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Summary: In order to elucidate the relationship between plasma dehydroepiandrosterone (DHA) and sulpiride-induced hyperprolactinemia (of 60 day duration) in normal men, five normal men (aged 2746) were administered daily 300 mg of sulpiride orally for 60 days to induce hyperprolactinemia. Plasma levels of prolactin, DHA and cortisol were measured by radioimmunoassay before sulpiride treatment, at day 14 and day 60 after initiation of the treatment. Plasma levels of prolactin after the administration rose significantly (P < 0.001) to 71.6–95.3 ng/ml in four out of the five subjects compared with those of the controls. In the same four subjects the mean DHA values in plasma were elevated significantly (P

The involvement of chronic inflammation in albuminuria and renal function was investigated in a cross-sectional study of 320 type 2 diabetic Chinese patients from the Singapore Diabetes Cohort Study. Plasma levels of TNF-α and its two cellular receptors and of IL-6 and C-reactive protein (CRP) were measured. A composite TNF-α score was extracted using principal component analysis. Multiple linear regression analysis was implemented to evaluate the relationship between log e (ln) albumin:creatinine ratio (ACR) and estimated GFR (eGFR) with the inflammatory variables and other clinical covariates. A Bonferroni correction was applied based on the total number of variables entered into regression analyses. ln ACR was significantly associated with TNF-α score independently of eGFR even after a Bonferroni correction. TNF-α score was also significantly associated with eGFR independently of ln ACR even after correction for multiple testing. These findings were similar when the individual molecules of the TNF-α system were analysed separately instead of using the composite TNF-α score. No association was observed for IL-6 and CRP with either renal trait. Diabetes duration was a significant predictor for ln ACR but not eGFR. Conversely, age was significantly associated with eGFR but not ln ACR. Activation of the TNF-α system may potentially exert independent effects on ln ACR and eGFR in type 2 diabetes. Because of the study design, one may also consider the possibility that changes in these renal traits may conversely be responsible for such an inflammatory response.

A highly sensitive separation procedure has been developed to investigate uranium and thorium activities and their isotopic ratios in environmental water samples in Tokushima, Japan. Uranium and thorium isotopes in environmental water samples were simultaneously isolated from interfering elements with extraction chromatography using an Eichrom UTEVA™ resin column. After the chemical separation, activities of U and Th isotopes coprecipitated with samarium fluoride (SmF3) were measured by α-spectrometry. It has been confirmed that uranium isotopes are isolated successfully from thorium decay chains by analyzing a test aqueous solution as a simulation of an environmental water sample. The separation procedure has been first applicable to the determination of U and Th activities and their isotopic ratios in a drinking well water named “Kurashimizu” in Tokushima City, Japan. The specific activities of 238U and 232Th in “Kurashimizu” were deduced to be within the upper limits of

A criticality accident occurred on September 30, 1999 at the uranium conversion facility of the JCO Company Ltd. in Tokai-mura, Japan. A collaborating scientific investigation team was organized in two groups, the first to carry out research on the environmental impact (the environmental research group) and the second to assess the radiation effects on residents (the biological research group). This report concerns only the activities of the environmental research group. Four investigative teams were sent on different dates to the accident site and its vicinity to collect samples. About 400 samples were collected and subjected to analysis. An outline of the sampling campaign is presented here along with a brief chronology of the accident and the preliminary key results obtained by the independent research group are summarised in this Special Issue of the Journal of Environmental Radioactivity.

The extraction behavior of gallium(III) and palladium(II) with 2-methyl-8-quinolinol (HMQ), 2-methyl-5-hexyloxymethyl-8-quinolinol (HMO 6 Q) and 5-hexyloxymethyl-8-quinolinol (HO 6 Q) from an acidic solution into supercritical fluid (SF) CO 2 were investigated. Furthermore, the pH of an acidic solution contacting with SF CO 2 was spectrophotometrically measured, and the distribution constants of HMO 6 Q between SF CO 2 and water were also determined at I = 0.1 M (H, Na)NO 3 , 45°C, and 8.6 – 20.4 MPa. Above pH 3, the pH of the aqueous phase in contact with SF CO 2 was levelled to about 3. On the other hand, below pH 3, the pH change is negligibly small. The distribution constant ( K D ,SF CO2 of HMO 6 Q between SF CO 2 and water at 20.4 MPa was about one tenth of the K D for heptane - water system, indicating that the solubility of HMO 6 Q in SF CO 2 is remarkably smaller compared with that in heptane. The Ga(III)-HMO 6 Q and Ga(III)-HO 6 Q complex extracted into SF CO 2 were assigned to be Ga(OH)(MO 6 Q) 2 and Ga(O 6 Q) 3 , respectively. Palladium(II) was extracted with HMQ as Pd(MQ) 2 from a weakly acidic solution. Even in the presence of HMQ, the Pd(II)-HMQ complex extracted from the higher HCl concentration should be H 2 PdCl 4 .

An X-band miniaturized traveling-wave tube (TWT) using a Spindt field emitter array (FEA) cathode was built. The FEA cathode has 542,000 molybdenum tips in an emission area 1.2 mm in diameter. It also has a trench current-limiter that shows low resistance in normal operation. A saturation output power of 28.2 W, a saturation power gain of 40 dB, and a beam transmission ratio of more than 99.3% have been achieved at a frequency of 11.5 GHz under 3% duty ratio.

The partition coefficient between heptane or chloroform and 0.1 M NaCI aqueous solution, and the acid dissociation constants of 5-alkyloxymethyl-8-quinolinol (HO„Q) were determined. Also, the extraction and back-extraction behavior, extraction equilibrium and kinetics, and the separation of Cu{11) [1, 2], Mo(VI), [3, 4], Pd(II), [5], Ga(IlI) [6], Co(Il) [7] and Ni(ll) [7] with novel 8-quinolinol derivatives (HA) have been investigated. Cu(II) was extracted with H08Q, HM08Q, and 5-(4-nitrophenylazo)-7-(4-ethyI-l-methytoctyl}-8-quinolinol (HNEQ) into chloroform as Cu(A)2. The extraction constant ( Kex) increases in the following order of Kelex 100 < 8-quinolinol

The thermodynamic parameters (ΔD, ΔH, ΔS) of protonation and of complexation of trivalent La, Nd, Gd, Dy and Lu with DTPA-bis(methoxyethylamide) (MEA), DTPA-bis(methylmethoxyethylamide) (MMEA) and DTPA-bis(hydroxyethylmethylmethoxyethylamide) (HEMEA) have been measured by potentiometric and calorimetric titration at I = 0.1 M and 25°C. Especially in the first two protonation steps, there are significant differences in the pKa and the protonation enthalpy among the three DTPA-bis(amides) and DTPA. The fractional proton population determined by NMR shifts for each basic site of MEA and MMEA is compared with the thermodynamic parameters of those compounds and discussed in terms of the role of NH and CO of the amide groups in the protonation. The complexation parameters are compared with other Ln-polyaminopolycarboxylate complexes to understand the role of the carboxylate, amino and methoxyethylamide groups of the DTPA-bis(amides). The luminescence lifetime of the Eu(III) complexes of the bisamide ligands indicated the coordination of a single water molecule to the metal in the aqueous complexes which is evidence that the DTPA-bis(amide) ligands have octadentate coordination with the Ln(III) ions.

Extraction of lanthanide(III) ions with 18-crown-6 (18C6) and trichloroacetate (tea) has been studied. The composition, hydration, and structure of the La(III) and Eu(III) complexes extracted into 1,2-dichloroethane were investigated by using several methods such as the liquid-liquid distribution technique, conductimetry, Karl Fisher titration, laser luminescence spectroscopy, and 1H NMR. The La(III) complex was found to be a monohydrate, La(tca)3(18C6)(H2O), while that of Eu(III) was a mixture of a monohydrate and a dihydrate, i.e., Eu(tca)3(18C6)(H20) and Eu(tca)3(18C6)(H20)2- The origin of the selectivity by 18C6 which gives much higher extractability of La(III) than of Eu(III) is explained by considering the hydration and probable structure of their complexes.

Synergistic enhancement of the extraction of aluminium(III) with acetylacetone (Hacac) in heptane and carbon tetrachloride was observed by the addition of 3,5-dichlorophenol (DCP).This phenomenon is due to the formation of association complexes of Al(acac)3 with DCP. From the extraction-equilibrium analysis, the association complexes were found to be Al(acac)3·n(DCP) (n=1-3) and the overall association constants (βass,n) were determined. The hydrogen bonding of the hydroxyl hydrogen of DCP with Al(acac)3 was evidenced by IR and 1H NMR spectroscopy. The βass,n values determined by IR were in good agreement with those’ obtained by the distribution method. The relationship between the hydrogen bond ability of tris(acetylacetonato)-metals(III) and their structure was discussed by comparison of βass,n for Al(acac)3 with those for some metal(III)-acac chelates studied so far.

The extraction of La(III), Gd(III), and Lu(III) with 18-crown-6 (18C6) has been studied using pentadecafluorooctanoate (PDFO) as a counter anion. Very high extractability of La(III) was observed in various organic solvents such as benzene, chloroform, 1,2-dichloroethane, and nitrobenzene. The predominant species extracted into benzene was found to be Ln(PDFO)3 (18C6), and the extraction constants (Kex,s1=[Ln(PDFO)3 (18C6)]org/[Ln3+][PDFO]3[18C6]org) were 1013.12 for La(III), 109.74 for Gd(III), and 109.67 for Lu(III). These values are 1010 times higher than those in the trichloroacetate-18C6 system reported previously. The present PDFO-18C6 system was superior to the picrate- and hexafluoroacetylacetonate-18C6 system for the separation efficiency of light lanthanides(III).

Glucose effectiveness (SG) and insulin sensitivity of sedentary and physically trained males were estimated by the minimal model approach. Trained subjects, who ran 86 +/- 10 km/wk and had 37% higher maximal oxygen consumption than that of sedentary subjects (56.2 +/- 1.2 vs. 40.9 +/- 1.4 ml.kg-1 x min-1, P < 0.01), were studied 16 h and 1 wk after their last training session. After overnight fasting, glucose was administered intravenously (300 mg/kg body wt) within 2 min, and insulin was infused (approximately 13-20 mU/kg given over 5 min) from 20 to 25 min after administration of glucose. Glucose disappearance constant values as an estimate of glucose tolerance were significantly higher in trained subjects after 16 h and 1 wk of their training session (3.29 +/- 0.48 and 3.60 +/- 0.64%/min) than in sedentary subjects (1.92 +/- 0.30%/min, P < 0.05). Insulin sensitivity in trained subjects measured after 16 h and 1 wk of their last training session (26.2 +/- 4.4 and 24.3 +/- 6.0 x 10(-5) min-1 x pM-1) was also higher than that of sedentary subjects (10.3 +/- 1.2 x 10(-5) min-1 x pM-1, P < 0.05). SG, the ability of glucose itself to increase peripheral glucose uptake and suppress hepatic glucose output, was significantly higher in trained subjects after 16 h and 1 wk of their last training session (0.028 +/- 0.003 and 0.030 +/- 0.004/min) than in sedentary subjects (0.017 +/- 0.002/min, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

We investigated whether phosphatidylinositol 3-kinase (PI3K) is phosphorylated and whether its specific activity is increased by insulin stimulation in vivo using Fao cells and antibodies raised against the 85 kDa subunit of PI3K, insulin-receptor substrate-1 (IRS-1), and phosphotyrosine (pTyr). PI3K activity was detected in the immunoprecipitate produced with anti-PI3K at a basal state. The activity was increased 2-3-fold by insulin stimulation, although the protein concentration of kinase in the anti-PI3K immunoprecipitates was the same before and after insulin stimulation. Both anti-pTyr and anti-IRS-1 antibodies immunoprecipitated the kinase activity only after insulin stimulation. After the first immunoprecipitation with anti-pTyr, the supernatant was immunoprecipitated once more with anti-PI3K. PI3K activity in the second immunoprecipitate revealed little difference between the basal and insulin-stimulated states, suggesting that most of the insulin-activated portion of PI3K was precipitated by anti-pTyr. Both IRS-1 and the insulin-receptor beta-subunit (95 kDa) were phosphorylated on tyrosine residues by insulin stimulation and immunoprecipitated with anti-pTyr. However, phosphorylation of neither subunit of PI3K (85 kDa or 110 kDa) was detectable in the immunoprecipitate produced with anti-pTyr. The 185 kDa pTyr-containing protein was immunoprecipitated with anti-PI3K after insulin stimulation, although there was little phosphorylation of the 85 kDa protein. pTyr in the 110 kDa protein immunoprecipitated with anti-PI3K was below detectable levels. These results indicate that the specific activity of PI3K is increased by insulin stimulation without detectable tyrosine phosphorylation of PI3K itself in Fao cells. The majority of the insulin-activated portion of PI3K is associated with pTyr-containing proteins including IRS-1, which suggests that this is important for activation of PI3K by insulin.

For the purpose of achieving a good efficiency and pulsed output of short-lived reaction products, we propose a laser-enhanced ion-guide ion source for an on-line isotope separator. Two-step resonant, three-color resonance ionization of Ba atoms was established in an off-line experiment and the ionization efficiency per pulse was measured to be 1.9%. In an on-line ion-guide experiment, it was found that the use of heavy gas was effective to stop the recoil atoms and that most of them remain in the gas until evacuation. While enhancement of the ionization efficiency by introduction of a laser beam to the ion-guide chamber has not been achieved so far, possible improvements are discussed.

Effect of 3,5-dichlorophenol (DCP) on the extraction of Fe(III) with acetylacetone (Hacac) in nonpolar organic solvents has been studied. It is found that a mixture of Hacac and DCP in heptane gives much higher extraction of Fe(III) than Hacac alone. Such novel enhancement effect is ascribable to the association of tris(acetylacetonato)iron(III) [Fe(acac)3] with DCP in the organic phase by hydrogen bonding. Association of Hacac with DCP has also been investigated and the intrinsic extraction equilibrium of Fe(III) is analyzed by using the equilibrium concentration of free Hacac and DCP. The association complexes are found to be Fe(acac)3 · n DCP (n=1, 2, 3) in heptane, and the overall association constants (βass, n) are determined to be log βass, 1 = 3.41, log βass, 2, = 5.97 and log βass, 3, = 7.50.

The effects of allogeneic bone marrow transplantation (BMT) on non-insulin-dependent diabetes mellitus (NIDDM) were examined using KK-Ay mice. KK-Ay mice reconstituted with KK-Ay bone marrow cells showed glycosuria, hyperinsulinemia, and hyperlipidemia. However, KK-Ay mice (H-2b) that had been lethally irradiated (9.0 Gy) and then reconstituted with T cell-depleted bone marrow cells from normal BALB/c mice (H-2d) showed negative urine sugar with decreases in serum insulin and lipid levels 4 mo after BMT. Morphological recovery of islets and glomeruli was also noted after allogeneic BMT. These findings suggest that BMT can be used to treat not only a certain type of NIDDM but also its complications such as hyperlipidemia and diabetic nephropathy.

The synergistic effect on the extraction of thorium(IV) was found by the combination of 2-thenoyltrifluoroacetone (Htta) and 1,10-phenanthroline (phen) or 4,7-diphenyl-1,10-phenanthroline (dpp) as a neutral bidentate ligand. Especially in the presence of dpp (1·10−3M) in benzene, the distribution ratio of thorium(IV) increased by a factor of about 300. Such synergistic enhancement of the extraction was ascribed to the formation of the adduct complex of Th(tta)4(phen) and Th(tta)4(dpp) in the organic phase. The extraction constant and the adduct formation constant were determined and discussed.

The synergic extraction of La(III), Eu(III), and Lu(III) with 2-thenoyltrifluoroacetone (Htta) and triphenylarsine oxide (tpao) in benzene has been studied. The extractability of lanthanoids, Ln(III), is significantly affected by the association of Htta with tpao in the organic phase. The associated species is Htta·tpao and the association constant is determined as 101.63. The intrinsic extraction equilibrium of Ln(III) is analyzed using the free concentration of Htta and tpao. The synergic enhancement is ascribable to the formation of the adduct complexes shown as Ln(tta)3tpao and Ln(tta)3(tpao)2 in the present extraction system. The adduct formation constants determined are very large as expected from the high basicity of tpao.

A novel interconnect design concept named "ASIS (application-specific interconnect structure)" is presented for 45 nm CMOS performance maximization. Basic scheme of ASIS is that corresponding to applications, such as high-performance, low-power or high reliability, interconnect structure as well as metal thickness is individually optimized in order to maximize chip-level performance matched to the application. Our investigation shows that for low power application, the increased resistivity of scaled-down Cu-wire is not a main issue, so that thinner wire is more advantageous. For high-performance application, partially double pitch structure for local and intermediate layers is advantageous. For high-reliability requirement, CuAl-alloy or CoWP cap-metal is quite effective for boosting reliability

A novel CoWP cap integration technology for lower leakage current and improved dielectric reliability is proposed for porous low-k/Cu interconnects, NH3 plasma treatment before SiCN deposition reduces leakage current and improves dielectric reliability such as time-dependent dielectric break-down (TDDB) of CoWP capped Cu interconnects. The TDDB lifetime much longer than 10 years is obtained. Moreover, the leakage current less than IE-14A/mm is obtained by low-k top (LKT) dielectric structure combined with the NH3 plasma treatment. In addition, 10% lower RC product is obtained by the LKT structure with CoWP cap

This paper describes an experiment of a temporal resolution control scheme of stored video traffic in a wireless LAN. The scheme switches the resolution between two levels according to the network load. We propose a simple method of detecting network congestion which uses only local information. We have implemented the scheme on a wireless LAN based on ALTAIR and have made performance measurement in terms of throughput and total output time. As a result, we observe that although the scheme does not improve the throughput performance, it is effective in suppressing an increase of the total output time due to the network delays.

This paper proposes two schemes for synchronization of stored voice and video media units (MUs) in wireless LANs. The schemes, called nondistinctive and distinctive, are based on interleaving of the two kinds of MU. The former does not distinguish between voice and video MUs in the interleaved stream, while the latter does. To evaluate their performance and confirm the effectiveness in comparison with the scheme of no-control, we developed an experimental system using the ALTAIR wireless LAN. The mean square error of synchronization, total pause time, throughput and total output time of the three schemes were measured. As a result, we see that the control of intrastream synchronization is indispensable for heavy traffic and that the interleaving serves as an effective mechanism for inter-stream synchronization. Then, it is shown that the nondistinctive scheme with an appropriate size of the voice MU should be employed.

We first built two traveling wave tubes (TWTs) using a Spindt-type field emitter array (FEA) cathode. The first FEA-TWT achieved excellent RF performances. However its beam transmission ratio was only 82%, in contrast with more than 99% of a conventional TWT. To improve the beam transmission ratio and other characteristics, we re-designed the FEA electron gun and fabricated a second experimental FEA-TWT. At the current less than 20 mA, the beam transmission ratio of the second TWT was improved as high as 98%. However, when the current was more than 20 mA, space charge effect became significant and beam transmission ratio was rapidly degraded. The test results indicated that the design criteria for FEA electron guns needed to take into consideration the strong influence of space charge and how a good beam transmission ratio could be obtained.

Since the human genome project has been almost completed in 2000, the year of 2001 is the first year of the postgenomic era. A variety of postgenome studies will be done in the next decade, including functional, comparative and structural genomics. These studies may open new area in medicine, because disease susceptibility and drug metabolism would be predicted from genetic characteristics of individuals. Genome studies may also shed a light on cell biology, brain research and regeneration medicine and promote these studies. Bioinformatics will become a basis of postgenome biology and medicine.

The introduction of Evidence-based medicine(EBM) for residency training is recommended by the Japanese Society of Internal Medicine. At our hospital, we put the emphasis on learning vital clinical epidemiology through clinical experience. When educating EBM to our residents, we especially focus on the diagnostic process, because the knowledge of clinical epidemiology is useful while making the diagnosis and evaluating the diagnostic hypothesis. In our daily conference among residents and medical educators, the logic of clinical epidemiology is used for evaluating the validity of clinical judgment on diagnosis. We suggest three components upon making a diagnosis: 1. Always suspect a particular disease when ordering a laboratory test 2. Know the sensitivity and specificity of the test 3. Apply the test result in order to reevaluate the pretest hypothesis In this article, interaction among staff and residents are presented and discussed with these components in our minds. By repeating these interactions, the residents will be able to understand the importance of EBM and will be able to apply it in the clinical practice.

To examine the possible role of endothelin in the initiation of parturition, endothelin-1-like immunoreactivity (ET-1-LI) in the amniotic fluid (AF) was determined by a sensitive radioimmunoassay (RIA) system. The concentrations of ET-1-LI in AF were 24.7 +/- 6.1 pg/ml (mean +/- SD, n = 6) at the second trimester and were significantly increased to 40.4 +/- 15.1 pg/ml (n = 6) at term. These ET-1-LI concentrations are about three- to fourfold higher than those observed in the maternal plasma. The gel permeation chromatography (GPC) profile of ET-1-LI extracted from second-trimester AF indicated that the ET-1-LI consisted of only one component of 6kET, the molecular weight of which was 6,000, larger than big ET-1. In contrast, ET-1-LI in the AF at term consisted of two components, ET-1 and 6kET. These findings suggest that the level of biologically active ET-1 in the AF increases markedly from second trimester toward term. A significant amount of ET-1-LI was also detected in the supernatant of amnion cell culture. The level of ET-1-LI in the culture medium after 12 h of incubation was almost comparable with that in AF at term. Thus, it is suggested that amnion tissue may be the major source of ET-1-LI in the AF. Together with the fact that ET-1 increases cytoplasmic calcium ion in the target cell, the results of present study raise the possibility that endothelin plays an important role in the initiation of parturition by triggering the production of prostaglandins in fetal membranes.

To examine the role of endothelin (ET) in the maternal and fetal circulation, the levels of endothelin-1-like immunoreactivity (ET-1-LI) in the plasma of maternal vein (MV), umbilical vein (UV), and umbilical artery (UA) were determined by a sensitive radioimmunoassay (RIA). Levels of ET-1-LI in MV did not show any significant change (9.9 +/- 1.5 pg/ml, n = 26) throughout normal pregnancy and were similar to those of normal nonpregnant women (10.7 +/- 2.5 pg/ml, n = 5). Levels of ET-1-LI in UV and UA obtained at normal deliveries at term were about three times higher than those in MV. In the patients with mild and severe pre-eclampsia, the levels of plasma ET-1-LI were significantly higher than those of normal pregnancy (14.3 +/- 2.2 pg/ml, n = 5 and 27.2 +/- 8.6 pg/ml, n = 5, respectively). However, in pregnant women with chronic hypertension, the levels of ET-1-LI did not increase when the hypertension did not worsen during pregnancy (11.4 +/- 1.6 pg/ml, n = 7). Moreover, in two pregnant women with abnormally stimulated coagulation, such as acute or subacute DIC, the levels of ET-1-LI were extremely high and returned gradually to those of normal nonpregnant women after the coagulation was normalized by treatment. These results suggest the possibility that ET-1 plays an important role in the pathophysiology of preeclampsia.

This paper reports the catalytic reduction of carbon dioxide to methanol achieved with a hydrogen fuel cell. This process involves a homogeneous and a heterogeneous catalysis. In the former, the catalyst consisting of a metal complex and methanol were applied, and in the latter Everitt's salt (K{sub 2}Fe{sup II}(Fe{sup II}(CN{sub 6}))) which functions as an electron relay was used. The initial {ital p}H of the catholyte was fixed at 2, and the {ital p}H of the anolyte was required to be higher than 1.75 for the hydrogen fuel cell with CO{sub 2} as oxidant to be feasible thermodynamically.

Clinical receptology encompasses broad areas, including receptor or postreceptor defects due to mutations of receptor or other genes, abnormalities due to receptor antibodies and secondary changes of receptors under various pathological conditions. Recent progress in molecular biology has succeeded in cloning genes of receptors, G-proteins and other cellular proteins that are involved in the signal transduction and clarified their germ-line and somatic mutations. It is of importance that mutations of receptors and G-proteins do not necessarily cause loss of function but sometimes cause gain of function of receptors or G-proteins, thus leading to hyperfunction. Molecular basis that causes either loss or gain of function has been studied but is not completely understood. Some examples of gain of function mutatious of G-protein coupled receptors, tyrosin kinase-type receptors and G alpha protein are shown. Another important aspect in receptor research is that mutation of a single receptor gene sometimes result in different phenotypes and even different modes of inheritance. For example, mutations of rhodopsin (a G-protein coupled receptor) gene cause retinitis pigmentosa of autosomal dominant type and autosomal recessive type and also cause congenital stationary night blindness. Exact mechanisms responsible for such differences are not completely understood. There are polymorphisms in some genes that may be involved in some diseases. An example is a polymorphism in beta 3-adrenergic receptor that is claimed but not clearly demonstrated to be a cause of obesity or type II diabetes. Such polymorphism is possibly a gene in polygenic diseases. Receptology is important for elucidating pathogenesis of complex diseases.

The success rate of surgical treatment for blowout type free wall rupture of the left ventricle following myocardial infarction has been reported as 4 to 24%. A 64-year-old woman was admitted to our hospital for inferior acute myocardial infarction with cardiogenic shock. In the catheter laboratory, her hemodynamics disclosed electro-mechanical dissociation, and we had to perform an emergent operation there. In order to preserve left ventricular volume and reduce the risk of bleeding, we adopted a modified method using both patch and felt strip sandwich methods which obtained favorable result. The patient was sent to a rehabilitation hospital on the 43rd post operative day because of a mild cerebral complication and she is now doing well with only a slight speaking disturbance at a follow-up period of 10 months.

In a series of experimental studies in dogs, we determined the exact site for the disruption of the atrioventricular conduction system by cryosurgical ablation which does not disturb the intraventricular conduction. The long-term symptomatic effects were evaluated in 9 patients with supraventricular tachycardia. In a total of 15 adult mongrel dogs, a thoracotomy was performed under pentobarbital anesthesia that was maintained during the procedure with artificial ventilation and cardiopulmonary bypass. The body temperature was maintained at 37 degrees C and throughout each experiment, the ECG was recorded by the conventional limb lead method while monitoring and recording the His bundle potentials from the catheter-electrode introduced via the internal carotid artery. The location in which the maximum His bundle potential was recorded was determined by intraoperative His bundle mapping through the right atrial incision. Cryoablation was performed by using -60 degrees C probes with a 5 mm tips. In 5 dogs (experiment A), we compared the effect of cryoablation at 2 different points on the interatrial septum, which were either 10 mm (10 mm point) or 5 mm (5 mm point) away from the site of the largest His bundle potential to the direction of the coronary sinus ostium. The two ablations were performed successively at 20 minute intervals. A second group consisting of 10 dogs, received cryoablation only at the 5 mm point (experiment B). In experiment A, atrioventricular block (AV block) was inconsistently achieved following cryoablation at the 10 mm point, whereas at the 5 mm point, the procedure was 100% successful in obtaining AV block without affecting the QRS morphology or H-V interval. In experiment B, we confirmed the reliability of the 5 mm point. Following cryoablation at the 5 mm point, coagulation necrosis in the region from the AV node to the penetrating portion of the His bundle were observed by pathological examination, however, the damage was only mild at the branching portion of the His bundle. Cryoablation was performed at the 5 mm point in 9 subjects. In all of these cases, complete AV block was successfully produced to terminate the tachycardias. The R-R interval of the escape rhythm in these patients gradually prolonged, and stabilized at 1500-1600 ms 3 years following the operation. In the long-term electrophysiological studies, all subjects had A-H block, and there were no subjects with prolonged H-V intervals observed. We conclude that cryoablation at the 5 mm point is an appropriate and effective choice for the treatment of supraventricular tachycardias.

A 26-year-old man with systemic lupus erythematosus (SLE) and a history of acute myocardial infarction developed portal hypertension accompanied by abnormal liver function and esophageal varices. As his clinical course suggested the possibility of antiphospholipid syndrome, a titer of anticardiolipin antibody (aCL) was serially measured using an enzyme immunoassay with β2-glycoprotein I as a cofactor. The titer of aCL increased with the development of portal hypertension, and promptly decreased with the improvement of liver function just after corticosteroid therapy. The long-term course in this case suggests that aCL may cause portal hypertension associated with SLE.

To assess clearance mechanisms of atrial and brain natriuretic peptides in the circulation, we examined the effects of a neutral endopeptidase (NEP) inhibitor and a clearance receptor ligand on plasma concentrations of the peptides in normal rats. Plasma concentrations of endogenous alpha-rat atrial natriuretic peptide (alpha-rANP) were not significantly elevated by intravenous infusion of a NEP inhibitor, phosphoramidon, but were elevated threefold by intravenous infusion of a clearance receptor ligand, des(Gln18-Gly22)-rANP(4-23)-NH2 [C-ANF(4-23)]. On the other hand, the clearance of alpha-rANP given intravenously at the pharmacological dose, 600 pmol/min/kg for 2 min, was decreased to one-third by the administration of phosphoramidon, although the administration of C-ANF(4-23) did not significantly decrease the clearance. The clearance of rat brain natriuretic peptide (rBNP) given at 600 pmol/min/kg for 2 min was approximately 38% lower than that of alpha-rANP. The effect of phosphoramidon on the clearance of rBNP was not significant and was similar to that of C-ANF(4-23). These results suggest that clearance receptor is involved in the clearance of the physiological levels of alpha-rANP and that NEP plays a major role in the clearance of a pharmacological dose of alpha-rANP, at which clearance receptors are thought to be saturated, and also indicate a pharmacokinetic difference between alpha-rANP and rBNP.

Steroid 11 beta-hydroxylase deficiency (11 beta OHD), an autosomal recessive hereditary disease, accounts for 5-8% of cases of congenital adrenal hyperplasia. In this study, we carried out a molecular genetic analysis of CYP11B1 encoding steroid 11 beta-hydroxylase (P450c11) from a Japanese patient affected with this disease. Nucleotide sequence analysis of polymerase chain reaction-amplified products of the patient's genome revealed the occurrence of a stop codon in exon 2 due to a point mutation, TGG-->TAG (Trp116-->Stop). To further analyze the role of CYP11B2 encoding steroid 18-hydroxylase (P450c18) in the 11 beta OHD patient, CYP11B2 of the patient was also amplified and sequenced. In contrast to CYP11B1, there was no mutation in CYP11B2. Restriction fragment length polymorphism analysis indicated that the 11 beta OHD patient is homozygous and his unaffected parents are heterozygous for the mutation. When a cDNA corresponding to CYP11B1 of the 11 beta OHD patient was transfected into COS-7 cells, steroid 11 beta-hydroxylase activity was not detectable in mitochondria of the cells. These results demonstrate that intact P450c11 was not produced at all due to the nonsense mutation in CYP11B1 of the patient without any mutation in CYP11B2.

The effectiveness and safety of MCI-028, a synthetic human corticotropin-releasing hormone (hCRH), as a diagnostic drug were examined in 65 healthy male and 24 healthy female adult volunteers. Mean maximum concentrations of plasma ACTH and cortisol after intravenous administration of 100 micrograms of MCI-028 were 3.0 and 2.0 times their basal concentrations, respectively, and there were no significant age or sex differences in the responses. Good reproducibility was observed in the responses in 59 male subjects who received a second administration after 1 to 2 weeks. Although slight adverse reactions such as mild and transient hot flushing were observed, these were not serious.

To investigate the involvement of brain natriuretic peptide in the circulation of pregnant women with pregnancy-induced hypertension.We determined the plasma levels of brain and atrial natriuretic peptides in a cross-sectional study of 36 normal pregnant women and 17 women with pregnancy-induced hypertension.During normal pregnancy, the plasma brain natriuretic peptide level was similar to that in nonpregnant women, but the plasma atrial natriuretic peptide level in the second trimester was significantly higher than that in nonpregnant women (P.05). In women with severe pregnancy-induced hypertension, the plasma brain natriuretic peptide level was eight times higher than that in normal pregnant women in the third trimester; the plasma atrial natriuretic peptide level in the same patients was three times higher than that in normal pregnancy. The plasma brain natriuretic peptide level showed a positive correlation with the mean blood pressure (r = 0.62, P.001).The present findings suggest that brain natriuretic peptide is increased in the plasma of women with pregnancy-induced hypertension and that brain natriuretic peptide, in concert with atrial natriuretic peptide, participates in maintaining homeostasis of the maternal circulation.