Public Relations and Communication Strategies in Construction of Large-Scale Cohorts and Biobank: Practice in the Tohoku Medical Megabank Project.

The Tohoku Medical Megabank Project was designed as part of the national reconstruction project for addressing the damage from the 2011 Great East Japan Earthquake. It is an integrated project involving the genome cohort study of 150,000 participants, integrated biobank construction, and multi-omics analyses. Public relations and communication activities emerged to be extremely important in the successful development of this project. To gain insights into the contributions of these activities, we divided the public relations and communication activities for the project into three phases based on the situations surrounding the project. Prior to the start of the cohort study (Phase I), a cooperative relationship was established with a focus on concluding cooperation agreements with local governments. Until the participants reached the target number (Phase II), we actively communicated with the media to publicize the project. During the phase in which use of the constructed biobank is promoted (Phase III), for ensuring the industrial utilization of the biobank, visits from the industry are promoted. Throughout the execution of these activities, we explored the best strategies for building relationships with multiple stakeholders like local government, media and industry. By paying attention to these phases that have been changing according to the project's progress, we were able to adapt the strategies and methods of public relations and communication. The success of these activities has enabled the overall project to progress smoothly. We hope that the process of designing our project's public relations and communication activities will be useful for other similar initiatives.

Wound healing after applying a gelatin-based hydrogel sheet to resected rat submandibular gland.

The present study was done to develop a useful experimental model for analysis of the effects of physiologically active substances on atrophy and regeneration of salivary gland acinar cells. Resection wounds (diameter, 3 mm) were made in the submandibular glands of 8-week-old Wistar rats (n = 24) for histochemical examination on Days 3, 5, 7, 10, 14, and 21 after implantation of a gelatin-based hydrogel sheet. The results showed that the sheet had nearly disappeared by Day 10. Regions around the resection wounds were classified as normal, atrophic, or necrotic. In atrophic regions, acinar cells atrophied after resection, and few acinar cells were observed on Day 7. On Days 5-7, striated and granular ducts resembled duct-like structures. On Day 10, newly formed acinar cells were confirmed by increased periodic acid-Schiff staining, and a greater number of mature cells was present thereafter. In necrotic regions, acinar and ductal cells were destroyed, and scattered enucleated acinar cells and duct-like structures were present, on Day 3; newly formed acinar cells were observed on Day 10. Thus, the experimental model demonstrated atrophy and regeneration of the submandibular gland and enabled analysis of the effects of sustained release of physiologically active substances contained within an implanted sheet.

Distribution of aquaporin-5, transforming growth factor-ß1 and laminin during regeneration of atrophic rat submandibular glands after duct ligation.

The aim of this study was to determine the localization of aquaporin-5 (AQP5), transforming growth factor-ß1 (TGF-ß1) and laminin during regeneration of the rat submandibular gland. After duct ligation for 7 days, the regenerating glands were collected on days 0, 1, 3, 7, and 14 after ligation release to study the process of regeneration. Immunohistochemical staining revealed apical expression of AQP5 in many acinar cells, strong expression in intercalated ducts (ICDs) of the normal submandibular gland at Day 14, and strong expression in duct-like structures (DLSs) during regeneration from Day 0 to 7. However, a few AQP5-negative acinar cells were detected during regeneration. At Day 0, immunopositivity for TGF-ß1 was detected in connective tissue. At Days 3 and 7 during regeneration, TGF-ß1 immunostaining was observed in DLSs, which were surrounded by α-smooth muscle actin-positive thickened myoepithelial cells. Laminin staining was strong in the thickened basement membrane of DLSs at Day 3 during regeneration, but weak around acinar cells at Day 14. These findings suggest that TGF-ß1 is involved in the environment around DLSs, myoepithelial cells and laminin, that DLSs have the same functional properties as ICDs, and that AQP5-negative acinar cells may be mucous cells.

Retrospective clinical study of 296 patients with mass lesions of the tongue.

To better understand the clinical features of mass lesions of the tongue, we retrospectively evaluated frequency, recurrence rate, and complications in 296 patients who had undergone surgery for such lesions. The diagnoses were fibroma (43.6%), mucous cyst (14.2%), papilloma (11.8%), hemangioma (7.8%), granuloma (6.4%), lipoma (1.4%), schwannoma (1.0%), ectopic tonsil (0.7%), and other (13.2%). Recurrence was noted in two patients (0.7%). Twenty-two patients (7.4%) developed surgical complications, including lingual nerve paralysis (6.4%), glossodynia (0.6%), and postoperative infection (0.3%). Lingual nerve paralysis was observed in the ventral portion (42.1%) of the tongue, apex (36.8%), lateral border (10.5%), and dorsum (10.5%). When all sites were considered together, there was no significant difference in the number of patients presenting with lingual nerve paralysis (P = 0.075). However, there were significant differences in lingual nerve paralysis at the lateral border (P < 0.05), apex (P < 0.05), and dorsum (P < 0.001) but not at the ventral portion (P > 0.05) in the size of the patients with versus without it which suggests that the risk of lingual nerve paralysis is higher at the ventral tongue, regardless of tumor size. These results shed light on the clinical features of mass lesions of the tongue.

Immunolocalization of FGF-2, -7, -8, -10 and FGFR-1-4 during regeneration of the rat submandibular gland.

Fibroblast growth factors (FGFs) and their receptors (FGFRs) play important roles in the development of the submandibular gland. Although regeneration of submandibular glands follows a similar process to their development, it is unknown how FGFs and FGFRs are distributed during regeneration of submandibular gland. The aim of this study was to determine the localization of FGFs and FGFRs during such regenerative processes. After 7 days' obstruction, the submandibular glands were collected at days 0, 1, 3, 7, 11 and 14 after duct release to study regeneration. The regenerative processes of the submandibular gland were investigated by immunohistochemistry for FGF-2, 7, 8, 10 and FGFR-1-4. Immunohistochemical staining revealed that FGF-2 was moderately expressed in the epithelial cells of duct-like structures (DLS) and newly formed acinar cells (NFAC) at days 0-7, and strongly in intercalated duct (ICD) at control gland and Day 7-14. FGF-7 was localized moderately in NFAC and DLS. FGF-8 was localized moderately in the epithelial cells of DLS during regeneration. Strong positive immunoreactions for FGF-10 were found in NFAC and the epithelial cells of DLS during regeneration, as well as the ICD and lateral surfaces of the maturing acinar cells (MAC). FGFR-1 was expressed moderately in the ICD, and weakly in the NFAC and MAC. Positive immunoreactions for FGFR-2 were not observed during regeneration. Additionally, FGFR-4 was detected strongly in the ICD and slightly in NFAC. These findings suggest that FGF-2, -7, -8 and -10 play important roles in NFAC, MAC, and DLS through FGFR-1 and -4 during regeneration of submandibular gland.

Immunohistological study of small Rho GTPases and ß-catenin during regeneration of the rat submandibular gland.

Our study immunohistochemically evaluated the localization patterns of small Rho GTPases and ß-catenin during regeneration of the rat submandibular gland. After 7 days of obstruction, regenerating glands were collected at days 0, 3, 7, 11 and 14 after duct release to study regeneration. RhoA was detected strongly and RhoC was detected weakly in the cytoplasm of newly formed acinar cells from day 3 to 7, and both RhoA and RhoC at the basal site and cytoplasm were detected moderately from day 11 to 14. RhoB was detected strongly and moderately in the cytoplasm of newly formed and matured acinar cells, respectively, and detected strongly in duct-like structures (DLSs) and intercalated ducts (ICDs). Rac1 was detected at the cell-cell and subcellular region, but ß-catenin was not observed in newly formed acinar cells. Rac1 immunolabeling gradually reduced, and the ß-catenin staining pattern became stronger. p-Rac1, a phosphorylated form of Rac1, was observed in the cytoplasm of newly formed acinar cells. At apical and subcellular region of DLSs and ICDs, Rac1 and ß-catenin were detected. These findings suggest that RhoA and RhoC might be involved in the actin cytoskeleton at the basolateral site of regenerating acinar cells, and RhoB might play a unique role in regenerating acinar cells and in DLSs and ICDs. Rac1 and ß-catenin at the cell-cell region might play important roles in cell-cell adhesion and the differentiation of regenerating acinar cells, as well as actin reconstruction at apical and subcellular regions of DLSs and ICDs.

Alteration of the actin cytoskeleton and localisation of the α6ß1 and α3 integrins during regeneration of the rat submandibular gland.

OBJECTIVES: Actin filaments, which are regulated by signal transduction via integrins, play important roles in the regulation of cell differentiation and polarity. The aim of this study was to assess alterations in the cytoskeleton and the localisation of integrins during regeneration of the rat submandibular gland. DESIGN: After obstruction for 7 days, the regenerating glands were collected at days 0, 1, 3, 7, 14 after duct release for analysis of regeneration. Alterations in the actin filaments were examined using phalloidin, which specifically binds to filamentous actin (F-actin), and the distributions of the α6ß1 and α3 integrins were examined immunohistochemically. RESULTS: F-actin was strongly localised at the apical region in the intercalated ducts of normal and day-14 glands and in duct-like structures during the regenerative process. Thereafter, actin accumulated at the basement membrane in mature acinar cells. A temporo-spatial correlation was found between the apical distribution of F-actin and α3 integrin staining. Diffuse α6ß1 integrin staining, which occurred at a distal site in α3 integrin-positive cells, was observed in immature cells at day 3. At day 14, α6ß1 integrin was detected at the basement membrane in terminal differentiated acinar cells. CONCLUSION: These findings suggest that duct-like structures have the same properties as intercalated ducts, that alterations in α3 to α6ß1 integrins regulate the generation of acinar cells from duct-like structures, and that the α6ß1 integrin is involved in the differentiation of acinar cells during regeneration of the rat submandibular gland.

IL-6 and soluble IL-6 receptor stimulate the production of MMPs and their inhibitors via JAK-STAT and ERK-MAPK signalling in human chondrocytes.

Elevated concentrations of IL-6 (interleukin-6) and sIL-6r (soluble IL-6 receptor) in the synovial fluid and serum of patients with arthritis have been implicated in joint cartilage destruction. This study examined the effects of IL-6 and sIL-6r on the expression of MMPs (matrix metalloproteinases), TIMPs (tissue inhibitor of metalloproteinases), the plasminogen activation system including tPA (tissue-type PA), uPA (urokinase-type PA) and PAI-1 (PA inhibitor type 1) using chondrocytes derived from normal human femur cartilage. The cells were cultured with or without 50 ng/ml IL-6 and/or 30 ng/ml sIL-6r in the presence or absence of the JAK3 (Janus kinase 3) inhibitor WHI-P131 or the MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular signal protein kinase) kinase] inhibitor PD98059 for up to 28 days. The expression of MMPs, TIMPs, uPA, tPA and PAI-1 was investigated at the mRNA and protein levels. MMP protein expression and pSTAT3 (phosphorylation of signal transducer and activator of transcription 3) and pERK (phosphorylation of ERK) were also measured. Treatment with both IL-6 and sIL-6r markedly increased the expression of MMP-1, MMP-13, TIMP-1 and PAI-1, while significantly decreasing the expression of tPA and uPA and stimulating pSTAT3 and pERK. Adding WHI-P131 or PD98059 decreased IL-6 and sIL-6r enhancement of MMP-1, -3 and -13. The results suggest that IL-6 and sIL-6r stimulate the production of MMPs and their inhibitor via JAK-STAT and ERK-MAPK signalling in chondrocytes.

Predictability of painful stimulation modulates subjective and physiological responses.

UNLABELLED: Clinical observations suggest that the perceived intensity of a painful event increases as the unpredictability of its occurrence increases. We examined the effect of varying stimulus predictability on the Somatosensory Evoked Potential (SEP), Pupil Diameter Response (PDR), Pain Report (PR), and Fear Report (FR) in 25 healthy female volunteers experiencing repeated noxious fingertip shocks. Each volunteer underwent high- and low-stimulus intensities in 4 stimulus patterns defined by stimulus sequence (SEQ) and interstimulus interval (ISI) as follows: A) serial stimulus intensity SEQ with fixed ISI; B) serial stimulus intensity SEQ with varied ISI; C) random stimulus intensity SEQ with fixed ISI; and D) random stimulus intensity SEQ with varied ISI. Results revealed that: (1) lower stimulus predictability led to higher PR and FR, greater PDR magnitude, and greater SEP amplitude; and (2) the 4 dependent measures showed the same response pattern across levels of stimulus predictability. These findings support the hypothesis that lower stimulus predictability is associated with higher reported pain and fear as well as greater physiological arousal. PERSPECTIVE: Patients undergoing painful procedures experience more distress when the occurrence of a painful event is unpredictable. Poor predictability increases pain, fear, and associated physiological arousal. Maximizing the predictability of painful events may improve the quality of patient care by minimizing associated levels of pain and fear.

IL-1beta stimulates the expression of prostaglandin receptor EP4 in human chondrocytes by increasing production of prostaglandin E2.

Prostaglandin (PG) E(2), which exerts its actions via the PG receptors EP1-4, is produced from arachidonic acid by cyclooxygenase (COX)-1 and COX-2. The aim of this study was to investigate the mechanisms by which interleukin (IL)-1beta induces the expression of PG receptors in cultured human chondrocytes and to explore the role of PGE(2) in this process. The cells were cultured with 0, 10, or 100 U/mL IL-1beta with or without 1 muM celecoxib, a specific inhibitor of COX-2, for up to 28 days. Expression of the genes encoding COX-1, COX-2, and EP1-4 was quantified using real-time PCR, and expression of the corresponding proteins was examined using immunohistochemical staining. PGE(2) production was determined using ELISA. IL-1beta treatment caused a marked dose- and time-dependent increase in the levels of PGE(2), COX-2, and EP4 as compared with the untreated control. It did not affect the expression of COX-1, and it decreased the expression of EP1 and EP2. EP3 expression was not detected in either the absence or the presence of IL-1beta. When celecoxib was also present, IL-1beta failed to stimulate PGE(2) production and EP4 expression, but its stimulatory effect on COX-2 expression and its inhibitory effect on EP1 and EP2 expression were unchanged. IL-1beta increases the production of PGE(2), COX-2, and the PG receptor EP4 in cultured human chondrocytes. The increase in EP4 expression appears to be a result of the increased PGE(2) production.

Pupil dilation response to noxious stimulation: effect of varying nitrous oxide concentration.

OBJECTIVE: This report examines the pain-related pupil dilation response (PDR), tracking it across mixture concentrations of nitrous oxide (N(2)O) in oxygen (O(2)) and relating its variation to change in long latency somatosensory evoked potentials (SEPs) and visual analogue scale (VAS) pain report. METHODS: We varied mixture concentrations of N(2)O in O(2) (0%, 10%, 30%, and 50%), measuring PDR, SEP and VAS responses to painful electrical fingertip stimulation at high and low intensities in 15 volunteers. RESULTS: Mixed effect model statistical analyses revealed that: (1) PDR increased significantly with stimulus intensity and constricted significantly with mixture concentration; (2) SEP and VAS decreased significantly with increasing mixture concentration; (3) PDR correlated with SEP amplitude and VAS across mixture concentrations; (4) subjects differed significantly in: (a) baseline PDR and SEP amplitudes, (b) rate of change of these measures across mixture concentrations; and (5) VAS increased significantly with stimulus intensity and decreased significantly with mixture concentration without significant individual differences. CONCLUSIONS: The findings support the hypothesis that the pain-related PDR is a complex brain-mediated response rather than a simple sympathetic reflex. SIGNIFICANCE: PDR may provide a useful indicator for studying the central processing of noxious stimuli and the effects of analgesic interventions.

Unusual cyst-like lesions in the parapharyngeal space associated with recurrence of tongue carcinoma.

A 54-year-old male presented with the complaint of a painful sore on the left side of his tongue. Our examination found an ulcer 15 x 20 mm in size on the left edge of the tongue, with peripheral indurations. The lesion was diagnosed histopathologically as squamous cell carcinoma (T2N0M0). Consequently, the lesion was surgical removed and radical neck dissection was performed. Four months after the operation, two unusual cyst-like lesions were identified in the parapharyngeal space by CT and MRI. A biopsy specimen revealed recurrent carcinoma with a cyst-like structure. The route of the tumor metastasis into the parapharyngeal space was obscured, but it was speculated that the excessive lymph accumulation was due to a lymphatic occlusion caused by the surgical procedure, proliferation of the metastatic carcinoma, or stagnation and accumulation of tissue fluid caused by parapharyngeal invasion by the recurrent lesion.

Subectodermal microfibrillar bundles are organized into a distinct parallel array in the developing chick limb bud.

In this study, a unique fiber system in the subectodermal mesenchyme of the chick limb bud was visualized immunohistochemically with the use of a novel monoclonal antibody termed "FB1." This antibody stained a subset of extracellular fibers in the embryonic mesenchyme. Among the fibers visualized, those running perpendicularly to the limb bud ectoderm became progressively prominent in their thickness and length, and organized into a parallel array in the subectodermal region. This fiber system was distinct from that of major collagens, fibronectin, or tenascin. A molecule immunoprecipitated with FB1 comigrated with JB3 antigen, or chicken fibrillin-2. The fibers visualized immunohistochemically by FB1 and JB3 were indistinguishable from each other, and ultrastructurally appeared to be bundles composed of tubular-like microfibrils that originated directly from the ectodermal basal lamina. They lacked the amorphous deposits that are characteristic of elastin. A similar array of subectodermal fibers was also found in the developing axilla and some truncal regions, again well before the development of a definitive dermis. These findings suggest that a parallel array of subectodermal FB1-positive fibers constitutes a precocious fiber system in the presumptive dermis prior to the substantial formation of collagenous fibers. These fibers could be developmentally linked to oxytalan fibers, which are known to be present in the papillary dermis in mature cutaneous tissue.