Juvenile migration of the exclusively pelagic cyprinid, Gnathopogon caerulescens (Honmoroko) in Lake Biwa, Central Japan.

Migration of wild and cultivated juvenile honmoroko Gnathopogon caerulescens of from the spawning and nursery areas in Lake Biwa were investigated, both in the Ibanaiko Lagoon and its outlet to Daido River, using beam-trawl surveys in 2013 and 2014. The study demonstrated migration of G. caerulescens from a nursery lagoon toward Lake Biwa after the juvenile stage. These findings appear to be the first direct evidence for migration of an exclusively pelagic cyprinid species from a littoral nursery to a pelagic adult habitat in a large deep lake.

Metabolomics analysis of saliva from patients with primary Sjögren's syndrome.

The recent development of salivary proteomics has led to the identification of potential biomarkers for diagnosing patients with primary Sjögren's syndrome (pSS). Here we sought to identify differentially produced salivary metabolites from pSS patients and healthy controls (HCs) that might be used to characterize this disease. We obtained salivary samples from 12 female pSS patients (mean age 44.2 ± 13.01) and 21 age-matched female HCs. The metabolite profiles of saliva were analysed by gas chromatography-mass spectrometry. The total metabolite levels in each of the samples were calculated and compared across the study participants. A total of 88 metabolites were detected across the study samples, 41 of which were observed at reduced levels in the samples from pSS patients. Principal component analysis (PCA) revealed a loss in salivary metabolite diversity in the pSS patient samples compared to the HC samples. The reduced presence of glycine, tyrosine, uric acid and fucose, which may reflect salivary gland destruction due to chronic sialoadenitis, contributed to the loss of diversity. Comparative PCA of the pSS patients revealed the presence of two subpopulations based on their metabolite profiles, and these two subpopulations showed a significant difference in the prevalence of major salivary glanditis (P = 0.014). In this study, we found that the salivary metabolite profile of pSS patients was less diverse than that of HCs and that the metabolite profiles in pSS patients were affected by the presence of major salivary glanditis.

Response of sex ratio to timing of breeding in the small cyprinid Gnathopogon caerulescens.

The influence of hatching date on the sex ratio of wild Gnathopogon caerulescens was examined. Cohorts reared from eggs collected in the early and middle parts of the spawning season showed almost balanced sex ratios, with female bias in some cohorts. Cohorts born later in the season mostly displayed male bias, and the mean proportion of males later in the season was significantly higher than in early- and mid-season cohorts. These results indicate that the sex ratio of G. caerulescens changes with the time of breeding, increasing along with the ambient water temperature of the lake.

Construction of monoenergetic neutron calibration fields using 45Sc(p, n)45Ti reaction at JAEA.

The 8 and 27 keV monoenergetic neutron calibration fields have been developed by using (45)Sc(p, n)(45)Ti reaction. Protons from a 4-MV Pelletron accelerator are used to bombard a thin scandium target evaporated onto a platinum disc. The proton energies are finely adjusted to the resonance to generate the 8 and 27 keV neutrons by applying a high voltage to the target assemblies. The neutron energies were measured using the time-of-flight method with a lithium glass scintillation detector. The neutron fluences at a calibration point located at 50 cm from the target were evaluated using Bonner spheres. A long counter was placed at 2.2 m from the target and at 60 degrees to the direction of the proton beam in order to monitor the fluence at the calibration point. Fluence and dose equivalent rates at the calibration point are sufficient to calibrate many types of the neutron survey metres.

Investigation of properties of the TIARA neutron beam facility of importance for calibration applications.

Evaluation of the properties for quasi-monoenergetic neutron calibration fields of high energies more than 20 MeV at TIARA is proceeding for development of the field. Among the properties needed for the development as the standard calibration field, we report on measurement of the neutron beam profile using an imaging plate with a polyethylene converter and on estimation of the contribution of scattered neutrons into the irradiation field based on pulse height distribution at various off-beam positions measured using an organic liquid scintillation detector.

Monoclonal autoantibodies that react with hormones also react with cells not containing those hormones.

Two immunoglobulin M monoclonal autoantibodies, PI-6 and AP-2, were found by immunofluorescence, hormone absorption, and enzyme-linked immunosorbent assay to react with insulin and GH, respectively. The same antibodies were also found to react with a variety of organs that do not contain those hormones. Absorption of PI-6 with insulin, but not with GH, and absorption of AP-2 with GH, but not with insulin, eliminated the capacity of these antibodies to react with all organs tested. It is concluded that these monoclonal antibodies are broadly reactive and recognize epitopes on more than one protein.

Cyclic guanidines. 17. Novel (N-substituted amino)imidazo[2,1-b]quinazolin-2 ones: water-soluble platelet aggregation inhibitors.

A series of novel 1,2,3,5-tetrahydroimidazo[2,1-b]quinazolin-2-one derivatives substituted with a secondary amino group has been prepared and tested for the activities of inhibiting platelet aggregation in rats in vitro and ex vivo. Most of the compounds were found to be the potent inhibitors of platelet aggregation. Some of the active compounds were soluble in water and effective via iv infusion in rats. Structure-activity relationships have indicated that a lipophilic secondary amino group located at position 6 or 7 contributed to retention of potent activity. Among the compounds studied, 7-piperidino-1,2,3,5-tetrahydroimidazo[2,1-b]quinazolin-2- one (13 g,DN-9693) was the most favorable compound.

Thromboxane A2 synthetase inhibitors. 2. Syntheses and activities of tetrahydronaphthalene and indan derivatives.

A series of 1-imidazolylalkyl-substituted or 5-thiazolylalkyl-substituted tetrahydronaphthalenecarboxylic acid and indancarboxylic acid derivatives were prepared and tested for the inhibitory activities of thromboxane A2 (TXA2) production in vitro and ex vivo. Most of the compounds showed potent TXA2 synthetase inhibitory activities in vitro and had long duration of inhibition of TXA2 production in rats when orally or intravenously administrated. The imidazole analogues had slightly less potency in vitro than the thiazole analogues, but the activities of the imidazole analogues in ex vivo models were equal or superior to the activities of the thiazole analogues. 6-(1-Imidazolyl-methyl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid hydrochloride hemihydrate (47a, DP-1904) was chosen for clinical studies.

Cyclic guanidines. 14. Imidazo[1,2-a]thienopyrimidin-2-one derivatives as blood platelet aggregation inhibitors.

A series of novel 1,2,3,5-tetrahydroimidazo[1,2-a]thieno[2,3-d]-, -[3,2,-d]-, and -[3,4-d]pyrimidin-2-one derivatives has been prepared and tested for the activity of inhibiting platelet aggregation in rats in vitro and ex vivo. These compounds were synthesized through the following reactions: sodium borohydride reduction of 2,4-dichlorothienopyrimidines, followed by ethoxycarbonylmethylation and successive amination. Most of the compounds were found to be potent inhibitors of blood and platelet aggregation. Structure-activity relationships have indicated the essential contribution of the lactam structure and lipophilic substituents on the thiophene ring to the effective interaction of the compounds with a receptor site on the platelet. Among the compounds studied, 1,2,3,5,6,7,8,9-octahydro-[1]benzothieno[2,3-d]imidazo[1,2-a]pyrimidin-2-one (9m) exhibited the most favorable activity.

Gold sodium thiomalate suppresses the differentiation and function of human dendritic cells from peripheral blood monocytes.

OBJECTIVE: Gold sodium thiomalate (GST) is a drug commonly used for the treatment of rheumatoid arthritis (RA). To clarify the mechanism of therapeutic effects of GST on RA, we investigated if GST affects the differentiation of dendritic cells (DC), which are thought to play a pivotal role in RA pathogenesis. METHODS: We generated immature DC (iDC) in vitro from PB monocytes during the 5 to 7-day culture in the presence of IL-4 and GM-CSF. Mature DC (mDC) were induced by adding TNF alpha on day 5 of the 7-day culture with GM-CSF and IL-4. DC capacity of stimulating T cells was examined in allogenic MLR using generated DC as stimulators. IL-12 production from DC was assayed with ELISA. RESULTS: We found that: 1) mDC generated in the presence of GST showed lower expression of CD1a, CD83, CD80, CD86, HLA-ABC and HLA-DR compared to control mDC on FACS analysis. 2) GST-treated mDC showed reduced capacity of stimulating allogenic T cells in mixed leukocyte reaction. 3) IL-12p70 production after stimulation with SAC or LPS plus IFN gamma was markedly reduced in GST-treated mDC. CONCLUSION: GST suppresses the differentiation and function of DC generated from peripheral blood monocytes. This previously unknown action may explain the in vivo effects of GST in the treatment of RA.

Age-related susceptibility to dibromochloropropane.

To compare the acute toxic responses of weanling and adult rats to dibromochloropropane (DBCP), male 4- and 9-week-old rats were given subcutaneously 250 mg/kg DBCP. As compared to 4-week-old rats, 9-week-old rats showed higher mortality, more progressive weight loss and severer tissue injuries in the testis, kidney, intestine and lymphoid organs. These results indicated that weanling rats were less susceptible to DBCP toxicity.

Analysis of mammalian metallothionein isoforms by high-resolution SDS-gel electrophoresis.

Metallothioneins (MTs) are cysteine-rich heavy metal-binding proteins, whose possible functions are thought to be the protection against toxic metals as well as the regulation of essential metals. It is known that there are several MT isoforms, but the biological roles of the individual isoforms have not been elucidated. To facilitate the functional analysis of these isoforms, we improved an analytical method of MTs developed previously, which is based on a denaturing gel electrophoresis of chemically modified MTs. The established technique makes it possible not only to separate MT isoforms with a high resolution, but to estimate the levels of the individual isoforms by analyzing directly crude cell extracts. By this method, six MT isoforms were identified in the extracts of Cd-exposed human cells. It was also revealed that there is an apparent heterogeneity of the rat liver MT; five isoforms were identified in the liver extracts of Cd-injected rats. The present method will be useful in the functional analysis of the MT isoforms, as well as in a variety of aspects of the MT studies.

IQI/Jic mice have thymic B cells.

The thymus of IQI/Jic mice aged 3 to 15 months was studied chronologically by flow cytometry and immunohistochemistry. Thymic B cells (Thy B) expressing the surface marker B220+IgM+ were detected in both sexes, but were more prominent in females. Thy B appeared as early as 4 months of age in female mice, and the incidence of Thy B-positive mice and average Thy B ratio in thymocytes increased with age, reaching over 90% and 15%, respectively, after 9 months of age. In males, Thy B-positive animals appeared around 9 months of age and its incidence and average ratio increased gradually to 53% and 5%, respectively, at 15 months. The Thy B-rich thymus was thickened with cortical atrophy and medullary hyperplasia. Small- to medium-sized Thy B crowded and often formed follicle-like structures in the medulla. When mice of various ages were injected with mercuric chloride to induce antinucleolar antibody, many Thy B-rich animals could not develop the antibody, implying that these animals are immunologically impaired. IQI/Jic can be a novel strain to elucidate the relationship between the presence of Thy B and disorders of the immune system.

Correlation of mast cells with spindle cell hyperplasia in the adrenal cortex of IQI/Jic mice.

IQI/Jic mice showed a high incidence of subcapsular spindle cell hyperplasia (SCH) in the adrenal cortex accompanied by prominent mast cell infiltration. SCH-positive animals appeared as early as at 3 months of age, with an incidence of 18% in males and 20% in females. Except for one mouse, all females older than 6 months had the lesion. In males, the incidence increased gradually until 9 months, and was then stable at 75-88% thereafter. The severity of SCH increased with age in both sexes, and the lesions were more prominent in females. Mast cells infiltrated mainly at the sites of spindle cell hyperplasia, and their density was associated with the severity on the lesion. A quantitative morphometric study confirmed a significant correlation between the severity of SCH and the density of mast cells. A histochemical study demonstrated that these mast cells were of the connective tissue-type. These observations indicate that IQI/Jic mice may be a useful strain to elucidate the pathogenesis of SCH in the adrenal cortex in association with mast cell function.

Subcapsular cell hyperplasia and mast cell infiltration in the adrenal cortex of mice: comparative study in 7 inbred strains.

Subcapsular cell hyperplasia (SCH) in the adrenal cortex of aged mice (13-15 months old) was frequent in both sexes of BALB/c, C3H/He, DBA/2J and IQI/Jic mice and in the females of A/J and C57BL/6, although the incidence and severity of SCH were considerably different among mouse strains. Mast cells were closely associated with SCH in the A/J, BALB/c, C57BL/6, DBA/2J and IQI/Jic mice, but not in the C3H/He strain. Compared with other strains, IQI/Jic mice had a significantly larger number of mast cells in the adrenal glands. Our findings suggest that mast cells may participate in the development of SCH, and IQI/Jic would be suitable for studying the pathogenesis of SCH and the role of mast cells in this lesion.

Deodorization of laboratory animal facilities by ozone.

Deodorizing effect of ozone was investigated comparing two types of compact ozonizing apparatus made on an experimental basis. The concentrations of ammonia and trimethylamine were examined as an indicator for deodorizing effect of ozone in animal rooms of rats and guinea pigs at laboratory animal facilities of three different universities. Both of the ozonizing apparatus were able to remove ammonia and trimethylamine in animal rooms, with no significant difference in the performance of the two apparatus.

Picryl chloride-induced allergic dermatitis in IQI/Jic female mice.

IQI/Jic (IQI) mice are an ICR-derived inbred strain developed in Japan, and it is known that aged females of this strain develop allergic dermatitis of spontaneous nature. In the present study, young IQI female mice which were sensitized with picryl chloride (PCL) to the shaved skin of abdomen and then topically applied with PCL to the ear at 4, 11, 18 and 25 days after the sensitization were examined. The ear swelling response increased rapidly after the 1st application, peaked after the 2nd one, and then gradually decreased. Histopathologically, edema with inflammatory cell infiltration developed after the 1st application and progressed after the 2nd one. The number of mast cells, CD4-positive cells and MHC class II-positive cells became prominent accompanied with epidermal thickening and dermal fibroplasia after the 4th application when clear elevation of total serum IgE levels was observed in many mice. Compared with the dermatitis induced in the same way in BALB/c female mice, the nature was similar with each other but the degree was obviously severer in IQI female mice. IQI female mice are considered to be a useful laboratory animal for the investigation of allergic dermatitis.

Sialadenitis in IQI/Jic mice: a new animal model of Sjögren's syndrome.

Focal infiltration of lymphocytes with parenchymal destruction was noted in both salivary and lacrimal glands of IQI/Jic mice. The sialadenitis was found in more than 80% of female mice at all ages examined. The lesion progressed after 6 months and became more prominent with age. In contrast, male mice had slight and stable salivary lesions independent of age, though the incidence increased with age. Infiltrating lymphocytes consisted of both T and B cells. The dominant lymphocytes in small foci were CD4+ cells, but the majority of infiltrating cells were B cells (B220+), followed by CD4+ T cells in larger lesions. The ductual epithelium in the foci aberrantly expressed MHC class II antigen. Eight of 24 15-month-old female mice with sialadenitis produced speckled-type IgG antinuclear autoantibody. These findings are similar to those in patients with Sjögren's syndrome. IQI/Jic mice could be a novel animal model of Sjören's syndrome.

Cumulative effects of 1,2-dibromo-3-chloropropane (DBCP) on kidney and testis.

Male rats were repeatedly given 1,2-dibromo-3-chloropropane (DBCP) at 10, 30, or 100 mg/kg twice a week for 12 weeks and were examined pathologically at the 12th, 24th and 36th week. DBCP produced primary lesions in kidneys and testes dose-dependently. The renal lesions were the lining of the proximal tubules in the outer medulla by enlarged, occasionally giant, epithelial cells. Testicular lesions were the atrophy of the seminiferous tubules. These lesions were qualitatively and quantitatively similar throughout the experiment. The results indicated that repeated exposure of relatively low doses of DBCP produced irreversible lesions in the kidney and testis, and that the effects on these tissues may be cumulative.

Antinucleolar autoantibody induced by mercuric chloride in mice: does sodium selenite inhibit autoantibody production?

Repeated exposure of subtoxic doses of mercuric chloride (HgCl2) can induce antinucleolar autoantibodies in susceptible mice. To study the immunopathological mechanism(s), sodium selenite (Na2SeO3), which is known to reduce the toxicity of mercury, is injected simultaneously with HgCl2 into mice. Equimolar Na2SeO3 nor the same amount of Se in Na2SeO3 as Hg in HgCl2 could not reduce antinucleolar autoantibody induction by HgCl2. These results indicate that the mechanism of autoimmunity induction by HgCl2 might be independent of its toxicity.