Functional expression of transient receptor potential vanilloid 3 (TRPV3) in corneal epithelial cells: Involvement in thermosensation and wound healing

Transient receptor potential vanilloid 3 (TRPV3), a member of the calcium-permeable thermosensitive TRP (thermoTRP) subfamily of receptors, is an important cutaneous sensor that detects thermal and chemical stimuli. TRPV3 is activated by innocuous warm temperature stimuli (>33° C) and a variety of physiologically active substances. While the corneal epithelium is known to respond to such stimuli, it is unknown whether TRPV3 is involved in this phenomenon. We show here that TRPV3 mRNA and protein are abundantly expressed in the epithelial cells of human and mouse cornea. Carvacrol, an agonist of TRPV3, elevated cytosolic Ca²⁺ concentration in both primary mouse corneal epithelial cells and cultured human corneal epithelial cells (HCE-T cells). The response to carvacrol was inhibited by ruthenium red, a TRPV channel antagonist. Moreover, repetitive agonist stimulation sensitized the response with gradually increasing amplitude, suggesting that the TRPV3 in the cornea has similar physiological and pharmacological characteristics to that in skin keratinocytes. Finally, a wound healing assay revealed that appropriate calcium ion influx via activated TRPV3 in corneal epithelial cells accelerated their proliferation. Thus, functional TRPV3 is present in corneal epithelial cells and may play a role not only in thermosensation, but also in the regulation of cell proliferation.     

Identification of serum proteins that bind with S100A8, S100A9 and S100A8/A9: Clinical significance of using proteins for monitoring the postoperative condition of liver recipients

BackgroundSerum proteins that non-specifically bind with human S100A8/A9 (h-S100A8/A9) have been proposed. Our aim was to isolate and identify these proteins, and verify their clinical significance for monitoring the postoperative condition of liver recipients, and further to discuss the transportation of human fibronectin (h-FN) with h-S100A8/A9 and its functional role in vivo.MethodsTo isolate the serum proteins, recombinant human S100A8, S100A9 and S100A8/A9 affinity columns were used. Proteins were identified by mass spectrometry. Two enzyme-linked immunosorbent assays (ELISA) were used to measure h-S100A8/A9 and h-FN in the sera of liver recipients. Flow cytometry was employed to detect h-S100A8/A9 and h-FN on immunological cells. Western blotting was used to confirm serum constituents using antibodies specific to each constituent.ResultsOne of the proteins was identified with h-FN, and its fluctuation pattern in the serum of the recipient was in contrast to that of CRP. Flow cytometry showed a positive reaction for h-S100A8/A9 and h-FN on neutrophils and monocytes, indicating that both proteins exist on these cells.ConclusionsThe h-FN could be transported with S100A8/A9 in blood and/or on immunological cells, and effectively prevent further attack by various internal oxidants or repair damaged liver tissue in vivo.     

Adipocytokines as new promising markers of colorectal tumors: Adiponectin for colorectal adenoma,and resistin and visfatin for colorectal cancer

Adipocytokines are adipocyte‐secreted hormones associated with some malignancies such as colorectal, breast, and prostate cancer. We hypothesized that changes in the levels of adipocytokines may indicate the carcinogenesis and progression of colorectal cancer and adenoma, and investigated the association of the blood levels of several adipocytokines through a case‐control study. Blood levels of adiponectin, leptin, resistin, visfatin, and C‐peptide at diagnosis were measured in 115 colorectal cancer patients and 115 age‐, sex‐, and body mass index‐matched controls. The same analysis was performed in 72 colorectal adenoma patients and 72 controls. Logistic regression models were used for estimating odds ratios and 95% confidence intervals, and one‐way anova was performed to determine the prevalence of each variable between two or more groups. Resistin and visfatin levels in cancer patients were significantly higher than those of controls on multivariate analysis (P = 0.03 and P < 0.01, respectively). Stage progression significantly correlated with resistin and visfatin levels (P < 0.01 for both). The adiponectin level in adenoma patients was significantly lower than that of controls on multivariate analysis (P = 0.04). Its level was inversely correlated with the number of adenoma (P = 0.02), but not correlated with the size of adenoma. Resistin and visfatin may be good biomarkers of colorectal malignant potential and stage progression. Adiponectin level may be a good biomarker of colorectal adenoma. (Cancer Sci 2010; 101: 1286–1291)     

Immunological evaluation of personalized peptide vaccination monotherapy in patients with castration‐resistant prostate cancer

(Cancer Sci 2010; 101: 601–608) We previously reported that personalized peptide vaccine (PPV) therapy in combination with leutenizing hormone‐releasing hormone (LH‐RH) analog and estramustine phosphate in certain cases is safe and capable of inducing both immune responses and clinical responses for metastatic castration‐resistant prostate cancer (CRPC) patients. In the present study, PPV monotherapy was given to CRPC patients. Twenty‐three patients with metastatic CRPC were treated with PPV without any additional treatment modalities, including LH‐RH analogs. Samples were analyzed for peptide‐specific cytotoxic T‐lymphocyte (CTL) precursor analysis and peptide‐reactive IgG. Toxicity and immunological and clinical responses were assessed on a three‐monthly basis. Seventeen patients were available for immunological and clinical evaluation. The vaccines were well tolerated, with grade 3 erythema at injection sites in only one patient. Augmentation of CTL or IgG responses to at least one of the peptides was observed in six of 17 (35%) and 15 of 17 (88%) patients tested, respectively. Among 57 peptides used, 9 and 36 peptides induced CTL and IgG responses, respectively. Delayed‐type hypersensitivity reaction was observed in eight of 17 patients. More than 30% prostate‐specific antigen (PSA) decline was observed in four of 17 patients. Of these, one patient achieved a complete PSA response and another patient showed a partial PSA response with profound shrinking of lymph node metastases and prostate. The overall median survival time was 24 months (range, 5–37 months). These results suggest that PPV monotherapy appears to be safe and capable of inducing peptide‐specific immune responses and clinical responses in CRPC patients. This trial was registered with University Hospital Medical Information Network (UMIN) number R000003339.     

Surgical strategy of brain tumors adjacent to the optic radiation using diffusion tensor imaging-based tractography

The present study evaluated the efficacy of diffusion tensor imaging (DTI)-based tractography in the surgery of brain tumors adjacent to the optic radiation. Of the 14 surgical cases included, 11 had metastatic brain tumors and 3 cerebral gliomas. Additionally, 4 of the 14 patients had pre-operative visual field defects, while the remaining 10 patients experienced no visual impairment. The optic radiations on the lesion side were evident in all 14 patients. On the basis of these tractographic findings, we employed optimal surgical approaches in each patient to avoid injury to the eloquent neural structures, including optic radiation, during surgery. Successful surgical resection was performed in all 14 patients. Of the 14 patients, 2 with visual field defects during the pre-operative period showed improvement in their visual field, and the remaining 12 patients experienced no visual deterioration. DTI-based tractography thus is a feasible modality for the surgical planning of brain lesions adjacent to the optic radiation.     

Influenza A (H5N1) Viruses from Pigs, Indonesia

Pigs have long been considered potential intermediate hosts in which avian influenza viruses can adapt to humans. To determine whether this potential exists for pigs in Indonesia, we conducted surveillance during 2005–2009. We found that 52 pigs in 4 provinces were infected during 2005–2007 but not 2008–2009. Phylogenetic analysis showed that the viruses had been introduced into the pig population in Indonesia on at least 3 occasions. One isolate had acquired the ability to recognize a human-type receptor. No infected pig had influenza-like symptoms, indicating that influenza A (H5N1) viruses can replicate undetected for prolonged periods, facilitating avian virus adaptation to mammalian hosts. Our data suggest that pigs are at risk for infection during outbreaks of influenza virus A (H5N1) and can serve as intermediate hosts in which this avian virus can adapt to mammals.     

Laparoscopic cytoreductive nephrectomy with cytokine therapy for metastatic renal cell carcinomas compared with open nephrectomy

Introduction: We retrospectively reviewed and compared the operation records and long‐term results of patients with metastatic renal cell carcinoma (mRCC) who underwent laparoscopic cytoreductive nephrectomy and those who underwent open procedure. Methods: A total of 75 patients with mRCC who underwent cytoreductive nephrectomy between 1997 and 2007 were studied: 23 patients in the laparoscopy group (LCN group) and 52 in the open group (OCN group). Most patients received interferon‐based cytokine therapy after surgery. Patients with tumor thrombus in the inferior vena cava were excluded from this study. Results: Operating time in the LCN group was significantly longer than in the OCN group (320.3 min vs 269.6 min, P=0.049). Blood loss was less in the LCN group (527.8 ml) than in the OCN group (1372.3 ml, P=0.072). Convalescence was shorter in the LCN group (18.1 d) than in the OCN group (32.9 d, P<0.0001). Median follow‐up periods were 15 months (range 2–110 months) and 17 months (range 1–103 months) in the LCN group and OCN group, respectively. There was no statistically significant difference between the two groups with regard to disease‐specific patient survival and progression‐free survival. Conclusions: Laparoscopic cytoreductive nephrectomy is a feasible alternative for patients with mRCC because its benefits include less blood loss and shorter convalescence. In addition, the long‐term oncological results of laparoscopic cytoreductive nephrectomy are comparable to those of the open procedure.     

Intestinal anisakiasis can cause intussusception in adults: An extremely rare condition

We report an extremely rare case of adult intussusception caused by anisakiasis. A 41-year-old man was admitted into our hospital for right lower abdominal colicky pain. Ultrasonography and computed tomography revealed the presence of intussusception. As pneumodynamic resolution by colonoscopy failed, surgery was performed. The anisakis body was found in the submucosal layer of the resection specimen. The patient was discharged 9 d after the operation. Anisakiasis may cause intussusception in any country wh...