Atomic and electronic structures of amorphous Ge(2)Sb(2)Te(5); melt-quenched versus ideal glasses.

To investigate an amorphous structure of Ge(2)Sb(2)Te(5) that satisfies the 8-N rule (so-called 'ideal glass'), we perform alternative melt-quench simulations on Si(2)As(2)Se(5) and replace atoms in the final structure with Ge-Sb-Te. The resulting structures have salient features of the 8-N rule such as the tetrahedral configuration for all Ge atoms and the localized Te lone pairs at the valence top. In addition, the average Ge-Te and Sb-Te distances are in good agreement with experiment. The energetic stability of the ideal glass supports the existence of this amorphous structure that is distinct from the melt-quenched glass. From the analysis of electronic structures and optical dielectric constants, it is concluded that the electronic character of the melt-quenched amorphous Ge(2)Sb(2)Te(5) lies in between the resonant p-bonding of the crystalline phase and the covalent bonding of the ideal glass.

Characterization of a proteolytic enzyme derived from a Bacillus strain that effectively degrades prion protein.

AIMS: The purpose of this paper was to screen candidate bacterial strains for the production of proteases suitable for application to the degradation of pathogenic forms of prion protein (PrP(Sc)). This paper describes the biochemical characteristics and proteolytic activity of the isolated protease. METHODS AND RESULTS: After screening more than 200 bacterial proteases for keratinolytic activity, we identified a Bacillus stain that produced a protease exhibiting high-degradation activity against a scrapie PrP(Sc). Sequence analysis indicated that this serine-protease belonged to the Subtilisin family and had optimum pH and temperature ranges of 9-10 and 60-70 degrees C. Western blotting analysis revealed that the protease was also capable of decomposing bovine spongiform encephalopathy-infected brain homogenate. In addition, the protease was demonstrated to degrade dried PrP(Sc) that had become firmly attached to a plastic surface considerably more effectively than proteinase K or PWD-1, a previously reported keratinase. CONCLUSIONS: These results indicate that the isolated protease exhibited higher activity for PrP(Sc) degradation compared with other proteases examined. SIGNIFICANCE AND IMPACT OF THE STUDY: This protease could be used under moderate conditions for the decontamination of precision instruments that are susceptible to PrP(Sc) contamination.

Boosting nitrification by membrane-attached biofilm.

Nitrification is a key step for reliable biological nitrogen removal. In order to enhance nitrification in the activated sludge (AS) process, membrane-attached biofilm (MAB) was incorporated in a conventional activated sludge tank. Simultaneous organic carbon removal and nitrification of the MAB incorporated activated sludge (AS + MAB) process was investigated with continuous wastewater treatment. The effluent TOC concentration of AS and the AS + MAB processes were about 6.3 mg/L and 7.9 mg/L, respectively. The TOC removal efficiency of both AS and AS + MAB were above 95% during the wastewater treatment, indicating excellent organic carbon removal performance in both processes. Little nitrification occurred in the AS process. On the contrary, successful nitrification was obtained with the AS + MAB process with nitrification efficiency of about 90%. The volumetric and surface nitrification rates were about 0.14 g/Ld and 6.5 g/m2d, respectively. The results clearly demonstrated that nitrification in the conventional AS process was boosted by MAB. Furthermore, the microfaunal population in the AS + MAB process was different from that in the AS process. The high concentration of rotifers in the AS + MAB process was expected to decrease the generation of excess sludge in the process.

Specific detection of prion antigenic determinants retained in bovine meat and bone meal by flow microbead immunoassay.

AIMS: The purpose of this study was to develop an effective method for detecting prion (PrP) antigenic determinants remaining in bovine meat and bone meal (MBM) using pressurized fluid extraction (PSE) equipment and flow microbead immunoassay (FMI). METHODS AND RESULTS: Using the FMI, bovine recombinant PrP could be determined quantitatively in the 7 pmol-7 nmol range using anti-PrP peptide polyclonal antibody-coupled microbeads and anti-PrP monoclonal antibody (SAF61) as a detection antibody. PSE extraction at 120 degrees C for 5 min under high pressure was most effective for eluting PrP determinants from bovine MBMs. The FMI was capable of detecting PrP determinants in bovine MBM extracts with high specificity and indicated that the MBMs contained high levels of PrP determinants. This assay was also applied to the detection of PrP(Sc) determinants in bovine MBM spiked with a scrapie-infected brain at a weight ratio of 50 : 1. CONCLUSIONS: These data indicate that this assay was effective for the specific detection of PrP determinants contained in bovine MBM extracts. SIGNIFICANCE AND IMPACT OF THE STUDY: To our knowledge, this is the first report detailing the detection of PrP determinants in bovine MBM. The assay could be applied to securing the safety of bovine MBM.

Cervical intradural disc herniation.

STUDY DESIGN: A case report of anterior en bloc resected cervical intradural disc herniation and a review of the literature. OBJECTIVE: To discuss the pathogenesis of cervical intradural disc herniation. SUMMARY OF BACKGROUND DATA: Including this study case, only 17 cases of cervical intradural disc herniation have been reported. There have been few detailed reports concerning the pathogenesis of cervical intradural disc herniation. METHODS: A cervical intradural disc herniation at C6-C7, with localized hypertrophy and segmentally ossified posterior longitudinal ligament, is reported in a 45-year-old man who had Brown-Sequard syndrome diagnosed on neurologic examination. Neuroradiologic, operative, and histologic findings, particularly the pathology of the anterior en bloc resected posterior vertebral portion of C6 and C7, were evaluated for discussion of the pathogenesis. RESULTS: Adhesion of dura mater and hypertrophic posterior longitudinal ligament was observed around a perforated portion of the herniated disc, and histologic study showed irregularity in fiber alignment accompanied by scattered inflammatory cell infiltration and hypertrophy in the posterior longitudinal ligament. The cervical intradural disc herniation was removed successfully and followed by C5-Th1 anterior interbody fusion with fibular strut graft. Neurologic recovery was complete except for minor residual sensory disturbance in the leg 7 years after the surgery. CONCLUSIONS: Cervical intradural disc herniation is an extremely rare condition. The pathogenesis remains obscure. Only 16 cases have been reported in the literature, and there has been little discussion concerning the local pathology of the herniated portion. The pathogenesis of the disease in the patient reported here was considered to be the adhesion and fragility of dura mater and posterior longitudinal ligament. This was caused by hypertrophy, with chronic inflammation and ossification of the posterior longitudinal ligament sustaining chronic mechanical irritation to the dura mater, leading to perforation of the herniated disc by an accidental force.

Simplification for measuring input function of FDG PET: investigation of 1-point blood sampling method.

UNLABELLED: The current method for quantitative FDG PET study requires application of multiple arterial blood sampling for measuring the input function, but the procedure is invasive and complicated. The purpose of this study was to establish a 1-point blood sampling technique that gives data comparable with the data of more elaborate serial arterial sampling. METHODS: We established a time point for 1-point arterial sampling that exhibited the highest correlation between plasma radioactivity at the time point and the real integrated value (IV) of the measured input function obtained by multiple arterial sampling in 120 patients and the smallest coefficient of variation of the real IV divided by plasma radioactivity at the time point in 120 patients. Scaling factors for estimation at each sampling point were determined, and a reference table was established to make the supposed input function. RESULTS: The optimal time for 1-point arterial sampling was 12 min after FDG injection. A good correlation was observed between the real IVs and those estimated from 1-point arterial blood sampling at 12 min using the supposed input function (n = 120; P < 0.001). The time point at which the difference between values of arterial and venous blood disappeared was 40 min after FDG injection. The percentage errors of IV estimation by 1-point sampling were 1.70% (n = 120) for arterial blood at 12 min and 3.64% (n = 10) for venous blood at 40 min. CONCLUSION: We conclude that the simplified 1-point sample method works in a manner that is comparable with serial arterial sampling and should be useful for clinical PET.

[Fluorine-18 labeled 6-fluoro-L-dopa: systematization and evaluation of its usefulness].

6-[18F]Fluoro-L-dopa (L-3,4-dihydroxy-6-[18F]fluorophenylalanine; 6-[18F]FDPA) is useful to assess presynaptic dopamine metabolism in central nervous system. In this paper, we report on the usefulness of the 6-[18F]FDOPA synthesis system developed for the routine synthesis. This system consists of the 6-[18F]FOPA synthesis and the separation units in conjunction with controller using a personal computer. The synthesis time of 6-[18F]FDOPA was 73 minutes. The typical yield and specific activity were 1.4-2.4 GBq and 244-270 MBq/mumol at the end of synthesis, respectively, under the irradiation condition of 50 microA for 130 minutes. The radiochemical yields of 6-[18F]FDOPA were 31.3-38.7% based on the [18F]acetylhypofluorite, and the results were affected with the condition of potassium acetate (AcOK) to produce gaseous [18F]acetylhypofluorite. This system is useful for the routine production of 6-[18F]FDOPA because of its high yield and high specific activity while maintaining AcOK in good condition, and decreasing the radiation exposure for chemist.

Solitary colonic metastasis of renal cell carcinoma seven years after nephrectomy: a case report.

An 83-year-old man, who had undergone right radical nephrectomy for renal cell carcinoma about 7 years previously, experienced melena and abdominal mass. Barium enema, colonoscopy, computed tomography, and arteriography showed a hypervascular mass on the transverse colon, and a partial transverse colectomy was performed. The postoperative histologic examination revealed that the tumor was a metastatic clear cell carcinoma.

[Effects of 5-fluorouracil in shrinking residual gastric cancer: a case report].

The patient was a 79-year-old man who underwent extensive gastrectomy and Billroth-II reconstruction for gastric ulcer in 1974. He complained of heartburn in November, 1992, and endoscopy for the residual stomach revealed IIb + IIa-like lesion mainly in the posterior wall of the anastomosed site, which was diagnosed as well differentiated adenocarcinoma. As the patient refused to be operated, 150 mg/day of 5-FU was administered. For 4 months before he decided to undergo operation, 12.9 g of 5-FU was administered in total. After rehospitalization, endoscopy of the residual stomach showed shrinkage of the lesion, and biopsy revealed no malignant findings. The pathological examination after total resection of the residual stomach showed atypism, but no evidence to support malignancy. He has continued to be well without sign of recurrence for 1 year since the operation. The administration of 5-FU is widely used as preoperative adjuvant chemotherapy. This case it is rare for 5-FU to cause the disappearance or falling off of malignant cells.

Development and preliminary application of high-performance liquid chromatographic assay of urinary metabolites of diazepam in humans.

A simple high-performance liquid chromatographic method for the measurement of diazepam (DZP) and its major metabolites, N-desmethyldiazepam (DMDZP), temazepam (TZP) and oxazepam (OZP) in urine was developed. Preliminary studies of DZP metabolism were also undertaken in four healthy volunteers after administration of a single oral dose (4 mg) of DZP. The assay allowed the simultaneous determination of all analytes in 1 ml of urine and the detection limit was 2 ng/ml with a signal-to-noise ratio of 3. None of 22 drugs and 17 metabolites, except for mianserin, maprotiline and imipramine N-oxide, interfered with the detection of DZP metabolites. Recoveries of the analytes and the internal standard (prazepam) were > 82%. Intra- and inter-assay coefficients of variation for all analytes were < 5.5 and 4.1%, respectively. The mean (+/- S.D.) cumulative urinary excretions of DMDZP, TZP and OZP over 96 h after a single oral administration of DZP were 3.9 +/- 0.4, 6.6 +/- 1.4 and 2.8 +/- 0.6% of the dose, respectively. The urinary excretion of DZP was under the detection limit.

[Carbon-11 labeled diacylglycerol for signal transduction imaging by positron CT: evaluation of the quality and safety for clinical use].

To elucidate the synaptic transmission in the neural system, we have been developing fundamental studies for intracellular signaling. For clinical application of carbon-11 labeled diacylglycerol (1-[1-11C]butyryl-2-palmitoyl-rac-glycerol: 11C-DAG) using positron emission computed tomography (PET), we evaluated the quality and the safety of 11C-DAG as the solution for injection. As a result, 11C-DAG was synthesized within 50 minutes, including the preparation step for injection. The half life time and energy spectrum of 11C-DAG were the same as the physical character of carbon-11, and other radioisotopes were not detected. In the quality control, 11C-DAG solution was negative in the examination of bacterial contamination and the pyrogen test in three successive synthesis procedures. In the acute toxicity test by administration of 11C-DAG and 100 mumol/kg of non-radioactive DAG to the rat intravenously, the systemic condition of the rat was not changed and no abnormalities were found in any organ 24 hours after administration. These findings indicated the safety of 11C-DAG solution. Clinical application of 11C-DAG using positron emission tomography may be useful to elucidate the dysfunction of intracellular signaling in disorders of higher cortical function such as Alzheimer disease.

[Carbon-11 labeled diacylglycerol for signal transduction imaging: effect of the solubilizer on the distribution and radiation dosimetry].

Carbon-11 labeled diacylglycerol (11C-DAG) has been developed as a signal transduction imaging agent for the CNS, and it can visualize the second messenger. For clinical application by positron CT (PET), the 11C-DAG solution must be prepared for intravenous injection. However, the 11C-DAG does not dissolve in water because of its lipophilicity and requires a solubilizer such as human serum albumin (HSA) and Tween 80 (TW-80). We examined the influence of these solubilizers on the tissue distribution of 11C-DAG, and estimated the radiation dosimetry. In the brain, uptake of 11C-DAG dissolved with HSA was 1.3-1.8 times higher than that of dissolved with TW-80. On the other hand, the lung and spleen showed a higher uptake of 11C-DAG using TW-80 than when using HSA. Especially, the lungs showed 20-40 times higher uptake than when using HSA. Also, the washout of radioactivity from tissue was slower, and the dose of radiation exposure was estimated to be higher, with TW-80 than with HSA. Therefore, between TW-80 and HSA with different solubilizing mechanisms, the later was suggested to be a better solubilizer of 11C-DAG.

[Case report and review of literature on seasonal distribution and pathogenesis of acute eosinophilic pneumonia in Japan].

A 49-year-old female was admitted because of high grade fever and dyspnea. Chest roentgenogram revealed diffuse reticulo-linear shadows. Laboratory findings showed peripheral blood eosinophilia, and blood gas analysis demonstrated severe hypoxemia. A few days after admission, her symptoms and signs improved, and the abnormal shadows on the chest roentgenograms decreased without treatment. To determine the diagnosis and evaluate the pathological findings and pathogenesis, we performed open lung biopsy. Bronchoalveolar lavage at the operation revealed increased total cell count and increased markedly, number of eosinophils, and the open lung biopsy specimen showed acute interstitial pneumonia with eosinophilic infiltration. We performed a study of precipitating antibodies against fourteen kinds of fungi and environmental provocation tests, with all results being negative. We diagnosed this case as having acute eosinophilic pneumonia clinicopathologically (Allen, 1989). We reviewed 22 cases with acute eosinophilic pneumonia previously reported in Japan including our case. These 22 cases demonstrated a seasonal tendency of onset in spring and summer. Eleven of 22 cases were tested for precipitating antibodies to several fungi, 3 of which showed positive results against Trichosporon cutaneum, Trichoderma viride and Aspergillus species. The clinical features of acute eosinophilic pneumonia resemble those of summer type hypersensitivity pneumonitis. Therefore, it is important to diagnose AEP on the basis of clinical symptoms, and precipitating antibody, viral titer and pathological findings.

[A case of radiation pneumonitis caused by treatment of lung cancer which revealed marked hypervasculality on bronchial arteriography].

A 44-year-old man was admitted to our hospital because of hemoptysis. He had been admitted to our ward in June 1991, after resection of a brain tumor at another hospital due to cerebral metastasis of lung cancer (adenocarcinoma). Systemic chemotherapy and pulmonary irradiation therapy were performed during the first hospitalization. Radiation pneumonitis occurred 1 month after the completion of radiotherapy, which responded to administration of corticosteroids. One year and 4 months later after the completion of radiotherapy, he was readmitted to our hospital because of hemoptysis. Chest computed tomogram and bronchoscopy showed no recurrence of lung cancer, so pulmonary arteriography and bronchial arteriography were performed to investigate the cause of hemoptysis. Pulmonary arteriograms showed diminished vascularity in the area of radiation fibrosis, but a bronchial arteriogram showed inflammatory hypervascularization in the same field. We considered that the bronchial arterial angiogenesis induced by radiation pneumonitis was the cause of hemoptysis. Bronchial arteriography is necessary in cases of radiation pulmonary fibrosis with hemoptysis without obvious recurrence of tumor. If the growth of new blood vessels in the bronchial artery can be induced by radiation therapy, the administration of anti-cancer agents to the bronchial artery should be considered in the treatment of recurrent lung cancer after radiation therapy.

Positron emission tomographic measurement of acute hemodynamic changes in primate middle cerebral artery occlusion.

Specific hemodynamic changes in acute ischemia were investigated using a middle cerebral artery occlusion primate model and positron emission tomography. The cerebral blood flow (CBF), cerebral blood volume, oxygen extraction fraction (OEF), and cerebral metabolic rate for oxygen were measured 1, 3, and 9 hours after occlusion. OEF showed an increase in ischemic areas, and especially where CBF was below 18 ml/100 gm/min 1 hour after occlusion the OEF increased significantly (0.69 +/- 0.20, p < 0.05). Nine hours after occlusion, the OEF values were lower compared to those 1 and 3 hours after occlusion. Areas where CBF ranged from 18 to 31 ml/100 gm/min showed an increase in OEF at all times (p < 0.05). Clearly, OEF changes remarkably in the acute stage.

Asbestos-related pleural thickenings in Japanese sake brewers.

Asbestos was long used as an additive material for the filtration of many kinds of alcoholic beverages. There has been, however, only one case report of a distiller in Italy showing pleural thickenings and lung parenchymal fibrosis due to exposure to asbestos. We report a retired Japanese sake brewer who showed bilateral calcified pleural plaques on chest X-ray films. X-ray diffraction analysis and energy disperse X-ray microanalysis demonstrated the additive material used for sake filtration to be almost pure chrysotile. Furthermore, 17 cases showing probably asbestos-related pleural thickenings were found on examination of 235 chest X-ray films of male workers at different sake breweries. These findings indicate that Japanese sake brewers should be listed as workers at possible risk of asbestos-related health problems.

A new method of myocardial revascularization by laser.

There are some problems in surgical treatment for those patients with small branches or diffuse stenotic lesions of the coronary arteries, for whom coronary artery bypass grafting can not be carried out at all. To resolve these problems, we have planned to supply arterial blood from the left ventricle into the ischemic myocardium through holes cut into the myocardium by laser. It was clearly recognized that arterial blood could be hemodynamically supplied from the left ventricle into the ischemic myocardium. In trials on dogs laser holes 0.2 mm in diameter have been shown microscopically to be patent even 3 years after their creation, thus this procedure could be used as a new method of myocardial revascularization. Consequently, myocardial revascularization by laser was employed in a 55-year-old male patient with severe angina pectoris who had undergone pericardiectomy 2 years before. He is doing well 5 years and 3 months after surgery.

Effects of N-methylmercaptoimidazole on the disposition of MPTP and its metabolites in mice.

The effects of N-methylmercaptoimidazole, an alternative substrate for flavin-containing monooxygenase, on the disposition of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its metabolites, 1-methyl-4-phenyl-1,3-dihydropyridine (MPDP+) and 1-methyl-4-phenylpyridine (MPP+) in plasma and in brain tissues were studied in mice. Pretreatment of mice with N-methylmercaptoimidazole caused a significant (P less than 0.01) increase in the plasma concentration of MPTP, whereas there was no significant change in the plasma concentrations of MPDP+ and MPP+. N-Methylmercaptoimidazole caused a significant (P less than 0.01) increase in the levels of MPTP, MPDP+ and MPP+ in both the striatum and cortex. The conversion rates of MPTP to MPDP+ to MPP+ in whole brain homogenates were not affected by N-methylmercaptoimidazole. These results suggest that N-methylmercaptoimidazole increases the amount of MPTP delivered from the peripheral to the central nervous system, presumably by inhibiting MPTP N-oxygenation via the hepatic microsomal flavin-containing monooxygenase. An increased level of striatal MPP+, caused by the oxidation of more MPTP by brain monoamine oxidase, appears to be the mechanism by which the neurotoxicity of MPTP is enhanced by N-methylmercaptoimidazole.

[Experimental and clinical studies on the laser application in the cardiovascular surgery; analysis of clinical experience of 112 patients].

Since 1980, we have applied lasers experimentally in the following three categories in the fields of cardiovascular surgery. That is, Group 1: New myocardial revascularization in the patients whose coronary arteries are too small or diffuse due to atherosclerosis, Group 2: Laser vascular anastomosis especially for small-caliber vessels, such as coronary artery bypass grafting, Group 3: Laser angioplasty for obstructive arterial disease. Subsequently, efficacy of laser application could be obviously recognized in these fields. On the basis of excellent results of our experimental studies, laser was clinically employed for 112 patients with anginal pain, intermittent claudication and renal failure. They consisted of new myocardial revascularization in one case and vascular anastomosis in 89 cases including 7 cases (LIMA-LAD2, SVG-LAD5) of the coronary artery bypass grafting and laser angioplasty in 22 cases including 5 cases (LAD3, RCA2) of intraoperative laser coronary angioplasty. Optimal conditions of vascular anastomosis were 20-40mW in output and 6-12sec/mm in irradiation time. On the other hand, optimal conditions for laser angioplasty were 6 watts in output and 3sec in irradiation time for each shot. Laser irradiation was carefully repeated according to the grade of atherosclerotic changes. These patients are doing well without any complications throughout laser. Our experimental and clinical experiences of laser application in the fields of the cardiovascular surgery were presented in detail.

Environmental designs for reading from imaging work stations: ergonomic and architectural features.

Despite the rapid progress made in the electronic design of imaging work stations for medicine, much less effort has gone into the design of environments in which such systems will be used. Based on studies of radiologist film reading sessions, considerable time will be spent working at such viewing systems. If the rooms in which the work stations are placed are not conducive to comfortable work, it will certainly not favor electronic viewing over film reading. In examining existing reading environments, it is also apparent that they are not optimal, even for film. Since some of the problems for film and electronic viewing overlap, such as heat generation (by the alternators, viewboxes, or work station electronics) and glare from light sources, it should be possible to develop solutions that are applicable to both environments, or to rooms that will feature both viewing systems. This paper will discuss some of the approaches to designing environments in which viewing of images is supported by the room architecture and engineering, rather than being degraded by it. To illustrate these points a design, based on the constraint of a real room size and available architectural materials, will be developed.