Neurological disorder and excessive accumulation of calcium in brain of clinically vitamin A-deficient rats

Three groups of rats were fed two types of synthetic diets for 52 d. The—A group was allowed free access to a vitamin A-deficient diet and showed classical signs of vitamin A deficiency. The brain was the only organ in our experiment where no significant weight difference was present among the three groups. In the brain, calcium concentration was significantly higher in the—A group when compared with the PF (Pair-fed; allowed restricted amount of control diet) and +A groups (allowed free access to control diet). In the tibia, calcium and magnesium concentrations were significantly lower in the—A group when compared with other two groups. Excessive accumulation of calcium in brain and apparently similar unbalance in bone, mineral concentration were observed in central nervous system (CNS) degenerative diseases. Our results suggest that abnormal metabolism of calcium and magnesium in some tissues and excessive accumulation of calcium in brain may be responsible for the development of neurological disorders in vitamin A-deficient rats.     

Effects of muscimol and baclofen on levels of monoamines and their metabolites in the El mouse brain

We compared the changes in monoamines and their metabolites in the El mouse brain induced by GABA-A and GABA-B receptor agonists. Muscimol was used as a GABA-A receptor agonist, and baclofen as a GABA-B receptor agonist. Muscimol (3 mg/kg) significantly increased the DOPAC level in all parts of the mouse brain and the HVA level in the cortex, striatum, and midbrain. No significant change was observed in the dopamine (DA) level. These findings suggest that muscimol may accelerate both the synthesis and catabolism of DA. Baclofen (20 mg/kg) increased the DA level in the hippocampus and midbrain, and the DOPAC level in the hippocampus. Muscimol increased 5-HIAA levels and decreased 5-HT levels. This result suggests that 5-HT metabolism is accelerated by muscimol. No change in 5-HT or 5-HIAA levels was induced by baclofen. The GABA-A receptor system seems to have a potent effect not only on DA neurons, but on 5-HT neurons. However, the GABA-B receptor system appears to have almost no effect on 5-HT neurons, though it appears to have some effect on DA neurons.     

Trypanosoma gambiense: Immune responses of neonatal rats receiving antibodies from the female

Offspring of control female rats received colostrum from females immune to Trypanosoma gambiense after birth. Subsequently, these offspring had high titers of agglutinating and phagocytosis-promoting activities in their sera. They were not protected against challenge infection, although a delay of parasitemia and extended survival were often observed. On the other hand, the offspring of immune females, which had received colostrum from control females after birth, showed low agglutinating and phagocytosis-promoting activities in their sera; 50% were protected against infection. It was concluded that antibodies (IgG) passing through the placenta of immunized females were more effective than antibodies (IgA) derived from colostrum from immunized females in protecting offspring against trypanosome infection. Phagocytosis-promoting activity was detected in both colostral IgA-rich fractions from the colostra of immunized females and serum IgA-rich fractions from the control females' offspring, which had received colostrum from immune females. Pepsin digestion resulted in the loss of such activity. It is possible that the phagocytosis-promoting activity of IgA antibodies was not present in the products obtained by means of pepsin treatment.     

Cytotoxicity and apoptosis produced by troglitazone in human hepatoma cells.

Troglitazone is an antidiabetic agent that increases the insulin sensitivity of target tissues in non-insulin-dependent diabetes mellitus. It has been reported that troglitazone causes severe hepatic injury in certain individuals. In the present study, the mechanism for the hepatic injury by troglitazone was investigated with human hepatoma cell lines. HepG2 cells were incubated with troglitazone, its metabolites M-1 (sulfate), M-2 (gulucronide), M-3 (quinone), and other thiazolidinediones (pioglitazone and rosiglitazone). Troglitazone exhibited time- and concentration-dependent cytotoxicity and M-3 also exhibited weak cytotoxicity. Troglitazone induced apoptotic cell death characterized by internucleosomal DNA fragmentation and nuclear condensation. As other thiazolidinediones, pioglitazone and rosiglitazone, did not induce cell death and apoptosis in the present study, the affinity to PPARgamma may not affect the induction of apoptosis by troglitazone. These results suggest that troglitazone induces apoptotic hepatocyte death which it may be one of the factors of liver injury in humans.     

EFA6A,an Exchange Factor for Arf6, Regulates NGF-Dependent TrkA Recycling From Early Endosomes and Neurite Outgrowth in PC12 Cells

Endosomal trafficking of TrkA is a critical process for nerve growth factor (NGF)-dependent neuronal cell survival and differentiation. The small GTPase ADP-ribosylation factor 6 (Arf6) is implicated in NGF-dependent processes in PC12 cells through endosomal trafficking and actin cytoskeleton reorganization. However, the regulatory mechanism for Arf6 in NGF signaling is largely unknown. In this study, we demonstrated that EFA6A, an Arf6-specific guanine nucleotide exchange factor, was abundantly expressed in PC12 cells and that knockdown of EFA6A significantly inhibited NGF-dependent Arf6 activation, TrkA recycling from early endosomes to the cell surface, prolonged ERK1/2 phosphorylation, and neurite outgrowth. We also demonstrated that EFA6A forms a protein complex with TrkA through its N-terminal region, thereby enhancing its catalytic activity for Arf6. Similarly, we demonstrated that EFA6A forms a protein complex with TrkA in cultured dorsal root ganglion (DRG) neurons. Furthermore, cultured DRG neurons from EFA6A knockout mice exhibited disturbed NGF-dependent TrkA trafficking compared with wild-type neurons. These findings provide the first evidence for EFA6A as a key regulator of NGF-dependent TrkA trafficking and signaling.     

Microarray analysis of tonsils in immunoglobulin A nephropathy patients

Background

Recently, combination of tonsillectomy and steroid pulse therapy was reported to be effective as the treatment of the immunoglobulin A nephropathy (IgAN). However, the gene expression difference between the tonsils in patients with IgAN and those in control patients is not established.

Methods

We performed tonsillectomy combined with steroid pulse as a treatment to IgAN, analyzed the gene expression in the tonsils (N = 23) using microarray, compared with those with patients suffering from chronic tonsillitis (N = 22). From some candidate genes related with IgAN, we confirmed the apolipoprotein B messenger RNA-editing enzyme catalytic polypeptides 2 (APOBEC2) gene expression in the tonsil and we also analyzed its expression levels and clinical features.

Results

Up-regulated genes seem to be categorized into two groups. One group belongs to the muscle related genes which might be caused by structural differences. The other group includes the immune system-related genes, such as APOBEC2, CALB2, DUSP27, and CXCL11. APOBEC2 was positively stained in the epithelium and the peripheral region of the germinal center in both tonsils. APOBEC2 expression level was negatively related with serum igg level, but did not correlate with clinical course after tonsillectomy.

Conclusion

We confirmed gene expression differences related with immune system and muscle structure. The APOBEC2 was confirmed to be elevated in the tonsils with IgAN patients, and the gene expression level was negatively related with serum igg level in overall patients. These results might be helpful to reveal the mechanism of IgAN.     

Pectate Lyase Pollen Allergens: Sensitization Profiles and Cross-Reactivity Pattern

BackgroundPollen released by allergenic members of the botanically unrelated families of Asteraceae and Cupressaceae represent potent elicitors of respiratory allergies in regions where these plants are present. As main allergen sources the Asteraceae species ragweed and mugwort, as well as the Cupressaceae species, cypress, mountain cedar, and Japanese cedar have been identified. The major allergens of all species belong to the pectate lyase enzyme family. Thus, we thought to investigate cross-reactivity pattern as well as sensitization capacities of pectate lyase pollen allergens in cohorts from distinct geographic regions.MethodsThe clinically relevant pectate lyase pollen allergens Amb a 1, Art v 6, Cup a 1, Jun a 1, and Cry j 1 were purified from aqueous pollen extracts, and patients´ sensitization pattern of cohorts from Austria, Canada, Italy, and Japan were determined by IgE ELISA and cross-inhibition experiments. Moreover, we performed microarray experiments and established a mouse model of sensitization.ResultsIn ELISA and ELISA inhibition experiments specific sensitization pattern were discovered for each geographic region, which reflected the natural allergen exposure of the patients. We found significant cross-reactivity within Asteraceae and Cupressaceae pectate lyase pollen allergens, which was however limited between the orders. Animal experiments showed that immunization with Asteraceae allergens mainly induced antibodies reactive within the order, the same was observed for the Cupressaceae allergens. Cross-reactivity between orders was minimal. Moreover, Amb a 1, Art v 6, and Cry j 1 showed in general higher immunogenicity.ConclusionWe could cluster pectate lyase allergens in four categories, Amb a 1, Art v 6, Cup a 1/Jun a 1, and Cry j 1, respectively, at which each category has the potential to sensitize predisposed individuals. The sensitization pattern of different cohorts correlated with pollen exposure, which should be considered for future allergy diagnosis and therapy.     

Relationship between interspecific pollen transfer and pistil length in sympatric congeners,Clerodendrum trichotomum and C. izuinsulare

Interspecific pollen transfer (IPT) often leads to reproductive interference. Although character displacement of reproductive traits in plants is often considered a consequence of reproductive interference, few studies have tested whether intraspecific variation in floral morphology changes the intensity of reproductive interference among pollinator-sharing plants. We investigated whether intraspecific variation in pistil length changes the proportion of IPT (interspecific pollen transfer) in sympatric populations of Clerodendrum trichotomum and C. izuinsulare on the two islands. On Toshima Island, C. izuinsulare flowers with shorter pistils were significantly less likely to receive C. trichotomum pollen, and there was a slight tendency for longer pistiles of C. trichotomum flowers to receive less C. izuinsulare pollen, suggesting that IPT has caused character displacement in pistil length in these congeneric plants. In contrast, we did not detect any relationship between pistil length and the proportion of IPT for the two species on Niijima Island. The discrepancy between the islands may reflect differences in pollinator assemblages.