Search PubMed⌕ Search

Biomedical subjects

N Arai

Publications and source records attributed to N Arai.

At least 55 records · Page 3Linked to original sources

Surgical indication for refractory childhood epilepsy.

Recent progress in surgical intervention for medically refractory epilepsy has helped to shed light on more complex epileptogenic problems in children and infants. Surgical treatment increasingly is being used in pediatric patients, but the indications for surgery in this age group have not been well defined. The developing child with a seizure disorder has several problems that are different from adults, such as neural plasticity, deleterious effects of seizures on developmental status, and spontaneous resolution of epilepsy. The critical age for irreversible brain dysfunction and the timing of surgery are the main issues for the treatment of children. Thus, earlier surgical intervention is generally recommended to prevent further detrimental seizure effects, but we still do not know the optimal age. Until the establishment of guidelines for pediatric epilepsy surgery, surgical indications should be determined by the prognosis and the presence of a resectable epileptogenic focus, which in turn are based on the localization of the epileptic focus, seizure frequency, severity, and cognitive function of each case, rather than just the patient's age.

Age Factors↗

A case of false median cleft of upper lip with IV-A holoprosencephaly that underwent cheiloplasty at 2.5 years of age.

Holoprosencephaly results from the incomplete development of midline structures within the cerebrum and encompasses a series of abnormalities of mid-facial development. Here, we report a case of male holoprosencephaly associated with false median cleft of upper lip. This patient belonged clinically to the DeMyer's group IV holoprosencephaly, semilobar type. An infant with this type of holoprosencephaly has been thought to die generally within 1 to 2 years after birth and to rarely benefit from an operation. In this case, the patient had cheiloplasty at the age of 2.5 years at the request of his parents and he lives currently, being 3 years and 2 months old.

Child, Preschool↗

Argadin, a new chitinase inhibitor, produced by Clonostachys sp. FO-7314.

A new chitinase inhibitor, designated as argadin (1), was isolated from the cultured broth of a fungal strain FO-7314. The strain was identified as Clonostachys sp. from the morphological characteristics. Argadin was purified from the cultured mycelium by a combination of cation exchange, adsorption and gel filtration chromatographic methods. The structure of argadin was elucidated as cyclo(Nomega-acetyl-L-arginyl-D-prolyl-homoseryl-histidyl-L- 2-aminoadipyl) in which homoseryl gamma-methylene bonded to histidyl alpha-amino residue. The IC50 value of argadin against Lucilia cuprina (blowfly) chitinase was 150 nM at 37 degrees C and 3.4 nM at 20 degrees C. Argadin arrested the moult of cockroach larvae upon injection into the ventral abdominal part.

Animals↗

L-DOPA cyclohexyl ester is a novel potent and relatively stable competitive antagonist against L-DOPA among several L-DOPA ester compounds.

We explored L-DOPA esters with chemically bulky structures to find a potent stable competitive antagonist against L-DOPA, compared to DOPA methyl ester (DOPA ME). In anesthetized rats, DOPA cyclohexyl ester (DOPA CHE), DOPA cyclopentyl ester (DOPA CPE) and DOPA cyclopentyldimethyl ester (DOPA CPDME) at 1 microgram microinjected into depressor sites of the nucleus tractus solitarii elicited or tended to elicit more marked antagonism against depressor responses to 60 ng L-DOPA, compared to DOPA ME. At 100 ng, DOPA CHE elicited the most potent antagonism. At 1 microgram, duration of the antagonistic activity of DOPA CHE was approximately three times longer than that of DOPA ME. During microdialysis of the nucleus accumbens, conversion from DOPA CHE at 1 microM perfused via probes to extracellular L-DOPA was the lowest among these compounds and less than one half of that from DOPA ME. Binding studies showed that the recognition site for L-DOPA differs from ionotropic glutamatergic, dopaminergic D1 and D2 receptors. We recently found that L-DOPA evoked by transient ischemia may act as a DOPA CHE-sensitive causal factor for glutamate release and resultant neuronal cell death. DOPA CHE is the most potent, relatively stable competitive antagonist against L-DOPA and is a useful mother compound to develop neuroprotective drugs.

Animals↗

Arisugacins C and D, novel acetylcholinesterase inhibitors and their related novel metabolites produced by Penicilium sp. FO-4259-11.

The mutant of Penicillium sp. FO-4259, an arisugacins A and B producing strain, was found to produce a series of metabolites, designated arisugacins C, D, E, F, G and H, which were structurally related to arisugacins A and B. These compounds were isolated from the culture broth and the physico-chemical and biological properties were examined. The IC50 values of arisugacins C and D against acetylcholinesterase (AChE) were 2.5 microM and 3.5 microM, respectively. However arisugacins E, F, G and H did not inhibit AChE at 100 microM. Though they showed only weak or no activity against AChE compared with arisugacins A and B, they may be useful for the study of the structure-activity relationship.

Cholinesterase Inhibitors↗

Argifin, a new chitinase inhibitor, produced by Gliocladium sp. FTD-0668. I. Taxonomy, fermentation, and biological activities.

A new chitinase inhibitor, named argifin, was isolated from the cultured broth of a fungal strain FTD-0668. The strain was identified as Gliocladium sp. from morphological characteristics. The IC50 value of argifin against Lucilia cuprina chitinase was 3.7 microM. Argifin arrested the moult of cockroach larvae upon injection into the ventral abdominal part.

Animals↗

Argifin, a new chitinase inhibitor, produced by Gliocladium sp. FTD-0668. II. Isolation, physico-chemical properties, and structure elucidation.

A new chitinase inhibitor, named argifin, was isolated from the cultured broth of a fungal strain Gliocladium sp. FTD-0668. Argifin was purified from the cultured mycelium by the combination of cation exchange, anion exchange, adsorption, and gel filtration chromatographic methods. The structure of argifin was elucidated as cyclo(N(omega)-(N-methylcarbamoyl)-L-arginyl-N-methyl-L-phenylalan yl-beta-L-aspartyl-beta-L-aspartyl-D-alanyl) by NMR experiments and other spectroscopic analyses.

Chitinases↗

[Rheumatoid arthritis-associated bronchiolitis successfully treated with erythromycin].

A 52-year-old man with a 4-year history of rheumatoid arthritis, and who had an episode of suspected BOOP in early 1994, was admitted to our hospital because of cough and fever. A chest X-ray film on admission showed small patchy infiltrates, and a computed tomographic (CT) scan showed centrilobular nodules and patchy infiltrates with thickened broncho-vascular bundles in both lungs. Transbronchial and thoracoscopic lung biopsies disclosed the coexistence of interstitial pneumonia with BOOP pattern, follicular bronchiolitis, and diffuse panbronchiolitis-like purulent and obliterative bronchiolitis. Due to findings of chronic sinusitis, the patient was treated with erythromycin for 8 weeks, and the abnormal CT shadows regressed. This was an interesting case of various pulmonary lesions associated with rheumatoid arthritis, and successfully treated with erythromycin.

Anti-Bacterial Agents↗

[Long-term prognosis of asthmatic patients treated with low-dose beclomethasone dipropionate].

To clarify the prognosis of asthmatics treated with low-dose of inhaled beclomethasone dipropionate (BDP), we retrospectively assessed 43 patients treated with initial dose of 200 or 400 micrograms/day for 5 years, and obtained the following results. 1) 15 patients achieved step-down therapy (group A), 17 patients maintained initial dose of BDP (group B), and 11 patients required step-up therapy of BDP or daily use of oral prednisolone (group C). 2) There was no significant difference in age, sex, duration of disease, severity of disease, peripheral eosinophil counts, %FEV1 and histamine PC20 before BDP treatment among three groups. The percentage of atopic asthmatics was significantly higher in group C than in group A. 3) There was no significant difference in symptom and histamine PC20 between after 1 year state and after 5 years state in three groups. 4) After 1 year from the start of BDP treatment, only 18% patients got symptom free and neither patients exceeded 20,000 micrograms/ml of histamine PC20 in group C. Long-term treatment of low-dose BDP inhalation was effective on mild/moderate asthmatics. Patients requiring step-up therapy had not got sufficient improvement in bronchial hyperresponsiveness after one-year treatment.

Adult↗

[Acute eosinophilic pneumonia induced by cigarette smoking: positive lymphocyte stimulation test of a cigarette extract].

A 21-year-old man was admitted to our hospital with high fever, general fatigue and dyspnea. Chest radiography on admission showed diffuse bilateral infiltrate shadows with Kerley's B lines, and a CT scan showed patches of infiltrates with thickened interlobular septa in both lungs. Examination of the bronchoalveolar lavage fluid and the clinical course led to a diagnosis of acute eosinophilic pneumonia. The patient improved without steroid therapy. We suspected that the disease was related to smoking because the patient had started smoking seven days before the onset of the symptoms. Because a lymphocyte stimulation test gave a positive reaction to a cigarette extract, a challenge test was done. After this, the patient had fever and hypoxemia. These findings suggest that cigarette smoking induces acute eosinophilic pneumonia.

Acute Disease↗

[A case of primary Sjögren's syndrome with interstitial pneumonia showing bronchiolitis obliterans organizing pneumonia pattern and lymphofollicular formation].

A 46-year-old woman with a 2-year history of xerostomia, who had had an episode of suspected Sjögren's syndrome in 1995, was admitted to our hospital because of a dry cough. Chest radiography on admission showed ground-glass infiltrates and reticular shadows in both lower lung fields. Primary Sjögren's syndrome was diagnosed by lip biopsy. Video-assisted thoracoscopic lung biopsies revealed the co-existence of interstitial pneumonia with the BOOP pattern and follicular bronchiolitis. Treatment with oral prednisolone improved the symptoms, and reduced the abnormal chest shadows. This was an interesting case of the BOOP pattern in a lung lesion associated with primary Sjögren's syndrome.

Administration, Oral↗

Two independent calcineurin-binding regions in the N-terminal domain of murine NF-ATx1 recruit calcineurin to murine NF-ATx1.

Intracellular calcium regulates events controlling nuclear translocation of nuclear factor of activated T cells (NF-AT). Calcium-dependent phosphatase calcineurin (CN) plays a central role in this process. Structural and functional analyses of the N-terminal domain of murine NF-ATx1, a member of the NF-AT family, have defined two distinct CN binding regions (CNBRs), CNBR1 and CNBR2, which are located in the region preceding the SP boxes of serine/proline-rich sequences and the region between the SP boxes and Rel similarity domain, respectively. The binding of murine NF-ATx1 (mNF-ATx1) to CN was abolished by deletion of these two regions, yet was unaffected by the individual deletion. In contrast, the nuclear translocation of mNF-ATx1 was much reduced when only CNBR2 was removed. Luciferase assay revealed that both regions are required for mNF-ATx1-dependent activation of the murine IL-2 promoter. Most importantly, recombinant CNBR2 bound CN with a higher affinity, and when expressed in Jurkat cells, it functioned as a dominant negative mutant that prevented the transcription driven by exogenous mNF-ATx1, probably by interfering with the function of CN. We propose that activation of mNF-ATx1 can be modulated through two distinct CN target regions. Our findings provide a new opportunity for pharmacological intervention with Ca2+-dependent signaling events.

Animals↗

Long-term result of arterial grafts interposed for arterial defects using the telescoping anastomotic technique: histological and angiographic study.

The arterial grafting model for arterial defects provides an ideal environment for the microvascular telescoping anastomosis because tension of the repaired vessel is maintained low and deformities of the inserted vessel end is minimal due to the thick arterial wall. The left femoral artery was grafted in 46 rats into the defect created in the right femoral artery using the telescoping anastomotic technique at both the proximal and distal anastomoses. The grafts were seen histologically and angiographically 3 to 4 months postoperatively in order to fairly evaluate the telescoping anastomosis in terms of long-term patency, stenosis, and changes in the outer and inner walls at the anastomosis. All arterial grafts were patent 3 to 4 months postoperatively and there were no aneurysms at the anastomoses. Enlargement of the graft diameter was minimal. The rate of stenosis at the anastomosis was smaller than that 1-day postoperatively. Even though the thick arterial wall was initially inserted and the intimal hyperplasia was still present at the anastomosis 3 to 4 months postoperatively, the long-term stenosis was relatively mild due to the atrophy in the overlapped walls.

Anastomosis, Surgical↗

GATA-3 significantly downregulates IFN-gamma production from developing Th1 cells in addition to inducing IL-4 and IL-5 levels.

IL-12 and IL-4 are dominant factors driving the development of Th1 and Th2 cells, respectively, by their activation of Stat-4 and Stat-6 signaling molecules. Activation of Stat factors, although specific, is a rapid event; however, differentiation of Th cells takes place over several days. Thus, it is unlikely that the expression of effector cytokines is mediated solely by Stat factors. Recently there have been indications that link other molecular factors to Th subset development. The transcription factor GATA-3 is selectively expressed in Th2 cells and has been shown to induce the expression of Th2 cytokines in developing Th1 cells. Using retroviral infection of naive T cells to introduce GATA-3 cDNA, we measured its direct effects on the development of Th1 cytokine production. We now show that ectopic expression of GATA-3 in developing Th1 cells significantly inhibits IFN-gamma, as well as enhancing IL-4 and IL-5 production. Furthermore, GATA-3 inhibits production of IFN-gamma by developing Th1 cells in the complete absence of IL-4. Thus, antagonism of Th1 development by GATA-3 may facilitate rapid divergence of Th subsets toward a Th2 phenotype in concert with other factors.

Animals↗

Cortical tubers without other stigmata of tuberous sclerosis: imaging and pathological findings.

There is immense variability in the clinical presentation of tuberous sclerosis and many incomplete forms (formes frustes) exist. To investigate the imaging characteristics of cortical tubers seen in tuberous sclerosis unaccompanied by other stigmata, we reviewed MRI and CT of six patients who met the criteria for a definitive diagnosis of TS, established solely by the presence of a histologically confirmed cortical tuber. Five of the patients had a solitary cortical tuber and the last had three lesions, one of which was resected and confirmed histologically. The other two lesions were included in our study. CT showed five tubers as low density, but three were not identified. No calcified or dense lesions were observed. MRI revealed peripheral components and inner cores of seven cortical tubers in five patients, with differing signal characteristics. The subcortical cores, with T1 and T2 prolongation, were separated from the overlying cortex. Abnormal inhomogeneous high signal was observed in both the cortex and subcortical white matter on proton-density weighted or FLAIR images. A radially orientated white-matter band was observed in one patient, and central depression of the expanded gyri in another. In one patient, a cortical tuber was atypical, with a thick cortex on T1-weighted images and a blurred grey/white matter junction with diffusely increased signal on T2-weighted images. Cortical tubers without other stigmata of tuberous sclerosis are shown to be distinct from focal cortical dysplasia.

Adolescent↗