The first probe of a FLASH proton beam by PET.

The recently observed FLASH effect related to high doses delivered with high rates has the potential to revolutionize radiation cancer therapy if promising results are confirmed and an underlying mechanism understood. Comprehensive measurements are essential to elucidate the phenomenon. We report the first-ever demonstration of measurements of successive in-spill and post-spill emissions of gammas arising from irradiations by a FLASH proton beam. A small positron emission tomography (PET) system was exposed in an ocular beam of the Proton Therapy Center at MD Anderson Cancer Center to view phantoms irradiated by 3.5 × 1010protons with a kinetic energy of 75.8 MeV delivered in 101.5 ms-long spills yielding a dose rate of 164 Gy s-1. Most in-spill events were due to prompt gammas. Reconstructed post-spill tomographic events, recorded for up to 20 min, yielded quantitative imaging and dosimetric information. These findings open a new and novel modality for imaging and monitoring of FLASH proton therapy exploiting in-spill prompt gamma imaging followed by post-spill PET imaging.

The first PET glimpse of a proton FLASH beam.

We demonstrate the first ever recorded positron-emission tomography (PET) imaging and dosimetry of a FLASH proton beam at the Proton Center of the MD Anderson Cancer Center. Two scintillating LYSO crystal arrays, read out by silicon photomultipliers, were configured with a partial field of view of a cylindrical poly-methyl methacrylate (PMMA) phantom irradiated by a FLASH proton beam. The proton beam had a kinetic energy of 75.8 MeV and an intensity of about 3.5 × 1010protons that were extracted over 101.5 ms-long spills. The radiation environment was characterized by cadmium-zinc-telluride and plastic scintillator counters. Preliminary results indicate that the PET technology used in our tests can efficiently record FLASH beam events. The instrument yielded informative and quantitative imaging and dosimetry of beam-activated isotopes in a PMMA phantom, as supported by Monte Carlo simulations. These studies open a new PET modality that can lead to improved imaging and monitoring of FLASH proton therapy.

B-RAF mutation and accumulated gene methylation in aberrant crypt foci (ACF), sessile serrated adenoma/polyp (SSA/P) and cancer in SSA/P.

BACKGROUND: Sessile serrated adenomas/polyps (SSA/Ps) are a putative precursor of colon cancer with microsatellite instability (MSI). However, the developmental mechanism of SSA/P remains unknown. We performed genetic analysis and genome-wide DNA methylation analysis in aberrant crypt foci (ACF), SSA/P, and cancer in SSA/P specimens to show a close association between ACF and the SSA/P-cancer sequence. We also evaluated the prevalence and number of ACF in SSA/P patients. METHODS: ACF in the right-side colon were observed in 36 patients with SSA/Ps alone, 2 with cancers in SSA/P, and 20 normal subjects and biopsied under magnifying endoscopy. B-RAF mutation and MSI were analysed by PCR-restriction fragment length polymorphism (RFLP) and PCR-SSCP, respectively, in 15 ACF, 20 SSA/P, and 2 cancer specimens. DNA methylation array analysis of seven ACF, seven SSA/P, and two cancer in SSA/P specimens was performed using the microarray-based integrated analysis of methylation by isochizomers (MIAMI) method. RESULTS: B-RAF mutations were frequently detected in ACF, SSA/P, and cancer in SSA/P tissues. The number of methylated genes increased significantly in the order of ACF

Fontan Failure and Thrombosis of Total Cavo-Pulmonary Connection Conduit.

The immediate postoperative period of Fontan operation is frequently complicated by hemodynamic instability, sometimes requiring fenestration of the conduit. Thrombosis of total cavo-pulmonary connection conduit warrants early intervention to prevent systemic and pulmonary embolism. We report a case of Fontan failure requiring fenestration; which was further complicated by thrombosis of total cavo-pulmonary connection conduit and managed with anticoagulants.

Estimation of friction of a single chemisorbed molecule on a surface using incident atoms.

Friction of a single molecule chemisorbed on a surface is a very fundamental property related to the dynamics of the diffusion of the molecule. We used a newly developed method, in which energy-controlled rare gas atoms collide with CO molecules on a stepped surface to displace CO molecules from initial terrace sites to final step sites. The friction coefficient of CO molecules on the surface was determined directly by comparing the experimentally measured increase in the number of CO molecules at step sites with classical molecular dynamics simulation results.

Usefulness of intraoperative color doppler ultrasonography in decision making regarding conversion of an accessory hepatic vein after a Fontan-type operation.

An accessory hepatic vein (AHV) after a Fontan-type operation will result in progressive desaturation if left intact. We report a case in which intraoperative color Doppler ultrasonography revealed the absence of AHV flow and reversed portal vein flow when the AHV was clamped, suggesting that simple ligation of the AHV would lead to liver dysfunction in the area affected. Based on the results of the ultrasonography evaluations, diversion of the AHV into the pulmonary circulation was performed without cardiopulmonary bypass, and the clinical outcome has been favorable.

Ammonia adsorption on and diffusion into thin ice films grown on Pt(111).

Ammonia adsorption on and diffusion into thin ice films grown on a Pt(111) surface were studied using Fourier transform infrared spectroscopy (FTIR) and thermal desorption spectroscopy. After exposing the crystalline ice film to ammonia molecules at 45 K (ammonia/ice film), we have detected an intriguing feature at 1470 cm(-1) in the FTIR spectra, which is derived from the adsorption of ammonia on the ice with a characteristic structure which appears in thin film range. The peak intensity of this feature decreases gradually as the thickness of the substrate ice increases. In addition, we have detected a feature at 1260 cm(-1) which appears after annealing the ammonia/ice film. The feature corresponds to the ammonia molecules which reach the ice/Pt(111) interface through the ice film. Intriguingly, the intensity of this feature decreases with the ice thickness and there is a linear relation of the peak intensity of the features at 1470 and 1260 cm(-1). We propose a model in which the solubility of the ammonia molecules is much higher for the thin ice film than that for the ideal ice.

Inhibition of bacterial and glucan adherence to various light-cured fluoride-releasing restorative materials.

OBJECTIVES: This study investigated the potential plaque adhesion properties of various light-cured fluoride-releasing restorative materials by measuring the amount of adhering radiolabeled bacteria and glucan. METHODS: Three resin-modified glass ionomer cements (RMGI) and two polyacid-modified resin composites (compomer) were used in this study. As a control, one light-cured resin composite was added. Disk-shaped specimens were made following the manufacturers' recommendations and the respective surfaces were finished with a 600-grit abrasive paper. Streptococcus sobrinus B13 was selected as a cariogenic bacterial strain. The amount of bacteria and glucan adhered to these specimens were measured after 3, 8 and 24h incubations with radiolabeled cariogenic bacteria and sucrose. RESULTS: After 3 and 8h incubations, the amount of adhered bacteria and glucan was small and there were no significant differences among the restorative materials except in the resin composite. Although after 24h incubation the amounts of adhered bacteria and glucan, significantly increased on the RMGIs and compomers, these were still significantly less than the resin composite except one compomer. Although at 3h no good correlation was found between the contact angles and the amount of bacteria and glucans, the correlation coefficients were high at 8 or 24h. In addition, the coefficients for bacteria were always higher than those for glucan irrespective of the incubation times. CONCLUSIONS: After 24h resin-modified glass ionomer cements and compomers showed significantly smaller amounts of adhered bacteria and glucans compared to resin composite with an exception of glucan adherence on one compomer.

Serum amino-terminal propeptide of type III procollagen and 7S domain of type IV collagen correlate with hepatic iron concentration in patients with chronic hepatitis C following alpha-interferon therapy.

BACKGROUND: It has been reported that chronic infection with hepatitis C virus is associated with excess iron deposits in the liver of subjects who are neither alcoholics nor recipients of blood transfusions. However, little is known about the relationship between hepatic iron concentration (HIC) and the serum levels of hepatic fibrogenesis markers, which were caused by interferon therapy for chronic hepatitis C. Therefore, changes in the serum amino-terminal propeptide of type III procollagen (P-III-P) and the 7S domain of type IV collagen (7S-IV) in 16 patients treated with alpha-interferon (IFN-alpha) were studied, and their HIC and histological assessment evaluated. Hepatic iron concentrations were measured by using liver biopsy specimens obtained before and 6 months after the cessation of treatment. METHODS AND RESULTS: Eight subjects (50%) who had normal alanine transaminase levels at 6 months after therapy showed significantly lowered HIC, and attenuated hepatic iron staining with decreased serum levels of P-III-P and 7S-IV compared to the remaining subjects. The HIC was significantly correlated with the serum levels of P-III-P and 7S-IV in all subjects. CONCLUSIONS: These findings suggest that IFN-alpha treatment may decrease stimuli for fibrogenesis, at least in part, by reducing the hepatic iron deposition in patients with chronic hepatitis C.

Characterization of bacteriocin N15 produced by Enterococcus faecium N15 and cloning of the related genes.

Enterococcus faecium N15 was isolated from nuka (Japanese rice-bran paste), which is utilized as starter in the fermenting of vegetables, and was found to produce a bacteriocin that exhibited a broad spectrum of activity, including activity against Listeria monocytogenes and Bacillus circulans JCM2504. The bacteriocin was sensitive to proteases (alpha-chymotrypsin, proteinase K, trypsin, and pepsin) and alpha-amylase, but it was resistant to lipase. The bacteriocin was resistant to heat treatment at 100 degrees C for 2 h, but its activity was completely lost after autoclaving at 121 degrees C for 15 min. It was active over a wide pH range from 2.0 to 10.0. The bacteriocin showed bactericidal activity against Lactobacillus sake JCM1157 at a concentration of 40 AU/ml. Its molecular weight was estimated by SDS-PAGE to be about 3-5 kDa. PCR primers were designed based on the conserved amino acid sequences of class IIa bacteriocins. A 3-kb DNA fragment was amplified and three open reading frames (ORFs) were found. The first encodes a probable immunity protein of 103 amino acid residues and shows complete homology with the putative immunity protein of E. faecium DPC1146. The second and third ORFs respectively encode a probable transposase gene and an inducing factor. The upstream region of the immunity gene, in which the bacteriocin structural gene is located, was amplified. A homology search revealed that the bacteriocin produced by E. faecium N15 exhibits complete identity to enterocin A, a bacteriocin produced by E. faecium DPC1146. PCR using the primers designed in this study is a rapid and sufficient method of screening for bacteriocin-producing strains.

Sequence and electrophysiological characterization of two insect-selective excitatory toxins from the venom of the Chinese scorpion Buthus martensi.

The two insecticidal peptides Bm32-VI and Bm33-I, isolated from the venom of the Chinese scorpion Buthus martensi induce paralytical symptoms typical of insect contractive toxins. They show, respectively, 74% and 77% homology with AaIT from Androctonus australis, comparable insecticidal activity and no vertebrate toxicity. Under voltage-clamp conditions, both toxins induced (1) an increased fast Na(+) current, (2) a shift in voltage dependence of Na(+) current activation, (3) the occurrence of a delayed current, and (4) a slow development of a holding current. Increased Na(+) conductance at negative potential values is responsible for axonal hyperexcitability and the contractive paralysis of insect prey.

Development of a Simple Culture Method for the Tissues Contaminated with Microorganisms and Application to Establishment of a Fish Cell line.

Cell cultures are good in vitro model systems in place of using living animals. In the present study, we developed a simple culture method in which tissues were pretreated with a low concentration of sodium hypochlorite solution (NaClO) to prevent not only bacteria but also fungi. Scales removed from a goldfish (Carassius auratus) body were treated with 70% ethanol and then with 0.3% of sodium hypochlorite solution, and cultured in vitro in an atmosphere containing 0.5% CO2. The doubling time of the established cells (GAKS) was 24 hr. The GAKS cells contained alkaline phosphatase activity (8.3+/-1.1 nmol/min/mg protein) and secreted 0.32+/-0.07 pg/ml endothelin during a 3 day culture of a full monolayer sheet.

[Coronary artery fistula with left atrial myxoma: report of a case].

A 64-year-old male was referred for surgical treatment of left atrial myxoma. Preoperative coronary angiography revealed coronary artery fistula from the left anterior descending artery and the circumflex artery draining into the main pulmonary artery. Operative treatment was performed including resection of the myxoma, patch closure of the atrial septal defect, and closure of the fistula with pledgeted mattress sutures from within the main pulmonary artery on cardiopulmonary bypass. His postoperative course was uneventful, and disappearance of the left atrial myxoma and the coronary artery fistula was ascertained by echocardiography and coronary angiography.

Subtalar arthrography in acute injuries of the calcaneofibular ligament.

We treated 43 acute tears of the calcaneofibular ligament by operation in 43 patients after subtalar arthrography. There were 22 men and 21 women with a mean age of 22.3 years (14 to 61). Anteroposterior (AP), lateral and oblique views were obtained with the foot in 45 degrees of internal rotation and the ankle in the neutral position. Any communication or leakage to the ankle, tendon sheaths, subcutaneous tissue and sinus tarsi was recorded. We examined an oblique view of the microrecess along the interosseous ligament and an AP view of the lateral recess just under the distal end of the fibula. We also studied a control group of 27 patients with isolated injuries of the anterior talofibular ligament without rupture of the calcaneofibular ligament. The findings in the two groups were significantly different when examined for leakage to the ankle (p=0.0002), to the peroneal tendon sheaths (p=0.0347) and to the subcutaneous tissue (p=0.0222), absence of the microrecess (p=0.0055) and presence of the lateral recess (p=0.0012). Many ankle sprains which involve tearing of the calcaneofibular ligament are accompanied by injuries of the subtalar joint. Combined injuries of the anterior talofibular ligament and calcaneofibular ligament, and isolated injury of the anterior talofibular ligament should be differentiated.

Marked, sustained expression of a novel 150-kDa oxygen-regulated stress protein, in severely ischemic mouse neurons.

The 150-kDa oxygen-regulated protein (ORP150) first was described with reference to the central nervous system in cultured astrocytes subjected to dense hypoxia. Subsequently its transcript was found in macrophages within human aortic atherosclerotic plaques, suggesting a role in protecting cells under hypoxic stress. In a mouse model of permanent focal brain ischemia, we aimed to elucidate the constitutive cellular localization in vivo of ORP150 in the central nervous system as well as the sequential alteration in its mRNA and protein expression during this severe ischemic insult. Immunohistochemical study demonstrated that ORP150 protein normally is present predominantly in neurons. The 78-kDa glucose-regulated protein, which is another well-known stress protein retained in the endoplasmic reticulum, also was stained in neurons. During the first 3 h after ischemia, ORP150 antigenicity was markedly enhanced in severely damaged neurons, while the amount of the glucose-regulated protein was decreased. Preceding this change, orp150 mRNA was selectively induced in neurons undergoing postischemic cytoskeletal proteolysis, as early as 1 h after middle cerebral artery occlusion. These results indicated that ORP150 might be regulated by transcriptional level as for many stress proteins, but unlike previously described other stress proteins it was translated in the center of ischemic lesions despite nearly complete energy depletion. In this paper, the biological potentials of ORP150 protein in the setting of brain ischemia in vivo will also be discussed.

Results of opening-wedge osteotomy for the treatment of a post-traumatic varus deformity of the ankle.

We performed a one-stage opening-wedge valgus osteotomy in nine patients to correct a post-traumatic progressive varus deformity of the ankle. The osteotomy site was stabilized with two, three, or four Kirschner wires or with a plate and screws (in one patient). The site of the osteotomy united within two months after the operation in eight patients and at six months in one patient who was fifty-nine years old. The average duration of follow-up was seven years and four months (range, two years and four months to thirteen years and two months). Postoperatively, the range of motion of the ankle was decreased in six patients and remained unchanged in three. However, none of the patients reported any limitation in the activities of daily living, and the four adolescent patients were able to participate in sports activities. The result was graded as excellent for four ankles, good for two, and fair for three.

Tarsal tunnel syndrome caused by coalition associated with a ganglion.

We examined seven patients with tarsal tunnel syndrome in one foot caused by talocalcaneal coalition and a ganglion. We excised the coalition and the ganglion in six of them. All the patients had pain, sensory disturbance in the sole, and a positive Tinel's sign. Older patients with a long history showed atrophy and weakness of the plantar muscles. Talocalcaneal coalition can be diagnosed on a plain lateral radiograph and an anteroposterior radiograph externally rotated 20 degrees, and confirmed by CT. MRI is also useful for diagnosis. The coalitions were medial, and the ganglion had developed from the incomplete part of the coalition; it was multilocular in some patients. After resection, there was early pain relief but sensory disturbances and Tinel's sign persisted. The postoperative results were excellent in one patient, good in four and fair in one.