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Biomedical subjects

K Harada

Publications and source records attributed to K Harada.

At least 541 records · Page 30Linked to original sources
PubMed1995

Comparison of venodilatory effect of amrinone and theophylline in human subjects.

Amrinone, a positive inotropic agent, is a selective phosphodiesterase III inhibitor and exerts vasodilatory effect on venous vessels. The present study was undertaken to compare the venodilatory effect of amrinone and theophylline, a nonselective phosphodiesterase inhibitor, in eight healthy male subjects. In a randomized crossover design, one of these drugs was infused into the dorsal hand vein preconstricted by phenylephrine and its diameter was measured using a linear variable differential transformer. The value of maximum vasodilation for amrinone (mean +/- standard deviation, 106% +/- 17%) was similar to that for theophylline (mean +/- standard deviation, 108% +/- 14%). However, the infusion rate of amrinone needed to induce 50% of maximum vasodilation was significantly less than that of theophylline (25 +/- 15 micrograms/minute vs. 192 +/- 87 micrograms/minute, respectively; P < 0.01). These findings suggest that the venodilatory activity of amrinone is more potent than that of theophylline in human subjects.

Adrenergic alpha-Agonists↗
PubMed1995

Effect of losartan, an angiotensin II receptor antagonist, on response of cortisol and aldosterone to adrenocorticotrophic hormone.

Many imidazole derivatives are shown to inhibit adrenal steroid biosynthesis. The present study was undertaken to examine an effect of another imidazole derivative, losartan (an angiotensin II receptor antagonist), on responses of cortisol and aldosterone to adrenocorticotrophic hormone (ACTH). Nine patients with essential hypertension were given placebo orally for 7 days and 50 mg of losartan for the next 9 days. Response of serum cortisol and plasma aldosterone to intramuscular ACTH injection were determined before and at the end of the treatment with losartan. Serum cortisol and plasma aldosterone significantly increased after ACTH injection in both periods of treatment (placebo and losartan). The increments in these parameters during treatment with losartan were not significantly different from those during treatment with placebo. These results suggest that the inhibitory effect of losartan on adrenal steroid biosynthesis is negligible.

Adrenocorticotropic Hormone↗
PubMed1995

Changes in transmitral and pulmonary venous flow patterns in the first day of life.

The purpose of this study was to see the relationship between changes in pulmonary venous flow velocities and those in transmitral flow velocities during the first day of life. A serial Doppler echocardiography was performed in 24 normal neonates at 2, 12, and 24 hours of age. The size of the ductus arteriosus was 4.3 +/- 0.5 mm at 2 hours and 2.1 +/- 0.7 mm at 12 hours, and closed in 21 of 24 neonates at 24 hours. The peak systolic pulmonary venous flow (peak S), peak diastolic pulmonary venous flow (peak D), peak D/S, peak velocity at early diastolic filling (peak E), and peak E/A, which were high at 2 hours, decreased significantly at 12 hours but remained constant thereafter. The size of the ductus arteriosus was found to be correlated with peak S, peak D, and peak D/S. There was a direct correlation between peaks E and D (r: 0.64, p < 0.01) as well as a direct correlation between peaks E/A and D/S (r: 0.36, p < 0.05). These results indicate that the diastolic pulmonary venous flow is determined by the same factors that influence the transmitral flow. These waveforms may reflect the increase in pulmonary circulatory volume by left-to-right shunting through the ductus arteriosus.

Blood Flow Velocity↗
PubMed1995

Growth inhibition of intracerebral rat glioma by transfection-induced human interferon-beta.

In our previous study on liposome-mediated transfection of the human interferon-beta (HuIFN-beta) gene into subcutaneously implanted human gliomas in nude mice, we found that HuIFN-beta was produced and secreted by the tumor cells and that the growth of solid tumors was completely inhibited. The present study investigated the growth-inhibitory effect of liposomes containing the HuIFN-beta gene inserted into a vector (pSV2IFN-beta) on T9 rat glioma implanted into the brains of rats. Tumor cells and liposomes containing pSV2IFN-beta or other additives were simultaneously injected into the brains of rats. HuIFN-beta was detected in solid gliomas growing in the brains of rats injected with liposomes and magnetic resonance imaging (MRI) showed that tumor growth was inhibited. In addition, the latent period until the appearance of neurological symptoms was significantly prolonged in rats treated with liposomes containing pSV2IFN-beta. However, the survival time of the treated rats was not significantly increased.

Animals↗
PubMed1995

Superoxide dismutases of muscle in mitochondrial encephalomyopathies.

Immunohistochemical analyses were made of the superoxide dismutases (Mn-SOD and Cu/Zn-SOD) in biopsied muscles from 7 patients with mitochondrial encephalomyopathies that included mitochondrial encephalomyopathy, lactic acidosis and strokelike episodes (MELAS), and chronic progressive external ophthalmoplegia (CPEO). Mn-SOD mainly was present in the subsarcolemmal region, but it also was found in a coarsely granular, reticular, or diffuse pattern of staining within the muscle fibers. These Mn-SOD-positive fibers corresponded almost completely to the ragged-red fibers. The immunoreaction for Cu/Zn-SOD was weakly positive in some of the muscle fibers positive for Mn-SOD. In CPEO, Mn-SOD-positive fibers predominantly showed decreased cytochrome c oxidase (COX) activity. In MELAS, Mn-SOD-positive fibers tended to be stained deeply for COX although a few were COX-negative. These findings suggest that Mn-SOD-positive fibers can be used to make a differential diagnosis between CPEO and MELAS and that in mitochondrial encephalomyopathies Mn-SOD in the ragged-red fibers may protect against oxidative stress.

Adult↗
PubMed1995

Reliable and sensitive method for determination of microcystins in complicated matrices by frit-fast atom bombardment liquid chromatography/mass spectrometry.

A reliable and sensitive method for determination of hepatotoxic microcystins in complicated matrices by frit-fast atom bombardment liquid chromatography/mass spectrometry (Frit-FAB LC/MS) is described. Immonium ions of constituent amino acids, which were obtained together with molecular ion species by FAB mass spectral analysis of standard microcystins RR, YR, LR, and [D-Asp3] and [Dha7]microcystins LR using flow injection system composed of Frit-FAB probe, showed potential for reliable identification of microcystins by Frit-FAB LC/MS. Frit-FAB LC/MS using a microbore column provided not only the baseline separation of standard microcystins RR, YR, and LR but 200-fold higher sensitivity than that using conventional column. Furthermore, when a selected ion monitoring (SIM) technique was used, the detection limits of microcystins RR, YR, and LR were 300, 350, and 400 pg, respectively, at a signal-to-noise ratio of 5:1, and calibration curves of each microcystin showed a linear relationship from 2 ng to 50 ng. Finally, identification and quantitative analyses of microcystins in water samples were carried out.

Chromatography, Liquid↗
PubMed1995

Novel monoclonal antibodies against microcystin and their protective activity for hepatotoxicity.

Six monoclonal antibodies (MAbs) to microcystin-LR (MCLR), a cyclic heptapeptide hepatotoxin isolated from the cyanobacterium Microcystis aeruginosa, were produced. They showed the protective effects on hepatotoxicity of MCLR in vitro and in vivo, and on the inhibition of protein phosphatase by MCLR. Competitive enzyme-linked immunosorbent assays with various microcystins revealed that the six MAbs recognized a part of the molecule, in particular, a tertial structure around Adda, 3-amino-9-methoxy-2,6,8,-trimethyl-10-phenyldeca-4,6-dienoic acid. The specificity of these MAbs varied slightly. In primary rat hepatocyte cultures, all MAbs showed protective effects against the MCLR-induced cell damages, assessed by morphological changes, lactate dehydrogenase release into the medium, and a calorimetric assay to measure the cell viability using a tetrazolium dye. The M8H5 MAb showing the highest affinity for MCLR blocked the lethal effects and hepatocellular damage to mice. In addition, M8H5 MAb recovered protein phosphatase 2A inhibition by MCLR in a dose-dependent manner, while phosphatase inhibition by okadaic acid was not affected. Thus, the MAbs specifically reacted with the microcystins and prevented their biological activities. This is the first report on the protective effects of specific monoclonal antibodies on MCLR-induced toxicity.

Animals↗
PubMed1995

Beta-adrenergic modulation of the collateral-dependent coronary microcirculation.

The effect of chronic, collateral-dependent perfusion on beta-adrenergic coronary microvascular responses was examined. Ameroid constrictors were placed on the proximal left circumflex (LCx) coronary artery in 16 pigs. In 8 pigs, heparinized saline containing vascular endothelial growth factor (VEGF) was administered into the perivascular space of the proximal LCx artery using an implanted osmotic pump. After 5-7 weeks, coronary arterial microvessels (70-150 microns) were studied in a pressurized (40 mm Hg) no-flow state with video-microscopy. beta-Adrenoceptor-mediated relaxations of isolated microvessels from the collateral-dependent LCx region to isoproterenol (P < 0.01) were markedly reduced, as were those to the adenylate cyclase activator forskolin (P < 0.01), compared to the respective response of vessels from the normally perfused left anterior descending artery region. Responses to the Gs-protein activator NaF showed a similar trend, but the differences were not significant. Chronic treatment with VEGF normalized responses to isoproterenol, NaF, and forskolin in the collateral-dependent LCx region. Blood flow in the LCx region increased in both control (P < 0.01) and VEGF-treated (P < 0.05) groups during rapid atrial pacing. The absolute increase in LCx blood flow was greater in the VEGF group than in the control group at rest (P < 0.05), but not during rapid pacing. Thus, beta-adrenergic microvascular relaxation is impaired in the collateral-dependent coronary microcirculation. The periadventitial delivery of VEGF improves myocardial perfusion to the collateral-dependent area and preserves beta-adrenergic-mediated relaxation of microvessels in the collateral-dependent myocardium.

Animals↗
PubMed1995

Cavernous sinus meningioma presenting as orbital apex syndrome. Diagnostic methods of dynamic MRI, spoiled GRASS (SPGR) image.

Orbital apex syndrome is a symptomatologic complex. In this paper, the usefulness of several clinical diagnostic MR methods in preparing for surgery is discussed. These include dynamic MRI and the spoiled GRASS (SPGR) image for a cavernous sinus meningioma presenting with orbital apex syndrome. A 53 year old man, who had right cavernous sinus tumor presenting with orbital apex syndrome, was examined by several new MRI techniques. The tumor was partially removed and fibroblastic meningioma was confirmed pathologically.

Humans↗
PubMed1995

Early blood-brain barrier disruption after high-dose single-fraction irradiation in rats.

We studied the effect of high-dose single-fraction irradiation on the permeability of the blood-brain barrier (BBB) in rat brains. Immunohistochemistry with an antibody to serum albumin was used as a sensitive method for detecting the extravasation of endogenous serum components. Extravasation of albumin was detected as early as 1 day after irradiation with 20 or 40 Gy. Immunoreactivity reached its maximum after 3 days, gradually decreased during the following few weeks and had disappeared by day 30. Extravasation was much greater after irradiation with 80 Gy and continued to increase during the whole period of the experiment (6 days). Disruption of BBB this early after irradiation has not been previously documented. The time course of observed serum albumin extravasation, however, agrees well with the previous ultrastructural evidence for increased BBB permeability after irradiation with 27 Gy in monkey brains. This transient impairment of BBB may contribute to the reversible neurological symptoms after radiosurgery. It may also allow drugs that normally not pass the BBB to do so and thus disperse in the brain when administered at this time.

Animals↗
PubMed1995

A super long-acting LH-RH analogue induces regression of hypothalamic hamartoma associated with precocious puberty.

We treated a 1-year-old female with a hypothalamic hamartoma and precocious puberty with leuprolide acetate depot, a super long-acting hormone-releasing hormone analogue (Tap-144-SR; [D-Leu6-[des-Gly10-NH2] LH-RH ethylamide acetate). The infant's major symptoms were genital bleeding and gynaecomastia. The LH-RH analogue (30 micrograms/kg) was injected subcutaneously once every 4 weeks. Clinical and laboratory manifestations of precocious puberty showed marked improvement. A follow-up after 16 months of treatment, the size of the tumour decreased significantly and remained unchanged for 2 years of further follow-up. To the best of our knowledge, this is the first hypothalamic hamartoma case in whom a decrease of tumour size under treatment with LH-RH analogue has been documented. But, because diagnosis of hamartoma is only based on neuroradiological and not on histological examinations, the possibility of a gangliocytoma cannot be excluded with certainty.

Delayed-Action Preparations↗
PubMed1995

Syringomyelia secondary to tonsillar herniation caused by posterior fossa tumors.

BACKGROUND: A number of patients diagnosed as having syringomyelia secondary to tonsillar herniation caused by posterior fossa tumors has recently been described, although the backgrounds of the affected patients were not studied. In order to determine the possible causative contribution of the tonsillar herniation, the present cooperative study was carried out. METHODS: A retrospective study was performed by five cooperating institutes. Magnetic resonance images (MRIs) of patients with posterior fossa tumors were reevaluated with particular attention to the existence of tonsillar herniation and syringomyelia. RESULTS: The total number of patients with posterior fossa tumors whose MRIs were reinvestigated was 164. In 24 out of the 164 patients, tonsillar herniation was apparent in the sagittal plane of the MRI. Syringomyelia was observed in five of the 24 cases with tonsillar herniation being a consistent associated finding. None of the individuals demonstrated any sensory disturbance directly corresponding to the syrinx formation. All but one of the five patients underwent surgical removal of the tumor, but no one required surgical treatment for the syrinx itself. Disappearance or shrinkage of the syrinx could be confirmed by postoperative MRIs in three of them. CONCLUSIONS: A simple mechanism of blockage of cerebrospinal fluid flow at the foramen magnum may play an important role in syrinx formation, as evidenced by the unexpectedly high incidence of cervical syrinx along with tonsillar herniation caused by posterior fossa tumors shown in the present study.

Adolescent↗
PubMed1995

Developmental changes in P300 wave elicited during two different experimental conditions.

Age-related correlations on auditory event-related potentials were studied using a task-relevant oddball paradigm in 175 normal subjects aged 4-21 years and age-related correlations in the "ignore" condition were studied in 108 normal subjects aged 1-21 years. In the ignore condition, subjects more than 4 years of age were instructed to read a book to divert attention from the auditory stimulus. From 4 to about 17 years of age, the latencies of task-relevant P300 in event-related potentials (ERPs) gradually shortened. In the ignore condition experiment, the P300 latency shortened progressively, but stabilized at about 12 years of age. Whereas P300 in the ignore condition likely corresponds to P3a described previously (passive attention), the conventional P300 wave corresponds to P3b (active attention). The findings indicate a developmental difference between the P3a and P3b potential.

Adolescent↗
PubMed1995

Mutations of a shuttle vector plasmid, pZ189, in Escherichia coli induced by boron neutron captured beam (BNCB) containing alpha-particles.

A shuttle vector, pZ189, carrying a bacterial suppressor tRNA marker gene (supF) was dissolved in Tris-EDTA buffer containing 0.3 M 10B-enriched boric acid and then irradiated with boron neutron captured beam (BNCB) produced by the nuclear reaction 10B (n,alpha) 7Li with thermal neutrons. A DNA repair-deficient mutant, KS46 (uvrA-), of Escherichia coli was transformed with the plasmid DNA, and the transformants carrying mutations on the supF gene were selected as nalidixic acid-resistant colonies. The mutation frequency (2.4 x 10(-4)) of pZ189 at the D10 dose was about 70 times greater than the spontaneous rate (3.5 x 10(-6)). The plasmid mutations were analyzed using DNA sequencers; 88% of them were base substitutions. A few minus-one frameshifts (7%) and deletions (5%) were detected. Among these base substitutions, transversions of G:C to T:A (42%) and G:C to C:G (29%) predominated. Twenty-seven percent of the base substitutions were G:C to A:T transitions; no A:T to G:C transitions were detected.

Alpha Particles↗
PubMed1995

Effect of local administration of epidermal growth factor on 9,10-dimethyl-1,2-benzanthracene-induced tumour formation in hamster cheek pouch.

The effect of local administration of epidermal growth factor (EGF) on 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced tumour formation was investigated in a hamster cheek pouch carcinogenesis model. DMBA-treated hamsters underwent either sialoadenectomy (groups 1 and 2) or a sham operation (groups 3 and 4). Thereafter, EGF (groups 1 and 3) or vehicle (groups 2 and 4) was applied to the cheek pouches for 6 weeks. Fourteen weeks after the beginning of the experiment, the number of cheek pouch tumours was significantly greater in EGF-treated hamsters than in vehicle-treated hamsters, irrespective of whether the submandibular glands had been removed. The number of forestomach tumours, induced by DMBA application to the cheek pouches, was also increased by EGF. These results suggest that EGF applied from the luminal side of the mucosa stimulates tumour formation in the hamster cheek pouch and forestomach.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1995

Direct 99mTc labeling of human immunoglobulin with an insoluble macromolecular Sn(II) complex.

An insoluble macromolecular Sn(II)(R-Sn) complex which strongly binds Sn(II) by chelation was applied to the direct 99mTc labeling of human immunoglobulin(IgG) to minimize the influence of Sn(II). 99mTc labeling was achieved at greater than 90% yield simply by the short-term mixing of IgGa containing > 2-SH groups per IgG molecule, 99mTc pertechnetate, and the R-Sn complex in pH 7 solution. The 99mTc-IgGa obtained by this labeling method has high stability based on the thiol-specific binding of 99mTc without transchelation from another weakly bound 99mTc-complex.

Animals↗