Search PubMed⌕ Search

Biomedical subjects

K Koyama

Publications and source records attributed to K Koyama.

At least 55 records · Page 3Linked to original sources

Screening for deletions in interval D16-22 of the Y chromosome in azoospermic and oligozoospermic Japanese men.

The genetic basis of infertility remains unclear in a majority of infertile men. In this study, the Y chromosome long arm involving the DAZ (deleted in azoospermia) gene was screened in order to evaluate the occurrence of microdeletion in Japanese infertile men. One hundred and fifty-seven infertile Japanese men with azoospermia and oligozoospermia were analyzed for microdeletions in interval D16-22 of the Y chromosome, using polymerase chain reaction with sequence-tagged site markers. Sixteen sets of oligonucleotide primers were synthesized for the polymerase chain reaction, and Southern blot analysis was also performed. The men were divided into five categories on the basis of sperm concentration: functional azoospermia (A; n = 24), azoospermia caused by obstruction (AO; n = 20), oligozoospermia I (OI, sperm concentration less than I x 10(5)/ml; n = 33), oligozoospermia II (OII, sperm concentration less than 1 x 10(6)/ml; n = 30), and oligozoospermia III (OIII, sperm concentration less than 1 x 10(7)/ml; n = 50). Thirty fertile men with a sperm concentration of more than 2 x 10(7)/ml were also analyzed as controls. Microdeletions were identified, in 12 (7.6%) of the 157 infertile men, as follows: 1 man in category A, 1 in category AO, 5 in category OI, 4 in category OII, and 1 in category OIII. No deletion was identified in the fertile men. One common region around sY240 was identified in 11 of the infertile men with microdeletions. This locus may contain specific genes for spermatogenesis. The sperm concentration in the ten oligozoospermic men with microdeletions was below 1 x 10(6)/ml. There were no correlations between the severity of spermatogenic defects and the extent of the microdeletions. These results suggested that genes in the interval D16-22 of the Y chromosome might have important roles in spermatogenesis.

Base Sequence↗

The proton uptake channel of bacteriorhodopsin as studied by a photoelectrochemical method.

A series of the mutant proteins (D96N, D96N/D85N, D115N, L93T, T46V, V49A) where the residues are located at the cytoplasmic domain of bacteriorhodopsin (bR) were studied photoelectrochemically and their photocurrent response characteristics at the electrode/electrolyte interface were compared with those of the wild-type bR. While the wild-type bR of normal proton pumping activity yields symmetrical cathodic (positive) and anodic (negative) responses, corresponding to proton release and proton uptake, respectively, these mutants, with the exception of D115N, showed diminished amplitudes in the negative response. This indicates retardation of proton translocation from the cytoplasmic surface to the retinal Schiff base. The mutation that gave the strongest influence on the negative response was D96N while moderate influence was obtained with L93T, T46V, and V49A. These results suggest that residues other than D96 also participate in the cytoplasmic proton uptake channel, either by interacting with D96 directly or by forming a hydrogen-bonded network with water molecules. The D96N/D85N double mutant yielded little response at neutral pH, but the response was partially recovered by addition of azide, while it was fully recovered in the single mutant D96N. The D115N mutant showed the response profile that closely resembles the wild-type, indicating that D115 is not crucially involved in the event of proton transfer relay at the cytoplasmic region. It was also found that every mutant in this study releases protons prior to uptake at the other membrane surface, as does the wild-type.

Azides↗

Expression of interleukin-18 and its receptor in mouse ovary.

PROBLEM: Interleukin-18 (IL-18) strongly induces interferon-gamma production and is produced not only by types of immune cells but also by types of non-immune cells. Ovulation is thought to be an inflammation-like reaction in which many pro-inflammatory cytokines are involved. We investigated whether IL-18 is involved in the functions of ovary. METHOD OF STUDY: The 4-week-old immature female mice were examined for IL-18 and IL-18 receptor (IL-18R) expression on their ovaries under stimulation with pregnant mare's serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) by immunohistochemical staining, Western blotting and reverse transcript-polymerase chain reaction. The IL-18R was blocked by the injection of anti-IL-18R monoclonal antibody to immature mice during PMSG-hCG stimulation, and the number of ovulated ova was counted. RESULTS: The expression of both proteins and mRNA of IL-18 and IL-18R were very low in immature ovaries before stimulation, but after PMSG injection both IL-18 and IL-18R increased dramatically in theca cells and reached a maximum level at the peri-ovulatory phase then slightly lowered, but still kept a high level during the luteal phase in the corpus luteum. The treatment of IL-18R monoclonal antibody to the mice during ovarian stimulation reduced the number of ovulated ova and inhibited the expansion of cumulus cells surrounding the ovum. CONCLUSION: IL-18 and IL-18R play roles in various kinds of function of ovary.

Animals↗

Resistance to fulminant hepatitis and carcinogenesis conferred by overexpression of retinoblastoma protein in mouse liver.

Previously, retinoblastoma (Rb) transgenic mice were produced under the control of the Rb gene promoter and showed dwarf characteristics. Here, we created transgenic mice, in which the human Rb gene was controlled by the hepatocyte nuclear factor-1 gene promoter/enhancer and was expressed primarily in the liver. The liver of these novel transgenic mice was normally developed. Intriguingly, these mice showed resistance to fulminant hepatitis induced by anti-Fas antibody as well as resistance to chemical carcinogenesis in the liver. These results show that the Rb protein acts as an anti-apoptotic and anti-oncogenic agent in vivo. Our novel construct may be useful as a gene cassette in gene therapy for prevention of fulminant hepatitis and hepatoma.

Animals↗

Protein binding of glufosinate and factors affecting it revealed by an equilibrium dialysis technique.

We investigated the protein binding of glufosinate ammonium (GLF) and several factors affecting this binding using human serum albumin (HSA) and human volunteer serum under various conditions. The mean ratios of the free GLF (RFr-GLF) to 4% HSA were examined in the sera of patients described elsewhere at GLF levels from 1 microg/mL to 500 microg/mL; the range was found to be only from 0.80 to 0.88. Neither the incubation temperature nor buffers containing different chloride ion concentrations had any effect on the RFr-GLF to HSA. Moreover, the addition of heparin, glycoprotein-alpha1-acid (AAG), and sodium azide had no effect on the RFr-GLF. However, pH of the isotonic phosphate buffer and the addition of palmitic or oleic acid were seen to have an effect. In this study, the mean RFr-GLF to healthy human serum was 0.99. This high value was evidenced that GLF was rapidly excreted through the renal route.

Adult↗

Reversal effect of sulpiride on rotational behaviour of rats with unilateral frontal cortex ablation: an alternative explanation for the pharmacological mechanism of its antidepressant effect.

The antidepressant effect of sulpiride has been generally explained as the result of its preferential blocking effect on self-inhibitory presynaptic dopamine autoreceptors at low doses. Low dose haloperidol has the same blocking effect. In rats with unilateral ablation of the frontal cortex, methamphetamine administration induced mild contralateral rotation 10 days after the operation. We examined whether low dose sulpiride and haloperidol would have the same effect on this rotational model. High dose sulpiride (100 mg/kg) or low dose haloperidol (0.05 mg/kg) prevented this methamphetamine-induced rotation. However, low dose (15 mg/kg) sulpiride clearly reversed the direction of rotation. This reversal effect of low dose sulpiride is not explained by the preferential blocking effect on dopamine autoreceptors. The results suggest that low dose sulpiride, unlike low dose haloperidol, has a prominent blocking effect on D2 receptors in the frontal cortex. This unique effect of sulpiride may be relevant to its clinical antidepressant and anxiolytic effects at low doses.

Animals↗

Detection of malignant tumors: whole-body PET with fluorine 18 alpha-methyl tyrosine versus FDG--preliminary study.

PURPOSE: To compare the diagnostic potential of whole-body positron emission tomography (PET) with fluorine 18 alpha-methyl tyrosine (FMT) with that of whole-body PET with 2-[fluorine 18]fluoro-2-deoxy-D-glucose (FDG). MATERIALS AND METHODS: Nineteen patients with or suspected of having malignant tumors and five healthy volunteers underwent whole-body PET with FMT and FDG. RESULTS: In comparison with FDG uptake, FMT uptake was significantly less in the brain, heart, lung, liver, and spine. On a lesion-by-lesion basis, the sensitivity of whole-body FMT PET for depicting malignant tumors was inferior to that of whole-body FDG PET, but this difference was not statistically significant (74% [26 of 35 lesions] vs 91% [32 of 35 lesions], P >.05). The positive predictive value of FMT PET was superior to that of FDG PET (87% [26 of 30 lesions] vs 63% [32 of 51 lesions], P <.001). The difference in uptake between benign and malignant lesions was significant with FMT PET (mean +/- SD, 1.64 +/- 0.96 vs 0.79 +/- 0.23; P <.001) but not with FDG PET (5.02 +/- 3.56 vs 4.02 +/- 2.90, P >.05). CONCLUSION: Whole-body FMT PET is clinically useful in the diagnosis of malignant tumors and may be effective in the depiction of primary and metastatic lesions in the cardiac region or in the brain.

Adult↗

Light and electron microscopy localization of the 11beta-hydroxysteroid dehydrogenase type I enzyme in the rat.

The 11beta-hydroxysteroid dehydrogenase type I enzyme (11betaHSD1) converts cortisone to cortisol in humans, and 11-dehydrocorticosterone to corticosterone in rodents. In the present study we used a new immunopurified polyclonal antibody, RAH113, to localize 11betaHSD1 at the light and electron microscopy levels in a wide range of rat tissues. 11betaHSD1 staining in the liver was of highest intensity around the central vein and decreased radially. In the lung, 11betaHSD1 was found at highest levels in the interstitial fibroblast, with levels in the type II pneumocyte an order of magnitude lower. RAH113 stained proximal tubules of the renal cortex and interstitial cells of the medulla and papilla. Adrenal 11betaHSD1 was confined to the glomerulosa and medulla, whereas the glucocorticoid-inactivating hydroxysteroid dehydrogenase isoform 11betaHSD2 was present in fascilulata/reticularis. 11betaHSD1 was found in parietal cells of the fundic region of the stomach, but not in the antrum. In the heart, 11betaHSD1 was detected in cells resembling interstitial fibroblasts of the endocardium and in the adventitial fibroblasts of blood vessels. Western blot analysis confirmed the presence of an antigen of the correct size (34 kDa) and intensity consistent with levels of enzyme activity previously reported in these tissues. Brain and testis also displayed the 34-kDa protein, confirming the expression of authentic 11betaHSD1 in these tissues. Electron microscopy of lung and kidney interstitial cells showed that 11betaHSD1 was localized both to the endoplasmic reticulum and the nuclear membrane. These results show that 11betaHSD1 is present in discrete cell populations where it may facilitate intracrine and paracrine glucocorticoid action in addition to its classical role of maintaining circulating glucocorticoids via activity in the liver.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗

A case of renovascular hypertension due to bilateral renal artery microaneurysm who succeeded in baby delivery.

We report the case of a young pregnant woman with bilateral renovascular hypertension due to renal microaneurysms from an unknown cause, who had a successful delivery. Pregnancy did not affect the disease activity even in the postpartum period. Her blood pressure was maintained within the normal range by administration of labetalol. Although the angiographic appearance of the symmetrical aneurysms in both renal artery beds from the interlobular to arcuate artery levels suggested polyarteritis nodosa of multiple microaneurysms in the bilateral interlobular arteries, the clinical features suggested other causes of renovascular hypertension, such as fibromuscular dysplasia and/or congenital microaneurysms. We were thus unable to reach a definitive diagnosis.

Adrenergic beta-Antagonists↗

Appraisal of intra-arterial infusion of prostaglandin E1 in patients undergoing major hepatic resection report of four cases.

In order to reduce risk for postoperative acute liver failure, prostaglandin E1 (PGE1) was administered either from the hepatic artery (HA) or the superior mesenteric artery (SMA) in four high-risk cases undergoing major hepatic resection. Two cases were subjected to HA PGE1 infusion for 3 or 4 days after surgery at a rate of 0.01 microg/kg/min. Both patients had hepatocellular carcinoma (HCC) associated with chronic hepatitis, and ICG R15 was 17.6% and 14.5%, respectively. Right hemihepatectomy and extended right hemihepatectomy were performed. Serum total bilirubin (T. Bil.) peak value was 2.2 mg/100 ml in Case 1 and 2.1 mg/100 ml in Case 2. In Case 1, decreased bile flow was observed immediately after cessation of PGE1. The other two cases were subjected to SMA PGE1 infusion for 5 or 6 days after surgery at the same rate. In Case 3, right hemihepatectomy was performed for HCC on a cirrhotic liver four weeks after right portal vein embolization, in which preoperative ICG R15 was 19.0%. Peak T. Bil level was 3.7 mg/100 ml with uneventful postoperative course. In Case 4 with a huge cholangioma, right trisegmentectomy was performed. Peak serum T. Bil level was 1.7 mg/100 ml in this uneventful postoperative course. In Case 3 and Case 4, portal blood flow, measured by Doppler ultrasonography, was markedly increased by PGE1 infusion. From these results, intra-arterial PGE1 infusion might be useful in prevention of postoperative liver failure after major hepatic resection.

Aged↗

Relations of alexithymic characteristics with eating attitudes and hostility in female college students.

We examined the correlations of alexithymic characteristics with the expression of unfavorable feelings such as anger and hostility and abnormal eating attitudes and behaviors in a sample of 278 Japanese female college students. Mean scores on the Eating Attitude Inventory, MMPI Hostility, and State-Trait Anger Expression Inventory were significantly higher for female college stUdents with alexithymic characteristics than for those with nonalexithymic characteristics. Multivariate analysis of covariance indicated that the significant relationships between alexithymic characteristics and oral control of the eating attitudes were controlled by scores on anger-in and anger control, suggesting that anger-in and anger control may mediate the relationship between alexithymic characteristics and abnormal eating attitudes.

Adult↗

[Endotoxin adsorption and continuous hemodiafiltration in three septic patients].

We report 3 patients in septic shock with panperitonitis. Endotoxin adsorption by polymixin B affinity column (PMX) and continuous hemodiafiltration (CHDF) were performed immediately after the surgery. Septic shock was not improved in patient 1 and 2 despite intensive care. Multimodal approach, including complete surgical repair, cardiovascular support and blood purification methods, is essential in treating septic patients.

Adsorption↗

[Severe pulmonary edema in a preeclamptic patient with peripartum cardiomyopathy].

We report a preeclamptic patient who revealed severe pulmonary edema. A 37-year-old woman, at 32-week gestation, underwent emergency cesarean section under general anesthesia. She had no particular past medical history. SpO2 was 84% (room air) on the arrival at the operating room, and a chest X-ray showed pulmonary edema. She was managed in the intensive care unit postoperatively, she received an intensive treatment (positive pressure ventilation, furosemide, and inotropic support), and was extubated successfully on the third postoperative day. From clinical course and echocardiographic findings, we consider that this pulmonary edema was caused by peripartum cardiomyopathy.

Adult↗

Intravenous nedaplatin and intraarterial cisplatin with transcatheter arterial embolization for patients with locally advanced uterine cervical cancer.

Nedaplatin is a platinum analog that has less renal toxicity and higher efficacy for uterine cervical cancer than cisplatin. Intraarterial cisplatin has been shown to be more effective than intravenous cisplatin in the treatment of cervical cancer. To improve the prognosis of cervical cancer, we studied combination chemotherapy of intravenous nedaplatin and intraarticular cisplatin with transcatheter arterial embolization (TAE). The criteria for selecting patients for this study were as follows: age 16-75 years, stage Ib2-IV according to the classification of the International Federation of Gynecology and Obstetrics (FIGO), performance status between 0 and 2, a creatinine clearance of >40 ml/min, adequate bone marrow and adequate renal and hepatic function. Thirty-two patients, aged 29-72 years (median: 55) were treated. FIGO stage was Ib2 in seven patients, IIa in seven patients, IIb in four, IIIa in one, IIIb in seven and IVa in six. Twenty-four patients had squamous cell carcinoma, three had adenocarcinoma and five had adenosquamous carcinoma. Written informed consent was obtained from all patients. Nedaplatin (30-70 mg/m2) was administered intravenously on day 1 and cisplatin (70 mg/m2) was administered intraarticularly via both uterine arteries on day 3 using the Seldinger method. TAE was then performed. This course of treatment was repeated every 3 weeks for 2-3 cycles. Response to the therapy was defined by magnetic resonance imaging. Partial response was found in 59% patients (19/32) and complete response in 34% (11/32), with an overall response rate of 94% (30/32). Myelosuppression was manageable. No grade 2 neurotoxicity was observed. The median follow-up was 32 months (6-53 months), with 84% of patients showing an overall survival of 1 year and 77% showing an overall survival of 2 years. These results show that this combination chemotherapy effected a high response rate. However, its influence on long-term survival remains to be determined.

Adenocarcinoma↗