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Biomedical subjects

H Nagashima

Publications and source records attributed to H Nagashima.

At least 19 recordsLinked to original sources

Molecular stability of chicken and rabbit immunoglobulin G.

Molecular stability of chicken egg yolk immunoglobulin G (IgY) and that of rabbit IgG were compared by measuring antibody activities and conformational changes. Stability of rabbit IgG to acid denaturation was much higher than that of IgY. Conformation of the IgY molecule was readily changed in acidic conditions, resulting in a rapid loss of antibody activity. Much less stable natures of IgY to heat-treatment and guanidine-HCl denaturation than rabbit IgG were also observed. Differences in the structure between the two immunoglobulins that might participate in their different stability were inferred from their amino acid sequence data. Importance of the intramolecular disulfide linkage in the rabbit light chain and some other structural differences were suggested.

Animals

Giant thrombosed vertebral artery aneurysm managed with extracranial-intracranial bypass surgery and aneurysmectomy. Case report.

A case is presented of a left giant thrombosed vertebral artery aneurysm in a 46-year-old man. The giant thrombosed aneurysm was successfully resected with trapping of the affected artery after right external carotid artery-posterior cerebral artery bypass surgery using a radial arterial graft. The clinical course is reported, and the details of the operative approach and techniques are discussed.

Humans

Synthesis of 1233A analogs and their inhibitory activity against hydroxymethylglutaryl coenzyme A synthase.

Simple and efficient syntheses of 1233A analogs were developed and the inhibitory activity of the analogs against hydroxymethylglutaryl coenzyme A (HMG-CoA) synthase was determined. Study of the structure-activity relationships revealed that not only the geometry in beta-lactone moiety but also the length of the carbon side chain is important for inhibitory activity against HMG-CoA synthase.

Animals

[Neuromuscular blocking effect of ORG9426, a new non-depolarizing muscle relaxant, and its recovery with various antagonists in vitro].

We evaluated the neuromuscular blocking effect of ORG9426, a new non-depolarizing muscle relaxant, and its recovery by means of washout or by antagonists in vitro, using phrenic nerve-hemidiaphragm preparations of rats. IC50 and IC90 of ORG9426 in single twitch were 10.62 +/- 0.58 microM and 15.75 +/- 0.95 microM; and those in train of four ratio were 9.04 +/- 0.38 microM and 11.87 +/- 0.42 microM, respectively. The potency of ORG9426 in vitro was compared with those of other non-depolarizing muscle relaxants. The order of potency among the non-depolarizing muscle relaxants was the following: d-tubocurarine greater than pipecuronium greater than pancuronium greater than vecuronium greater than ORG9426. There was no difference between ORG9426 and vecuronium in the recovery from block with washout, neostigmine, 4-aminopyridine, 3, 4-diaminopyridine, and edrophonium. In conclusion, the potency of ORG9426 is relatively low, and it can be easily antagonized by anti-cholinesterases and aminopyridines.

Aminopyridines

[The acute and chronic effects of bunazosin on exercise capacity estimated by the anaerobic threshold in patients with chronic congestive heart failure].

To study the effect of bunazosin on exercise capacity in patients with congestive heart failure (NYHA II-III), anaerobic thresholds (AT, VO2, ml/min/kg) were measured before (control) and after initial 1 = 2mg administration of bunazosin (acute phase; N = 14) and after two weeks of bunazosin therapy (3mg/day, 1mg t. i. d., chronic phase; N = 6). AT were determined by Wasserman's V-slope method during ergometer exercise test with a ramp loading (10 watt/min). AT increased significantly from control during both acute (14.2 +/- 2.7 to 16.9 +/- 3.6 ml/min/kg p < 0.005) and chronic (13.6 +/- 2.5 to 16.7 +/- 1.0 p < 0.05) phase. Additionally, work (watt) attained at AT increased significantly from control during both acute (33.6 +/- 19.2 to 52.6 +/- 30.2 p < 0.005) and chronic (35.8 +/- 25 to 49.3 +/- 15 p < 0.05) phase. Pressure-rate-products (PRP, x 10(2) mmHg/min) at AT increased significantly from control during the acute phase (119 +/- 35 to 240 +/- 50 p < 0.005) alone. In the chronic phase, PRP decreased significantly at the work level equal to AT during control (from 207 +/- 41 to 187 +/- 39 p < 0.05). These data suggest that bunazosin has favorable acute and chronic effects on exercise capacity in patients with congestive heart failure.

Adult

[The effect of ionized calcium concentration on muscle contraction and on the effect of non-depolarizing neuromuscular blocking agent].

The influence of serum ionized calcium (Ca2+) on the muscle contraction and on the effect of non-depolarizing neuromuscular blocking agent, d-tubocurarine (dTc), was investigated. The isolated phrenic nerve-diaphragma preparation of the rat was stimulated directly and indirectly at 0, 0.4, 0.7, 1.4, 2.5 mM of total calcium concentration (Ca2+: 0, 0.39, 0.52, 1.12, 2.32 mM, respectively). With indirect stimulation, no contraction was observed from 0 to 0.4 mM of calcium, but the twitch tension returned to 100 percent of control at over 0.7 mM of calcium. However, with direct stimulation, the twitch tension was obtained up to 100 percent of control independent of Ca2+ concentration. The ED50 of dTc was correlated well with the serum Ca2+. These findings suggest that the decrease of serum Ca2+ concentration interferes with the muscle contraction and potentiates the effect of dTc. We speculate that the site of its action may be primarily prejunctional.

Animals

Cryopreservation of mouse half-morulae and chimeric embryos by vitrification.

Mouse half-morulae were cryopreserved less than or equal to 1, 3, 6, and 12 hr after bisection by the vitrification method using 25% glycerol and 25% 1,2-propanediol as cryoprotectant. The developmental rates of the frozen-thawed half-embryos to blastocysts in vitro were 77.8% (63/81), 82.0% (41/50), 92.1% (117/127), and 0% (0/37), respectively. Sixty-one of the half-embryos that had been vitrified 6 hr after the bisection followed by transfer to five recipients resulted in a total of ten (16.4%) normal fetuses. Chimeric mouse embryos constructed by two half-morulae were also vitrified 6 and 16 hr after aggregation. Survivors were obtained from the former case: 40 (80.0%) of 50 frozen-thawed embryos developed in vitro to blastocysts, and, after transfer, six chimeric offspring were obtained from the 34 vitrified chimeric embryos. These results showed that mouse half-morulae and chimeric embryos could be cryopreserved by the vitrification method. It seems possible to manufacture a chimeric mouse embryo of defined genotypic composition that can be analyzed during its frozen state using the identical half-embryos of the components.

Animals

Presynaptic interaction between vagal and sympathetic innervation in the heart: modulation of acetylcholine and noradrenaline release.

It is generally accepted that there is a functional antagonism between the sympathetic and parasympathetic (vagal) effects on the heart. In this study guinea-pig right atria loaded either with [3H]noradrenaline or [3H]choline were used and the release of [3H]noradrenaline or [3H]acetylcholine in response to field stimulation was measured under conditions when the negative feedback modulation was excluded. Strong evidence was obtained for a one-sided interaction between the sympathetic and vagal nerves at the level of the prejunctional axon terminals that send the final chemical message to the heart muscle affecting heart rate and force. Acetylcholine released from the vagal nerve inhibited its own release and also decreased the release of noradrenaline from the sympathetic axon terminals through muscarinic receptor stimulation. But muscarinic receptors located on cholinergic axon terminals are different from those present on the noradrenergic axon terminals. There is a significant difference in the dissociation constants (Kd) of different antimuscarinic drugs: The Kd values of pancuronium on vagal and sympathetic axon terminals were 5.68 +/- 0.41 and 7.20 +/- 0.25, respectively. By contrast, noradrenaline released from the sympathetic nerves or exogenous noradrenaline were not able to modulate the release of acetylcholine from the cholinergic axon terminals even under condition when the negative feedback modulation of acetylcholine release was excluded. These findings indicate that vagal axon terminals are not equipped with alpha 2- or alpha 1-adrenoceptors. However, noradrenaline released from the sympathetic axon terminals was able to inhibit its own release via alpha 2-adrenoceptor stimulation.

Acetylcholine

The neuromuscular effects of ORG9426 in patients receiving balanced anesthesia.

In searching for a nondepolarizing muscle relaxant with intermediate duration but more rapid onset of action than the presently available compounds, the neuromuscular and circulatory effects of ORG9426 were investigated in two studies in humans receiving fentanyl, droperidol, thiopental, and nitrous oxide-oxygen anesthesia. Eighty patients, randomly assigned to one of four groups of 20 each, received 0.12, 0.16, 0.20, or 0.24 mg/kg ORG9426. In the first study, the doses (in milligrams per kilogram) of ORG9426 that caused 50% (ED50), 90% (ED90), or 95% (ED95) neuromuscular block were determined by the individual dose-response method; they were 0.170, 0.268, and 0.305 mg/kg, respectively. In the second study, after induction of anesthesia, patients received 0.6 mg/kg (about 2 x ED95) of ORG9426, either in a single bolus (group 1) or in two unequal (0.1 and 0.5 mg/kg) increments 4 min apart (group 2). After the administration of 0.6 mg/kg ORG9426, maximal neuromuscular block developed in 1.5 +/- 0.12 min in group 1 and in 1.2 +/- 0.14 min in group 2. Patients tracheas were intubated after development of the maximal neuromuscular effect of the intubating dose and after the recording of heart rate and systolic and diastolic blood pressure. There was no difference in the clinical duration of the intubating doses, which were 40.0 +/- 3.2 (15-73) min in group 1 and 39.3 +/- 2.4 (19-57) min in group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Giant aneurysms of the horizontal segment of the anterior cerebral artery: report of two cases.

Two cases of giant aneurysm of the horizontal segment of the anterior cerebral artery (A1) are presented. The rare occurrence of a giant aneurysm in this location necessitates evaluation of the cross-flow through the anterior communicating artery when planning surgical strategy. On the basis of angiographic findings, trapping of the A1 on both sides of the aneurysm neck was performed in Case 1, and aneurysmorrhaphy utilizing an angioplastic multiple-clipping method of A1 endarterectomy was accomplished in Case 2. The postoperative courses of both patients were satisfactory.

Aged

Extradural block in obstetric patients: review of experience with gravity administration.

Charts of 2284 obstetric patients who received extradural block with gravity administration of local anaesthetic were evaluated retrospectively. Despite a 1.3% incidence of vascular puncture and a 1.8% incidence of dural puncture, accidental intravascular or intrathecal injection of local anaesthetic did not occur. We propose that this method may be safer than the traditional "injection by needle" technique, and has a high degree of "visualization" of the otherwise "blind" extradural block procedure.

Anesthesia, Epidural

Thalamic atrophy following cerebral infarction in the territory of the middle cerebral artery.

We investigated shrinkage of the ipsilateral thalamus following infarction in the territory of the middle cerebral artery in 33 patients who were admitted less than or equal to 2 days after the stroke and who were followed by computed tomography for greater than 1 year with no recurrences. The thalamic area was measured on the computed tomograms, and the ratio of the ipsilateral area to the contralateral area was calculated. All values were compared with values from the initial computed tomogram taken less than or equal to 2 days after the stroke. The values of the ratio on follow-up computed tomograms decreased gradually in 15 patients. In these cases, the area of the ipsilateral thalamus was significantly reduced after 1 year (p less than 0.01) and marked atrophy was observed. These results demonstrate the significance of remote changes over a long period of time after focal cerebral infarction.

Atrophy

Cloning of hepatitis C virus genomes and their properties.

A random primed lambda gt11-cDNA library was constructed from donors plasma presumably infected by blood-borne non-A, non-B hepatitis (hepatitis C:HC) agent and immunoscreened with serum pooled from patients with acute or chronic HC. Twelve lambda gt11-cDNA clones were isolated that was shown to encode antigens associated specifically with HC infection in Japan as well as in USA. Of these two, as well as another clone which is specific only to Japanese HC infection, have unique nucleotide sequences and were extensively studied. They are not derived from host DNA and have no homology to the sequences of known human viruses including hepatitis A, B and D viruses, Ebstein-Barr virus, coxsackievirus, immunodeficiency virus type 1 or Japanese encephalitis virus. These results suggest that they are derived from the genome of HC agent(s). In addition, of these, one clone seems to encode epitopes derived from both the core and the surface polypeptides of the agent.

Antigens, Viral

Neuromuscular and cardiovascular effects of pipecuronium.

Pipecuronium bromide (Arduan) is a bisquaternary, steroid-type neuromuscular blocking agent in clinical use in Eastern Europe. Before its introduction into clinical practice in the USA, in the first phase of this study the neuromuscular potency of pipecuronium was determined under "balanced" and enflurance anaesthesia by the cumulative log dose-response method in 30 patients each. In the second phase the intubation and onset times, clinical duration of the first and repeated doses, spontaneous recovery index, reversibility of its residual neuromuscular effect by an anticholinesterase and its effect on heart rate and blood pressure was compared with the same variables observed in patients, anaesthetized with identical techniques but who had received vecuronium or pancuronium. The neuromuscular potency of pipecuronium was greater under enflurane (ED95 = 23.6 +/- 1.1 micrograms.kg-1 (mean +/- SEM)] than under balanced (ED95 = 35.1 +/- 17 micrograms.kg-1) anaesthesia. Pipecuronium was more potent than vecuronium under both balanced (ED95 = 45.8 micrograms.kg-1) and enflurane anaesthesia (ED95 = 27.4 micrograms.kg-1). Following the administration of 2 x ED95 doses there were no clinically significant differences in the intubation or onset times of pipecuronium, vecuronium and pancuronium. Under balanced anaesthesia the clinical duration of 2 x ED95 dose of pipecuronium (110.5 +/- 0.3 min) or pancuronium (115.8 +/- 8.1 min) were similar and about three times longer than that of vecuronium (36.3 +/- 2.1 min). The recovery indices of pipecuronium (44.5 +/- 8.2 min) and pancuronium (41.3 +/- 4.2 min) were also similar and about three times longer than that of vecuronium (14.3 +/- 1.4 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Temperature dependence of rat diaphragm muscle contractility and fatigue.

The diaphragm is a skeletal muscle of mixed fiber type that is unique in its requirement to maintain contractile function and fatigue resistance across a wide range of temperatures to sustain alveolar ventilation under conditions of hypo- or hyperthermia. The direct effect of temperature (15-41 degrees C) on rat diaphragm isometric contractility and fatigue was determined in vitro. As temperature decreased from 37 to 15 degrees C, contraction and relaxation times increased, and there was a left shift of the diaphragm's force-frequency curve, with decreased contractility at 41 and 15 degrees C. Fatigue was induced by 10 min of stimulation with 30 trains/min of 5 Hz at a train duration of 900 ms. Compared with 37 degrees C, fatigue resistance was enhanced at 25 degrees C, but no difference in fatigue indexes was evident at extreme hypothermia (15 degrees C) or hyperthermia (41 degrees C). Only when the fatigue program was adjusted to account for hypothermia-induced increases in tension-time indexes was fatigue resistance evident at 15 degrees C. These findings indicate that despite the diaphragm's unique location as a core structure, necessitating exposure to in vivo temperatures higher than found in limb muscle, the temperature dependence of rat diaphragm muscle contractility and fatigue is similar to that reported for limb muscle of mixed fiber type.

Animals