Gene expression profile of renal proximal tubules regulated by proteinuria

BACKGROUND: Proximal tubules activated by reabsorption of protein are thought to play significant roles in the progression of kidney diseases. Thus, identification of genes related to proteinuria should provide insights into the pathological process of tubulointerstitial fibrosis. METHOD: Gene expression profiles were constructed by means of direct sequencing procedures to identify genes induced in the mouse kidney proximal tubules (PT) exposed to proteinuria. RESULTS: By comparing the gene expression of control PT to that of disease model PT, the abundantly expressed genes in control PT were down-regulated presumably because of potentially toxic effects of proteinuria. From the more than 1000 up-regulated genes, an immunity related gene, thymic shared antigen-1 (TSA-1), and a novel gene, GS188, were selected for further characterization. The increased expression of TSA-1, a member of the Ly-6 family, and of GS188 in response to proteinuria was confirmed by Northern analysis, immunohistochemistry, in situ hybridization and laser microdissection along with real-time PCR analysis. Full length cloning of GS188 identified it as a family member of LR8 that was reported to express predominantly in fibroblasts. CONCLUSIONS: The gene expression profiles showed that the expression patterns in PT were changed dramatically by proteinuria. The profiles include novel genes that should be further characterized to aid the understanding of the pathophysiology of progressive kidney diseases.     

A gastric duplication cyst with an aberrant pancreatic ductal system: report of a case

We report an extremely rare case of a gastric duplication cyst together with an aberrant pancreatic ductal system, which communicated with the stomach rather than the pancreatic ductal system with no evidence of pancreatitis. A 46-year-old woman developed severe abdominal pain after a 10-year history of occasional mild abdominal pain. Upper gastrointestinal barium radiography showed a rigidity of the stomach wall, and gastroscopy revealed a fistula orifice at a greater curvature of the gastric body. Subsequent endoscopic suction of mucous secretion from within the fistula provided immediate pain relief. Abdominal computed tomography and ultrasonography showed a cystic mass contiguous with the stomach wall. Surgical exploration revealed an uncommon anomaly of a gastric duplication cyst with the aberrant pancreatic lobe. The patient made an uneventful recovery and remains well 4 years after surgery. We also herein review ten other similar cases of this uncommon congenital anomaly reported in the literature. Received: August 20, 2001 / Accepted: January 8, 2002     

Surgical outcomes of foramen magnum decompression for syringomyelia associated with Chiari I malformation: relation between the location of the syrinx and body pain

Background  

There have been few reports about the relation between the morphology of syrinxes and body pain in syringomyelia associated with Chiari I malformation. To investigate this phenomenon, the relation between the location of the syrinx and body pain before and after foramen magnum decompression (FMD) were evaluated.     

Low-level Er:YAG laser irradiation enhances osteoblast proliferation through activation of MAPK/ERK

Although the use of high-level Er:YAG laser irradiation has been increasing in periodontal and peri-implant therapy, the effects of low-level Er:YAG laser on surrounding tissues and cells remain unclear. In the present study, the effects of low-level Er:YAG laser irradiation on osteoblast proliferation were investigated. Cells of the osteoblastic cell line MC3T3-E1 were treated with low-level Er:YAG laser irradiation with various combinations of laser settings (fluence 0.7–17.2 J/cm²) and in the absence or presence of culture medium during irradiation. On day 1 and/or day 3, cell proliferation and death were determined by cell counting and by measurement of lactate dehydrogenase (LDH) levels. Further, the role of mitogen-activated protein kinase (MAPK) pathways in laser-enhanced cell proliferation was investigated by inhibiting the MAPK pathways and then measuring MAPK phosphorylation by Western blotting. Higher proliferation rates were found with various combinations of irradiation parameters on days 1 and 3. Significantly higher proliferation was also observed in laser-irradiated MC3T3-E1 cells at a fluence of approximately 1.0–15.1 J/cm², whereas no increase in LDH activity was observed. Further, low-level Er:YAG irradiation induced the phosphorylation of extracellular signal-regulated protein kinase (MAPK/ERK) 5 to 30 min after irradiation. Although MAPK/ERK 1/2 inhibitor U0126 significantly inhibited laser-enhanced cell proliferation, activation of stress-activated protein kinases/Jun N-terminal kinase (SAPK/JNK) and p38 MAPK was not clearly detected. These results suggest that low-level Er:YAG laser irradiation increases osteoblast proliferation mainly by activation of MAPK/ERK, suggesting that the Er:YAG laser may be able to promote bone healing following periodontal and peri-implant therapy.     

Regulation of ER molecular chaperone prevents bone loss in a murine model for osteoporosis

Endoplasmic reticulum (ER) stress response is important for protein maturation in the ER. Some murine models for bone diseases have provided significant insight into the possibility that pathogenesis of osteoporosis is related to ER stress response of osteoblasts. We examined a possible correlation between osteoporosis and ER stress response. Bone specimens from 8 osteoporosis patients and 8 disease-controls were used for immunohistochemical analysis. We found that ER molecular chaperones, such as BiP (immunoglobulin heavy-chain binding protein) and PDI (protein-disulfide isomerase) are down-regulated in osteoblasts from osteoporosis patients. Based on this result, we hypothesized that up-regulation of ER molecular chaperones in osteoblasts could restore decreased bone formation in osteoporosis. Therefore, we investigated whether treatment of murine model for osteoporosis with BIX (BiP inducer X), selective inducer BiP, could prevent bone loss. We found that oral administration of BIX effectively improves decline in bone formation through the activation of folding and secretion of bone matrix proteins. Considering these results together, BIX may be a potential therapeutic agent for the prevention of bone loss in osteoporosis patients.     

Application of Polyethylene Glycolic Acid Felt with Fibrin Sealant to Prevent Postoperative Pancreatic Fistula in Pancreatic Surgery

Objective

The purpose of this nonrandomized retrospective study was to report our new procedures using polyethylene glycolic acid (PGA) felt with fibrin sealant to prevent severe pancreatic fistula in patients undergoing pancreatic surgery.

Methods

From 2000 to 2008, 54 and 63 patients underwent pancreaticoduodenectomy (PD) and distal pancreatectomy (DP), respectively. Of those patients, we applied PGA felt with fibrin sealant to 18 PD patients and 26 DP patients. In PD patients, the PGA felt was wrapped around the pancreatic suture site, while in DP patients, the PGA felt was wrapped around the predictive division site. The pancreaticojejunostomy site in PD patients and the cut stump in DP patients were coated with fibrin sealant. We compared the occurrence rates for severe postoperative pancreatic fistula (POPF) that occurred after PD or DP both with and without our new procedures.

Results

Before introduction of our procedures, severe POPF developed in 14 of 36 PD patients (39%) and 10 of 37 DP patients (27%). In contrast, after introduction of our procedures, the incidence of POPF was only one in both of 18 PD (6%; P?=?0.016) and 26 DP (4%; P?=?0.017) patients.

Conclusion

In summary, our procedure using PGA felt with fibrin sealant may reduce the risk of severe POPF.     

Expression of potential molecular markers in prostate cancer: correlation with clinicopathological outcomes in patients undergoing radical prostatectomy

The objective of this study was to evaluate the expression levels of multiple potential molecular markers in prostate cancer to clarify the significance of these markers as prognostic indicators in patients undergoing radical prostatectomy (RP). This study included a total of 193 patients with clinically organ-confined prostate cancer who underwent RP without any neoadjuvant therapies. Expression levels of 12 proteins, including Ki-67, p53, androgen receptor (AR), matrix metalloproteinase (MMP)-2, MMP-9, vascular endothelial growth factor, Aurora-A, Bcl-2, clusterin, heat shock protein 27 (HSP27), HSP70, and HSP90, in RP specimens obtained from these 193 patients were measured by immunohistochemical staining. Of the 12 molecules, Ki-67, p53, AR, MMP-2, MMP-9, and HSP27 expression were significantly associated with several conventional prognostic factors. Univariate analysis identified these 6 markers as significant predictors for biochemical recurrence as well, while prostate-specific antigen, Gleason score, seminal vesicle invasion (SVI), surgical margin status (SMS), lymph node metastasis, and tumor volume were also significant. Of these significant factors, Ki-67 expression, SVI, and SMS appeared to be independently related to biochemical recurrence by multivariate analysis. Furthermore, there were significant differences in biochemical recurrence-free survival according to positive numbers of these three independent risk factors. These findings suggest that consideration of expression levels of potential molecular markers in RP specimens, in addition to conventional prognostic parameters, would contribute to accurate prediction of biochemical recurrence following RP in patients with clinically localized prostate cancer, and that combined evaluation of Ki-67 expression, SVI, and SMS would be particularly useful for further refinement of the system in predicting biochemical outcome.     

Brain metastasis in malignant pleural mesothelioma presenting as intratumoral hemorrhage

A 51-year-old man presented with a rare case of brain metastasis of malignant pleural mesothelioma (MPM) manifesting as intratumoral hemorrhage. He had undergone several treatments such as left pneumonectomy, pleurectomy, chemotherapy with cis-diamminedichloroplatinum and gemcitabine hydrochloride, and irradiation. Five years later, computed tomography revealed right parietal metastasis with intratumoral hemorrhage and the patient was treated by surgery and irradiation. Six months after the surgery, recurrent intratumoral hemorrhage occurred and a second surgery was performed. MPM has a poor prognosis and brain metastasis is rare, but long-term survival has recently improved through the application of multi-modality approaches. Therefore, the number of opportunities for treating MPM metastasis will increase in the near future. Intratumoral hemorrhage may occur in patients with solitary brain metastasis of MPM, so surgery should be considered as a general candidate treatment for metastatic tumors.     

Detection of acute subdural hemorrhage using intraoperative MR imaging during glioma surgery: a case report

Intraoperative MRI (iMR) and neuronavigation have substantially changed the principles of surgery for brain tumors. iMR provides updated information on anatomical data and unanticipated brain events, thereby allowing safer and more accurate surgery. We herein report a case of unanticipated intracranial hemorrhage in an iMR imaging suite. The patient was a 53-year-old man with a chief complaint of generalized convulsion. MRI showed a lesion in the right temporal lobe about 6.0 cm in diameter. The tumor was resected using an iMR system and neuronavigation. The first iMR images showed a residual tumor in the medial temporal lobe. No brain events were detected at this time. We obtained updated navigation data and performed additional resection. After completion of the planned tumor resection, additional iMR images were taken. The second iMR images confirmed that the tumor had been completely removed, but they also revealed a contra-lateral subdural hemorrhage. After expedited closure of the original incision, left unilateral craniotomy was performed and the hematoma was evacuated. Fortunately, the patient had no new neurological deficits. The use of iMR imaging allowed the complete removal of the tumor and facilitated prompt and effective identification of an unanticipated life-threatening complication.     

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.