Use of a stackable surgical guide to improve the accuracy of the lateral wall approach for sinus grafting in the presence of a sinus septum.

The identification and management of interfering maxillary sinus septa is essential to anticipate and prevent membrane perforation and other complications during sinus grafting. A computer-guided sinus approach based on a new magnetic stackable surgical guide was planned, to transfer the exact position of the septum and optimize the positioning of the lateral access windows. This technique reduces the risk of sinus membrane injury, thereby increasing the safety and efficacy of the procedure.

Overcoming the ceiling effects of experts' motor expertise through active haptic training.

One of the most challenging issues among experts is how to improve motor skills that have already been highly trained. Recent studies have proposed importance of both genetic predisposition and accumulated amount of practice for standing at the top of fields of sports and performing arts. In contrast to the two factors, what is unexplored is how one practices impacts on experts' expertise. Here, we show that training of active somatosensory function (active haptic training) enhances precise force control in the keystrokes and somatosensory functions specifically of expert pianists, but not of untrained individuals. By contrast, training that merely repeats the task with provision of error feedback, which is a typical training method, failed to improve the force control in the experts, but not in the untrained. These findings provide evidence that the limit of highly trained motor skills could be overcome by optimizing training methods.

Pacemaker-associated infection caused by ST81/SCCmec IV methicillin-resistant, vancomycin-intermediate Staphylococcus aureus in Japan.

A 76-year-old Japanese man was admitted to hospital for treatment of fever and skin lesion at the implantation site of his pacemaker. During his hospitalization, vancomycin-intermediate Staphylococcus aureus (MIC 4 µg/mL) with reduced susceptibility to daptomycin was isolated from venous blood. This isolate was identified as methicillin-resistant S. aureus with SCCmec IV and was genotyped as sequence type 81, coa VIIa and spa type t7044, harbouring blaZ, aac(6')-aph(2″) and enterotoxin(-like) genes sea, seb, sek, sel, selx and selw. The patient was successfully treated with daptomycin, minocycline and sulfamethoxazole/trimethoprim. We describe the identification of sequence type 81/SCCmec IV vancomycin-intermediate S. aureus from pacemaker-associated septicaemia.

Novel short-duration heating balloon dilatation with uniform temperature distribution: the heating conditions to suppress neo-intimal hyperplasia.

We investigate the relation between the influences on smooth muscle cells and the chronic performances of our novel short-duration heating balloon dilatation to reveal the heating conditions which can suppress the neo-intimal hyperplasia after our heating dilatations. The temperature of prototype balloon catheter surface was measured during short-duration heating balloon dilatation ex vivo. There existed 2 °C temperature variations in the long direction of prototype balloon catheter at a maximum. The neo-intimal hyperplasia occupancy rate after our short-duration heating dilatations were measured in vivo porcine study. The neo-intimal hyperplasia was suppressed most at 75 °C in balloon peak temperature in vivo. The estimated dead rate of smooth muscle cells at this condition was about 13% by the Arrhenius equation. We think that the suppression of neo-intimal hyperplasia was obtained after our short-duration heating dilatation due to the proper decrease of smooth muscle cells by heating and no thermal damages to the adventitia and surrounding tissues.

The Tokyo subway sarin attack--lessons learned.

The sarin gas attack in the Tokyo subway system is reviewed from a clinical toxicology perspective. Based on the lessons learned from this attack, the following areas should be addressed on a global scale. First, an adequate supply of protective equipment is required, including level B protective equipment with a pressure demand breathing apparatus. In addition, a system should be established that enables a possible cause to be determined based on symptoms, physical findings, general laboratory tests, and a simple qualitative analysis for poisonous substances. If an antidote is needed, the system should enable it to be administered to the victims as quickly as possible. Preparation for a large-scale chemical attack by terrorists requires the prior establishment of a detailed decontamination plan that utilizes not only mass decontamination facilities but also public facilities in the area. A system should be established for summarizing, evaluating, and disseminating information on poisonous substances. Finally, a large-scale scientific investigation of the Tokyo sarin attack should be conducted to examine its long-term and subclinical effects and the effects of exposure to asymptomatic low levels of sarin.

Superiority of minipool nucleic acid amplification technology for hepatitis B virus over chemiluminescence immunoassay for hepatitis B surface antigen screening.

BACKGROUND AND OBJECTIVES: The Japanese Red Cross (JRC) have developed a fully automated multiplex (MPX) nucleic acid amplification technology (NAT) system for hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus 1 (HIV-1). This is used to test serologically negative blood units from volunteer, non-remunerated donors. The system utilizes a 50-sample pool for NAT screening with an input volume of each pool. This results in a significantly higher sensitivity for hepatitis B than that seen with highly sensitive hepatitis B surface antigen (HBsAg) testing. MATERIALS AND METHODS: From 1 February 2000 to 15 October 2001, over 11 million donations, which were serologically negative, were tested using the MPX NAT system. Donations found to be HBV DNA positive were further tested by using the chemiluminescence immunoassay (CLIA). RESULTS: Out of 181 HBV DNA-positive donations, 96 (53%) and 76 (42%) were negative by individual enzyme immunoassay (EIA) and CLIA testing, respectively. CONCLUSIONS: The sensitivity of the 50-sample pool MPX NAT system was higher than that of individual HBsAg screening by CLIA. By adopting this NAT-screening system, the JRC has improved the safety of the blood supply and maintained supply across Japan.

Effects of aflastatin A, an inhibitor of aflatoxin production, on aflatoxin biosynthetic pathway and glucose metabolism in Aspergillus parasiticus.

Aflastatin A inhibits aflatoxin production by Aspergillus parasiticus via an unknown mechanism. We found that aflastatin A clearly inhibited production of norsolorinic acid, an early biosynthetic intermediate of aflatoxin, at a concentration of 0.25 microg/ml. Reverse-transcriptase polymerase chain reaction (RT-PCR), and real-time quantitative PCR (TaqMan PCR) experiments indicated that the transcription of genes encoding aflatoxin biosynthetic enzymes (pksA, ver-1, and omtA) and a gene encoding a regulatory protein for expression of the biosynthetic enzymes (aflR) were significantly reduced by the addition of aflastatin A. We also found that aflastatin A elevated the glucose consumption and ethanol accumulation by A. parasiticus, and repressed transcription of genes involved in ethanol utilization. These results suggest that aflastatin A inhibits a very early step in aflatoxin biosynthesis prior to the transcription of aflR and can influence glucose metabolism in the fungus.

Intraperitoneal PACAP administration decreases blood glucose in GK rats, and in normal and high fat diet mice.

PACAP is an islet peptide that serves as an endogenous amplifier of glucose induced insulin secretion. Furthermore, we has recently found that PACAP also potentiates insulin stimulated glucose uptake in adipocytes. Therefore, an antidiabetic action of PACAP is possible. In the present study, we examined the effect of PACAP treatment of the hyperglycemia in GK rats, an animal model of type 2 diabetes, and in high fat fed C47BL/6J mice, an animal model for glucose intolerance. GK rats housed with normal diet exhibited a normal level of blood glucose until three weeks old but significant hyperglycemia at eight weeks. When GK rats were treated with daily PACAP38 (i.p. injection, 6 pmol/kg) from age three weeks, development of hyperglycemia was prevented. In high fat fed mice, i.p. administration of PACAP27 for five (25 nmol/kg twice daily) reduced plasma glucose levels to 6.9 +/- 0.2 mmol/l compared to 8.1 +/- 0.2 mmol/l in saline injected animals (p < 0.001) without altering baseline insulin levels. We conclude that PACAP reduces circulating glucose in animal models of type 2 diabetes and glucose intolerance. The mechanism of this action needs to be established.

Blasticidin A derivatives with highly specific inhibitory activity toward aflatoxin production in Aspergillus parasiticus.

Blasticidin A (1), an antibiotic, has strong inhibitory activity toward aflatoxin production by Aspergillus parasiticus. We prepared some derivatives of 1 and examined their biological activities. Among them, derivatives 3 and 4 without the tetramic acid moiety of 1 maintained inhibitory activity toward aflatoxin production, but did not show antifungal activity or toxicity. RT-PCR experiments indicated that derivatives 3 and 4 as well as 1 significantly reduced the expression of genes encoding aflatoxin biosynthetic enzymes (pksA, ver-1 and omtA) and a regulatory gene (aflR) in A. parasiticus. These results suggested that derivatives 3 and 4 can inhibit aflatoxin production more specifically than 1 by inhibiting an early step prior to the expression of aflR in the pathway of aflatoxin biosynthesis.

Nurr1, an orphan nuclear receptor, is a transcriptional activator of endogenous tyrosine hydroxylase in neural progenitor cells derived from the adult brain.

Adult rat-derived hippocampal progenitor cells express many of the molecules implicated in midbrain dopaminergic determination, including FGF receptors 1, 2 and 3, the sonic hedgehog receptor components Smo and Ptc, and the region-specific transcription factors Ptx3 and Nurr1. Here we use undifferentiated progenitors to probe the events leading to the dopaminergic phenotype and find that the influences of Nurr1 can be temporally and mechanistically uncoupled from the patterning influences of sonic hedgehog and FGF-8 or the more generic process of neuronal differentiation itself. In gain-of-function experiments, Nurr1 is able to activate transcription of the tyrosine hydroxylase gene by binding a response element within a region of the tyrosine hydroxylase promoter necessary for midbrain-specific expression. This activation is mediated through a retinoid X receptor independent mechanism and occurs in all precursors, regardless of differentiation status. Overexpression of Nurr1 does not affect proliferation or stimulate neuronal differentiation and has no influence on the expression of other dopaminergic markers. This uncoupling of tyrosine hydroxylase expression from other dopaminergic markers suggests that the midbrain dopaminergic identity is dictated by a combination of pan-dopaminergic (e.g., Shh/FGF-8) and region-specific (Nurr1) mechanisms.

Comparison of a hypervariable segment in the human dopamine D4 receptor (DRD4) gene between the Japanese and Mongolian populations.

Amplifiable length polymorphism (AmpFLP) genotyping and direct sequencing of a hypervariable segment in the human dopamine D4 receptor (DRD4) gene were performed from genomic DNA of 100 unrelated Japanese and Mongolian individuals. The 4-repeat allele (314 bp) was the most prevalent and appeared at 0.88 and 0.82 in the Japanese and Mongolian populations, respectively. Homogeneity test of distribution showed no significant deviation from the observed frequencies of genotypes between the Japanese and Mongolian populations, but sequence analysis of the 4-repeat allele indicated that there could be ethnic differences between the two populations at the nucleotide level. The DRD4 allele and genotype frequencies in 10 patients with Parkinson's disease did not differ from those in the control Japanese population. In one Parkinsonian patient, however, a nucleotide change in one of the 4-repeat alleles was discovered. These results suggest that there could be ethnic and/or individual differences in the specific nucleotide changes within the repeat sequence because some alleles with the same number of repeat units had sequence variations. Thus, the DRD4 polymorphism exists at two levels and therefore could be a useful marker for forensic identification and anthropological studies.

Purification and characteristics of membrane-bound chitinase of anaerobic ruminal fungus Piromyces communis OTS1.

A membrane-bound chitinase from cell wall fractions of the anaerobic ruminal fungus, Piromyces communis OTS1, was purified by affinity chromatography, gel filtration, and chromatofocusing. The molecular size of the chitinase was estimated by gel filtration to be 42.4 kDa and by SDS-PAGE to be 44.8 kDa, and its pI was 4.4. Activity was inhibited by Hg2+ and allosamidin. The activity at 39 degrees C was greatest at pH 6.0. It had an 'endo' type action. Solubilization tests indicated that plasmalemma-bound chitinase was held in place by an electrostatic type interaction. Characterization of the membrane-bound chitinase was more similar to that of extracellular chitinase than cytosolic chitinase. This suggested that membrane-bound chitinase was the origin of extracellular chitinase.

[A case of progressive right coronary ostial stenosis after Carrel patch method using gelatin-resorcin-formalin glue].

A 31-year-old man with type A chronic aortic dissection associated with annuloaortic ectasia underwent the concomitant graft replacement of the total aortic root and the transverse aortic arch. The two coronary arteries were reconstructed using the Carrel patch method. The false lumen of right coronary artery was closed by injection of GRF glue into the dissected space and compressing the dissected layers. Postoperative course was uneventful, and the patient has returned to normal daily life 2 months after surgery. Remarkable progression of the right coronary artery ostial stenosis was observed by coronary angiography 6 months after surgery. The remarkable progression of stenosis may occur in association with injection of GRF glue into the dissected space, although the exact etiology of the progressive stenosis remains obscure.

Insulin secretion from isolated rat islets induced by the novel hypoglycemic agent A-4166, a derivative of D-phenylalanine.

A derivative of D-phenylalanine, A-4166, reportedly evokes a more rapid and short-lived hypoglycemic action in vivo than any of the currently available sulfonylureas. This novel oral hypoglycemic agent is structurally different from sulfonylureas. Therefore, studies were designed to elucidate the mechanisms by which A-4166 stimulates insulin secretion. Insulin release from incubated or perifused rat islets was dose-dependently stimulated by 10 to 200 mumol/l A-4166, in the presence of 2.8 mmol/l glucose. Both A-4166 and tolbutamide evoke a prompt rise in insulin secretion followed by a sustained gradually decreasing release from perfused islets in the presence of low glucose, although A-4166 appeared to be more sensitive than tolbutamide to subthreshold glucose concentration. Diazoxide abolished the initial release and blunted sustained release. Removing calcium from the perifusate abolished insulin release within 15 minutes. A-4166 inhibited [3H]-glibenclamide binding to HIT cell membranes and 86Rb efflux from ATP-depleted or diazoxide-treated cells. These results suggest that the insulin release induced by A-4166 is relevant to this agent occupying the tolbutamide binding sites. Therefore, one possible mechanism accounting for the more rapid and short-lived hypoglycemic action of A-4166 in vivo, as compared with tolbutamide, may involve the reported differences in the bioavailability of A-4166.

Preparation of biotinylated allosamidins with strong chitinase inhibitory activities.

NaIO4 oxidation of allosamidin (1), a strong inhibitor of family 18 chitinases, followed by a coupling with Biotin Hydrazide afforded its mono- and dibiotinylated derivatives, 4 and 6. Reduction of 4 by NaBH4 afforded its reduced form 5. Each of these three biotinylated derivatives maintained strong chitinase inhibitory activity. Especially, 6 inhibited a Trichoderma chitinase as strongly as 1.