Space plasma physics: space experiments with particle accelerators.

Electron and plasma beams and neutral gas plumes were injected into the space environment by instruments on Spacelab 1, and various diagnostic measurements including television camera observations were performed. The results yield information on vehicle charging and neutralization, beam-plasma interactions, and ionization enhancement by neutral beam injection.

Changes of ROS during a two-day ultra-marathon race.

To assess oxidative stress (OS) induced by endurance exercise, concentrations of serum reactive oxygen species (ROS) were determined in 70 Japanese male amateur runners completing a two-day ultra-marathon race. Serum ROS levels were analyzed at three time points: before the race (baseline), after the 1st day race (mid-race), and after the 2nd day race (goal) (post-race). The means (SE) of ROS were 151.4(3.7) (U. CARR.), 168.7(4.4), and 156.8(4.4), respectively. Significant positive trends were noted between age and serum ROS concentrations at the three race points (p<0.05 for all). After adjusting for age, BMI and average monthly running distance, the baseline serum ROS concentrations were positively associated with completion times of the first-day race, in particular (p<0.05), suggesting that the concentrations may predict physical performance. The ROS production increased at mid-race (p<0.05), but the levels returned to baseline levels at post-race, indicating that an antioxidant defense system may develop post-race to reduce OS.

Relationship between ethanol consumption and TBL2 rs17145738 on LDL-C concentration in Japanese adults: a four season 3-day weighed diet record study.

BACKGROUND: LDL cholesterol (LDL-C) concentration is modified by dietary and genetic factors; however, little is known about the details of this relationship. Our aim was to investigate the associations taking into account dietary assessment methods, seasonal effects and missing values. METHODS: Study subjects completed food frequency questionnaires (FFQ) and supplied 3-day weighed dietary records (WDRs) and blood samples in four seasons. Approximately 660,000 single nucleotide polymorphisms (SNPs) were measured. Candidate SNPs related to LDL-C concentration were systematically selected. Multiple imputation was applied for missing values. A total of 312 repeated measures data were used for analyses. After adjusting for season and subjects as fixed and random effects, effects of nutrient intake and SNPs on LDL-C concentration were assessed according to three dietary assessment methods: the FFQ and first and four season 3-day WDRs (4 s-3d WDRs). RESULTS: For LDL-C concentration, ethanol consumption derived from all three dietary assessment methods was consistently associated (P < 0.09 for all). Positive and negative relationships were consistently shown with rs651007 and rs1160985 in the first and four seasons; but the latter remained after adjusting for total dietary fiber intake derived from the FFQ and 4 s-3d WDRs (P < 0.05, excepting the first 3-day WDRs). rs599839 was negatively associated after cholesterol intakes derived from the first and 4 s-3d WDRs were considered (P < 0.05 and 0.07, respectively). Each rs17145738 and ethanol consumption based on the 4 s-3d WDRs was related to LDL-C concentration (P < 0.05). Seasonal variations of LDL-C concentration were observed only in summer. CONCLUSIONS: In contrast to nutrient intake, ethanol consumption was shown to be comprehensively related to LDL-C concentration, regardless of dietary assessment methods. Taking into account seasonal effects, critical relationships with LDL-C concentration for some SNPs, after adjustment for specific nutrients, were revealed. Our findings can be used to help to interpret the relationships between dietary and genetic factors on LDL-C concentration in large-scale epidemiological studies.(10/10 keywords).

A genome-wide association study of coping behaviors suggests FBXO45 is associated with emotional expression.

Individuals use coping behaviors to deal with unpleasant daily events. Such behaviors can moderate or mediate the pathway between psychosocial stress and health-related outcomes. However, few studies have examined the associations between coping behaviors and genetic variants. We conducted a genome-wide association study (GWAS) on coping behaviors in 14088 participants aged 35 to 69 years as part of the Japan Multi-Institutional Collaborative Cohort Study. Five coping behaviors (emotional expression, emotional support seeking, positive reappraisal, problem solving and disengagement) were measured and analyzed. A GWAS analysis was performed using a mixed linear model adjusted for study area, age and sex. Variants with suggestive significance in the discovery phase (N = 6403) were further examined in the replication phase (N = 7685). We then combined variant-level association evidence into gene-level evidence using a gene-based analysis. The results showed a significant genetic contribution to emotional expression and disengagement, with an estimation that the 19.5% and 6.6% variance in the liability-scale was explained by common variants. In the discovery phase, 12 variants met suggestive significance (P < 1 × 10-6 ) for association with the coping behaviors and perceived stress. However, none of these associations were confirmed in the replication stage. In gene-based analysis, FBXO45, a gene with regulatory roles in synapse maturation, was significantly associated with emotional expression after multiple corrections (P < 3.1 × 10-6 ). In conclusion, our results showed the existence of up to 20% genetic contribution to coping behaviors. Moreover, our gene-based analysis using GWAS data suggests that genetic variations in FBXO45 are associated with emotional expression.

High frequency of fibroblast growth factor (FGF) 8 expression in clinical prostate cancers and breast tissues, immunohistochemically demonstrated by a newly established neutralizing monoclonal antibody against FGF 8.

Fibroblast growth factor (FGF) 8, also known as androgen-induced growth factor, was originally isolated from an androgen-dependent mouse mammary Shionogi carcinoma SC-3 cell line, in which it was shown to have androgen-regulated properties. We previously demonstrated that Fgf 8 transcripts were detected in several human prostate and breast cancer cell lines and that recombinant FGF 8 was mitogenic to an androgen-sensitive prostate cancer LNCaP cell line. In this study, to characterize the roles of FGF 8 in clinical hormone-responsive cancers, we established a monoclonal antibody against FGF 8. In Western blots, this antibody specifically interacted with a FGF 8b isoform that was identical between mouse and human but was not identical to other murine 8a and 8c isoforms. In a cell growth assay using SC-3 cells, the newly established anti-FGF 8 antibody blocked androgen- and FGF 8-stimulated growth but not basic FGF-stimulated growth. Immunohistochemical analyses by use of the established anti-FGF 8 antibody demonstrated that FGF 8 was frequently expressed in human prostate cancers, appearing in 40 of 43 cases (93%), whereas both prostatic hyperplasia specimens and normal prostate tissues included in biopsy specimens were negative for FGF 8 expression. On the other hand, FGF 8 was detected in normal ductal and lobular epithelial cells in breast tissues. FGF 8 was also frequently expressed in various breast diseases, including fibroadenomas (5 of 5 cases, 100%), intraductal papillomas (3 of 3 cases, 100%), ductal hyperplasias (3 of 6 cases, 50%), and breast cancers (8 of 12 cases, 67%). Androgen receptors were also immunohistochemically detected in FGF 8-positive prostate cancers (40 of 40 cases, 100%) and FGF 8-positive breast diseases (17 of 19 cases, 89%). These findings strongly suggest that FGF 8 is involved in hormone-related tumorigenesis of the prostate and breast.

Immunotactoid glomerulopathy characterized by steroid-responsive massive subendothelial deposition.

We report a case of immunotactoid glomerulopathy with unique histologic findings in serial biopsies. A 73-year-old man complained of developing general edema. Laboratory data on admission presented moderate renal dysfunction with nephrotic syndrome. There was no evidence of systemic disease that might cause secondary glomerulopathy. Light microscopy of the renal specimen revealed lobulation of glomerular tufts and massive endothelial deposition of hyaline-like periodic acid-Schiff-positive substance with neutrophilic infiltration. The deposits were positive for immunoglobulin by immunohistochemical stains but negative for Congo red stain. Electron microscopy disclosed the deposition of microtubular structure (60 nm in diameter) predominantly in the subendothelial area and to some extent in the subepithelial and mesangial areas. Some of the tubules were extremely large (100 to 130 nm in diameter) and displayed a unique scroll structure in cross-section. The patient was treated with two sessions of plasma exchange and subsequent oral prednisolone (30 mg/d). Proteinuria and renal dysfunction improved significantly in the following 2 months. Second and third renal biopsies revealed disappearance of the deposit along with the improvement of proteinuria and renal dysfunction. Because similar microtubular structures were found in neutrophils in the glomerulus as well as in the urinary sediment, phagocytosis was suggested as a possible mechanism for removal of the deposit.

Isolation of an androgen-inducible novel lipocalin gene, Arg1, from androgen-dependent mouse mammary Shionogi carcinoma cells.

Here we report isolation of an androgen-regulated novel gene from an androgen-dependent mouse mammary Shionogi carcinoma SC-3 cell line. Using a polymerase chain reaction-based subtraction method and Northern blotting analysis, we isolated four androgen-inducible genes from SC-3 cells. Nucleotide sequencings identified three of the genes as cyclin D1, beta-catenin, and fatty acid synthase, respectively, but the fourth, a gene tentatively named as Arg1 (androgen-regulated gene 1), remained undefined. The cloned 2.0-kb sized Arg1 cDNA encoded 414 amino acid sequences. The deduced amino acid sequences, sharing about 30% homology with cathepsin family members at a protein level, had relatively conserved residues around the three proteinase active sites reported earlier. In Northern blotting, Arg1 mRNA was found in kidney, heart, lung, and to a lesser degree, in spleen and liver. Its transcripts were also detected in male reproductive organs on RT-PCR. In addition, its expression levels in prostate were markedly reduced after castration. Unexpectedly, Arg1-expressing COS1 cells showed no significant proteinase activity to various synthesized substrates under neutral or acidic conditions in this study. This might have been due to the replacement of the cysteinyl active site for proteinase to serine residue in the Arg1 amino acid sequences. Given that Arg1 also contains a lipocaline signature known as a binding motif for small hydrophobic molecules at the center of its amino acid sequences, Arg1 is a lipocalin family gene regulated by androgens in prostate and Shionogi carcinoma cells.

Predominant expression of fibroblast growth factor (FGF) 8, FGF4, and FGF receptor 1 in nonseminomatous and highly proliferative components of testicular germ cell tumors.

Nonseminomatous components within testicular germ cell tumors affect patient prognosis to varying degrees. These components are well known to mimic early embryonic totipotential tissues. Prompted by the recent observation that fibroblast growth factor (FGF) 8, FGF4, and FGF receptor (FGFR) 1 are required for the growth of early postimplantational embryonic tissues, we investigated the expressions of FGF8, FGF4, and FGFRI in surgically resected specimens of primary testicular germ cell tumors using an immunohistochemical method. All cases of embryonal carcinoma (14 cases), yolk sac tumor (3 cases), and choriocarcinoma (3 cases) showed positive immunostaining for FGF8, FGF4, and FGFR1. In contrast, out of 13 cases of seminoma, immunostaining was negative for FGF8, FGF4, and FGFR1 in 8 cases (61.5%), 6 cases (46.1%), and 7 cases (53.8%), respectively. In 7 cases of mature and immature teratoma, most areas showed negative immunostaining. In addition, the Ki-67 labeling index showed extremely high mitogenic activity in embryonal carcinoma, yolk sac tumor, and choriocarcinoma, which are precisely the carcinomas with the highest expressions of FGF8, FGF4, and FGFR1. It is in keeping with the immunohistochemical result that murine teratocarcinoma P19 cells were shown to express FGF8, FGF4, and FGFRI only under undifferentiated growth conditions. Taken together, these findings confirm the involvement of FGF8, FGF4, and FGFR1 in highly proliferative conditions of nonseminomatous germ cell tumors.

Therapy-related leukemia with a novel 21q22 rearrangement.

We present a case of a 59-year-old Japanese man with therapy-related acute myeloblastic leukemia (AML) after the chemotherapy for non-Hodgkin's lymphoma (NHL). Accumulated doses of cyclophosphamide, procarbazine, doxorubicin, mitoxantrone, and etoposide were 18,300 mg, 3000 mg, 580 mg, 100 mg, and 4150 mg, respectively, which had been administered for the treatment of NHL. Myeloblasts in the peripheral blood increased 43 months after the onset of NHL. He was diagnosed as having AML (M2; FAB classification). The karyotype of the bone marrow cells in the present case contained the following abnormalities: t(2;21)(q21;q22), t(8;21)(q22;q22), and add(13)(q34). In the present case, 645 base pairs of chimeric mRNA were detected by reverse transcription-polymerase chain reaction, indicating the presence of AML1/MTG8 rearrangement. Translocation (2;21)(q21;q22) has not been described previously to our knowledge. It is interesting that the breakpoint of 21q22 existed both in t(2;21) and t(8;21). The disrupted AML1 gene resulting from two 21q22 rearrangements may be involved in the pathogenesis of AML in the present case. The clinical importance of therapy-related AML having the 21q22 rearrangement remains to be examined.

Extensive neuronal localization and neurotrophic function of fibroblast growth factor 8 in the nervous system.

Fibroblast growth factor (FGF) 8 has been well established to play a critical role in the early development of the central nervous system (CNS). We report here extensive neuronal localization and neurotrophic function of FGF8 in the nervous system. In sections of mouse embryos at E10.5, FGF8 was immunohistochemically found in neurons at the marginal zones of the CNS and in the dorsal root ganglia (DRG). Neuronal localization of FGF8 was marked at later embryonic stages and in adults, involving most of the central and peripheral neurons, including intermuscular enteric neurons, DRGs, and paraaortic sympathetic ganglia. Functionally, FGF8 promoted neurite outgrowth in human neuroblastoma SK-N-MC cells as well as in rat pheochromocytoma PC12 cells, suggesting that FGF8 acts as a neurotrophic factor. FGF8 also supported neuronal survival and differentiation in cultured human neural progenitor cells. In a cell growth assay, treatment with 50 ng/ml FGF8 on human cultured neuroblastoma SK-N-MC and IMR32 cells attenuated the growth of both. In accordance with these in vitro findings, the immunohistochemical analysis on human neurological diseases showed that FGF8 expression is evident in differentiating histological types of neuroblastoma and ganglioneuroblastoma, and that the levels of FGF8 immunoreactivity in the substantia nigra from Parkinson's disease are significantly lower than those in age-matched controls. Taken together, the present findings strongly suggest that FGF8 acts as a more generalized neurotrophic factor than previously reported.

Adult T cell leukemia lymphoma (ATL) localized in the right tibial bone.

A 56-year-old man was admitted complaining of pain in the right tibia. He was diagnosed as having adult T-cell leukemia/lymphoma (ATL/L) in the right knee joint by roentgenographic and histological examination. Monoclonal integration of HTLV-I proviral DNA was demonstrated in the bone tumor cells, although polyclonal integration was observed in the peripheral blood. These results led us to make a diagnosis of ATL with localized growth in the right knee joint. The osteolytic bone change was progressive despite radiation therapy. Complete remission was achieved after amputation of his right lower leg and two courses of chemotherapy. Resection of the localized lesion might be useful in cases of ATL, but further studies are necessary to confirm this conclusion.

Relative validity of a semi-quantitative food frequency questionnaire versus 28 day weighed diet records in Japanese female dietitians.

OBJECTIVE: To assess the relative validity of a semi-quantitative food frequency questionnaire (SQFFQ) against 28 day weighed diet records (WDRs). SUBJECTS AND METHODS: The SQFFQ was administered to 106 (21 male and 85 female) Japanese dietitians in Aichi Prefecture in autumn, 1996 and four-season consecutive 7 day WDRs were carried out during 1996-1997. We evaluated validity of intakes of 15 foods and 31 macro- and micro-nutrients based on the SQFFQ against those according to 28 day WDRs among 79 Japanese female dietitians. RESULTS: Mean daily intakes of selected foods and nutrients determined by the SQFFQ were generally equivalent to those measured by 28 day WDRs. Pearson's de-attenuated correlation coefficients (CCs) with log-transformation and energy-adjustment between intakes of selected foods and nutrients quantified by the SQFFQ and 28 day WDRs (minimum-median-maximum) ranged from 0.17 (beverages)-0.52 to 0.74 (rice), and Spearman's rank CCs with energy-adjustment ranged from 0.28 (confectionery)-0.42 to 0.68 (rice). Respective Pearson's CCs for intakes of nutrients were 0.28 (PUFAs)-0.51 to 0.73 (magnesium), and Spearman's rank CCs ranged from 0.23 (n-3 PUFAs)-0.45 to 0.71 (magnesium). Favorably higher agreement for intakes of foods/nutrients was achieved along with lower disagreement. CONCLUSIONS: Satisfactorily higher relative validity was attained in Japanese female dietitians with the SQFFQ. This calibrated questionnaire seems therefore appropriate for administration to Japanese dietitians to clarify associations between diet and health/disease. SPONSORSHIP: A grant-in-aid from the Ministry of Education, Science, Sports and Culture (06454242).

Discrepancies in dietary intakes and plasma concentrations of fatty acids according to age among Japanese female dietitians.

OBJECTIVE: To clarify the influences of age on dietary intakes and plasma concentrations of fatty acids (FAs) in Japanese female dietitians. SUBJECTS AND METHODS: In autumn 1996, we estimated dietary FA intakes based on 7 day weighed diet records and analyzed plasma FA concentrations in 79 healthy Japanese female dietitians, and investigated their relationships with age, dividing into three age groups (young (32-42 y), middle-aged (43-50 y) and elderly (51-66 y)). RESULTS: Dietary intakes of total FA, saturated FAs, monounsaturated FAs, n-3 polyunsaturated FAs (PUFAs) and alpha-linolenic acid (18:3n-3) were significantly highest in the middle-aged group, and lowest in the elderly. Similar trends were observed for dietary intakes of n-6 PUFAs and linoleic acid (18:2n-6), but there were no differences with regard to eicosapentaenoic acid (EPA; 20:5n-3), docosahexaenoic acid (DHA; 22:6n-3) and n-3 highly unsaturated FAs (HUFAs=EPA+22:5n-3+DHA). On the other hand, plasma concentrations of all FAs except for arachidonic acid (20:4n-6) demonstrated positive correlations with age. Moreover, plasma concentrations of EPA in all age groups, DHA in the elderly and n-3 HUFAs in the middle-aged and the elderly were all positively correlated with dietary intakes. CONCLUSIONS: We should take into account the influence of age on dietary habit and lipid metabolism when interpreting associations between dietary FA intakes and plasma FA concentrations.

Interleukin 4 is a crucial cytokine in controlling Trypanosoma brucei gambiense infection in mice.

The role of interleukin 4 (IL-4) was studied in relation to host defense during Trypanosoma brucei gambiense IL3253 (IL3253) infection in mice. BALB/c/A-+/+ (BALB/c), BALB/c/A-nu/nu (nude) and C.B-17/Icr-scid/scid (SCID) mice were infected intraperitoneally with 5 x 10(3) bloodstream forms (BSFs) of the trypanosome. The BALB/c mice showed high resistance to IL3253 infection with sporadic parasitemia. The nude mice were also able to control IL3253 infection and experienced low, but persistent parasitemia. However, the SCID mice, which have no functional T- and B-cells, showed high susceptibility to IL3253 infection with more than 1 x 10(8) BSFs/ml. Serum IL-4 levels in the infected BALB/c mice were increased on days 12-18 post-infection (PI). In BALB/c mice depleted of CD4+ T-cells by monoclonal antibody (mAb) treatment, parasitemia was persistent, ranging from 1 x 10(4) to 1 x 10(6) BSFs/ml and was significantly higher than that of the other groups. IL-4 was not detected in the serum of CD4+ T-cells-depleted mice. On the other hand, anti-IL-4-treated IL3253-infected BALB/c mice relapsed significantly longer than the control mice (p < 0.01). These findings suggest that the CD4+ T-cells may control the levels of parasitemia in IL3253 infection through the IL-4 pathway.

Determination of ion temperature by two-probe method.

A simple method is proposed to estimate the ion temperature of collision-free plasma using a cylindrical and a spherical Langmuir probe. This method is based on the difference in the ion-temperature dependence of the ion-current collection between these probes as predicted theoretically by Laframboise. Curves necessary for the ion-temperature determination are given and are applied to a low-density xenon plasma. Agreement of the probe characteristics with Laframboise's theory was also demonstrated.

A laboratory model for interstellar chemical evolution.

The chemistry in a supersonic plasma source flow was studied as a laboratory model for interstellar chemical evolution. It is important to match the similarity parameters for cosmic and laboratory conditions, which connect the temporal and spatial scales of the two cases. The apparatus simulated the conditions in a molecular cloud with respect to molecular-ionic reaction fraction, temperature, and non-equilibrium kinetics. The plasma flow was found to be cold enough, by the radical expansion, to produce polyatomic molecules. From the simple atomic plasma as reactant, cyanopolyyne and unsaturated hydrocarbons were synthesized in the present experiment. These molecules are also inherent in molecular clouds. The reaction mechanism is discussed.

Haemangiopericytoma of infratemporal fossa.

Haemangiopericytomas (HPCs) are rare vascular tumours that commonly involve the soft tissues of the trunk and lower extremities. In the head and neck, the most common sites are the nasal cavity and the paranasal sinuses, and unusually, the orbital region, the parotid gland, and the neck. We report a patient with HPC that originated in the infratemporal fossa and involved the pterygopalatine and the middle cranial fossae, apparently the first such case to be reported. Although the patient has undergone resection on three separate occasions, the tumour recurred. We then performed an extended resection using the infratemporal fossa approach type D. The patient has shown no recurrence in the past five years. Although histopathologic confirmation of this malignancy may be difficult, extensive resection remains the most effective treatment in such cases.

[Epidemiology and primary prevention of colorectal cancer].

The incidence of and mortality from colorectal cancer are increasing in Japan, as is its proportion among all malignant neoplasms. Thus, primary prevention of this cancer is crucial. Colorectal cancer is caused by interactions between host and environmental factors, with accumulation of gene alterations, such as activation of oncogenes and inactivation of suppressor genes, and generally involves an adenoma-carcinoma sequence. Carcinogenesis progresses with multi-factor, multi-hit and multi-stage mechanisms. According to the report by WCRF/AICR, convincing preventive factors include eating vegetables (not fruit) and physical activity (colon only), while probable risk factors are red meat and alcohol. Possible preventive factors include dietary fiber, starch and carotenoids, whereas possible risk factors include high body mass, fat and heavily cooked meat. Such preventive and risk factors for colorectal cancer are discussed in this review.

[Multiple intrapulmonary rheumatoid nodules].

A 66-year-old woman who had been treated at a nearby hospital since 1977 for rheumatoid arthritis complained of cough. Chest X-ray films disclosed multiple nodular shadows with cavitation in the fields of both lungs. The patient was admitted to our hospital and a thoracoscopic lung biopsy was performed. Histologically, the nodule consisted of necrotizing granuloma, indicating a necrobiotic nodule. Rheumatoid nodule was diagnosed because the patient exhibited rheumatoid arthritis. The chest X-ray shadow disappeared without medication. Rheumatoid nodules without coniosis are uncommon, but should be considered in the differential diagnosis of lung nodular lesions in patients with rheumatoid arthritis.