Detecting halfmetallic electronic structures of spintronic materials in a magnetic field.

Band-gap engineering is one of the fundamental techniques in semiconductor technology and also applicable in next generation spintronics using the spin degree of freedom. To fully utilize the spintronic materials, it is essential to optimize the spin-dependent electronic structures in the operando conditions by applying magnetic and/or electric fields. Here we present an advanced spectroscopic technique to probe the spin-polarized electronic structures by using magnetic circular dichroism (MCD) in resonant inelastic soft X-ray scattering (RIXS) under an external magnetic field. Thanks to the spin-selective dipole-allowed transitions in RIXS-MCD, we have successfully demonstrated the direct evidence of the perfectly spin-polarized electronic structures for the prototypical halfmetallic Heusller alloy [Formula: see text]. RIXS-MCD is a promising tool to probe the spin-dependent carriers and band-gap induced in the buried magnetic layers in an element specific way under the operando conditions.

Adrenal nodularity and somatic mutations in primary aldosteronism: one node is the culprit?

CONTEXT: Somatic mutations in genes that influence cell entry of calcium have been identified in aldosterone-producing adenomas (APAs) of adrenal cortex in primary aldosteronism (PA). Many adrenal glands removed for suspicion of APA do not contain a single adenoma but nodular hyperplasia. OBJECTIVE: The objective of the study was to assess multinodularity and phenotypic and genotypic characteristics of adrenals removed because of the suspicion of APAs. DESIGN AND METHODS: We assessed the adrenals of 53 PA patients for histopathological characteristics and immunohistochemistry for aldosterone (P450C18) and cortisol (P450C11) synthesis and for KCNJ5, ATP1A1, ATP2B3, and CACNA1D mutations in microdissected nodi. RESULTS: Glands contained a solitary adenoma in 43% and nodular hyperplasia in 53% of cases. Most adrenal glands contained only one nodule positive for P450C18 expression, with all other nodules negative. KCNJ5 mutations were present in 22 of 53 adrenals (13 adenoma and nine multinodular adrenals). An ATP1A1 and a CACNA1D mutation were found in one multinodular gland each and an ATP2B3 mutation in five APA-containing glands. Mutations were always located in the P450C18-positive nodule. In one gland two nodules containing two different KCNJ5 mutations were present. Zona fasciculata-like cells were more typical for KCNJ5 mutation-containing nodules and zona glomerulosa-like cells for the other three genes. CONCLUSIONS: Somatic mutations in KCNJ5, ATP1A1, or CACNA1D genes are not limited to APAs but are also found in the more frequent multinodular adrenals. In multinodular glands, only one nodule harbors a mutation. This suggests that the occurrence of a mutation and nodule formation are independent processes. The implications for clinical management remain to be determined.

Nonmagnetic ground states and phase transitions in the caged compounds PrT2Zn20 (T = Ru, Rh and Ir).

We performed electrical resistivity ρ, magnetic susceptibility χ, specific heat C and electron diffraction measurements on single-crystalline samples of PrT2Zn20 (T = Ru, Rh and Ir). The three compounds show the Van Vleck paramagnetic behavior, indicating the nonmagnetic crystalline electric field (CEF) ground states. A Schottky-type peak appears at around 14 K, irrespective of the T element, which can be moderately reproduced by a doublet­triplet model. For T = Ru, a structural transition occurs at Ts = 138 K, below which no phase transition appears down to 0.04 K. On the other hand, for T = Ir, antiferroquadrupole (AFQ) ordering arising from the nonmagnetic Γ3 doublet takes place at TQ = 0.11 K. For T = Rh, despite a structural transition between 170 and 470 K, the CEF ground state is still the non-Kramers Γ3 doublet. However, no phase transition due to the Γ3 doublet was observed even down to 0.1 K.

Association study of TRAF1-C5 polymorphisms with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in Japanese.

OBJECTIVE: The primary aim of this study was to investigate the association of polymorphisms of TRAF1-C5, a newly identified rheumatoid arthritis (RA) risk locus in Caucasians, with susceptibility to RA and systemic lupus erythematosus (SLE) in Japanese populations. Gene expression levels of TRAF1 and C5 to assess the functional significance of genotypes were also analysed. METHODS: A multicentre association study consisting of 4 RA case-control series (4397 cases and 2857 controls) and 3 SLE case-control series (591 cases and 2199 shared controls) was conducted. Genotyping was performed using TaqMan genotyping assay for two single nucleotide polymorphisms (SNPs) that showed the best evidence of association in the previous Caucasian studies. Quantifications of TRAF1 and C5 expression were performed with TaqMan expression assay. RESULTS: Significant differences in allele frequency for both SNPs were observed between RA and control subjects (combined odds ratio = 1.09), while no significant difference was detected between patients with SLE and controls. Interestingly, alleles rs3761847 A and rs10818488 G had increased the risk for RA in the present study, while they decreased the risk in the original studies. A significant difference was found between risk allele carriers and non-carriers of rs10818488 for the expression level of TRAF1 in phorbol myristate acetate-stimulated lymphoblastoid cell lines (p = 0.04). CONCLUSION: Association of TRAF1-C5 locus with RA susceptibility was detected in the Japanese populations with modest magnitude, while no significant association was observed for SLE. Significant positive effect of genotype on the expression of TRAF1 might support the genetic association between TRAF1 and RA.

Intractable ulcer caused by Mycobacterium shinshuense: successful identification of mycobacterium strain by 16S ribosomal RNA 3'-end sequencing.

An extremely rare case of intractable ulcer caused by Mycobacterium shinshuense is described. A 59-year-old Japanese woman developed an ulcerated subcutaneous induration on the upper arm. Ziehl-Neelsen staining revealed positive bacilli. Tissue culture isolated Mycobacterium species, but standard identification techniques (including molecular biological approaches such as DNA-DNA hybridization) could not distinguish the precise causative pathogen, although it was narrowed down to three possibilities: Mycobacterium marinum, Mycobacterium ulcerans and M. shinshuense. Finally, a novel 16S rRNA sequencing method enabled the diagnosis of M. shinshuense infection. The epidemiology of the cutaneous infection caused by this mycobacterium has yet to be elucidated, but a review of reported cases indicated that ulcers having some resemblance to those caused by M. ulcerans infection were found in nonendemic areas and that M. shinshuense could be considered as the cause. The approach introduced in this report could provide a powerful tool for the identification of this organism.

Increased tacrolimus trough levels in association with severe diarrhea, a case report.

It is well known that during diarrhea episodes decreased cyclosporine and tacrolimus levels are often observed, usually requiring an increase in dose. An increase in tacrolimus trough levels is infrequently recognized as a potential cause of the adverse effect of severe diarrhea. Herein, we report the case of a renal transplant patient who displayed increased tacrolimus trough levels during an episode of gastroenteritis with severe diarrhea. The patient is 32-year-old male who received a renal transplant from his mother. Immunosuppression was initiated with tacrolimus in combination with mycophenolate mofetil and prednisone. The postoperative course was uneventful. The function of the transplanted kidney was normal. Eight months after transplantation he presented to our hospital with a history of high fever, abdominal pain, nausea and severe diarrhea. He was admitted with a diagnosis of enterocolitis of unknown etiology. The blood trough level of tacrolimus had increased from 6.7 ng/mL to 28.7 ng/mL after the onset of diarrhea. A therapeutic trough level of tacrolimus was reached 6 weeks after complete relief of diarrhea. Tacrolimus shows large variability in bioavailability after oral administration, both due to intestinal metabolism by cytochrome P450 (CYP3A4) and active secretion from enterocyte into intestinal lumen by P-glycoprotein. The epithelial cells of the intestine, may be destroyed abrogating P-glycoproteins during the course of enterocolitis, thereby increasing the levels of tacrolimus. It is recommended to monitor trough levels of tacrolimus during severe diarrhea of any nature to prevent tacrolimus-related complications.

Case report. Phaeohyphomycosis caused by Phialophora verrucosa developed in a patient with non-HIV acquired immunodeficiency syndrome.

A 53-year-old woman had asymptomatic multiple nodules on her gluteal region for 6 months. She had a history of systemic corticosteroid treatment for Evans' syndrome. Recently she had developed an immunodeficiency condition with CD4+ cell depletion without an HIV infection and a normal serum gamma globulin level. A smear from the purulent exudate of the nodules revealed many brown-coloured hyphae, spores and few large dark-brown cells. A short, hairy, dark-brown coloured colony was cultivated on Sabouraud glucose agar. Slide culturing revealed only a Phialophora-type conidia formation, and the fungus was diagnosed as Phialophora verrucosa. Severe immunosuppressive condition (non-HIV acquired immunodeficiency syndrome) of this patients after systemic corticosteroid treatment for Evans' syndrome predisposed an opportunistic cutaneous fungal infection due to P. verrucosa. Cases with cutaneous infection due to P. verrucosa reported in Japan are summarized and discussed.

[Education of medical mycology for dermatologists in Japan].

Inquiries were made to estimate the level of dermatological practice and to elucidate the mycological education of 147 recruits who applied to take the specialized examination offered by the Japanese Dermatological Association in August 2000. The potassium hydroxide (KOH) examination was performed on the following percentages of the 147 recruits: for tinea corporis, 79.6%; tinea manuum, 76.9%; pityriasis versicolor and tinea cruris, 74.1% and oral candidiasis, 70.1% respectively. Culture examination was applied by 30.6% of the recruits for sporotrichosis, 19.7% for dematiaceous fungal infection and 15.6% for kerion. Ninety-five percent of the recruits had been trained at university hospitals. Another inquiry was made to directors of 380 dermatology clinics (88 university hospitals and 292 other clinics), in June 2000. KOH-examinations had been made at 94% of the university hospitals and 83% of the other clinics for all of suspected mycosis, whereas culture examinations were made at only 8% and 3% respectively. Further mycological examinations such as identification of the isolates to species level had been made at 73% of the university hospitals. It is postulated that 88% of the university hospitals have facilities to offer a medical mycology education to dermatologists. From these results it is concluded that the available mycological education is insufficient to satisfy the levels of dermatology specialists for clinical practice.

Isotachophoretic separation behavior of rare-earth EDTA chelates and analysis of minor rare-earth elements in an iron ore by bidirectional isotachophoresis-particle-induced X-ray emission.

Mobilities of 16 anions of rare-earth-EDTA 1:1 chelate (RE-EDTAs) were isotachophoretically measured by using two leading electrolytes (pH 3.6 and 6.0) in order to assess their separation behavior. The leading electrolyte was 20 mM hydrochloric acid. The pH of the solution was adjusted to 3.6 by adding beta-alanine and to 6.0 by adding histidine. The obtained mobilities were very close to each other in the range 20.1x10(-5)-21.9x10(-5) cm2 V(-1) s(-1) with the minimum mobilities for Pr-EDTA and Nd-EDTA for pH 3.6 and 6.0, respectively, and pH dependence was hardly observed. On the basis of the above knowledge. minor rare-earth elements in a standard iron ore sample were determined as RE-EDTAs by bidirectional isotachophoresis-particle-induced X-ray emission (PIXE), where the Fe(II) matrix digested by alkali fusion was separated as Fe(II)Phen3(2+) (phen = 1,10-phenanthroline). Since 5% of the total iron was still detected as Fe(III)EDTA- and might disturb PIXE analysis of RE-EDTA-, itaconic acid was used as the spacer for Fe(III)EDTA- and RE-EDTA-. The fractions of RE-EDTA- were successfully analyzed off-line by a multielemental analytical method, PIXE [analytical result (3.62% (w/w) as RE2O3]; the nominal value was 3.37% (w/w) as RExOy.

Interleukin-2 binds to ganglioside GD(1b).

We have developed a solid matrix immunoassay to determine the binding of interleukin-2 (IL-2) to specific gangliosides. The assay establishes that recombinant human IL-2 binds to ganglioside GD(1b) but not to any other gangliosides (GM(1), GM(2), GM(3), GD(1a), GD(2), GD(3), and GT(1b)). The binding varies with the ratio of GD1b and IL-2. This assay enables distinguishing the nature of the sugar moiety of the ganglioside recognized by IL-2 and establishes the dosimetry of the ganglioside-IL-2 interaction. Since rIL-2 is administered systematically into stage IV melanoma patients, we have examined 45 tumor biopsies for GD(1b) content. The incidence of GD(1b) in tumor biopsies is 51%. We postulate that GD(1b) associated on the tumor or in the circulation of cancer patients may bind to rIL-2 and prevent the availability of rIL-2 to augment antitumor-immune response.

Intramuscular spindle cell lipoma: Case report and review of the literature.

Spindle cell lipoma (SCL) is a relatively rare adipocytic neoplasm and is histologically characterized by a mixture of uniform spindle cells and mature fat cells. It occurs predominantly in male patients aged 45-65 years, and in most cases it arises in the subcutaneous tissue of the neck or shoulder. Although the neoplasm sometimes affects unusual sites, only three cases have been reported in which the lesion was intramuscular. Here we present a case of SCL arising in skeletal muscle; to our knowledge, the first report in 10 years. The tumor occurred in the neck of a 50-year-old male patient. Magnetic resonance imaging (MRI) revealed a lipomatous tumor within the right trapezius muscle. The tumor was localized beneath the fascia and was excised completely at surgery. Histologically, the tumor was typical of a spindle cell lipoma with no evidence of malignancy. An immunohistochemical study revealed all spindle cells were strongly positive for CD34. Differential diagnosis is discussed with a review of the literature.

Does human melanoma express carcinoembryonic antigen?

BACKGROUND: Several investigators have proposed that carcinoembryonic antigen (CEA), an immunogenic antigen expressed by colon carcinoma, may also be expressed by human melanoma. Because sialyl Lewisx (sLex), the carbohydrate moiety of CEA, has been identified in melanoma, we compared CEA and sLex levels in colon carcinoma cells and melanoma cells. METHODS: CEA levels were assessed for expression on the cell surface and in cell lysates of cutaneous melanoma cell lines by two different kinds of ELISA, and by Western blot analysis of immunoprecipitated CEA using monoclonal antibodies (Mabs) T84-66 and COL-1, which have defined specificities for CEA. Colon carcinoma cells and purified CEA were positive controls. RESULTS: Both Mabs reacted strongly with cell surface and cell lysates of colon cancer. Mab T84-66 reacted well with cell surface but not cell lysates of melanoma. COL-1 reacted poorly with cell surface but its binding increased with the density of melanoma cell lysates. Both Mabs intensely stained the blots of purified CEA and colon carcinoma lysates immunoprecipitated with the respective Mabs, but failed to stain the immunoprecipitates of melanoma cell lysates. Both Mabs bound to lysates immunoprecipitated with anti-sLex Mab in colon carcinoma, but not in melanoma. Cell-surface expression of CEA and sLex was significantly correlated (r2: 0.88) in colon cancer cells but not in melanoma. CONCLUSION: Our results confirm the presence of CEA in colon carcinoma but not in human cutaneous melanoma cell lines.

The role of thymidine phosphorylase in the pathogenesis of allergic rhinitis.

The activity and distribution of thymidine phosphorylase (TP) in the nasal mucosa of patients with nasal allergy was examined and compared with those in healthy subjects. TP activity was analyzed by spectrophotometry and expression was examined by immunoblotting and immunohistochemical staining using a monoclonal antibody specific to TP. The expression level of TP detected by immunoblotting showed a correlation with the activity detected by spectrophotometry. In nasal mucosa obtained from patients with nasal allergy, the level of TP was significantly higher than that from normal subjects. Eosinophils, basal cells in mucosal epithelium and fibroblasts in nasal mucosa obtained from patients with nasal allergy were stained with anti-TP monoclonal antibody. Strong staining of eosinophils present in nasal discharge was observed. The present results indicate that an increased number of TP-expressing cells, especially eosinophils in nasal mucosa, might be associated with the pathogenesis of nasal allergy.

Gangliosides as targets for immunotherapy for pancreatic adenocarcinoma.

BACKGROUND: Pancreatic adenocarcinoma cells express gangliosides and sialyl Lewis (sLe) antigens. It is not known whether these carbohydrate antigens can be targeted by immunotherapy. The authors measured the expression of GM(2) and sLe antigens on the surface of pancreatic carcinoma cells and the serum levels of total gangliosides, GM(2), and antiganglioside antibodies in patients with pancreatic carcinoma. METHODS: Cell surface GM(2) and sLe antigens were measured by cell suspension enzyme linked immunoadsorbent assay (ELISA) in four pancreatic carcinoma cell lines. Sera from 20 pancreatic carcinoma patients and 20 age- and gender-matched healthy volunteers were analyzed for antiganglioside and anti-sLe immunoglobulin (Ig) M titers by ELISA. Serum levels of total gangliosides and GM(2) also were measured. RESULTS: All cell lines expressed GM(2) and sLe antigens. When compared with age- and gender-matched volunteers, patients had significantly higher serum levels of total gangliosides (25.6 +/- 9.0 mg/dL vs. 15.6 +/- 2.7 mg/dL; P < 0.001), GM(2) (0.278 +/- 0.415 mg/dL vs. 0.013 +/- 0.018 mg/dL; P = 0.02), ELISA units of anti-GM(2) IgM antibody (368 +/- 95 vs. 155 +/- 25; P = 0.04) and anti-GD(1b) IgM antibody (351 +/- 91 vs. 138 +/- 26; P = 0.03), but not anti-sLe(x) IgM (1389 +/- 345 vs. 1081 +/- 224; P = 0.46) or anti-sLe(a) IgM antibody (1097 +/- 253 vs. 1200 +/- 315; P = 0.80). Patients with unresectable tumors had higher serum levels of total gangliosides compared with patients with resectable tumors, and a serum level > 25 mg/dL was found to correlate significantly with poor overall survival (P < 0.02). CONCLUSIONS: Increased serum levels of total gangliosides and GM(2) may reflect shedding or release of gangliosides from the surface of tumor cells. Production of IgM antibody against GM(2) and GD(1b) indicates that these gangliosides are immunogenic antigens that may be potential targets for effective active immunotherapy.

Cell-surface expression of complement restriction factors and sialyl Lewis antigens in oral carcinoma: relevance to chemo-immunotherapy.

Oral squamous cell carcinomas overexpress tumor-associated antigens, yet these antigens do not induce an immune-mediated anti-tumor response. The absence of an anti-tumor immune response may be due to poor immunogenicity of the tumor antigens or due to presence of factors that restrict immune functions. We have analyzed the expression of the tumor-associated sialyl LewisA (sLeA) and sialyl LewisX (sLeA) antigens, the complement restriction factors (CD59, CD46 and CD55) and the apoptosis associated factors Fas and Fas Ligand. Sialyl Lewis antigens (sLeA and sLeX), are immunogenic in that they elicit complement-fixing IgM antibodies. These antigens are associated with aggressive invasive behavior, tumor progression and poor disease-free survival of patients with human carcinomas. Human oral squamous carcinoma cell lines, SCC12 and SCC71, were analyzed for the density of Sialyl Lewis antigens, CD59, CD46, CD59, Fas and FasL on the cell surface. Expression of these antigens on the cell surface was determined employing a cell-suspension ELISA with monospecific monoclonal antibodies. In both oral carcinoma cell lines, the density of expression of sLeX was higher than that of sLeA and SCC71 had a very low level of sLeA expression. Both cell lines expressed a high density of CD59 and slightly lower levels of CD46 and CD55 on the cell surface, suggesting that even if host antibodies are accessible to the target antigens such as sLeX, they could not mediate complement-dependent cytotoxicity. The SCC lines expressed very low levels of Fas and FasL indicating that there maybe a lack of these signaling molecules for apoptosis. Our data suggests that passive immunotherapy or tumor killing by antibody-complement interaction may require downregulation of complement restriction factors.

Anti-metastatic efficacy and safety of MMI-166, a selective matrix metalloproteinase inhibitor.

The anti-metastatic efficacy and safety of a newly-developed matrix metalloproteinase (MMP) inhibitor were examined. MMI-166, a N-sulfonylamino acid derivative, inhibited the enzyme activity of MMP-2, 9, and 14 but not MMP-1, 3 or 7. Daily oral administration of MMI-166 resulted in potent inhibition of metastatic lung colonization of Lewis lung carcinoma injected via the tail vein and liver metastasis of C-1H human colon cancer implanted into the spleen at inhibition levels of 43% and 63%, respectively. Daily administration of MMI-166 also resulted in prolonged survival of mice given intraperitoneal implantation of Ma44 human lung cancer cells. The anti-metastatic activity of MMI-166 was as effective as that of other MMP inhibitors with broad inhibitory spectrum. MMI-166 did not affect in vitro tumor cell growth. Neither body weight losses nor hematotoxicity was observed during long-term treatment, indicating the safety of MMI-166 in mice. These results indicate that the selective MMP inhibitor MMI-166 has therapeutic potential as an anti-metastasis agent.