Increased levels of serum matrix metalloproteinase-3 in haemodialysis patients with dialysis-related amyloidosis

Background: It is recognized that matrix metalloproteinase‐3 (MMP‐3) is abundantly expressed in active rheumatoid synovium, and that serum level of MMP‐3 is a useful marker for diagnosis of rheumatoid arthritis and for evaluation of prognosis in joint destruction. Little is known about serum MMP‐3 levels in haemodialysis (HD) patients, and thus, the association between serum MMP‐3 and dialysis‐related amyloidosis (DRA) has yet to be elucidated. Methods: Serum levels of MMP‐3 were measured by enzyme immunoassay in 150 HD patients, 90 without DRA and 60 with DRA, before HD. Simple regression analysis was performed to investigate the relationship between serum level of MMP‐3 and clinical parameters, including age, HD duration, C‐reactive protein and β2 microglobulin (BMG). Results: Serum levels of MMP‐3 were significantly higher in HD patients with DRA than in HD patients without DRA (258.2 ± 118.1 vs 201.5 ± 98.4 pg/mL, P = 0.0017), and both levels were significantly higher than those of healthy subjects (45.6 ± 13.4 pg/mL, P < 0.0001). Serum MMP‐3 levels significantly correlated with serum levels of BMG (r = 0.197, P = 0.0164) and HD duration (r = 0.168, P = 0.0427). Moreover, serum MMP‐3 levels significantly correlated with serum BMG levels in HD patients without DRA (r = 0.341, P = 0.0012), but not in HD patients with DRA. Conclusion: Our results suggest that matrix metalloproteinase activity increases in HD patients, which may be associated with BMG and DRA.     

Insidious progression of paraparesis secondary to type III spinal meningeal cyst: a study of six difficult cases

STUDY DESIGN: Case report. SETTING: Neuro-orthopaedic Unit, Fukui University Hospital, Japan. CASE REPORT: We studied six patients with insidious progression of paraparesis caused by thoracic and thoracolumbar spine type III spinal meningeal cyst and intradural arachnoid cyst, who underwent microsurgical decompression. Histologically, some samples showed oedematous and hypertrophic changes of the arachnoidal tissue together with occasional tophaceous deposits and calcification. Surgical treatment was complete excision of the cyst, or wide fenestration of these membrane, and close a communicating fistula, if detectable. All patients improved neurologically after microscopic surgery. CONCLUSION: We stress the significance of neuroimaging and neurological assessment in patients with gradual progression of paraparesis caused by intradural arachnoid cyst, but surgical procedure and timing of operative intervention require further considerations.     

Regions downstream from the WW domain of dystrophin are important for binding to postsynaptic densities in the brain

In order to investigate the mechanism of dystrophin localization in the central nervous system (CNS), we generated adenovirus vectors that contained minidystrophin or truncated minidystrophin cDNA. We infected a primary neuronal culture derived from mdx mouse hippocampus with these viruses. Minidystrophin was observed along the plasma membrane as punctate dots or very short segments. In double immunofluorescence staining with anti-dystrophin and anti-postsynaptic density-95 antibodies, we observed that these proteins entirely colocalized. On the other hand, the truncated minidystrophin, which has deleted WW, cysteine-rich and C-terminal domains, was homogenously expressed in cytoplasm, neurites and axons. These findings suggest that a binding site to postsynaptic densities exists in the region extending from the WW domain to the C-terminal domain of dystrophin and that this site is necessary for binding to membrane.     

Cordectomy for post-traumatic syringomyelia

Summary We performed cordectomy, a surgical technique that is infrequently used at present, for a patient with post-traumatic syringomyelia (following complete paraplegia of both lower limbs due to dislocation fracture of the 9th thoracic vertebra), yielding a favourable result. We recommend cordectomy as a surgical technique to which spinal surgeons should give utmost consideration for patients with post-traumatic syringomyelia demonstrating progressive symptoms assumed to be attributable to the syrinx and with an anatomically transected spinal cord of the mid-to-lower thoracic vertebral level. Correspondence: Yuichi Kasai MD, Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi Tsu-city Mie, 514-8507, Japan.     

Correlation between voxel based morphometry and manual volumetry in magnetic resonance images of the human brain

This is a comparative study between manual volumetry (MV) and voxel based morphometry (VBM) as methods of evaluating the volume of brain structures in magnetic resonance images. The volumes of the hippocampus and the amygdala of 16 panic disorder patients and 16 healthy controls measured through MV were correlated with the volumes of gray matter estimated by optimized modulated VBM. The chosen structures are composed almost exclusively of gray matter. Using a 4 mm Gaussian filter, statistically significant clusters were found bilaterally in the hippocampus and in the right amygdala in the statistical parametric map correlating with the respective manual volume. With the conventional 12 mm filter,a significant correlation was found only for the right hippocampus. Therefore, narrow filters increase the sensitivity of the correlation procedure, especially when small brain structures are analyzed. The two techniques seem to consistently measure structural volume.     

Incidental inverted papilloma during the clinical follow-up of superficial transitional cell carcinoma in the urinary bladder

A 76-year-old woman presented with gross hematuria. She had received transurethral resections (TURBT) twice for superficial bladder tumors near the right orifice. All pathologic findings demonstrated low grade superficial transitional cell carcinoma (TCC). Cystoscopy showed the tumor lesions during the follow-up. Bladder tumors were completely harvested and pathologic examination revealed inverted papilloma. However, recurrent tumors were detected at the same location after 4 months' follow up. Although she came to our hospital for the purpose of TURBT, she complained of severe neck pain and was suddenly dead. Autopsy findings showed that dissecting aortic aneurism was the cause of death and the bladder tumor was low grade superficial TCC. The case reported here had a very rare pathologic finding with a history of superficial tumors located in the same areas in the urinary bladder.     

Percutaneous endoscopy-guided biopsy of an intracystic tumor with a mammary ductoscopy

BACKGROUND: Intracystic abnormalities of the breast may result from debris, intracystic papilloma, or rarely breast cancer. Intracystic tumors cannot be diagnosed based on imaging examinations or fine needle aspiration alone, and therefore excisional biopsy must be performed. We have treated many cases who had nipple discharge with mammary ductoscopy since 1992, and we have used this method to diagnose intracystic tumors. METHODS: An endoscope was inserted into the cyst percutaneously, and the intracystic tumor was biopsied using forceps. RESULTS: Six intracystic tumors were biopsied with the endoscope. Four of six cases were cancer, and two were benign papillomas. CONCLUSION: We were able to visualize and accurately biopsy intracystic tumors of the breast using mammary ductoscopy.     

iNOS-dependent DNA damage in patients with malignant fibrous histiocytoma in relation to prognosis

Malignant fibrous histiocytoma (MFH) is one of the most common soft tissue sarcomas. MFH has been proposed to be a lesion accompanied with inflammatory responses. During chronic inflammation, reactive nitrogen and oxygen species generated from inflammatory cells are considered to participate in carcinogenesis by causing DNA damage. 8-nitroguanine is a mutagenic nitrative DNA lesion formed during chronic inflammation. We examined whether nitrative DNA damage is related to the prognosis of MFH patients. We performed immunohistochemical analyses to examine the distribution of DNA damage and the expression of inflammation-related molecules including inducible nitric oxide synthase (iNOS), nuclear factor-kappaB (NF-kappaB), and cyclooxygenase-2 (COX-2) in clinical specimens from 25 patients with MFH. We also analyzed the correlation of DNA damage or the expression of these genes with the prognosis of MFH patients. Immunohistochemical staining revealed that the formation of 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), an oxidative DNA lesion, occurred to a much greater extent in MFH tissue specimens from deceased patients than in live patients. iNOS, NF-kappaB and COX-2 were colocalized with 8-nitroguanine in MFH tissues. It is noteworthy that the statistical analysis using the Kaplan-Meier method demonstrated strong 8-nitroguanine staining to be associated with a poor prognosis. In conclusion, 8-nitroguanine appears to participate in not only the initiation and promotion of MFH, but also in the progression of MFH, and could therefore be used as a promising biomarker to evaluate the prognosis of cancer patients.     

Activation of downstream epidermal growth factor receptor (EGFR) signaling provides gefitinib-resistance in cells carrying EGFR mutation

Patients with pulmonary adenocarcinoma carrying the epidermal growth factor receptor (EGFR) mutation tend to display dramatic clinical response to treatment with the EGFR tyrosine kinase inhibitor gefitinib. Unfortunately, in many cases the cancer cells eventually acquire resistance, and this limits the duration of efficacy. To gain insight into these acquired resistance mechanisms, we first prepared HEK293T cell line stably transfected with either wild-type (WT) or mutant (L858R) EGFR, and then expressed oncogenic K-Ras12V mutant in the latter transfectant. Although 293T cells expressing wild-type EGFR did not show any growth inhibition by gefitinib treatment similarly to the non-transfected cells, the cells expressing the EGFR-L858R were exquisitely sensitive. Consistently, phospho-Akt levels were decreased in response to gefitinib in cells expressing EGFR-L858R but not in cells with EGFR-WT. In contrast, 293T cells expressing both EGFR-L858R and oncogenic K-Ras were able to proliferate even in the presence of high concentration of gefitinib probably by inducing Erk1/2 activation. We also expressed K-Ras12V in the gefitinib-sensitive pulmonary adenocarcinoma cell line PC-9, which harbors an in-frame deletion in the EGFR gene. The activated K-Ras inhibited the effects of gefitinib treatment on cell growth, cell death induction and levels of phospho-Akt, as well as phospho-Erk. These data indicate that activated Ras could substitute most of the upstream EGFR signal, and are consistent with the hypothesis that mutational activation of targets immediately downstream from the EGFR could induce the secondary resistance to gefitinib in patients with lung cancer carrying EGFR mutation.