Examination of micro-superficial lesions of up to 5 mm in size in the pharyngolaryngeal region.

OBJECTIVE: For low-grade intraepithelial neoplasia cases, pharyngolaryngeal lesions equal to or less than 5 mm in size do not generally progress to invasive carcinoma. However, micro-superficial lesions equal to or less than 5 mm that showed rapid growth have been recently encountered. This study aimed to identify the characteristics of preferential progression of lesions equal to or less than 5 mm in size. METHOD: Gross findings, endoscopic findings and pathological results of 55 lesions measuring equal to or less than 5 mm in diameter were retrospectively reviewed to identify factors that distinguish squamous cell carcinoma or high-grade intraepithelial neoplasia from low-grade intraepithelial neoplasia or non-atypia lesions. RESULTS: The overall sensitivity, specificity, accuracy, and positive and negative predictive value of background colouration and intrapapillary capillary loop pattern in differentiation of squamous cell carcinoma or high-grade intraepithelial neoplasia from low-grade intraepithelial neoplasia or non-atypia lesions were all 100 per cent. CONCLUSION: Diagnosis based on background colouration and the intrapapillary capillary loop pattern on narrow-band imaging facilitates the pathological examination of lesions measuring equal to or less than 5 mm.

Reappraisal of classification of distal cholangiocarcinoma based on tumour depth.

BACKGROUND: In the eighth edition of the AJCC cancer staging classification, the T system for distal cholangiocarcinoma (DCC) has been revised from a layer-based to a depth-based approach. The aim of this study was to propose an optimal T classification using a measured depth in resectable DCC. METHODS: Patients who underwent pancreatoduodenectomy for DCC at 32 hospitals between 2001 and 2010 were included. The distance between the level of the naive bile duct and the deepest cancer cells was measured as depth of invasion (DOI). Invasive cancer foci were measured as invasive tumour thickness (ITT). Log rank χ2 scores were used to determine the cut-off points, and concordance index (C-index) to assess the survival discrimination of each T system. RESULTS: Among 404 patients, DOI was measurable in 182 (45·0 per cent) and ITT was measurable in all patients, with median values of 2·3 and 5·6 mm respectively. ITT showed a positive correlation with DOI (rS = 0·854, P < 0·001), and the cut-off points for prognosis were 1, 5 and 10 mm. Median survival time was shorter with increased ITT: 12·4 years for ITT below 1 mm, 5·2 years for ITT at least 1 mm but less than 5 mm, 3·0 years for ITT at least 5 mm but less than 10 mm, and 1·5 years for ITT 10 mm or more (P < 0·001). This classification exhibited more favourable prognostic discrimination than the T systems of the seventh and eighth editions of the AJCC (C-index 0·646, 0·622 and 0·624 respectively). CONCLUSION: ITT is an accurate approach for depth assessment in DCC. The four-tier ITT classification with cut-off points of 1, 5 and 10 mm seems to be a better T system than those in the seventh and eighth editions of the AJCC classification.

Digitised evaluation of speech intelligibility using vowels in maxillectomy patients.

Among the functional disabilities that patients face following maxillectomy, speech impairment is a major factor influencing quality of life. Proper rehabilitation of speech, which may include prosthodontic and surgical treatments and speech therapy, requires accurate evaluation of speech intelligibility (SI). A simple, less time-consuming yet accurate evaluation is desirable both for maxillectomy patients and the various clinicians providing maxillofacial treatment. This study sought to determine the utility of digital acoustic analysis of vowels for the prediction of SI in maxillectomy patients, based on a comprehensive understanding of speech production in the vocal tract of maxillectomy patients and its perception. Speech samples were collected from 33 male maxillectomy patients (mean age 57.4 years) in two conditions, without and with a maxillofacial prosthesis, and formant data for the vowels /a/,/e/,/i/,/o/, and /u/ were calculated based on linear predictive coding. The frequency range of formant 2 (F2) was determined by differences between the minimum and maximum frequency. An SI test was also conducted to reveal the relationship between SI score and F2 range. Statistical analyses were applied. F2 range and SI score were significantly different between the two conditions without and with a prosthesis (both P < .0001). F2 range was significantly correlated with SI score in both the conditions (Spearman's r = .843, P < .0001; r = .832, P < .0001, respectively). These findings indicate that calculating the F2 range from 5 vowels has clinical utility for the prediction of SI after maxillectomy.

ß-Glucans in food modify colonic microflora by inducing antimicrobial protein, calprotectin, in a Dectin-1-induced-IL-17F-dependent manner.

Dectin-1 (gene symbol: Clec7a) is a receptor for ß-glucans that play an important role for the host defense against fungi. Recently, we showed that Clec7a-/- mice are resistant against dextran sodium sulfate (DSS)-induced colitis because of regulatory T-cell population expansion in the colon. The regulatory T-cell expansion is caused by expansion of commensal Lactobacillus murinus whose growth is suppressed by an antimicrobial protein, calprotectin S100A8/A9. In this report, we showed that S100A8 was mainly produced by mouse colonic epithelial cells. S100A8 was not induced directly by Dectin-1 but by Dectin-1-induced cytokines, especially interleukin-17F (IL-17F), that were produced by several types of innate immune cells including CD11c+/CD11b+ myeloid cells in colonic lamina propria. S100A8/A9 heterodimer preferentially suppressed the growth of L. murinus that was increased in both Clec7a-/- and Il17f-/- mice. Furthermore, similar expansion of L. murinus and DSS-colitis resistance were observed in mice fed with ß-glucan-free food. These observations suggest that food-derived ß-glucans control the specific commensal microbiota via the Dectin-1-IL-17F-calprotectin axis to maintain the intestinal homeostasis.

Outcomes of fulvestrant therapy among japanese women with advanced breast cancer: a retrospective multicenter cohort study (JBCRG-C06; Safari).

PURPOSE: This retrospective study evaluated the effect of clinical background and treatment line on time to treatment failure (TTF) in advanced/metastatic breast cancer (AMBC) patients receiving F500 in Japan (UMIN 000015168). METHODS: Patients who commenced F500 treatment were registered at 16 sites in Japan. Correlations between baseline clinicopathological factors, treatment line, and TTF were investigated by Kaplan-Meier analysis. TTF data were analyzed using univariate analysis and multivariate analysis with a Cox proportional hazards model. RESULTS: Data for 1072 patients were available; 1031 patients (96.2%) were evaluable for efficacy. F500 was administered as first-line treatment in 2.0%, second-line in 22.7%, third-line in 26.7%, and ≥fourth-line in 48.6% patients. Median TTF was 5.4 months. Multivariate analysis found that earlier F500 use (first and second vs. third vs. ≥fourth line; hazard ratio (HR) = 0.80, 95% confidence interval (CI) 0.74-0.86; P < 0.001), longer period from AMBC diagnosis to F500 use (≥3 vs. <3 years; HR 0.60, 95% CI 0.51-0.70; P < 0.001), and no prior palliative chemotherapy administered for unresectable or metastatic breast cancer (no vs. yes; HR 0.69, 95% CI 0.60-0.80; P < 0.001) were associated with significantly longer TTF. Among 691 patients, where information on histologic/nuclear grade was available, a low grade was also associated with a longer TTF, but this finding was not maintained among patients with recurrent breast cancer (N = 558). Among women with recurrent breast cancer, a longer DFI between a patient's initial breast cancer diagnosis and their recurrence was associated with a longer TTF on F500 therapy. CONCLUSIONS: Our study showed that treatment period of F500 was longer when used in earlier-line treatment. For patients on F500, TTF was also longer for patients who had not received prior palliative chemotherapy and for those who had a longer period from their AMBC diagnosis to F500 use.

Optogenetic activation of axon guidance receptors controls direction of neurite outgrowth.

Growth cones of extending axons navigate to correct targets by sensing a guidance cue gradient via membrane protein receptors. Although most signaling mechanisms have been clarified using an in vitro approach, it is still difficult to investigate the growth cone behavior in complicated extracellular environment of living animals due to the lack of tools. We develop a system for the light-dependent activation of a guidance receptor, Deleted in Colorectal Cancer (DCC), using Arabidopsis thaliana Cryptochrome 2, which oligomerizes upon blue-light absorption. Blue-light illumination transiently activates DCC via its oligomerization, which initiates downstream signaling in the illuminated subcellular region. The extending axons are attracted by illumination in cultured chick dorsal root ganglion neurons. Moreover, light-mediated navigation of the growth cones is achieved in living Caenorhabditis elegans. The photo-manipulation system is applicable to investigate the relationship between the growth cone behavior and its surrounding environment in living tissue.

Prognostic evaluation of mucin-5AC expression in intrahepatic cholangiocarcinoma, mass-forming type, following hepatectomy.

AIM: This study aimed to investigate the clinicopathological predictors of survival in patients with intrahepatic cholangiocarcinoma, mass-forming type (ICC-MF), following curative intent hepatectomy. METHODS: Clinical characteristics and outcomes were analyzed in a series of 42 patients who underwent curative hepatectomy for ICC-MF between February 1987 and December 2012. The relationship between immunohistochemical expression profiles of mucin (MUC) core proteins (MUC2, MUC5AC, and MUC6) and surgical outcomes was examined. RESULTS: The overall median follow-up period was 2.6 years (0.2-17.9). Bile duct reconstruction (p = 0.017), lymph node metastasis (p = 0.049), maximal mass diameter ≥5.0 cm (p = 0.002), and MUC5AC expression (p = 0.003) were identified as significant adverse predictors of overall survival by univariate analysis. Bile duct reconstruction (p = 0.048), maximal mass diameter ≥5.0 cm (p = 0.002), and MUC5AC expression (p = 0.005) were found to be independent predictors of poor prognosis by multivariate analysis. Maximal mass diameter ≥5.0 cm (p = 0.011) was found to be an independent predictor for the tumor recurrence. There was a strong correlation between MUC5AC expression and lymph node metastasis (p = 0.021). MUC6 expression was more frequent in patients with concurrent MUC5AC expression (p = 0.019). CONCLUSIONS: MUC5AC expression was significantly related to long-term prognosis and aggressive tumor development, and may be a useful prognostic marker.

Face, content and concurrent validity of the Mimic® dV-Trainer for robot-assisted endoscopic surgery: a prospective study.

OBJECTIVE: The aim of this study was to determine whether any correlation exists between the performance of the Mimic® dV-Trainer (Mimic Technologies, Seattle, Wash., USA) and the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, Calif., USA). METHODS: Twelve participants were recruited, ranging from residents to consultants. We used four training tasks, consisting of 'Pick and Place', 'Peg Board', 'Thread the Rings' and 'Suture Sponge', from the software program of the Mimic dV-Trainer. The performance of the participants was recorded and measured. Additionally, we prepared the same tasks for the da Vinci Surgical System. All participants completed the tasks using the da Vinci Surgical System and were assessed according to time, the Objective Structured Assessment of Technical Skill checklist and the global rating score for endoscopic suturing assessed by two independent blinded observers. After performing these tasks, the participants completed a questionnaire that evaluated the Mimic dV-Trainer's face and content validity. The final results for each participant for the Mimic dV-Trainer and the da Vinci Surgical System were compared. RESULTS: All participants ranked the Mimic dV-Trainer as a realistic training platform that is useful for residency training. There was a significant relationship between the Mimic dV-Trainer and the da Vinci Surgical System in all four tasks. We verified the reliability of the assessment of the checklist and the global rating scores for endoscopic suturing assessed by the two blinded observers using Cronbach's alpha test (r = 0.803, 0.891). CONCLUSIONS: We evaluated the concurrent validity of the Mimic dV-Trainer and the da Vinci Surgical System. Our results suggest the possibility that training using the Mimic dV-Trainer may therefore be able to improve the operator's performance during live robot-assisted surgery.

Single-incision plus one port laparoscopic anterior resection for rectal cancer as a reduced port surgery.

BACKGROUND: Only limited data in the literature about single-incision laparoscopic rectal surgery, because the laparoscopic stapler does not allow low rectal transection without sufficient distal margins from the umbilicus port. We have developed single-incision plus one port laparoscopic anterior resection of the rectum (SILS+1-AR) as a reduced port surgery in which we can utilize the incision for drainage as an additional access route for laparoscopic procedures including the transection the lower rectum. METHODS: A Lap protector (LP) mini was inserted through a 2.5 cm transumbilical incision, and an EZ-access was mounted to LP and three 5-mm ports were placed in EZ-access. A 12 mm port was inserted in right lower quadrant. Almost all the procedures were performed with usual laparoscopic instruments, and the operative procedures were much the same as in usual laparoscopic low anterior resection of the rectum using a flexible 5mm scope. The rectum was transected normally using only one endoscopic linear stapler inserted from the right lower quadrant port. RESULTS: We underwent modified SILS+1-AR in 16 patients with advanced rectal cancer. In all cases, there was no need to extend the skin incision. We transected the lower rectum with one laparoscopic stapler in all six cases. Postoperative follow-up did not reveal any umbilical wound complications or recurrences. CONCLUSIONS: The safety and feasibility of SILS+1-AR for advanced rectal cancer was established in this study. However, further studies are needed to prove the advantages of this procedure to conventional laparoscopic law anterior resection.

Single-incision laparoscopic colectomy using the Gelport system for early colon cancer.

BACKGROUND: Laparoscopic surgery has spread quickly during the past twenty years, and has become one of the important treatments in the field of colorectal surgery. Recently, natural orifice transluminal endoscopic surgery (NOTES) has been studied as the next generation of minimally-invasive surgery, but the feasibility and safety of the NOTES method have not been evaluated. In such a situation, single-incision laparoscopic surgery has attracted interest from surgeons worldwide. However, single-incision laparoscopic colorectal surgery has not yet been standardized. METHODS: From February 2010, single-incision laparoscopic colectomy was performed for 7 patients presenting with early colon cancer. All procedures were performed by two experts with the License of Endoscopic Surgical Skill Qualification System (ESSQS) of Japan Society for Endoscopic Surgery (JSES) in the field of colorectal Surgery. RESULTS: We used the Gelport system (Applied Medical, Rancho Santa Margarita, CA, USA) as the access port and 3 trocars of different sizes (Ethicon, Inc., Cincinnati, OH, USA). Using this technique, we did not experience any difficulties or use any articulated instruments. All of the present 7 patients underwent the single-incision laparoscopic colectomy successfully and had no complications. CONCLUSION: Single-incision laparoscopic surgery using the Gelport was performed safely in the present cases. The use of the Gelport as an access port can address the technical difficulty associated with this new technique.

FUS immunoreactivity of neuronal and glial intranuclear inclusions in intranuclear inclusion body disease.

AIMS: Recent studies have shown that fused-in-sarcoma (FUS) protein is a component of 'neuronal' intranuclear inclusion bodies (INIBs) in the brains of patients with intranuclear inclusion body disease (INIBD). However, the extent and frequency of FUS-immunoreactive structures in INIBD are uncertain. METHODS: We immunohistochemically examined the brain, spinal cord and peripheral ganglia from five patients with INIBD and five control subjects, using anti-FUS antibodies. RESULTS: In controls, the nuclei of both neurones and glial cells were intensely immunolabelled with anti-FUS and neuronal cytoplasm was weakly positive for FUS. In INIBD, neuronal and glial INIBs in the brain and spinal cord were positive for FUS. FUS-positive INIBs were also found in the peripheral ganglia. The proportion of FUS-positive neuronal INIBs relative to the total number of inclusion-bearing neurones ranged from 55.6% to 83.3% (average 73.2%) and that of FUS-positive glial INIBs ranged from 45.9% to 85.7% (average 62.7%). The nucleus and cytoplasm of inclusion-bearing neurones and glial cells showed no FUS immunoreactivity. CONCLUSIONS: These findings suggest that FUS is incorporated into INIBs in both neurones and glial cells and that loss of normal FUS immunoreactivity may result from reduced protein expression and/or sequestration within inclusions.

Epstein-Barr virus load for early detection of lymphoproliferative disorder in pediatric renal transplant recipients.

AIM: The aims of this study were to establish a protocol for monitoring Epstein-Barr virus (EBV) infection for identification of pediatric renal transplant recipients with a high risk of developing posttransplant lymphoproliferative disorder (PTLD) and to predict the development of PTLD. SUBJECTS AND METHODS: Peripheral blood mononuclear cells (PBMCs) and plasma EBV loads were measured by nested PCR (n-PCR) and real-time PCR (r-PCR) every 1 - 3 months after grafting in 17 pediatric recipients who were seronegative for EBV before grafting (4 with EBV-associated symptoms, including 2 with PTLD (Group A); 6 with asymptomatic persistent high EBV loads in PBMCs of > 1,000 copies/µgDNA for over 6 months (Group B); and 7 with neither EBV-associated symptoms nor persistent high EBV loads in PBMCs (Group C)). RESULTS: n-PCR revealed EBV-DNA in PBMCs from all patients. The EBV genome was present in plasma in 3 (75%), 1 (17%), and 0 (0%) in Groups A, B and C (p < 0.01 for A vs. B and A vs. C). EBV loads detected by r-PCR in PBMCs were significantly higher in Groups A (p < 0.05) and B (p < 0.01) compared to Group C. EBV genomes in plasma were detected by n- and r-PCR in only the 2 cases with PTLD. One patient with lymphadenitis in Group A and 1 patient in Group B had EBV-DNA in plasma based on n-PCR, but the viral loads using r-PCR were < 250 copies/ml. CONCLUSION: EBV loads in PBMCs alone are insufficient for predicting EBV-associated symptoms including PTLD. Plasma EBV loads (over 250 copies/ml) estimated by r-PCR may be useful to distinguish PTLD from other EBV-associated diseases or asymptomatic viremia.

Prospective study of biliary cytology in suspected perihilar cholangiocarcinoma.

BACKGROUND: The diagnostic value of biliary cytology for hilar bile duct stricture is uncertain. This study prospectively examined three methods for the evaluation of biliary cytology in a consecutive group of patients. METHODS: Preoperative bile sampling by aspiration through a drainage catheter (aspiration samples), saline flush through a drainage catheter (saline samples) or direct sampling from a drainage bag (bag samples) was performed in consecutive patients with suspected perihilar cholangiocarcinoma who underwent resection after endoscopic nasobiliary drainage or percutaneous transhepatic biliary drainage. All bile sampling was performed three times on separate days. The accuracy of cytology in the diagnosis of carcinoma was determined. RESULTS: Of 100 consecutive patients with hilar strictures, 97 had histologically proven cholangiocarcinoma. The proportion of these 97 patients who had a positive finding on cytology in at least one of three sampling sessions was 55 per cent for aspiration samples, 48 per cent for bag samples and 38 per cent for saline samples (P = 0·021, aspiration versus saline). Tumour length correlated significantly with overall positivity. For aspiration samples, sensitivity was 55 per cent, specificity was 100 per cent and accuracy 56·0 per cent. CONCLUSION: For biliary cytology, sampling by catheter aspiration is more effective than catheter flushing or sampling from a drainage bag. Repeated sampling increases sensitivity. Biliary cytology has modest diagnostic yield, but is easy to perform, highly specific, and can provide a definitive diagnosis.

Correlation between genotype and supernumerary tooth formation in cleidocranial dysplasia.

INTRODUCTION: Cleidocranial dysplasia (CCD, MIM#119600), for which the responsible gene is RUNX2, is a genetic disorder characterized by hypoplasia or aplasia of the clavicles, patent fontanelles, and a short stature. Supernumerary teeth and delayed eruption and impaction of permanent teeth are frequently associated with CCD. Our previous study reported wide intrafamilial variation in supernumerary tooth formation associated with a mutation in the RUNT-domain of RUNX2, suggesting a low correlation between the genotype and supernumerary tooth formation. To further clarify this point, a more precise evaluation was performed. DESIGN: Gene mutational analysis of nine Japanese individuals with CCD was performed. Dental and skeletal characteristics were examined based on patient examinations and radiographs. RESULTS: Four different gene mutations, including one novel mutation in RUNX2 gene (NM_001024630), were identified. Among them, four individuals had the R225Q mutation, three siblings had the P224S mutation, and the other two individuals had different frame-shift mutations. Wide variations in supernumerary tooth formation were observed in individuals with identical gene mutations, and discordance was seen between monozygotic twins. Asymmetric supernumerary tooth formation was noted in five out of the nine individuals. CONCLUSION: Individuals with identical gene mutations showed a wide variation in the supernumerary tooth formation. Not only the genotype but also environmental factors and a complex system including epigenetics and copy number variation might regulate supernumerary tooth formation in CCD.

Caveolin-1 expression is a distinct feature of chronic rejection-induced transplant capillaropathy.

Peritubular capillary basement membrane multilayering (PTCBMML) is a pathological landmark of chronic rejection-induced transplant capillaropathy (TC), but its cellular mechanisms are not fully understood. We observed de novo caveolae formation in endothelial cells in TC under electron microscopy. To examine the role of caveolae and their structural components in TC, biopsy samples from cases of chronic rejection were double-immunostained for Caveolin-1 (Cav-1) and Pathologische Anatomie Leiden-endothelium (PAL-E; a marker of peritubular capillary [PC]). Thirty-two cases of chronic rejection (group I) were compared with 18 cases of interstitial fibrosis and tubular atrophy with no evidence of any specific etiology (IF/TA; group II) and eight cases of peritubular capillaritis (group III). The Cav-1/PAL-E immunoreactivities in groups I-III (%Cav-1/PAL-E) were 41.8+/-23.1%, 8.1+/-7.3% (p < 0.01 vs. group I) and 12.7+/-7.4% (p < 0.01 vs. group I), respectively. Furthermore, multiple linear regression models demonstrated that %Cav-1/PAL-E was independently associated with the PTCBMML grade and reduced PC number. No correlation was observed between %Cav-1/PAL-E and PC C4d deposition in group I. We conclude that de novo caveolae formation in PC endothelia is involved in TC in chronic rejection.

Monitoring of Epstein-Barr virus load and killer T cells in pediatric renal transplant recipients.

AIM: The aim of this study is to establish a monitoring method to prevent Epstein-Barr virus (EBV)-associated symptoms including post-transplant lymphoproliferative disorder (PTLD) that occur after pediatric renal transplantation. SUBJECTS AND METHODS: Circulating EBV loads were quantified by real-time PCR every 1 - 3 months after grafting in 22 pediatric recipients (13 EBV-seronegative [R(-)] and 9 EBV-seropositive [R(+)] recipients before grafting). The peripheral blood cell populations of non-specific activated killer cells (CD8+HLA-DR+ phenotype) in 13 R(-) recipients and EBV-specific cytotoxic T cells (CTLs) reactive with a tetramer expressing HLA-A24-restricted EBV-specific antigens in 8 of 13 R(-) recipients were determined by flow cytometry. RESULTS: EBV-associated symptoms including PTLD (2 cases) were found in 4 R(-) and none of the R(+) recipients. The maximum of EBV load in the R(-) group was significantly higher that in the R(+) group. In R(-) recipients, 4 symptomatic cases had significantly more EBV genome than asymptomatic cases. EBV-specific CTLs were detected in 6 of the 8 R(-) recipients, but these CTLs could not be detected in 1 of the 2 cases at onset of PTLD. The percentage of CD8+HLA-DR+ cells was significantly higher in asymptomatic recipients than in recipients with EBV-associated symptoms whose EBV loads were over 400 copies/microg DNA. CONCLUSION: Monitoring of killer T cells and EBV loads may allow assessment of the risk of EBV-associated symptoms, and high EBV loads and low EBV-specific and/or non-specific CTL responses may be predictive for development of EBV-associated symptoms such as PTLD.

Partial bladder transplantation with en bloc kidney transplant--the first case report of a 'bladder patch technique' in a human.

Transplantation of the urinary bladder has not been reported in humans. We transplanted a portion of the donor bladder with an en bloc kidney graft in a 12-month-old girl. The child had a congenital hypoplastic single kidney with an ectopic ureteral opening into the vagina. Her native bladder was extremely small. Bilateral kidneys were transplanted en bloc with their ureters connected to a patch of the donor bladder, which encompassed the bilateral ureterovesical junctions (UVJs) (bladder patch technique). Approximately one-third of the donor bladder wall was used. The bladder patch reperfused well via blood supply from the ureters. Posttransplant cystoscopy with retrograde cystogram revealed a viable transplanted bladder with normal emptying of transplanted ureters. No reflux across the donor UVJs was seen in a voiding cystourethrogram. The child is doing well with normal renal function at 18-month follow-up.

Diversity of supernumerary tooth formation in siblings with cleidocranial dysplasia having identical mutation in RUNX2 : possible involvement of non-genetic or epigenetic regulation.

INTRODUCTION: Cleidocranial dysplasia (CCD, MIM #119600) is an autosomal-dominant disorder characterized by hypoplasia or aplasia of clavicles, patent fontanelles and short stature. The responsible gene has been identified as RUNX2. CCD is also accompanied by characteristic dental abnormalities, e.g. supernumerary teeth, delayed eruption and impaction of permanent teeth. Intrafamilial variations of skeletal abnormalities are reported but those of dental abnormalities are obscure. To clarify this point, a precise examination of the dental features of CCD siblings having identical mutation was performed. DESIGN: Gene mutational analysis of three Japanese CCD siblings and their father was performed. Skeletal and dental characteristics were examined by the inquiry and radiographs. RESULTS: Three siblings uniformly showed patent fontanelles and short stature. They and their father had a novel missense mutation in the RUNT-domain (P210S) of RUNX2. The siblings were completely discordant for the dental characteristics with the position and number of supernumerary teeth being completely different. The youngest, a 12-year-old boy, had six supernumerary teeth, which appeared symmetrically around the maxillary canines and mandibular premolars. The second, a 15-year-old girl, had four supernumerary teeth which appeared around the mandibular incisors. The oldest, a 17-year-old boy, had 11 supernumerary teeth, which were symmetrically around the mandibular lateral dentition and asymmetrically around the maxillary incisors and premolars. CONCLUSION: The present study suggests the involvement of non-genetic or epigenetic regulation in supernumerary tooth formation in CCD.

Glomerular expression of plasmalemmal vesicle-associated protein-1 in patients with transplant glomerulopathy.

Transplant glomerulopathy (TG) is a prominent feature of chronic rejection that is characterized by double contours of the glomerular capillaries (GC). In this report, we demonstrate that one of the histopathological features of TG is a phenotypic change of glomerular endothelial cells which is illustrated by increased caveolae formation. To verify the endothelial changes in this disease, we examined the expression of plasmalemmal vesicle-associated protein-1 (PV-1), a glycoprotein associated with plasmalemmal vesicles (caveolae), in the glomeruli of TG patients using pathologische anatomie Leiden-endothelium (PAL-E) antibody. Twenty-six cases of chronic allograft nephropathy (CAN) with TG were examined, compared with 16 cases of CAN without TG, type I MPGN (4 cases), and transplant glomerulitis (8 cases). Overall, 24 of 26 (92.3%), 4 of 16 (25%), 0 of 4, 0 of 8 cases were PAL-E-positive for GC, respectively. Further, the extent of glomerular PAL-E expression was positively correlated with both the grade of TG (rs= 0.72, p = 0.0003) and proteinuria (g/day) (rs= 0.51, p = 0.02). A correlation was not observed between glomerular PAL-E positivity and peritubular capillary C4d deposits (Yetes chi = 0.23, p = 0.89). In summary, the present study demonstrates expression of PV-1 in the GC of TG which is correlated with the grade of TG and proteinuria.