Temporal evaluation of the microwave ablation zone and comparison of CT and gross sizes during the first month post-ablation in swine lung.

PURPOSE: The purpose of this study was to investigate the development and evolution of the microwave ablation (MWA) lesion in the normal lung by using a swine model at various time points and to compare post-procedural computed tomography (CT) and gross pathologic findings during the first month post-ablation. MATERIALS AND METHODS: Twenty-seven percutaneous MWA procedures were performed on swine lungs at 100W for either 2min (low dose, 18 ablations) or 10min (high dose, 9 ablations). Animals were sacrificed at either 2 days (n=5) or 28 days (n=5) after ablation. All animals underwent CT imaging immediate post-treatment and prior to sacrifice, with additional imaging at 7 and 14 days for the 28-day cohort. After euthanasia, lungs and trachea were removed en bloc and underwent gross pathology analysis. RESULTS: In both dose treatment groups, CT measurements of the ablation zone were maximum at Day 7 (low dose: 7.50±3.08 cm3; high dose: 24.87±11.34 cm3) and significantly larger compared to the immediate post-ablation measurements (low dose: 2.54±1.81 cm3; P=0.00011; high dose: 9.14±3.42 cm3; P=0.00374). No significant differences in dimensions were observed between CT and gross pathologic images for both high and low dose ablations in both cohorts. CONCLUSION: The treatment zone following MWA in the lung can vary in the sub-acute setting, achieving largest size at 7 days post-treatment. Furthermore, measurements from CT closely matched with gross pathologic ablation size.

Infant formula with galacto-oligosaccharides (OM55N) stimulates the growth of indigenous bifidobacteria in healthy term infants.

The objective of the study was to investigate whether an infant formula supplemented with galacto-oligosaccharides (GOS; OM55N) was able to stimulate the growth of indigenous bifidobacteria and to establish microbiota similar to that of breastfed infants. A randomised, double-blind, placebo-controlled trial was performed using 35 healthy term infants (31-54 days of age; 42±6 days) to determine whether infant formula with 0.3 g/dl GOS (OM55N) stimulated the growth of bifidobacteria in the infants' guts. At the trial onset and 2 weeks after, the infants' faecal samples were examined for microbiota composition (bacterial abundance and α-diversity) and faecal characteristics. Among the 35 infants, 5 were withdrawn and 8 were excluded from the final evaluation before breaking the blinding since the indigenous bifidobacteria were not detected at the trial onset. After 2 weeks, the abundance of Bifidobacteriaceae was significantly increased in the GOS feeding group compared to the control (+11.6±24.1% vs -3.9±13.0%; P=0.043). The Shannon index, which accounts for both abundance and evenness of the present species, was significantly decreased with GOS supplementation (-0.1±0.4 vs +0.4±0.4; P=0.014). Faecal characteristics such as pH and organic acids were similar in both groups, with no statistical differences. No adverse side effects related to the formula consumption were reported. Although the concentration of GOS was relatively low, the infant formula with GOS increased the abundance of bifidobacteria and resulted in a reduced α-diversity of the microbiota.

Simple model of pH-induced protein denaturation.

The pH-induced conformational changes of proteins are systematically studied in the framework of a hydrophobic-polar (HP) model, in which proteins are dramatically simplified as chains of hydrophobic (H) and polar (P) beads on a lattice. We express the electrostatic interaction, the principal driving force of pH-induced unfolding that is not included in the conventional HP model, as the repulsive energy term between P monomers. As a result of the exact enumeration of all of the 14- to 18-mers, it is found that lowest-energy states in many sequences change from single "native" conformations to multiple sets of "denatured" conformations with an increase in the electrostatic repulsion. The switching of the lowest-energy states occurs in quite a similar way to real proteins: it is almost always between two states, while in a small fraction of ≥16-mers it is between three states. We also calculate the structural fluctuations for all of the denatured states and find that the denatured states contain a broad range of incompletely unfolded conformations, similar to "molten globule" states referred to in acid or alkaline denatured real proteins. These results show that the proposed model provides a simple physical picture of pH-induced protein denaturation.

Metabolomic investigation of pathogenesis of myxosporean emaciation disease of tiger puffer fish Takifugu rubripes.

Serum biochemical analysis was undertaken to study the pathophysiological details of emaciation disease of the tiger puffer fish Takifugu rubripes (Temminck and Schlegel). Serum parameters were measured by biochemical analysis using automated dry chemistry and gas chromatography/mass spectrometry (GC/MS). Serum concentrations of albumin, amylase, calcium, creatinine, glucose and total protein were significantly lower in the emaciated fish when compared with those of normal fish. Regression analyses found close correlation between concentrations of total protein, albumin, amylase, glucose and progress of the disease. In contrast, serum alanine aminotransferase increased significantly in emaciated fish indicating liver function disorder. Further, GC/MS metabolic profiling of the puffer serum showed that the profile of the emaciated fish was distinct to that of non-infected control. The serum content of amino acids including glycine, 5-oxo-proline and proline, and ascorbic acid, fumaric acid and glycerol increased significantly in serum in moderately emaciated fish. The serum glucose, linolenic acid and tyrosine level decreased significantly in the late phase of the disease. Our results clearly show that prolonged intestinal damage caused by myxosporean infection impairs absorption of nutrients, resulting in extreme emaciation.

Potential probiotic thermophiles isolated from mice after compost ingestion.

AIMS: The oral administration of a compost produced by the fermentation of marine animals with thermophiles confers health benefits for fish and pigs. This study aimed to isolate the beneficial bacteria from this compost that would modulate the physiological conditions of host animals. METHODS AND RESULTS: The compost extract was orally administrated to germ-free mice for 21 days, and thereafter, the culturable bacterial population within the caeca was surveyed. Sequence analyses of the 16S rRNA gene from the two predominant thermophilic isolates revealed organisms that were closely related to Bacillus thermoamylovorans and Bacillus coagulans. These bacteria could grow at 37°C, but more abundantly at 50-55°C, and they were minor components of the original compost extract. When an individual bacterial strain or a mixture of strains was administered to the conventionally maintained mice, their levels of faecal immunoglobulin A, an indicator of the gut immune response, were markedly raised. In addition, their feeding efficiency also changed among the tested mouse groups. CONCLUSIONS: These two kinds of thermophilic bacterial species, isolated from the caeca after compost ingestion to the germ-free mice, are candidate probiotics that could function in the mammalian gut. SIGNIFICANCE AND IMPACT OF THE STUDY: This study revealed that the compost used in agriculture can contain potential probiotic thermophiles.

CT-fluoroscopy in chest interventional radiology: sliding scale of imaging parameters based on radiation exposure dose and factors increasing radiation exposure dose.

AIM: To verify the usefulness of a sliding scale of imaging parameters to reduce radiation exposure during chest interventional radiology (IR), and to identify factors that increase radiation exposure in order to obtain acceptable computed tomography (CT)-fluoroscopy image quality. MATERIALS AND METHODS: The institutional review board approved this retrospective study, for which the need for informed consent was waived. Interventional radiologists determined the optimal CT-fluoroscopy imaging parameters using the sliding scale based on the radiation exposure dose. The imaging parameters were changed from those generating low radiation (120 kV/10 mA, 1.2 mGy/s) to others generating higher radiation exposure until acceptable image quality was obtained for each procedure. Validation of the imaging parameter sliding scale was done using regression analysis. Factors that increase radiation exposure were identified using multiple regression analysis. RESULTS: In 125 patients, 217 procedures were performed, of which 72 procedures (33.2%, 72/217) were performed with imaging parameters of minimum radiation exposure, but increased radiation exposure was necessary in 145 (66.8%, 145/217). Significant correlation was found between the radiation exposure dose and the percentage achievement of acceptable image quality (R(2) = 0.98). Multivariate regression analysis showed that high body weight (p < 0.0001), long device passage (p < 0.0001), and lesions above the aortic arch (p = 0.04) were significant independent factors increasing radiation exposure. CONCLUSION: Although increased radiation exposure dose might be necessary to obtain acceptable chest CT-fluoroscopy images depending on the patient, lesion, and procedure characteristics, a sliding scale of imaging parameters helps to reduce radiation exposure.

Partial lower axillary dissection for patients with clinically node-negative breast cancer.

OBJECTIVE: To evaluate retrospectively the outcomes of partial lower axillary lymph node dissection caudal to the intercostobrachial nerve in patients with clinically node-negative (N(0)) breast cancer. METHODS: Numbers of dissected and metastatic nodes, overall and disease-free survival rates, postoperative complication rates, and axillary recurrence were compared between patients who underwent breast cancer surgery with partial axillary node dissection (n = 1043) and historical controls who underwent conventional dissection (n = 1084). RESULTS: The 5-year overall and disease-free survival rates were 95.6% and 89.7%, and 94.9% and 88.4%, respectively, in the partial dissection and conventional dissection groups; the differences were not significant. Mean duration of surgery (41.6 min versus 60.9 min), intraoperative blood loss (28.0 ml versus 51.3 ml), volume of lymphatic drainage at 2 weeks postoperatively (488 ml versus 836 ml), and persistent arm lymphoedema (0.0% versus 11.8%) were significantly different between the partial and conventional dissection groups, respectively. CONCLUSIONS: Partial axillary lymph node dissection was associated with similar survival rates (but lower postoperative complication rates) compared with conventional axillary dissection and is recommended in patients with N(0) breast cancer.

Spatial distribution of hexabromocyclododecanes (HBCDs), polybrominated diphenyl ethers (PBDEs) and organochlorines in bivalves from Japanese coastal waters.

In order to elucidate the spatial distribution of brominated flame retardants (BFRs) in the Japanese coastal environment, hexabromocyclododecanes (HBCDs), polybrominated diphenyl ethers (PBDEs) and organochlorines (OCs: PCBs, DDTs, CHLs, HCHs, HCB) were determined in bivalves (oysters and mussels) collected from Japanese coastal waters. HBCDs and PBDEs were detected in all samples analyzed. Concentration ranges of HBCDs were 12-5200 ng g(-1) lipid wt., followed by PCBs (20-3100 ng g(-1))>PBDEs (3.1-86 ng g(-1) lipid wt.). The highest concentration of HBCDs was found in the Osaka region. This result indicates that HBCDs are ubiquitous and predominant compounds in bivalves from the Japanese coastal waters. Since no species differences between oysters and mussels were observed for the bioaccumulation properties of HBCDs and PBDEs, oysters could be utilized for BFR contamination monitoring worldwide as an alternative to mussels. Global comparisons between oysters and mussels showed that HBCD concentrations in Japan are among the highest levels reported from Asia and Europe. Estimated dietary exposures of HBCDs and PBDEs through seafood were 0.45-34 ng kg body weight(-1)d(-1), and 0.054-6.8 ng kg body weight(-1)d(-1), respectively. These exposure levels were more than 1000 times lower than the lowest observable effects or no observable adverse effects levels for HBCDs and PBDEs, respectively.

Intractable bronchopleural fistula caused by radiofrequency ablation: endoscopic bronchial occlusion with silicone embolic material.

A 58-year-old man with primary lung cancer underwent lung radiofrequency (RF) ablation. Pneumothorax developed 12 days after lung RF ablation. Despite chest drainage for 1 month, air leakage continued through a bronchopleural fistula. Bronchial occlusion was performed with a silicone embolus, causing cessation of the air leakage.

Eukaryotic-like protein kinases in the prokaryotes and the myxobacterial kinome.

Ser/Thr/Tyr kinases, which together comprise a major class of regulatory proteins in eukaryotes, were not believed to play an important role in prokaryotes until recently. However, our analysis of 626 prokaryotic genomes reveals that eukaryotic-like protein kinases (ELKs) are found in nearly two-thirds of the sequenced strains. We have identified 2697 ELKs, most of which are encoded by multicellular strains of the phyla Proteobacteria (Myxococcales), Actinobacteria, Cyanobacteria, and Chloroflexi, and 2 Acidobacteria and 1 Planctomycetes. Astonishingly, 7 myxobacterial strains together encode 892 ELKs, with 4 of the strains exhibiting a genomic ELK density similar to that observed in eukaryotes. Most myxobacterial ELKs show a modular organization in which the kinase domain is located at the N terminus. The C-terminal portion of the ELKs is highly diverse and often contains sequences with similarity to characterized domains, most of them involved in signaling mechanisms or in protein-protein interactions. However, many of these architectures are unique to the myxobacteria, an observation that suggests that this group exploits sophisticated and novel signal transduction systems. Phylogenetic reconstruction using the kinase domains revealed many orthologous sequence pairs and a huge number of gene duplications that probably occurred after speciation. Furthermore, studies of the microsynteny in the ELK-encoding regions reveal only low levels of synteny among Myxococcus xanthus, Plesiocystis pacifica, and Sorangium cellulosum. However, extensive similarities between M. xanthus, Stigmatella aurantiaca, and 3 Anaeromyxobacter strains were observed, indicating that they share regulatory pathways involving various ELKs.

Combination therapy of an anticancer drug with the FNIII14 peptide of fibronectin effectively overcomes cell adhesion-mediated drug resistance of acute myelogenous leukemia.

We investigated whether FNIII14, a 22-mer peptide derived from fibronectin (FN) that potently impairs interaction of FN with beta1-integrin, could overcome cell adhesion-mediated drug resistance (CAM-DR) induced by very late antigen (VLA)-4-to-FN interaction in acute myelogenous leukemia (AML). Two AML cell lines, U937 cells and HL-60 cells, and fresh leukemic cells from six AML patients with high alpha4-integrin expression exhibited CAM-DR to cytosine arabinoside (Ara C) through VLA-4-to-FN interaction, while fresh leukemic cells from two AML patients with low alpha4-integrin expression did not display CAM-DR to Ara C. FNIII14 impaired VLA-4-to-FN interaction and restored sensitivity to Ara C in the CAM-DR leukemic cells. In these CAM-DR leukemic cells, upregulation of Bcl-2, which was induced through the focal adhesion kinase/Akt signal pathway upon VLA-4-to-FN interaction, was inhibited by FNIII14 treatment. In a mouse model of minimal residual disease (MRD) in bone marrow, 100% survival was achieved by combining FNIII14 with Ara C, whereas Ara C alone prolonged survival only slightly. The myelosuppression induced by Ara C was not augmented by the combination of FNIII14 in mouse experiments. Thus, the combination of anticancer drugs and FNIII14 holds promise to eradicate MRD in bone marrow after chemotherapy.

Preparation and characterization of activated carbon derived from the thermo-chemical conversion of chicken manure.

Physico-chemical properties of a bioorganic char were modified by pyrolysis in the presence of NaOH, and with subsequent physical activation of carbonaceous species with CO2 a value-added activated carbon was fabricated. Bioorganic char is produced as a co-product during the production of bio-fuel from the pyrolysis of chicken litter. Untreated char contains approximately 37 wt% of C and approximately 43-45 wt% of inorganic minerals containing K, Ca, Fe, P, Cu, Mg, and Si. Carbonization and chemical activation of the char at 600 degrees C in the presence of NaOH in forming gas (4% H2 balanced with Ar) produced mainly demineralized activated carbon having BET (Brunauer, Emmett, and Teller) surface area of 486 m2/g and average pore size of 2.8 nm. Further physical activation with CO2 at 800 degrees C for 30 min resulted in activated carbon with BET surface area of 788 m2/g and average pore size of 2.2 nm. The mineral content was 10 wt%. X-ray photoelectron spectroscopy (XPS) indicated that the latter activation process reduced the pyrrolic- and/or pyridonic-N, increased pyridinic-N and formed quaternary-N at the expense of pyrrolic- and/or pyridonic-N found in the untreated char.

Ten-year follow-up results of a randomised controlled study comparing level-I vs level-III axillary lymph node dissection for primary breast cancer.

The most appropriate level of axillary dissection for breast cancer remains unclear. The present randomised study compared the treatment results of level-I vs level-III dissection in T1/2/3 and N0/1a/1b (1987 UICC classification) breast cancer without distant metastasis. Between 1995 and 1997, 522 patients were enrolled, and 514 were eligible. They were stratified into breast-conserving surgery or mastectomy, and then further stratified into level-III dissection (group-A, n=258) or level-I dissection (group-B, n=256). All patients were given oral 5-fluorouracil at 200 mg day-1 and tamoxifen at 20 mg day-1, daily for 2 years. Group-A resulted in a significantly longer operation time (77.0 vs 60.5 min, P<0.0001) and significantly larger blood loss (62.1 vs 48.1 ml, P<0.0001) than group-B, but in no significant differences in the frequencies of arm oedema and shoulder disturbance. Group-A resulted in a significantly larger number of dissected nodes than group-B (18.7 vs 14.8, P<0.0001), but in no differences in the number of involved nodes (1.54 vs 1.44). There were no significant differences in the 10-year overall and disease-free survival rates: 89.6 and 76.6% for group-A vs 87.8 and 74.1% for group-B, respectively. In conclusion, level-III dissection resulted in a longer operation time and greater blood loss than level-I, but did not improve the survival rate. Level-III dissection is not a recommended surgery for T1-3/N0-1b breast cancer.

Clinical outcomes of multilevel anterior corpectomy and fusion as a revision surgery of the cervical spine: report of seven cases.

STUDY DESIGN: Report of seven cases. OBJECTIVE: There is no general consensus on the best surgical procedures for late-onset complications of cervical operations. We reported seven patients who had been treated effectively by multilevel anterior corpectomy and fusion (ACF) as revision surgery of the cervical spine. SETTING: Gifu University Hospital, Gifu, Japan. METHOD: Multilevel ACF using autogenous fibular strut graft as revision surgery was performed on seven patients: four patients having disorders of adjacent discs after anterior discectomy and fusion and three patients having postlaminoplasty disorders. Japanese Orthopedic Association scores (JOA scores) of the cervical myelopathy and severity of radicular and axial pains were used to evaluate outcomes. RESULTS: Rigid osseous fusion was achieved in all patients. JOA scores of the cervical myelopathy and the radicular pain, which had worsened just before the revision surgery, were improved significantly. CONCLUSION: In the present seven patients who had variety of pathological conditions with various previous surgeries, multilevel ACF using strut graft was effective as a revision procedure in ameliorating their symptoms.

Regression of papular elastolytic giant cell granuloma using narrow-band UVB irradiation.

A 71-year-old Japanese man presented with asymptomatic, firm, brown-red papules on the dorsum of his left hand and back. A biopsy specimen revealed granulomatous infiltration consisting of multinucleated giant cells and histiocytes in the upper dermis. Elastic fibers were absent in the upper dermis, having been phagocytosed by giant cells. These papular elastolytic giant cell granuloma lesions regressed very well with narrow-band ul traviolet B irradiation, with only residual brown pigmentation left after treatment.

Ichthyosis bullosa of Siemens: its correct diagnosis facilitated by molecular genetic testing.

Ichthyosis bullosa of Siemens (IBS, MIM 146800) is a unique congenital ichthyosis characterized by mild epidermal hyperkeratosis over flexural areas, blister formation and the development of superficially denuded areas of hyperkeratotic skin. It is clinically difficult to distinguish severe IBS from mild bullous congenital ichthyosiform erythroderma (BCIE, MIM 113800). In the current literature, 19 IBS families with keratin 2e (K2e) mutations have been reported, despite only five IBS families having been reported before the first identification of K2e mutation in 1994. We studied four patients from three Japanese IBS families. They had previously been misdiagnosed as having BCIE before the correct diagnosis was made after mutation detection. To detect the pathogenic mutations, we performed direct sequencing of the entire coding regions of KRT2E encoding K2e in the patients and healthy family members. K2e mutations, a 1469T-->C transition (L490P) and a 1477G-->A transition (E493K) within the conserved 2B helix termination motif of the rod domain were detected in the families and the definite diagnosis of IBS was made in the four cases. The present results indicate that IBS is not such a rare entity as was previously thought, and accurate diagnosis is now available by mutation analysis.