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BackgroundA standardized pathology management tool for melanocytic skin lesions may improve patient care by simplifying interpretation and categorization of the diverse terminology currently extant.ObjectiveTo assess an online educational intervention that teaches dermatopathologists to use the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx), a schema collapsing multiple diagnostic terms into 5 classes ranging from benign to invasive melanoma.MethodsPracticing dermatopathologists (N = 149) from 40 US states participated in a 2-year educational intervention study (71% response rate). The intervention involved a brief tutorial followed by practice on 28 melanocytic lesions, with the goal of teaching pathologists how to correctly use the MPATH-Dx schema; competence using the MPATH-Dx tool 12-24months postintervention was assessed. Participants' self-reported confidence using the MPATH-Dx tool was assessed preintervention and postintervention.ResultsAt preintervention, confidence using the MPATH-Dx tool was already high, despite 68% lacking prior familiarity with it, and confidence increased postintervention (P = .0003). During the intervention, participants used the MPATH-Dx tool correctly for 90% of their interpretations; postintervention, participants used the MPATH-Dx tool correctly for 88% of their interpretations.LimitationsFuture research should examine implementing a standardized pathology assessment schema in actual clinical practice.ConclusionDermatopathologists can be taught to confidently and competently use the MPATH-Dx schema with a simple educational tutorial followed by practice.

ImportanceA standardized pathology classification system for melanocytic lesions is needed to aid both pathologists and clinicians in cataloging currently existing diverse terminologies and in the diagnosis and treatment of patients. The Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) has been developed for this purpose.ObjectiveTo revise the MPATH-Dx version 1.0 classification tool, using feedback from dermatopathologists participating in the National Institutes of Health–funded Reducing Errors in Melanocytic Interpretations (REMI) Study and from members of the International Melanoma Pathology Study Group (IMPSG).Evidence ReviewPracticing dermatopathologists recruited from 40 US states participated in the 2-year REMI study and provided feedback on the MPATH-Dx version 1.0 tool. Independently, member dermatopathologists participating in an IMPSG workshop dedicated to the MPATH-Dx schema provided additional input for refining the MPATH-Dx tool. A reference panel of 3 dermatopathologists, the original authors of the MPATH-Dx version 1.0 tool, integrated all feedback into an updated and refined MPATH-Dx version 2.0.FindingsThe new MPATH-Dx version 2.0 schema simplifies the original 5-class hierarchy into 4 classes to improve diagnostic concordance and to provide more explicit guidance in the treatment of patients. This new version also has clearly defined histopathological criteria for classification of classes I and II lesions; has specific provisions for the most frequently encountered low–cumulative sun damage pathway of melanoma progression, as well as other, less common World Health Organization pathways to melanoma; provides guidance for classifying intermediate class II tumors vs melanoma; and recognizes a subset of pT1a melanomas with very low risk and possible eventual reclassification as neoplasms lacking criteria for melanoma.Conclusions and RelevanceThe implementation of the newly revised MPATH-Dx version 2.0 schema into clinical practice is anticipated to provide a robust tool and adjunct for standardized diagnostic reporting of melanocytic lesions and management of patients to the benefit of both health care practitioners and patients.

Background Synoptic reporting is recommended by many guideline committees to encourage the thorough histologic documentation necessary for optimal management of patients with melanoma. Methods One hundred fifty-one pathologists from 40 US states interpreted 41 invasive melanoma cases. For each synoptic reporting factor, the authors identified cases with "complete agreement" (all participants recorded the same value) versus any disagreement. Pairwise agreement was calculated for each case as the proportion of pairs of responses that agreed, where paired responses were generated by the comparison of each reviewer's response with all others. Results There was complete agreement among all reviewers for 22 of the 41 cases (54%) on Breslow thickness dichotomized at 0.8 mm, with pairwise agreement ranging from 49% to 100% across the 41 cases. There was complete agreement for "no ulceration" in 24 of the 41 cases (59%), with pairwise agreement ranging from 42% to 100%. Tumor transected at base had complete agreement for 26 of the 41 cases (63%), with pairwise agreement ranging from 31% to 100%. Mitotic rate, categorized as 0/mm2 , 1/mm2 , or 2/mm2 , had complete agreement for 17 of the 41 cases (41%), with pairwise agreement ranging from 36% to 100%. Regression saw complete agreement for 14 of 41 cases (34%), with pairwise agreement ranging from 40% to 100%. Lymphovascular invasion, perineural invasion, and microscopic satellites were rarely reported as present. Respectively, these prognostic factors had complete agreement for 32 (78%), 37 (90%), and 18 (44%) of the 41 cases, and the ranges of pairwise agreement were 47% to 100%, 70% to 100%, and 53% to 100%, respectively. Conclusions These findings alert pathologists and clinicians to the problem of interobserver variability in recording critical prognostic factors. Lay summary This study addresses variability in the assessment and reporting of critical characteristics of invasive melanomas that are used by clinicians to guide patient care. The authors characterize the diagnostic variability among pathologists and their reporting methods in light of recently updated national guidelines. Results demonstrate considerable variability in the diagnostic reporting of melanoma with regard to the following: Breslow thickness, mitotic rate, ulceration, regression, and microscopic satellites. This work serves to alert pathologists and clinicians to the existence of variability in reporting these prognostic factors.

Expert radiologists can quickly extract a basic "gist" understanding of a medical image following less than a second exposure, leading to above-chance diagnostic classification of images. Most of this work has focused on radiology tasks (such as screening mammography), and it is currently unclear whether this pattern of results and the nature of visual expertise underlying this ability are applicable to pathology, another medical imaging domain demanding visual diagnostic interpretation. To further characterize the detection, localization, and diagnosis of medical images, this study examined eye movements and diagnostic decision-making when pathologists were briefly exposed to digital whole slide images of melanocytic skin biopsies. Twelve resident (N = 5), fellow (N = 5), and attending pathologists (N = 2) with experience interpreting dermatopathology briefly viewed 48 cases presented for 500 ms each, and we tracked their eye movements towards histological abnormalities, their ability to classify images as containing or not containing invasive melanoma, and their ability to localize critical image regions. Results demonstrated rapid shifts of the eyes towards critical abnormalities during image viewing, high diagnostic sensitivity and specificity, and a surprisingly accurate ability to localize critical diagnostic image regions. Furthermore, when pathologists fixated critical regions with their eyes, they were subsequently much more likely to successfully localize that region on an outline of the image. Results are discussed relative to models of medical image interpretation and innovative methods for monitoring and assessing expertise development during medical education and training.

International audience; We measured an Al K-edge x-ray absorption near edge structure (XANES) spectrum of Al doped NiO for anode materials of lithium ion batteries. We found that the spectrum of the Al doped NiO is similar to that of γ-Al2O3. Calculated site-specific XANES spectra strongly correspond to the coordination nature around the absorbing Al ion, indicating aggregation of cation vacancies surrounded by Al ions in the Al doped NiO. These finding could be useful to understand how Li ions migrate in the anode.

The thermoelectric properties of ternary full-Heusler alloys, Co2 YZ, which are in a ferromagnetic state up to high temperature above 300 K, were measured and are discussed in terms of the crystal structure and electronic states. Among the full-Heusler alloys studied, the Co2MnSi sample exhibited the highest absolute value of Seebeck coefficient and also the highest electrical conductivity in the temperature range from 300 K to 1023 K. The highest power factor of 2.9 × 10−3 W/m-K2 was obtained for the Co2MnSi sample at 550 K, demonstrating the potential of half-metallic full-Heusler alloys as thermoelectric materials.

Pulsed field gel electrophoresis (PFGE) and random amplified polymorphic DNA (RAPD) methods were applied for molecular typing of 130 Mannheimia (Pasteurella) haemolytica serotype A1 isolates obtained from 13 prefectures in Japan. These isolates were divided into 15 ApaI PFGE profiles that formed six distinct clusters (clusters A–F). Fifty-three (40·7%) isolates were classified in cluster B, and 20·0, 13·8, 12·3, 6·9 and 6·1% of isolates were in clusters E, A, F, D and C, respectively. The isolates of cluster B were differentiated into seven subtypes (B1–B7) and subtype B5 contained 63% (34/53) of isolates. RAPD revealed four banding patterns (types I–IV), and among 130 isolates 60·7% (79/130) of isolates were RAPD type I. All of the RAPD type I isolates were grouped into clusters A–C by PFGE. There was no relationship between molecular typing and geographic origin of these isolates. These results indicate that isolates of M. haemolytica A1 strain with various molecular profiles have already spread in Japan and may have caused sporadic infections.

SUMMARYA total of 105 033 eggs were collected across Japan from June 2010 to January 2011 and tested for Salmonella Enteritidis to provide data for the risk profiling of S. Enteritidis in eggs by the Food Safety Commission of Japan. S. Enteritidis isolates were recovered from three samples (20 eggs/sample) and these samples were different in regard to sampling period, grading and packaging centre and farm. The prevalence of S. Enteritidis in commercial eggs in Japan is estimated at ∼0·003% which was a tenfold decrease in prevalence compared to similar surveillance in the mid 1990s. The decrease in the contamination in commercial eggs is considered a contributory factor in the decrease of foodborne diseases associated with S. Enteritidis in this period.

The X-linked lymphoproliferative disease (XLP) is an inherited immunodeficiency characterized by an abnormal responses to infection with Epstein-Barr virus (EBV), resulting in fatal infectious mononucleosis, hypogammaglobulinemia, virus-associated hemophagocytic syndrome, and malignant lymphoma. Mutations in the gene coding for a T cell-specific SLAM-associated protein (SAP) have been recently identified in XLP patients. We report on a 1-year-old boy representing fulminant hemophagocytic syndrome. He developed high fever, lymphadenopathy, hepatosplenomegaly with liver dysfunction, and pancytopenia with marrow hemophagocytosis. EBV DNA was abnormally increased in the blood. Polymerase chain reaction failed to amplify SAP mRNA and genomic DNA products from the patient' As peripheral blood. A large deletion of the SAP gene was confirmed by fluorescence in situ hybridization (FISH). FISH analysis also disclosed that the patient's mother was a carrier. We conclude that FISH can be useful in the diagnosis of XLP with large deletions of the SAP gene and its carrier state.

S-PED means a superconducting power electronics device. We made some thermally controlled S-PED which is a normally-on device. They work up to 100 Hz as a full wave rectifier. For the power supply of superconducting magnets, the flux pump can be used as SPEED (superconducting power electronics excitation device). In this paper, we describe the turn off characteristics of one of the S-PED (type d). The relations between generated resistance, gate-trigger energy and channel current were obtained.

Round-robin tests were conducted in order to investigate a simple and easy method for preparing a standard gas mixture of volatile organic hazardous air pollutants from their mixed solution by 16 members of the Association for Environmental Analysis in Osaka. Seven compounds (acrylonitrile, dichloromethane, chloroform, 1, 2-dichloroethane, benzene, trichloroethylene, and tetrachloroethylene) were accurately weighed into a vial one by one. An aliquot of this liquid mixture was transferred into a glass vessel (1 or 21) using a microsyringe, and then vaporized. The resulting gas mixtures (about 300 ppm each) were evaluated as a first standard gas by gas chromatography. The obtained results prove this method to be accurate and precise for the preparation of a standard gas mixture.

p16 and p15 genes are putative tumor suppressor genes located on chromosome 9p21. In acute leukemias, alterations of p16 and p15 genes have been reported to occur exclusively in lymphoid lineage. We analyzed alterations of p16 and p15 genes in 46 acute leukemias with MLL gene rearrangements by Southern blot analysis, and investigated the association with clinical characteristics. We identified homozygous deletion of p16 and p15 genes in five (19%) of 27 acute lymphoblastic leukemias (ALLs) and in two (11%) of 19 acute myeloid leukemias (AMLs). Patients with homozygous deletion of p16 and p15 genes showed higher average leukocyte counts (343 x 10(9)/l vs 271 x 10(9)/l) and lower estimated 2-year survival rates than those with normal p16 and p15 genes (14.3 vs 30.7%), although the differences were not statistically significant. In addition, we investigated mutation of p16 gene by polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) in 31 patients, but no mutation was found in the patients tested. Our results suggest that alterations of p16 and p15 genes are involved in a subset of acute leukemias with MLL gene rearrangement not only of lymphoid but also of myeloid phenotype. Homozygous deletion of p16 and p15 genes may be a possible adverse prognostic factor, although further analysis would be needed to confirm it.

The ETV6/TEL gene has been reported to fuse to PDGFRbetab MDS1/EVI1, BTL, ACS2, STL, JAK2, ABL, CDX2, TRKC, AML1, and MN1. Among them, PDGFRbeta, ABL, JAK2, and TRKC are tyrosine kinases (TK). We identified a novel ETV6 partner gene, ARG (ABL-related gene or ABL2), another TK gene in a cell line established from a patient with acute myelogenous leukemia (AML-M3) with a t(15;17)(q22;q11.2) and a t(1;12)(q25;p13), which has the remarkable feature to differentiate to mature eosinophils in culture with all-trans retinoic acid and cytokines. The ETV6/ARG transcripts consisted of exon 1 to 5 of ETV6 and the 3' portion of ARG starting from exon 1B or exon 2, resulting in an open reading frame for a fusion protein consisting of the entire PNT oligomerization domain of ETV6 and all of the functional domains of ARG including the TK domain. This is the same protein structure as identified in the other ETV6 TK fusion proteins. The reciprocal ARG/ETV6 transcript was not expressed, and the normal ETV6 allele was not deleted or rearranged. Although the ABL is known to be involved in various human malignancies, ARG has not been involved in human malignancies despite its high homology to ABL. Thus, this is the first report showing involvement of ARG in human leukemia. The ETV6/ARG protein may be involved in the unique differentiation capacity of this cell line. (Blood. 2000;95:2126-2131)

The effects of a protein-restricted diet on renal recovery following renal ischemia were studied. The renal function was assessed by measuring the inulin clearance (CIN), the p-aminohippurate clearance (CPAH), and the percent fractional sodium excretion (%FENa) 24 h after 45 min renal ischemia. In rats fed with a regular diet (containing 19.6% protein), CIN was 10.0 +/- 2.2 microL/min/100 g body weight (BW), CPAH 0.08 +/- 0.02 mL/min/100 g BW, and %FENa 14.8 +/- 2.0, 24 h after renal ischemia. In contrast, feeding rats with a no-protein diet (0% protein) for 1 week prior to the ischemic insult significantly improved renal recovery (CIN 48.0 +/- 9.3 microL/min/100 g BW, CPAH 0.16 +/- 0.04 mL/min/100 g BW, and %FENa 2.43 +/- 0.58). Feeding rats with a no-protein diet for 3 weeks prior to ischemic insult further improved the renal recovery (CIN 113 +/- 30 microL/min/100 g BW, CPAH 0.47 +/- 0.17 mL/min/100 g BW, and %FENa 1.55 +/- 0.29). When rats fed with a regular diet were exposed to 45 min of ischemia, the survival rate on day 7 was 16.7%. In rats fed with the no-protein diet for 1 week and for 3 weeks, the 7-day survival rate was 100% in each case. The survival rate of rats fed for 3 days instead of 7 days with the no-protein diet was 87.5%. When a no-protein feeding was shortened to 1 day, no beneficial effects were observed and survival rate was 14.3%. (ABSTRACT TRUNCATED AT 250 WORDS)

The authors describe the method of reducing the fan noise, especially the impeller noise, of a household refrigerator. The fan in the refrigerator tested is a propeller fan, and the fan unit consists of an impeller, which has four blades, a rear board, which covers the evaporator, and a front board, which has a number of openings. The flow through the openings freezes food in the freezer. By measuring the internal flow with a laser Doppler velocimeter, it was made clear that the flow through the impeller was not symmetrical to the axis. The unsymmetrical flow seems to be caused by the restrictions of flow passages, and it might produce the impeller noise. The search for the sound source by the sound intensity method indicated that the noise was radiated through the openings of the front board. Guiders were installed on the rear board in the fan unit to guide the flow away from the openings. As a result, the impeller noise was reduced, whereas the flow was kept almost the same. >

The aim of this study was to clarify the epidemiological association and bacteriological characteristics of human and animal Staphylococcus aureus isolates. Pulsed-field gel electrophoresis showed that pulsotypes (PT) of isolates from bulk milk differed from PT from human isolates, suggesting that there is no epidemiological association between isolates from these 2 sources. The absence of a common PT could result from the lack of contact between the sources. Methicillin-resistant S. aureus from human secretions and S. aureus from bulk milk in Japan consisted of 1 and 2 dominant clusters, respectively, whereas methicillin-susceptible S. aureus from humans consisted of assorted clusters. Isolates belonging to the dominant clusters showed the coagulase serotype, the capsule serotype, detection of exotoxin genes, and antimicrobial susceptibility. Isolates from bulk milk did not show the penicillin-binding protein 2a gene, and 252 of 275 isolates belonging to the 2 dominant clusters of bulk milk were susceptible to ampicillin, cefazolin, erythromycin, chloramphenicol, oxacillin, and vancomycin. Moreover, the LukM/LukF'-PV leukotoxin gene was detected in 233 of 275 isolates belonging to the dominant clusters in bulk milk isolates. These results support the hypothesis that a number of factors play a role in the adaptation of S. aureus isolates to specific hosts.

A 35-year-old female presented with partial complex seizures. Computed tomography (CT) showed a slightly high density mass over the right frontal convexity, with heterogeneous contrast enhancement. T1-weighted magnetic resonance (MR) imaging showed the tumour as a hypo-intense lesion, with faint reticular enhancement after intravenous injection of gadolinium-diethylenetriaminepenta-acetic acid. The tumour was totally removed. The specimen was extremely soft and moist. The histological diagnosis was microcystic meningioma. The tumour cells were composed of typical meningothelial cells and stellate cells. The degenerative character of the tumour may be reflected in the poor enhancement on CT and MR imaging. This faint enhancement effect may be a neuro-imaging characteristic indication of this rare microcystic variant of meningioma.

Ataxia telangiectasia (AT) carrier-derived lymphoblastoid cell lines (AT-LCLs/hetero) with suboptimal ATM protein expression were examined for the regulation of radiosensitivity, apoptosis, and mitotic spindle checkpoint in response to DNA-damaging agents. Although AT-LCLs/hetero showed intermediate radiation sensitivity, as determined by clonogenic assay, they were resistant to early-onset apoptosis, as much as AT patient-derived LCLs (AT-LCLs/homo). Furthermore, two of three AT-LCLs/hetero showed defective mitotic spindle checkpoint control in response to X-ray irradiation, which is a recently characterized biological feature in AT-LCLs/homo. Our findings indicate that carriers of ATM mutation have biological abnormalities due to haploinsufficiency of ATM protein or dominant-negative effect of mutant ATM protein. Thus, although it is still controversial whether ATM mutation carriers are at higher risk for cancer during adulthood, our findings based on in vitro biological indicators support the notion that at least some of such carriers are at a higher risk for cancer development than those without ATM mutation. Our findings may help to reevaluate epidemiological studies on cancer susceptibility in AT carriers.

We examined the regulation of apoptosis, radiosensitivity, and spindle checkpoint in response to DNA-damaging agents in ataxia telangiectasia (AT)-derived lymphoblastoid cell lines (AT-LCLs), which lack AT mutated (ATM) protein expression. In addition to the previous findings that AT-LCLs are defective in regulation of cell cycle at the G1, S, and G2-M checkpoints in response to X-ray irradiation (X-IR) and are highly sensitive to X-IR (J. Biol. Chem., 271: 20486-20493, 1996), we showed for the first time that AT-LCLs were defective in X-IR-associated spindle checkpoint control. The cells were also resistant to early apoptosis as much as LCLs derived from patients with Li-Fraumeni syndrome (LFS-LCLs). Terminal deoxynucleotidyl transferase-mediated nick end labeling assay of LCLs, however, demonstrated a significant increase in apoptotic cells among AT-LCLs cultured over a longer period after X-IR. These findings were in contrast to those of LFS-LCL, which showed very little increase in terminal deoxynucleotidyl transferase-mediated nick end labeling-positive population, even in cells with hyperploidy. Thus, although early apoptosis and cell cycle controls in response to DNA damage are disrupted in both ATM and p53 mutations, cells from AT patients are much more susceptible to late-onset apoptosis than those of LFS. These differences may depend on the level of accumulation of DNA damage and/or threshold that triggers late-onset cell death in ATM or p53 mutations. Our findings allow a better understanding of the role of ATM in p53-dependent and independent signal transduction pathways in response to DNA damaging agents.

Case Report A 44-year-old woman presented complaining of a slightly tender left inguinal mass, of which she had been aware for about I month. On physical examination. the mass was relatively hard and could not be pushed back into the abdominal cavity. Sonography revealed a pedunculated, solid 3-cm mass in the left inguinal area (Fig. 1A). The stalk of the mass extended into the abdominal cavity and seemed to be continuous with the uterine corpus (Fig. 1B). Beside the mass, the left ovary could be identifled adjacent to the uterus; therefore, the mass

Lymphoblastoid cell lines (LCLs) with heterozygous p53 mutations at residues 286A, 133R, 282W, 132E, and 213ter were established from five independent Li-Fraumeni syndrome families. When cell cycle regulation in response to gamma-irradiation was studied, these LCLs showed an abnormal G1 checkpoint associated with defective inhibition of cyclin E/cyclin-dependent kinase 2 activity in all cases except for 282W LCL, which showed a normal G1 checkpoint. On the other hand, the control of S-phase-G2 as determined by cyclin A/cyclin-dependent kinase 2 activity was defective in all these LCLs. The mitotic checkpoint was also defective in the two LCLs analyzed as either competent or incompetent for G1 arrest. When radiation-induced apoptosis, which requires wild-type p53 function under optimal conditions, was studied, all of these LCLs showed significant failure compared to normal LCLs. These findings indicate that although p53-dependent transactivation and G1-S-phase cell cycle control are variably dysregulated, the induction of apoptosis and control of the cell cycle at S-phase-G2 and the mitotic checkpoint in response to DNA-damaging agents are consistently dysregulated in heterozygous mutant LCLs. This suggests that these dysfunctions underlie, at least in part, the susceptibility of Li-Fraumeni syndrome families to cancer. Furthermore, the approach presented is a potentially useful method for studying individual carriers of different germ-line p53 mutations and different biological features.

The presence of the mycobacterial insertion sequence IS901 was studied by PCR with reference strains of Mycobacterium avium complex; 122 veterinary strains of mycobacteria, mainly M. avium complex, isolated from swine; and 15 clinical strains. Four kinds of DNA extraction methods for PCR were compared. Use of the commercial extraction matrix allowed for the faster and easier preparation of PCR-amplifiable DNA than use of NaOH heating extraction or sodium dodecyl sulfate extraction of pretreated mycobacteria. It also provided more effective protection than boiling extraction against the destruction of DNA. Four reference strains of serovars 1 to 3 possessed IS901. Nine reference strains of serovars 1, 4 to 6, 8 to 11, and 21 possessed only IS901 insertion sites. A novel PCR product was found in the other reference strains of serovars 7, 12 to 17, 19, and 20 and two clinical strains of serovar 15. It is suggested that the primers that amplified the insertion portion of IS901 divided the M. avium complex into M. avium, Mycobacterium intracellulare, and other mycobacteria. None of the 110 strains of M. avium complex isolated from swine possessed IS901. It is suggested that the absence of IS901 might be characteristic of swine-derived strains of M. avium complex.

The effect of dietary octacosanol, a long-chain alcohol, on lipid metabolism was investigated in rats fed on a high-fat diet for 20 d. The addition of octacosanol (10 g/kg diet) to the high-fat diet led to a significant reduction (P < 0·05) in the perirenal adipose tissue weight without decrease of the cell number, suggesting that octacosanol may suppress lipid accumulation in this tissue, whereas no effect was seen in the epididymal adipose tissue weight and in the lipid content in liver. Octacosanol supplementation decreased the serum triacylglycerol concentration, and enhanced the concentration of serum fatty acids, probably through inhibition of hepatic phosphatidate phosphohydrolase (EC3·1·3·4). Though the activity of hormone-sensitive lipase (EC3·1·1·3) was not influenced by octacosanol, higher activities of lipoprotein lipase (EC3·1·1·34) in the perirenal adipose tissue and the total oxidation rate of fatty acid in muscle were observed. Lipid absorption was not affected by the inclusion of octacosanol. Thus, the present results suggest that the dietary incorporation of octacosanol into a high-fat diet affects some aspects of lipid metabolism.

Background: Our previously published data show that Adipose-derived regenerative cells (ADRCs) enhance the long term retention of autologous fat grafting compared to non-cell-enhanced grafts. To further understand the time course of growth factor expression of ADRCs, we developed an in vivo xenogenic fat graft model.Materials and Methods: Male NCR nude mice were used as recipients to avoid immune rejection of human ADRCs. Inguinal fat pads from male C57Bl6 mice were minced and used as donor fat for transplantation. Human ADRCs from three healthy donors were isolated using the automated Celution® 800/CRS System (Cytori Therapeutics, San Diego, USA) and mixed with minced mouse fat at a concentration of 5x10E5/ml. The mixture was grafted into the dorsal subcutaneous space of nude mice. Grafted samples were harvested at day 0, day 1, day 7, day 14, day 28, day 56 and day 84, for a total of seven different time points (N=4 per time point). DNA and RNA was isolated for further human-specific detection of IGF-1 and VEGF-A and human-specific single copy DNA using real time RT-PCR. All data were normalized to time 0 samples as 100%.Results: Both of human IGF-1 and VEGF-A expression were detected in the first two weeks after fat grafting, and each of the human growth factor showed its unique pattern. For IGF-1, the highest expression level of 100±7.5% was detected at time 0 with a decline to 0.9±0.7% that was maintained for two weeks. By day 14 only 0.22% of the original signal was detected and no more signal could be detected after day 28. In contrast, on day 1 VEGF-A expression showed an increase to 212±82.6% of the time 0 value. It further declined to 30±23% on day 7 and 8.7±11.7% on day 14. After day 28 no more VEGF-A expression could be detected. The engraftment of ADRCs, measured by DNA content, declined to 12±10.7% on day 1 and remained at around 1% until day 14. By day 28, only 0.14% of human DNA signal could be detected and no more signal could be found after day 56.Conclusion: These findings demonstrate that this xenogenic approach allows the evaluation of single growth factor expression of human ADRCs in vivo using a mouse background when studying cell-enhanced fat grafting. It also allows quantitative assessment of cell survival. By using this model we find that human ADRCs secrete several growth factors within the grafts and that each growth factor has its own unique profile. Furthermore, it becomes evident that ADRCs are active for several days after implantation before growth factor expression subsides. This is an important safety feature of this adult cell therapy source since continued, high level expression of growth factors would not be desirable in cases of reconstruction after breast cancer removal, when concerns of residual tumor cells exist. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4124.

A new human leukemia cell line with megakaryocytic features, designated UT-7, was established from the bone marrow of a patient with acute megakaryoblastic leukemia. Surface marker analysis revealed that the majority of the cells reacted with monoclonal antibodies against platelet glycoprotein Ib (CD42b), glycoprotein IIb/IIIa (CD41a), MY 7 (CD13), MY 9 (CD33), and glycophorin A antigens. Cytogenetic analysis showed a human male near-tetraploid karyotype with a modal chromosome number of 92-96. Flow cytometry-derived DNA histograms demonstrated that the majority of the cells spontaneously contained 4 N DNA ploidy levels. Ultrastructural study showed that platelet peroxidase activity was weakly positive but myeloperoxidase activity was negative. Ferritin and theta-granule, which have been used as ultrastructural markers for the erythroid lineage, could not be detected. In response to phorbol myristate acetate, platelet factor 4 and beta-thromboglobulin, which were specifically synthesized in the process of megakaryocyte maturation, dramatically increased in UT-7 cells. This was accompanied by an increase in cell size, ploidy level, platelet peroxidase activity, and the surface density of glycoprotein IIb/IIIa antigen. These findings suggest that UT-7 is a new leukemic cell line with megakaryocytic features and with the potential to differentiate into cells with more mature megakaryocytic properties in response to phorbol myristate acetate. This cell line showed strict dependency on interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor, or erythropoietin. The maximal effective doses of IL-3, granulocyte-macrophage colony-stimulating factor, and erythropoietin for proliferation in liquid culture were 10 units/ml, 1 ng/ml, and 1 unit/ml, respectively. These concentrations were comparable to the doses that maximally stimulate the clonal growth of normal hemopoietic cells. IL-6 could stimulate the proliferation of UT-7 cells but not maintain the line in long-term culture. UT-7 cells may be a useful model for (a) the analysis of gene regulation of megakaryocytic maturation-associated proteins expressed in the process of megakaryocytic differentiation and (b) the study of signal transduction of hemopoietic factors associated with megakaryocytopoiesis.

Background Increasingly, medications are consumed outside of clinical settings, with relatively little professional oversight. Despite this trend, previous studies of medication errors have focused on clinical settings. Methods We examined all US death certificates from January 1, 1983, to December 31, 2004 (N = 49 586 156), particularly those with fatal medication errors (FMEs) (n = 224 355). We examined trends in 4 types of FMEs that vary according to the relative importance of alcohol/street drugs and the relative likelihood of professional oversight in the consumption of medications. Results The overall FME death rate increased by 360.5% (1983-2004). This increase far exceeds the increase in death rates from adverse effects of medications (33.2%) or from alcohol and/or street drugs (40.9%). The increase in FMEs varies markedly by type. Type 1 (domestic FMEs combined with alcohol and/or street drugs) shows the largest increase (3196%). In contrast, type 4 (nondomestic FMEs not involving alcohol and/or street drugs) shows the smallest increase (5%). Types 2 and 3 show intermediate increases. Type 2 (domestic FMEs not involving alcohol and/or street drugs) increased by 564%. Type 3 (nondomestic FMEs combined with alcohol and/or street drugs) increased by 555%. Thus, domestic FMEs combined with alcohol and/or street drugs have become an increasingly important health problem compared with other FMEs. Conclusions These findings suggest that a shift in the location of medication consumption from clinical to domestic settings is linked to a steep increase in FMEs. It may now be possible to reduce FMEs by focusing not only on clinical settings but also on domestic settings.

This paper presents the concept of dividing a local office service area under the present telephone network into blocks of switching areas to make up a local network with small, distributed switching nodes because switching costs will become much cheaper relative to cable laying costs due to LSI technology progress. In this paper, cable laying cost and switching cost are taken as the two main factors in determining future local network configurations. First, the cable laying cost is formulated using cable duct and circuit length. Next, the switching system cost is formulated based on the relation between capability and cost of components such as gates and memories. Finally, local telephone network cost is calculated, using the cost formulas obtained and data available at present. The conclusion is that from the cost-effective point of view, conventional local network office service areas should be divided into 9 to 16 blocks.

Cell-mediated and humoral immune responses in mice after challenge exposure with Mycoplasma pulmonis were investigated. The cell-mediated immune response was determined by means of the delayed-type footpad swelling and the humoral immune response by means of the indirect haemagglutination test. Delayed-type footpad swelling and serum antibody titres were detected at one week after the challenge exposure and persisted for 7 weeks until the end of the experiment. However, there was a poor correlation between the degree of delayed-type footpad swelling and that of serum antibody titre. Delayed-type footpad swelling in mice with gross pneumonic lesions was less than that of mice with no gross lesions. A weak negative linear correlation was observed between the delayed-type footpad swelling and the number of M. pulmonis isolated from lungs.

A boy, 10 years old, who came to the division of orthopedic surgery for his fracture of right clavicle, showed remarkable appearances of biochemical and radiologic abnormalities of rickets.He suffered from epilepsy following influenza vaccination at seven months after birth and has received anticonvulsant medication over nine years.At about four months since he has been treated with Ethosuximide and Diazepam instead of the administrations of Diphenylhydantoin, Trimethadion, Primidone, Phenobarbital, Mephobarbital and Acetazolamide, enlargements of the antebrachial bone ends disappeared; fraying and cupping of the metaphyses and the wide growth discus on X-ray were almost improved; and elevation of the serum alkaline phosphatase activity (29 B. U.) decreased to 11 B. U..

A new technique for parallel transmission of digital and analog signals over a single telephone channel is presented. The modulation scheme treated in this paper is quadrature amplitude modulation, wherein the digital and analog information are mapped separately as in phase and quadrature components. In the realization of the high-speed parallel transmission, adaptive equalization and carrier phase control are significant problems. In the hybrid QAM modem a two-dimensional error signal cannot be measured accurately at the demodulator output. This causes difficulty in implementing the conventional decision directed circuitry, which is usually employed in the adaptive equalizer and the carrier phase control circuit. The new decision directed schemes which are applicable to parallel transmission are derived by using an error signal measurement defined independent of the analog part. Computer simulation for the parallel transmission scheme of 4.8 kbit/s digital and 2.4 kHz sampled analog sequences is carried out for a typical dispersive telephone channel. Simulation results show that this scheme is useful for high fidelity analog signal transmission.

Cytogenetic, immunologic, and electron microscopic studies were performed on the blast cells of 28 pediatric patients with Down's syndrome, 13 with acute leukemia (DS-AL) and 15 with transient myeloproliferative disorders (DS-TMD). Clonal chromosome abnormalities were found in the cells of all patients with DS-AL but not those with DS-TMD. The younger ages and higher hemoglobin concentrations, platelet counts, and WBC counts of DS-TMD patients provided a clinical contrast with the frankly leukemic cases. Myelodysplastic syndrome, characterized by a small percentage of leukemic blast cells, was observed in 11 of the 13 patients with DS-AL compared with none in the DS-TMD group. Electron microscopy disclosed a positive platelet peroxidase reaction in each of the 11 DS-TMD patients and in nine of the 13 DS-AL patients. Immunologic studies revealed antiplatelet- megakaryocyte antigens on the blast cells of the majority of patients in both study groups. Our findings suggest that the blast cells in cases of DS-AL and DS-TMD arise from cells of the megakaryocytic lineage or from a myeloid progenitor with the capacity for megakaryocytic differentiation. The high risk of the development of AL in patients with DS who are less than 3 years old may be related to increased megakaryocyte proliferation in this age group.

The proximal nephron of C57 beige mice with a genetic defect analagous to the Chédiak-Higashi syndrome (CHS) has been compared with that of normal C57 black mice. The concanavalin A-horseradish peroxidase (Con A-HRP) technique stained the brush border of the proximal straight tubule heavily in black mice and weakly in beige mice. In beige mice this method stained the brush border of the proximal convoluted tubules weakly and the brush border of the proximal straight tubules only negligibly. Periodic acid-Schiff staining showed no such difference between beige and black mice but revealed an increase distally in the size of the CHS inclusions in the proximal straight tubule of beige mice. Immunostaining visualized abundant lysozyme in the first portion of the proximal nephron but none in the more distal segments of beige and black mice alike. At the ultrastructural level, the proximal convoluted tubules of black mice contained two morphologic types of heterophagosomes, which apparently differed in accord with the stage of their development. Proximal straight tubules contained morphologically different heterophagic bodies. The mature stages of these heterophagosomes were greatly enlarged in CHS mice. With the periodic acid-thiocarbohydrazide-silver proteinate (PA-T-SP) method for localizing glycoprotein ultrastructurally, the microvillar brush border, apical invaginations of the plasmalemma, Golgi cisternae, and lysosomal inclusions stained selectively in the proximal nephron in both strains. The proximal straight nephron of beige mice after staining with the PA-T-SP method appeared depleted of the strongly reactive apical invaginations in some areas, particularly where large heterophagosomes bordered the apical plasmalemma. The enlarged secondary lysosomes of heterophagic origin in beige mice varied in showing both diffuse and focal PA-T-SP reactivity. Lysosomal acid phosphatase activity appeared decreased, and peroxisomes were normal in size but increased in number in the proximal nephron of beige mice.

Cytogenetic, immunologic, and electron microscopic studies were performed on the blast cells of 28 pediatric patients with Down's syndrome, 13 with acute leukemia (DS-AL) and 15 with transient myeloproliferative disorders (DS-TMD). Clonal chromosome abnormalities were found in the cells of all patients with DS-AL but not those with DS-TMD. The younger ages and higher hemoglobin concentrations, platelet counts, and WBC counts of DS-TMD patients provided a clinical contrast with the frankly leukemic cases. Myelodysplastic syndrome, characterized by a small percentage of leukemic blast cells, was observed in 11 of the 13 patients with DS-AL compared with none in the DS-TMD group. Electron microscopy disclosed a positive platelet peroxidase reaction in each of the 11 DS-TMD patients and in nine of the 13 DS-AL patients. Immunologic studies revealed antiplatelet-megakaryocyte antigens on the blast cells of the majority of patients in both study groups. Our findings suggest that the blast cells in cases of DS-AL and DS-TMD arise from cells of the megakaryocytic lineage or from a myeloid progenitor with the capacity for megakaryocytic differentiation. The high risk of the development of AL in patients with DS who are less than 3 years old may be related to increased megakaryocyte proliferation in this age group.