Roles of the Maltese cross form in the development of parasitemia and protection against Babesia microti infection in mice

Babesia microti, a hemoprotozoan parasite of rodents, is also important as a zoonotic agent of human babesiosis. The Maltese cross form, which consists of four masses in an erythrocyte, is characteristic of the developmental stage of B. microti. Monoclonal antibody (MAb) 2-1E, which specifically recognizes the Maltese cross form of B. microti, has been described previously. In the present study, we examined the roles of the Maltese cross form during the infectious course of B. microti in mice. The number of the Maltese cross form increased in the peripheral blood of infected mice prior to the peak of parasitemia. With confocal laser scanning microscopy, MAb 2-1E was found to be reactive with the ring form, with the parasites undergoing transformation to the Maltese cross form and subsequent division, and also with extracellular merozoites. Furthermore, the Maltese cross form-related antigen (MRA) gene was isolated from a B. microti cDNA library by immunoscreening with MAb 2-1E, and the nucleotide sequence was determined. Genomic analyses indicated that the MRA gene exists as a single-copy gene in B. microti. Immunization of mice with recombinant MRA induced significant protective immunity against B. microti infection. These findings indicate that the Maltese cross form plays important roles in both the development of parasitemia and the protective response against the infection.     

Spontaneous perforation of choledochal cyst: a case with unusual distribution of fluid in the retroperitoneal space

Images of perforated choledochal cysts typically show an intraperitoneal fluid collection. We report a case with, in addition to free intraperitoneal fluid, fluid collection in the right-side anterior pararenal and perirenal spaces. Surgery confirmed the presence of a perforation at the junction of the cystic duct and the common bile duct. This perforation may explain the biliary leakage extending into the free peritoneal space as well as into the anterior pararenal space and the hepatoduodenal ligament. Anterior pararenal and perirenal spaces communicate with the infrarenal space, and this may result in extension of the fluid into the perirenal space from the anterior pararenal space.     

Unique three-way translocation, t(3;14;18)(q27;q32;q21), in follicular lymphoma

A 43-year-old woman was diagnosed as having stage IV follicular lymphoma. Phenotypically, the lymphoma cells were CD5(-), CD10(+), CD19(+), CD20(+), CD23(-), HLA-DR(+), and IgM-lambda(+). Conventional chromosomal analysis showed a three-way t(3;14;18)(q27;q32;q21) in the lymphoma cells, which was confirmed by spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH). Immunohistochemistry revealed that both BCL2 and BCL6 proteins were expressed in the lymphoma cells, whereas only the BCL6 gene, and not the BCL2 gene, was rearranged by Southern blotting. The patient received combination chemotherapy and has been well for 3 years. This is the first reported case showing a three-way translocation involving 2 major lymphoma-specific abnormalities, 3q27 and t(14;18)(q32;q21).     

Characterization of htAKR, a novel gene product in the aldo-keto reductase family specifically expressed in human testis

In human testis, expression of a novel member of the aldo-keto reductase family was identified. Based on its testis-specific expression, we termed this protein human testis aldo-keto reductase (htAKR). In addition to four major isoforms, the existence of multiple alternatively spliced products of htAKR was detected using RT-PCR followed by nested PCR. htAKR was a homologue of mouse liver keto-reductase, AKR1E1, with close similarity in their genomic organizations. htAKR4, the longest isoform, was expressed as a non-fused native form. It exhibited a limited activity toward 9,10-phenanthrenequinone, while no activity toward the steroids or prostaglandins was demonstrated. Using the laser capture microdissection technique and RT-PCR, expression of htAKR was detected in testicular germ cells as well as in interstitial cells. The levels of htAKR mRNA in the tissues obtained from seminoma were much lower than those in normal testes. A significant decline in the htAKR expression was observed when NEC8, a cell line originated from a human testicular germ cell tumour, was exposed to phorbol 12-myristate 13-acetate or 5alpha-dihydrotestosterone. These results indicate that the expression of htAKR, down-regulated in the testicular tumour, is possibly controlled by mitogenic and hormonal signals.     

Identification of ribosomal phosphoprotein P0 of Neospora caninum as a potential common vaccine candidate for the control of both neosporosis and toxoplasmosis

The characterization of the cross-reactive antigens of two closely related apicomplexan parasites, Neospora caninum and Toxoplasma gondii, is important to elucidate the common mechanisms of parasite-host interactions. In this context, a gene encoding N. caninum ribosomal phosphoprotein P0 (NcP0) was identified by immunoscreening of a N. caninum tachyzoite cDNA expression library with antisera from mice immunized with T. gondii tachyzoites. The NcP0 was encoded by a gene with open reading frame of 936 bp, which encoded a protein of 311 amino acids. The NcP0 gene existed as a single copy in the genome and was interrupted by a 432 bp intron. The NcP0 showed 94.5% amino acid identity to T. gondii P0 (TgP0). Anti-recombinant NcP0 (rNcP0) sera recognized a native parasite protein with a molecular mass of 34 kDa in Western blot analysis. Immunofluorescence analysis showed that the NcP0 was localized to the surface of N. caninum tachyzoites. A purified anti-rNcP0 IgG antibody inhibited the growth of N. caninum and T. gondii in vitro in a concentration-dependent manner. These results indicate that P0 is a cross-reactive antigen between N. caninum and T. gondii and a potential common vaccine candidate to control both parasites.     

Spermatogenesis-specific association of SMCY and MSH5

The status of chromatin during spermatogenesis is dynamically regulated by specific histone codes or stage-specific histone changes. The functional links between such epigenetic regulation and proteins regulating meiosis are largely unknown. In mammals, genes encoded on the Y chromosome are thought to possess male-specific biological functions. While genes located within the azoospermia factor region (AZF) are known to be involved in spermatogenesis, the physiological function of individual genes is not known. SMCY is a gene mapped to the AZF, and in this report, we analyzed the function of SMCY protein during spermatogenesis. Biochemical identification of the proteins with which it interacted showed that SMCY formed a distinct complex with MSH5, a critical meiosis-regulatory protein in the human testicular germ cell line, NEC8. As anticipated, histone H3K4 demethylase activity was detected. Immunohistochemical analysis revealed the co-localization of SMCY with MSH5 at a specific stage of meiotic prophase progression during murine spermatogenesis. Our results suggest that SMCY may have a male-specific function as a histone H3K4 demethylase by recruiting a meiosis-regulatory protein to condensed DNA.     

Rheumatoid factor is correlated with disease activity and inflammatory markers in antineutrophil cytoplasmic antibody-associated vasculitis

Background

Some patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) also have positivity of rheumatoid factor (RF). However, the clinical significance of this occurrence remains unknown in AAV patients. The aim of this study was to clarify an association between the presence of RF and clinical features in patients with AAV.

Results

Forty-seven patients diagnosed with AAV who were not complicated with RA were enrolled in this study. We compared clinical manifestations of AAV between an RF-positive subset (n?=?29) and an RF-negative subset (n?=?18). The Birmingham Vasculitis Activity Score (BVAS) was higher (P?=?0.026) in the RF-positive subset than in the RF-negative subset. The levels of CRP and ESR were higher in the RF-positive patients (P?=?0.020 and P?=?0.007, respectively) compared to the RF-negative subset. IgM-RF titers were significantly correlated with the BVAS (r?=?0.50, P?=?0.0004). In addition, the IgM-RF titers had significant correlations with the levels of CRP (r?=?0.41, P?=?0.004), ESR (r?=?0.39, P?=?0.016), IgM (r?=?0.36, P?=?0.016) and IgG (r?=?0.37, P?=?0.015). The frequency of commencement of dialysis therapy, usage of mechanical ventilation and mortality were higher in the RF-positive subset than in the RF-negative subset.

Conclusions

In patients with AAV, RF titers were significantly correlated with disease activity and the levels of inflammatory markers. The presence of RF could be a poor prognostic factor in patients with AAV.

     

Role of the vestibular system in the arterial pressure response to parabolic-flight-induced gravitational changes in human subjects

This study examined how different weighting coefficients imposed on individual finger force regulate bimanual finger force coordination patterns under the influence of bilateral coupling and visual information of the force output. The weighted sum of the two forces was computed as the total force output to match two target force levels (10% and 35% MVC) in separate conditions, and visual feedback of the total force output was provided in the experiment. The results revealed higher performance error at 35% in comparison with 10% MVC with the greatest error at the unequal coefficient setting. The correlation between the individual forces and the force output ratios correlated nonlinearly with the weighting coefficient ratios; however, the extent of change was much smaller than the coefficient ratios. The results suggest that bilateral coupling and task constraints interact to determine the coordination strategy. The irregularity of the individual finger forces increased with the weighting coefficient while the irregularity of the total force remained the same. The results support the hypothesis that the organization of redundant motor coordination patterns emerges from the interactive effect of the constraints on movement.