Whole genome expression microarray reveals novel roles for Kif4 in monocyte/macrophage cells.

OBJECTIVE: Kinesin superfamily member 4 (Kif4), a conventional kinesin, is a microtubule-dependent molecular motor. The active movement of Kif4 participates in several cellular functions, including DNA repair, mitosis, the transport of macromolecules, survival of neurons and even tumorigenesis and progression. However, the role of Kif4 in monocyte/macrophage cells has not been reported. Our work aimed to increase understanding and further investigations of Kif4 in monocyte/macrophage cells. MATERIALS AND METHODS: RAW264.7 cells were transfected with Kif4 small interfering RNA (siRNA), and whole genome expression microarray analysis was employed to analyze gene expression after cells treatment with or without Kif4 siRNA. RESULTS: Our data found multiple differentially expressed genes which were enriched in the top 5 biological processes about innate immune response, immune response, response to interferon-beta, immune system process and cellular response to interferon-beta. 23 most significant pathways had been identified and enriched pathways indicated enrichment in peroxisome, lysosome, fatty acid metabolism, cell adhesion molecules and so on. CONCLUSIONS: Our work may help understand the roles of Kif4 in monocyte/macrophage cells and would give useful information on basic research and the function of monocyte/macrophage cells.

Expression of Kif5b protein is significantly associated with the progression, recurrence and prognosis of oral squamous cell carcinoma.

OBJECTIVE: Kinesin family member 5b (Kif5b), a conventional kinesin, mainly participates in lysosome and mitochondria transportation. Some studies have indicated that Kif5b may be associated with the development of a variety of tumors. However, the role Kif5b plays in oral squamous cell carcinoma (OSCC) has yet to be determined. Our study aimed at investigating the expression level of Kif5b in primary OSCC and discussing its clinical significance in patients' outcomes. PATIENTS AND METHODS: We measured Kif5b expression in 82 OSCC tissue samples with immunohistochemistry. The associations between the expression level of Kif5b and clinicopathological characteristics as well as patients' survival were statistically assessed. RESULTS: Kif5b level was significantly associated with tumor size (p=0.034), histological differentiation (p=0.028), disease recurrence (p=0.018), surrounding tissue invasion (p=0.045), recurrence time (p=0.036) and survival status (p=0.030). Kaplan-Meier cumulative survival analyses indicated that high expression of Kif5b was linked to worse overall survival (p=0.0112) and disease-free survival (p=0.0085). The univariate and multivariate Cox proportional hazard analysis further identified the expression status of Kif5b as an independent variable that correlated with patients' survival and recurrence. Furthermore, in 54 early-stage, clinically node negative OSCC patients, Kif5b expression were correlated with histological differentiation (p=0.034), disease recurrence (p=0.038) and surrounding tissue invasion (p=0.029). Univariate and multivariable logistic regression results showed that only Kif5b expression level could influence the probability of recurrence. CONCLUSIONS: Our results reveal that Kif5b expression is associated with poor clinical outcome in OSCC and even in early-stage, clinically node negative OSCC and may be a potential target for OSCC treatment.

Success of dental implants in vascularised fibular osteoseptocutaneous flaps used as onlay grafts after marginal mandibulectomy.

We have evaluated the survival of dental implants placed in vascularised fibular flap onlay grafts placed over marginal mandibulectomies and the effects on marginal bone loss of different types of soft tissue around implants under functional loading. From 2001-2009 we studied a total of 11 patients (1 woman and10 men), three of whom had had ameloblastoma and eight who had had squamous cell carcinomas resected. A total of 38 dental implants were placed either at the time of transfer of the vascularised fibular ostoseptocutaneous flaps (nine patients with 30 implants) or secondarily (two patients with eight implants). Four patients were given palatal mucosal grafts to replace intraoral skin flaps around the dental implants (n=13), and the other seven had the skin flaps around the dental implants thinned (n=25) at the second stage of implantation of the osteointegrated teeth. All vascularised fibular osteoseptocutaneous flaps were successfully transferred, and all implants survived a mean (range) of 73 (33-113) months after occlusal functional loading. The mean (SD) marginal bone loss was 0.5 (0.3) mm on both mesial and distal sides in patients who had palatal mucosal grafts, but 1.8 (1.6) mm, and 1.7 (1.5) mm, respectively, on the mesial and distal sides in the patients who had had thinning of their skin flaps. This difference is significant (p=0.008) with less resorption of bone in the group who had palatal mucosal grafts. Palatal mucosa around the implants helps to reduce resorption of bone after functional loading of implants.

The risk of bacteria in foam sclerotherapy: does the condition of the air in outpatient vs. operating rooms make a difference?

BACKGROUND: Foam sclerotherapy has been one of the most frequently applied therapeutic methods for the treatment of varicose veins and venous malformation. Few studies have investigated the sterile condition of the air used for foam creation. OBJECTIVES: To evaluate the bacterial conditions in foam created from the air in outpatient and operating rooms used for sclerotherapy treatment, in order to provide the basis for clinical applications in foam sclerotherapy. MATERIALS AND METHODS: In this study, we measured the amount of airborne microorganisms in the air in the operating room, and in the outpatient room, the polidocanol (POL) foam created using the air in the respective rooms, and the microorganisms present in the liquid POL. We used the settle plate method for air sampling. We used the Tessari method to generate foam. The experiment was repeated three times. RESULTS: Typical bacterial colonies were formed on nutrient agar plates in both the outpatient room and operating room air groups. No colonies were cultivated in the liquid POL. Although the use of sterile or nonsterile air in sclerotherapy produces significantly different results in the counts of colony-forming units, there was no difference in the foam created using sterile or nonsterile air (i.e. no colonies were cultivated on either foam). CONCLUSIONS: There is no increased risk of infection when using foam sclerotherapy in outpatient rooms compared with using foam created under sterile operating-room conditions.

Diagnostic value of CT perfusion imaging for parotid neoplasms.

OBJECTIVES: To assess the value of CT perfusion imaging in the differentiation of different histological categorization of benign tumours from malignant tumours in patients with parotid neoplasms. METHODS: CT perfusion was successfully performed in 62 patients with parotid neoplasms whose diagnoses were confirmed by surgery or biopsy. The software generated a tissue time-density curve (TDC) and measured blood volume, blood flow, mean transit time and capillary permeability surface product. One-way ANOVA and receiver operating characteristic curves were used to analyse the difference and diagnostic efficacies of all perfusion data between each one of the benign tumours and malignancies. Statistical significance was assigned at the 5% level. RESULTS: Pleomorphic adenomas mainly had a gradually ascending TDC. Warthin tumours showed a fast ascent followed by a fast descent. The TDC of basal cell adenomas had a fast ascension followed by a plateau, then a gradual descent. Malignant tumours mainly showed a rapidly ascending curve with a stable plateau. Significant differences were observed in blood flow, blood volume and mean transit time between pleomorphic adenomas and malignant tumours (p < 0.05) as well as in blood flow and blood volume between the Warthin tumours, the basal cell adenomas and the malignant tumours (p < 0.05). Differences in permeability surface between the basal cell adenomas and malignant tumours were significant (p < 0.01). CONCLUSION: CT perfusion of parotid gland could provide TDC and perfusion data, which were useful in the differentiation of different histological benign tumours and malignant tumours in the parotid gland.

[Aspects of microsurgical reconstruction for lower extremity defects]. / Aspekte der mikrochirurgischen Rekonstruktion an der unteren Extremität.

The interdisciplinary approach to lower extremity reconstruction between orthopaedic and plastic surgeons is the basis for an efficient soft-tissue coverage. The joint team and the transfer of local, regional and free flaps have been shown to reduce the rate of amputation. After the spread of microsurgical techniques and further innovations, e. g., bony reconstruction by vascularized bone grafts, microsurgery now plays an important role in lower extremity reconstruction. Main considerations for the microsurgical approach are the choice of flap type aiming at good functional results with a stable soft-tissue coverage. The use of innervated flaps and functioning muscle transfer have led to an increased patient satisfaction and quality of life. Timing of reconstruction has been shown to have an impact on the results of microsurgical reconstruction. The importance of "composite tissue allotransplantation - CTA" applied for lower extremity reconstruction has to be evaluated in further studies.

The physiology, microcirculation and clinical application of the shunt-restricted arterialized venous flaps for the reconstruction of digital defects.

Reconstruction of digital defects using the venous flap offer several advantages but remained unpopular owing to levels of venous congestion rates. We performed animal studies to test the hypothesis that an arterio-venous shunt increases pressure for peripheral flap perfusion and decreases venous congestion. Using an abdominal adipofascial flap model in six male Sprague-Dawley rats, microcirculation was modified as follows: type I - arterial flap; type II - flow-through arterio-venous flap (AVF); and type III - shunt-restricted AVF. In type I flaps, blood flow was observed to be unidirectional in both arterioles and venules. In type I flaps, blood flow was observed to be unidirectional in both arterioles and venules. In type II flaps, blood flow oscillated without a dominant direction and came to a standstill. In type III flaps, blood flowed proximally in a reverse direction whereas distally, flow was similar to type I flaps. In a clinical series, 21 patients received a total of 22 shunt-restricted AVFs. All 22 clinical flaps survived; four flaps suffered epidermolysis but recovered without full thickness loss.

A reappraisal of functional reconstruction of extension of the knee following quadriceps resection or loss.

The current indications for functional restoration of extension of the knee following quadriceps resection or loss require reappraisal. The contribution of pedicled and free functional muscle transfer is likely to be over-emphasised in many studies, with good functional outcomes predominantly reported only in the context of cases with residual quadriceps function. In cases with total quadriceps resection or loss, all forms of reconstruction perform poorly. Furthermore, in smaller resections with loss of two or fewer components of the quadriceps, minimal impairment of function occurs in the absence of functional reconstruction, suggesting that functional restoration may not be warranted. Thus there is a paradox in the current approach to quadriceps reconstruction, in that small resections are likely to be over-treated and large resections remain under-treated. This review suggests a shift is required in the approach and rationale for reconstructing functional extension of the knee after quadriceps resection or loss. A classification based on current evidence is suggested that emphasises more clearly the indications and rationale for functional transfers.

Self-perceived health and return to work following work-related hand injury.

BACKGROUND: Return to work is an important outcome following traumatic work-related hand injuries. It is unclear how psychosocial factors affect the time to return to work following traumatic work-related hand injury. AIMS: To investigate the relationships between hand injury severity, self-perceived health, demographics and time off work (TOW) following traumatic work-related hand injuries and the influence of psychosocial factors on the readiness of return to work. METHODS: Data from 120 traumatic work-related hand injured patients were gathered. The Modified Hand Injury Severity Score (MHISS) and Short Form Health Survey (SF-36) were used to assess the severity of hand trauma and self-perceived health, respectively. The relationships between MHISS, SF-36, demographics and TOW were analysed by multiple regression analysis. RESULTS: Mean duration of TOW was 127 days for patients with a mild MHISS, 108 days for a moderate score, 160 days for a severe score and 236 days for those with a major score. A positive correlation between MHISS and duration of TOW was identified. Self-perceived physical functioning was found to have a negative correlation with TOW, whereas self-perceived mental health was positively correlated with TOW. CONCLUSIONS: This study highlights the importance of self-perceived health in considering return to work following traumatic work-related hand injury.

Preoperative circulating C-reactive protein levels predict pathological aggressiveness in oral squamous cell carcinoma: a retrospective clinical study.

OBJECTIVES: Previous studies have demonstrated a relationship between elevated serum C-reactive protein (CRP) levels and shorter survival in cancer patients. Few studies, however, have investigated the role of serum CRP levels in oral squamous cell carcinoma. The present study was conducted to analyze the relationship between preoperative CRP levels, clinicopathologic factors, and prognosis in oral squamous cell carcinoma patients. DESIGN: Retrospective clinical study. SETTING: University teaching hospital. PARTICIPANTS: Eighteen oral cavity leukoplakia and 59 oral squamous cell carcinoma patients between November 2006 and November 2009 from the Chang Gung Memorial Hospital. OUTCOME MEASURES: Clinicopathologic parameters, disease-free survival and overall survival were correlated with CRP levels. METHODS: Serum CRP levels were measured preoperatively, and all oral cavity cancer patients underwent curative intent radical surgery with or without postoperative adjuvant therapy. RESULTS: The CRP levels in leukoplakia patients were used to analyze if factors (including diabetes and liver cirrhosis, smoking, alcohol drinking and areca quid chewing) influence CRP levels, and the results demonstrated they were not associated with CRP elevation (> 5.0 mg/L) (P > 0.05). In oral cancer patients, elevated CRP levels were associated with tumor status (P = 0.005), tumor stage (P = 0.054), bone invasion (P = 0.033), lymph node metastasis (P = 0.004) and lymph node extra-capsular spread (P = 0.018). Patients with higher CRP levels showed poorer disease-free survival (log rank test, P < 0.001) and overall survival (log rank test, P = 0.013). CONCLUSIONS: Preoperative serum CRP levels are associated with advanced tumor stage, bone invasion, lymph node metastasis, lymph node extra-capsular spread and patients' survival. CRP is thus potentially a prognostic indicator, but studies with longer follow-up will be needed to confirm its reliability.

Radiosensitization and anti-tumour effects of cytosine deaminase and thymidine kinase fusion suicide gene in human adenoid cystic carcinoma cells.

Herpes simplex virus thymidine kinase (HSV-TK) and Escherichia coli cytosine deaminase (CD) can convert innocuous prodrugs into cytotoxic metabolites and are being investigated for use in gene therapy for cancer. Human adenoid cystic carcinoma (ACC-2) cells transduced with a CD/HSV-TK fusion gene (ACC-2/CD-TK cells) were found to be more sensitive to radiation than ACC-2 cells when exposed to 5-fluorocytosine (5-FC; 40 microg/ml) plus ganciclovir (0.1 microg/ml) for 48 h before irradiation. Analysis of radiation survival curves for cells exposed to 5-FC plus ganciclovir before irradiation showed that ACC-2 cells had a higher capacity for sublethal damage repair (D(q) value) and greater cellular radiosensitivity (D(0) value) than ACC-2/CD-TK cells. Colony formation rate after 2 Gy of irradiation was significantly greater for ACC-2 than for ACC-2/CD-TK cells when cells were treated with 5-FC plus ganciclovir before irradiation. This study, therefore, indicates that addition of radiation might substantially improve the therapeutic potential of CD-TK fusion gene therapy of human adenoid cystic carcinomas.

Effect of cryopreservation on the immunogenicity of osteoblasts.

BACKGROUND: Tissue-engineered bone is the most perspective and ideal prosthesis for bone defects. But the immunological reaction in allograft is unavoidable. To date there has not been an analysis of the effect of cryopreservation on osteoblast immunogenicity. In this study, we investigated the effects of fluid nitrogen cryopreservation on immunogenicity of osteoblasts. MATERIALS AND METHODS: The osteoblasts were harvested and cultured from the tibial periosteum of New Zealand rabbits, examined by alkaline phosphatase (ALP) and alizarin red S stains, and then cryopreserved for 90 days. Cryopreserved (group C) and fresh (group F) osteoblasts were labeled by the immunofluorescene technique, and the MHC class I antigen was examined by flow cytometric (FC) assay. At the same time, by establishing an osteoblast and lymphocyte mixed culture model (OLMC), the immunogenicity of osteoblasts was examined. RESULTS: The positive rate of MHC class I antigen in group F was 46.36%+/-3.15%, while in group C it was 26.43%+/-2.57%. The MHC I antigen expression was significantly stronger in fresh cells than that in cryopreserved ones (P<.01). In the OLMC assay, the stimulation index (SI) of group F was 3.55+/-0.78, which was significantly higher than that of group C (1.83+/-0.41; P<.01). CONCLUSIONS: The FC assay and OLMC experiments showed that osteoblasts surface antigen expression and allostimulatory function were greatly reduced by cryopreservation. Fluid nitrogen cryopreservation is an ideal method to reduce the immunogenicity in allograft.

Bipaddled radial forearm flap for the reconstruction of bilateral buccal defects in oral submucous fibrosis.

Oral submucous fibrosis can result in progressive closure of the mouth. A total of 10 patients with advanced oral submucous fibrosis were surgically treated. The procedure consisted of (1) release of all the intraoral fibrotic tissue, (2) masticatory muscle myotomy and coronoidotomy, and (3) reconstruction with a bipaddled radial forearm flap. Preoperative mouth opening was 0-5mm (mean 2.3mm). The intraoperative mouth opening was 12-20mm (mean 16 mm) after submucous release, and 32-42 mm (mean 35.5mm) after further release via myotomy and coronoidotomy. The proximal flap included one perforator in four patients and two perforators in the remaining six patients. The flaps were 8-9 cm in length and 2-2.5 cm in width. Nine flaps survived uneventfully. Arterial thrombosis was noted in one flap, which was successfully salvaged. Temporomandibular joint subluxation developed in one patient. Two patients needed flap revision due to bulkiness. The postoperative mouth opening was 18-38 mm (mean 28.2mm) after a mean of 21 months' follow-up, and the mean increase was 25.9 mm. A bipaddled radial forearm flap, using a single donor site, can cover two separate buccal defects after release of oral submucosal fibrosis and obviate the need for a second free flap.

Autosomal dominant inherence of multiple supernumerary teeth.

The case is presented of 16 supernumerary teeth in an 11-year-old Chinese female patient with congenital cardiopathy. It was found that the patient's mother had the same clinical manifestation. A detailed investigation into the family history was carried out. Though the etiology of this dental anomaly remains unclear, genetics as a key factor in the development of supernumerary teeth is highlighted.

Alterations of p16INK4a tumour suppressor gene in mucoepidermoid carcinoma of the salivary glands.

Mucoepidermoid carcinoma (MEC) is common in the salivary glands, but alterations of the p16(INK4a) tumour suppressor gene are largely unknown. The aim of this study was to analyse p16(INK4a) gene alterations in MEC, and evaluate their significance for carcinogenesis. Thirty-eight salivary glands with MEC and six normal salivary glands were studied for p16(INK4a) alterations. In the MEC-affected group, there were 23.7% (9/38) and 13.2% (5/38) cases of homozygous deletion, and 5.3% (2/38) and 2.6% (1/38) cases of point mutation in p16(INK4a) exon 1 and exon 2, respectively. Hypermethylation of the p16(INK4a) gene promoter was found in 13 cases (13/38, 34.2%). Alterations of the p16(INK4a) gene were not found in the normal salivary glands. These findings suggest that the main mechanisms of inactivation of the p16(INK4a) gene in MEC of the salivary glands are promoter hypermethylation and homozygous deletion.

Functional MR imaging of the human sensorimotor cortex after toe-to-finger transplantation.

BACKGROUND: A model of toe-to-finger transplantation has been used in studying peripheral nerve regeneration and central reorganization. It was found that recovery of sensory perception depends not only on peripheral reinnervation but also on central integrative mechanisms. OBJECTIVE: Our aim was to investigate functional changes of the brain and somatotopic representation of the transplanted toes after toe-to-finger transplantation. MATERIALS AND METHODS: Six patients who had toe-to-finger transplantation from 3 to 8 years earlier underwent motor and sensory functional MR imaging studies of transplanted toes and opposite corresponding normal fingers. The motor task was performed by repetitively tapping of the transplanted toe or finger against the thumb, whereas the sensory task was applied by tactilely stimulating the pulp of the transplanted toe or finger. RESULTS: The main activation areas from both types of stimulations were located in the expected location of the finger homunculus of the primary sensorimotor cortex. In addition, activated volumes from the transplanted toes were significantly greater than those from the opposite fingers (P = .017 for motor task and P = .005 for tactile sensory task, paired samples Student t test). CONCLUSIONS: Functional recruitment in the primary sensorimotor cortex seemed to have occurred following toe-to-finger transplantation. The transplanted toe was somatotopically represented in the hand area.

Reliability of zone IV in the deep inferior epigastric perforator flap: a single center's experience with 74 cases.

From March 2000 to June 2002, 74 deep inferior epigastric perforator (DIEP) flaps were performed in 73 female patients for oncological post-mastectomy breast reconstruction in Chang Gung Memorial Hospital. The mean age was 44.2 years and mean body weight was 56.6 kg. Twenty-five breast reconstructions were immediate and 49 were delayed. The average size of the flap was 30.1x12.0 cm and the mean number of perforators was 2.2. The average weight of the harvested flap was 595 g and 85.6% (mean: 509 g) of the flap was used for shaping the new breast mound. Zone IV was not discarded, except in one case. Total flap failure and donor site morbidity was not encountered. Only one flap was revised due to venous congestion (1.4%) and successfully salvaged. Partial flap loss occurred in two patients (2.7%). Fat necrosis was detected in 10 cases (13.5%) and sizes ranged from 2x2 to 4x5 cm. The numbers of perforators and the percentage of the used flap weight/total flap weight were not related to the complications. The free DIEP flap and inclusion of zone IV is a reliable and valuable method of breast reconstruction and provides superior aesthetic outcomes.

Clinical experience of 1284 free anterolateral thigh flaps.

The past decade has witnessed yet another rebirth in reconstructive surgery with the introduction of the so-called "perforator flaps". The demonstration of safe harvest of skin flaps based on dissection of cutaneous pedicles regardless of the course taken (through muscle or septum) has been revolutionary in allowing much greater choice in donor sites. Based on our experience in 1284 cases, the anterolateral thigh (ALT) region has proven itself to be an ideal donor site with reliable vascularity, ease of harvest and tremendous versatility. Inclusive in this flap is a large cutaneous territory, multiple components (adipofascial, muscle, fascia and skin) and possibility of chimeric applications. Although particularly useful in the head and neck (911 cases), the ALT flap was applied to reconstruct defects throughout the body. Donor site morbidity is limited as well. In short, the anterolateral thigh flap represents one of the most useful soft tissue flaps for free tissue transplantation.

Debrisoquine 4-hydroxylase (CYP2D6) genetic polymorphisms and susceptibility to schizophrenia in Chinese patients from Taiwan.

Debrisoquine 4-hydroxylase (CYP2D6) is one of the cytochrome P450 enzyme families that metabolize many compounds. Polymorphic activities of debrisoquine 4-hydroxylase were suggested to be associated with some complex diseases, such as cancer and Parkinson's disease. Schizophrenia is also a complex disorder, and hence we are interested in understanding if the CYP2D6 gene is a susceptibility gene for schizophrenia in Chinese. We determined the genotype and allele frequencies of four molecular variants of CYP2D6 gene (i.e. 188C/T, 1934G/A, 2938C/T and 4268C/G) in 162 Chinese schizophrenic patients and 94 non-psychotic control subjects from Taiwan. No significant differences of allele or genotype frequencies of three polymorphisms (i.e. 188T/C, 2938C/T and 4268C/G) were detected between patients and control subjects. The 1934A allele, which accounts for the majority of poor metabolizers in Caucasians, was not detected in either patients or control subjects, indicating that the 1934A allele is very rare in Chinese. Our data suggest that the CYP2D6 gene may not be a susceptibility gene for schizophrenia in Chinese schizophrenic patients.