Interstitial Pneumonia Developed in HTLV-I Carriers: Report of Two Cases

Two carriers of human T-cell lymphotropic virus type I (HTLV-I) with interstitial pneumonia are described. The first case, a 60-year-old man, was admitted with cough and dyspnea on exertion. Light microscopy of a lung specimen obtained by a transbronchial lung biopsy (TBLB ) showed thickening of the alveolar walls with infiltration of lymphocytes and fibrosis of the pulmonary parenchyma. Immunohistochemical analysis of the TBLB specimen showed positive staining in the lymphocytes for UCHL-1. This case was suspected as HTLV-I associated bronchiolo-alveolar disorder. The second case, a 74-year-old man, visited our hospital because of a persistent productive cough and dyspnea on exertion. Light microscopy of the TBLB showed a slight thickening of the alveolar walls and fibrosis of the pulmonary parenchyma with minimal infiltration of lymphocytes. Only 2.2% of the bronchoalveolar lavage fluid consisted of lymphocytes. The findings of the second case suggest that some factors other than T-lymphocytes may be related with the development of interstitial pneumonia in HTLV-I carriers. Interstitial pneumonia in HTLV-I carriers may be caused by as yet undiscovered mechanisms. A cohort study involving residents of an area where HTLV-I is endemic should be conducted to clarify the mechanism of pulmonary involvement in HTLV-I carriers

A nocturnal decline of salivary pH associated with airway hyperresponsiveness in asthma

Salivary pH is associated with esophageal acid reflux and neutralization of esophageal acid. In this study, we assessed the association between nocturnal decline of salivary pH and airway hyperresponsiveness. Salivary pH was serially assessed in 9 patients with mild asthma (7 men and 2 women ;mean age 33.3 years ;mean %predicted FEV1.0 89.4%) and 10 healthy volunteers (6 men and 4 women ; mean age 31.2 years) using a pH indicator tape. The buffering capacity of saliva was defined as the median effective dose (ED50) for acidification of saliva with 0.01 N HCl, and airway responsiveness was defined as the dose of methacholine producing a 35% fall in Grs (PD35-Grs). There was a significant correlation between the values obtained from the pH indicator tape and those obtained from the electrometric pH meter. Using the indicator tape for sequential monitoring, we observed a nocturnal fall (pH) in salivary pH in all subjects. A significant correlation was found between airway hyperresponsiveness (PD35-Grs) and eitherpH or ED50 in mildly asthmatic patients. Vagal reflux dysfunction might contribute to nocturnal salivary pH as well as to airway hyperresponsiveness in mild asthmatics

Sunitinib Versus Sorafenib as Initial Targeted Therapy for mCC-RCC With Favorable/Intermediate Risk: Multicenter Randomized Trial CROSS-J-RCC

Purpose: The present study compared the efficacy of sunitinib and sorafenib as first-line treatment of metastatic clear cell renal cell carcinoma (mCC-RCC) with favorable or intermediate Memorial Sloan Kettering Cancer Center (MSKCC) risk. Patients and methods: Treatment-naive patients with mCC-RCC were randomized to receive open-label sunitinib followed by sorafenib (SU/SO) or sorafenib followed by sunitinib (SO/SU). The primary endpoint was first-line progression-free survival (PFS). The secondary endpoints were total PFS and overall survival (OS). Results: Of the 124 patients enrolled at 39 institutions from February 2010 to July 2012, 120 were evaluated. The median first-line PFS duration was 8.7 and 7.0 months in the SU/SO and SO/SU groups, respectively (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.42-1.08). The total PFS and OS were not significantly different between the SU/SO and SO/SU groups (27.8 and 22.6 months; HR, 0.73; 95% CI, 0.428-1.246; and 38.4 and 30.9 months; HR, 0.934; 95% CI, 0.588-1.485, respectively). The subgroup analysis revealed that the total PFS with SU/SO was superior to the total PFS with SO/SU in the patients with favorable MSKCC risk and those with Conclusions: No statistically significant differences were found in first-line PFS, total PFS, or OS between the 2 treatment arms (ClinicalTrials.gov identifier, NCT01481870)

Changing trends in prognostic factors for patients with multiple myeloma after autologous stem cell transplantation during the immunomodulator drug/proteasome inhibitor era

We evaluated the clinical significance of prognostic factors including the International Staging System (ISS) and modified European Group for Blood and Marrow Transplantation response criteria in 1650 Japanese patients with multiple myeloma (MM) who underwent upfront single autologous stem cell transplantation (ASCT). We categorized patients into two treatment cohorts: pre-novel agent era (1995-2006) and novel agent era (2008-2011). The combined percentage of pre-ASCT complete response and very good partial response cases (463 of 988, 47%) significantly increased during the novel agent era compared with the pre-novel agent era (164 of 527, 31%; P < 0.0001). The 2-year overall survival (OS) rate of 87% during the novel agent era was a significant improvement relative to that of 82% during the pre-novel agent era (P = 0.019). Although significant differences in OS were found among ISS stages during the pre-novel agent era, no significant difference was observed between ISS I and II (P = 0.107) during the novel agent era. The factors independently associated with a superior OS were female gender (P = 0.002), a good performance status (P = 0.024), lower ISS (P < 0.001), pre-ASCT response at least partial response (P < 0.001) and ASCT during the novel agent era (P = 0.017). These results indicate that the response rate and OS were significantly improved, and the ISS could not clearly stratify the prognoses of Japanese patients with MM who underwent upfront single ASCT during the novel agent era. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association

On-line microdevice for stress proteomics

The handing of the cells or tissues is essential for proteomics research or drug screening, where labor is not avoidable. The steps of cell wash, protein extraction, protein denaturing are complicated procedures in conventional method using centrifugation and pipetting in the laboratory. This is the bottle-neck for proteome research. To solve these problems, we propose to utilize the nanotechnology, which will improve the proteomics methodology. Utilizing the nanotechnology, we developed a novel microseparation system, where centrifugation and pipetting are needless. This system has a nanostructured microdevice, by which the cell handling, protein extraction, and antibody assay can be performed. Since cell transfer is needless, all cells are corrected without any loss during the cell-pretreatment procedures, which allowed high reproducibility and enabled the detection of low amount of protein expression. Utilizing the microdevice, we analyzed the stress induced proteins. We further succeeded the screening of food that was useful for immunity and found that an extraction from seaweed promoted the apoptosis of T-lymphoblastic cells. Here, we present an on-line microdevice for stress proteomics

Mobile DHHC palmitoylating enzyme mediates activity-sensitive synaptic targeting of PSD-95

Protein palmitoylation is the most common posttranslational lipid modification; its reversibility mediates protein shuttling between intracellular compartments. A large family of DHHC (Asp-His-His-Cys) proteins has emerged as protein palmitoyl acyltransferases (PATs). However, mechanisms that regulate these PATs in a physiological context remain unknown. In this study, we efficiently monitored the dynamic palmitate cycling on synaptic scaffold PSD-95. We found that blocking synaptic activity rapidly induces PSD-95 palmitoylation and mediates synaptic clustering of PSD-95 and associated AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-type glutamate receptors. A dendritically localized DHHC2 but not the Golgi-resident DHHC3 mediates this activity-sensitive palmitoylation. Upon activity blockade, DHHC2 translocates to the postsynaptic density to transduce this effect. These data demonstrate that individual DHHC members are differentially regulated and that dynamic recruitment of protein palmitoylation machinery enables compartmentalized regulation of protein trafficking in response to extracellular signals

Review of juxtaglomerular cell tumor with focus on pathobiological aspect

Juxtaglomerular cell tumor (JGCT) generally affects adolescents and young adults. The patients experience symptoms related to hypertension and hypokalemia due to renin-secretion by the tumor. Grossly, the tumor is well circumscribed with fibrous capsule and the cut surface shows yellow or gray-tan color with frequent hemorrhage. Histologically, the tumor is composed of monotonous polygonal cells with entrapped normal tubules. Immunohistochemically, tumor cells exhibit a positive reactivity for renin, vimentin and CD34. Ultrastructurally, neoplastic cells contain rhomboid-shaped renin protogranules. Genetically, losses of chromosomes 9 and 11 were frequently observed. Clinically, the majority of tumors showed a benign course, but rare tumors with vascular invasion or metastasis were reported. JGCT is a curable cause of hypertensive disease if it is discovered early and surgically removed, but may cause a fatal outcome usually by a cerebrovascular attack or may cause fetal demise in pregnancy. Additionally, pathologists and urologists need to recognize that this neoplasm in most cases pursues a benign course, but aggressive forms may develop in some cases