Big mitogen-activated protein kinase 1 (BMK1)/extracellular signal regulated kinase 5 (ERK5) is involved in platelet-derived growth factor (PDGF)-induced vascular smooth muscle cell migration

Big mitogen-activated protein kinase 1 (BMK1), also known as extracellular signal-regulated kinase 5 (ERK5), is a newly identified member of the mitogen-activated protein (MAP) kinase family. Recently, several studies have suggested that BMK1 plays an important role in the pathogenesis of cardiovascular disease. To clarify the pathophysiological significance of BMK1 in the process of vascular remodeling, we explored the molecular mechanisms of BMK1 activation in vascular smooth muscle cells (VSMCs). From the results of co-immunoprecipitation and immunoblotting analyses, it was found that platelet-derived growth factor (PDGF), a known potent mitogen, activated BMK1 and triggered the Gab1-SHP-2 interaction in rat aortic smooth muscle cells (RASMCs). The abrogation of SHP-2 phosphatase activity by transfection of the SHP-2-C/S mutant suppressed PDGF-stimulated BMK1 activation. Infection with an adenoviral vector expressing dominant-negative MEK5alpha, which can suppress PDGF-stimulated BMK1 activation to the control level, inhibited PDGF-induced RASMC migration. Moreover, we observed an increase of BMK1 activation in injured mouse femoral arteries. From these findings, it is suggested that BMK1 activation leads to VSMC migration induced by PDGF via Gab1-SHP-2 interaction, and that BMK1-mediated VSMC migration may play a role in the pathogenesis of vascular remodeling.     

Usefulness of leg-crossing for maintaining blood pressure in a sitting position in patients with orthostatic hypotension--case reports

The authors report a case with idiopathic orthostatic hypotension in which the patient prevents his blood pressure from falling to a symptomatic level by leg-crossing in a sitting position. Including 4 other patients with orthostatic hypotension and 5 normal subjects, their study found that the changes in blood pressure with leg-crossing inversely correlated with those induced by assuming seated posture from a supine position. Leg-crossing may, therefore, be one of the useful nonpharmacologic measures for maintaining blood pressure in a sitting position in patients with orthostatic hypotension.     

A case report of spinal epidural hematoma complicated after open heart surgery]

The authors reported the first case of acute spinal epidural hematoma (SEH) developed after open heart surgery. The patient was noticed that her legs felt weak and numb on the first postoperative day evening. On the next day morning, neurological examination revealed that flaccid paralysis of both legs and also loss of all sensory perception below the level of Th-6 spine bilaterally. The prolonged effect of anesthesia and painless onset made delayed recognition of the lesion. SEH (Th5-7) was diagnosed with MRI and decompressive surgery was immediately done, sixty hours after the beginning of cardiac operation. But in this case neurological deficits were not changed. We concluded that a routine diagnostic approach was very important procedure to find out this serious complication for all patients underwent open heart surgery in early period of its onset.     

Impact response of periodontal tissues

A new impact response method using a fracture of a pencil-lead to produce an excitation pulse is proposed. Impact excitations (rectangular pulse, triangular pulse and half-sine pulse) are strictly given in physical and mathematical definitions and complete solutions to the impact excitations are provided for Noyes' model of the human tooth. When a relatively long triangular pulse is applied to Noyes' model, which can express the physical characteristic of periodontal tissues, a sinusoidal damped vibration of a single degree-of-freedom model is approximately obtained. The acceleration response is characterised by the physical parameters (T, δ and A_o) and mechanical elements (m₁, c₁ and k) of which a single degree-of-freedom model is composed. By means of this method, the values of the parameters and elements in the cases of healthy maxillary, healthy mandibular and pathological mandibular incisors are obtained. The single degree-of-freedom model can express the high-frequency spectra of Noyes' model. The pathological tooth is characterised by a longer damped time constant and a larger acceleration maximum. This impact response method can effectively be applied to clinical diagnosis in view of the physical parameters and mechanical elements which have been derived.     

Myopathy phenotype in transgenic mice expressing mutated PABPN1 as a model of oculopharyngeal muscular dystrophy

Autosomal dominant oculopharyngeal muscular dystrophy (OPMD)is a late-onset disorder characterized clinically by progressiveptosis, dysphagia and limb weakness, and by unique intranuclearinclusions in the skeletal muscle fibers. The disease is causedby the expansion of a 10-alanine stretch to 12–17 alanineresidues in the poly(A)-binding protein, nuclear 1 (PABPN1;PABP2). While PABPN1 is a major component of the inclusionsin OPMD, the exact cause of the disease is unknown. To elucidatethe molecular mechanism and to construct a useful model fortherapeutic trials, we have generated transgenic mice expressingthe hPABPN1. Transgenic mice lines expressing a normal hPABPN1with 10-alanine stretch did not reveal myopathic changes, whereaslines expressing high levels of expanded hPABPN1 with a 13-alaninestretch showed an apparent myopathy phenotype, especially inold age. Pathological studies in the latter mice disclosed intranuclearinclusions consisting of aggregated mutant hPABPN1 product.Furthermore, some TUNEL positive nuclei were shown around degeneratingfibers and a cluster of it in the lesion in necrotic musclefibers. Interestingly, the degree of myopathic changes was moreprominent in the eyelid and pharyngeal muscles. Further, muscleweakness in the limbs was apparent as shown by the fatigabilitytest. Nuclear inclusions seemed to develop gradually with aging,at least after 1 week of age, in model mouse muscles. We establishedthe first transgenic mouse model of OPMD by expressing mutatedPABPN1, and our model mice appear to have more dramatic alternationsin myofiber viability. ^* To whom correspondence should be addressed. Tel: +81 963736083; Fax: +81 963736599; Email: yamamura{at}gpo.kumamoto-u.ac.jp     

Influences of intra-aortic balloon pumping on superior mesenteric flow dynamics

The influences of intra-aortic balloon pumping (IABP) on arterial flow of the superior mesenteric artery were assessed by Doppler echocardiography. The subjects were 13 patients postoperatively, requiring IABP support to control low cardiac output state, in which distal aspects of balloons were distal to the superior mesenteric artery. Superior mesenteric flow velocity integral in systole (IntS) and that in diastole (IntD) were measured from superior mesenteric flow pattern, and the sum of IntS and IntD (IntS + IntD) was calculated ON and OFF balloon pumping (IABP ON-OFF test). The same parameters were obtained with balloon inflating on every other beat (IABP 1:2 test); the cardic cycle with balloon assist was defined as "1:2 ON", and that without balloon assist was defined as "1:2 OFF". 1) IABP ON-OFF test. IABP increased IntS from 7.07 +/- 2.56 cm to 9.20 +/- 3.19 cm (p less than 0.05), IntD from 3.00 +/- 1.18 cm to 3.62 +/- 1.40 cm (p less than 0.05), and IntS + IntD from 10.07 +/- 3.48 cm to 12.82 +/- 4.04 cm. Cardiac output increased from 3.89 +/- 1.34 l/min to 4.24 +/- 1.64 l/min with IABP support. The increments in IntS, IntD and IntS + IntD with IABP are attributed, to a large extent, to an increase in cardiac output. 2) IABP 1:2 test. Without balloon inflation, IntS increased (1:2 ON; 7.16 +/- 2.91 cm, 1:2 OFF; 8.41 +/- 3.30 cm, p less than 0.05), and IntD decreased (1:2 ON; 3.51 +/- 1.60 cm, 1:2 OFF; 2.33 +/- 1.25 cm, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

New technique of posterior mitral annuloplasty

We have developed a new technique of mitral annuloplasty applicable in patients with rheumatic mitral regurgitation. This technique is designed to advance anteriorly the posterior annulus and leaflet and to gain more coaptation area. Technical details of this procedure are presented.     

Antihypertensive effect of E-643, a new alpha-adrenergic blocking agent

Summary To determine whether E-643, a new -blocking agent, would reduce the blood pressure, regardless of the posture, a 1 mg dose was given 3 times daily for 7 consecutive days, to 8 male and 7 female inpatients, aged 37–73 years, with essential hypertension. Blood pressure and pulse rate were measured daily in the supine, sitting and standing positions. Before and after the treatment with E-643, plasma levels of noradrenaline, adrenaline, dopamine--hydroxylase, renin and aldosterone were determined, samples being obtained with the subjects recumbent and after standing upright for 60 min. A significant reduction in the systolic and diastolic blood pressures was evident in the supine (172±31/100±12 151±28/89±14 mmHg), sitting (158±22/101±11 138±28/89±15 mmHg) and standing (153±32/103±21 129±31/89±20 mmHg) positions. The reduction in blood pressure remained unchanged throughout the period of administration of E-643. Pulse rate was not affected when the subjects were supine (67±10 69±10 beats/min), but was increased in the sitting (68±10 73±9 beats/min) and standing (73±10 81±11 beats/min) positions. The increased pulse rate tended to decline during continued administration of E-643. Treatment with E-643 produced no significant change in plasma levels of adrenaline, noradrenaline, dopamine--hydroxylase, renin and aldosterone. The antihypertensive effect of treatment was more prominent in the patients with higher levels of plasma catecholamines and dopamine--hydroxylase, and was less prominent in those with higher plasma renin and aldosterone. Two patients had temporary bouts of dizziness and visual disturbances, but there were no subjective complaints during treatment.     

Molecular mechanism of chemical modification of cellular nucleic acid bases by 4-hydroxyaminoquinoline 1-oxide

The O-acyl derivative of 4-hydroxyaminoquinolone, the proposed ultimate metabolite in carcinogenesis by the parent compound, was proposed to undergo a nitrogen-oxygen heterolysis to produce three types of reaction intermediates: a nitrenium, a carbonium, and nitrene intermediates, which were considered to give N(4)-substituted 4-aminoquinoline 1-oxide (4-AQO), 3-substituted 4-AQO, and 4-AQO, respectively, in reactions with nucleophiles including nucleic acid bases. Chemical modification of cellular DNA by this carcinogen is discussed.     

A case of aconitine poisoning saved with cardiopulmonary bypass

"Torikabuto" is a kind of plant which contains deadly poison. Its ingredient is aconitine alkaloids. We report a case of aconitine poisoning with fatal arrhythmia and acute pulmonary edema who was saved with cardio pulmonary bypass. A 41-year-old male ate to mistake "Torikabuto" for wild plant. He developed symptoms of dysarthria and admitted to our hospital. He developed ventricular tachycardia and fibrillation soon after his admission. Then he developed cardiogenic shock. He was resuscitated and supported with a percutaneous cardio pulmonary bypass. Ventricular tachycardia disappeared 24 hours after admittion. About 1 week later, cardio pulmonary bypass was terminated and about 3 months later, he discharged from our hospital.