Spin Hall magnetoresistance induced by a nonequilibrium proximity effect.

We report anisotropic magnetoresistance in Pt|Y(3)Fe(5)O(12) bilayers. In spite of Y(3)Fe(5)O(12) being a very good electrical insulator, the resistance of the Pt layer reflects its magnetization direction. The effect persists even when a Cu layer is inserted between Pt and Y(3)Fe(5)O(12), excluding the contribution of induced equilibrium magnetization at the interface. Instead, we show that the effect originates from concerted actions of the direct and inverse spin Hall effects and therefore call it "spin Hall magnetoresistance."

Perilesional treatment of metastatic melanoma with interferon-beta.

Previous trials with various treatments have not shown satisfactory therapeutic results for cutaneous metastasis of malignant melanoma (MM). We report three patients who were treated with peritumoral injection of interferon (IFN)-beta for multiple skin metastases of MM. The metastatic tumours were infiltrated by significant numbers of CD8+ TIA+ cytotoxic lymphocytes, and the numbers of CD4+ cells and human leucocyte antigen-DR+ cells increased after IFN-beta injection. These results suggest that the peritumoral administration of IFN-beta enhanced the antitumour immune response against the MM, suggesting that it is a promising supportive treatment for skin metastasis of MM.

Imaging of silkworm meiotic chromosome by atomic force microscopy.

Although structural information of mitotic chromosomes has been accumulated, little information is available for meiotic chromosome structures. Here, we applied atomic force microscopy (AFM) to investigate the ultrastructures of the silkworm, Bombyx mori, meiotic pachytene chromosome in its native state with nanometer scale resolution. Two levels of DNA folding were observed on the meiotic chromosome surface, 50-70 nm granules, which were considered to be 30 nm chromatin fibers, and spherical protrusions of 400-600 nm, which were considered to be chromomeres and arranged on the surface of the chromosome parallel to the chromosome longitudinal axis. These observations suggested that AFM study is an excellent approach for obtaining information concerning the silkworm pachytene chromosome higher order structure.

Pressure effect in a shock-wave-plasma interaction induced by a focused laser pulse.

The effect of ambient pressure on the interaction between a laser plasma bubble and a shock wave involving a Richtmyer-Meshkov instability was experimentally studied via framing Schlieren visualization. A sharp plasma interface could be formed without any separation material that causes undesired disturbances. The fundamental vortex structure which was produced via baroclinic effects was self-similar with respect to the laser energy-ambient pressure ratio. Yet, the higher the ambient pressure, the more high-wave-number instabilities were enhanced so as to contaminate the self-similarity.

Dysplastic ganglioneurocytoma with increased glucose metabolism: a heterotopia with unique histopathology.

A 1 year and 7 month old boy was incidentally found to have an intracranial mass lesion at the frontal base. The mass was 45 x 54 x 47 mm in size, contained a calcification, a few small cysts, and extended downward to the sphenoid sinus and upper pharynx. The signal intensity of the lesion on magnetic resonance imaging was iso-high on T1-weighted images, and slightly high on T2-weighted images, and it did not enhance with gadolinium injection. Although there was no obvious mass effect, 18F-fluorode-oxyglucose positron-emission tomography demonstrated increased uptake, and a surgical resection was performed suspecting a neoplastic lesion. Histologically, the lesion consisted of small to large anomalous neurons and glial cells but lacked normal cortical architecture. Cellularity was high in some portion with MIB-1 labeling index of 2%, but there was no cellular atypia suggestive of neoplasm. Therefore, this lesion was considered to be a dysplasia that does not fit into the previously described entity. We suggest this lesion would be better described as dysplastic ganglioneurocytoma.

The effects of vitamin A derivative etretinate on the skin of MRL mice.

MRL/Mp-lpr/lpr (MRL/lpr) mice are characterized by the disorder of apoptosis due to defects in Fas antigens and autoimmune symptoms including spontaneous lupus erythematosus (LE)-like skin lesions. MRL/Mp- + / + (MRL/n) mice do not carry the defect of lpr mutation nor do they exhibit skin disorders during the first six months of life. Retinoids are known to inhibit the proliferation of skin fibroblasts, collagen synthesis, modulate immune responses, and apoptosis by Fas ligand upregulation in skin fibroblasts. We examined changes in dermal thickness and appearance of skin disorders in five months old MRL/lpr mice by oral treatment with etretinate, a retinoic acid derivative. Etretinate treated MRL/lpr mice did not have skin lesions or dermatopathological characteristics including an increase in cells infiltrating the dermis. The mean dermal thickness of MRL/lpr and MRL/n mice treated with etretinate decreased significantly and apoptotic cells density in the dermis of MRL/lpr mice with etretinate was significantly higher compared with the control group (P < 0.05) although MRL/lpr mice have a defect within the Fas antigen. We assumed that etretinate reduced dermal thickness, and suppressed the appearance of skin lesions by inducting apoptosis and perhaps regulation of cytokine expression.

Effects of cortisol on muscle proteolysis and meat quality in piglets.

The present study was conducted to examine the effects of cortisol on muscle proteolysis and meat quality. Male piglets (n=14) were assigned to one of two treatment groups at 28 days of age. After 7 days adaptation period, each group was fed a commercial diet (86% total digestible nutrients, 21.5% crude protein) or the same commercial diet containing cortisol (120mg/kg diet) for 7 days from 35 days of age. All piglets were slaughtered at 42 days of age. The serum triiodothyronine (T3) concentration, µ- and m-calpain and proteasome activities and the content of easily releasable myofilament, which contains intermediates of the breakdown of myofibrils in the m. longissimus dorsi (LD) at slaughter were measured as parameters of muscle proteolysis. Serum T3 levels and µ-calpain activity were increased (P<0.01), as was the amount of easily releasable myofilament and m-calpain and proteasome activities were higher (P<0.05) in LD from cortisol-treated piglets than from non-treated controls. At 24 h postmortem, LD of cortisol-treated piglets showed higher (P<0.01) drip loss and lighter (P<0.05) color than those of the control. The results clearly show that the administration of cortisol increases serum T3 concentration and muscle proteolysis and reduces productivity and meat quality.

Identification of AFLP makers linked to non-seed shattering locus (sht1) in buckwheat and conversion to STS markers for marker-assisted selection.

Shattering habit in buckwheat has two forms: brittle pedicel and weak pedicel. Brittle pedicel is observed in wild buckwheat, but not in cultivated buckwheat. Brittle pedicel in buckwheat is produced by two complementary, dominant genes, Sht1 and Sht2. The sht1 locus is linked to the S locus; almost all common buckwheat cultivars possess the allele sht1. To detect molecular makers linked to the sht1 locus, we used amplified fragment-length polymorphism (AFLP) analysis in combination with bulked segregant analysis of segregating progeny of a cross between a non-brittle common buckwheat and a brittle self-compatible buckwheat line. We screened 312 primer combinations and constructed a linkage map around the sht1 locus by using 102 F2 plants. Five AFLP markers were linked to the sht1 locus. Two of these, e54m58/610 and e55m46/320, cosegregated with the sht1 locus without recombination. The two AFLP markers were converted to STS markers according to the sequence of the AFLPs. The STS markers are useful for marker-assisted selection of non-brittle pedicel plants and provides a stepping-stone for map-based cloning and characterization of the gene encoding non-brittle pedicel.

Susceptibility of T cell receptor-alpha chain knock-out mice to ultraviolet B light and fluorouracil: a novel model for drug-induced cutaneous lupus erythematosus.

The anticancer agent 5-fluorouracil (FU) frequently induces cutaneous lupus erythematosus (LE) lesions on sun exposed sites. Based on this observation, we have tried to establish a cutaneous LE model of C57BL/6 J (B6) mice, B6 T cell receptor (TCR)-alpha(-/-) mice and B6 TCR-delta(-/-) mice treated with FU and/or ultraviolet B light (UVBL) in order to clarify the role of T cells and the cytokine profile of cutaneous lupus lesions. Cutaneous LE-like skin lesions could be induced in TCR-alpha(-/-) mice with low FU (0.2 mg) plus UVBL, and in B6 mice treated with a high dose of FU (2.0 mg) plus UVBL. In contrast, low FU plus UVBL induced such skin lesions in TCR-delta(-/-) mice at a very low incidence. Specifically, the skin lesions of TCR-alpha(-/-) mice with low FU plus UVBL appeared more rapidly and were more severe than lesions in B6 mice. The former had the common characteristic features of human chronic cutaneous LE such as typical histology, positive IgG at the dermoepidermal junction, low antinuclear antibody and low mortality. Furthermore, a Th1 response was induced in the development of drug-induced cutaneous LE. FU and UVBL-induced cutaneous LE-like eruption is an excellent model for better understanding the pathomechanisms of skin lesion development in LE.

Oxidative one-carbon cleavage of the octyl side chain of olanexidine, a novel antimicrobial agent, in dog liver microsomes.

1. The oxidative one-carbon cleavage reaction in the octyl side chain of olanexidine [1-(3,4-dichlorobenzyl)-5-octylbiguanide], a new potent biguanide antiseptic, was characterized in dog liver microsomes. 2. Olanexidine was initially biotransformed to a monohydroxylated metabolite, 8-[5-(3,4-dichlorobenzyl)-1-biguanidino]-2-octanol (DM-215), and DM-215 was subsequently oxidized to the diol derivative, 8-[5-(3,4-dichlorobenzyl)-1-biguanidino]-1,2-octandiol (DM-220). DM-220 was further biotransformed to 2-hydroxy aldehyde derivative, 2-hydroxy carboxylic acid derivative, and an oxidative C-1-C-2 bond cleavage metabolite, 7-[5-(3,4-dichlorobenzyl)-1-biguanidino] heptanoic acid [DM-223 (C7), a seven-carbon chain derivative], after incubation with dog liver microsomes. 3. DM-223 formation required NADPH as a cofactor and was inhibited by quinidine and quinine, relatively selective inhibitors of CYP2D subfamilies in dogs. 4. The results suggest that the one-carbon fragment of the octyl side chain of olanexidine could be removed by the oxidative C-C bond cleavage with the possible involvement of cytochrome P450 systems such as CYP2D subfamily. This oxidative C-C bond cleavage reaction by cytochrome P450s could play an important role in the removal of one-carbon fragment of other drugs or endogenous compounds containing aliphatic chains.

Voxel-based analysis of MRI reveals anterior cingulate gray-matter volume reduction in posttraumatic stress disorder due to terrorism.

MRI studies using the manual tracing method have shown a smaller-than-normal hippocampal volume in patients with posttraumatic stress disorder (PTSD). However, these studies have yielded inconsistent results, and brain structures other than the hippocampus have not been well investigated. A recently developed, fully automated method called voxel-based morphometry enables an exploration of structural changes throughout the brain by applying statistical parametric mapping to high-resolution MRI. Here we first used this technology in patients with PTSD. Participants were 9 victims of the Tokyo subway sarin attack with PTSD and 16 matched victims of the same traumatic event without PTSD. The voxel-based morphometry showed a significant gray-matter volume reduction in the left anterior cingulate cortex (ACC) in trauma survivors with PTSD compared with those without PTSD. The severity of the disorder was negatively correlated with the gray-matter volume of the left ACC in PTSD subjects. There were no significant differences in other gray-matter regions or any of the white-matter regions between two groups. The present study demonstrates evidence for structural abnormalities of ACC in patients with PTSD. Together with previous functional neuroimaging studies showing a dysfunction of this region, the present findings provide further support for the important role of ACC, which is pivotally involved in attention, emotional regulation, and conditioned fear, in the pathology of PTSD.

Atomic force microscopic imaging of 30 nm chromatin fiber from partially relaxed plant chromosomes.

We have developed a procedure for partially relaxing the barley metaphase chromosomes and exposing fibrous structures from the chromosomes. The observation by atomic force microscopy (AFM) showed that the fibrous structures are typically 0.5 to 1 microm long and 40 to 50 nm in diameter. In higher magnification imaging, we found the fibrous structures were composed of aligned granules and looked like "knobby fiber." These observations are consistent with previously reported features of chromatin fiber observed by AFM and scanning electron microscopy, suggesting that the structures correspond to 30 nm chromatin fibers. We observed the chromatin fiber extending straight from the periphery of the chromosomes in most cases, but fibers with different shapes, such as loop and spiral, were also observed. The procedure reported here will provide a new approach for observing the organization of chromatin fiber to higher-order structures by AFM and other high-resolution microscopy.

Slow acetylator genotypes as a possible risk factor for infectious mononucleosis-like syndrome induced by salazosulfapyridine.

We report two patients with infectious mononucleosis-like syndrome induced by salazosulfapyridine (SASP). In both cases, high fever, skin rash, liver dysfunction and atypical lymphocytosis developed 3 weeks after initiating treatment with SASP. SASP is known to be mainly metabolized by N-acetyltransferase 2 (NAT2), and acetylation phenotypes (rapid, intermediate and slow acetylator) correlate with NAT2* genotypes. In our two patients, we investigated NAT2* genotypes by the polymerase chain reaction-restriction fragment length polymorphism method. We identified NAT2*6/*7 in one patient, and NAT2*6/*5 in the other, suggesting that both were slow acetylator phenotypes. In 20 healthy volunteers we found no slow acetylator genotypes. Genotyping prior to medication may be useful in evaluating patients with a high risk of severe systemic reaction to SASP.

DC electric-field-induced DNA stretching for AFM and SNOM studies.

An effective method of DNA stretching on mica surfaces is proposed for an extremely low concentration of DNA. The method is based on an electric field and well applied on the concentration range from 57 x 10(-3) to 57 x 10(-6) ng/ml. The stretching exists in a gap between positive and negative electrodes. The difference in the stretching efficiency among the different surfaces of bare mica, Mg2+ soaked mica and AP-mica is discussed. The best performance of the stretching is found from the surface of AP-mica for the same experimental condition of sample concentration and applied voltage. Finally, from a Scanning near-field optical microscope image, it is found that well-stretched DNA molecules have shown more similar optical resolution, which is inferred from an optical fiber probe, itself.

[A successfully resected case of giant malignant mediastinal germ cell tumor].

A 14-year-old male was admitted for complaints of dyspnea and cough. Chest radiography revealed a huge mass in the right lung field. The serum alpha fetoprotein (AFP) level was elevated to 1,251 ng/ml. Histological findings of the specimens obtained by needle biopsy revealed a mature teratoma with non-seminoma. After 2 courses of chemotherapy [cisplatin (CDDP) and etoposide (VP-16)], serum AFP level decreased to 25 ng/ml, and the tumor was resected with pericardium (the tumor size was 14 x 10 x 20 cm). Two courses of chemotherapy were administered again postoperatively with normalization of serum AFP level. The patient has no sign of recurrence of the tumor.

Tyrosine 759 of the cytokine receptor gp130 is involved in Listeria monocytogenes susceptibility.

Interleukin-6 family cytokines have been implicated in adaptive and innate immunity, hematopoiesis, and inflammation. This cytokine family shares a signal-transducing receptor subunit called gp130. gp130(F759/F759) knockin mice carry a point mutation at the SHP2-binding site of gp130 due to the replacement of tyrosine-759 (Y759 for human gp130) with phenylalanine (F). To explore the effect of this point mutation on the host response to bacterial infection, gp130(F759/F759) knockin mice were infected with Listeria monocytogenes. gp130(F759/F759) knockin mice began to die at 3 to 4 days post infection (p.i.) and showed higher mortality than did controls. Listeria titers at 3 days p.i. in the peritoneal cavity, spleen, and liver were significantly higher in gp130(F759/F759)knockin mice than in controls. Nitric oxide production, upregulation of the mRNA levels of a variety of cytokines, and listericidal activity in gp130(F759/F759) macrophages were unchanged. However, gp130(F759/F759) knockin mice displayed significantly lower levels of interferon (IFN)gamma in serum and in the culture supernatant from peritoneal exudate cells and splenocytes, in response to Listeria infection. These results suggest that the Y759 point mutation in gp130 attenuates the early phase of defense against Listeria infection, possibly owing to insufficient elevation of IFNgamma levels, and thus gp130 is a possible candidate gene for Listeria susceptibility.

Coronary endothelial dysfunction in the insulin-resistant state is linked to abnormal pteridine metabolism and vascular oxidative stress.

OBJECTIVES: We investigated whether abnormal pteridine metabolism is related to coronary endothelial dysfunction in insulin-resistant subjects. BACKGROUND: Depletion of tetrahydrobiopterin (BH(4)) and elevation of the 7,8-dihydrobiopterin (BH(2)) (activating and inactivating cofactors of nitric oxide synthase [NOS], respectively) contribute to impairment of NO-dependent vasodilation through reduction of NOS activity as well as increased superoxide anion generation in insulin-resistant rats. METHODS: Thirty-six consecutive nondiabetic, normotensive and nonobese subjects with angiographically normal coronary vessels were studied. Traditional coronary risk factors, plasma pteridine levels, activities of erythrocyte dihydropteridine reductase (DHPR), the recycling enzyme that converts BH(2) to BH(4) and lipid peroxide (LPO) levels were measured and coronary endothelial function was assessed with graded infusions of acetylcholine (ACh). RESULTS: When we divided patients into tertiles based on insulin sensitivity, we observed stepwise decreases in the maximal ACh-induced vasodilation and plasma BH(4)/7,8-BH(2) ratio, and increases in coronary LPO production as insulin sensitivity decreased. The ACh-induced vasodilation was positively correlated with insulin sensitivity, BH(4)/7,8-BH(2) ratio and DHPR activity. Furthermore, BH(4)/7,8-BH(2) was inversely correlated with DHPR activity and insulin sensitivity. In multiple stepwise regression analysis, BH(4)/BH(2) was independently related to ACh-induced vasodilation and accounted for 39% of the variance. However, no significant correlation existed between other traditional risk factors and BH(4)/7,8-BH(2). CONCLUSIONS: These results indicate that both abnormal pteridine metabolism and vascular oxidative stress are linked to coronary endothelial dysfunction in the insulin-resistant subjects.

Difference between forward and backward swimming speeds of the single polar-flagellated bacterium, Vibrio alginolyticus.

The forward and backward swimming speeds and periods of a Vibrio alginolyticus strain that has a single polar flagellum were measured. The backward swimming speeds were 1.5 times greater than the forward ones on average and the average period of backward swimming was shorter than forward swimming. However, the swimming speed and period were not correlated. Similar results were obtained for a mutant that has a 1.6 times longer flagellum on average.

Brain tumour imaging with carbon-11 choline: comparison with FDG PET and gadolinium-enhanced MR imaging.

The purpose of this study was to assess the clinical potential of methyl-11C-choline (11C-choline) in the diagnosis of brain tumours. To this end, the results of 11C-choline positron emission tomography (PET) in 22 patients suspected of having brain tumours were compared with the findings of contrast-enhanced magnetic resonance (MR) imaging and fluorine-18 fluorodeoxyglucose PET. A histopathological diagnosis was made for each patient during open surgery. The standardised uptake values of brain tumours and the tumour-to-white matter count (T/W) ratios were determined. The degree of 11C-choline accumulation noted in PET images was compared with the gadolinium-enhanced areas of MR images. The mean T/W ratio of 11C-choline in high-grade gliomas was found to be higher than that in low-grade gliomas. This difference was statistically significant (mean+/-SD: 8.7+/-6.2, n=9 versus 1.5+/-0.7, n=5, P<0.03) when data pertaining to the prominent uptake of 11C-choline in a patient with a pilocytic astrocytoma were excluded. 11C-choline PET failed to detect non-neoplastic lesions in two patients. Areas of 11C-choline accumulation in PET scans were larger than areas enhanced on MR images in five cases involving high-grade gliomas. 11C-choline PET differentiated between low-grade gliomas and high-grade gliomas, but did not differentiate between low-grade gliomas and non-neoplastic lesions. The combination of 11C-choline PET and MR imaging may provide investigators with an accurate means by which to identify high-grade gliomas.