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Biomedical subjects

M Hara

Publications and source records attributed to M Hara.

At least 541 records · Page 30Linked to original sources

[Properties of a hemolysin produced by group C streptococci isolated from hemolytic streptococcal infection in formosan squirrels].

The hemolysin produced by group C streptococci (GCH) has an isoelectric point (pI) of 5.6 and a molecular weight of 32,000 and shows hemolytic activity in the absence of 2-mercaptoethanol (2-ME). The hemolytic activity of GCH was compared to that of streptolysin S (SLS). These hemolysins did not differ with respect to the binding and release of hemoglobin (Hb). GCH was bound to phospholipids on the membranes of target erythrocytes, followed by the rapid released of K+ and slow Hb release after a relatively long lag time. GCH showed a lower hemolytic efficiency than SLS, reflecting the fact that these hemolysins destroy erythrocytes by slightly different mechanisms.

Animals↗

Plasma plasminogen activator inhibitor-1, tissue plasminogen activator and serum lipoprotein(a) after reperfusion therapy in acute myocardial infarction: comparison between sequential and direct percutaneous transluminal coronary angioplasty.

To determine which reperfusion therapy for acute myocardial infarction (AMI) is advantageous to avoid subsequent thrombotic coronary occlusion, 8 patients with AMI were studied. Four of them (group S) underwent sequential PTCA following unsuccessful intracoronary thrombolysis and the others (group D) direct PTCA. Serial changes in plasma plasminogen activator inhibitor-1 (PAI-1), plasma tissue plasminogen activator (t-PA) antigen and serum lipoprotein(a) levels were compared between the two groups. In group S, plasma PAI-1 levels showed no significant serial change after PTCA. However, in group D, plasma PAI-1 levels increased significantly 4-24 h after PTCA. We suggest that more attention should be focused on the prevention of thrombotic coronary closure as well as mechanical abrupt occlusion after direct PTCA.

Angioplasty, Balloon, Coronary↗

Urinary excretion of podocalyxin indicates glomerular epithelial cell injuries in glomerulonephritis.

Immunofluorescent study of urine sediments was performed to detect glomerular epithelial cell injuries using specific monoclonal antibody against podocalyxin, a glycoprotein that is prominently expressed on glomerular epithelial cells. Three kinds of structures (casts, granules and cells) were stained in urine sediments from various glomerular diseases. The presence of podocalyxin in urines was confirmed by absorption test, immunoelectron microscopy and Western blotting. Podocalyxin was detected in the urinary sediments of patients with various forms of glomerulonephritis, particularly those with acute onset. The amount of their urinary excretion apparently indicates the degree of the glomerular epithelial cell injuries in glomerular diseases.

Adolescent↗

Renal lesion of type Ia glycogen storage disease: the glomerular size and renal localization of apolipoprotein.

In order to investigate the glomerular size and renal localization of apolipoprotein in type Ia glycogen storage disease, a renal biopsy was performed in two proteinuric patients. Histopathological examination of the biopsy specimens revealed focal sclerotic glomerular sclerosis in both patients. The mean glomerular area was 21.6 +/- 11.6 x 10(3) microns 2, indicating enlargement of the glomeruli. Immunohistochemical staining of the specimens for apolipoprotein showed localization of apolipoprotein AI on the inner side of the glomerular capillary wall, and in proximal tubular epithelial cells. In one patient with a history of several episodes of hypoglycemia, treatment with corn starch improved the carbohydrate and lipid metabolic profile and reduced the daily urinary protein excretion from 2.23 to 0.5 g. These results suggest that focal sclerotic glomerular lesions associated with type Ia glycogen storage disease may be related to disorders of carbohydrate and lipid metabolism.

Adult↗

Role of recruited neutrophils in interleukin-8 production in dog trachea after stimulation with Pseudomonas in vivo.

Cell-free supernatant of Pseudomonas aeruginosa (PA) recruits neutrophils into the airways indirectly by inducing the production of chemotactic factors, including interleukin-8 (IL-8). PA products stimulate IL-8 expression selectively in surface airway epithelium, gland ducts, serous cells, and recruited neutrophils. To examine the relative contribution of neutrophils in IL-8 release in the airway lumen, we studied the effect of inhibition of neutrophil recruitment on IL-8 concentration in tracheal fluid after introduction of PA supernatant into the dog trachea in vivo. Tracheal superfusion with PA supernatant caused neutrophil recruitment and increased the IL-8 concentration in the tracheal lumen; NPC 15669 inhibited both effects. To study whether migration of neutrophils into the airway lumen per se induces their expression of IL-8, we compared effects of local introduction of IL-8 and of PA supernatant into the trachea on IL-8 expression in neutrophils recruited into the trachea. PA supernatant, but not exogenous IL-8 alone, induced IL-8 mRNA expression in neutrophils recruited into the trachea. To determine what product(s) of PA stimulate IL-8 expression in neutrophils, we examined neutrophils isolated from peripheral blood. PA supernatant induced IL-8 production in neutrophils, an effect reproduced by PA lipopolysaccharide and inhibited by polymyxin B. These results suggest that neutrophils recruited into the airway lumen play a major role in local IL-8 production in airways in response to bacteria such as PA, depending on the presence of stimuli such as lipopolysaccharide.

Animals↗

Synthesis and evaluation of novel nonpeptide angiotensin II receptor antagonists: imidazo[4,5-c]pyridine derivatives with an aromatic substituent.

Starting from recently reported nonpeptidic angiotensin II (AII) receptor antagonists, we have designed and prepared a new series of 6-arylimidazo[4,5-c]pyridine derivatives. Variation of phenyl groups at the 4-, 6- or 7-position of imidazo[4,5-c]pyridine showed that substitution at the 6-position resulted in receptor-binding activity almost as potent as that of DuP 753. This led to synthesis and evaluation of an extensive series of 6-aryl-imidazo[4,5-c]pyridine derivatives. Some of them were 4-fold more potent in vitro than DuP 753, but only showed weak antihypertensive activity in vivo when given orally to rats.

Angiotensin Receptor Antagonists↗

Synthesis and evaluation of novel pyrazolo[1,5-alpha]pyrimidine derivatives as nonpeptide angiotensin II receptor antagonists.

A novel series of 6-alkyl-7-oxo-4,7-dihydropyrazolo[1,5-alpha]pyrimidine-3-carboxyli c acid derivatives was prepared as angiotensin II (AII) receptor antagonists. When evaluated in an in vitro binding assay using COS cells transfected with a cDNA encoding a human AT1 angiotensin II receptor, the compounds in this series showed Ki values in the range of 0.4-4.0 nM. In anesthetized spontaneously hypertensive rats (SHRs), administration of the 6-propyl derivative 4d (1 mg/kg, i.v.) reduced the mean blood pressure (MBP) by a maximum of more than 30 mmHg from the normal value.

Angiotensin II↗

Adrenergic receptor-mediated Cl- transport in rabbit corneal endothelial cells.

Adrenoceptor-mediated Cl- transport in cultured rabbit corneal endothelium was examined using a Cl(-)-sensitive fluorescent dye. The intracellular Cl- concentration ([Cl-]i) in the endothelial cells was estimated to be about 30 mM. Noradrenaline (0.001-0.1 mM) transiently decreased the [Cl-]i in a dose-dependent manner. Such a decrease in [Cl-]i was completely antagonized by pretreatment with the alpha-adrenoceptor antagonist phentolamine (0.1 mM). The selective alpha 2-adrenoceptor agonist UK 14304-18 (5-bromo-6-[(4H,5H-imidazol-2-yl)amino]quinoxaline, 0.1 mM) persistently decreased the [Cl-]i, but neither the alpha 1-adrenoceptor agonist phenylephrine (0.1 mM) nor the beta-adrenoceptor agonist isoproterenol (0.1 mM) had any effect. The alpha 2-adrenoceptor agonist/antagonist yohimbine (0.1 mM) persistently and more strongly decreased the [Cl-]i than UK 14304-18 did. The yohimbine-induced decrease in the [Cl-]i was not further altered by UK 14304-18 or phenylephrine, but partly reversed by noradrenaline, isoproterenol and an adenylate cyclase activator, forskolin (0.1 mM). The yohimbine-induced decrease in [Cl-]i was inhibited by the carbonic anhydrase inhibitor acetazolamide (1 mM), and Cl-/HCO3- exchange inhibitors, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, but not by the H(+)-ATPase inhibitor N,N'-dicylohexylcarbodiimide. The forskolin-induced recovery in [Cl-]i was inhibited by the Na+/K+/Cl- cotransport inhibitor bumetanide (0.1 mM), but not by the Cl- channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Electrocardiographic abnormalities in patients with Cushing's syndrome.

The electrocardiograms in 8 patients with Cushing's syndrome and 4 with Cushing's disease were studied. The patients were divided into group A with electrocardiographic abnormalities and group B without. The mean age was significantly higher in group B than in group A. However, blood pressure, mean heart rate and the plasma adrenocorticotropic hormone level showed no significant differences between the two groups. In group A, the plasma concentration of cortisol had a tendency to be higher than in group B (A vs. B: 281 +/- 100 ng/ml, 188 +/- 9 ng/ml, respectively). Echocardiography performed on three of four patients in group A revealed cardiac hypertrophy. While, in group B, echocardiography performed on two patients showed no hypertrophic findings. As a result, it seems that the electrocardiographic changes are correlated with the plasma level of cortisol via myocardial hypertrophy.

Adrenocorticotropic Hormone↗

Differences in cellular transport of tri-iodothyronine and thyroxine: cell cycle-dependent alteration of tri-iodothyronine uptake.

Cellular and nuclear uptake of tri-iodothyronine (T3) and thyroxine (T4) was examined using the cultured cell line derived from rat liver, clone 9, and rat hepatoma, dRLH-84. The saturable cellular uptake of T3 and T4 was demonstrated in these cells. First we examined the cell cycle-dependent alteration of thyroid hormone uptake. Cellular T3 uptake was minimal in the early G1 phase and increased in the late G1 phase, reaching a maximal level in the S phase. Alterations in nuclear T3 uptake were in accordance with the changes in cellular T3 uptake. On the other hand, cellular and nuclear T4 uptake was unchanged throughout the cell cycle, suggesting the T3 specificity of the cell cycle-dependent alteration of cellular hormone transport. Next we examined the effect of sodium butyrate on the cellular transport of thyroid hormones. After treatment with 5 mM sodium butyrate, cellular and nuclear uptake of T3 was increased, reaching a maximal level (four- to sevenfold increase) after 48 h. When cells were incubated for 48 h with various concentrations of sodium butyrate, T3 uptake was enhanced by 1 mM sodium butyrate, reaching a maximal level with 5 mM. Although cellular T4 uptake was also increased after treatment with sodium butyrate, the degree and time-course of the increase were different from those of T3. The maximal increase in cellular T4 uptake (two- to threefold increase) was attained 20 h after treatment. Despite the increase in cellular T4 uptake, nuclear T4 uptake was decreased after treatment with sodium butyrate. For both T3 and T4, the enhanced cellular uptake was due to the increased Vmax without changes in the Michaelis-Menten constant. These data indicate that cellular transport of T4 is different from that of T3 in rat hepatic cells.

Animals↗

Human T-lymphotropic virus type I associated myelopathy treated effectively with lymphocytapheresis using a leukocyte removal filter.

The patient, a 61-year-old woman, received a blood transfusion at the age of 33 years. Weakness of the lower extremities developed at the age of 42 and the diagnosis of human T-lymphotropic virus type I (HTLV-I) associated myelopathy was made. Somatosensory evoked potential examination showed that the latency of P27 evoked by peroneal nerve stimulation was 44 msec. Lymphocytapheresis was performed 3 times with one-week intervals using a leukocyte removal filter. The muscle weakness began to improve on the second day after the second lymphocytapheresis and the sensory impairment began to improve on the third day after the third lymphocytapheresis. The delayed latency of P27 improved after the lymphocytapheresis. The effectiveness of lymphocytapheresis in this case suggests that lymphocytes are involved in the pathogenesis of HTLV-I associated myelopathy.

Evoked Potentials, Somatosensory↗

Atrial natriuretic peptide stimulates Cl- transport in retinal pigment epithelial cells.

To study the regulatory role of atrial natriuretic peptide (ANP) on the Cl- transport activity of retinal pigment epithelial (RPE) cells, RPE cells from rabbits were cultured and exposed to ANP and other reagents under perfusion. The changes in intracellular Cl- concentration ([Cl-]i) were continuously recorded using a Cl(-)-sensitive fluorescent dye. The cGMP content was estimated by radioimmunoassay. ANP increased the cGMP content and the [Cl-]i in RPE cells. A guanylate cyclase activator, nitric oxide, and a cell permeable cGMP precursor, 8-Br-cGMP, also increased the level of cGMP and the [Cl-]i. A guanylate cyclase inhibitor, LY83583, an inhibitor of cGMP-dependent protein kinase, KT5823, and an inhibitor of Na+/K+/2Cl- cotransporter, bumetanide, diminished or abolished the ANP-induced increase in [Cl-]i. ANP facilitates Cl- accumulation in RPE cells, which is mediated by guanylate cyclase, cGMP-dependent protein kinase, and the Na+/K+/2Cl- cotransporter.

Aminoquinolines↗

The clecarmycins, new antitumor antibiotics produced by Streptomyces: fermentation, isolation and biological properties.

In the course of screening for microbial products with antitumor activity, new antitumor agents, clecarmycins, were isolated from culture broth of Streptomyces sp. DO-114. The antibiotics were produced in a fermentation medium supplemented with a highly porous polymer resin which adsorbs antibiotics and results in a increase of titer. Active materials were separated from the polymer resin by solvent extraction procedure and two components named clecarmycin A1 and C were isolated by silica gel column chromatography. These were active against bacteria, and showed antiproliferative activities against human HeLa S3 cells. Clecarmycins exhibited antitumor activity against leukemia P388 and sarcoma 180 in mice.

Animals↗

[Cerebral blood flow increase and P300 latency prolongation by intravenous injection of acetazolamide--investigation in lacunar cerebral infarction and healthy subjects].

The cerebral blood flow and the P300 were measured before and 20 minutes after intravenous injection of 17 mg/kg acetazolamide in 15 cases of lacunar cerebral infarction and 10 healthy subjects. In cerebral infarction, the study was performed within 2 weeks after the onset. The cerebral blood flow except the infarcted area was increased significantly by the intravenous injection of acetazolamide in the lacunar cerebral infarction group and the healthy subject group. The blood flow decrease around the infarcted area (intracerebral steal phenomenon) by the intravenous injection of acetazolamide was not observed in any case. The N200 latency and the P300 latency were prolonged significantly by the intravenous injection of acetazolamide in the lacunar cerebral infarction group and in the healthy subject group but the N100 latency and the P200 latency did not show any significant changes. Despite the increase in cerebral blood flow, cerebral function may be decreased by intravenous injection of acetazolamide.

Acetazolamide↗

[Stereotactic radiosurgery using a linear accelerator (LINAC): simulation and positioning].

Stereotactic radiosurgery using a Gamma unit obtains good results for small intracranial diseases, arteriovenous malformation (AVM) and acoustic neurinoma. In stereotactic radiosurgery using a linear accelerator (LINAC), many fundamental problems are to be solved. 1) accuracy of a LINAC, 2) making the collimators for high energy X-ray narrow beams, 3) dosimetry for high energy X-ray narrow beams, 4) irradiation methods for stereotactic radiosurgery, 5) fixation of a patient's head and 6) simulation of a target. The usefulness of our method for simulation of a target and for positioning for radiosurgery was investigated. High energy X-ray narrow beams obtained with the collimators for narrow beams (field sizes: 9mm phi, 18mm phi and 27mm phi) satisfy clinical requirements for stereotactic radiosurgery, as indicated by dose profiles and isodose curves. No dosimetry method for high energy X-ray narrow beams has been established yet. Of the main irradiation methods for stereotactic radiosurgery, the method using multiple non-coplanar converging arcs needs no drastic reconstruction for use with LINAC. A patient's head was completely fixed by the stereotactic frame (Patil stereotaxic system or Leksell micro-stereotactic system). Simulation of a target was performed under CT scan. On CT image, the center of a target was determined and the three-dimensional coodinate on the stereotactic head frame target was settled so that the target would be reached. The three-dimensional coordinate for the target was coincided with the isocenter of a LINA by the laser beams of three-directional pointers. Afterwards, the target position was finely adjusted, by using the target positioner manipulator system.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗