Direct adrenergic inputs to sacral autonomic neurons: using a double-immunostaining method at the light and electron microscopic levels

Relationships between adrenergic fibers and cholinergic neurons were examined in the rat sacral intermediolateral nucleus using a double-immunostaining method at light and electron microscopic levels. Adrenergic fibers were immunohistochemically stained brown by peroxidase reaction, and cholinergic neurons in the same sections were stained bluish green by β-galactosidase reaction. In the light microscope, many cholinergic neurons were seen in the intermediolateral nucleus and some of them were surrounded by adrenergic fibers. In the electron microscope, adrenergic fibers made synapses with the cholinergic neurons in the intermediolateral nucleus. These results suggest that adrenergic fibers directly influence the activity of the sacral parasympathetic preganglionic neurons.     

Detection of numerical alterations of chromosomes 3, 7, 17 and X in low-grade intracystic papillary tumors of the breast by multi-color fluorescencein situ hybridization

Intracystic papillary tumors of the breast comprise intraductal papillomas and low-grade papillary carcinomas. To determine chromosomal alterations that may be characteristic of these tumors, chromosomes 3, 7, 17 and X were examined in 10 intraductal papillomas and 14 low-grade papillary carcinomas using multicolor fluorescentin situ hybridization. In papillary carcinomas, numerical/structural alterations in chromosome 17 and the accumulation of numerical alterations in chromosomes 3, 7 and X were detected in 21% (3/14) and 15% (2/13) of the cases, respectively. These changes were not detected in papillomas. Loss of chromosome 17p was detected in only one of the 11 DNA-diploid carcinomas, whereas alterations in all four chromosomes were present in a case of DNA-aneuploid carcinoma. Numerical alterations of chromosomes 3, 7, 17 and X do not appear to be involved in the development of low-grade papillary carcinomas with DNA diploidy, but rather accumulate during the formation of DNA-aneuploid carcinoma cells in association with other chromosome alterations.     

Frequent methylation-associated silencing of a candidate tumor-suppressor, CRABP1, in esophageal squamous-cell carcinoma

Epigenetic alterations and the resulting inactivation of tumor suppressor genes often contribute to the development of various cancers. To identify novel candidates that may be silenced by aberrant methylation in esophageal squamous-cell carcinoma (ESCC), we analysed ESCC cell lines by a recently developed method known as bacterial artificial chromosome array-based methylated CpG island amplification (BAMCA), and selected candidates through BAMCA-assisted strategy. In the course of this program, we identified frequent CpG methylation-dependent silencing of the gene encoding cellular retinoic acid binding protein 1 (CRABP1) in our panel of ESCC cell lines. Expression of CRABP1 mRNA was restored in gene-silenced ESCC cells after treatment with 5-aza 2'-deoxycytidine. The DNA methylation status of the CRABP1 CpG island with clear promoter activity correlated inversely with expression of this gene. CpG methylation of CRABP1 was frequently observed in primary ESCC tissues as well. Restoration of CRABP1 expression in ESCC cells lacking the protein reduced cell growth by inducing arrest at G(0)-G(1), whereas knockdown of the gene in cells expressing CRABP1 promoted cell growth. Among 113 primary ESCC tumors, the absence of immunoreactive CRABP1 was significantly associated with de-differentiation of cancer cells and with distant lymph-node metastases in the patients. These results indicate that CRABP1 appears to have a tumor-suppressor function in esophageal epithelium, and its epigenetic silencing may play a pivotal role during esophageal carcinogenesis. Its expression status in biopsies or resected tumors might serve as an index for identifying ESCC patients for whom combined therapeutic modalities would be recommended.     

TERC identified as a probable target within the 3q26 amplicon that is detected frequently in non-small cell lung cancers.

PURPOSE: Cell lines derived from non-small cell lung cancers (NSCLCs) revealed frequent high-level gains of chromosomal DNA at 3q23-q29 when examined by comparative genomic hybridization (CGH). Within this amplicon, a minimal common region of amplification in lung tumors had been mapped to 3q26 by earlier studies. The aim of the present work was to identify specific targets of the 3q26 amplification in NSCLCs. EXPERIMENTAL DESIGN: We examined genomic alterations in 19 NSCLC cell lines (10 derived from squamous cell carcinomas and 9 from adenocarcinomas) by using CGH and fluorescence in situ hybridization. We determined amplification and expression levels of four candidates (EVI1, TERC, SNO, and PIK3CA) in those cell lines and also in 25 primary NSCLC tumors. Because the TERC gene encodes the RNA component of human telomerase, we examined telomerase activity by the telomeric repeat amplification protocol (TRAP) assay. RESULTS: Copy numbers of EVI1 and TERC increased more than those of SNO and PIK3CA in our panel of NSCLC cell lines. Significant correlation between amplification and expression levels was observed only for TERC (P = 0.006), however, among these four candidate genes. Expression of TERC was also up-regulated in 24 (96%) of 25 primary NSCLC tumors compared with their nontumorous counterparts (P = 0.0001), and elevated expression of TERC was associated with high levels of telomerase activity (P = 0.048). CONCLUSIONS: TERC is a likely target of the 3q26 amplification, and, therefore, may be a useful biomarker for diagnosis and an attractive, novel target for molecular therapy of NSCLC.     

Laparoscopic resection of epidermoid cyst arising from an intrapancreatic accessory spleen: a case report with a review of the literature

We describe a rare case of epidermoid cyst arising in an intrapancreatic accessory spleen that presented as a cystic mass in the tail of the pancreas, and for which laparoscopic distal pancreatectomy was performed successfully. A 36-year-old woman with a cystic mass in the tail of the pancreas, which had been discovered incidentally at a medical checkup, was referred to our department for further examination. Endoscopic retrograde cholangiopancreatography, endoscopic ultrasonography and positron emission tomography demonstrated a multilocular cyst in the tail of the pancreas without any evidence of malignancy, although differential diagnosis was extremely difficult because of the neoplasm-like appearance of the lesion. Therefore, we performed laparoscopic distal pancreatectomy under a preoperative diagnosis of mucinous cystic neoplasm. Postoperative pathologic examination demonstrated an epidermoid cyst arising from a heterotopic spleen within the pancreas. This is the first report of successful laparoscopic distal pancreatectomy for an epidermoid cyst arising in an intrapancreatic accessory spleen. One virtually has no chance to diagnose an epidermoid cyst in an accessory spleen on the basis of preoperative diagnostic workup, and consequently the type of surgical resection (open vs. laparoscopic) would be conditioned by factors other than the clinical entity suspected at the preoperative period.     

The brain finger protein gene (ZNF179), a member of the RING finger family,maps within the Smith-Magenis syndrome region at 17p11.2

Smith-Magenis syndrome (SMS) is caused by a microdeletion of 17p11.2 and comprises developmental and growth delay, facial abnormalities, unusual behavior and sleep problems. This phenotype may be due to haploinsufficiency of several contiguous genes. The human brain finger protein gene (ZNF179), a member of the RING finger protein family, has been isolated and mapped to 17p11.2. FISH analyses of metaphase or interphase chromosomes of 6 patients with SMS show that ZNF179 was deleted in one of the 2 homologs (17p11.2), indicating a possible association of the defect of this gene with the pathogenesis of SMS. Furthermore, using a prophase FISH ordering system, we sublocalized ZNF179 proximally to LLGL which lies on the critical region for SMS. Am. J. Med. Genet. 69:320–324, 1997. © 1997 Wiley-Liss, Inc.