), 12-iso-delta7-PGA1 methyl ester (NAG-0093), and ent-delta7-PGA1 methyl ester (NAG-0022) possess a cross-conjugated dienone structure around the five-member ring with unnatural configurations at C(12) and/or C(15) and were found to be far more potent than native PGA1 in inhibiting cell growth and causing G1 arrest in A172 human glioma cells. These three analogs induced the expression of p21 at both RNA and protein levels in a time- and dose-dependent fashion. Kinase assays with A172 cells treated with these analogs revealed that both cyclin A- and E-dependent kinase activities were markedly reduced, although cyclin D1-dependent kinase activity was unaffected. Immunoprecipitation-Western blot analysis showed that the decrease in cyclin A-dependent kinase activity was due to an increased association of p21 with cyclin A-cyclin-dependent kinase 2 complexes, whereas the decrease in cyclin E-dependent activity was due to a combined mechanism involving reduction in cyclin E protein itself and increased association of p21. Thus, these newly synthesized PGA1 analogs may prove to be powerful tools in cancer chemotherapy as well as in investigations of the structural basis of the antiproliferative activity of A series prostaglandins.

Antineoplastic Agents↗
PubMed1998

Paracrine effects of bFGF and KGF on the process of mouse blastocyst implantation.

Implantation is a complex process that requires the interaction of the blastocyst, and subsequently, that of the developing embryos with the endometrium. Several growth factors and cytokines are involved in implantation, but the details of their actions as related to the regulation of blastocyst implantation remain unclear. In the present study, the RT-PCR method was used to determine the gene expression of basic fibroblast growth factor (bFGF), keratinocyte growth factor (KGF), FGF receptor 1 (FGFR1), FGF receptor 2 (FGFR2), and KGF receptor (KGFR) in mouse embryos and in the stromal and epithelial cells of the uterine endometrium. Basic FGF and KGF mRNA were expressed in the endometrial cells, but were not expressed in the embryos. The mRNAs of receptors for bFGF and KGF were expressed in the blastocysts and in the in vitro implanting embryos, suggesting that bFGF and KGF may exert paracrine effects on blastocyst implantation. In this mouse model of blastocyst implantation, it was found that transforming growth factor alpha (TGF-alpha) at the concentrations of 1 ng/ml and 10 ng/ml significantly enhanced the blastocyst attachment and trophoblast spreading and increased trophoblast surface area. Relatively high concentrations of bFGF (100-500 ng/ml) significantly enhanced the rates of blastocyst attachment and of trophoblast spreading and promoted the expansion of the surface area of the implanting embryos. Unlike the rates of blastocyst attachment and trophoblast spreading, the surface area of the spreading embryos was significantly increased by addition of KGF (1-100 ng/ml). These results suggest that the bFGF and KGF derived from the endometrial cells exert paracrine effects on the process of implantation by stimulating trophoblast outgrowth through their cognate receptors.

Animals↗
PubMed1998

Pathogenetic significance of increased levels of interleukin-8 in the peritoneal fluid of patients with endometriosis.

OBJECTIVE: To investigate the role of interleukin-8 (IL-8) in peritoneal fluid of patients with endometriosis in the pathogenesis of endometriosis. DESIGN: Peritoneal fluid was collected by laparoscopy. Endometrial and endometriotic stromal cells were obtained from normal endometrium and from chocolate cyst linings of the ovary. SETTING: Department of Obstetrics and Gynecology of Tottori University Hospital, Yonago, Japan. PATIENT(S): Forty women who underwent either laparoscopy or laparoscopic surgery. MAIN OUTCOME MEASURE(S): The peritoneal fluid concentration of IL-8 was analyzed by enzyme-linked immunosorbent assay, and the correlation between the IL-8 concentration and the extent of active endometriosis was investigated. The effect of IL-8 on cell proliferation was examined by tetrazolium bromide and thymidine incorporation. The expression of IL-8 receptor was examined in stromal cells by reverse transcription polymerase chain reaction. RESULT(S): The level of IL-8 in peritoneal fluid was significantly higher in patients with endometriosis than in patients without endometriosis. A significant correlation was noted with the extent of active endometriosis. Interleukin-8 significantly increased the number of cells and DNA synthesis in the endometrial and endometriotic stromal cells in a dose-dependent manner. Transcripts of IL-8 receptor type A were detected in stromal cells. CONCLUSION(S): The present study suggests that IL-8 found in the peritoneal fluid of patients with endometriosis contributes to the pathogenesis of endometriosis.

Antigens, CD↗
PubMed1998

Autocrine effects of transforming growth factor-alpha on the development of preimplantation mouse embryos.

PURPOSE: We wished to explore the role of transforming growth factor (TGF)-alpha in mouse embryonic development. METHODS: We examined the gene expression of TGF-alpha and epidermal growth factor receptor (EGFR) in mouse blastocysts by the reverse transcription-polymerase chain reaction and evaluated the effects of TGF-alpha on the development of preimplantation mouse embryos using TGF-alpha antisense oligodeoxynucleotide. Mouse teratocarcinoma F9 cells were also a subject of this study. RESULTS: Gene transcripts of TGF-alpha and EGFR were present in both blastocysts and F9 cells. TGF-alpha significantly stimulated the rate of blastocoel expansion in early-cavitating blastocysts and the proliferation of F9 cells. Northern blot analysis showed that TGF-alpha gene expression in F9 cells was markedly suppressed in the presence of TGF-alpha antisense oligodeoxynucleotide. TGF-alpha antisense oligonucleotide significantly reduced the rate of blastocoel expansion and the growth of F9 cells. The inhibitory effects of TGF-alpha antisense oligonucleotide on blastocysts and F9 cells were reversed by the addition of TGF-alpha. CONCLUSIONS: The present observations suggest that TGF-alpha acts as an autocrine factor in the development of preimplantation mouse embryos.

Animals↗
PubMed1998

Vascular levels and cGMP-increasing effects of nicorandil administered orally to rats.

We examined a relation between cyclic guanosine monophosphate (cGMP) production in thoracic aorta, as an indicator probably reflecting the vascular response, and the vascular as well as plasma levels of nicorandil administered orally to rats. Nicorandil (3 mg/kg) given orally was rapidly absorbed, reaching the maximal plasma (approximately 2,600 ng/ml) and vascular concentrations (approximately 176 ng/g) at 15 min after the dosing and thereafter decreased rapidly. Even 2 h after the dosing, the level of the vascular cGMP formation in vivo remained significantly higher (approximately 1,000 fmol/mg increase from the control level) in the nicorandil-treated group, compared with the vehicle-treated one, and was enough to develop pronounced muscle relaxation in in vitro aortic preparations. However, it seems that the vascular cGMP increase in vivo was not always correlated to the plasma concentration of nicorandil, because the plasma concentration (approximately 750 ng/ml corresponding to 3.5 microM) at 2 h after the dosing, caused only relatively low cGMP production (300-400 fmol/mg increase from the control level), when tested in in vitro aortic preparations. Our study may indicate, therefore, that the vascular cGMP elevation in vivo is due to the content of nicorandil effectively remaining at its vascular targets of action as well as the plasma nicorandil concentration.

Administration, Oral↗
PubMed1998

Expression of c-kit messenger ribonucleic acid in human oocyte and presence of soluble c-kit in follicular fluid.

The c-kit protooncogene receptor and its ligand stem cell factor (SCF) regulate the proliferation and survival of germ cells as well as hematopoietic cells and melanocytes. In adult rodent ovary, c-kit and SCF play important roles in follicular development. However, little information about c-kit in the human ovary is available. In this study, we examined the expressions of c-kit messenger ribonucleic acid (mRNA) and c-kit protein in human oocytes, granulosa cells, and follicular fluid obtained from the women who underwent in vitro fertilization or laparoscopic examination. Expression of c-kit mRNA was detected by RT-PCR in the oocytes and granulosa cells. Western blot analysis showed the presence of soluble c-kit protein in the follicular fluid, and lower levels of c-kit protein were detected in the granulosa cells and the supernatant of granulosa cell cultures. The concentration of soluble c-kit in follicular fluid measured by enzyme-linked immunosorbent assay showed significant correlation with fluid volume and follicular fluid concentrations of estradiol, testosterone, and androstenedione. In summary, we found for the first time the presence of c-kit mRNA and soluble c-kit protein in human oocytes and follicular fluid. The results suggested that in human ovary, c-kit may play an important role in follicular development.

Adult↗
PubMed1997

Expression of transforming growth factor alpha (TGF-alpha) gene in mouse embryonic development.

PURPOSE: The expression of genes for TGF-alpha, epidermal growth factor (EGF), and the EGF receptor (EGFR) in mouse blastocysts was evaluated by the reverse transcription-polymerase chain reaction (RT-PCR). We evaluated the effects of TGF-alpha and EGF on the development of mouse embryo prior to implantation. RESULTS: The results revealed the presence of transcripts of TGF-alpha and EGFR. However, EGF mRNA was not observed in repeated experiments. None of these growth factors influenced the rate of development from the two-cell stage to the blastocyst stage when added to the culture medium. These effects were further examined on measuring the incorporation of tritiated thymidine and leucine, providing indices of the synthesis of DNA and protein, respectively. A concentration of only 0.1 ng/ml of TGF-alpha, which shares a cell surface receptor with EGF, stimulated the synthesis of both DNA and protein. EGF at a concentration of 10 ng/ml stimulated the synthesis of DNA and protein by blastocysts. To explore autocrine effects of TGF-alpha on the rate of blastocoel expansion, TGF-alpha antisense oligodeoxynucleotides was used to reduce expression of the TGF-alpha gene. TGF-alpha at a concentration of 0.1 ng/ml stimulates the rate of blastocoel expansion in early cavitating mouse blastocysts. In contrast, TGF-alpha antisense oligonucleotides significantly reduced the rate of expansion. CONCLUSIONS: Our present observations suggest that TGF-alpha/EGF and the EGFR may be involved in regulating embryonic development. In particular, TGF-alpha may serve as an autocrine factor in the regulation of embryonic development.

Animals↗
PubMed1997

Increased interleukin-6 levels in peritoneal fluid of infertile patients with active endometriosis.

OBJECTIVE: Our purpose was to investigate the relationship between the levels of interleukin-6, interleukin-6 soluble receptor, and tumor necrosis factor-alpha in peritoneal fluid and the size and number of active red endometriotic lesions. STUDY DESIGN: In a university hospital 39 women of reproductive age underwent either laparoscopy for infertility workup or laparoscopic surgery for ovarian chocolate cysts. Peritoneal fluid was collected by laparoscopy. Active lesions, such as red flamelike lesions, glandlike lesions, and red vesicles, were scored according to the revised American Fertility Society classification system according to the size and number of active lesions. Peritoneal fluid levels of interleukin-6, interleukin-6 soluble receptor, and tumor necrosis factor-alpha levels were determined by enzyme-linked immunosorbent assays. The relationship between peritoneal fluid concentrations of interleukin-6 and tumor necrosis factor-alpha and the score of active endometriosis was investigated. RESULTS: Peritoneal fluid levels of interleukin-6 and tumor necrosis factor-alpha were significantly higher in patients with endometriosis compared with patients without endometriosis. The concentrations in patients with active endometriosis increased as the size and the number of active lesions increased. Cyclic variations in interleukin-6 concentrations were seen in peritoneal fluid from patients with endometriosis; the concentrations in the secretary phase were significantly higher than those in the proliferative phase. CONCLUSIONS: Increased peritoneal fluid levels of interleukin-6 in patients with active red endometriosis may relate to endometriosis-associated infertility and to the pathogenesis of endometriosis.

Adult↗
PubMed1996

Chlamydia trachomatis antibody titres by enzyme-linked immunosorbent assay are useful in predicting severity of adnexal adhesion.

The aim of this study was to investigate the relationship between chlamydia infection and adnexal adhesion. A total of 131 infertile women who were otherwise asymptomatic underwent chlamydia antibody testing and laparoscopy. These women had additional infertility factors. Serum concentration of anti-Chlamydia trachomatis immunoglobulins G and A were determined prospectively by means of an enzyme-linked immunosorbent assay (ELISA). Results were compared with the tubal patency and severity of adnexal adhesion. Sensitivity, specificity, positive and negative predictive value, and likelihood ratios of anti-C.trachomatis antibody titres for the presence of adnexal adhesion were calculated. Patients who were positive for chlamydia antibody had a significantly higher incidence of tubal occlusion than those who were negative (47.1 versus 25.0%). Adnexal adhesion scores were significantly higher in the patients who were positive for chlamydia antibody than those in patients who were negative (17.1 versus 8.5). Adnexal adhesion scores were significantly correlated with anti-chlamydia antibody titre by ELISA [immunoglobulin (Ig) G: r = 0.60, Ig A: r = 0.61]. As the antibody titre by ELISA rose, the specificity, positive predictive value and the positive likelihood ratio all increased. In conclusion, C.trachomatis antibody testing is a simple and inexpensive means of predicting pelvic damage and laparoscopic examination may be recommended for patients with high anti-C.trachomatis antibody titres by ELISA.

Adnexal Diseases↗
PubMed1996

The movements of fetuses with congenital myotonic dystrophy in utero.

The movements in two fetuses with congenital myotonic dystrophy were recorded on fetal actocardiograms. The two fetuses showed gross movements associated with FHR accelerations as normal fetus. One of them showed swallowing on amniofetogram, and hiccuping on fetal actocardiogram. Both, however, were extremely hypotonic and neither displayed any gross movement, respiratory movement or swallowing postnatally. Intubation and nasal feeding were required for a long period of time after birth in both cases. The buoyancy of amniotic fluid may help the affected fetus to make gross movement in utero.

Adult↗
PubMed1996

[The usefulness of percutaneous transhepatic cholecyst puncture (PTCCP) with ultrasoundimage control for acute cholecystitis].

Percutaneous transhepatic cholecyst puncture (PTCCP) is a unique treatment for acute cholecystitis by using of 21 gauge PTC needle with ultrasoundimage control. The procedure is as follows. A percutaneous transhepatic puncture of the gallbladder is made with ultrasonic guidance. After suction removal of the contents of the gallbladder, saline with antibiotics is injected. Finally PTC needle is removed after removal of the injected saline. We carried out PTCCP in 35 patients with acute cholecystitis, and compared its clinical effect with those of PTCCD (46 cases) or conservative treatment of antibiotics administration (38 cases). The treatment of PTCCP removed the clinical symptoms of acute cholecystitis rapidly compared with the conservative treatment and it made the hospitalization shorter compared with the treatment of PTCCD. PTCCP was also performed without any severe complications for patients with underlying diseases. The curative rate of PTCCP was the same as those of other former treatments. It was concluded that PTCCP is a safe, convenient, and useful treatment of acute cholecystitis.

Acute Disease↗
PubMed1994

Assessment of functional integrity of frozen-thawed mouse embryos by albumin and leucine uptake.

To assess the effects of freezing-thawing on metabolic functions of embryos prior to implantation, we measured the uptake of [125I]bovine serum albumin (BSA) and [3H]leucine in 2-cell mouse embryos, that were freshly collected (control), exposed to cryoprotectants (non-frozen), and frozen-thawed, and in morulae and blastocysts cultured from these 2-cell embryos. No significant difference in [125I]BSA uptake by 2-cell embryos was observed among the three groups. However, [125I]BSA uptake by blastocysts in the frozen-thawed group was significantly reduced compared with the control and non-frozen groups. [3H]leucine uptake by 2-cell embryos in the frozen-thawed and non-frozen groups was significantly less than in the control group. Fluorescein diacetate staining was performed in the control and frozen-thawed 2-cell embryos. The intensity of fluorescence after fluorescein diacetate exposure did not differ between the control and frozen-thawed embryos. The present study with mouse embryos suggests that freezing-thawing procedures impair the metabolic functions, in particular the membrane transport system, of embryos. Measurements of BSA and leucine uptake in embryos may be useful for evaluating the quality of frozen-thawed embryos.

Animals↗
PubMed1994

Effects of human serum supplementation on fertilization and development of mouse embryos.

Serum is generally used as a protein supplement in culture media for human in vitro fertilization (IVF). To determine the effects of serum supplementation on the development of preimplantation embryos, one-cell and two-cell mouse embryos fertilized in vitro and in vivo were cultured in BWW medium supplemented with preovulatory patient serum (PS), human fetal cord serum (HCS), or bovine serum albumin (BSA). The rates of fertilization and development of embryos fertilized in vitro and in vivo were suppressed when the embryos were cultured with PS or HCS as compared with BSA. In the medium supplemented with HCS, growth of in vitro fertilized embryos was retarded at an earlier embryonic stage than was the case with embryos fertilized in vivo. These results suggest that the in vitro fertilized embryo culture model is more sensitive to culture conditions than is the in vivo fertilized embryo culture model. Incorporations of [3H]uridine and [3H]leucine were measured using embryos that developed to the blastocyst stage in a medium supplemented with HCS or BSA. Blastocysts cultured with HCS showed significantly higher incorporations of [3H]uridine and [3H]leucine than those cultured with BSA. While serum supplementation in culture media has adverse effects on embryo cleavage, it augments synthesis of RNA and protein.

Animals↗
PubMed1994

Monitoring serum tryptic activity and effect of trypsin inhibitor on rat acute pancreatitis.

The effect of a novel synthetic trypsin inhibitor, 4-(2-succinimidoethylthio)-phenyl 4-guanidinobenzoate methanesulfonate (E3123), on severe acute pancreatitis was studied in trypsin-taurocholate-induced acute experimental pancreatitis in rats. Rats were divided into four groups according to difference of subdivided doses of E3123 with fixing the total dose at 3 mg/kg body weight. Group A: 1.5 mg/kg of E3123 subcutaneously (SC) each at 1 h before and after induction of pancreatitis. Group B: 1 mg/kg SC each at 1 h before, 1 and 3 h after induction. Group C: 1.5 mg/kg SC each at 1 and 3 h after induction. Group D: 1.5 mg/kg SC each at 3 and 5 h after induction of pancreatitis. The survival rate at 24 h was significantly improved in group B (77% in group B, vs. 36% in paired control; p < 0.01) and in group C (70 vs. 38%; p < 0.05), but not in group A or D. Residual tryptic activity of serum alpha 2-macroglobulin trypsin complex (alpha 2M-TRY) was reduced after the injection of E3123 though immunoreactive trypsin remained unchanged in the early phase of pancreatitis. The reduction of alpha 2M-TRY reflected the inhibitory capacity of E3123 in plasma. E3123 showed favorable effects on the initial stage of severe acute pancreatitis and the effects were probably based on the inhibition of alpha 2M-TRY activity in serum.

Acute Disease↗
PubMed1994

Regulation of pancreatic polypeptide release is mediated through M3 muscarinic receptors.

The purpose of this study was to determine the regulation of pancreatic polypeptide (PP) release by using pirenzepine (a specific M1 muscarinic receptor antagonist), 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP, a specific M3 muscarinic receptor antagonist), atropine (a nonspecific muscarinic receptor antagonist), and loxiglumide (cholecystokinin, CCK, receptor antagonist) in dogs. In conscious dogs with chronic gastric and duodenal fistulas, release of PP and exocrine pancreatic secretion were stimulated by constant intravenous infusion of CCK-8 (200 ng/kg/h). Graded doses of pirenzepine (0.18-4.7 mmol/kg/h), 4-DAMP (6.7-180 nmol/kg/h), or atropine (0.89-24 nmol/kg/h) dose-dependently reduced plasma PP responses to CCK-8 without influence on exocrine pancreatic secretion. ID50 calculated from these results were 492 +/- 150 nmol/kg/h for pirenzepine, 10.7 +/- 1.8 nmol/kg/h for 4-DAMP and 19.4 +/- 5.2 nmol/kg/h for atropine. A similar sequence in the inhibitory potency was observed in 2-deoxy-D-glucose (2-DG, 100 mg/kg)-stimulated PP release, exocrine pancreatic, and gastric secretions. On the other hand, loxiglumide, a CCK receptor antagonist, did not influence PP release stimulated by 2-DG. These findings suggest that both CCK- and 2-DG-stimulated PP releases are mainly under cholinergic nerve control mediated by M3 muscarinic receptor in dogs.

Animals↗
PubMed1994

[Effects of repeated sevoflurane anesthesia on hepatic and renal function in a pediatric patient].

A 10-yr-old boy with an injured lower extremity received sevoflurane anesthesia 5 times within 40 days. Laboratory tests for hepatic and renal function i.e., serum transaminase (glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, gamma-glutamyl transpeptidase), serum cholinesterase, plasma protein, serum cholinesterase, serum bilirubine, serum lactic dehydrogenase, serum prothrombin time, blood urea nitrogen, serum creatinine, beta 2-microglobulin, N-acetyl-D-glucosamidase and 24 hr-creatinine clearance remained within normal ranges throughout his perioperative period. Repeated sevoflurane anesthesia did not exert any adverse effect on hepatic and renal function in this patient.

Anesthesia, Inhalation↗
PubMed1993

Sensitive method for determination of nicorandil in human plasma by reversed-phase high-performance liquid chromatography with ultraviolet detection.

A sensitive method for the determination of nicorandil, an anti-anginal drug, has been developed. The method involves solid-phase extraction of the drug and an internal standard using a Bond-Elut PH extraction column, liquid-liquid extraction with methyl acetate and dichloromethane, and reversed-phase high-performance liquid chromatography on a mu Bondapak C18 column with an ultraviolet detector. The limit of determination in plasma was 3 ng/ml and the intra-day coefficient of variation (n = 7) was less than 10%.

Anti-Arrhythmia Agents↗