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Biomedical subjects

M Nagashima

Publications and source records attributed to M Nagashima.

At least 19 recordsLinked to original sources

Structure-function studies of the epidermal growth factor domains of human thrombomodulin.

Structure-function relationships in the 6 epidermal growth factor-like domains of human thrombomodulin (TME, residues 227-462) were studied by deletion mutagenesis. Purified and characterised proteins were used for kinetic studies. Deletion of EGF1, EGF2 and residues 310-332 in EGF3 had no effect on thrombin binding (Kd) or on kcat/KM for protein C activation by the thrombin-thrombomodulin complex. Deletion of the rest of EGF3 and the interdomain loop between EGF3 and EGF4 had no effect on Kd but decreased kcat/KM to 10% of TME. Deletion of residues 447-462 of EGF6 had no effect on kcat/KM but increased Kd for thrombin approximately 6-fold. Thus, the region 333-350 in EGF3-4 is critical for protein C activation by the thrombin-thrombomodulin complex and the region 447-462 in EGF6 is critical for thrombin binding.

Base Sequence

Glibenclamide does not block arterial relaxation caused by vasoactive intestinal polypeptide.

Vasoactive intestinal polypeptide (VIP) caused a concentration-dependent relaxation in rabbit mesenteric artery with intact endothelium. The relaxant response to VIP was inhibited by the removal of the endothelium or by pretreatment with methylene blue, but not by pretreatment with glibenclamide. A small but significant relaxant response to VIP in the endothelium-denuded artery was also unaffected by glibenclamide. These findings indicate that ATP-sensitive K+ channels are not involved in the endothelium-dependent or endothelium-independent arterial relaxation elicited by VIP.

Animals

Motility and sensation of the rectosigmoid and the rectum in patients with anorectal malformations.

Motility of the rectosigmoid and rectum and reservoir function of the rectum after surgery for anorectal malformations were investigated in 32 patients (17 with high type, 6 with intermediate type, and 9 with low type anomaly) aged 5 to 16 years. All 32 patients were examined manometrically as well as with a newly devised myoelectrical method. Manometry showed that the values of maximum anal pressure and anorectal pressure difference in the high type were significantly lower than those in the low type. However, the incidence of contractile activity of the rectosigmoid was not significantly different between these two groups. The threshold sensation pressure and the maximum tolerable pressure in the high type were significantly higher than those in the low type, and the rectal compliance in the high type was significantly lower than that in the low type. Electromyography was recorded at 8 cm and 5 cm from the anal verge. Two types of slow waves were observed, a faster rhythm and a slower rhythm. Their frequency was similar in the three groups. However, the numbers of spike bursts in the high type and intermediate type were significantly higher than those in the low type. These results indicate that in addition to an inadequate anal resting pressure a loss of optimal rectal sensation or rectal reservoir function might be associated with fecal incontinence in the high type and that increased spike bursts might play some role in rectal motility.

Adolescent

Role of adrenergic neuronal activity in the yawning induced by tacrine and NIK-247 in rats.

The present experiments were performed to investigate the potential role of central adrenergic neurons in regulating occurrence of yawning in rats. Intraperitoneal injection of tacrine (THA) or 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta(b)-quinoline monohydrate HCl (NIK-247), cholinesterase inhibitors, induced yawning, which was markedly increased by pretreatment with the beta-adrenoceptor antagonist, pindolol. The yawning evoked by tacrine or NIK-247 given alone or in combination with pindolol was inhibited by pretreatment with scopolamine but not by mecamylamine or spiperone. Treatment with tacrine or NIK-247 increased acetylcholine content of the striatum, but this effect was not enhanced by pindolol, which per se did not affect basal acetylcholine content. Moreover, pretreatment with the central adrenaline synthesis inhibitors, (+-)-2,3-dichloro-alpha-methylbenzylamine HCl (LY-78335) and 2-cyclooctyl-2-hydroxyethylamine HCl (UK-1187A), increased tacrine-induced yawning. Subcutaneous injection of talipexole (B-HT 920), a dopamine D2 receptor agonist, evoked yawning, which was also increased by pindolol, LY-78335, and UK-1187A. These receptors antagonists and synthesis inhibitors per se did not cause yawning responses. The results suggest that the beta-adrenoceptor blockade and the inhibition of adrenaline synthesis facilitate the occurrence of yawning induced by cholinergic and dopaminergic agonists, and thus the central adrenergic neuronal systems may be implicated in the regulation of yawning responses.

Acetylcholine

Hyperthermia induced by the dopamine D1 receptor agonist SK&F38393 in combination with the dopamine D2 receptor agonist talipexole in the rat.

The present experiments were performed to investigate the effects of dopamine D1 receptor agonists given alone or in combination with dopamine D2 receptor agonists on body temperature in rats. The selective dopamine D1 receptor agonist, 1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol (SK&F38393), produced hyperthermia. However, the dopamine D2 receptor agonist, B-HT 920 (talipexole), and the newly synthesized dopamine D2 receptor agonist, (S)-2-amino-4,5,6,7-tetrahydro-6-propylamino-benzothiazole (SND 919), did not change the temperature. Interestingly, the SK&F38393-induced hyperthermia was enhanced by talipexole and SND 919. The drastic hyperthermia induced by combined administration of dopamine D1 and D2 receptor agonists was blocked by either the dopamine D1 receptor antagonist, SCH23390, or the dopamine D2 receptor antagonist, spiperone. On the other hand, treatment with prazosin, yohimbine, propranolol, scopolamine, or methysergide failed to affect the marked hyperthermia. The present results suggest that a functional link between dopamine D1 and D2 receptors may be synergistic in the regulation of body temperature and that concurrent stimulation of both dopamine D1 and D2 receptors thereby produces marked hyperthermia in the rat.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben

Linear IgA bullous dermatosis associated with rheumatoid arthritis.

A case of linear IgA bullous dermatosis associated with rheumatoid arthritis is described. The eruption consisted of multiple irregular erythematous plaques and small numbers of tense vesicles mainly on the trunk. An immunofluorescence study showed linear IgA and IgG deposition along the basement membrane zone, whereas C3 deposition was not found. IgA or IgG anti-basement membrane zone antibody was not detected in the serum. Treatment with dapsone resulted in good control of the eruption. Coexistence of linear IgA bullous dermatosis and rheumatoid arthritis has not been reported previously.

Aged

Differential effects of cyclosporine and etretinate on serum cytokine levels in patients with psoriasis.

BACKGROUND: The in vivo effects of cyclosporine and etretinate on the immune system are still unclear. OBJECTIVE: Our purpose was to determine the effects of these drugs on in vivo production of various cytokines. METHODS: Serum cytokine levels were measured sequentially by radioimmunoassay in psoriasis patients treated with either cyclosporine or etretinate. RESULTS: Interferon-gamma levels were initially elevated and rapidly returned to baseline levels before clinical improvement in both treatment groups. A transient increase before the relapse was also observed in some patients. Etretinate treatment resulted in a substantial decrease in tumor necrosis factor-alpha levels, whereas an unpredictable increase was found during the late phase of cyclosporine treatment. CONCLUSION: The in vivo effects of antipsoriatic drugs on cytokine production are different from those demonstrated in vitro. Measurement of serum cytokine levels is useful for monitoring patients with psoriasis.

Administration, Oral

Thermography in a child with varicocele.

A 12-year-old boy with a left-sided varicocele (Grade 3) was assessed preoperatively and followed postoperatively by computer-assisted infrared thermography. The temperature of the left scrotum was 35.4 degrees C before surgery which was 4 degrees C higher than that of the right scrotum. After ligation of the left internal spermatic vein and removal of the varicocele, scrotal thermograms 39 days and 12 months after operation were normal. Therefore, it seems that thermography is very valuable in the evaluation of testicular function in children with varicocele, in whom semen analysis is impossible.

Child

Induction of topoisomerase II-mediated DNA cleavage by the plant naphthoquinones plumbagin and shikonin.

Plumbagin and shikonin, plant metabolites which have naphthoquinone structures, induced mammalian topoisomerase II-mediated DNA cleavage in vitro. Treatment of a reaction mixture containing these naphthoquinones and topoisomerase II at an elevated temperature (65 degrees C) resulted in a great reduction in DNA cleavage, suggesting that the mechanism of the topoisomerase II-mediated DNA cleavage induced by these naphthoquinones is through formation of a cleavable complex, as seen with antitumor agents such as 4'-(9-acridinylamino)methanesulfon-m-anisidide and demethylepipodophyllotoxin ethylidene-beta-glucoside. Lawson and lapacol, which are structurally related plant metabolites with naphthoquinone moieties, could not induce topoisomerase II-mediated DNA cleavage. Plumbagin and shikonin induced a similar DNA cleavage pattern with topoisomerase II which was different from the cleavage patterns induced with other known topoisomerase II-active drugs. A DNA-unwinding assay with T4 DNA ligase showed that shikonin, lawson, and lapacol did not intercalate into DNA, while plumbagin and 2-methyl-1,4-naphthoquinone intercalate into DNA, but to a lower degree than 4'-(9-acridinylamino)methanesulfon-m-anisidide does.

Animals

Strong correlation between the number of CAG repeats in androgen receptor genes and the clinical onset of features of spinal and bulbar muscular atrophy.

X-linked spinal and bulbar muscular atrophy (SBMA), a motor neuron disease associated with androgen insensitivity, is caused by androgen receptor gene mutations with an increased number of tandem CAG repeats in exon 1. We investigated the increased number of CAG repeats in androgen receptor genes of 19 SBMA patients and found that this correlated strongly with the age at onset of muscle weakness. Thus, SBMA is the first genetic disease in which a strong correlation between the degree of genetic abnormality (number of CAG tandem repeats) and clinical phenotypic expression is demonstrable. The results further indicate that androgen gene mutation is directly involved in the degeneration of motor neurons.

Adult

Screening of children with arrhythmias for arrhythmia development during diving and swimming--face immersion as a substitute for diving and exercise stress testing as a substitute for swimming.

We compared face immersion and exercise stress testing by diving and swimming as screening methods for arrhythmias induced by immersion in water. The subjects were 64 children with various arrhythmias who were tested using 5 methods: diving, swimming, face immersion in 25 degrees C water, face immersion in 6 degrees C water, and a treadmill exercise test. Significant arrhythmias occurred during diving or swimming in 51 children, with 44 developing arrhythmias while diving. Both tachyarrhythmias and bradyarrhythmias were seen during diving, but 17 children who also showed significant arrhythmias while swimming mostly had tachyarrhythmias. A comparison with the incidence of arrhythmias produced by diving showed that face immersion in cold water had a sensitivity of 88.6%, a specificity of 85.0%, a predictive value of 92.9%, and an accuracy of 87.5%. Arrhythmias were alleviated in 12.5%, unchanged in 79.7%, and aggravated in 7.8% of the subjects. Face immersion thus appeared to be a useful and adequate screening substitute for diving. Exercise testing was also compared with swimming (sensitivity, 52.9%; specificity, 100%; predictive value, 100%; and accuracy, 87.5%). Arrhythmias were alleviated in 12.5% and unchanged in 87.5% of patients. Although exercise testing produced many false-negatives, all of the severe arrhythmias were reproduced.

Adolescent

[Double valve replacement for secondary atrioventricular regurgitation due to dilated cardiomyopathy--a case report].

A successful surgical case of double valve replacement for a patient with dilated cardiomyopathy was performed. A 45-year-old man was admitted to our hospital with paroxysmal atrial fibrillation and congestive heart failure. Echo cardiogram and cineangiography showed dilatation and decreased contraction of the left ventricle. A diagnosis of dilated cardiomyopathy was established since neither coronary artery disease nor valvular disease were observed. He was treated with medication of diuretics and pacemaker implantation. However, mitral and tricuspid regurgitation occurred and progressed 7 years later. Since then, he repeated admission and discharge against the strong medication. He became medically uncontrollable at the age of 58. Because of this, surgical treatment had to be considered. Double valve replacement for mitral and tricuspid valve was performed on September, 1989. Avoidance of cardiopulmonary bypass was only possible with the aid of catecholamine. Poor left ventricular function and pleural effusion frequently shown on chest X-ray film complicated the postoperative course. And with hospital treatment, he discharged three months after the operation. He has been doing well without any significant complaint during the past two years and cardiomegaly has been decreasing as well.

Cardiomyopathy, Dilated

[Atrioventricular block in acute inferior myocardial infarction].

The underlying mechanism of atrioventricular block (AVB) in acute inferior myocardial infarction (AIMI) is not clearly understood. In 33 (27 males and 6 females) of 123 patients with AIMI, second and/or high degree AVB was observed. In 14 of the 33 patients (42%), AVB transiently appeared within 24 hours after the onset of AIMI. In 13 patients (39%) AVB appeared after 24 hours. In the remaining 6 patients (18%), AVB appeared within 24 hours and disappeared thereafter. Among these 3 groups, there were no significant differences in age, sex, serum enzymes, the appearance of high degree AVB, pump failure or Forrester's classification II, III and IV and the necessity of temporary pacing. One mg of atropine sulfate was administrated intravenously 35 times in 19 patients. When AVB improved or the ventricular rate increased more than 30%, the drug was regarded as effective. Atropine was more effective when administrated after 24 hours (11%, less than or equal to 24 hours vs 60%, greater than 24 hours, p less than 0.05), and in patients with a slight degree of AVB (28% in high degree vs 80% in second degree, p less than 0.05) and rapid ventricular rate during high degree AVB (0%, less than 40/min vs 45%, greater than or equal to 40/min, p less than 0.05). In the 6 patients not responding to atropine, 250 mg of aminophylline was given intravenously for 15 min. The effect was not seen in 4 patients, including 3 patients to whom it was administrated within 3 days after the onset of AIMI, and one patient to whom it was given on the 5th day. Aminophylline improved atrioventricular conduction on the 5th to 10th day after the onset of AIMI in 2 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine