Revealing Color Forces with Transverse Polarized Electron Scattering.

The Spin Asymmetries of the Nucleon Experiment measured two double spin asymmetries using a polarized proton target and polarized electron beam at two beam energies, 4.7 and 5.9 GeV. A large-acceptance open-configuration detector package identified scattered electrons at 40° and covered a wide range in Bjorken x (0.3

Observation of Λ(4)H Hyperhydrogen by Decay-Pion Spectroscopy in Electron Scattering.

At the Mainz Microtron MAMI, the first high-resolution pion spectroscopy from decays of strange systems was performed by electron scattering off a (9)Be target in order to study the Λ binding energy of light hypernuclei. Positively charged kaons were detected by a short-orbit spectrometer with a broad momentum acceptance at 0° forward angles with respect to the beam, efficiently tagging the production of strangeness in the target nucleus. Coincidentally, negatively charged decay pions were detected by two independent high-resolution spectrometers. About 10(3) pionic weak decays of hyperfragments and hyperons were observed. The pion momentum distribution shows a monochromatic peak at pπ≈133 MeV/c, corresponding to the unique signature for the two-body decay of hyperhydrogen Λ(4)H→(4)He+π(-), stopped inside the target. Its Λ binding energy was determined to be BΛ=2.12±0.01 (stat)±0.09 (syst)MeV with respect to the (3)H+Λ mass.

Observation of the (Λ)(7)He hypernucleus by the (e, e'K+) reaction.

An experiment with a newly developed high-resolution kaon spectrometer and a scattered electron spectrometer with a novel configuration was performed in Hall C at Jefferson Lab. The ground state of a neutron-rich hypernucleus, (Λ)(7)He, was observed for the first time with the (e, e'K+) reaction with an energy resolution of ~0.6 MeV. This resolution is the best reported to date for hypernuclear reaction spectroscopy. The (Λ)(7)He binding energy supplies the last missing information of the A = 7, T = 1 hypernuclear isotriplet, providing a new input for the charge symmetry breaking effect of the ΛN potential.

The NADH-ubiquinone oxidoreductase 1 alpha subcomplex 5 (NDUFA5) gene variants are associated with autism.

OBJECTIVE: Autism appears to have a strong genetic component. The product of the NADH-ubiquinone oxidoreductase 1 alpha subcomplex 5 (NDUFA5) gene is included in the mitochondrial electron transport chain. METHOD: We performed a case-control study of 235 patients with autism and 214 controls and examined three single-nucleotide polymorphisms (SNPs) within this gene in a Japanese population. We then conducted a transmission disequilibrium test (TDT) analysis in 148 autistic trios. RESULTS: In the case-control study, two SNPs (rs12666974 and rs3779262) showed a significant association with autism (P=0.00064 and 0.00046 respectively). Furthermore, a haplotype containing these two SNPs showed a significant association (P-global=0.0013, individual haplotype A-A: P=0.010). In TDT analysis, the global and A-A haplotype P-values also indicated significant associations. Minor allele and genotype frequencies were decreased in the autistic subjects. CONCLUSION: We found significant association between the NDFA5 gene and autism.

Highly restricted T cell repertoire shaped by a single major histocompatibility complex-peptide ligand in the presence of a single rearranged T cell receptor beta chain.

The T cell repertoire is shaped by positive and negative selection of thymocytes through the interaction of alpha/beta-T cell receptors (TCR) with self-peptides bound to self-major histocompatibility complex (MHC) molecules. However, the involvement of specific TCR-peptide contacts in positive selection remains unclear. By fixing TCR-beta chains with a single rearranged TCR-beta irrelevant to the selecting ligand, we show here that T cells selected to mature on a single MHC-peptide complex express highly restricted TCR-alpha chains in terms of Valpha usage and amino acid residue of their CDR3 loops, whereas such restriction was not observed with those selected by the same MHC with diverse sets of self-peptides including this peptide. Thus, we visualized the TCR structure required to survive positive selection directed by this single ligand. Our findings provide definitive evidence that specific recognition of self-peptides by TCR could be involved in positive selection of thymocytes.

Three-body nonmesonic weak decay of the (Lambda)12C hypernucleus.

We have measured the branching ratio of the three-body process in the nonmesonic weak decay of Lambda12C to be 0.29+/-0.13. This result was obtained by reproducing the nucleon and the nucleon pair yields introducing a measured final state interaction. At the same time, we have determined the absolute decay widths, Gamma(n) and Gamma(p), along with Gamma2N, whose relative ratio has been a long-standing puzzle. Including the three-body process, we have successfully reproduced the nucleon energy distribution, the coincidence two-nucleon angular correlation, and the momentum sum distribution simultaneously.

Organ-specific autoimmunity in mice whose T cell repertoire is shaped by a single antigenic peptide.

Organ-specific autoimmune diseases have been postulated to be the result of T cell response against organ-specific self-peptides bound to MHC molecules. Contrary to this paradigm, we report here that transgenic mice lacking MHC class I expression and expressing an MHC class II I-A(b) molecule that presents only a single peptide (E alpha 52-68) spontaneously develops peripheral nervous system-specific autoimmune disease with many of the histopathological features found in experimental allergic neuritis. Reciprocal bone marrow chimeras produced using susceptible and resistant lines revealed that bone marrow-derived cells determined disease susceptibility. While the expression of the I-A(b)-E alpha 52-68 complex in the periphery was readily detectable in both lines, its expression on thymic dendritic cells responsible for tolerance induction was markedly lower in the susceptible line than in the resistant line. Consistent with this, CD4(+) T cells that can be activated by the I-A(b)-E alpha 52-68 complex were found in the susceptible line, but not in the resistant line. Such CD4(+) T cells conferred the disease to the resistant line by adoptive transfer, and administration of Ab specific for the I-A(b)-E alpha 52-68 complex inhibited disease manifestation in the susceptible line. These results indicate that disease development involves systemic T cell reactivity to I-A(b)-E alpha 52-68 complex, probably caused by incomplete negative thymocyte selection.

Expression of uncoupling protein 1 in bovine muscle cells.

Uncoupling protein 1 (Ucp1) is predominantly expressed in brown/beige adipocytes in mammals. Although myogenic cells have been suggested to commit to a brown adipocyte lineage through the induction of Prdm16 expression, Prdm16 is also expressed in skeletal muscle. Thus, we examined expression of Ucp1 in bovine myogenic cells. Considering that Ucp1 is a principle molecule that induces energy expenditure in brown/beige adipocytes, expression of Ucp1 is not preferable in beef cattle because of potential decrease in energy (fattening) efficiency. The RT-PCR analyses revealed the expression of Ucp1 in the skeletal muscle of cattle; expression levels were markedly lower than those in the brown fat of calves. Immunohistochemical analyses showed that Ucp1 surrounded muscle fibers, but not adipocytes residing in skeletal muscle. Myosatellite cells cultured in myogenic medium showed an increase in the expression levels of myogenic regulatory factors ( < 0.05), while those in cells cultured in adipogenic medium were decreased ( < 0.05). The Ucp1 expression was also detected in myosatellite cells; expression levels were greater in cells after myogenic culture for 12 d than in those after myogenic culture for 6 d ( < 0.05) and were decreased when cells were cultured in adipogenic medium ( < 0.05). The Prdm16 expression was not affected by culture conditions, suggesting that the expression of Ucp1 is not regulated by that of Prdm16. The results of the present study provide an insight into the unexpected expression of Ucp1 in bovine skeletal muscle, which suggests the necessity for further studies on Ucp1-mediated energy expenditure in bovine skeletal muscle.

Difference between follistatin isoforms in the inhibition of activin signalling: activin neutralizing activity of follistatin isoforms is dependent on their affinity for activin.

We demonstrate the difference between the follistatin isoforms (FS-288 and FS-315), two activin-binding proteins, in the neutralizing activity for activin signalling. Transcriptional reporter assay using 3TP-Lux, an activin-responsive reporter construct, showed that the inhibitory effect of FS-288 on activin-induced transcriptional response is more potent than that of FS-315. The potency was not influenced by the presence of heparan sulfates, by which FS, in particular FS-288, associates with cell surfaces at a high affinity. Furthermore, FS-288 inhibited the binding of activin to its type II receptor more markedly than did FS-315, as evidenced by surface plasmon resonance and affinity cross-linking experiments. Moreover, the Kd of FS-288 and FS-315 for activin A was estimated to be 46.5+/-0.37 pM and 432+/-26 pM, respectively, by surface plasmon resonance experiments. These results indicate that the different potency between the two FS isoforms in the inhibition of activin activities depends on their affinity for activin A.

Correlation between Bcl-X expression and B-cell hybridoma apoptosis induced by activin A.

In this study, we examined the role of bcl-XL and bcl-XS in apoptotic cell death of HS-72 cells induced by activin A. Immunoblot analysis revealed that a band of Bcl-XL was detected in HS-72 cells cultured with or without activin A. Although untreated HS-72 cells did not express Bcl-XS, the expression of Bcl-XS was significantly increased when cultured with activin A. We also investigated the expression of Bcl-XS and Bcl-XL in HS-72 cells cultured with activin A in the presence of protein kinase C inhibitor 1-(5-isoquinotinesulfonyl)-2-methylpiperazine dihydrochloride (H7), which suppressed apoptosis in HS-72 cells induced by activin A. Exposure to H7 apparently increased the level of Bcl-XL in HS-72 cells cultured with or without activin A. In contrast, no detectable band of Bcl-XS was found in HS-72 cells cultured with activin A and H7. These findings indicate that Bcl-XL upregulation and Bcl-XS downregulation induced by H7 might correlate with the suppression of activin A-induced apoptosis in B-lineage cells.

The role of activin type I receptors in activin A-induced growth arrest and apoptosis in mouse B-cell hybridoma cells.

Activins transduce their signals by binding to activin type I receptors and activin type II receptors, both of which contain a serine/threonine kinase domain. In this study, we established stable transfectants expressing two types of activin receptors, ActRI and ActRIB, to clarify the role of these receptors in activin signalling for growth inhibition in HS-72 mouse B-cell hybridoma cells. Over-expression of ActRI suppressed activin A-induced cell-cycle arrest in the G1 phase caused by inhibition of retinoblastoma protein phosphorylation through induction of p21CIP1/WAF1, a cyclin-dependent kinase inhibitor, and subsequent apoptosis. In contrast, HS-72 clones that over-expressed ActRIB significantly facilitated activin A-induced apoptosis. These results indicate that ActRI and ActRIB are distinct from each other and that the ActRI/ActRIB expression ratio could regulate cell-cycle arrest in the G1 phase and subsequent apoptosis in HS-72 cells induced by activin A.

Dielectric property measurement of ocular tissues up to 110 GHz using 1 mm coaxial sensor.

Measurement of the dielectric properties of ocular tissues up to 110 GHz was performed by the coaxial probe method. A coaxial sensor was fabricated to allow the measurement of small amounts of biological tissues. Four-standard calibration was applied in the dielectric property measurement to obtain more accurate data than that obtained with conventional three-standard calibration, especially at high frequencies. Novel data of the dielectric properties of several ocular tissues are presented and compared with data from the de facto database.

Human leukocyte antigen and season of birth in Japanese patients with schizophrenia.

OBJECTIVE: Five Japanese studies, to the authors' knowledge, without exception, have consistently shown an increased frequency of human leukocyte antigen (HLA)-DR1 in patients with schizophrenia. This suggests an association between HLA-DR1 and schizophrenia in the Japanese population. The mechanism of the association is unknown; however, prenatal infections may be involved. The present study explored factors, including winter birth, that might correlate with this mechanism. Age at onset and gender were also studied. METHOD: Factors were compared between Japanese patients with schizophrenia with and in those without HLA-DR1 (N=60 and N=307, respectively). RESULTS: A significantly higher incidence of births in February and March was observed in patients with (31.7%) than those without (15. 6%) HLA-DR1. No association was found between the presence of HLA-DR1 and other variables. CONCLUSIONS: Although this result is preliminary, it may suggest an interaction between HLA and winter birth in the development of schizophrenia in the Japanese population.

Possible role of hepatocyte growth factor/scatter factor and activin A produced by the target organ in liver metastasis.

The molecular mechanism of organ-specific metastasis to the liver remains largely unknown. However, it is conceivable that paracrine growth factors produced by a target organ induce migration and proliferation of malignant cells to that organ, and this is the cause of organ-specific metastasis. In this study, we investigated the effect of hepatocyte growth factor/scatter factor (HGF/SF) and activin A, which are known to be produced by the liver, on the motility and growth of liver-metastatic cell line FBJ-LL. HGF/SF and activin A induced motility synergistically, but they did not affect the proliferation of FBJ-LL cells. Expression of the HGF/SF receptor, the c-met gene, and the activin-receptor type IA, type IB, and type IIA genes in FBJ-LL cells was detected by reverse transcription polymerase chain reaction. These findings suggest that both HGF/SF and activin A promote organ-specific metastasis to the liver by induction of migration through their specific receptors on liver-metastatic cells.

Serum carboxy-terminal cross-linked telopeptide of type I collagen reflects bone metastasis in hepatocellular carcinoma.

Carboxy-terminal telopeptide of type I collagen (ICTP) is a degradation product of type I collagen. In this study, we investigated the usefulness of measuring the serum ICTP concentration for diagnosing and monitoring bone metastasis from hepatocellular carcinoma (HCC). The serum concentrations of ICTP, type I procollagen carboxy-terminal propeptide (PICP), type III procollagen aminoterminal propeptide (PIIIP), type IV collagen (Ty IV), type IV collagen 7S-domain (7S), and hyaluronic acid (HA) were measured in patients with liver cirrhosis, HCC with or HCC without bone metastasis, and in healthy controls. The diagnostic efficiency of the serum ICTP and fibrosis marker levels in the HCC patients with and without bone metastasis was evaluated using receiver operating characteristic curves. We also retrospectively examined the changes in the serum ICTP levels before and after bone metastasis in the HCC patients. The serum ICTP level was significantly higher in the HCC patients with bone metastasis than in the patients with other diseases and the healthy controls. The serum PICP, PIIIP, Ty IV, 7S and HA levels of the HCC patients with bone metastasis did not differ significantly from those of the patients without bone metastasis. The diagnostic efficiency for HCC with bone metastasis was 87% for ICTP, 51% for PICP, 65% for Ty IV, 55% for PIIIP and 51% for HA. During the follow-up, the changes in the serum ICTP values paralleled the behavior of bone metastasis. These results indicate that the measurement of serum ICTP concentration is useful for detecting and monitoring HCC patients with bone metastasis.

Relation of type II transforming growth factor-beta receptor to hepatic fibrosis and hepatocellular carcinoma.

Hepatocarcinogenesis is closely related to hepatic fibrosis. In this study, we investigated the relationship of type II transforming growth factor-beta receptor (T beta RII) to hepatic fibrosis and hepatocellular carcinoma (HCC). In vivo: liver tissues were obtained from 30 patients (10 chronic hepatitis, 7 cirrhosis, 13 HCC). Protein expression and immunolocalization of T beta RII were examined by Western blot analysis and immunohistochemistry. In vitro: T beta RII protein expression in hepatoma cell lines (HepG2, Hep3B, HLE, HLF and Huh7) was examined by Western blot analysis. Next, we transfected T beta RII cDNA to Huh7, and compared the change of cell number and observed the induction of apoptosis after TGF-beta1 treatment using a FACScan flow cytometer. In vivo: T beta RII immunolocalization in liver tissues was significantly decreased in patients with HCC compared with that of patients with chronic hepatitis or liver cirrhosis. In Western blot analysis, T beta RII expression in tissues attenuated in comparison with that in non-tumor tissues in some patients with HCC. In vitro: T beta RII protein expression in HLE, HLF and Huh7 cells was weaker than that in HepG2 and Hep3B cells. In Huh7 cells transfected T beta RII cDNA, cell arrest and apoptosis were obviously induced. These results indicated that human HCC has a reduced expression of T beta RII for TGF-beta1. This may provide a selective growth advantage to HCC to escape the inhibitory growth signals of TGF-beta1, and may be linked with critical steps in the growth of hepatoma cells.

Follistatin-like immunoreactivity in the cytoplasm and nucleus of spermatogenic cells in the rat.

Immunohistochemistry using an antiserum raised against the synthetic follistatin peptide (residues 123-134) was used, in the present study, to detect the stage-specific appearance of immunoreactive follistatin in the rat testis. Follistatin immunoreactivity was not found in Sertoli and Leydig cells, while it was clearly detected in spermatogenic cells. Follistatin-like immunoreactivity was detected in the cytoplasm and nucleus of late pachytene spermatocytes. Although the reaction in the cytoplasm disappeared after meiosis, it continued to be intense in the nucleus from pachytene spermatocytes to round spermatids. This finding indicated that follistatin or its closely related peptide produced in late pachytene spermatocytes migrates from the cytoplasm to the nucleus. We subjected rat testis homogenate to affinity chromatography on a sulfate-cellulofine and anti-follistatin Cys (123-134)-Affi-Gel Hz column followed by reverse-phase HPLC and analyzed the resulting fractions by Western blotting using follistatin antiserum. Three major bands at 57, 45 and 39 kDa or four bands at 52, 44, 39 and 34 kDa were detected in crude preparations from rat testis homogenate, under reducing or non-reducing SDS-PAGE respectively. The protein from rat testis, which was recognized by anti-follistatin (123-134) antiserum, exhibited a characteristic pattern for follistatin on SDS-PAGE, i.e. slower migration under reducing conditions than under non-reducing conditions, suggesting that it was follistatin or its closely related protein. Follistatin or its closely related protein may be a stage-specific modulator of spermatogenesis. Since follistatin-like immunoreactivity was not found in oocytes in any stage of development from embryonic to adult rats, it may act in an event specific to spermatogenesis, such as nuclear condensation.

Increased expression of vascular endothelial growth factor is associated with tumor progression in hepatocellular carcinoma.

Vascular endothelial growth factor is a potent direct-acting angiogenic factor. Early in hepatocarcinogenesis, hepatocellular carcinomas do not show hypervascularity; at later stages, they require abundant arterial blood flow. We investigated the role of vascular endothelial growth factor in hepatocellular carcinoma arterialization. We studied 51 patients with hepatocellular carcinoma. All patients had undergone hepatic arteriography. Vascular endothelial growth factor expression was investigated by immunohistochemistry (n = 51) and in situ hybridization (n = 13), and the changes in vascular endothelial growth factor expression were evaluated in relation to tumor differentiation and changes in tumor vascularity. The expression of vascular endothelial growth factor isoforms in hepatocellular carcinomas was also analyzed by reverse transcriptase-polymerase chain reaction (n = 10). Vascular endothelial growth factor expression was detected in hepatoma cells and hepatic stellate cells, and increased vascular endothelial growth factor expression was associated with tumor dedifferentiation. Vascular endothelial growth factor expression in hypervascular hepatocellular carcinomas was greater than in those not showing hypervascularity. The major vascular endothelial growth factor isoforms expressed in hepatocellular carcinoma were 121 and 165. These findings indicate that vascular endothelial growth factors 121 and 165 play a critical role in the process of angiogenesis in hepatocellular carcinomas.

Asymmetry in the nonmesonic weak decay of polarized (5)(Lambda)He hypernuclei

We have measured the asymmetric emission of protons from the nonmesonic decay of polarized (5)(Lambda)He produced by the (pi(+), K+) reaction. (5)(Lambda)He is an s-shell hypernucleus and its polarization is due to the Lambda. One expects to obtain direct information on the elementary weak Lambda-->p-->np process. The asymmetry parameter has been determined to be 0.24+/-0.22. The implication of the result is discussed.

Clinical observations of juvenile nonprogressive muscular atrophy localized in hand and forearm.

Twenty-seven patients with juvenile nonprogressive muscular atrophy localized in the hand and forearm were analyzed. The clinical characteristics were juvenile male occurrence, insidious onset, specific distribution of localized muscular atrophy and a stationary course. On electromyography, denervation voltage (or giant NMU) is found in the atrophied muscles and sometimes in contralateral nonatrophied ones. Sensory disturbance was not remarkable. Although the etiological factor was not known, strenuous exercise of arms in sports was noted frequently in the history.