Direct Transmission of H. pylori from Challenged to Nonchallenged Mice in a Single Cage

To understand whether direct transmission of H. pylori occurs from infected mouse to noninfected mouse, the system using a mouse model we developed previously was tested. Six nude mice were challenged with H. pylori inocula; one group consisted of one challenged nude mouse 1 week after inoculation raised with four nonchallenged nude mice in a single cage. For the single cage, a polycarbonate cage or a mesh-floor cage was used. Then three groups were kept in a polycarbonate cage and the other three groups kept in a mesh-floor cage to avoid H. pylori transmission through stool. After coraising for 1, 2, or 3 weeks, all mice were sacrificed to determine the existence of H. pylori in the stomach, saliva, and stool by culture or PCR and H. pylori-associated gastritis. RAPD fingerprinting patterns using different primers of isolated strains from challenged and nonchallenged mice were compared to understand the origin of transmitted strains. During 3 weeks after coraising of H. pylori challenged and nonchallenged mice, H. pylori was detected in the stomachs in 3 of 12 nonchallenged mice in the polycarbonate cage and in 2 of 12 nonchallenged mice in the cage with a steel mesh floor. H. pylori was detected from saliva or stool in two nonchallenged, infected mice in the polycarbonate cage. Moreover, RAPD fingerprinting using different primers of the total five strains isolated from five nonchallenged, infected mice in both cages showed the same pattern and concordance with that of the challenged strain and the strains isolated from challenged mice. It is demonstrated that intimate interaction is the cause of H. pylori transmission via saliva and stool.     

Inflammatory Bone Loss in Experimental Periodontitis Induced by Aggregatibacter actinomycetemcomitans in Interleukin-1 Receptor Antagonist Knockout Mice

The interleukin-1 receptor antagonist (IL-1Ra) binds to IL-1 receptors and inhibits IL-1 activity. However, it is not clear whether IL-1Ra plays a protective role in periodontal disease. This study was undertaken to compare experimental periodontitis induced by Aggregatibacter actinomycetemcomitans in IL-1Ra knockout (KO) mice and wild-type (WT) mice. Computed tomography (CT) analysis and hematoxylin-and-eosin (H&E) and tartrate-resistant acid phosphatase (TRAP) staining were performed. In addition, osteoblasts were isolated; the mRNA expression of relevant genes was assessed by real-time quantitative PCR (qPCR); and calcification was detected by Alizarin Red staining. Infected IL-1Ra KO mice exhibited elevated (P, <0.05) levels of antibody against A. actinomycetemcomitans, bone loss in furcation areas, and alveolar fenestrations. Moreover, protein for tumor necrosis factor alpha (TNF-α) and IL-6, mRNA for macrophage colony-stimulating factor (M-CSF), and receptor activator of NF-κB ligand (RANKL) in IL-1Ra KO mouse osteoblasts stimulated with A. actinomycetemcomitans were increased (P, <0.05) compared to in WT mice. Alkaline phosphatase (ALP), bone sialoprotein (BSP), osteocalcin (OCN)/bone gla protein (BGP), and runt-related gene 2 (Runx2) mRNA levels were decreased (P, <0.05). IL-1α mRNA expression was increased, and calcification was not observed, in IL-1 Ra KO mouse osteoblasts. In brief, IL-1Ra deficiency promoted the expression of inflammatory cytokines beyond IL-1 and altered the expression of genes involved in bone resorption in A. actinomycetemcomitans-infected osteoblasts. Alterations consistent with rapid bone loss in infected IL-Ra KO mice were also observed for genes expressed in bone formation and calcification. In short, these data suggest that IL-1Ra may serve as a potential therapeutic drug for periodontal disease.     

A case of paracoccidioidomycosis with severe adrenal insufficiency

Paracoccidioidomycosis (PCM) is the most common systemic fungal disease in central-south America, but is rare in Japan. We experiensed a case of PCM in a patient, who came from Bolivia and presented with mouth pain and reduced dietary intake but no fever. Adrenal insufficiency was diagnosed with extremely high serum adrenocorticotropic hormone (ACTH) and was resolved with hormone supplementation. The PCM was treated with trimethoprim-sulfamethoxazole which was switched to itraconazole and improvement was achieved.     

Impact of glutathione S-transferase T1 gene polymorphisms on acute cellular rejection in living donor liver transplantation

It has previously been demonstrated that glutathione S-transferase T1 (GSTT1) genetic mismatch between recipient and donor is a risk factor for developing immune-mediated hepatitis following liver transplantation and for antibody-mediated rejection in renal transplantation. Little is known whether the GSTT1 gene polymorphism affects the incidence of acute cellular rejection (ACR) following living donor liver transplantation (LDLT). Patients underwent LDLT at Nagoya University or Kyoto University, Japan, between 2004 and 2009. Genotyping of GSTT1 genes (null or present genotype) was conducted in recipients and donors. A total of 155 LDLT cases were examined. Forty-seven recipients (30.3%) developed early ACR. There was no association of recipient GSTT1 genotype with ACR incidence. However, ACR incidence was significantly higher in recipients transplanted from GSTT1 present genotype donors than in those transplanted from GSTT1 null genotype donors [odds ratio (OR) = 2.64, 95% confidence interval (CI) = 1.12–5.83, p = 0.016]. Moreover, GSTT1 recipient/donor genotype mismatch (present/null or null/present) was significantly associated with ACR development (OR = 2.28, 95% CI = 1.12–4.61, p = 0.022). The genotyping of GSTT1 in recipients and donors might be useful to stratify the liver transplant recipients according to risk of ACR.     

In vivo bioluminescence imaging of magnetically targeted bone marrow‐derived mesenchymal stem cells in skeletal muscle injury model

The purpose of this study is to clarify the kinetics of transplanted mesenchymal stem cells (MSCs) in rat skeletal muscle injury model and the contribution of the magnetic cell delivery system to muscle injury repair. A magnetic field generator was used to apply an external magnetic force to the injury site of the tibia anterior muscle, and 1 × 10⁶ MSCs labeled with ferucarbotran–protamine complexes, which were isolated from luciferase transgenic rats, were injected into the injury site. MSCs were injected with and without an external magnetic force (MSC M+ and MSC M? groups, respectively), and phosphate‐buffered saline was injected into injury sites as a control. In vivo bioluminescence imaging was performed immediately after the transplantation and, at 12, 24, and 72 h, and 1 and 4 weeks post‐transplantation. Also, muscle regeneration and function were histologically and electromechanically evaluated. In vivo bioluminescence imaging showed that the photon of the MSC M+ group was significantly higher than that of the MSC M? group throughout the observation period. In addition, muscle regeneration and function in the MSC M+ group was histologically and functionally better than that of the MSC M? group. The results of our study indicated that magnetic cell delivery system may be of use in directing the transplanted MSCs to the injury site to promote skeletal muscle regeneration. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 754–759, 2013     

Atypical Pneumocystis jiroveci pneumonia with multiple nodular granulomas after rituximab for refractory nephrotic syndrome

Background

Rituximab, an anti-CD20 antibody that targets B cells, is a promising agent against steroid-dependent and steroid-resistant nephrotic syndrome in children.

Case-Diagnosis/Treatment

We report a 3-year-old boy who presented with atypical Pneumocystis jiroveci pneumonia (PCP) following administration of rituximab for refractory nephrotic syndrome. He had received cyclosporine and daily prednisolone for over 1?year. Following rituximab therapy, a hazy shadow was observed on his chest X-ray. Chest-computed tomography revealed multiple nodular lesions in bilateral lungs, although his clinical symptoms were subtle. PCR analysis demonstrated the presence of Pneumocystis DNA in his bronchoalveolar lavage. Lung wedge resection of the nodular lesion exhibited granulomas containing a few cysts of P. jiroveci that primarily consisted of T cells and histiocytes and lacked B cells. A deficiency of B cells following rituximab treatment suggests a dramatic effect on the immune response and, therefore, could result in granulomatous PCP. Nodular granulomatous lesions of PCP comprise an emerging concept previously reported in adults with hematological disease, bone marrow transplant, or treatment with rituximab. We report the first pediatric case of nodular PCP. Granulomatous PCP can be life-threatening. Moreover, bronchoalveolar lavage often fails to demonstrate the presence of P. jiroveci DNA. Wedge biopsy is warranted for definitive diagnosis. Our patient fully recovered with sulfamethoxazole/trimethoprim treatment because of early detection.

Conclusions

The indication of rituximab for refractory nephrotic syndrome has increased recently. Therefore, recognition of the risk of atypical PCP is important. Our findings suggest that PCP prophylaxis should be considered following rituximab therapy.     

NATURAL SKIN REDUCTION AND BREAST RECOVERY USING A TISSUE EXPANDER AFTER ENUCLEATION OF A GIANT BREAST TUMOUR

We report a new use of the tissue expander for reshaping a breast after resection of a giant tumour. After resection of giant fibroadenomas, two patients had expanders inserted into the tissue defect and gradually reduced in size over five months. This facilitated healing and natural skin shrinkage and resulted in a natural shape and size.     

Isoform transition from four-repeat to three-repeat tau underlies dendrosomatic and regional progression of neurofibrillary pathology

Regional progression of neurofibrillary tangles (NFTs) around the hippocampus was traced on thick sections double immunofluorolabeled with RD3 and RD4 antibodies, specific for three- and four-repeat tau, respectively. As reported, the cubic density of all tau-positive neurons was predominant in the entorhinal cortex and cornu ammonis (CA)1, and decreased progressively to the CA2–4 subregions. Among the three isoform profiles (RD3+/4?, RD3+/4+, and RD3?/4+), this regional gradient was replicated with RD3+/4? and RD3+/4+ neurons, while RD3?/4+ neurons exhibited the reverse gradient. Comparison of the subregion pairs confirmed a consistent profile shift along this gradient in every case regardless of the abundance of NFTs. To clarify the underlying mechanism of this regional profile shift, intraneuronal intensity of RD3 and RD4 immunoreactivity (IR) was quantified. Although their intensities were both lower in dendrites than in the soma, this gradient was steeper with RD4, leaving RD3 IR in dendrites. Dendritic arborization was abundant in RD3?/4+ pretangles, attenuated in RD3+/4+ neurons, and further attenuated in RD3+/4? ghost tangles. These findings suggest that dendritic RD4 IR retracts first, leaving RD3 IR in the dendrites. Taken together, this dendrite-oriented retraction initiates the gradual shift from RD3?/4+ pretangle neurons to RD3+/4? ghost tangles by way of RD3+/4+ NFTs. This intraneuronal profile shift may be a basis for the regional gradation featured by the similar profile shift during progression of NFT pathology.