Quantitative analysis of MEG using modified sLORETA for clinical application.

OBJECTIVE: To determine whether standardised low-resolution brain electromagnetic tomography modified for a quantifiable method (sLORETA-qm) can be used for quantitative analysis in magnetoencephalography (MEG). METHODS: Somatosensory evoked fields (SEFs) were obtained from 10 hemispheres of five healthy volunteers stimulated on the median nerve at 0.75, 1.0, 1.25, 1.5, 1.75 and 2.0 x threshold of thenar muscle twitch (TMT). N20 m intensity changes were analysed quantitatively using sLORETA-qm. Then, SEFs were measured with stimulation on the median nerve at 1.5 x TMT from 47 hemispheres in 24 subjects. sLORETA-qm intensity and the equivalent current dipole (ECD) moment of N20 m were calculated, and relationships between the values were evaluated. RESULTS: sLORETA-qm intensity increased linearly with stimulus intensity between 0.75 and 1.5 x TMT, and tended to reach a plateau or decrease at higher stimulus intensities. The distribution of sLORETA-qm intensity after natural logarithmic transformation was normal and a close correlation was found between the ECD moment and sLORETA-qm intensity (r(s)=0.91, p<0.001). CONCLUSIONS: The results of this study focusing on N20 m suggested that sLORETA-qm is reliable for quantitative analysis of MEG as well as ECD models. SIGNIFICANCE: sLORETA-qm appears promising for quantitative analyses of MEG for which ECD models are inappropriate.

Novel, potent, and selective phosphodiesterase-4 inhibitors as antiasthmatic agents: synthesis and biological activities of a series of 1-pyridylnaphthalene derivatives.

The structural requirements for potent and selective PDE4 inhibition were revealed in a 1-pyridylnaphthalene series, and the best compound (3kg, T-2585.HCl) was chosen for further biological evaluation (PDE4 inhibition IC50 = 0.13 nM, selectivity PDE3/4 ratio = 14 000). Compound 3kg showed potent antispasmogenic activities (ED50 = 0.063 mg/kg for reduction of antigen-induced bronchoconstriction, intravenously; ED50 = 0.033 mg/kg for reduction of histamine-induced bronchoconstriction, intraduodenally) in guinea pigs with little cardiovascular effects. Furthermore, 3kg induced significantly weaker emetic effects than RP73401 after oral administration in ferrets and intravenous administration in dogs (3kg, none of 4 ferrets vomited at a dose of 10 mg/kg, po and none of 8 dogs vomited at a dose of 0.3 mg/kg, iv; RP73401, 4 of 8 ferrets vomited at a dose of 3 mg/kg, po and 6 of 8 dogs vomited at a dose of 0.3 mg/kg, iv); that is compatible with the lower affinity for the high-affinity rolipram binding site (3kg, 2.6 nM; RP73401, 0. 85 nM). This may imply that 3kg has an improved therapeutic ratio because of a broad margin between the Ki value of binding affinity and the IC50 value of PDE4 inhibition (ratio = 0.050).

[Management strategies for unruptured cerebral aneurysms].

We discussed management strategies for unruptured aneurysms by an analysis of 62 treated and 48 untreated cases. The treated cases were divided into the following two groups; Group A consisted of 38 patients with 46 aneurysms treated during our initial 13 years (7 males, 31 females, 54 +/- 9 years old), and Group B of 24 patients with 32 aneurysms (8 males, females 16, 57 +/- 9 years old) during the last 3 years. In Group A, 36 patients were treated with neck clipping, except for two patients, who had giant aneurysms treated with internal carotid ligation and bypass surgery. All the patients in Group B were treated with either clipping or endovascular coil embolization. Our indications for coil embolization include patients with aneurysms located in paraclinoid internal carotid or basilar arteries, or with multiple aneurysms requiring more than one operation, or with a systemic risky disease for general anesthesia. In group A, 2.6% of cases resulted in death during operation and 10.3% of cases resulted in morbidity, while in group B, there was neither mortality nor morbidity caused by clipping, except for a patient with mild hemiparesis who had been treated with clipping for SAH caused by a procedure of coil embolization. The 50 aneurysms of 48 untreated patients have been observed without any neurosurgical treatment during periods of 6 months to 10 years with a mean of 2 years 7 months. Eventually, four aneurysms resulted in SAH, which cases were treated with emergency clipping or coil embolization. The high rupture rate (3.1% per year) in the natural history may suggest that some aneurysms are more likely to rupture than generally considered. We also reviewed operative findings of all entry clipping cases; more than 80 percent of aneurysms, including those measuring less than 5 mm in diameter, had red colored, thin wall domes with or without bleb. Our conclusion is that surgical indications are for a complementary use of clipping and coil embolization.

Development of malignant glioma 15 months after anterior temporal lobectomy in a patient with temporal lobe epilepsy.

We report a 36-year-old woman, who had previously undergone anterior temporal lobectomy for intractable temporal lobe seizures; fifteen months later, magnetic resonance (MR) images showed a space-occupying lesion in the temporal lobectomy cavity. After a second operation, a histopathological examination showed a grade III astrocytoma. The fortuitous co-occurrence of temporal lobe epilepsy and a tumour was suspected, but histopathological and immunohistochemical examination of original resected temporal lobe parenchyma did not show evidence of neoplasm. The patient had not undergone postoperative radiotherapy and had not experienced viral infections. We propose that two factors possibly associated with the development of glioma were chemical exposure from anticonvulsant agents and trauma from resection of the anterior temporal lobe during initial surgery.

Cytotoxicity of cis-[((1R,2R)-1,2-cyclohexanediamine-N,N')bis(myristato)]-platinum (II) suspended in Lipiodol in a newly established cisplatin-resistant rat hepatoma cell line.

The cytotoxic activity of cis-[((1R,2R)-1,2-cyclohexanediamine-N, N')bis(myristato)]platinum (II) (SM-11355) was evaluated in a cisplatin (CDDP)-resistant tumor cell line, and compared with that of CDDP. H4-II-E / CDDP with acquired resistance to CDDP was established by continuous exposure of a rat hepatic tumor line, H4-II-E, to increasing concentrations of CDDP over 12 months. Compared with the parental cell line, this cell line exhibited an 8.8-fold increase in resistance to CDDP and was not cross-resistant to 1,2-diaminocyclohexane platinum (II) dichloride (DPC). There were no differences in sensitivity to six non-platinum antitumor drugs between H4-II-E and H4-II-E / CDDP, which suggests that H4-II-E / CDDP is not multidrug-resistant. Intracellular platinum accumulation and the formation of a platinum-DNA adduct following CDDP exposure were significantly reduced in H4-II-E / CDDP compared to the parental cell line. The acquired CDDP resistance in H4-II-E / CDDP appeared to be predominantly due to reduced CDDP uptake. H4-II-E / CDDP was also resistant to CDDP suspended in Lipiodol (CDDP / Lipiodol), but was not cross-resistant to SM-11355 suspended in Lipiodol (SM-11355 / Lipiodol). Also, there were no differences in intracellular platinum accumulation or the formation of platinum-DNA adducts after SM-11355 / Lipiodol exposure between H4-II-E and H4-II-E / CDDP. These results suggest that acquired CDDP resistance in H4-II-E / CDDP does not influence the cytotoxic activity of SM-11355 / Lipiodol.

Spinal arteriovenous malformation associated with a radicular arteriovenous fistula suggested a metameric disease. A case report.

SUMMARY: A spinal intramedullary arteriovenous malformation (AVM) associated with a radicular arteriovenous fistula (AVF) is reported. The patient had mild myelopathy and low back pain. Spinal angiography revealed the AVM fed by the anterior spinal artery via left T10, T11 and right L1 radiculomedullary arteries and the radiculopial arteries of left L1, L2 and right T11, L3 levels and the radicular AVF at the left L4 level. There were three radiculomedullary arteries within four levels in our case. This spinal AVM associated with a radicular AVF is considered a genetic nonhereditary lesion with metameric link.

Solution-phase synthesis of an anti-human immunodeficiency virus peptide, T22 ([Tyr5,12,Lys7]-polyphemusin II), and the modification of Trp by the p-methoxybenzyl group of Cys during trimethylsilyl trifluoromethanesulfonate deprotection.

T22 ([Tyr5,12,Lys7]-polyphemusin II) was previously synthesized by a solid-phase method and was found to have a strong anti-human immunodeficiency virus (HIV) activity, comparable to that of 3'-azido-2',3'-dideoxy-thymidine (AZT). In the present study, the solution-phase synthesis of T22 was attempted in order to produce this peptide on a large scale. An 18-residue peptide amide corresponding to the entire amino acid sequence of T22 was synthesized by assembling four peptide fragments and two amino acid derivatives, followed by thioanisole-mediated deprotection with 1 M trimethylsilyl trifluoromethanesulfonate (TMSOTf) in trifluoroacetic acid followed by air-oxidation. During this deprotection, a significant by-product derived from the transfer of the p-methoxybenzyl (MBzI) group from the sulfhydryl group of the cysteine residue to the side chain of the tryptophan residue was formed. This side reaction was found to be efficiently suppressed by adopting a two-step deprotection procedure using silver trifluoromethanesulfonate (AgOTf)-TMSOTf or trimethylsilyl bromide (TMSBr)-TMSOTf.

Molecular parameters for the anti-human immunodeficiency virus activity of T22 ([Tyr5,12, Lys7]-polyphemusin II).

T22 ([Tyr5,12, Lys7]-polyphemusin II) was found to exhibit strong anti-human immunodeficiency virus (HIV) activity and exert its effects on a virus-cell fusion process. In the present study, the all-D enantiomer of T22 and its related compounds were synthesized to examine the molecular parameters required for the interaction of T22 with membrane components of cells or viruses in order to exert this anti-HIV activity. The anti-HIV activity of these analogs was investigated in comparison with their membrane permeability with aspect to large unilamellar vesicles (LUVs). The all-D enantiomer of T22 exhibited a 20-fold lower anti-HIV activity compared with T22, whereas they both showed the same membrane permeability. No positive correlation between anti-HIV activity and membrane permeability was observed. These results suggest that the anti-HIV activity of T22 is mediated through the interaction with chiral component(s) of the cell or virus.

A novel anti-HIV synthetic peptide, T-22 ([Tyr5,12,Lys7]-polyphemusin II).

Tachyplesin and polyphemusin are antimicrobial peptides recently isolated from the hemocytes of horseshoe crabs (Tachypleus tridentatus and Limulus polyphemus). We synthesized them and their analogs and examined their antiviral activity against human immunodeficiency virus (HIV) type 1 in vitro. The infection of human T cells with the virus was markedly inhibited by some of them at low concentrations. In this structure-activity study, we found that [Tyr5,12, Lys7]-polyphemusin II, which was designated as T22, had extremely high anti-HIV activity. Its 50% inhibitory concentration (EC50) was 0.008 micrograms/ml, while its 50% cytotoxic concentration (CC50) was 54 micrograms/ml and these values were comparable to those of AZT. This result indicates that T22 would be a potential candidate for the therapy of HIV infection.