Possible involvement of IkappaB kinase 2 and MKK7 in osteoclastogenesis induced by receptor activator of nuclear factor kappaB ligand.

Recent studies have revealed the essential role of the receptor activator of nuclear factor kappaB (NF-kappaB) ligand (RANKL) in osteoclast differentiation and activation. Adenovirus vector could efficiently transduce genes into RAW264.7 cells, which differentiate into osteoclast-like multinucleated cells in the presence of RANKL. The role of NF-kappaB and c-jun N-terminal kinase (JNK) activation in RANKL-induced osteoclast differentiation was investigated using an adenovirus vector carrying the dominant negative 1kappaB kinase 2 gene (AxIKK2DN) or dominant negative MKK7 gene (AxMKK7DN). IKK2DN and MKK7DN overexpression in RAW cells specifically suppressed the NF-kappaB activation and JNK activation in response to RANKL, respectively, without affecting other signaling pathways. Either inhibition of NF-kappaB or JNK pathways dose-dependently inhibited osteoclast formation induced by RANKL. These results suggest that both NF-kappaB and JNK activation are independently required for osteoclast differentiation.     

Oral styletted intubation under video control in a patient with a large mobile glottic tumour and a difficult airway

PURPOSE: With fibreoptic intubation, advancement of the endotracheal tube (ETT) through the glottis is blind. Thus, in patients with a laryngeal tumour, there is a potential for damage to the tumour. Previously, we proposed the use of a fibreoptic bronchoscope (FOB)-video camera system to permit visualization of tube passage. We used this technique successfully in a patient with a known difficult airway and a large glottic tumour. CLINICAL FEATURES: A 61-yr-old man with a known history of difficult laryngoscopic intubation underwent laryngeal microsurgery for recurrence of a glottic tumour. As preoperative indirect laryngoscopy revealed a large, mobile, and pedunculated glottic lesion obstructing the glottic opening, we planned a conventional awake fibreoptic intubation. Endoscopy showed that the tumour partially obstructed the glottis and the space between the tumour and the glottic opening was very narrow. To avoid damage to the tumour, we changed to an alternative fibreoptic intubation technique. The FOB attached to a video camera was passed nasally and a jaw thrust manoeuver was applied, providing an excellent view of the larynx. An anesthesiologist inserted the ETT with a curved stylet orally, and carefully advanced the tube tip into the space between the tumour and the glottic opening under video control. Absence of damage to the tumour and passage of the tube between the cords were confirmed visually. CONCLUSION: This alternative intubation technique, providing a view of the tube passage into the glottis, was a reasonable method to avoid potential damage to the glottic tumour by blind tube passage during conventional fibreoptic intubation.     

Prevalence and correlates of prostatitis in the health professionals follow-up study cohort

PURPOSE: Prostatitis is an ill-defined condition whose symptoms overlap with benign prostatic hyperplasia (BPH). Little is known about the prevalence and correlates of prostatitis, or factors that distinguish prostatitis from BPH. We examined these issues in a large, nationwide sample of healthy men. MATERIALS AND METHODS: In 1992, 31,681 United States health professionals without prostate cancer provided information on urological diagnoses, lower urinary tract symptoms, and demographic, clinical and lifestyle factors. We calculated age adjusted odds ratios and 95% confidence intervals for these correlates predicting a history of prostatitis. We also compared characteristics of men with prostatitis to those with BPH. RESULTS: The prevalence of a self-reported history of prostatitis was 16%. Men reporting a history of BPH had 7.7-fold greater odds of a history of prostatitis, those with moderate or severe lower urinary tract symptoms had 1.8 and 2.8-fold greater odds, respectively, those with a history of sexually transmitted disease had 1.8-fold greater odds and those reporting stress at home or work had 1.5- and 1.2-fold greater odds, respectively. The 2,163 men with prostatitis alone were younger and had less severe urinary tract symptoms (but a similar pattern of symptoms) than the 4,575 men with BPH alone. CONCLUSIONS: Self-reported prostatitis was common among healthy men of all ages but there was considerable overlap with self-reported BPH. Prostatitis had several identifiable correlates that may aid in its recognition.     

Lateral thrust of anterior cruciate ligament-insufficient knees and posterior cruciate ligament-insufficient knees

Leaving anterior cruciate ligament (ACL) insufficiency and posterior cruciate ligament (PCL) insufficiency untreated frequently leads to osteoarthritis (OA). The purpose of this study was to evaluate dynamically the lateral thrust of ACL-insufficient knees and PCL-insufficient knees, and from the findings investigate the relationship between cruciate ligament insufficiency and OA occurrence. An acceleration sensor was attached to the affected and control anterior tibial tubercles, acting in medial-lateral and perpendicular directions. The lateral thrust immediately after heel strike was measured continuously by a telemeter under stabilised walking conditions. When compared to the contralateral healthy knee, the peak value of lateral acceleration immediately after heel strike was significantly larger in the ACL-insufficient knee; and lateral thrust was increased, but not significantly, in the PCL-insufficient knee. Given that lateral thrust of the knee during walking increases due to ACL or PCL injury, it may be a principal contributor to OA progression.     

Heart allograft tolerance without development of posttransplant cardiac allograft vasculopathy in chimerism-based, drug-induced tolerance

BACKGROUND: Recently, we have described a drug (cyclophosphamide [CP] plus busulfan [BU])-induced skin allograft tolerance in mice that can regularly overcome fully H-2-mismatched barriers. Using this method, we have investigated whether or not this regimen can prolong the survival of heart allografts and inhibit the development of posttransplant cardiac allograft vasculopathy (CAV). METHODS: The components of the method are intravenous administration of 1 x 108 allogeneic spleen cells on day 0, intraperitoneal injection of 200 mg/kg of CP and 30 mg/kg of BU on day 2, and intravenous injection of T cell-depleted 1 x 107 allogeneic bone marrow cells from the same strain of mice on day 3. Heart grafting was performed on day 28. Chimerism in peripheral blood was followed by flow cytometric analysis, and histological analysis was performed at various times after grafting. RESULTS: In a fully major histocompatability complex (MHC)-mismatched combination of B10.D2 (H-2d, IE+)-->B10 (H-2b, IE-), stable, multilineage-mixed chimerism was observed permanently. B10.D2 heart grafts were accepted permanently in a donor-specific manner, and posttransplant CAV did not develop. CONCLUSIONS: These results demonstrated that the drug-induced tolerance recently established by us can regularly induce a long-lasting heart allograft tolerance without development of CAV.     

Very low but stable glomerular filtration rate after living kidney donation: is the concept of “chronic kidney disease” applicable to kidney donors?

Background  

Renal prognosis and outcome of Japanese kidney donors, who have lower preoperative glomerular filtration rate (GFR) and are generally older than their counterparts abroad, have scarcely been investigated. Here, the longitudinal changes in renal function of Japanese kidney donors were studied to clarify the prevalence and consequences of low GFR.     

Gene Expression Profile Prospectively Predicts Peritoneal Relapse After Curative Surgery of Gastric Cancer

Background

Peritoneal relapse is the most common pattern of tumor progression in advanced gastric cancer. Clinicopathological findings are sometimes inadequate for predicting peritoneal relapse. The aim of this study was to identify patients at high risk of peritoneal relapse in a prospective study based on molecular prediction.

Methods

RNA samples from 141 primary gastric cancer tissues after curative surgery were profiled using oligonucleotide microarrays covering 30,000 human probes. Firstly, we constructed a molecular prediction system and validated its robustness and prognostic validity by 500 times multiple validation by repeated random sampling in a retrospective set of 56 (38 relapse-free and 18 peritoneal-relapse) patients. Secondly, we applied this prediction to 85 patients of the prospective set to assess predictive accuracy and prognostic validity.

Results

In the retrospective phase, repeated random validation yielded ~68% predictive accuracy and a 22-gene expression profile associated with peritoneal relapse was identified. The prediction system identified patients with poor prognosis. In the prospective phase, the molecular prediction yielded 76.9% overall accuracy. Kaplan–Meier analysis of peritoneal-relapse-free survival showed a significant difference between the “good signature group” and “poor signature group” (log-rank p = 0.0017). Multivariate analysis by Cox regression hazards model identified the molecular prediction as the only independent prognostic factor for peritoneal relapse.

Conclusions

Gene expression profile inherent to primary gastric cancer tissues can be useful in prospective prediction of peritoneal relapse after curative surgery, potentially allowing individualized postoperative management to improve the prognosis of patients with advanced gastric cancer.     

Prognostic Significance of Immunohistochemically Detected Blood and Lymphatic Vessel Invasion in Colorectal Carcinoma: Its Impact on Prognosis

Background The prognostic significance of blood vessel invasion (BVI) and lymphatic vessel invasion (LVI) is unclear. Because of the absence of specific markers for venous and lymphatic vessels, earlier studies could not reliably distinguish between BVI and LVI. Methods By immunostaining for podoplanin and CD34 antigen, we retrospectively investigated LVI and BVI in 419 tissue specimens of colorectal carcinoma. We performed univariate and multivariate analysis of the clinicopathologic features, frequency of recurrence, and outcome of patients with or without LVI and BVI. Results The use of hematoxylin and eosin (H&E) staining to identify BVI and LVI yielded a false positive rate of 9.1% and false negative rate of 12.6%. The incidence of BVI was significantly higher among tumors with LVI than tumors without LVI (P <.001). In logistic multivariate analysis, only LVI (P < .001) was associated with lymph node metastasis and BVI (P = .015) was associated with distant recurrence. Calculating the prognostic relevance, both two invasion types correlated with decreased survival in univariate analysis (both P <.001). In multivariate analysis, BVI (P =.024), lymph node status (P =.003) and tumor stage (P <.001) remained statistically significant factors for survival. Conclusions Our results suggest that immunohistologic evaluation of BVI and LVI could be useful in colorectal carcinoma indicating the risk of lymph node metastasis and recurrence, thereby contributing to prognostic evaluation.     

Relationship among alpha-synuclein accumulation, dopamine synthesis, and neurodegeneration in Parkinson disease substantia nigra

The histologic hallmark of Parkinson disease (PD) is loss of pigmented neurons in the substantia nigra (SN) and locus ceruleus (LC) with accumulation of alpha-synuclein (alphaS). It has been reported that tyrosine hydroxylase (TH)-negative pigmented neurons are present in these nuclei of patients with PD. However, the relationship between TH immunoreactivity and alphaS accumulation remains uncertain. We immunohistochemically examined the SN and LC from patients with PD (n = 10) and control subjects (n = 7). A correlation study indicated a close relationship among decreased TH immunoreactivity, alphaS accumulation, and neuronal loss. In addition, 10% of pigmented neurons in the SN and 54.9% of those in the LC contained abnormal alphaS aggregates. Moreover, 82.3% of pigmented neurons bearing alphaS aggregates in the SN and 39.2% of those in the LC lacked TH immunoreactivity, suggesting that pigmented neurons in the SN have a greater tendency to lack TH activity than those in the LC. Recent studies have shown that this decrease of TH activity leads to a decrease of cytotoxic substances and that decreased dopamine synthesis leads to a reduction of cytotoxic alphaS oligomers. Therefore, the decrease of TH immunoreactivity in pigmented neurons demonstrated here can be considered to represent a cytoprotective mechanism in PD.     

Gender differences in 3D morphology and bony impingement of human hips

For the proper diagnosis or treatment of hip joint disorders caused by anatomical abnormalities, the normal hip joint morphology must be studied to understand its influence on the maximum range of motion (ROM) until bony impingement by focusing on gender differences. Acetabular and femoral morphologies were analyzed from 3D CT images of 106 normal hip joints from elderly men (n = 36 joints) and women (n = 70 joints), and measurements of ROM until bony impingement were made in four directions (flexion, extension, and external and internal rotation at 90° flexion) using surface models of the pelvis and femur reconstructed from the CT data. Gender differences were found not only in joint orientation, including anteversion and inclination of the acetabulum and femoral neck anteversion, but also in the shape around the joint, including the acetabular rim and the femoral neck. This ROM study also showed gender differences in all four standard directions. In conclusion, significant gender differences were observed in the acetabular and femoral morphology, which led to significant gender differences in ROM until bony impingement. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:333–339, 2011