Garlic attenuates histological and histochemical alterations in livers of Schistosoma mansoni infected mice

Interest in screening for new anti-schistosomal agents is growing because of increased concerns about resistance to and safety of praziquantel. We investigated the anti-schistosomal action of prophylactic and therapeutic doses of garlic on the histological and histochemical alterations caused by Schistosoma mansoni infection. Livers of infected mice were characterized by granulomas, periportal inflammation and fibrosis, hepatocyte vacuolation, fatty degeneration and necrosis, and hypertrophy and pigmentation of Kupffer cells. Significant depletion of carbohydrates and increased lipid vacuoles also were observed. All garlic regimens caused suppression of granuloma formation and amelioration of histological and histochemical changes; the continuous treatment protocol produced the best results. Garlic appears to be a safe and economical anti-schistosomal adjuvant for attenuating the pathogenicity of schistosomiasis.     

Several 4-Substituted Glutamic Acid Derivatives and Small Peptides in Some Liliaceae Plants

Acidic non-protein amino acids and peptides in five species belonging to the family Liliaceae —Smilax china, Lilium maximowiczii, Tulipa gesneriana, Allium cepa and A. sativum— were surveyed. Two new amino acids —4-hydroxymethyl- and 4-ethyl-4-hydroxyglutamic acid— were isolated from bulbs of T. gesneriana. The first unequivocal identification of 4-ethylglutamic acid was performed from the same plant tissue. A new dipeptide —S-(2-carboxy-n-propyl)cysteinyl glycine— was isolated from A. cepa. Besides the compounds described above, 4-methylene-, 4-methyl- and 4-hydroxy-4-methylglutamic acid were isolated from S. china, L. maximowiczii, and T. gesneriana, but 4-ethylideneglutamic acid was isolated only from T. gesneriana. 4-Methyleneglutamic acid showed no appreciable biological activity, although this aminoacid has an α,β-unsaturated carboxyl group and reacts easily with cysteine in vitro. The most abundant free amino acid in the plant tissues examined in this study is arginine; nevertheless, acidic N_α-acylarginine derivatives which have been found in S. china and L. maximowiczii and published elsewhere could not be detected in bulbs of T. gesneriana, A. cepa, and A. sativum.     

Estimation of Dietary Pb and Cd Intake from Pb and Cd in Blood or Urine

Successful trials were made to estimate the dietary daily intake of lead (Pb) and cadmium (Cd) via foods from the levels of the metals in blood or urine. In practice, 14 and 15 reports were available for Pb and Cd in blood (Pb-B and Cd-B), urine (Pb-U and Cd-U) and 24-h diet duplicates (Pb-D and Cd-D), respectively, from which 68 pairs each of Pb or Cd in blood and food duplicates [each being geometric mean (GM) values for the survey sites] were obtained. Regression analysis revealed that there was a significant correlation between Pb-B and Pb-D, and also between Cd-B and Cd-D, suggesting that it should be possible to estimate both Pb-D and Cd-D from Pb-B and Cd-B, respectively. For Cd-U, the number of available cases was limited (20 pairs), but a significant correlation was detected between Cd-U (as Cd-U_cr, or Cd levels in urine as corrected for creatinine concentration) and Cd-D. Care should be taken in estimating Pb-D from Pb-B, as the ratio of Pb-D over Pb-B may decrease as a function of increasing Pb-B levels. The Pb-D (μg/day) for typical Japanese women with Pb-B of 15 μg/l was best estimated to be 13.5 μg/day. No Cd-B- or Cd-U_cr-dependent change was detected in case of Cd. The best estimate of Cd-D for Cd-B at 1.5 μg/l should be about 19.4 μg/day.     

Biotransformation of 1-Nitropyrene in Intestinal Anaerobic Bacteria

Mutagenic nitroaromatic compounds have recently been found in photocopies, urban atmosphere, automobile exhaust and wastewater. 1-Nitropyrene (1-NP) is readily formed when pyrene, ubiquitous in the environment, is exposed to nitrogen dioxide in the urban atmosphere or in automobile exhaust, and is highly mutagenic, inducing 449 his⁺ revertants/plate/nmol from Salmonella typhimurium strain TA98 in the absence of S9 fraction in the Salmonella-microsome test. It is possible to swallow sputum or some food containing 1-NP and it would come into contact with the normal bacterial flora. We determined the 1-NP nitroreductase activity in environmental and laboratory bacterial strains. We found that the mutagenicity of 1-NP mixed with the feces of a healthy man or a culture of anaerobic bacteria was decreased. The product proved to be 1-aminopyrene (1-AP), based on its fluorescence spectrum, its mass spectrum, and its characteristic thin layer chromatographic and high performance liquid chromatographic patterns. The 1-NP nitroreductase activity of aerobic bacteria was low, but crude extracts from the anaerobic bacteria, i.e., Bacteroides fragilis, B. thetaiotaomicron, B. vulgatus, Fusobacterium mortiferum, F. nucleatum, Clostridium perfringens, C. sporogenes, Bifidobacterium adolescentis, B. bifidum, Eubacterium lentum, E. limosum, and Peptostreptococcus anaerobius, all easily converted 1-NP to 1-AP and proportionally decreased the mutagenic activity of 1-NP.     

Evidence for cryptic northern refugia in the last glacial period in Cryptomeria japonica

MethodsGenetic diversity and structure were examined using 20 microsatellite markers in 37 populations of C. japonica. The locations of glacial refugia were assessed using STRUCTURE analysis, and potential habitats under current and past climate conditions were predicted using SDM. The process of genetic divergence was also examined using the approximate Bayesian computation procedure (ABC) in DIY ABC to test the divergence time between the gene pools detected by the STRUCTURE analysis.ConclusionsThe combined evidence from microsatellites and SDM clearly indicates that climatic changes have shaped the genetic structure of C. japonica. The gene pool detected in northern Tohoku district is likely to have been established by cryptic northern refugia on the coast of the Japan Sea to the west of the Archipelago. The gene pool in Yakushima Island can probably be explained simply by long-term isolation from the other gene pools since the LGM. These results are supported by those of SDM and the predicted divergence time determined using ABC analysis.     

Classification and characteristics of Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis in a nationwide,prospective, inception cohort study

Introduction

We investigated the clinical and serological features of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in Japan using data from a nationwide, prospective, inception cohort study.

Methods

In total, 156 Japanese patients with newly diagnosed AAV were classified according to the European Medicines Agency (EMEA) algorithm with exploratory surrogate markers for AAV-related non-granulomatous pulmonary lesions, predefined as alveolar haemorrhage and interstitial lung disease (ILD), and their clinical and serological features were evaluated.

Results

Using the EMEA algorithm, we identified 14 patients (9.0%) with eosinophilic granulomatosis with polyangiitis (EGPA), 33 (21.2%) with granulomatosis with polyangiitis (GPA), 78 (50.0%) with microscopic polyangiitis and renal-limited vasculitis (MPA/RLV), and 31 (19.9%) with unclassifiable vasculitis. The average ages of patients with EGPA (male/female, 5/9), GPA (12/21), and MPA/RLV (35/43) and unclassifiable (9/22) were 58.0, 63.6, 71.1, and 70.6 years, respectively. Myeloperoxidase (MPO)-ANCA and proteinase-3 ANCA positivity was 50.0% and 0% for EGPA, 54.6% and 45.5% for GPA, 97.4% and 2.6% for MPA/RLV, and 93.5% and 3.2% for unclassifiable, respectively. According to the Birmingham Vasculitis Activity Score (BVAS), cutaneous (71.4%) and nervous system (92.9%) manifestations were prominent in EGPA and ear, nose, and throat manifestations (84.9%) and chest manifestations (66.7%) in GPA. Renal manifestations developed frequently in MPA/RLV (91.0%) and GPA (63.6%). The average serum creatinine levels were 0.71 mg/dL for EGPA, 1.51 mg/dL for GPA, 2.46 mg/dL for MPA/RLV, and 0.69 mg/dL for unclassifiable. The percentages of patients with ILD were 14.3% for EGPA, 9.0% for GPA, 47.4% for MPA/RLV, and 61.3% for unclassifiable. Patients with ILD (n = 61) had significantly lower BVAS (P = 0.019) with fewer ear, nose, and throat and cardiovascular manifestations than patients without ILD (n = 95).

Conclusions

MPO-ANCA-positive MPA/RLV is the most common form of AAV in Japanese patients, and one-half of patients with GPA were positive for MPO-ANCA. ILD is an important clinical manifestation in Japanese patients with AAV. Unclassifiable vasculitis with MPO-ANCA positivity and ILD may represent a novel variant of MPA.

Trial Registration

The University Hospital Medical Information Network Clinical Trials Registry: UMIN000001648. Registered 28 February 2009.     

The Mobile FG Nucleoporin Nup98 Is a Cofactor for Crm1-dependent Protein Export

Nup98 is a mobile nucleoporin that forms distinct dots in the nucleus, and, although a role for Nup98 in nuclear transport has been suggested, its precise function remains unclear. Here, we show that Nup98 plays an important role in Crm1-mediated nuclear protein export. Nuclear, but not cytoplasmic, dots of EGFP-tagged Nup98 disappeared rapidly after cell treatment with leptomycin B, a specific inhibitor of the nuclear export receptor, Crm1. Mutational analysis demonstrated that Nup98 physically and functionally interacts with Crm1 in a RanGTP-dependent manner through its N-terminal phenylalanine-glycine (FG) repeat region. Moreover, the activity of the Nup98-Crm1 complex was modulated by RanBP3, a known cofactor for Crm1-mediated nuclear export. Finally, cytoplasmic microinjection of anti-Nup98 inhibited the Crm1-dependent nuclear export of proteins, concomitant with the accumulation of anti-Nup98 in the nucleus. These results clearly demonstrate that Nup98 functions as a novel shuttling cofactor for Crm1-mediated nuclear export in conjunction with RanBP3.     

Euphausiid distribution, abundance and succession in North Atlantic warm-core ring 82B

Zooplankton collections were made with a multiple opening/closingnet and environmental sensing system (MOCNESS) both day andnight in warm-core ring 82B in the North Atlantic Ocean andat night in the Slope Water between March and August 1982. Speciessuccession of euphausiids in 82B was presented during the lifespanof this warm-core ring, aiming at providing basic informationon possible response of North Atlantic marine ecosystem to globalwarming. Species succession of euphausiids (32 species) in thislong-lived warm-core ring was investigated. Major physical changesof 82B occurred in March to April by convective mixing and thermostadcooling, in April/May by stratification of the surface watersand in August by the interaction with Gulf Stream. Substantialchanges in species composition were observed that correspondedto these physical changes. Four different patterns were foundin temporal change in abundance of warm-water species. Therewere species that decreased in number from March to August,species that decreased from March to June, but increased inAugust, species that increased from Match to August and speciesthat showed no systematic trend. These differences may be attributableto a species tolerance to the thermostad temperature decreaseand their vertical distribution. There was also a large changefrom April to June with ascendance of the transition species,Thysanoessa gregaria. Cold-water species had variable patternsof abundance in 82B and occurred more abundantly in the SlopeWater than in the ring. The monthly percentage decrease in theabundance of warm-water species in 82B was high compared withthat of cold-water species in cold-core rings as a result ofthe more rapid changes in the physical structure and the shorterlifetimes of warm-core rings in the western North Atlantic.