Monoclonal antibody production to human and bovine 2′:3′-cyclic nucleotide 3′-phosphodiesterase (CNPase): high-specificity recognition in whole brain acetone powders and conservation of sequence between CNP1 and CNP2

Monoclonal antibodies against human and bovine 2′:3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) were generated by fusing FOX-NY myeloma cells with spleen cells from RBF/Dn mice previously immunized with the purified brain antigens. The enzyme isolated from bovine brain was quite basic, with an isoelectric point of 9.71 and both the bovine and human enzymes consisted of a closely spaced doublet at approximately 44 and 46 kDa on SDS-PAGE. Six monoclonals were identified as strongly recognizing the enzyme on both ELISA plates and on immunoblots of whole brain protein. Four monoclonals very weakly cross-reacted with guinea pig myelin basic protein. In contrast with two previous reports, some of our monoclonal antibodies did immunostain 2 or 3 protein bands in peripheral nerve, two bands closely corresponding to those immunostained in central nervous system (CNS) myelin, the Wolfgram protein fraction and in acetone powders of whole brain. Each of the 6 monoclonals reacting strongly on immunoblots recognized the enzyme in from 2 to 5 of the species examined (human, bovine, rat, mouse and rabbit). In addition, all 6 monoclonals that immunostained the enzyme in whole brain, myelin and Wolfgram protein immunoblots recognized both CNP1 (44 kDa) and CNP2 (46 kDa). The two closely spaced protein bands observed on SDS-PAGE and previously stained on immunoblots of CNS CNPase using polyvalent rabbit anti-bovine CNPase antisera, and now different monoclonal antibodies, appear to be immunologically related and to contain highly conserved sequences.     

Expression profile of chemokines and chemokine receptors in epithelial cell layers of oral lichen planus

BACKGROUND: To understand the immunopathological features of oral lichen planus (OLP), we analyzed the expression of chemokines in the epithelial cell layers. Methods: Epithelia from OLP or healthy gingiva were collected by laser microdissection. The chemokine and chemokine receptor expressions in the epithelia were analyzed by DNA microarray. RESULTS: High levels of MIP-3alpha/LARC/CCL20 and its receptor CCR6 were expressed in the lesional epithelia. Furthermore, DC-CK1/CCL18, ELC/CCL19, SDF-1/CXCL12 and CXCR4 expressions were also increased. Immunohistologial analysis showed that high numbers of Langerhans cells (LCs) were present in the epithelia of OLP. Lesional epithelia also expressed high levels of the ligands specific for CXCR3 (e.g. MIG/CXCL9, IP-10/CXCL10 and I-TAC/CXCL11) and CCR5 (e.g. RANTES/CCL5). CONCLUSIONS: Infiltration of LCs is orchestrated by CCR6. Further, LCs residing in the lesional epithelia may be a mature phenotype. Moreover, infiltration of T cells in OLP could be mediated by signaling pathways through CXCR3 and CCR5.     

ANALYSIS OF BURIED BUMPER SYNDROME AFTER PERCUTANEOUS ENDOSCOPIC GASTROSTOMY DUE TO USE OF A BUTTON‐TYPE KIT

Background: Buried bumper syndrome (BBS) is a rare complication of percutaneous endoscopic gastrostomy (PEG). Along with the widespread use of the button‐type kit, BBS is encountered frequently. Methods: In the present study, we examined causes and treatments for BBS among 1400 patients who had undergone PEG. Results: The causes of BBS after PEG were classified into two categories: early causes consisted of wound infection, inappropriate size of kit and severe lordosis, while late causes were inappropriate exchange of kit, rough management or weight gain. The treatments for BBS could be determined by the degree of wound infection, fistula and burial of the bumper. Conclusion: We prepared a flowchart for replacement, by which BBS can be managed safely and quickly without surgical or endoscopic intervention.     

ENDOSCOPIC OBSERVATION OF MUCOSAL SPREAD LESION OF CHOLANGIOCARCINOMA USING PERORAL CHOLANGIOSCOPY WITH NARROW BAND IMAGING

A 69‐year‐old man was admitted to Toho University Omori Medical Center complaining of icterus. Abdominal computed tomography, magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography were suspicious of cholangioma of inferior bile duct. Peroral cholangioscopy using narrow band imaging (NBI) was performed and it was possible to diagnose the mucosal spread lesions of cholangioma. Histological findings reflected the endoscopic findings. Mucosal spread lesions of cholangiocarcinoma were successfully diagnosed using the CHF‐B260 for NBI.     

CLINICAL EVALUATION OF PERORAL CHOLANGIOSCOPY FOR BILIARY DISEASE USING NARROW BAND IMAGING

Regarding peroral cholangioscopy (POCS) for biliary disease, due to the recent appearance of a video cholangioscope that can obtain high‐quality images, it is possible to observe subtle changes of the biliary mucosa. In addition to the conventional observation method using POCS, the biliary mucosa with also observed with narrow band imaging (NBI) in one case of chronic cholangitis and four cases of extra hepatic bile duct tumor (three surgical cases). In the conventional observation method, the vessels in the surface layer of the biliary mucosa could be observed more clearly using NBI. In one case in which a tumor was observed, the irregularity of the biliary mucosa became clear on NBI, and the vessels inside a papillary tumor could also be easily observed. In another case of bile duct tumor, the conventional observation method showed a region in the proximity of the tumor where the vessels could not be seen clearly, but they could be seen clearly on NBI. In all of the cases, the bile juice was seen as red on NBI, which disturbed the observation. With POCS using NBI, it was possible to observe the vessels and irregularities in the surface layer of the biliary mucosa more clearly than with conventional observation methods.     

Obstinate cough as a sole presenting symptom of non-metastatic renal cell carcinoma

Renal cell carcinoma (RCC) causes many kinds of symptoms such as hypercalcemia, hypertension, polycythemia and fever. Here we describe a rare case of RCC presenting with a persistent cough. After radical nephrectomy, the obstinate cough disappeared. When the tumor recurred locally, the cough also recurred. Furthermore, the cough disappeared completely again after the removal of the recurrent tumor. Although all the clinical findings suggested that the RCC caused the cough, we could not identify a specific humoral substance responsible for the cough.     

First-line high-dose chemotherapy combined with peripheral blood stem cell transplantation for patients with advanced extragonadal germ cell tumors

BACKGROUND: The objective of this study was to evaluate the efficacy and safety of first-line high-dose chemotherapy (HDCT) combined with peripheral blood stem cell transplantation (PBSCT) for patients with advanced extragonadal germ cell tumors (EGGCT). METHODS: Six male patients with advanced non-seminomatous EGGCT were treated with HDCT combined with PBSCT following 2-3 cycles of conventional-dose induction chemotherapy. The regimens used for HDCT were carboplatin, etoposide and ifosfamide (ICE) in five patients and ICE plus paclitaxel (T-ICE) in one patient, and that for induction therapy was cisplatin, etoposide and bleomycin (PEB) in all patients. As a rule, HDCT was continuously administered until alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin normalized (beta-HCG). RESULTS: Following 1-6 courses of HDCT (median, 4 courses), beta-HCG and AFP were normalized in all patients, and five and one patient were diagnosed as showing partial remission and stable disease, respectively. Five patients underwent surgical resection of residual tumors after HDCT, yielding necrotic tissue in two, mature teratoma in two, and viable cancer tissue in one, and the surgical margin was negative in all patients. At a median follow-up of 36 months, five patients were alive and disease-free, whereas the remaining one died of disease progression. Although all patients had grade 3 hematological toxicity, there was no treatment-related death by combining PBSCT. CONCLUSIONS: First-line HDCT with PBSCT could be safely administered to patients with advanced EGGCT, and the antitumor effect of this treatment was comparatively favorable. First-line HDCT therefore may represent an attractive option for patients with advanced EGGCT.     

Long-term results of first-line sequential high-dose carboplatin, etoposide and ifosfamide chemotherapy with peripheral blood stem cell support for patients with advanced testicular germ cell tumor

OBJECTIVE: Standard chemotherapy shows relatively low long-term survival in patients with poor-risk testicular germ cell tumor (GCT). First-line high-dose chemotherapy (HD-CT) may improve the result. High-dose carboplatin, etoposide, ifosfamide chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) was investigated as first-line chemotherapy in patients with advanced testicular GCT. METHODS: Fifty-five previously untreated testicular GCT patients with Indiana 'advanced disease' criteria received three cycles of bleomycin, etoposide and cisplatin (BEP) followed by one cycle of HD-CT plus PBSCT, if elevated serum tumor markers were observed after three cycles of the BEP regimen. RESULTS: Thirty patients were treated with BEP alone, because the tumor marker(s) declined to normal range. Twenty-five patients received BEP and HD-CT. One patient died of rhabdomyolysis due to HD-CT. Three and six (13% and 25%) out of 24 patients treated with BEP and HD-CT achieved marker-negative and marker-positive partial responses, respectively. The other patients achieved no change. Fifteen (63%) are alive and 14 (58%) are free of disease at a median follow-up time of 54 months. Severe toxicity included treatment-related death (4%). CONCLUSIONS: HD-CT with peripheral stem cell support can be successfully applied in a multicenter setting. HD-CT demonstrated modest anticancer activity for Japanese patients with advanced testicular GCT and was well tolerated. This regimen might be examined for further investigation in randomized trials in first-line chemotherapy for patients with poor-risk testicular GCT.     

Sequential bilateral minimum incision endoscopic radical nephrectomy in dialysis patients with bilateral renal cell carcinomas

Since 1998, we have performed minimum incision endoscopic surgery (MIES) for renal cell carcinoma (RCC). For seven dialysis patients with bilateral RCC, we have performed sequential bilateral MIES radical nephrectomy. It was carried out by retroperitoneal approach through a single minimum incision that narrowly permitted extraction of the specimen using endoscopy and direct stereovision, without trocar ports, without gas insufflation and without the insertion of the hands of operators into the operative field. Although six of the seven patients had multiple complications in addition to chronic renal failure (CRF), bilateral kidneys were successfully removed by sequential MIES radical nephrectomy without major operative complication. Postoperative recovery was prompt with all patients resuming oral feeding and walking by the second postoperative day. Sequential bilateral MIES radical nephrectomy, leaving the peritoneal cavity intact and without imposing circulatory stress caused by gas insufflation, is a feasible treatment for bilateral RCCs in dialysis patients.