MAEBL is essential for malarial sporozoite infection of the mosquito salivary gland

Malarial sporozoites mature in the oocysts formed in the mosquito midgut wall and then selectively invade the salivary glands, where they wait to be transmitted to the vertebrate host via mosquito bite. Invasion into the salivary gland has been thought to be mediated by specific ligand-receptor interactions, but the molecules involved in these interactions remain unknown. MAEBL is a single transmembrane-like protein that is structurally related to merozoite adhesive proteins. We found MAEBL of the rodent malaria parasite, Plasmodium berghei, to be specifically produced by the sporozoites in the oocyst and localized in their micronemes, which are secretory organelles involved in malarial parasite invasion into the host cell. A targeted disruption experiment of the P. berghei MAEBL gene revealed that it was essential for sporozoite infection of the salivary gland and was involved in the attachment to the salivary gland surface. In contrast, the disruption of the MAEBL gene did not affect sporozoite motility in vitro nor infectivity to the vertebrate host. These results suggest that P. berghei MAEBL is a sporozoite attachment protein that participates in specific binding to and infection of the mosquito salivary gland.     

Facial nerve regeneration using basic fibroblast growth factor‐impregnated gelatin microspheres in a rat model

Basic fibroblast growth factor (bFGF) plays a crucial role in the regeneration of peripheral nerve defects by affecting nerve cells, Schwann cells and fibroblasts, and by promoting axon outgrowth from the proximal nerve stump. However, the use of exogenous bFGF for in vivo regeneration of the peripheral nerves is limited by its short in vivo half‐life. In this study, a drug delivery system for bFGF was developed that uses acidic gelatin hydrogel, which sustainably released bFGF in vivo over several weeks; its ability to promote peripheral nerve regeneration was also examined. In 8‐week‐old Lewis rats, 7‐mm gaps were made in the buccal branch of the left facial nerve. Acidic gelatin hydrogel microspheres (10 µl) with or without bFGF (50 µg) were infused into a 10 mm silicone tube using a micropipette, and the silicone tube was then implanted into the gap. A 1‐mm long nerve stump was inserted into each end of the tube. Histological examination at 7 weeks after implantation revealed (1) a significantly increased rate of nerve regeneration, (2) inducement of a number of regenerating nerve axons, and (3) a better degree of maturation of nerve axons in the bFGF microsphere group than that in the bFGF‐free microsphere group. Copyright © 2014 John Wiley & Sons, Ltd.     

Identification of oxytetracycline as a chondrogenic compound using a cell-based screening system

To effectively treat degenerative joint diseases including osteoarthritis (OA), small chemical compounds need to be developed that can potently induce chondrogenic differentiation without promoting terminal differentiation. For this purpose, we screened natural and synthetic compound libraries using a Col2GFP-ATDC5 system and identified oxytetracycline (Oxy) as a chondrogenic compound. Oxy induced cartilaginous matrix synthesis and mRNA expressions of chondrocyte markers in ATDC5 cells. In addition, Oxy suppressed mineralization and mRNA expressions of terminal chondrocyte differentiation markers in ATDC5 cells, primary chondrocytes, and cultured metatarsal bones. Oxy’s induction of Col2 mRNA expression was decreased by the addition of Noggin and was increased by the addition of BMP2. Furthermore, Oxy increased mRNA expression of Id1, Bmp2, Bmp4, and Bmp6. These data suggest that Oxy induces chondrogenic differentiation in a BMP-dependent manner and suppresses terminal differentiation. Oxy may be useful for treatment of OA and also for regeneration of cartilage tissue.     

Upper extremity deep vein thrombosis treated by a filter in the superior vena cava placed intraoperatively to allow safe esophageal surgery: Report of a case

Upper extremity deep vein thrombosis (UEDVT) is an infrequent but dangerous vascular event, especially for patients undergoing thoracic surgery. However, there is no standard perioperative management to reduce the risk of pulmonary thromboembolism in such patients. We describe how we performed successful esophagectomy in a patient with UEDVT treated by placing a filter in the superior vena cava during surgery.     

Prognosis of Japanese Metastatic Renal Cell Carcinoma Patients in the Cytokine Era: A Cooperative Group Report of 1463 Patients

Background

Incidence rate of renal cell carcinoma (RCC) differs among countries. The rates of Asian countries are lower than those of countries in North America or Europe but are exceptionally high in Japanese males. Approximately 30% of patients with RCC have metastasis at initial diagnosis, and another 30% have metastasis after nephrectomy. Clinical studies of risk factors in patients with metastatic RCC (mRCC) are mainly based on data from non-Asian patients.

Objectives

We aimed to investigate the prognosis of Japanese patients and their prognostic factors.

Design, setting, and participants

The subjects of this study were 1463 patients who were clinically diagnosed with RCC with metastasis in 40 Japanese hospitals between January 1988 and November 2002.

Measurements

The primary end point was overall survival calculated from first diagnosis of mRCC to death or last follow-up. We also investigated the relationship between survival and clinical features.

Results and limitations

The median overall survival time was 21.4 mo. The estimated survival rates at 1, 3, 5, and 10 yr were 64.2%, 35.2%, 22.5%, and 9.1%, respectively; they contrasted with data from the United States of 54%, 19%, 10%, and 6%, respectively for the same periods. A high percentage of patients had undergone nephrectomy (80.5%) and metastasectomy (20.8%), both of which were shown to prolong survival.

Conclusions

The median survival time in the present study was approximately twice as long as that of previous studies from North America or Europe. Early diagnosis of metastasis, nephrectomy, metastasectomy, and cytokine-based therapy seemed to improve the prognosis of RCC patients in the present study.     

Accelerated expression of a Myc target gene Mina53 in aggressive hepatocellular carcinoma

Aim: Expressions of the myc target genes Mina53 and mimitin are high in esophageal squamous cell carcinoma and colon cancer, and their relationship to cell proliferation and patient prognosis has been reported. Because c‐myc gene expression is closely related to hepatocellular carcinoma (HCC) growth or formation and/or maintenance, we examined the Mina53 and mimitin expressions in HCC. Methods: Surgically resected 53 HCC tissues were immunohistochemically examined for Mina53 and mimitin expressions and their relationship to clinicopathological factors. Results: Diffuse Mina53 expression was observed in the nuclei of cancer cells in the tumor nodule, but was often strong at the periphery of tumor nodules. Diffuse or scattered expression of mimitin was observed in the cytoplasm of HCC cells in tumor nodules. Mina53 expression was higher in poorly differentiated HCC than in well‐differentiated HCC, and significant relationship to histological grade was observed. The cases with a high Mina53 expression also had a high expression of a proliferation marker MIB‐1. This suggested the involvement of Mina53 in cell proliferation. Mina53 expression was high in the tumors of >2 cm of diameter than in ≤2 cm (P < 0.01). Mimitin expression tended to be high in tumors of >2 cm, but no significant relationship was observed either to histological grade, MIB‐1 expression, or the other clinicopathologic factors. Conclusions: Our findings suggested that Mina53 expression is accelerated in HCC with a lower histological grade, with cell proliferation capability, or with a larger diameter, and Mina53 is related to biological malignancy of HCC.     

Effect of total knee arthroplasty on disease activity in patients with established rheumatoid arthritis: 3-year follow-up results of combined medical therapy and surgical intervention

Though excellent clinical results have been reported for total knee arthroplasty (TKA) in rheumatoid arthritis (RA) patients, the medium-term effect of TKA on RA disease activity remains unknown. This analysis aimed to assess changes in disease activity after TKA in patients with established RA. We analyzed the systemic effects of TKA on RA disease activity 3 years after intervention. Routine clinical and laboratory assessments were recorded at baseline, less than less than 0.5 years after TKA, and 3 years after TKA. Of the registered RA patients, 130 TKA patients were followed for 3 years after surgery. RA disease activity was measured using the Disease Activity Score 28 (DAS28). Patients were divided into three groups by preoperative baseline DAS28: low (DAS28 ≤ 3.2, n = 8), moderate (DAS28 > 3.2 but ≤5.1, n = 68), and high (DAS28 > 5.1, n = 54) disease activity. The postoperative DAS28 (<0.5 years [DAS1] and 3 years [DAS3] after surgery) scores of each patient were compared to their baseline (DAS0) scores using the paired t-test. The mean DAS28 decreased from 4.85 (DAS0) to 4.14 (DAS1; P = 1.07E-12), and this decrease was sustained at 3 years (DAS3 = 3.97; P = 4.73E-15). Subanalysis results revealed a systemic effect of TKA on disease activity in patients with moderate or high disease activity (DAS0 = 4.33; DAS1 = 3.72 [P = 5.94E-06]; DAS3 = 3.81 [P = 7.89E-06]; and DAS0 = 5.79; DAS1 = 4.86 [P = 1.14E-08]; DAS3 = 4.37 [P = 1.03E-11], respectively). While no significant changes in medication were noted, the average dose of prednisolone tended to decrease over time. We conclude that TKA, which is known to result in good clinical outcomes for damaged knees, has a secondary systemic effect on RA disease activity. Combination therapy consisting of medical treatment and surgical intervention is thought to effectively improve the condition of RA patients who have destructive arthritis in the knee joint, with the effect lasting for at least 3 years.     

Accurate and simple method for quantification of hepatic fat content using magnetic resonance imaging: a prospective study in biopsy-proven nonalcoholic fatty liver disease

Background

To assess the degree of hepatic fat content, simple and noninvasive methods with high objectivity and reproducibility are required. Magnetic resonance imaging (MRI) is one such candidate, although its accuracy remains unclear. We aimed to validate an MRI method for quantifying hepatic fat content by calibrating MRI reading with a phantom and comparing MRI measurements in human subjects with estimates of liver fat content in liver biopsy specimens.

Methods

The MRI method was performed by a combination of MRI calibration using a phantom and double-echo chemical shift gradient-echo sequence (double-echo fast low-angle shot sequence) that has been widely used on a 1.5-T scanner. Liver fat content in patients with nonalcoholic fatty liver disease (NAFLD, n = 26) was derived from a calibration curve generated by scanning the phantom. Liver fat was also estimated by optical image analysis. The correlation between the MRI measurements and liver histology findings was examined prospectively.

Results

Magnetic resonance imaging measurements showed a strong correlation with liver fat content estimated from the results of light microscopic examination (correlation coefficient 0.91, P < 0.001) regardless of the degree of hepatic steatosis. Moreover, the severity of lobular inflammation or fibrosis did not influence the MRI measurements.

Conclusions

This MRI method is simple and noninvasive, has excellent ability to quantify hepatic fat content even in NAFLD patients with mild steatosis or advanced fibrosis, and can be performed easily without special devices.