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An important method to improve the sensitivity of a nuclear magnetic resonance (NMR) system is to increase the quality factor ( Q ) of the pickup coils. In this paper, we focus on the following three items: 1) effect of the surface resistance ( R s) of the YBa2Cu3O7-δ (YBCO) films on the Q of the NMR pickup coil; 2) relationship between coil line width and current flowing through coil; and 3) effect of Si-ion irradiation to YBCO films on the Q of the NMR pickup coils. In the study of 1), we examined the Q of the NMR pickup coils made by YBCO films with different R s and found that reduction of R s is useful in increasing the Q of the NMR pickup coils. In the study of 2), we simulated the current flowing in the NMR coils by an electromagnetic simulator, and found that wider microstrip lines of the NMR pickup coil increase the current. In the study of 3), we examined Si-ion irradiation effect to reduce R s of YBCO films, and found low irradiation energy and low irradiation density of Si-ion is useful to decrease R s and useful to obtain the high Q NMR pickup coils.

In this study, we examined the effect of Si-ion irradiation on Rs of YBCO thin films. We measured Rs 90 and Rs0 of YBCO thin films in a magnetic field applied both normal and parallel to the film plane. Si-ion irradiation conditions were configured as follows: irradiation energy = 50–500 keV, irradiation ion density = 1–8 × 10 12 ion/ cm2. We found that the Rs90 decreased through ion irradiation, and Si-ion irradiation with an irradiation energy of 200 keV and an irradiated ion density of 4 × 1012 ion/cm2 being the most effective configuration for reducing Rs90 in high magnetic fields. Magnetic field-dependent Rs0 was quite small for all YBCO films with and without ion irradiation. When a magnetic field is applied parallel to the film plane, the blocking layers of the YBCO act as strong pins, therefore, R s0 in the magnetic field is small without introduction of artificial pins. However, we found that the Rs0 of YBCO films became small with Si-ion irradiation than that of the YBCO film without Si-ion irradiation, that the condition of ion energy 200 keV and ion irradiation density 1 × 10 12 ion/cm2 could reduce Rs0 most.

We investigated the effect of artificial pinning centers (APCs) in YBa 2 Cu 3 Oy (YBCO) thin films to reduce the surface resistance (Re). The introduction of APCs can increase the critical current density (Jc), so APCs are expected to decrease Re of YBCO thin films. To clarify the effect, we chose Si ion irradiation and neutron irradiation for introducing APCs. Si ions of 500 keV and 4 × 10 12 ion/cm 2 and neutrons of 1.34 × 10 12 n/cm 2 at 1 MeV conversion were irradiated in YBCO thin films with a thickness of 300 nm deposited on CeO 2 -buffered Al 2 O 3 substrates. δω and δφ of YBCO thin films without APC were less than 1.0 degree and less than 2.0 degrees, respectively, and these values were not changed very much by Si ion and neutron irradiations. Re of YBCO thin films with and without Si ion irradiation and neutron irradiation was measured using a dielectric resonator method. The applied magnetic field was up to 5T. The magnetic field dependence of R(0) e was smaller than that of R(90) e in all YBCO thin films. We found that R(90) e of Si ion irradiated and neutron irradiated YBCO thin films was reduced, and that R(90) e of Si ion irradiated thin films was about 1/3 that of unirradiated thin films at 20 K and at 5 T. In addition, R(0) e of all the YBCO thin films decreased somewhat as the magnetic field increased at 20 K. As a result, we found that the irradiation of Si ions into YBCO thin films was effective for reducing Re under a magnetic field, and it was revealed that the effect was stronger than the addition of oxide fine particles which was previously reported.

Direct effects of human uremic serum on the production of endothelin-1 in cultured porcine endothelial cells were examined in this study. Uremic serum decreased the level of monomeric endothelin-1 secreted into the culture medium by endothelial cells. This effect occurred at a transcriptional step because uremic serum decreased the endothelin-1 mRNA level in those cells. For the partial characterization of this inhibitory activity, uremic serum was fractionated with a centricut column. Uremic serum contains humoral factor(s) larger than 50 kD which suppress the endothelin-1 mRNA level in cultured endothelial cells.

Fatty acid translocase (FAT)/CD36 is a multi-functional membrane protein participating in uptake of long-chain fatty acids and oxidized low density lipoprotein, playing an important role in lipid homeostasis. We reported the dual promoter structures of the mouse and human FAT/CD36 genes in relation to the tissue-specific expression and regulation by peroxisome proliferator-activated receptors (PPARs) (Sato et.al. J. Biol. Chem. 277, 15703-15711, 2002). However, these structures alone could not explain a large induction of the mRNA by a PPAR ligand in the mouse intestine. To learn more about the tissue-specific transcriptional regulation of the FAT/CD36 gene for lipid homeostasis at the whole body level, we cloned the cDNA for the induced mRNA in the mouse intestine and identified third promoter close to the first common exon of the gene. The human gene also has essentially the same gene organization. RT-PCR and Northern blot analyses showed that the three promoters are differentially used in various mouse tissues and the cultured human cells. The physiological significance of these complex promoter structures was suggested by the differential responsiveness to a peroxisome proliferator-activated receptor ligand and the differences in translational efficiencies or stabilities of the mRNA among the isoforms.

Specific direct radioimmunoassay of angiotensin II (AT II) in human plasma was developed to evaluate the dynamics of endogenous AT II in various types of hypertension. Detection limit of this method was less than 2.3 pg/ml, and normal value is less than 25 pg/ml. Cross reactivity of antibody with AT I and III was 0.037% and 21%, respectively. There were good correlation between the value measured by direct method, and that of extraction method (r = 0.96, P < 0.01) and plasma renin activity (r = 0.80, P < 0.01). By oral administration of ACE inhibitor (captopril 50 mg), AT II levels were suppressed to 10 pg/ml or less in most patients with essential hypertension, renal parenchymal hypertension and renovascular hypertension up to 2 h. However, AT II levels in patients treated with ACE inhibitors chronically were not different from the AT II levels in patients without ACE inhibitor. In primary aldosteronism AT II was extremely low levels. AT II markedly increased by the stimulation test using furosemide (1 mg/kg i.v.). These results suggest that this method may be useful to clarify the pathophysiology of hypertension and the escape of the inhibition by ACE inhibitor.

Pituitary dysfunction occasionally results from brain tumors or the surgical resection of brain tumors. The authors examined two patients with hypogonadotropic secondary amenorrhea, who had undergone surgical removal of brain tumors. Changes in immunoreactive gonadotropin-releasing hormone (GnRH) secretion are of interest in patients with a gonadotropin and gonadal steroid deficit, because both steroid and pituitary feedback systems are altered by tumors or tumor resection. The authors thus measured GnRH, luteinizing hormone, and follicle-stimulating hormone levels every 15 minutes for 4 hours by radioimmunoassay and investigated qualitative and quantitative changes in the pulsatile patterns of these hormones in two hypogonadotropic hypogonadism patients. They also performed similar multiple measurements of GnRH in two normal cycle women in follicular phase and two postmenopausal women. The concentration of plasma GnRH in two hypopituitarism patients was compared with that in two normal cycle women and two postmenopausal women. The study showed that the peripheral blood level of GnRH was significantly lower in two hypopituitarism patients than in both normal cycle and postmenopausal women, and that the pulsatile frequency was not different among these three groups. These findings suggest that alteration of feedback systems results in a decrease in the blood level of GnRH, and that pulses of GnRH maintain normal fluctuation despite the alteration of the hormonal circumstances in two hypogonadotropic hypogonadism patients.

To examine whether plasma platelet-derived growth factor (PDGF) levels are elevated in the coronary circulation of patients with unstable angina, the plasma PDGF levels in the coronary sinus and aortic root were simultaneously examined in 14 patients with unstable angina, 15 with stable exertional angina, and 15 control subjects. The mean plasma PDGF level (pg/ml) in the coronary sinus was significantly higher (p less than 0.01) in patients with unstable angina than in those with stable exertional angina and in control subjects (502.1 +/- 98.7 vs 301.3 +/- 62.5, and 312.7 +/- 62.6). However, there were no significant differences in mean plasma PDGF levels in the aortic root among the 3 groups. It is concluded that PDGF release is increased in the coronary circulation in patients with unstable angina.

Production of chromogranin (Cg)A and B derived peptides [pancreastatin (PST), GAWK, CCB] was studied using human lung carcinoma derived cell lines. PST-like immunoreactivity (LI) was detected in the culture medium in 3 of 6 small cell lung carcinoma (SCLC) cell lines, while GAWK- and CCB-LIs were detected in 5 of 6 and all the 6 SCLC cell lines, respectively. CCB-LI was produced in large amounts in SCLC cell lines as compared to PST- and GAWK-LIs. In non-SCLC cell lines, on the other hand, PST- and GAWK-LIs were not detected. CCB-LI was detected in 1 of 7 non-SCLC cell lines, but not detected in the remainder. PST, GAWK and CCB-LIs, secreted by these cell lines, consisted of several peaks, and these peaks were different among cell lines. This suggests that processing of CgA and B is different in the cell lines. Production of CgA and B derived peptides seems to be a characteristic feature of SCLC, and among them, CCB LI may be a useful marker for SCLC.

A radioimmunoassay (RIA) for serum thymic factor (facteur thymique serique) was established. This assay could detect less than 0.5 pg of serum thymic factor without the interference by other thymic hormones, including thymopoietin II and thymosin alpha 1. Both zinc-free and zinc-bound serum thymic factor showed a similar standard curve, indicating that this RIA could detect both forms of serum thymic factor in the same way. We observed that two procedures were required prior to the measurement in order to measure serum thymic factor content in plasmas; the first, the extraction procedure to remove substances interfering with the assay nonspecifically; the second, the storage of the sample with ethylenediamine tetraacetic acid disodium salt to inhibit the proteases in the plasma to degrade serum thymic factor. By employing this assay system, we observed that cord blood plasmas contained significantly higher level of serum thymic factor than did adult blood plasmas.

Plasma levels of platelet-derived growth factor (PDGF) were measured in 24 normal control subjects, 31 patients with stable angina pectoris, 25 patients with unstable angina pectoris, and 31 patients with acute myocardial infarction (AMI) by a sensitive direct radioimmunoassay. The plasma PDGF level in normal control subjects was 273 +/- 25 pg/ml; there was no significant correlation between the plasma PDGF level and age. Plasma PDGF levels in patients with unstable angina pectoris and acute myocardial infarction were significantly lower than those in normal control subjects and patients with stable angina pectoris (p less than 0.05). In patients with acute myocardial infarction the plasma PDGF level in the chronic phase was significantly higher than that in the acute phase (p less than 0.05). These observations raise the possibility that PDGF is involved in the pathophysiology of ischemic heart disease.

Serum levels ob biochemical markers for acute myocardial infarction (AMI) can be increased in patients with chronic renal failure (CRF) or skeletal muscle injury, creating diagnostic confusion. We evaluated the clinical utility of cardiac troponin I (cTnI) as a marker of AMI, particularly in patients with CRF.Subjects consisted of 59 healthy volunteers and 102 patients: 61 with CRF undergoing hemodialysis (CRF-HD), 10 with CRF under conservative therapy (CRF-CT), 21 with renal disease (RD), and 10 with muscle disease (MD). Patients with RD, CRF, and MD were evaluated to verify the absence of myocardial injury. We developed an immunoradiometric assay to measure serum cTnI using monoclonal antibodies. The lower limit of detection was 0.33 micro g/l. Serum cTnI, creatine kinase (CK), CK-MB, cardiac troponin T (first-, second-, and third-generation assay: cTnT-I, cTnT-II, and cTnT-III), and cardiac myosin light chain 1 (cMLC1) were measured.cTnI was not detected in healthy volunteers or patients with CRF, RD, or MD. In patients with CRF-HD, elevated levels occurred in 4.9% (3/61) for CK, 0% (0/61) for CK-MB, 39.5% (15/38) for cTnT-I, 7.3% (3/41) for cTnT-II, 13.0% (3/23) for cTnT-III, and 77.0% (47/61) for cMLC1; and in patients with MD the levels were increased in 70% (7/10) for CK, 50% (5/10) for CK-MB, 44.4% (4/9) for cTnT-I, 20% (2/10) for cTnT-II, and 50% (5/10) for cMLC1.cTnI is a highly specific marker for AMI and is particularly useful for detecting AMI in patients with CRF or MD. Serum levels of biochemical markers for acute myocardial infarction (AMI) can be increased in patients with chronic renal failure (CRF) or skeletal muscle injury, creating diagnostic confusion. We evaluated the clinical utility of cardiac troponin I (cTnI) as a marker of AMI, particularly in patients with CRF.

Inhibin levels were measured by a double antibody heterologous radioimmunoassay in the peripheral serum of 75 pregnant women throughout gestation and in serum from the umbilical vein and artery, which was obtained at the time of delivery. For reference, samples were obtained from 20 nonpregnant women in the early (days 0 to 3), mid (days 4 to 8), and late (days 9 to 14) luteal or follicular phase. Maternal serum levels of inhibin (mean +/- SEM) in early (6 to 12 weeks) gestation (36.4 +/- 2.6 U/ml, n = 36) were significantly (p less than 0.01) higher than those in serum from nonpregnant women in the mid (23.9 +/- 2.5 U/ml, n = 19) or late (11.3 +/- 0.6 U/ml, n = 19) luteal phase. Inhibin levels in maternal serum fell to 15.9 +/- 1.4 U/ml (n = 24) in mid (14 to 20 weeks) gestation and then gradually increased during late (21 to 40 weeks) gestation to peak levels of 49.4 +/- 5.1 U/ml (n = 9) at 36 to 37 weeks. Inhibin levels declined in parallel with human chorionic gonadotropin concentrations during the first trimester (r = 0.587 at p less than 0.01). Significant positive correlations (p less than 0.001) were observed between serum levels of inhibin and 17 beta-estradiol (r = 0.560), progesterone (r = 0.648), and human placental lactogen (r = 0.715) during mid and late (20 to 40 weeks) gestation. Inhibin levels in umbilical vein serum (38.5 +/- 1.3 U/ml, n = 5) were not different from those in umbilical artery serum (39.4 +/- 3.6 U/ml) but were significantly (p less than 0.01) lower than those in maternal serum (50.9 +/- 5.3 U/ml), which was obtained at the time of delivery. By day 5 of puerperium, serum levels of inhibin in the maternal vein were extremely low (2.3 +/- 0.1 U/ml, n = 7); these levels were nearly one fifth lower than follicular phase levels of 10.9 +/- 3.4 U/ml (n = 38). We propose that maternal inhibin in early gestation is secreted from the corpus luteum of pregnancy but that increasing inhibin levels during mid and late gestation result from inhibin that is produced by the placenta. The lack of an umbilical arterial-venous gradient for inhibin and the higher levels of inhibin in maternal serum argue against a fetal source of inhibin in the maternal circulation. The physiologic function of inhibin that is produced by the corpus luteum and by the placenta remains to be determined.

遺伝子組換えヒトエリスロポエチンを用いた放射免疫測定法を新たに開発し, 特異性, 感度, 再現性ともに優れた臨床応用可能な血中エリスロポエチン (EPO) 濃度の測定系を確立した. その容量反応曲線は3-250mU/mlの範囲で直接測定が可能であり, 最小測定限界は5mU/mlであった.本法によって測定したEPOは長期透析患者428例において16.1±8.6mU/ml (m±SD), 正常人86例において17.1±7.2mU/mlであり, 両群間に有意差を認めなかった. 透析患者のEPOは貧血の程度に比して相対的に極めて低値と考えられ, またEPOとHtとの間には相関を認めなかった. 大量の輸血を受けた患者群と非輸血群のEPOはほぼ同値であったが, 一部の高度貧血患者では低値の傾向があり, 輸血を繰り返す必要があった. 正常人, 透析患者ともにEPOは加齢にともなって増加する傾向があったが, 正常人では70歳以上でやや減少した. 透析期間が長いほどHtが高い症例が増加する傾向があるが, 透析期間とEPOの間には有意の相関を認めなかった. 腎不全の原因疾患別にみると, 多発性骨髄腫のEPDは他疾患の患者群よりも有意に高値であった. 多発性嚢胞腎では貧血は軽度であり, EPOはやや高値の傾向を示した. なお, 蛋白同化ステロイド・鉄剤投与の有無, 網状赤血球数, 血液尿素窒素, 血清クレアチニン, 血清鉄, 血清フェリチンとEPOとの間には, 相関を認めなかった.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was administered (50 to 800 micrograms/m2) once daily as a half-hour intravenous (IV) infusion for 14 days to seven patients with malignant lymphoma. In all patients, administration of rhG-CSF not only ameliorated the decrease in absolute neutrophil count after the cytotoxic chemotherapy but also enhanced superoxide (O2-) release in neutrophils stimulated by N-formyl-methionyl-leucyl-phenylalanine (FMLP). The priming effect of rhG-CSF on neutrophil O2- release was rapid (evident within 6.5 hours) and sustained at least for 24 hours after a single IV administration of rhG-CSF. The responsiveness to further in vitro challenge of rhG-CSF was lost or reduced in neutrophils isolated after rhG-CSF treatment, indicating that neutrophils already primed in vivo by rhG-CSF are desensitized to this factor. In contrast to the results obtained with FMLP, when phorbol myristate acetate (PMA) was used as stimulus, no consistent enhancement of O2- release was observed, suggesting that rhG-CSF modulates the signal transduction pathways linked to FMLP receptors rather than increases the components of the O2- producing enzyme complexes. Administration of rhG-CSF also rapidly (evident within 15 minutes) caused an increase in expression of neutrophil C3bi-receptors that was sustained for at least 24 hours after a single IV administration of rhG- CSF. Pharmacokinetic study of rhG-CSF showed a half-life (t1/2) of 114 min. These findings show that rhG-CSF is a potent activator for neutrophil functions both in vivo and in vitro.

In order to reevaluate the earlier varying data regarding circulatory gonadotropin-releasing hormone (GnRH), we assayed extracted GnRH from the plasma frequently collected at mid-cycle in 11 women. For the analysis of episodic GnRH patterns and basal levels, blood samples were obtained at 6 h intervals for 72 h and at 15 min intervals for 2 h every 12 h throughout the experimental period. All blood samples were assayed for GnRH and selected samples for LH, FSH, estradiol and progesterone. For GnRH assay, 5 or 6 ml of blood was mixed with 60 mg of ethylenediaminetetraacetic acid, disodium salt, and 3 mg of phenylmethylsulfonyl floride immediately after blood collection. These enzyme inhibitors prevented the destruction of GnRH in the blood at room temperature for at least 4 h. Plasma GnRH was extracted through several steps including florisil absorption, acidic extraction and washing with organic solvent. Nonspecific immunoreactivity in the plasma was markedly decreased through this extraction process. Our assay values (approximate range, 0.1-2.0 pg/ml) of plasma GnRH in normal women corresponded to the low range of those obtained by others who used the alcohol extraction method. The basal levels of GnRH did not change significantly throughout 3 different periods, i.e., before, during and after the LH surges, and fluctuated between a small range of 0.11 and 1.44 pg/ml. Although the peak levels of GnRH observed in its episodic patterns did not change between the periods before and during the LH surges, they decreased significantly after the LH surge compared with those seen during the LH surges (0.93 +/- 0.07 vs 1.17 +/- 0.09 pg/ml, p less than 0.05). The present data demonstrate that immunoreactive GnRH in the extracted peripheral plasma does not change significantly in its mean, basal and peak levels during the periovulatory period except for a minor but significant decrease in the peak levels shortly after an LH surge.

In order to investigate whether endogenous GHRH and somatostatin were involved in the mechanism of the paradoxical GH rise after TRH injection, changes in serum GH and plasma GHRH were examined before and after TRH injection in 12 cancer patients and changes in serum TSH and GH were similarly studied in 76 cancer patients including 31 GH-responders and 45 GH-nonresponders to TRH. TRH stimulated GH secretions without altering the circulating GHRH concentration in 4 of the 12 cancer patients. There was neither a significant correlation between the increase from the basal to maximum GH and GHRH after TRH injection in the 12 cancer patients nor a reciprocal relationship between the increase in GH and TSH after TRH injection in the 76 cancer patients. These findings suggested that the paradoxical GH rise after TRH injection in cancer patients was exerted by its direct action at the pituitary level, and not mediated through the hypothalamus.