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Biomedical subjects

K Takano

Publications and source records attributed to K Takano.

At least 235 records · Page 13Linked to original sources
PubMed1996

Dynamic pulmonary SPECT of xenon-133 gas washout.

UNLABELLED: A triple-detector SPECT data acquisition mode of "continuous repetitive rotation acquisition" was applied to dynamic pulmonary SPECT with 133Xe gas. METHODS: Subjects included 7 healthy volunteers, 22 patients with a space-occupying mass lesion, 22 with obstructive lung disease and 10 with restrictive lung disease. Following rebreathing of 133Xe, equilibrium and washout SPECT images during spontaneous breathing were acquired every 30 sec for 5-7 min. Regional 133Xe washout was assessed by the real half-time (T1/2) and mean transit time (MTT) images. RESULTS: SPECT and MTT images represented a gravity-induced gradient of ventilation in normal lungs and detailed the distribution of heterogeneous 133Xe washout in patient's lungs with or without abnormalities on chest x-ray CT. The T1/2 (111.4 +/- 26.4 sec) and its coefficient of variation (0.36 +/- 0.13) in obstructive lung diseases were significantly different from those (56.8 +/- 3.9 sec and 0.16 +/- 0.15) in restrictive lung diseases (p < 0.001, p < 0.05, respectively). Comparison of SPECT and planar studies assessed in 19 patients revealed superiority of SPECT in detecting ventilatory abnormalities and a high correlation of T1/2 between the two studies ( r= 0.977, p < 0.001). CONCLUSION: This modality has excellent potential for elucidating the distribution and nature of ventilatory abnormalities.

Administration, Inhalation↗
PubMed1995

CCAAT/enhancer-binding proteins alpha and beta interact with the silencer element in the promoter of glutathione S-transferase P gene during hepatocarcinogenesis.

We have previously identified a silencer in the glutathione S-transferase P (GST-P) gene which is strongly and specifically expressed during chemical hepatocarcinogenesis. At least three trans-acting factors bind to multiple cis-elements in the silencer. One of them, Silencer Factor-B (SF-B), is identical with CCAAT/enhancer-binding protein beta (C/EBP beta) and binds to GST-P Silencer 1 (GPS1). Many C/EBP beta binding sites are recognized by each of the C/EBP isoforms. Western blot analyses of C/EBP isoforms during chemical hepatocarcinogenesis revealed a decrease of C/EBP alpha expression. However, there was no change in C/EBP beta level. In the nuclear extracts from normal liver, C/EBP alpha was the dominant form that bound to GPS1, whereas both C/EBP alpha and C/EBP beta bound to GPS1 in the nuclear extracts from carcinogenic liver. Furthermore, transfection assays showed that C/EBP alpha not only repressed the GST-P promoter activity but also attenuated the transcriptional stimulation by C/EBP beta. These observations strongly suggest that the ratio of C/EBP alpha to C/EBP beta is one of the important factors for the GST-P silencer activity, and the decrease of this ratio during hepatocarcinogenesis reduces the silencer activity and, consequently, increases the GST-P expression.

Animals↗
PubMed1995

Contribution of hydrophobic residues to the stability of human lysozyme: calorimetric studies and X-ray structural analysis of the five isoleucine to valine mutants.

In order to understand the contribution of hydrophobic residues to the conformational stability of human lysozyme, five Ile mutants (Ile --> Val) in the interior of the protein were constructed. The thermodynamic parameters characterizing the denaturation of these mutant proteins were determined by scanning calorimetry, and the three-dimensional structure of each mutant protein was solved at high resolution by X-ray crystallography. The thermodynamic analyses at 64.9 degrees C and at pH 2.7 revealed the following. (1) The stabilities of all the mutant proteins were decreased as compared with that of the wild-type protein. (2) The changes in the calorimetric enthalpies were larger than those in the Gibbs energies, and were compensated by entropy changes. (3) The destabilization mechanism of the mutant proteins differs, depending on the location of the mutation sites. X-ray analyses showed that the overall structures of all the mutant human lysozymes examined were identical to that of the wild-type protein, and only small structural rearrangements were observed locally around some of the mutation sites. The most striking change among the mutant proteins was found in the mutant protein, 159V, which contains a new water molecule in the cavity created by the mutation. The thermodynamic stabilities of the mutant proteins are discussed in light of the high-resolution X-ray structures of the wild-type and five mutant human lysozymes examined.

Calorimetry, Differential Scanning↗
PubMed1995

Regional ventilatory evaluation using dynamic SPET imaging of xenon-133 washout in obstructive lung disease: an initial study.

Regional ventilatory abnormalities in obstructive lung disease were evaluated by dynamic single-photon emission tomography (SPET) of pulmonary washout of xenon-133 (133Xe) gas. The subjects included seven healthy volunteers. 17 patients with obstructive lung disease, and seven patients with restrictive lung disease. Following 6 min of inhalation of 133Xe gas (60-72 MBq/l), equilibrium and subsequent washout SPET images during spontaneous breathing were sequentially acquired every 30 s for 6-7 min, using a triple-head SPET system with the return mode of continuous repetitive rotating acquisition. A gravity-induced gradient of ventilation was demonstrated in the volunteers' lungs. Compared with the normal subjects, all the patients with obstructive disease showed abnormal 133Xe retention on the washout SPET images, with or without abnormalities on chest X-ray computed tomography, whereas the patients with restrictive disease did not show any significant delays in washout. This modality may assist in the evaluation of the three-dimensional dynamic process of ventilatory abnormalities in obstructive lung disease.

Adult↗
PubMed1995

Protein kinase C-mediated inhibition of an inward rectifier potassium channel by substance P in nucleus basalis neurons.

In nucleus basalis neurons, substance P (SP) causes a slow excitation, mediated through a pertussis toxin-insensitive G protein, by suppressing an inward rectifier K+ channel. Here we report that SP applied outside the patch pipette inhibited the single-channel activity, recorded on-cell, of the inward rectifier. The PKC inhibitors staurosporine and PKC(19-36) suppressed this effect in whole-cell mode and in on-cell single-channel mode. A diacylglycerol analog mimicked the SP effect, and PKC(19-36) suppressed this analog effect. SP irreversibly suppressed the inward rectifier in neurons treated with okadaic acid. These results indicate that a diffusible messenger mediates the SP effect, that its signal transduction involves phosphorylation by PKC, and that dephosphorylation by a serine/threonine protein phosphatase mediates its recovery.

Alkaloids↗
PubMed1995

Frequent natural killer cell abnormality in children in an area highly contaminated by the Chernobyl accident.

Since January 1991, we have been performing thyroid surveys and hematologic and immunologic screening on children in Chechersk, Belarus, a city situated in one of the areas most seriously contaminated with high levels of radionuclides after the Chernobyl accident. Ten children selected from 713 children because of goiter did not show a decrease in humoral immunity or in the number and function of T cells. By contrast, natural killer (NK) cell activity against K562 cells was depressed in 4 of these 10 children. The clinical and laboratory findings indicated that previously reported diseases with NK cell dysfunction could be excluded. A comparative analysis of NK cell activity in children from areas with and without high 137Cs levels revealed a high frequency of abnormal NK cell activity only in children from the area contaminated by radioactive fallout. In addition, there was no correlation between NK cell activity and NK cell number as percentage in the children from the area with high 137Cs levels. Neither activity nor number of NK cells was correlated with the body content of 137Cs. Thus, the frequent abnormality of NK cell function may not have been due to actual internal exposure to the long-lived radionuclide.

Adolescent↗
PubMed1995

Glomerulonephritis associated with MRSA infection: a possible role of bacterial superantigen.

We report 10 cases of glomerulonephritis following methicillin-resistant Staphylococcus aureus (MRSA) infection. The clinical features of this syndrome were an abrupt or insidious onset of rapidly progressive glomerulonephritis (RPGN) with nephrotic syndrome and occasionally purpura, following MRSA infection. The renal histologic findings showed a variety of types of proliferative glomerulonephritis with varying degrees of crescent formation; immunofluorescence revealed of glomerular deposition of IgA, IgG, and C3. Laboratory findings showed polyclonal increases of serum IgA and IgG, with high levels of circulating immune complexes (ICs). Increased numbers of DR+CD4+, and DR+CD8+T cells were observed in the peripheral circulation, with a high frequency of T cell receptor (TCR) V beta + cells. MRSA produced enterotoxins C and A and toxic shock syndrome toxin (TSST)-1, all of which are known to act as superantigens. From the above observations, we speculate that post-MRSA glomerulonephritis may be induced by superantigens causing production of high levels of cytokines, and polyclonal activation of IgG and IgA. The formation of ICs containing IgA and IgG in the circulation result in development of glomerulonephritis and vasculitis. Accordingly, microbial superantigens may play an important role in the pathogenesis of this unique syndrome of nephritis and vasculitis.

Adult↗
PubMed1995

Occupational exposure in pediatric cardiac catheterization.

Radiation doses to staff involved with pediatric cardiac catheterization were measured using thermoluminescent dosimeters in 18 procedures. The average doses to the lens and thyroid, and the effective dose per procedure to the main operating physicians was 88, 180, and 8 microSv, respectively; to assistant physicians, 23, 51, and 2 microSv; and to technicians, 23, 27, and 2 microSv. In some procedures, the dose to the technician's hand approached 1,500 microSv. The doses received by physicians were proportional to cineangiographic time but with no correlation with integrated currents. The number of procedures which may be performed in a year by individual staff members was estimated to be 430 and 2,780 procedures for physicians and assistants, respectively. It was suggested that the front of the neck is an adequate position for the dosimeter to measure doses during pediatric catheterization.

Adolescent↗
PubMed1995

Zonisamide: electrophysiological and metabolic changes in kainic acid-induced limbic seizures in rats.

We studied the pharmacological mechanism of zonisamide (ZNS) using an electrophysiological and autoradiographical method in a limbic seizure model in rats. Limbic seizure status epilepticus was induced by a unilateral microinjection of kainic acid (KA) into the amygdala. Initially, observed seizures were limited to the side of the injected amygdala and then propagated to bilateral sensorimotor cortex. Eighty minutes after injection, secondarily generalized seizure status epilepticus was induced, with each seizure lasting approximately 30 s and recurring every 5 min. ZNS 100 mg/kg was administered intravenously (i.v.) during the generalized seizure. Forty minutes after ZNS administration, epileptic activity was observed only at the KA-injected amygdalar site and spikes were not observed in the bilateral sensorimotor cortex. We studied local cerebral glucose utilization (LCGU) after ZNS or saline administration using an autoradiographical method in the same limbic seizure preparation. In the ZNS group, LCGU decreased in the ipsilateral sensorimotor cortex and hippocampus, whereas in the controls LCGU increased in these structures. On the other hand, ZNS did not suppress the epileptic activity of the primary focus and no decrease in LCGU was observed in the KA-injected amygdala. ZNS inhibited seizure propagation from the epileptogenic focus but did not suppress the epileptic activity of the focus. Our results suggest that ZNS is effective for the treatment of secondarily generalized seizure.

Animals↗
PubMed1995

Mechanisms of action of somatostatin on human TSH-secreting adenoma cells.

The mechanisms of somatostatin (SRIH) action on thyroid-stimulating hormone (TSH) secretion were examined using human TSH-secreting adenoma cells. SRIH (10(-7) M) inhibited TSH secretion through a pertussis toxin-sensitive G protein. SRIH also inhibited forskolin- and 8-bromo-adenosine 3',5'-cyclic monophosphate (8-BrcAMP)-induced TSH secretion. The mechanisms of this inhibition were investigated by measuring intracellular Ca2+ concentration ([Ca2+]i) and by electrophysiological experiments. Application of 10(-7) M SRIH reduced the [Ca2+]i, whereas forskolin and 8-BrcAMP increased the [Ca2+]i. Simultaneous application of SRIH abolished the forskolin-and the 8-BrcAMP-induced [Ca2+]i increase, indicating that the SRIH-induced decrease in [Ca2+]i was independent of the reduction in intracellular cAMP. Under current clamp using the whole cell clamp, 10(-7) M SRIH hyperpolarized the membrane and arrested Ca(2+)-dependent action potentials, which accounted for the SRIH-induced decrease in [Ca2+]i. Voltage clamp experiments revealed that this membrane hyperpolarization resulted from the activation of an inward-rectifying K+ current through a pertussis toxin-sensitive G protein. Intracellular injection of cAMP (100 microM) through the patch pipette did not abolish the SRIH-induced K+ current, indicating that the activation of SRIH-induced K+ channels was independent of intracellular cAMP. From these data, we concluded that SRIH-induced membrane hyperpolarization was responsible for the [Ca2+]i decrease, which in turn inhibited TSH secretion. Application of thyrotropin-releasing hormone (TRH; 10(-7) M) caused an increase in the [Ca2+]i, composed of an initial transient increase followed by a sustained increase. SRIH inhibited the sustained increase in [Ca2+]i. SRIH also inhibited the TRH-induced decrease in the membrane conductance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1995

Long-term effects of growth hormone treatment on height in Turner syndrome: results of a 6-year multicentre study in Japan. Committee for the Treatment of Turner Syndrome.

Patients with Turner syndrome have many somatic characteristics, including short stature. We report the results of a 6-year multicentre clinical trial of recombinant human growth hormone (GH) therapy in 63 patients with Turner syndrome. Twenty-six patients received GH at a dose of 0.5 IU/kg/week, while 37 received GH, 1.0 IU/kg/week, by daily subcutaneous injection. At the start of GH treatment, there was no significant difference between the two groups in chronological age, bone age, height or growth rate. Both treatment groups showed a significant growth increase during treatment. The current mean height of the 12 patients over the age of 16 treated with GH, 0.5 IU/kg/week, is 145.1 +/- 4.7 cm, and in the 16 patients treated with GH, 1.0 IU/kg/week, is 144.0 +/- 2.2 cm. In conclusion, treatment with GH does increase final height in patients with Turner syndrome. However, further studies are needed to determine the optimum age for the initiation of GH therapy, the best dose regimen and the optimal time and manner of sex and anabolic steroid use.

Body Height↗
PubMed1995

Rapid and accurate estimation of creatinine clearance in the muscle-wasted elderly by computed tomography.

To develop a new method for accurately predicting creatinine clearance (Ccr) in the debilitated elderly without urine collections, the total muscle volume of both thighs (MV thigh), as a new predictive parameter, was calculated using computed tomography in 68 debilitated patients aged 61-92 years. A regression line between 24-hour urinary creatinine excretion and MV thigh was divided by serum creatinine (Scr), and then the following formula was derived: Ccr (ml/min) = 9 x [MV thigh (cm3) - 100]/[1,000 x Scr (mg/dl)] Predicted Ccr by the new method more closely correlated with measured Ccr (r = 0.862) than did predicted Ccr by Cockcroft and Gault's method (the C-G method) (r = 0.727). Statistical analysis of prediction error (= predicted Ccr-measured Ccr) suggested that the new method could provide more accurate and less biased estimations of Ccr than did the C-G method, even in patients with renal insufficiency. By using computed tomography, we have proposed a more accurate method for predicting Ccr of the debilitated elderly than the C-G method, although the new method has inherent disadvantages of radiation exposure and high cost.

Aged↗
PubMed1995

Increase of plasma sialic acid upon UV-B irradiation in mouse.

In many inflammatory conditions including burns, the plasma sialic acid level rises as an acute responder. Sunburn is a kind of burn. In this study, sunburn was experimentally caused in mice by UV-B irradiation and their plasma sialic acid levels were measured. The levels increased, and reached the maximum 3 d after irradiation. This level was maintained for about 2 d, then it returned to normal within about one week. The increase in the level correlated with the UV dose and the severity of inflammation resulting in sunburn. This assay system was applied to assess the virtue of UV-cut cream in experimental sunburn.

Animals↗
PubMed1995

The penumbra, therapeutic time window and acute ischaemic stroke.

There is a great deal of evidence that an ischaemic penumbra exists in animals and humans after the occurrence of focal brain ischaemia (Hossmann, 1994). The concept of the penumbra leads to the idea of a therapeutic time window. Because, if the region of irreversible injury (infarction) after focal ischaemia evolves in time and space, then the possibility of therapy to interfere becomes a tenable hypothesis. All of the acute stroke therapies given after onset have their basis from this hypothesis of a therapeutic time window (Fisher, 1995). As previously alluded to, a more apt term might be a window-shade, because this metaphor suggests a more dynamic event. The time and location of potentially salvageable ischaemic brain tissue after ischaemic stroke is a moving target and many unanswered questions remain. The data from animal stroke models support 2-3 hours as the time when intervention is likely to be beneficial in rats. Non-human primate data are scarce, but the few studies available do imply that at 3-4 hours after stroke onset some ischaemic tissue remains potentially salvageable. In humans, we really do not know what the time window is and we must remember that it is likely to be highly variable among individuals. This variability relates to many factors including the status of collateral flow, patient age, coexistent metabolic abnormalities (i.e. hyperglycaemia), premorbid medications and many other confounding variables. All acute stroke intervention trials are trying to initiate therapy within 6-8 hours after onset and the earlier, presumably the better. However, this approach is based upon population averaging, since we have had no convenient and reliable mechanism to determine, if an individual patient has viable tissue when therapy can be started. The availability of an imaging modality that could distinguish the presence and extent of salvageable ischaemic tissue would greatly facilitate stroke therapy trials and ultimately the selection of patients when proven therapies are available. The new MRI techniques might afford this possibility. As we enter the exciting era of effective therapy for acute ischaemic stroke, the issues surrounding the therapeutic time window(shade) will become more critical, because it is this critical time that will define the success or failure of our interventions. Therefore it is incumbent upon basic stroke researchers and clinicians to continue to define the ischaemic penumbra and to develop readily applicable mechanisms to identify and treat this moving target.

Animals↗
PubMed1995

[Complete remission in acute myeloblastic leukemia (M0) after treatment with rhG-CSF].

A 57-year-old man was admitted because of fever and night sweat. The bone marrow was hypercellular with 86.4% blast cells. The diagnosis of AML (M0) was made, because the blast cells were negative for peroxidase stain and had CD13 and no lymphoid antigens in marker analysis. The patient was treated with BH-AC.TMP, BH-AC.MVP and low dose Ara-C without any hematological improvement, and even additional treatment with medium dose Ara-C resulted in 66.4% blast cells in the bone marrow. Subsequent administration of rhG-CSF (150 micrograms/day) by continuous intravenous infusion resulted in the decrease of the blast cells in the bone marrow to a level that was evaluated as complete remission. He remains in complete hematological remission at present. As shown in this case, rhG-CSF might be an effective agent for the treatment of AML, even if the mechanism of its effectiveness is unclear at present. Further clinical studies should will supply useful information to analyze the pathophysiology of AML.

Granulocyte Colony-Stimulating Factor↗
PubMed1995

[Evaluation of regional pulmonary 133Xe-gas washout with dynamic SPECT imaging obtained by a triple-headed SPECT system with continuous repetitive rotating acquisition mode].

The clinical potential of the dynamic SPECT in studying pulmonary washout of Xenon-133 (133Xe), using a triple-headed SPECT system (Toshiba GCA 9300A/HG, Japan) with continuous repetitive rotating acquisition mode, was preliminarily investigated in 6 healthy volunteers and 23 patients with various lung diseases. The equilibrium image was initially acquired for 1 min after breathing 133Xe gas (370 MBq) in a closed circuit for 6 min, and subsequently serial 133Xe-washout SPECT images were continuously acquired every 60 sec for 5-6 min. As the ventilation index, the real half time of regional activity was evaluated. The SPECT study demonstrated the gravity-induced gradient on ventilation in the normal subjects. In the various lung diseases, it allowed us to demonstrate visually and quantitatively the dynamic process and three-dimensional distribution of ventilation abnormalities, with or without chest radiographic abnormalities. These results indicate clinical potential of pulmonary dynamic SPECT of 133Xe-washout for elucidating the distribution and nature of ventilation abnormalities in various lung diseases.

Adult↗
PubMed1994

Hypercoagulable state under low-intensity warfarin anticoagulation assessed with hemostatic markers in cardiac disorders.

The hemostatic condition under low-intensity anticoagulation in cardiac disorders is not fully elucidated. The aim of this study was to ascertain whether hemostatic molecular markers are a useful assessment for anticoagulation to detect the hypercoagulable state. A hematologic study was performed in 75 outpatients, without thromboembolic episodes, treated with low-intensity anticoagulation (average international normalized ratio [INR] 1.72) because of potential cardiac sources of arterial emboli, and in 40 age-matched control subjects. The average level of thrombin-antithrombin III complex (TAT) was significantly lower in patients than in control subjects (p = 0.005), and the mean value of D-dimer was not statistically different between patients and control subjects. Although TAT correlated moderately with D-dimer (r = 0.45, p = 0.0001), INR did not correlate with TAT or D-dimer. Elevated TAT > 3.0 ng/ml and/or D-dimer S 150 ng/ml were observed in 15 patients (20.0%), whereas the remaining 60 patients (80.0%) had no obvious increase in the level of TAT or D-dimer at overall INR. Antithrombin III activity did not correlate significantly with INR, but protein C activity and free protein S antigen showed a significant negative relation to INR (r = 0.82, r = 0.62, respectively, p = 0.0001). Low-intensity anticoagulation was sufficient to reduce coagulation and subsequent fibrinolytic activation in cardiac disorders, but may not be sufficient in some patients with elevated TAT or D-dimer concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Antithrombin III↗