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Biomedical subjects

E Nakai

Publications and source records attributed to E Nakai.

At least 19 recordsLinked to original sources

Peptide based interleukin-1 beta converting enzyme (ICE) inhibitors: synthesis, structure activity relationships and crystallographic study of the ICE-inhibitor complex.

Based on the X-ray structure of the complex of Ac-Tyr-Val-Ala-Asp-H (L-709049) and interleukin-1 beta converting enzyme (ICE), we synthesized compounds which were derived from 2-NapCO-Val-Pro-Asp-CH2OPh (1) to obtain a potent inhibitor in the cell assay. Among these compounds, (3S)-N-methanesulfonyl-3-[[1-[N-(2-naphthoyl)-L-valyl]-L-prolyl]amino]- 4-oxobutanamide (27c) showed high potency not only in the enzyme assay but also cell assay with IC50 values of 38 nM and 0.23 microM, respectively. Compound 27c, with a c log P value of 1.76, had a more hydrophilic character compared with 1. Compound 27c also dose dependently inhibited LPS-primed ATP-induced IL-1 beta release in mice. The crystal structure of the complex of compound 27c and ICE revealed that compound 27c had further interactions with ICE in the naphthoyl group at the P4 position and in the methyl group of the methanesulfonamidecarbonyl group at the P1 position, compared with L-709049. To our knowledge, compound 27c is the first example that shows a strong inhibitory activity without the carboxyl group at the P1 position.

Animals

Percutaneous transluminal angioplasty for intracranial arteriosclerotic lesions.

We report 17 cases of intracranial arterial stenosis treated by percutaneous transluminal angioplasty (PTA), including 9 on the intracranial internal carotid (ICA), 4 on the middle cerebral (MCA), and 4 on vertebrobasilar artery (VBA) system. All patients had ischaemic brain symptoms and stenoses of more than 60% (calculated angiographically). We treated four patients by PTA for residual stenoses after thrombolysis for acute occlusion. We used PTA balloon catheters 2.0-3.5 mm in diameter for all procedures. As a rule, the balloon was inflated for 1 min at 6 atm. All arteries were successfully dilated (stenosis less than 50%) except for one treated by PTA for residual MCA stenosis after thrombolysis. The patient died of a massive infarct due to MCA reocclusion caused by arterial dissection. Stenosis recurred in 4 of 16 patients. Repeat PTA was successfully carried out in these cases. However, stenosis recurred in one of these patients 3 months after PTA, but the patient is being followed because he is asymptomatic. PTA of intracranial arteries is effective, but its indications should be based strictly on potential risks, such as acute occlusion derived from arterial dissection.

Aged

Transplantation of autologous sympathetic ganglion into the brain with Parkinson's disease. Long-term follow-up of 35 cases.

Transplantation of autologous sympathetic ganglion was performed in 35 patients with Parkinson's disease. Approximately half the patients showed improvement of parkinsonian symptoms over the 3 years following transplantation. The patients showed amelioration of bradykinesia and gait disturbance, but tremor and muscle rigidity were not improved by transplantation. The other half of the patients did not show amelioration after transplantation. No serious complications were encountered, though mild ptosis was observed in all patients. The mechanism of improvement of symptoms might be the release of dopamine from the grafted sympathetic ganglion. Transplantation of autologous sympathetic ganglion can be a therapeutic modality for Parkinson's disease.

Adult

Iatrogenic arteriovenous fistula of the middle meningeal artery caused during embolization for meningioma--case report.

A 73-year-old female developed middle meningeal arteriovenous fistula during embolization of a falx meningioma. The cause of this complication was thought to be perforation by the guide wire during catheterization at the sharp bend in the sphenoidal portion of the middle meningeal artery. Embolization of the fistula and the feeding artery to the meningioma with polyvinyl alcohol particles 250-355 microns size resulted in complete obliteration of the fistula. Computed tomography showed no epidural or subdural hematoma. Introduction of the microcatheter beyond the sharp bend in the middle meningeal artery should not be attempted to avoid the possibility of iatrogenic middle meningeal arteriovenous fistula.

Aged

Transluminal angioplasty for arteriosclerotic disease of the distal vertebral and basilar arteries.

OBJECTIVE: Percutaneous transluminal angioplasty (PTA) for the distal vertebral and basilar artery is now being performed in selected patients with haemodynamically significant lesions of the posterior cerebral circulation. Its effect and overall results were examined. PATIENTS AND METHODS: A balloon dilatation catheter specifically developed for these procedures, with a 2.0-3.5 mm balloon diameter, at 6 atmospheres of pressure, was used. Angioplasty was performed in 12 patients (including six whose initial results have been reported) with angiographically documented stenotic lesions involving either the intracranial vertebral artery (C1-C2 portion) or the basilar artery, and satisfying the following criteria: (1) clinical symptoms suggestive or consistent with a transient ischaemic attack refractory to medical treatment, or small infarction of the posterior circulation; and (2) angiographically documented stenosis greater than 70%. Two of 12 patients had complete thrombosis of the distal vertebral and basilar artery and PTA was performed after successful intra-arterial thrombolysis. RESULTS: Successful results, without complications, were obtained in eight patients, with complete resolution of vertebrobasilar ischaemic symptoms. Immediate complications occurred in four patients including two with vessel dissection, and two with thromboembolism. The two patients with acute arterial dissection were reoperated but developed small infarctions with permanent neurological deficits. The two patients with thromboembolic complication showed transient neurological deficit. The overall stenosis ratio decreased from a mean of 84% pretreatment to 44% after the angioplasty procedure. Restenosis occurred in two patients. Long term clinical follow up in 11 patients who survived more than six months showed resolution of ischaemic symptoms after PTA in all except for one with a restenosis who had recurrent transient ischaemic attacks. CONCLUSION: Transluminal angioplasty may be an effective procedure to treat vertebrobasilar ischaemia secondary to high grade arteriosclerotic disease affecting either the distal vertebral or basilar artery regions that do not respond to medical treatment.

Acute Disease

[Super selective amytal test for functional evaluation of the brain--a less invasive functional test].

In the neurosurgical field, it is very important to evaluate localized function of the affected region preoperatively. In order to investigate lateralized and localized brain function, we have developed an alternative to the original Wada test, and refer to it as the super selective amytal test (SSAT). We performed super selective catheterization of the target artery after conventional carotid angiography, injected Amytal (amobarbital, 30-100 mg) through a micro-catheter, and identified potential local function. In ten cases, including AVM, aneurysm, and brain tumor, we investigated localized function of the affected site preoperatively by SSAT, and chose our treatment based on the results of this test. There was a good correlation between the results of the SSAT and the results of surgery in every case. There were no prolonged neurological complications of this test. Evaluation of the results of the SSAT should be interpreted under precise DSA control, since blood flow in the brain differ among individuals. This test may contribute to our knowledge of localized function in the cerebral cortex and deep brain areas in neurosurgical patients.

Adult

[Endovascular treatment of cerebral vasospasm with intra-arterial papaverine infusion].

Thirty-one cases of cerebral vasospasm following subarachnoid hemorrhage were treated with intraarterial papaverine infusion. Symptomatic cases were nineteen, and asymptomatic cases were twelve. Papaverine (120 mg/saline 50 ml, 30 min) was injected superselectively to vasospastic vessels through a microcatheter. The rate of symptomatically improved cases was 63% initially, but about two thirds of those cases had recurrence within a day. The 63% of symptomatic cases showed infarction in spite of papaverine infusion. Three cases of recurrent vasospasm after intra-arterial papaverine underwent PTA and showed good dilatation of vasospastic vessels. The complications of our intra-arterial papaverine were hypotension in two cases, convulsion in one case and transient disturbed consciousness in one case. We experienced no fatal complications. Overall outcome was ADL1 (19%), ADL2 (25%), ADL3 (44%), ADL4 (0%), ADL5 (6%), and death (6%). Since the effect of intra-arterial papaverine infusion is of short duration and weak, combination of PTA and papaverine may be necessary. It is recommended to use papaverine for vasospasm in distal arteries such as M2, A1, A2, and to carry out PTA for proximal arteries such as ICA and M1.

Adult

[Effects on cognitive function and activities of daily living after stereotactic thalamotomy for Parkinson's disease].

Stereotactic thalamotomy was performed in ten patients with Parkinson's disease for the suppression of their tremor. After VL-thalamotomy, contralateral tremor and rigidity disappeared or was significantly reduced. Activities of daily living (ADL) measured by functional independence measure and Parkinson's disability score were improved postoperatively in all patients. There was significant improvement in anxiety index. However, other neuropsychological tests showed no significant change postoperatively. ADL improved after thalamotomy. It is concluded that stereotactic VL-thalamotomy is a useful treatment which improves ADL without cognitive dysfunction.

Activities of Daily Living

Studies on beta-lactam antibiotics. IV. An improved synthesis of 3-(isothiazolylthiomethyl)cephalosporins and its application to new derivatives.

An improved synthesis and in vitro activity of cephalosporins with a (4-carboxy-3-hydroxy-5-isothiazolyl)thiomethyl group at the 3-position and its application to the preparation of new derivatives are described. These compounds showed excellent activity against Gram-negative bacteria including beta-lactamase producing strains. Among them, 2f was the most interesting because of its broad spectrum of antibacterial activity, including Gram-positive bacteria, and its outstanding inhibitory potency against Pseudomonas aeruginosa.

Animals

Acute subdural hematoma associated with vacuolated meningioma--case report.

A 67-year-old male presented with a left temporal convexity vacuolated meningioma associated with acute subdural hematoma manifesting as sudden headache, nausea, and vomiting without neurological deficit. Magnetic resonance imaging disclosed an extra-axial mass as mixed low- and high-signal intensities and a crescent high-intensity area in the left convexity. Histological examination diagnosed meningotheliomatous meningioma with vacuolated components and hemorrhagic foci. The tumor and hematoma were removed without postoperative complications.

Aged

[Acute subdural empyema due to peptostreptococcus].

A very rare case of acute subdural empyema due to peptostreptococcus was reported. A 11-year-old-girl was admitted to our hospital with high grade fever, unconsciousness and rt hemiparesis. CT scans showed the mass effect caused by the subdural empyema over the left frontotemporal region. Subdural empyema was evacuated by the craniotomy. Peptostreptococcus was found in the pus obtained during the operation. However, CT scans 10 days after the operation revealed another subdural empyema in the left frontal base and interhemispheric fissure, which was removed again by the craniotomy using coronal incision 14 days after the first operation. Frontal sinusitis was also demonstrated by CT scan. Killian's operation to the frontal sinusitis was performed by otorhinolaryngologists at the same time. Six weeks after the second operation, she was discharged without any neurological deficits. Peptostreptococcus is one of the indigenous microflora of the oral cavity, skin, gastrointestinal tract and genitourinary system and may be a causative microorganism in every type of human infection due to its abnormal localization. There is a controversy concerning surgical management subdural empyema. Both the burr hole drainage of pus and the craniotomy are advocated. Associated otorhinologic lesions must not be overlooked. Otorhinologic consultation should immediately be obtained so that the drainage of an infected paranasal or mastoid sinus can be performed at the time of craniotomy. This is critical to prevent the recurrence of the subdural empyema from further extension of the extracranial disease.

Acute Disease

Stereotactic hyperthermia for brain tumors.

We have developed a localized hyperthermia system using computed tomography-stereotactic surgery as malignant brain tumor therapy. In an experimental study, the temperature in the area of the cat brain within 20 mm from a radiofrequency electrode reached more than 43.7 degrees C. Intravenous administration of MCNU during hyperthermia caused a significant increase of MCNU content in the heated brain as compared with a control brain. In the clinical study, localized radiofrequent hyperthermia using stereotactic surgery was performed on 7 malignant deep-seated gliomas and 21 metastatic brain tumors. Especially, combination therapy of stereotactic hyperthermia and chemotherapy was effective treatment for gliomas less than 30 mm deep in the brain.

Adolescent

Stereotactic evacuation of hypertensive cerebellar hemorrhage using plasminogen activator.

Treatment for hypertensive cerebellar hemorrhage still remains controversial as to whether direct surgical procedure is indicated or not. This is so even after the introduction of CT scan which easily demonstrates the location and size of the hematoma and the presence of hydrocephalus. In this paper, we present our experience of 20 patients with cerebellar hemorrhage treated by stereotactic evacuation using Komai's CT-stereotactic apparatus. All the patients had vertigo, cerebellar symptoms, dysfunction of brain stem or consciousness disturbance. The hematomas on CT scan were more than 28 mm in diameter. Acute obstructive hydrocephalus occurred in 90% of the patients with hematoma 40 mm or larger in size. The patients with consciousness disturbance were immediately operated on after the attack, and a drainage tube was placed in the hematoma cavity to drain cerebrospinal fluid and liquefied hematoma for one to eight days. On the other hand, when patients with hematoma around 30 mm in diameter complained vertigo for about two weeks, they also were operated on stereotactically. After the operation, their symptoms improved rapidly. The stereotactic operation could aspirate about 85% of the estimated hematoma volume and improved the hydrocephalus, except in one case in which the patient rapidly deteriorated to coma level with a large cerebellar hemorrhage and brain stem damage. This stereotactic evacuation of cerebellar hematoma using a plasminogen activator is effective for not only the removal of hematoma, but also for the treatment of secondary hydrocephalus following obstruction of the fourth ventricle by cerebellar hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Three-dimensional correlation between auditory brainstem response and auditory tract in hypertensive pontine hematoma].

A three-dimensional reconstructed display using a microcomputer represents the spatial correlation between the nuclei of auditory tract and pontine hematoma. Stereotaxic evacuation of hematoma was performed on seven cases of pontine hemorrhage. By making a comparison between preoperative and postoperative findings of ABR and this display, we examined the effect of the surgical intervention on ABR findings. ABR was recorded according to the standard way (100 dBSL, 2000 click stimuli). Hematoma was drawn on the Atlas of the Human Brainstem and Cerebellar Nuclei by Farhad Afshar. The data plotted on digitizer was inputted and processed under our computer program that enables the brainstem and hematoma visualized and rotated three-dimensionally at our option. The results were as follows: a) ipsilateral dominance in human auditory tract in terms of the origin of ABR waves, b) delayed latency time of wave II which was supposed to be based on an influence upon the ipsilateral superior olivary nucleus, c) that of wave III upon the ipsilateral lateral lemniscus, d) four cases of them showed an improvement of I-III interpeak latency time, which suggested the decompressive effect on caudal aspect of pons.

Adult

Mode of cell growth of Malassezia (Pityrosporum) as revealed by using plasma membrane configurations as natural markers.

The mode of cell growth of Malassezia was studied by freeze-fracture using the plasma membrane configurations of this organism as natural markers. The plasma membrane of the mature cell bodies of M. pachydermatis had a ring swelling, and on each side of the ring, one set of straight and spiral grooves and circumvallate bulgings. The cell always divided at the ring swelling (M. pachydermatis) or depression (M. furfur), soon followed by budding there. A new set of similar configurations formed on the bud. In all the 12 strains of Malassezia studied, the spiral grooves in the mother and bud parts were both left-handed but opposite in the direction of elongation. By comparing distances between the spiral grooves in short and long buds and in mothers, the bud tip was suggested as the major, and adjacent regions as the minor, sites of wall growth. Some characterizations of the plasma membrane invaginations, especially in relation to the mode of cell growth, were also described.

Cell Membrane