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Biomedical subjects

Tsunehisa Makino

Publications and source records attributed to Tsunehisa Makino.

At least 19 recordsLinked to original sources
PubMed2005

Development of a simple method for predicting the levels of di(2-ethylhexyl) phthalate migrated from PVC medical devices into pharmaceutical solutions.

This study deals with the development of a simple method for predicting the elution levels of di-2-ethylhexyl phthalate (DEHP) from medical devices made of polyvinyl chloride (PVC) by using the physicochemical properties of pharmaceutical injections as a marker. GC-MS analysis showed that the release of DEHP from medical grade PVC product was concentration-dependently increased by extraction with two kinds of lipophilic injections (Sandimmun and Prograf) and three kinds of surfactants (HCO-60, Tween 80, and SDS). The solubility of lipophilic pigments such as Sudan III, methyl yellow, and 1,4-diamino-anthraquinone against these solutions were also increased in a concentration-dependent manner, in which methyl yellow showed the highest response regarding the increase of optical density (O.D.). Further, electrical conductivity and static contact angle to the PVC sheet of the solutions were also increased or decreased in the same manner. As a result of the comparative study, significant correlation was found between DEHP release levels and these three physicochemical properties, particularly methyl yellow solubility, of the solutions tested. To evaluate the relationship in detail, DEHP release levels from PVC tubing and methyl yellow solubility of 53 injections used in gynecologic and obstetric fields were determined. None of the hydrophilic medicines showed any significant release of DEHP, and all showed low solubility of methyl yellow. On the other hand, the lipophilic medicines releasing a large amount of DEHP showed high solubility of methyl yellow (greater than O.D. 0.8). These results indicate that a significant proportional relationship exists between DEHP release potency and methyl yellow solubility of pharmaceutical solutions, and the risk of DEHP exposure to the patients administered pharmaceuticals through transfusion set could be easily predicted by the solubility test without complicated elution tests of DEHP using GC-MS or LC-MS.

Diethylhexyl Phthalate↗
PubMed2005

Stir bar sorptive extraction with in situ de-conjugation and thermal desorption gas chromatography-mass spectrometry for measurement of 4-nonylphenol glucuronide in human urine sample.

4-Nonylphenol glucuronide (NP-G) in human urine samples was analyzed using stir bar sorptive extraction (SBSE) with in situ de-conjugation by beta-glucuronidase and thermal desorption (TD)-gas chromatography-mass spectrometry (GC-MS). Distilled water (1 ml), 1.0 M ammonium acetate solution (100 microl) and beta-glucuronidase (10,000 units ml(-1), 10 microl) were added to human urine sample (1 ml), and extraction was commenced for 90 min at 37 degrees C while stirring at 250 rpm with a stir bar coated with a 500-microm-thick polydimethylsiloxane (PDMS) layer. Then, the stir bar was subjected to TD-GC-MS in the selected ion monitoring (SIM) mode. The calibration curve was made by SBSE method using 4-nonylphenol (NP) as the standard solution. The method showed good linearity and the correlation coefficients were 0.999 over the concentration range of 5-500 nM. Moreover, to optimize the conditions for SBSE with in situ de-conjugation and the recovery test, NP-G was synthesized by a biochemical technique in our laboratory. The limits of detection (S/N = 3) and quantitation (S/N > 10) for NP were 0.2 ng ml(-1) (1.0 nM) and 1.1 ng ml(-1) (5.0 nM), respectively. The average recoveries in the human urine samples (n = 6) spiked with NP-G at levels of 20 and 100 nM were 104.1 (R.S.D. 7.1%) and 100.6% (R.S.D. 9.2%), respectively, with correction using the added internal standard, 4-(1-methyl) octylphenol-d(5). The method enabled the precise determination of the standard and was applicable to the detection of trace amounts of NP-G in human urine samples.

Acetates↗
PubMed2005

Exposure to bisphenol A is associated with recurrent miscarriage.

BACKGROUND: Little is known about the influence of high exposure to bisphenol A on recurrent miscarriage and immunoendocrine abnormalities. METHODS: Serum bisphenol A, antiphospholipid antibodies (aPLs), antinuclear antibodies (ANAs), natural killer cell (NK) activity, prolactin, progesterone, thyroid-stimulating hormone (TSH) and free T4 were examined in 45 patients with a history of three or more (3-11) consecutive first-trimester miscarriages and 32 healthy women with no history of live birth and infertility. Subsequent pregnancy outcome and embryonic karyotype of abortuses were examined prospectively. RESULTS: The mean+/-SD values for bisphenol A in patients were 2.59+/-5.23 ng/ml, significantly higher than the 0.77+/-0.38 ng/ml found for control women (P=0.024). High exposure to bisphenol A was associated with the presence of ANAs but not hypothyroidism, hyperprolactinaemia, luteal phase defects, NK cell activity or aPLs. A high level of bisphenol A in itself did not predict subsequent miscarriage. CONCLUSION: Exposure to bisphenol A is associated with recurrent miscarriage.

Abortion, Habitual↗
PubMed2005

Stir bar sorptive extraction with in situ derivatization and thermal desorption-gas chromatography--mass spectrometry for measurement of phenolic xenoestrogens in human urine samples.

A high-sensitivity analytical method that uses stir bar sorptive extraction (SBSE) with in situ derivatization and thermal desorption (TD)-gas chromatography-mass spectrometry (GC-MS) for the simultaneous measurement of trace amounts of phenolic xenoestrogens (PXs), such as 2,4-dichlorophenol (DCP), 4-tert-butylphenol (BP), 4-tert-octylphenol (OP), 4-nonylphenol technical isomers (NP), pentachlorophenol (PCP) and bisphenol A (BPA), in human urine samples was developed. The urine sample (1 ml) was de-conjugated by adding beta-glucuronidase and sulfatase. Then, protein precipitation was performed by the addition of acetonitrile. After centrifugation, the supernatant was diluted with purified water and subjected to SBSE with in situ derivatization and TD-GC-MS. The detection limits of DCP, BP, OP, NP, PCP and BPA in the urine samples were 20, 10, 10, 50, 20 and 20 pg ml-1 (ppt), respectively. The calibration curves for PXs were linear and had correlation coefficients higher than 0.99. The average recoveries of those analytes in the urine samples were higher than 95% (RSD: <10%, n=6) with correction using the added surrogate standards. This simple, accurate, sensitive and selective method can be used in the determination of PXs in human urine samples.

Adult↗
PubMed2005

Impact of ovarian endometrioma on oocytes and pregnancy outcome in in vitro fertilization.

OBJECTIVE: To evaluate the effect of endometriosis and the presence of an ovarian endometrioma on outcomes of conventional in vitro fertilization (IVF). DESIGN: Retrospective study. SETTING: Reproductive Unit, Department of Obstetrics and Gynecology, Tokai University Hospital. PATIENT(S): Group A: 80 cycles with ovarian endometriomas; group B: 248 cycles with endometriosis but without endometrial cysts at the time of oocyte retrieval; group C: 283 cycles undergoing IVF because of tubal factor without endometriosis. INTERVENTION(S): All conventional in vitro fertilization-embryo transfer (IVF-ET) with previous diagnostic laparoscopy. An endometrioma was diagnosed by direct aspiration at the time of oocyte retrieval. MAIN OUTCOME MEASURE(S): Retrieved number of oocytes, fertilization rate, embryo quality, implantation rate, pregnancy rate, and live birth rate for all cases. In group A, the number of retrieved oocytes in relation to the volume of the endometrioma and affected laterality. RESULT(S): Fewer oocytes were retrieved from groups A and B than from group C (P<.005). The number of retrieved oocytes was not dependent on the volume of endometrial cyst(s). Fertilization rates were similar among the groups. Group A had slightly but not significantly higher rates of morphologically good-quality embryos (group A: 67.2%, group B: 63.0%, group C: 58.1%), implantation (group A: 14.1%, group B: 11.7%, group C: 11.3%), and pregnancy (group A: 25.3%, group B: 22.3%, group C: 23.9%). CONCLUSION(S): Endometriosis affects oocyte number but not embryo quality or pregnancy outcome, irrespective of the presence of an ovarian endometrioma.

Adult↗
PubMed2005

Characterization of a murine anti-laminin-1 monoclonal antibody (AK8) produced by immunization with mouse-derived laminin-1.

Laminin-1 is a structural glycoprotein that forms an integral part of the scaffolding of basement membranes, and plays an important role during embryonic development. We have recently demonstrated a significant association between anti-laminin1 antibodies (Abs) and reproductive failure, such as recurrent spontaneous abortions and infertility-associated endometriosis in both human and mouse studies. In the present study, we established an IgM (micro, kappa) monoclonal anti-laminin-1 Ab (AK8) by immunizing mice with mouse Engelbreth-Holm-Swarm sarcoma (EHS)-derived laminin-1. The AK8 monoclonal antibody (mAb) reacted with particular peptide sequences from the globular G domain of mouse laminin-alpha1 chain of using ELISA and Western blot techniques. The peptide tertiary structure of the epitope recognized by AK8 mAb was predicted using eight synthesized domain peptide sequences and three consensus sequences obtained by phage displayed random peptide library. Basement membranes of endometrium of pregnant mice and humans were immunostained with AK8 mAb. Thus, AK8 mAb recognized a common structure present in the G domain of the laminin-alpha1 chain in both mice and humans. The passive immunization of mice with AK8 mAb may represent a suitable animal model for anti-laminin-1 Ab-mediated reproductive failure.

Amino Acid Sequence↗
PubMed2005

Preconception peripheral natural killer cell activity as a predictor of pregnancy outcome in patients with unexplained infertility.

PROBLEM: Preconception high peripheral natural killer (NK) cell activity in women with recurrent spontaneous abortion can predict subsequent miscarriages. We have examined prospectively, for the first time, the pregnancy rate in patients with unexplained infertility by measuring the peripheral NK activity. METHOD OF STUDY: We tested the peripheral NK activity of 94 infertile women who despite treatment were unable to conceive for 6 or more months (mean; 2.4 years). Peripheral NK activity was measured by a chromium-51 release cytotoxicity assay. Women were followed for 2 years and assessed. RESULTS: In 77 patients who were followed for 2 years, 28 had conceived but 49 did not. The peripheral NK activity of the group that became pregnant (mean +/- S.D.; 34.5 +/- 13.8%) was significantly lower than that of non-conception group (42.3 +/- 13.3%, P = 0.017). CONCLUSIONS: Our finding suggests that elevated peripheral NK activity in patients with unexplained infertility is a risk factor for attaining pregnancy success.

Abortion, Habitual↗
PubMed2004

Determination of 4-tert.-octylphenol and 4-nonylphenol in laboratory animal feed sample by stir bar sorptive extraction followed by liquid desorption and column-switching liquid chromatography-mass spectrometry with solid-phase extraction.

A novel analytical method has been developed for the determination of 4-tert.-octylphenol (OP) and 4-nonylphenol (NP) in laboratory animal feed samples, which involves stir bar sorptive extraction (SBSE) followed by liquid desorption (LD) and column-switching liquid chromatography-mass spectrometry (CS-LC-MS) with solid-phase extraction (SPE). The method required correction by stable isotopically labeled surrogate standards, deuterium 4-tert.-octylphenol (OP-d) and [2H5] 4-(1-methyl)octylphenol (m-OP-d5). A feed sample was homogenized with methanol by ultrasonication. After centrifugation, the supernatant was subjected to extraction for 120 min at room temperature (25 degrees C) using a stir bar coated with polydimethylsiloxane. After the extraction, the analyte was desorbed from the stir bar by LD using acetonitrile. Then, the liquid sample was analyzed by CS-LC-MS with SPE. The average recoveries from laboratory feed samples spiked with OP and NP at 20 ng g(-1) were 99.5 and 103.8%, respectively, with correction using the added surrogate standards. The limits of quantification were 1 ng g(-1) for OP and 5 ng g(-1) for NP in feed sample. The measurement of OP and NP in commercial laboratory animal feed samples resulted in the detection of sub ng g(-1) NP

Animal Feed↗
PubMed2004

Stir bar sorptive extraction and thermal desorption-gas chromatography-mass spectrometry for the measurement of 4-nonylphenol and 4-tert-octylphenol in human biological samples.

Alkylphenols, 4-nonylphenol (NP) and 4-tert-octylphenol (OP), in human urine and plasma samples were analyzed using stir bar sorptive extraction (SBSE) in combination with thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS). The method involved correction by stable isotopically labeled surrogate standards, 4-(1-methyl)octylphenol-d5 (m-OP-d5) and deuterium 4-tert-octylphenol (OP-d). A biological sample was extracted for 60 min at room temperature (25 degrees C) using a stir bar coated with a 500 microm thick polydimethylsiloxane (PDMS) layer. Then, the stir bar was analyzed by TD-GC-MS in the selected ion monitoring (SIM) mode without any derivatization step. The average recoveries in human urine and plasma samples spiked with NP and OP at levels of 0.5 and 10 ng ml-1 were between 95.8 and 99.8% with correction using the added surrogate standards. The limits of quantitation were 0.2 ng ml-1 for NP and 0.02 ng ml-1 for OP. We measured the background levels of NP and OP in five human urine and three human plasma samples from healthy volunteers. NP and OP were not detected in all human urine samples (N.D. < 0.2 ng ml-1 for NP, and N.D. < 0.02 ng ml-1 for OP). However, 0.2-0.3 ng ml-1 for NP and 0.1-0.2 ng ml-1 for OP in human plasma samples were observed by this method.

Gas Chromatography-Mass Spectrometry↗
PubMed2004

Serum carbohydrate antigen elevations in endometrial adenocarcinomas: characterization of DU-PAN-2 expression as a tumor marker.

AIM: To characterize serum elevations of carbohydrate antigens; DU-PAN-2, CA19-9, sialyl Lewisx and CA125 in endometrial adenocarcinomas (EMACs), particularly focusing on the clarification of DU-PAN-2 expression profiles. METHODS: Sixty-four resected EMACs of endometrioid type were used. The preoperative serum values of four markers were measured and comparatively analyzed regarding the relationship between histological grade and clinicopathological stage. RESULTS: The overall ratios of positive cases were 26.2% for DU-PAN-2, 25.0% for CA19-9, 13.6% for sialyl Lewisx, and 35.5% for CA125. DU-PAN-2 decreased as the grading went up (G1: 410.3 +/- 243.8 to G3: 246.7 +/- 90.0 U/mL), however, the reverse was true with CA19-9 (G1: 123.9 +/- 147.4 to G3: 320.0 +/- 180.0 U/mL). Sialyl Lewisx showed a strong tendency towards high elevation in G1 (346.3 +/- 102.6 U/mL), compared to G3 (< 2.5 U/mL). CA125 increased markedly as the grading went up (G1: 43.5 +/- 6.3 to G3: 578.0 +/- 10.0 U/mL). During staging-up from I + II to III + IV, the positive ratios inclined in all four markers as follows: DU-PAN-2, 18.4-53.3%; CA19-9, 20.4-40.0%; sialyl Lewisx, 11.4-22.2%; CA125, 31.8-44.4%. Serum elevations and positive ratios were correlated for DU-PAN-2, CA19-9 and CA125, while the reverse relationship was found for sialyl Lewisx. CONCLUSION: It is suggested that DU-PAN-2 tends to be produced more in well-differentiated components of EMACs than in poorly differentiated ones. Since approximately half the cases with EMAC were serologically positive for DU-PAN-2 in stage III + IV, the marker is believed to be of much use for monitoring the cases with an extrauterine extent.

Adenocarcinoma↗
PubMed2004

Antiphosphatidylethanolamine antibodies in recurrent early pregnancy loss and mid-to-late pregnancy loss.

AIM: Associations have been reported between antiphospholipid antibodies (aPL), mainly anticardiolipin antibodies (aCL) and/or the lupus anticoagulant, and recurrent pregnancy losses (RPL). However, relatively few studies describing antiphosphatidylethanolamine antibodies (aPE) have been reported. We describe the prevalence of aPL to both cardiolipin and phosphatidylethanolamine in patients with RPL. METHODS: Patients with recurrent early pregnancy losses (n = 145) and mid-to-late pregnancy loss(es) (n = 26) were screened for aPE and aCL. RESULTS: In patients with recurrent early pregnancy losses, prevalence of immunoglobulin G (IgG) aPE (17.9%, P = 0.001) and immunoglobulin M (IgM) aPE (12.4%, P = 0.01) was significantly higher than in the control group. In patients with mid-to-late pregnancy loss(es), prevalence of IgM aPE (19.2%, P = 0.008) and IgG aCL (23.1%, P = 0.02) was significantly higher than in the control group. CONCLUSION: Our data suggest that aPE may be a risk factor in patients with mid-to-late pregnancy loss(es) as well as recurrent early pregnancy losses.

Abortion, Habitual↗
PubMed2004

Anesthesia and acoustic stress-induced intra-uterine growth retardation in mice.

Stress interferes with reproduction, adversely influencing implantation and fetal growth, and sometimes even leading to abortion. Here, we attempted to evaluate the early gestational effects of uncomfortable sound on pregnant mice and their offspring. Ten-week-old pregnant Jcl:ICR mice were exposed to sound (100 dB, random frequency between 9-34 kHz) for 8 hours on the 3(rd), 5(th) and 7(th) gestational days (GD). The effects of general anesthesia were also investigated, with or without acoustic stress. All groups were examined on the 18(th) GD for fetal growth. Fetal weight, number of ossified sacrococcygeal vertebrae and placental weight were all significantly reduced (P<0.0001) when stress was induced on the 7(th) GD, but not on the 3(rd) or 5(th) GD. This intra-uterine growth retardation (IUGR) was significantly inhibited by general anesthesia (P<0.0001), although general anesthesia alone induced significant IUGR (P<0.0001) when compared with control mice. This suggests that acoustic exposure indirectly exerts an effect on fetal growth, possibly via a psycho-maternal pathway. We also found that analysis of the number of ossified sacrococcygeal vertebrae is the most sensitive tool for the study of IUGR.

Acoustics↗
PubMed2004

Platelet inhibition by single low-dose aspirin, using the newly developed aggregometry with the laser light scattering method.

Low-dose aspirin (acetylsalicylic acid 81 mg/day, LDA) is often used as an antiplatelet drug in the treatment of cardiovascular and cerebrovascular diseases as well as for patients with anti-phospholipid antibody syndrome. In this study, we explored the duration of the inhibitory effect of a single LDA on platelet aggregation, using the newly developed aggregometry with the laser light scattering method. Five healthy volunteers (females between 23 and 30 years old) ingested 81 mg of buffered aspirin. Platelet aggregation was measured with adenosine 5'-diphosphate before the ingestion and at the 1st, 2nd, 4th, 6th, and 8th day thereafter. The results showed that the effect of 81 mg of aspirin continues for at least 8 days, which suggested that the intermittent administration of 81 mg of aspirin (a few times a week) might be an alternative way to induce the anti-platelet effect.

Adult↗
PubMed2004

Uterine body cancer mass screening at Tokai University Hospital.

A total of 1,512 women participated in mass screenings for uterine body cancer (UBC) from 1998 to 2003 at Tokai University Hospital. Their rate in the examinees of uterine cervical cancer (UCC) mass screenings was 4.7%. Among the 1,512 examinees, endometrial cytological abnormalities (class III or higher) were found in 17 (1.1%) cases. As a result, UBC was detected in two patients (0.13%). One case was diagnosed as class V, adenocarcinoma, and she underwent hysterectomy. In another case, adenocarcinoma was found to be associated with atypical endometrial hyperplasia in hysterectomy specimens. For the remaining 15 cases diagnosed as class III, the cytological abnormalities disappeared after a follow-up except for 3 patients who were not followed at Tokai University Hospital. In a comparison of the examinees with or without genital bleeding, the cytological abnormalities were more frequently detected in the former group; 4.2% (6/142) vs. 0.6% (5/819) (p < 0.05). We recommend examinees aged 40 years or higher with a complaint of genital bleeding to participate in UBC mass screening for detection of endometrial adenocarcinoma at early stages.

Adenocarcinoma↗
PubMed2004

Developing and establishing an ideal method of continuous-infusion epidural analgesia for delivery using the double-catheter method.

We evaluated the efficacy of a new method of induction of epidural obstetric analgesia devised by us. The upper and lower catheters used for the epidural double-catheter method were connected to a compression-type disposable injector (Coopdech Syrinjector). 0.125 % bupivacaine + 2 microg/ml fentanyl (6 ml/h) were serially injected via the upper catheter. In the latter half of Stage 1 of labor, the same drugs were continuously infused via the lower catheter (4 ml/h). The mean number of additional drug doses administered via the upper catheter was 0.67+/-0.90 (range: 0-3) when the analgesia induction was commenced after the cervix was dilated to 8 cm in nulliparous women or 6 cm in multiparous women. The method of analgesia was found to be more effective than the conventional method (uncombined continuous infusion of a local anesthetic) for alleviating the pain of the latter half of Stage 1, and Stage 2 of labor. The mean number of additional drug doses injected via the lower catheter was 0.37+/-0.57(range: 0-2). The number of additional doses in the 49 women averaged 0.16 per hour and 1.04 per delivery. Thus, good results were obtained.

Adjuvants, Anesthesia↗
PubMed2004

Preservation of tubal function following methotrexate treatment for ectopic pregnancy.

To evaluate methotrexate (MTX) administration as a conservative treatment for ectopic pregnancy, we reviewed the medical records of 248 cases (210 patients) of MTX treatment for tubal pregnancies at our department between December 1985 and December 2003, and compared its pregnancy prognosis with that of laparoscopic salpigotomy (59 patients). With the MTX treatment, 185 patients were successfully treated, and the subsequent pregnancy rate and ectopic pregnancy rate were 48.4 % and 18.4 %, respectively, while those rates were 49.2 % and 18.6 %, respectively, after the salpigotomy. These results suggest that MTX treatment is comparable to the more conservative operation. To clarify the (dys/) function of the ectopic implantation tubes and MTX-treated tube (s), we excluded patients who had a contra-lateral healthy tube, and extracted 40 patients as "the affected tube group", where the pregnancy-related parameters were not adversely affected. The findings suggest that MTX is not necessary to preserve tubal function.

Adult↗
PubMed2003

Measurement of bisphenol A levels in human blood serum and ascitic fluid by HPLC using a fluorescent labeling reagent.

A sensitive column-switching HPLC method with fluorescence detection was developed for the determination of bisphenol A (BPA) in human blood serum and ascitic fluid samples. 4-(4,5-Diphenyl-1H-imidazol-2-yl)benzoyl chloride (DIB-Cl) was used as the fluorescent label, and the excess reagent was removed by a column-switching technique. Liquid-liquid extraction with chloroform was used for the pretreatment of serum and ascitic fluid samples. BPA in both the samples could be determined in the concentration range of 0.1-7.0 ppb with the detection limit of 0.04 ppb at a signal-to-noise ratio of 3. The recoveries of BPA spiked to serum and ascitic fluid were 78.6 and 77.7%, respectively. The mean concentrations of BPA (n=9) in maternal and umbilical cord blood sera obtained from healthy pregnant women were 0.46+/-0.20 and 0.62+/-0.13 ppb, respectively. BPA levels (n=21) in blood sera and ascitic fluid obtained from the patients with sterility were also determined to be 0.46+/-0.20 and 0.56+/-0.19 ppb, respectively. Relationships of BPA concentrations were observed between maternal and umbilical cord blood serum samples (r=0.626), as well as blood serum and ascitic fluid samples (r=0.785).

Ascitic Fluid↗