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.

Gab1 acts as an adapter molecule linking the cytokine receptor gp130 to ERK mitogen-activated protein kinase.

Gab1 has structural similarities with Drosophila DOS (daughter of sevenless), which is a substrate of the protein tyrosine phosphatase Corkscrew. Both Gab1 and DOS have a pleckstrin homology domain and tyrosine residues, potential binding sites for various SH2 domain-containing adapter molecules when they are phosphorylated. We found that Gab1 was tyrosine phosphorylated in response to various cytokines, such as interleukin-6 (IL-6), IL-3, alpha interferon (IFN-alpha), and IFN-gamma. Upon the stimulation of IL-6 or IL-3, Gab1 was found to form a complex with phosphatidylinositol (PI)-3 kinase and SHP-2, a homolog of Corkscrew. Mutational analysis of gp130, the common subunit of IL-6 family cytokine receptors, revealed that neither tyrosine residues of gp130 nor its carboxy terminus was required for tyrosine phosphorylation of Gab1. Expression of Gab1 enhanced gp130-dependent mitogen-activated protein (MAP) kinase ERK2 activation. A mutation of tyrosine 759, the SHP-2 binding site of gp130, abrogated the interactions of Gab1 with SHP-2 and PI-3 kinase as well as ERK2 activation. Furthermore, ERK2 activation was inhibited by a dominant negative p85 PI-3 kinase, wortmannin, or a dominant negative Ras. These observations suggest that Gab1 acts as an adapter molecule in transmitting signals to ERK MAP kinase for the cytokine receptor gp130 and that SHP-2, PI-3 kinase, and Ras are involved in Gab1-mediated ERK activation.

Tissue-specific autoregulation of the stat3 gene and its role in interleukin-6-induced survival signals in T cells.

Signal transducer and activator of transcription 3 (STAT3) mediates signals of various growth factors and cytokines, including interleukin-6 (IL-6). In certain IL-6-responsive cell lines, the stat3 gene is autoregulated by STAT3 through a composite IL-6 response element in its promoter that contains a STAT3-binding element (SBE) and a cyclic AMP-responsive element. To reveal the nature and roles of the stat3 autoregulation in vivo, we generated mice that harbor a mutation in the SBE (stat3(mSBE)). The intact SBE was crucial for IL-6-induced stat3 gene activation in the spleen, especially in the red pulp region, the kidney, and both mature and immature T lymphocytes. The SBE was not required, however, for IL-6-induced stat3 gene activation in hepatocytes. T lymphocytes from the stat3(mSBE/mSBE) mice were more susceptible to apoptosis despite the presence of IL-6 than those from wild-type mice. Consistent with this, IL-6-dependent activation of the Pim-1 and junB genes, direct target genes for STAT3, was attenuated in T lymphocytes of the stat3(mSBE/mSBE) mice. Thus, the tissue-specific autoregulation of the stat3 gene operates in vivo and plays a role in IL-6-induced antiapoptotic signaling in T cells.

Low-temperature resistance of higher plants is significantly enhanced by a nonspecific cyanobacterial desaturase.

A broad-specificity delta 9 desaturase gene was cloned from the cyanobacterium Anacystis nidulans. The enzyme introduces a cis-double bond at the delta 9 position of both 16 and 18 carbon saturated fatty acids linked to many kinds of membrane lipids. The gene was stably introduced into tobacco plants under transcriptional control of the cauliflower mosaic virus 35S promoter, and the enzyme was targeted into plastids by the transit peptide of the pea RuBisCO small subunit. The transgenic plants had a highly reduced level of saturated fatty acid content in most membrane lipids and exhibited a significant increase in chilling resistance.

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.

Behavior of DNA fibers stretched by precise meniscus motion control.

A modified DNA combing method, which can precisely locate straightened DNA fibers on a substrate, has been developed. Precise motion control of a DNA solution droplet on hydrophobic surfaces has allowed detailed analyses of DNA straightening behavior. Our method provides a technique for consistently straightening lambda phage DNA on a trace of droplet motion, though the straightened DNAs had several variations in their alignments. The dependence of the straightened DNA frequency upon motion rate, fluidity in the droplet and environmental humidity was investigated. Visualization of the solution flow in the moving droplet indicated that flows circulating parallel to the contour of the droplet markedly bias the direction of straightening in relation to the site in the droplet. As a result, the alignment variations caused by the site specificity of the bias direction revealed that environmental humidity significantly alters the straightening behavior.

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.

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.

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.

A novel CEA-cross-reacting antigen of molecular weight 140,000 expressed on human lymphoid cell lines.

To investigate the possible expression of the carcinoembryonic antigen (CEA) gene family products on lymphoid cells, we screened 28 human cell lines derived from malignant lymphoid cells for reactivity with monoclonal antibodies (MAbs) against CEA and nonspecific cross-reacting antigen (NCA), which is one of the CEA gene family members. Six cell lines (four B cell lines and two non-T, non-B cell lines) were found to react, by a membrane immunofluorescence test, with an MAb, F34-187, which recognizes an antigenic determinant shared between CEA and NCA. None of the 15T cell lines was reactive with any MAbs tested. A glycoprotein antigen isolated with F34-187 from the cell surface showed an apparent molecular mass of ca 140 and 70 kDa in the glycosylated and deglycosylated forms, respectively, and was unreactive with MAbs specific for CEA or NCA, suggesting that the antigen is a new member of the CEA gene family.

Differential modulation of chorionic gonadotropin (CG) subunit messenger ribonucleic acid levels and CG secretion by progesterone in normal placenta and choriocarcinoma cultured in vitro.

The ability of progesterone to modulate the production and secretion of human CG (hCG) in both normal placenta and choriocarcinoma was compared by culturing explants of each trophoblastic tissue in the presence or absence of progesterone. The cellular level of messenger RNAs (mRNAs) encoding hCG alpha, hCG beta, and human placental lactogen (hPL) were quantitatively estimated by mean grain count per syncytial nucleus on the tissue sections hybridized in situ with labeled complementary DNA probes corresponding to these mRNAs. Immunoreactive hCG, hCG alpha, and hCG beta in the media and explanted tissues were measured by the homologous RIAs, and hPL was assayed by hPL-RIA kit. Addition of progesterone at concentrations of 5-20 micrograms/ml into the culture of normal early placenta caused a decrease in the cellular levels of hCG alpha mRNA and hCG beta mRNA after a 24-h culture, and exhibited a decline in immunoreactive hCG and hCG alpha levels released into the media together with a decrease in immunoreactive hCG alpha and hCG beta levels in the explanted tissues after a 48-h culture. The addition of progesterone neither affected the cellular levels of hPL mRNA nor immunoreactive hPL levels in the media and tissues. On the other hand, addition of 17 beta-estradiol at concentrations similar to those used with progesterone did not alter the levels of immunoreactive hCG and hCG alpha in the media or explanted placental tissues, while lower concentrations (1-10 ng/ml) of 17 beta-estradiol caused an increase in immunoreactive hCG alpha levels in the media and cultured tissues. These findings suggest that the suppressive effect observed with progesterone is not likely to be a toxic effect of steroid, but is rather selective on hCG production and secretion by normal placenta. Thus, progesterone may be a factor responsible for the inhibitory regulation of hCG production and secretion by normal placenta. However, in contrast to normal placenta, the choriocarcinoma culture in vitro did not respond to progesterone. The steroid was without significant effect on the cellular levels of hCG alpha mRNA and hCG beta mRNA, and on the levels of immunoreactive hCG and hCG alpha in the media and explanted tissues. These results suggest that the inhibitory regulation of hCG production and secretion in choriocarcinoma is different from that in normal early placenta.

Analysis of serum ErbB-2 protein and HLA-DRB1 in Japanese patients with lung cancer.

We investigated the relationship between ErbB-2 and HLA in order to clarify the clinical and genetic factors related to Japanese patients with lung cancer. Thirty-nine of the 73 lung cancer patients (53.4%) had elevated levels of ErbB-2. Only seven of 23 (30. 4%) patients with small cell carcinoma had elevated ErbB-2 levels. The prevalence of ErbB-2 positivity was highest (23 of 32; 71.8%) in patients with adenocarcinoma, while that in patients with squamous cell carcinoma was 50% (9 of 18). The frequencies of HLA A33, B44, B62, and B75 were lower in the lung cancer patients than in the control group. HLA-DR9 was higher in frequency in lung cancer patients than in the healthy controls (P<0.05), but HLA-DR6 was lower in frequency in lung cancer patients than in controls (P<0.01). DRB1*0901 was significantly higher in frequency in lung cancer patients than in controls (P<0.05). On the other hand, DRB1*0802, DRB1*1302 and the DRB1*14 group (*1401, *1403, *1405, *1406, and *1407) were completely absent in lung cancer patients. The frequencies of HLA B35, B52, B62, DRB1*0404, and DRB1*0406 were higher in the ErbB-2-positive lung cancer patients than in the ErbB-2-negative lung cancer patients. However, these types of HLA were not included in significant frequencies in our group of lung cancers. Our results suggest that some HLA-antigens/alleles participate in the pathogenesis of lung cancer in Japanese patients. In addition, the relationship between HLA-associated genetic factors and ErbB-2 seems to be weak. These findings suggest that ErbB-2 is correlated with prognostic factors for lung cancer independently of HLA-associated genetic factors.

Changes of immunological markers after autologous peripheral blood stem cell transplantation.

PURPOSE: Recently high-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) has become an important treatment for hematological and solid tumors. METHODS: Immunological parameters were examined before and after PBSCT in 9 patients with lung cancer and 13 patients with malignant lymphoma. Findings were compared with those for bone marrow transplantation (BMT). Peripheral blood cells were analyzed for phenotype and the levels of cytokines and soluble factors were measured. RESULTS: After PBSCT, activated T cells (CD3+HLA-DR+ cells, CD8+HLA-DR+ cells) and suppressor/cytotoxic T cells (CD8+CD11b- cells) were significantly higher in the patients with lung cancer than in those with malignant lymphoma. Serum levels of interleukin-4 and soluble interleukin-2 receptor were also significantly higher in the patients with lung cancer than in those with lymphoma. On the other hand, the serum levels of interferon gamma, tumor necrosis factor alpha, interleukin-6, soluble human leukocyte antigen class 1, and soluble thrombomodulin were significantly increased after bone marrow transplantation. The transfused peripheral stem cells of lung cancer and lymphoma patients had a similar number of granulocyte/macrophage-colony-forming units, but lung cancer patients had significantly more CD34-positive cells. CONCLUSION: By reinfusing large numbers of autologous immune cells, PBSCT may accelerate immune reconstitution, with T cells being likely to have a marked therapeutic potential. The changes after PBSCT were greater in patients with lung cancer than in lymphoma patients. These blood cells are potent mediators of anticancer activity and could play an important role in the elimination of autologous malignant cells.

Hydrolysis of ATP dependent on homologous double-stranded DNA and single-stranded fragments promoted by RecA protein of Escherichia coli.

RecA protein is essential to general genetic recombination in Escherichia coli. In the presence of ATP, a stoichiometric amount of recA protein forms D-loops from superhelical closed-circular DNA (form I DNA) and homologous single-stranded fragments, and subsequently dissociates the D-loops. Under appropriate conditions, the hydrolysis of ATP by recA protein depends on the presence of both double-stranded DNA and homologous single-stranded fragments (homology-dependent hydrolysis). In the presence of form I DNA, most of the homology-dependent hydrolysis of ATP by recA protein is related to the dissociation of D-loops rather than the formation of D-loops. RecA protein also promoted the homology-dependent hydrolysis of ATP in the presence of nicked-circular DNA (form II DNA), but unlike the case of form I DNA, this hydrolysis was associated with an increase in the amount of mature D-loops that were detected by the D-loop assay. When double-stranded DNA was superhelical, the homology-dependent hydrolysis of ATP continued at the same rate even after all the D-loops were dissociated. This correlates with our earlier observation that in the process of formation and dissociation of D-loops, form I DNA was converted to an inactive substrate without any apparent damage to the DNA, probably by the formation of a complex with recA protein. All of the observations described above can be explained by a model in which a common mechanism causes dissociation of D-loops from form I DNA, inactivation of form I DNA, and growth of D-loops in form II DNA. The mechanism might involve cooperative binding of recA protein to the duplex DNA from the site of the nascent D-loop, resulting in unidirectional unwinding of the duplex DNA.

Effect of disopyramide on systolic and early diastolic time intervals in patients with hypertrophic cardiomyopathy.

The present study clarified the effect of disopyramide on left-ventricular function in patients with hypertrophic cardiomyopathy (5 obstructive type: HOCM, 21 non-obstructive type: HNCM). The systolic and early diastolic time intervals were assessed 3 hours after a single oral administration of 100-mg disopyramide. The following parameters were evaluated at rest and after administration of disopyramide: 1) left-ventricular ejection time index (LVETI), 2) pre-ejection period index (PEPI), 3) the interval from aortic component of the second heart sound to mitral valve opening (IIA-MVO), and 4) the interval from MVO to O point of apexcardiogram (MVO-O). LVETI in HNCM did not change after disopyramide but that in HOCM was significantly shortened (P less than .05). PEPI in both HOCM and HNCM was significantly prolonged after administration of disopyramide. IIA-MVO time in both HOCM and HNCM was not influenced by disopyramide. MVO-O time in both HOCM and HNCM was significantly shortened after disopyramide. These results suggest that 1) shortening of LVETI in HOCM after disopyramide seemed to be due to the decrease in pressure gradient, 2) PEPI prolongation after disopyramide reflected the decrease in myocardial contractility, and 3) shortening of MVO-O time after disopyramide indicated the improvement of left-ventricular filling. The authors conclude that disopyramide may be an important new therapeutic agent in the treatment of patients with hypertrophic cardiomyopathy.

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.

Intraoperative ultrasonography versus cholangiography during laparoscopic cholecystectomy: a prospective comparative study.

BACKGROUND: The purpose of this study was to compare the functional utility of intraoperative ultrasonography (IOUS) and cholangiography (IOC) during a laparoscopic cholecystectomy for the treatment of gallstone disease. STUDY DESIGN: A prospective study comparing IOUS and IOC was carried out in 65 patients. Intraoperative ultrasonography was conducted first using a 7.5-MHz linear array probe. After IOUS, IOC was then conducted in all patients. The respective usefulness of IOUS and IOC in the identification of gallstones, detection of hepatobiliary structures, and demonstration of congenital anomalies was then compared. RESULTS: Intraoperative ultrasonography was successful in all 65 patients, and IOC was successful only in 54. The time required for IOUS was significantly shorter (p < 0.0001) than for IOC. Intraoperative ultrasonography imaged the hepatic ducts and their confluence, the common hepatic duct, the common bile duct, and the ampulla of Vater in 97, 100, 97, and 51% of cases, respectively. Intraoperative cholangiography, on the other hand, depicted these structures in 85, 89, 100, and 94% of cases, respectively. Intraoperative ultrasonography demonstrated the cystic duct and its confluence in 94% of cases. Biliary anomalies were identified by IOUS in 12 patients and by IOC in 13. Intraoperative ultrasonography could detect the hilar vascular structures in most patients and visualized anomalies of the hepatic arteries in 5 patients. In this series, 5 patients had choledocholithiasis. The sensitivities, specificities, positive and negative predictive values, and accuracies in identifying these bile duct stones were 80, 98, 80, 98, and 97% by IOUS, and 80, 97, 67, 98, and 95% by IOC, respectively. CONCLUSIONS: Intraoperative ultrasonography is superior to cholangiography with respect to its safety, shorter examination period, and ease of administration in all patients. In addition, IOUS is also better for identifying subtle anatomic detail. Intraoperative ultrasonography compares favorably with IOC in terms of utility in exploring bile ducts for stones. Intraoperative ultrasonography is an effective procedure for biliary exploration during a laparoscopic cholecystectomy.

Ileal varices associated with recurrent bleeding in a patient with liver cirrhosis.

We report a rare case of massive and recurrent bleeding from ileal varices in a patient with hepatitis C virus-positive liver cirrhosis. A 66-year old woman, who had undergone laparotomy and blood transfusion 36 years before (because of an extrauterine pregnancy) and endoscopic sclerotherapy for esophageal varices 1 year previously, was admitted to our hospital with loss of bright red blood per rectum. The bleeding was massive and recurrent, and frequent blood transfusions were required. Endoscopic studies failed to find the bleeding site. In the venous phase of selective superior mesenteric angiography, mesenteric varices in the lower part of the abdominal cavity were observed. Laparotomy was performed to control the repeated bleeding which had lasted for more than 1 month. Varices communicating with the right ovarian vein were found on the ileal wall and segmental resection of the ileum was performed. Histological examination demonstrated a massive varicose vein and several dilated veins in the submucosa. The patient's postoperative course was favorable, with no hemorrhagic events during a follow-up of more than 6 months after surgery. Ileal varices should be considered in the diagnosis of a patient who presents with lower gastrointestinal bleeding and portal hypertension.