Paragonimiasis in a person whose symptoms were shown 22 years after emigrating to Japan from Laos

We report a patient, a 52-year-old man from Laos, who had come to Japan at 30 years of age, but had maintained a habit of eating raw freshwater crabs. The patient visited a physician for left chest pain in January 2007. Infiltration and mass-like shadows were noted in the left superior and inferior lobes on chest X-ray. Diagnosis could not be made by bronchial brushing, but eggs were present in sputum cytology 3 days after bronchoscopy. Therefore, paragonimiasis was diagnosed. The peripheral eosinophil count had increased to 2550/μl and the serum IgE level was elevated, at 71000 IU/ml. Multiple-dot enzyme-linked immunosorbent assay (ELISA) for specific IgG antibodies in serum was positive for Paragonimus westermani and P. miyazakii. Paragonimiasis may have been caused by the style of Laotian cooking without heating. Because the habit of eating raw freshwater crabs is common in Laos, Laos is one of the countries where paragonimiasis is prevalent. For patients from Laos with lung diseases, differentiation including paragonimiasis is required.     

Primary retroperitoneal neoplasms: CT and MR imaging findings with anatomic and pathologic diagnostic clues.

Primary retroperitoneal neoplasms are a rare but diverse group of benign and malignant tumors that arise within the retroperitoneal space but outside the major organs in this space. Although computed tomography and magnetic resonance imaging can demonstrate important characteristics of these tumors, diagnosis is often challenging for radiologists. Diagnostic challenges include precise localization of the lesion, determination of the extent of invasion, and characterization of the specific pathologic type. The first step is to determine whether the tumor is located within the retroperitoneal space. Displacement of normal anatomic structures of the retroperitoneum is helpful in this regard. For tumors that are located within the retroperitoneum, the next step is to identify the organ of origin. Specific signs, including the "beak sign," the "embedded organ sign," and the "phantom (invisible) organ sign," are useful for this purpose. When there is no definite sign that suggests the organ of origin, the diagnosis of a primary retroperitoneal tumor becomes likely. Awareness of specific patterns of spread, specific tumor components, and tumor vascularity help in further narrowing the differential diagnosis. Attention to these diagnostic clues is essential in making an accurate radiologic diagnosis of primary retroperitoneal tumors and in obtaining clinically significant information. Copyright RSNA, 2003.     

Air-stable, storable, and highly efficient chiral zirconium catalysts for enantioselective Mannich-type, aza Diels-Alder, aldol, and hetero Diels-Alder reactions

For the synthesis of optically active compounds, chiral catalysts have attracted much attention because large quantities of optically active molecules can be prepared from a small amount of a chiral source. However, many chiral catalysts are often unstable in air (oxygen) and/or in the presence of water. This is especially the case in chiral Lewis acid catalysis, because most Lewis acids are air- and moisture-sensitive. Therefore, many catalysts are prepared in situ in an appropriate solvent just before use, and they cannot be stored for extended periods. We have developed air-stable, storable, and highly efficient chiral zirconium Lewis acids. The catalysts promoted asymmetric Mannich-type, aza Diels-Alder, aldol, and hetero Diels-Alder reactions efficiently with high enantioselectivities. A key to stabilizing the catalysts is an appropriate combination of chiral zirconium Lewis acids with molecular sieves, and the zirconium-molecular sieves-combined catalysts can be stored for extended periods in air at room temperature without loss of activity. Moreover, it has been demonstrated that the catalysts can be recovered and reused.     

Phase 1 study of crisaborole in Japanese healthy volunteers and patients with atopic dermatitis

Crisaborole ointment, 2%, is a non-steroidal phosphodiesterase 4 inhibitor for the treatment of mild to moderate atopic dermatitis (AD). This parallel-cohort, phase 1 study was conducted to investigate skin irritation potential and safety of crisaborole in healthy Japanese adults (cohort 1) and the safety and pharmacokinetic profile of crisaborole and metabolites AN7602 and AN8323 in Japanese adults with mild to moderate AD (cohort 2). In cohort 1, 20 healthy volunteers received single applications of crisaborole and vehicle simultaneously on separate locations under 48-h occlusion. In cohort 2, 12 patients with mild to moderate AD received crisaborole (n = 10) or vehicle (n = 2) twice daily for 8 days. Skin irritation and safety were assessed in cohort 1. Pharmacokinetics and safety were assessed in cohort 2. Skin irritation index (scale 0–400) was 40.0 for crisaborole and 5.0 for vehicle. No treatment-emergent adverse events (TEAE) were reported in cohort 1. The most common TEAE in the crisaborole group in cohort 2 were application site irritation (n = 7) and application site pain (n = 4). Crisaborole was rapidly absorbed, with limited systemic exposure between days 1 and 8 that was comparable with that seen in US-based participants in previous trials. Crisaborole had higher skin irritation than vehicle under occlusion in healthy Japanese adults and had an acceptable safety profile in Japanese adults with mild to moderate AD.     

Critical roles of c-Kit tyrosine residues 567 and 719 in stem cell factor-induced chemotaxis: contribution of src family kinase and PI3-kinase on calcium mobilization and cell migration

Stem cell factor (SCF) has crucial roles in proliferation, survival, and differentiation of hematopoietic stem cells and mast cells through binding to c-Kit receptor (KIT). Chemotaxis is another unique function of SCF. However, little is known about the intracellular signaling pathway of SCF/KIT-mediated cell migration. To investigate the signaling cascade, we made a series of 22 KIT mutants, in which tyrosine (Y) residue was substituted for phenylalanine (F) in the cytoplasmic domain, and introduced into BAF3 cells or 293T cells. On stimulation with SCF, BAF3 expressing KIT(WT)(WT) showed cell migration and Ca(2+) mobilization. Among 22 YF mutants, Y567F, Y569F, and Y719F showed significantly reduced cell migration and Ca(2+) mobilization compared to WT. In Y567F, Lyn activation on SCF stimulation decreased and C-terminal Src kinase (Csk) suppressed KIT-mediated Ca(2+) influx and cell migration, suggesting that Y567-mediated Src family kinase (SFK) activation leads to Ca(2+) influx and migration. Furthermore, we found that p38 mitogen-activated protein kinase (p38 MAPK) and Erk1/2 were also regulated by Y567/SFK and involved in cell migration, and that p38 MAPK induced Ca(2+) influx, thereby leading to Erk1/2 activation. In Y719F, the binding of phosphatidylinositol 3'-kinase (PI3K) to KIT was lost and KIT-mediated cell migration and Ca(2+) mobilization were suppressed by PI3K chemical inhibitors or dominant-negative PI3K, suggesting the involvement of Y719-mediated PI3K pathway in cell migration. Combination of Csk and the PI3K inhibitor synergistically reduced cell migration, suggesting the cooperation of SFK and PI3K. Taken together, these results indicate that 2 major KIT signaling pathways lead to cell migration, one is Y567-SFK-p38 MAPK-Ca(2+) influx-Erk and the other is Y719-PI3K-Ca(2+) influx.     

Near-triploidy and near-tetraploidy in hematological malignancies and mutation of the p53 gene

Hyperdiploidy of > or =58 chromosomes is reported in 0.5-3% of hematological malignancies, but reports of near-triploidy (58-80 chromosomes) and near-tetraploidy (81-103 chromosomes), are few. We examined these chromosome abnormalities and analyzed the relationship with the mutation of the p53 gene. Thirty-one of 979 adult patients (3.2%) with hematological malignancies were identified as having near-triploid or near-tetraploid (tri-/tetraploid) chromosomes. These included 11 with B-cell neoplasms, seven with Hodgkin's lymphoma, five with T-cell neoplasms, four with myelodysplastic syndromes and four with acute myeloid leukemias. All patients had concurrent complex chromosome aberrations. Deletion of one allele of the p53 gene was found in two patients and a point mutation of the p53 gene was detected in five patients. Although abnormalities of the p53 gene have been reported in about 10% of hematological malignancies, these were found in seven of 31 (23%) patients with tri-/tetraploidy. These findings suggest that the abnormality of the p53 gene may be closely related with tri-/tetraploidy. The four myelodysplastic syndrome (MDS) patients with tri-/tetraploidy had a significantly worse prognosis than those with diploid cytogenetics (n = 35; P < 0.002). In B-cell neoplasms (n = 3), triploidy was associated with a worse prognosis than tetraploidy (n = 8) and diploidy (n = 130; P < 0.02).     

Gore-Tex jump graft for portal vein thrombosis following living donor liver transplantation

Portal vein thrombosis is a rare surgical complication following liver transplantation, which remains a cause of graft loss and death. We describe here the treatment of portal vein thrombosis following living donor liver transplantation using an extended left lobe graft. The patient was treated with a Gore-Tex vascular jump graft extra-anatomically interposed between the recipient superior mesenteric vein and the donor umbilical vein. This technique allowed the hepatic hilum to be left untouched and supplied suitable blood flow to the hepatic allograft. Our experience suggests that this innovative technical solution can be helpful in the effort to rescue cases of hepatic allograft with vascular complications.     

Usefulness of a 50-meter round walking test for fall prediction in the elderly requiring long-term care

[Purpose] This study aimed to verify the usefulness of a 50-m round walking test developed as an assessment method for walking ability in the elderly. [Subjects] The subjects were 166 elderly requiring long-term care individuals (mean age, 80.5 years). [Methods] In order to evaluate the factors that had affected falls in the subjects in the previous year, we performed the 50-m round walking test, functional reach test, one-leg standing test, and 5-m walking test and measured grip strength and quadriceps strength. [Results] The 50-m round walking test was selected as a variable indicating fall risk based on the results of multiple logistic regression analysis. The cutoff value of the 50-m round walking test for determining fall risk was 0.66 m/sec. The area under the receiver operating characteristic curve was 0.64. The sensitivity of the cutoff value was 65.7%, the specificity was 63.6%, the positive predictive value was 55.0%, the negative predictive value was 73.3%, and the accuracy was 64.5%. [Conclusion] These results suggest that the 50-m round walking test is a potentially useful parameter for the determination of fall risk in the elderly requiring long-term care.Key words: 50-meter round walk test, Local elderly individuals, Falls