Biomedical subjects

T Hata

Publications and source records attributed to T Hata.

At least 145 records · Page 8Linked to original sources

PubMed1998

Barotropic phase transitions and pressure-induced interdigitation on bilayer membranes of phospholipids with varying acyl chain lengths.

The bilayer phase diagrams of a series of 1, 2-diacylphosphatidylcholines containing linear saturated acyl chain (C=13, 14, 15, 16, 17 and 18) were constructed by two kinds of high-pressure optical methods. One is the observation of isothermal barotropic phase transition and the other is the isobaric thermotropic phase transition. The temperature of the main transition from the ripple gel (Pbeta') phase to the liquid crystal (Lalpha) phase for each lipid was elevated by pressure. The slope of the temperature-pressure diagram, dT/dP, was in the range of 0.21-0. 23 K MPa-1 depending on the acyl chain length. The temperature of the pretransition from the lamellar gel (Lbeta') phase to the Pbeta' phase for each lipid was also elevated by pressure. The slope of phase boundary, dT/dP, for the pretransition was in the range of 0. 12-0.14 K MPa-1. Both temperatures of the main and pretransition under ambient pressure increased with an increase in acyl chain length. The chain length dependences of the pretransition and main transition temperatures describe smooth curves with no evidence of odd/even discontinuities. Pressure-induced interdigitated gel (LbetaI) phase was observed beyond 300 MPa for 14:0-PC, 175 MPa for 15:0-PC, 100 MPa for 16:0-PC, 80 MPa for 17:0-PC and 70 MPa for 18:0-PC, respectively. The minimum pressure for the interdigitation of lipid bilayer membranes decreased with an increase in acyl chain length in a manner of non-linear relation. The slopes of phase boundary between Lbeta' and LbetaI phases transformed from the negative slope to the positive slope as the pressure increases.

Lipid Bilayers↗

PubMed1998

Barotropic phase transitions of dioleoylphosphatidylcholine and stearoyl-oleoylphosphatidylcholine bilayer membranes.

In order to understand the effect of cis unsaturation on the thermotropic and barotropic phase behavior of phospholipid bilayer membranes, the phase transitions of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) bilayer membranes were observed by high-pressure optical method. With respect to DOPC bilayer membrane, the so-called main transition between the liquid crystalline (Lalpha) and the lamellar gel (Lbeta) phases was observed in water at above 0 degrees C under high pressure, in addition to the transition between the Lalpha and the lamellar crystalline (L(C)) phases in 50% aqueous ethylene glycol. The pressure of main transition increased linearly with an increase in temperature. Extrapolation of temperature (T)-pressure (P) phase boundary to ambient pressure suggests the temperature of the main transition to be -40.3 degrees C, which has never been found by the DSC method. On the other hand, the temperature of L(C)/Lalpha phase transition in 50% aqueous ethylene glycol was found to be -12.0 degrees C at ambient pressure. The main transition temperatures for DSPC, SOPC and DOPC are 55.6, 6.7 and -40.3 degrees C, respectively, at ambient pressure. The substitution of cis unsaturated chain for saturated chains of DSPC brings about the depression of the main transition temperature by about 48 (+/-1) degrees C for each chain. The volume changes (deltaV) associated with the transitions were calculated from the transition enthalpy (deltaH) and the slope of T-P diagram (dT/dP) by means of the Clapeyron-Clausius equation. The value of deltaV for the main transition of SOPC bilayer membranes was reduced to half the volume change for DSPC bilayers, which means the introduction of the cis double bond in the acyl chain of lipids brings about the reduction of deltaV because of the disordered packing of unsaturated chains in the gel phase of lipid bilayer membranes.

Biophysical Phenomena↗

PubMed1998

Inhibition of influenza virus RNA polymerase by 5'-capped short RNA fragments.

We have demonstrated that 5'-capped short RNA fragments inhibit the expression of chloramphenicol acetyltransferase (CAT) in the murine 76 cell line, derived which expresses the genes for the RNA polymerases (PB1, PB2, and PA) and the nucleoprotein (NP) of influenza virus in response to treatment with dexamethasone. We have synthesized 5'-capped short RNA fragments (8-13 ntds long) with a 5'-capped structure (m7GpppGm) using T7 RNA polymerase. The 5'-capped short RNA fragments (8-13 ntds long) were encapsulated in liposomes and were tested for their inhibitory effect by a CAT-ELISA assay using the clone 76 cells. The RNA fragments that were 9-12 ntds long showed inhibitory effects. In particular, the 9 ntds long RNA fragment, was highly inhibitory. On the other hand, the inhibitory effect of the 13 ntds long RNA fragment was considerably decreased in comparison with the other short RNA fragments. The minimal RNA chain length required for priming activity was found to be 12 ntds long. Furthermore, the 5'-capped RNA fragments exhibited higher inhibitory activities than the antisense phosphorothioate oligonucleotide (PB2-AUG-as, 20 ntds long) complementary to the site of the PB2-AUG initiation codon. Liposome encapsulation protected the RNA fragments in serum-containing medium and substantially improved their cellular accumulation.

DNA-Directed RNA Polymerases↗

PubMed1998

Interleukin-15 (IL-15) can replace the IL-2 signal in IL-2-dependent adult T-cell leukemia (ATL) cell lines: expression of IL-15 receptor alpha on ATL cells.

Interleukin-15 receptor (IL-15R) and IL-2R have the same beta and gamma chains, but IL-15R has a specific alpha chain distinct from that of IL-2Ralpha, which is indispensable for the high affinity binding of IL-15. In the present study, we examined four IL-2-dependent adult T-cell leukemia (ATL) cell lines for their IL-15R expression. All cell lines bound IL-15, which was not inhibited by a 100-fold excess amount of IL-2, proliferated in response to IL-15 to the same degree as to the stimulation with IL-2, and were maintained without IL-2. The responses to 1L-15 were inhibited by the antibodies against IL-2R beta or gamma chains but was not by the IL-2R alpha chain antibody. [125I]-IL-15 exhibited a single high-affinity binding with an apparent kd of 0.17 nmol/L. Reverse transcription-coupled polymerase chain reaction (RT-PCR) showed that the cell lines had the mRNA of IL-15R alpha. The cell lines also had IL-15 mRNA. Despite the presence of IL-15 mRNA, the cell lines did not secrete IL-15, and the culture supernatants of fresh ATL cells and plasma from the patients did not contain a detectable amount of IL-15 with a few exceptional cases, although fresh ATL cells also responded to IL-15. These results suggest that ATL cells have the complete form of IL-15R and respond to IL-15. Such an IL-15-dependent cell proliferation mechanism might be used in the development of ATL and for the invasion and proliferation of ATL cells in the visceral organs.

Adult↗

PubMed1998

Autonomic neuropathy in transgenic mice caused by immunotoxin targeting of the peripheral nervous system.

Autonomic neuropathy in several neurodegenerative disorders results from disturbance in physiological functions of different cell types in the central and peripheral nervous systems. For a clearer understanding of the etiology and pathogenesis of the autonomic disorders it is necessary to create animal models in which degeneration of the causative neuronal types can be induced. Immunotoxin-mediated cell targeting (IMCT) is a novel transgenic mouse technology for eliminating selective cell types with the cytotoxic activity of a recombinant immunotoxin anti-Tac(Fv)-PE40. In this study we conditionally disrupted peripheral catecholaminergic cells with IMCT to generate a mouse model developing autonomic failure based on primary defects of the sympathetic nervous system. Transgenic mice expressing human interleukin-2 receptor alpha subunit under the control of the dopamine beta-hydroxylase gene promoter were intravenously treated with a proper dose of anti-Tac(Fv)-PE40. The immunotoxin induced a selective loss of the target cells in peripheral tissues of the transgenic mice and an impairment of catecholamine metabolism in the tissues. Targeting of the peripheral catecholaminergic cells resulted in severe and progressive phenotypic abnormalities mainly characterized by cardiac dysfunction, hypoactivity, and hypothermia, which explain development of autonomic neuropathy. Our IMCT strategy is useful for elucidating the involvement of different neuronal types and their interactions in the development and symptom of autonomic disorders.

Animals↗

PubMed1998

A multivariate logistic regression analysis in predicting malignancy for patients with ovarian tumors.

OBJECTIVE: Our objective was to improve the preoperative diagnosis of ovarian malignancy using a multivariate logistic regression analysis on the basis of demographic, serologic, gray-scale morphological, and Doppler variables. METHODS: One hundred seventy-one patients with ovarian tumors (120 benign, 51 malignant including 9 tumors of low malignant potential) were studied with transvaginal B-mode, color, and pulsed Doppler ultrasonography before surgery. Based on the gray-scale ultrasound imaging, each tumor was classified as a unilocular cyst, multilocular cyst, unilocular cyst with solid parts, multilocular cyst with solid parts, or solid tumor. Intratumoral blood flow velocity waveforms were recorded on all tumors except unilocular cyst and were evaluated for resistance index (RI) and peak systolic velocity (PSV). Serum CA 125 levels were also measured. RESULTS: Twenty tumors were unilocular cysts and were all benign. Seventy tumors including all unilocular cysts which showed no flows were all benign. The remaining 101 tumors (50 benign, 51 malignant including 9 tumors of low malignant potential) presented intratumoral blood flows. Univariate and multivariate logistic regression analyses were conducted to identify variables predictive of ovarian malignancy in these 101 tumors. The variables included age, menstrual state, serum CA 125 levels, B-mode classification, RI, and PSV. In univariate analysis, menopause, the positivity of CA 125 (> or = 35 U/ml), and PSV larger than or equal to 10.4 cm/s were found to be significantly associated with malignant tumors. The PSV value of 10.4 cm/s was the median in benign tumors. Multivariate analysis showed that serum CA 125 levels (> or = 35 U/ml) (P = 0.002) and PSV (> or = 10.4 cm/s) (P < 0.001) were to be independent predictors of malignancy. CONCLUSION: These results suggest that intratumoral PSV is the strongest means of differentiating benign from malignant ovarian tumors with suspicious gray-scale ultrasonographic findings.

Adolescent↗

PubMed1998

Electrophysiological effects of amrinone on the automaticity and membrane current system of the rabbit sinoatrial node cells.

To elucidate the physiological role of phosphodiesterase (PDE) in cardiac pacemaker cells, we studied the electrophysiological effects of amrinone, an inhibitor of PDE type III, on the spontaneous action potential (AP) and membrane currents, using small preparations (0.2 x 0.2 x 0.1 mm) of rabbit sinoatrial (SA) node cells. Amrinone (0.1-1.0 mM) progressively increased the AP amplitude, maximal rate of depolarization, and spontaneous firing frequency, shortened the AP duration, and made the threshold potential more negative. In voltage-clamp experiments using double microelectrode techniques, 0.1 mM amrinone increased the Ca2+ current (I(Ca)) obtained on step depolarization from -40 to -10 mV by 25.86% +/-4.6% (P < 0.05, n = 6), the delayed rectifier K+ current (I(K)) tail obtained on repolarization from 10 to -60 mV by 22.8%+/-4.7% (P < 0.05, n = 6), and the hyperpolarization-activated inward current (Ih) at -90 mV by 19.5%+/-7.3% (P < 0.05, n = 6), respectively. Amrinone did not affect the slope factors of either the inactivation curve for I(Ca) (finfinity curve) or the activation curve for the delayed rectifier I(K) (pinfinity curve). These results suggest that this PDE III inhibitor exerts a positive chronotropic action by enhancing the availability and the conductance of all the tested membrane currents in rabbit SA node cells.

Action Potentials↗

PubMed1998

[A case report of intrathoracic aneurysm of left subclavian artery].

A case of intrathoracic aneurysm of the left subclavian artery is reported. The case was 68-year-old male. Chest CT and angiography revealed an aneurysm of left subclavian artery (LSA) located the proximal portion of LSA. The chest was opened by fourth intercostal thoracotomy. We evaluated the intima of distal aortic arch and LSA by introperative direct echography using a small probe (finger tip size). Since there was no calcification or mural thrombi at the distal aortic arch, the aneurysm was resected using partial cardiopulmonary bypass and the orifice of LSA was closed direct suture. LSA was reconstructed with knitted Dacron graft (8 mm). Postoperative course was uneventful.

Aged↗

PubMed1998

Pharmacokinetics and pharmacodynamics of FK143, a nonsteroidal inhibitor of steroid 5 alpha-reductase, in healthy volunteers.

The pharmacokinetics and pharmacodynamics of FK143, a new nonsteroidal inhibitor of steroid 5 alpha-reductase, were investigated in healthy volunteers, with use of plasma FK143 concentrations and serum dihydrotestosterone levels as an index for pharmacologic effects. The area under the plasma concentration-time curve from zero to infinity [AUC(0-infinity)] and maximum plasma concentration [Cmax] were increased dose proportionally after oral administration (100 to 500 mg) while subjects were in the fed state. The AUC(0-infinity) and Cmax after 500 mg oral administration during fed conditions were significantly larger than those during the fasted state, suggesting an increase of the absorption of FK143. Dihydrotestosterone concentrations after a single administration of FK143 (100 to 500 mg) during fed conditions decreased to about 65% of predose values and thereafter slowly recovered to the same levels as predose values at 168 hours. A combined pharmacokinetic-pharmacodynamic model was constructed with use of changes in dihydrotestosterone concentrations. The pharmacokinetic-pharmacodynamic profiles of FK143 after repeated administration were predictable with use of the pharmacokinetic-pharmacodynamic parameters obtained after a single administration of FK143.

5-alpha Reductase Inhibitors↗

PubMed1998

Cross tolerance to environmental stress and endotoxin.

Mild DIC-like phenomena develop in rodents exposed to environmental stress, induced by prolonged fluctuation in ambient temperature, known as SART (specific alternation of rhythm in temperature) stress, the symptoms being essentially similar to those produced by endotoxin. The aim of the present study was to investigate whether common mechanisms are involved in the stress-induced DIC-like phenomena and endotoxaemia. The mortality in mice after intraperitoneal injection with endotoxin at 8.3, 16.7 and 33.3 mg/kg increased in a dose-dependent manner. In the mice exposed to stress for 7 days, the death rate following endotoxin at 8.3 mg/kg was markedly lower than that in unstressed mice, although no difference was detected between the two groups following endotoxin at 16.7 and 33.3 mg/kg. Conversely, repeated administration of endotoxin at a low dose, 0.5 mg/kg, during exposure to stress for 7 days inhibited the stress-induced thrombocytopenia and hypofibrinogenemia. These findings indicate the development of cross tolerance to prolonged environmental stress and endotoxin, implying involvement of a common mechanism.

Animals↗

PubMed1998

Three-dimensional ultrasonographic assessments of fetal development.

OBJECTIVE: To visualize fetal surface anatomic structures in advancing gestation by use of three-dimensional ultrasonography with a specially developed abdominal three-dimensional transducer. METHODS: One hundred six normal fetuses from 9 to 40 weeks' gestation were studied with a specially developed abdominal three-dimensional transducer (3.5 MHz). This imaging system can provide conventional two-dimensional ultrasonography images and also can generate within seconds high-quality three-dimensional images in the surface and transparent modes with no need for an external workstation. We determined percentage of surface anatomic structures visualized at each trimester using two-dimensional and three-dimensional ultrasonography. RESULTS: The number and the clarity of surface anatomic structures increased from the first to the third trimester of pregnancy. The image quality was less distinct in the first trimester because of the small fetal size. The ability to view the fetal face, hands, and feet was better with three-dimensional ultrasonography than with two-dimensional ultrasonography in the first trimester (P < .05), whereas fetal genitals were viewed better with two-dimensional ultrasonography than with three-dimensional ultrasonography in the second and third trimesters (P < .05). CONCLUSION: Three-dimensional ultrasonography provides a new means of visualizing surface anatomic structures of the fetus in utero. Our results suggest that three-dimensional ultrasonography has the potential to be a supplement to two-dimensional ultrasonography and should be useful in evaluating fetal abnormalities in high-risk pregnancies.

Embryonic and Fetal Development↗

PubMed1998

Retinoic acids induce growth inhibition and apoptosis in adult T-cell leukemia (ATL) cell lines.

Adult T-cell leukemia (ATL) is a peripheral T-cell neoplasm caused by human T-cell leukemia virus type I (HTLV-I). Despite the administration of combined intensive chemotherapy, the reported survival time of patients with acute and lymphoma types of ATL is less than 10 months. We therefore examine the effects of all-trans-retinoic acid (ATRA), 9-cis-RA and 13-cis-RA and tried to elucidate the mechanisms of inducing growth inhibition and apoptosis by these RAs using four ATL cell lines established in our laboratory. All the investigated RAs inhibited cell growth and the cells were arrested at the G1 phase. Apoptosis was induced in three out of four cell lines. Among the growth regulatory proteins examined, the level of p21Waf1/Cip1 protein was found to increase after RA treatment, thus resulting in pRb hypophosphorylation which also induced the arrest of the cells at the G1 phase. In addition, the p53 level decreased at the same time. Fas-FasL system and the downregulation of CD25 (IL-2R/alpha) expression did not seem to be involved. Based on these findings, the ability of RAs to induce a remission of ATL is thus strongly suggested.

Adult↗

PubMed1998

The development of a sensitive and specific enzyme immunoassay for FK480, a novel cholecystokinin type-A receptor antagonist, in human plasma.

A sensitive and specific enzyme immunoassay for FK480, a novel cholecystokinin type-A (CCK-A) receptor antagonist, was developed to study the pharmacokinetics of the drug at low-dose administration using a specific monoclonal antibody. The high performance liquid chromatography (HPLC) method had been used for studying toxicokinetics, but its determination limit (2.5 ng ml-1) was too high for use in clinical studies. Subsequently we developed an enzyme immunoassay (EIA) using rabbit anti-FK480 serum (polyclonal antibody). It had higher sensitivity (0.1 ng ml-1) when 0.5 ml of plasma was used but its specificity was low because of the cross-reactivity of the metabolites of FK480. Therefore we produced several monoclonal antibodies for FK480 by cell fusion, and selected the antibody which was least cross-reactive for the isolated metabolites of FK480. Finally we developed a sensitive and specific EIA using this monoclonal antibody. The lower limit of quantification of this method was 0.2 ng ml-1 when 0.2 ml of human plasma was used. The coefficient of variation over the calibration range (0.2-10 ng ml-1) was less than 15%. We used this method for clinical studies, and it showed a good correlation to the HPLC method when plasma concentration was 2.5 ng ml-1 or more.

Animals↗

PubMed1998

Mycosis fungoides with involvement of the oral mucosa.

Mycosis fungoides (MF) is a T-cell lymphoma that predominantly affects the skin. Involvement of the oral tissues in MF is rare. A case of MF with involvement of the maxillary gingiva and cervical lymph nodes is presented. Electron-beam radiation with 40 Gy and systemic chemotherapy with vincristine and interferon gamma produced almost complete remission of the oral lesion while the persistent pain was relieved.

Antineoplastic Agents, Phytogenic↗

PubMed1998

Cytotoxic scalarane sesterterpenes from a sponge, Hyrtios erecta.

Novel scalarane sesterterpenes (1-4) were isolated from a sponge, Hyrtios erecta (order Dictyoceratida). They were characterized by means of spectral analyses, X-ray crystallography, and chemical reactions. Compound 1 showed potent in vitro and in vivo antitumor activities. In addition, the structure-activity relationship was also discussed using computer-assisted structure matching of 1 and aragusterols.

Animals↗

PubMed1998

Maternal ophthalmic artery Doppler velocimetry in normotensive pregnancies with small-for-gestational-age infants.

Our purpose was to evaluate whether the maternal ophthalmic artery pulsatility index in normotensive pregnancies with small-for-gestational-age (SGA) fetuses is different from that in normotensive pregnancies with appropriate-for-gestational-age (AGA) fetuses. The cross-sectional study involved a group of normotensive pregnant women at > 34 weeks' gestation; 16 had fetuses that were AGA and 13 had fetuses that were SGA. Color and pulsed Doppler ultrasonography was performed in the ophthalmic arteries in each case and the pulsatility index and mean velocity were calculated. The heart rate and mean arterial blood pressure were also recorded. The pulsatility index of the ophthalmic artery (2.04 +/- 0.39) in normotensive pregnant women with SGA fetuses was significantly lower than that (2.87 +/- 0.64) in normotensive pregnant women with AGA fetuses (p < 0.05). The mean velocity (15.0 +/- 2.7 cm/s) in the women with SGA fetuses was significantly higher than that (10.2 +/- 2.7 cm/s) in the women with AGA fetuses (p < 0.05). There was no significant difference in maternal heart rate or mean arterial blood pressure between the groups. These results suggest that vascular resistance in the maternal orbital circulation is reduced in pregnancies that are normotensive but which are associated with SGA fetuses.

Adult↗

PubMed1998

Three-dimensional ultrasonographic assessment of fetal hands and feet.

OBJECTIVE: The aim of this study was to describe fetal hands and feet using three-dimensional ultrasonography. DESIGN: This was a randomized prospective study. METHODS: Ninety-seven fetuses from 12 to 40 weeks' gestation were studied with a specially developed trans-abdominal three-dimensional transducer (3.5 MHz). The imaging system used in this study can provide conventional two-dimensional ultrasound images and can also generate, within seconds, high-quality three-dimensional images in the surface and transparent modes with no need for an external workstation. The rate of visualization of the hands/fingers and feet/toes at each gestational-age interval was calculated using two-dimensional and three-dimensional ultrasonography. RESULTS: The ability to visualize fetal hands/fingers and feet/toes was better with three-dimensional than with two-dimensional ultrasonography in the late first trimester (detection rates were 65% and 41% by three-dimensional ultrasonography for hands and feet, respectively, and 41% and 12%, respectively, by two-dimensional ultrasonography). For the early second trimester, detection rates were 82% for hands and 72% for feet by three-dimensional ultrasonography, and 54% for hands and 45% for feet by two-dimensional ultrasonography. Optimal visualization of the fetal fingers using three-dimensional ultrasonography was achieved between 28 and 35 weeks of gestation, although at this stage there were no significant differences in detection rates for hands and feet between two- and three-dimensional imaging. During this period it was possible with three-dimensional ultrasonography adequately to depict at least one hand in 93% of the fetuses at 28-31 weeks and in 88% at 32-35 weeks. The percentage of visualization of at least one fetal foot between 16 and 35 weeks using three-dimensional ultrasonography ranged from 50 to 85%. Before 15 weeks or after 36 weeks, the respective percentages decreased. CONCLUSIONS: Three-dimensional ultrasonography provides a novel means of visualizing fetal fingers and toes. Our observations suggest that three-dimensional ultrasonography may enhance the diagnostic potential of two-dimensional ultrasonography and might be useful in identifying fetal malformations and anatomical markers of chromosomal abnormalities prenatally in high-risk pregnancies.

Embryonic and Fetal Development↗

PubMed1998

A clinicopathological aspect of chorionic villous hemorrhage leading to formation of intervillous thrombosis.

Recently it was reported that chorionic villous hemorrhage (CVH) had a significant association with retroplacental hemorrhage (RPH). In this study, to determine whether CVH has a correlation with RPH or intervillous thrombosis (IVT), placentas associated with CVH were clinico-histopathologically investigated and compared to those with IVT. Obstetric complications in 32 cases with CVH were compared with 258 cases with IVT. Placental abruption was significantly higher (18.7%) in the CVH group than in the IVT group (5.03%) and the incidences of intrauterine fetal death (IUFD) as well as intrauterine growth retardation (IUGR) were also significantly higher (18.7% and 9.37%) in the CVH group than in the IVT group (3.10% and 2.32%). Of the pathological characteristics of the placentas with CVH, IVT was found in 46.8%, but marginal or retroplacental hemorrhages were seen in 34.3%, compared to 14.2% of the IVT group. Premature infants with low birth weight (under 2000 g) and before 36 weeks of gestation were born in 53.1% and 34.3% of cases with CVH placentas. CVH was not only located near the basal plate of the placentas and decidual hemorrhages, but was also highly associated with chorangiosis in 75% of cases. Using histological and ultrastructural studies in CVH cases, villous stroma was filled with fetal erythrocytes and leakage of blood cells was observed through a disruption of the trophoblast layer of hemorrhagic villi. In conclusion, it is suggested that CVH may rather be related to formation of the intervillous thrombosis than to RPH.

Chorionic Villi↗