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Biomedical subjects

Y Toma

Publications and source records attributed to Y Toma.

At least 19 recordsLinked to original sources
PubMed1998

Lactoferrin and interleukin-6 interaction in amniotic infection.

Lactoferrin (Lf) has been found in most biological fluids including amniotic fluid and cervical mucoids in pregnant women, and released from neutrophils in response to the inflammation. As Lf possesses antimicrobial properties, it is widely considered to be an important component of the host defence against microbial infections. It is known that premature labor is caused by amniotic infection with the increase of prostaglandin production. High concentration of the inflammatory cytokines: interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) in the amniotic fluid has been known. However, changes of Lf in amniotic fluid with infection has not been reported. In the present study, Lf concentrations in amniotic fluid were measured under the intra-uterine infections state and the biological significance of Lf was investigated. The effects of Lf on the IL-6 and IL-6mRNA production in cultured amnion cells were also investigated. The concentrations of Lf and IL-6 in amniotic fluid with CAM were 8.76 +/- 0.65 micrograms/ml and 6.92 +/- 4.88 ng/ml (n = 28) respectively and both were significantly higher (p < 0.01) than those without CAM [0.86 +/- 0.81 microgram/ml and 0.34 +/- 0.25 ng/ml (n = 31)]. Significant positive correlation (r = 0.91, p < 0.01) between Lf and IL-6 levels in amniotic fluid was found. IL-6 production induced by lipopolysaccharide (LPS) (100 ng/ml) in cultured amnion cells was significantly inhibited (p < 0.05) under the physiological concentration of Lf in amnion. Total RNA was extracted from the amniotic cells by guianizine solution. RT-PCR procedure and product analysis were performed from one microgram aliquote of total RNA. beta-actin was used as an international standard and c-DNA samples were followed by 30 cycles of PCR. RT-PCR product of IL-6 mRNA was detected by Southern hybridization. Expression of IL-6 mRNA was inhibited by the addition of Lf. From the results, the possibility that Lf might suppress amniotic IL-6 production under the condition of amniotic infection is suggested. It is also suggested that Lf might act as self defence mechanism from intra-uterine infection.

Amnion↗
PubMed1998

Inhibitory effects of catecholamines and maternal stress on aromatase activity in the fetal rat brain.

OBJECTIVE: Aromatization in the the fetal brain is thought to be involved both in sex differentiation during early development and in adult sexual behavior. Although recently the relationship between aromatase and catecholamine has been discussed, the effect of stress on aromatase in the fetal brain has not been clarified. Therefore, in the present study, localization of aromatase and the inhibitory effects of catecholamines and maternal stress on aromatase activity in the fetal rat brain were examined. METHODS: Localization of aromatase cytochrome P-450 using a specific polyclonal antiserum against human placenta aromatase was examined, and the inhibitory effects of dopamine and norepinephrine on aromatase activity in vitro were studied. Further, the influences of intrauterine stress on aromatase activity in the prenatal rat brain were evaluated in vivo. RESULTS: Aromatase-immunoreactive neurons are located principally in the medial amygdaloid nucleus. Aromatase activity in the fetal rat brain was competitively inhibited by dopamine and norepinephrine, with Ki values of 120 microM and 100 microM, respectively. Aromatase activity in the fetal brain was significantly lower in stressed rats given 1.5% salt water (89.2 +/- 17.5 fmol/mg/hr; n = 4) (p < 0.05) than in the control group (123.1 +/- 10.0 fmol/mg/hr; n = 4). CONCLUSION: Aromatase activity in the prenatal rat brain is influenced by catecholamine metabolism during intrauterine stress.

Amygdala↗
PubMed1997

Diverse function of aromatase and the N-terminal sequence deleted form.

The diverse function of human placental aromatase including estradiol 6alpha-hydroxylase and cocaine N-demethylase activity are described, and the mechanism for the simultaneous metabolism of estradiol to 2-hydroxy- and 6alpha-hydroxyestradiol at the same active site of aromatase is postulated. Comparison of aromatase activity is also made among the wild type and N-terminal sequence deleted forms of human aromatase which are recombinantly expressed in Escherichia coli. Aromatase cytochrome P450 was reconstituted and incubated with [6alpha,7alpha-(3)H2,4-(14)C]estradiol, 7-ethoxycoumarin, and [N-methyl-(3)H3]cocaine. 6Alpha-hydroxy[7alpha-(3)H,4-(14)C]estradiol was isolated as the metabolite of estradiol and the 3H-water release method based on the 6alpha-3H label was established. The initial rate kinetics of the 6alpha-hydroxylation gave Km of 4.3 microM, Vmax of 4.02 nmol min(-1) mg(-1), and turnover rate of 0.27 min(-1). Testosterone competed dose-dependently with the 6alpha-hydroxylation and showed the Ki of 0.15 microM, suggesting that they occupy the same binding site of aromatase. The deethylation of 7-ethoxycoumarin showed Km of 200 microM, Vmax of 12.5 nmol min(-1) mg(-1) and turnover rate of 1.06 min(-1). The N-demethylation of cocaine was analysed by the 3H-release method, giving Km of 670 microM, Vmax of 4.76 nmol min(-1) mg(-1), and turnover rate of 0.49 min(-1). All activity was dose-responsively suppressed by anti-aromatase P450 monoclonal antibody MAb3-2C2. The N-terminal 38 amino acid residue deleted form of aromatase P450 was expressed in particularly high yield giving a specific activity of 397 +/- 83 pmol min(-1) mg(-1) (n = 12) of crude membrane-bound particulates with a turnover rate of 2.6 min(-1).

Aromatase↗
PubMed1997

[Gonadal dysfunction].

Function of hypothalamic-pituitary-ovarian axis is an essential factor for the maintenance of regular cycles in mature women. The disturbance of function of those organs causes gonadal dysfunction such as anovulation, amenorrhea and menstrual disorders. Therefore, the correct diagnosis for the assessment of CNS and ovarian function is clinically important to treat the patients those who have an menstrual disorders. In this review, the mechanism of normal gonadal cycles and the diagnostic method and the treatment of gonadal dysfunction are described.

Amenorrhea↗
PubMed1996

Diverse functions of aromatase: O-deethylation of 7-ethoxycoumarin.

In studying the diverse functions of aromatase we found that purified and reconstituted aromatase also catalyzes O-deethylation of 7-ethoxycoumarin. Aromatase cytochrome P450 was purified from human term placentas by monoclonal antiaromatase P450 antibody-Sepharose 4B column chromatography. Kinetic analysis of the O-deethylation of 7-ethoxycoumarin by reconstituted aromatase showed Km of 200 microM, Vmax of 12.5 nmol.min-1.mg-1, and turnover rate of 1.06 min-1. 7-Ethoxycoumarin competitively inhibited androstenedione aromatization, the Ki was 180 microM. Fadrozole (CGS16949A), a specific competitive aromatase inhibitor, and MAb3-2C2, an antiaromatase P450 monoclonal antibody, inhibited both aromatase and 7-ethoxycoumarin O-deethylase activities dose responsively. The IC50 of Fadrozole was 33 nM for aromatase and 67 nM for 7-ethoxycoumarin O-deethylase. The IC50 of MAb3-2C2 was 1.1 micrograms IgG for aromatase and 4.0 micrograms IgG for 7-ethoxycoumarin O-deethylase. These results indicate that the two enzyme activities are catalyzed by the same active site of the cytochrome P450. Contrary to the previous postulate on the mechanism-based inactivation of microsomal aromatase by 4-androstene-3,6,17-trione, we found that with purified aromatase, both the initial 19-hydroxylase and the after lyase reactions are simultaneously inactivated by the steroid suicide inhibitor.

Androstenes↗
PubMed1996

Echographical assessment of the early stage of experimental atherosclerosis of the descending aorta in rabbits.

To assess the early stage of atherosclerosis of the thoracic descending aorta, we evaluated morphological atheromatous lesions (atherosis) and the stiffness parameter of the artery (beta; sclerosis) in 24 male rabbits using echography. Male Japanese white rabbits weighing 2.5-3.0 kg were fed a diet containing 1% cholesterol for 7 (n = 8) or 14 weeks (n = 8). Rabbits fed a normal diet were used as controls (n = 8). Atheromatous lesions were evaluated with intravascular ultrasound (IVUS: Aloka, 20 MHz, 6F). We also calculated beta using M-mode echography (7.5 or 10 MHz) and direct aortic pressure measurement. Thickening of the intima-media complex was clearly observed with IVUS in the 14-week group but was not detected in the others. Histologically, only a thin layer of foamy cells on the intima (thickness < 20 microns) was observed in the 7-week group. The value of beta was significantly increased in both the 7-week (4.7 +/- 2.2) and 14-week groups (4.5 +/- 0.8) compared with controls (1.7 +/- 0.9, both p < 0.01). These results suggest that the development of atherosis might be preceded by vascular sclerosis during the early stage of atherosclerosis when the serum cholesterol level is high: at a time when the thin layer of foamy cells could not be detected by conventional IVUS.

Animals↗
PubMed1996

Aromatase and estrogen 2-hydroxylase activities of human placental microsomes in pregnancy-induced hypertension.

2-Hydroxylation is one of the major metabolic pathways of estrogens and is believed to be catalyzed by a form of cytochrome P450. Recently it has been reported that estrogen 2-hydroxylase activity in human placenta is catalyzed by aromatase. Some investigators suggested the effect of catechol estrogen on human placental steroidogenesis which may be related to pregnancy-induced hypertension (PIH) through the inhibition of catechol-O-methyltransferase (COMT) activity. In order to better understand the interrelationship between placental aromatase and estrogen 2-hydroxylase activities in PIH patients, both activities were evaluated in the PIH placentas. Human placental microsomes obtained from PIH patients were incubated with [1 beta-3H]androstenedione or [2-3H]estradiol in the presence of NADPH. Aromatase and estrogen 2-hydroxylase activities were assessed by the tritium water method. The immunosuppression patterns of both activities due to monoclonal antiaromatase cytochrome P450 antibody (MAb3-2C2) were studied. Estrogen 2-hydroxylase activity was significantly higher in PIH placentas (4.7 +/- 0.9 pmol/min/mg protein, n = 7) than in normal placentas (3.0 +/- 0.7 pmol/min/mg protein, n = 7). When the PIH placental microsomes were subjected to immunosuppression by 1 to 100 micrograms IgG of MAb3-2C2, estrogen 2-hydroxylase activity was suppressed by 94 to 65% whereas aromatase activity was strongly suppressed by 72 to 17%, respectively. From our results of high estrogen 2-hydroxylase activity in PIH placentas, it is assumed that there is a different estrogen catalyzing mechanism in PIH placentas.

Antibodies, Monoclonal↗
PubMed1995

Sequence of the flounder (Paralichthys olivaceus) growth hormone-encoding gene and its promoter region.

The flounder (Paralichthys olivaceus) growth hormone (GH)-encoding gene (fGH) and its promoter region were cloned and sequenced following amplification of genomic DNA by the polymerase chain reaction. The fGH gene is 2.1-kb long and consists of six exons and five introns. In the 5'-flanking region of the determined transcription start point, a potential TATA box is located at -24, and Pit-1/GHF-1-binding site candidates are located in the -70 to -53 and -133 to -141 regions.

Amino Acid Sequence↗
PubMed1993

Pubic-type dislocation of the hip combined with fracture of the ipsilateral greater trochanter. A case report.

Traumatic anterior dislocation of the hip is a relatively uncommon injury, and when it does occur it is frequently combined with osteochondral fracture of the femoral head or the acetabulum. Anterior dislocation of the hip with an associated fracture of the ipsilateral greater trochanter is extremely rare. This paper presents a case of this rare type of injury and clarifies the mechanism of the injury using a cadaver specimen.

Adult↗
PubMed1993

[Echocardiographic assessment of heart failure].

In the last two decades M-mode and two-dimensional echocardiography yielded outstanding improvements in diagnostic cardiology by providing readily available morphological and functional information of the heart as well as the great vessels. Recent advance of Doppler echocardiography makes it possible not only to examine the blood flow velocity but also to estimate the pressure gradient in the cardiovascular system. Moreover, advent of transesophageal echocardiography permits the routine visualization of certain cardiac regions that often cannot be visualized from the transthoracic views, such as the left atrial appendage and pulmonary vein. By using these echocardiographic techniques, the presence, severity, and hemodynamic consequences of heart failure due to various cardiovascular diseases can be determined noninvasively and repeatedly.

Adult↗
PubMed1992

Effect of changing afterload and inotropic states on inner and outer ventricular wall thickening.

Effect of changing afterload and inotropic states on inner and outer ventricular wall thickening. Am. J. Physiol. 263 (Heart Circ. Physiol. 32): H109-H116, 1992.--To study the differing behaviors of the inner (IH) and outer halves (OH) of the left ventricular (LV) free wall during an increasing afterload and changing inotropic states, we determined the LV pressure (LVP) and transmural (TM) and OH wall thickness (WTTM and WTOH) by sonomicrometry in 11 anesthetized dogs. The percent systolic wall thickening (% delta WT) and the fractional contribution (FC) were calculated. At rest, % delta WT of TM, IH, and OH were 22 +/- 1 (mean +/- SE), 33 +/- 3, and 13 +/- 2 (P less than 0.01 vs. IH), respectively. The FC of IH and OH were 74 +/- 5 and 29 +/- 4% (P less than 0.01 vs. IH), respectively. During increasing afterload by aortic constriction (AC) without drugs, % delta WT in IH was reduced to 22 +/- 2%, associated with unchanged % delta WT in OH (12 +/- 3%), whereas the FC of IH and OH were not altered from resting values. During AC with dobutamine infusion (3 micrograms.kg-1.min-1), the % delta WT and FC in each layer were not reduced from resting values. On the other hand, during AC with propranolol (2 mg bolus iv), the reduction of % delta WT in IH was greater (from 29 +/- 4 to 15 +/- 6%, P less than 0.01) than that in OH (from 11 +/- 2 to 10 +/- 3%; P less than 0.01 vs. IH). The FC in the IH was decreased (56 +/- 16%) by AC with propranolol, so that the difference in FC between IH and OH became insignificant (FCOH 40 +/- 13%, P greater than 0.1 vs. FCIH).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Mechanism of augmented left atrial pump function in myocardial infarction and essential hypertension evaluated by left atrial pressure-dimension relation.

To analyze left atrial (LA) pump function in normal subjects, in patients with essential hypertension and in patients with a healed myocardial infarction, LA dimension (aortic-root echogram) and pressure (catheter-tip manometer) were simultaneously recorded in 25 patients (8 normal subjects, 7 with hypertension and 10 with myocardial infarction). The pressure-dimension relation of the left atrium was composed of 2 loops: the A loop (expressing the pump function of the left atrium) and the V loop. LA dimension at the beginning of active LA shortening was significantly greater in hypertensive subjects (33 +/- 3 mm) and in those with myocardial infarction (32 +/- 4 mm) than in normal subjects (28 +/- 3 mm) (p less than 0.01, p less than 0.05, respectively). The area of the A loop significantly increased in subjects with hypertension (48 +/- 3 mm Hg.mm, p less than 0.01) and in subjects with myocardial infarction (29 +/- 10 mm Hg.mm, p less than 0.05), compared with normal subjects (20 +/- 8 mm Hg.mm). The mean fractional shortening velocity of the left atrium significantly increased in subjects with hypertension, compared with normal subjects and those with myocardial infarction (p less than 0.05 for both). LA peak wall tension during the LA active contraction period significantly increased with hypertension and with myocardial infarction, compared with normal subjects (p less than 0.01, p less than 0.05, respectively). The area of the A loop was directly proportional to the LA dimension at the beginning of active LA shortening (r = 0.53), p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Characteristics of blood flow velocity patterns of central systemic veins in healthy adults assessed by Doppler echocardiography.

To evaluate the differences in shape and phase lag of the flow velocity curves in the superior (SVC) and inferior (IVC) venae cavae and the hepatic vein (HV), Doppler echocardiographic examination was performed in 40 healthy adults (aged 20 to 67 years, mean +/- SD: 39 +/- 12 years). Flow velocity patterns in each vein were characterized by 4 major deflections: S wave, a systolic forward flow; D wave, a diastolic forward flow; A wave, a small backward flow or reduction of diastolic forward flow due to atrial contraction; and O wave, a small backward flow or reduction of forward flow after the second heart sound. Except for a reduced phasic flow in a collapsed IVC, the venous flow velocity recordings in each vein demonstrated very similar pulsatile patterns and small differences in mean time lags of less than 50 msec. In general, the lowest values of peak A/peak S, peak O/peak S and peak D/peak S were observed in HV flow and the highest in IVC flow. Backflows of A and O waves were prominent in HV flow, but small and least frequent in IVC flow. These data suggest that the baseline of the central venous flow recordings might shift downward in HV flow and upward in IVC flow. However, even if both the baseline shift and amplitude of the flow curve were normalized in each venous flow velocity curve, apparent differences in shape of the flow velocity curves would remain. We concluded that the characteristics and differences of each central venous flow velocity pattern should be noted in studies of these areas.

Adult↗
PubMed1990

Effects of the partial beta 1-adrenergic agonist, xamoterol, on hemodynamics and regional myocardial function during acute coronary occlusion in dogs.

Xamoterol is a partial beta 1-adrenergic agonist that has combined beta 1-stimulating and beta 1-blocking actions. We studied the effects of xamoterol on hemodynamics and regional left ventricular (LV) function after circumflex coronary artery occlusion in eight anesthetized dogs. Left ventricular systolic wall thickening (%WT: sonomicrometry) was measured in nonischemic, marginal, and ischemic zones. Xamoterol (350 micrograms/kg i.v.) increased the maximum LV pressure (dP/dt) by 62% and aortic flow (AOF) by 52% and decreased LV end-diastolic pressure (EDP) but did not change heart rate (HR) and peak LV pressure (LVP). Xamoterol increased %WT in nonischemic (23.6 +/- 2.3 to 35.1 +/- 2.6%, p less than 0.05) and marginal (5.0 +/- 0.6 to 12.0 +/- 1.5%, p less than 0.05), but not in the ischemic region [-5.7 +/- 0.7 to -2.7 +/- 0.3%, not significant (NS)]. The beta 1-blocking action of xamoterol was evaluated. Xamoterol significantly attenuated the increase in HR and maximum dP/dt caused by isoproterenol (0.1 microgram/kg/min). %WT in each region was maintained at the level caused by xamoterol after isoproterenol. Thus, xamoterol improved cardiac function, yet prevented excessive stimulation by catecholamine in the presence of acute myocardial ischemia.

Acute Disease↗
PubMed1990

Change of left atrial systolic pressure waveform in relation to left ventricular end-diastolic pressure.

The relation between the left atrial systolic pressure waveform and left ventricular end-diastolic pressure was observed in 17 patients who underwent diagnostic cardiac catheterization. Left atrial pressure and left ventricular pressure were simultaneously recorded from a multisensor catheter before and during angiotensin infusion. Left ventricular systolic pressure and left ventricular end-diastolic pressure were 133 +/- 17 and 12.3 +/- 3.2 mm Hg, respectively, before angiotensin infusion and increased to 168 +/- 18 (p less than 0.01) and 19.4 +/- 4.5 mm Hg (p less than 0.01), respectively, during infusion. The left atrial systolic pressure curve consisted of two positive waves--a first wave (A) and a second wave (A'). The A and A' wave pressures were 11.6 +/- 2.3 and 10.2 +/- 3.9 mm Hg, respectively, before angiotensin infusion and 16.5 +/- 2.9 (p less than 0.01) and 18.1 +/- 4.7 mm Hg (p less than 0.01), respectively, during infusion. The ratio of A'/A of left atrial systolic pressure was 0.81 +/- 0.27 before angiotensin infusion and 1.08 +/- 0.14 (p less than 0.01) during infusion. The ratio of A' to A of left atrial systolic pressure was linearly related to left ventricular end-diastolic pressure before and during (p less than 0.01) angiotensin infusion. The amplitude of the A wave exceeded that of the A' wave at normal left ventricular end-diastolic pressures. However, as the left ventricular end-diastolic pressure increased either at rest or during angiotensin infusion, the amplitude of the A' wave increased and often exceeded that of the A wave. These results suggest that the second (A') wave might be attributed to the increased reflection associated with increased left ventricular end-diastolic pressure.

Adult↗
PubMed1989

Left atrial conduit function for left ventricular filling dynamics in patient with myocardial infarction.

This study observed the left function in determining filling dynamics of the left ventricle in patients with myocardial infarction. The study consisted of eight control subjects and ten patients with myocardial infarction. The left ventricular filling volume is considered to be composed of the left atrial passive emptying, active emptying, and conduit volumes. The change of left ventricular filling volume was correlated with that of conduit volume (r = .87, P less than .01). However, the change of left ventricular filling volume did not have any correlation to those of left atrial passive emptying and active emptying volumes. These results suggested that the left atrial conduit function was important in determining filling dynamics of the left ventricle.

Adult↗
PubMed1989

Hemodynamic benefits of long-term bunazosin (alpha-1 blocker) therapy in rats with myocardial infarction and heart failure.

To determine whether bunazosin (alpha 1-adrenoceptor blocking agent) can alter the hemodynamic profile of chronic heart failure secondary to myocardial infarction, the drug was administered to Wistar rats 4 weeks after coronary ligation, and continued for 4 weeks. In rats without bunazosin treatment, the left ventricular end-diastolic pressure (LVEDP) and the total vascular resistance index (TVRI) increased as a function of infarct size, while the cardiac index (CI) decreased. But in infarcted rats with bunazosin treatment, the mean aortic pressure and TVRI were reduced, the LVEDP was modestly lessened, and the CI was maintained. The greatest increase in CI after the treatment occurred in rats with infarcts of small and moderate size. Thus, long-term therapy with bunazosin improved LV dysfunction, relative to the size of infarction. This study suggests the beneficial effects of bunazosin therapy in patients with chronic heart failure.

Adrenergic alpha-Antagonists↗