The functions of oxytocin in the female are thought to be confined to the processes of milk ejection and parturition. In this study the role of oxytocin in the body’s response to stressful stimuli has been examined. Physical immobilization of rats and forced swimming caused large increases in the secretion of the hormone, whereas vasopressin levels remained unchanged. These findings classify oxytocin, in contrast to vasopressin, as a so-called ‘stress hormone’ and suggest its importance in processes other than those related to reproduction.

Purpose: The aim of the present study was to identify human genes that might prove useful in the diagnosis and therapy of primary breast cancer. Experimental Design: Twenty-four matched pairs of invasive ductal breast cancer and corresponding benign breast tissue were investigated by a combination of laser microdissection and gene expression profiling. Differential expression of candidate genes was validated by dot blot analysis of cDNA in 50 pairs of matching benign and malignant breast tissue. Cellular expression of candidate genes was further validated by RNA in situ hybridization, quantitative reverse transcription-PCR, and immunohistochemistry using tissue microarray analysis of 272 nonselected breast cancers. Multivariate analysis of factors on overall survival and recurrence-free survival was done. Results: Fifty-four genes were found to be up-regulated and 78 genes were found to be downregulated. Dot blot analysis reduced the number of up-regulated genes to15 candidate genes that showed at least a 2-fold overexpression in >15 of 50 (30%) tumor/normal pairs. We selected phosphatidic acid phosphatase type 2 domain containing 1A (PPAPDC1A) and karyopherin a2 (KPNA2) for further validation. PPAPDC1A and KPNA2 RNA was up-regulated (fold change >2) in 84% and 32% of analyzed tumor/normal pairs, respectively. Nuclear protein expression of KPNA2 was significantly associated with shorter overall survival and recurrence-free survival. Testing various multivariate Cox regression models, KPNA2 expression remained a highly significant, independent and adverse risk factor for overall survival. Conclusions: Gene expression profiling of laser-microdissected breast cancer tissue revealed novel genes that may represent potential molecular targets for breast cancer therapy and prediction of outcome.

The missing link in the evidence for an active endogenous renin angiotensin system in the brain has been the demonstration of local angiotensin synthesis in the central nervous system in vivo. In this report the extraction and characterization of angiotensin I and angiotensin II from the brain of rats is described. The accumulation of angiotensin I was enhanced in hypertensive rats when the conversion to angiotensin II was blocked in vivo by the converting enzyme inhibitor captopril.

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Common fragile sites (CFSs) are seen as chromosomal gaps and breaks brought about by inhibition of replication, and it is thought that they cluster with tumor breakpoints. This study presents a comprehensive analysis using conventional and molecular cytogenetic mapping of CFSs and their expression frequencies in two mouse strains, BALB/c and C57BL/6, and in human probands. Here we show that induced mouse CFSs relate to sites of spontaneous gaps and breaks and that CFS expression levels in chromosome bands are conserved between the two mouse strains and between syntenic mouse and human DNA segments. Furthermore, four additional mouse CFSs were found to be homologous to human CFSs on the molecular cytogenetic level (Fra2D-FRA2G, Fra4C2-FRA9E, Fra6A3

Differential expression of genes encoding claudins in CRC suggests that these tight junction proteins may be associated to and involved in tumorigenesis. CLDN1 is frequently up-regulated in large proportion of CRC and may represent potential target molecule for blocking studies in CRC.

The purpose of this study was to assess the diagnostic accuracy of whole-body MRI (WB-MRI) at 1.5 T or 3 T compared with FDG-PET-CT in the follow-up of patients suffering from colorectal cancer. In a retrospective study, 24 patients with a history of colorectal cancer and suspected tumour recurrence underwent FDG-PET-CT and WB-MRI with the use of parallel imaging (PAT) for follow-up. High resolution coronal T1w-TSE and STIR sequences at four body levels, HASTE imaging of the lungs, contrast-enhanced T1w- and T2w-TSE sequences of the liver, brain, abdomen and pelvis were performed, using WB-MRI at either 1.5 T (n = 14) or 3 T (n = 10). Presence of local recurrent tumour, lymph node involvement and distant metastatic disease was confirmed using radiological follow-up within at least 5 months as a standard of reference. Seventy seven malignant foci in 17 of 24 patients (71%) were detected with both WB-MRI and PET-CT. Both investigations concordantly revealed two local recurrent tumours. PET-CT detected significantly more lymph node metastases (sensitivity 93%, n = 27/29) than WB-MRI (sensitivity 63%, n = 18/29). PET-CT and WB-MRI achieved a similar sensitivity for the detection of organ metastases with 80% and 78%, respectively (37/46 and 36/46). WB-MRI detected brain metastases in one patient. One false-positive local tumour recurrence was indicated by PET-CT. Overall diagnostic accuracy for PET-CT was 91% (sensitivity 86%, specificity 96%) and 83% for WB-MRI (sensitivity 72%, specificity 93%), respectively. Examination time for WB-MRI at 1.5 T and 3 T was 52 min and 43 min, respectively; examination time for PET-CT was 103 min. Initial results suggest that differences in accuracy for local and distant metastases detection using FDG-PET-CT and WB-MRI for integrated screening of tumour recurrence in colorectal cancer depend on the location of the malignant focus. Our results show that nodal disease is better detected using PET-CT, whereas organ disease is depicted equally well by both investigations.

In the present publication the synthesis of the galactose binding protein and the /?-methylgalactoside transport system in Escherichia coli K12 has been shown to be coregulated. With the use of mutants of different regulatory behavior with respect to the galactose operon and the phosphoenolpyruvate-dependent phosphotransferase system, the following information about the regulation of the simultaneous synthesis of the galactose binding protein and the /?-methylgalactoside transport system was obtained.1. Fucose acts as inducer for both the galactose binding protein and the transport system. 2. GalK mutants, endogenously induced with respect to the galactose operon, also show endogenous induction of the transport system.3. The induction by fucose as well as endogenous induction is inhibited by 5 mM methyl-lthio-@-D-galactopyranoside.4. GalR+, galR and galR8 mutants can show full inducibility, excluding the function of galR in the regulation of the p-methylgalactoside transport system. 5. Deletions of the entire galactose operon exhibit high yet inducible transport activities excluding the existence of a regulator gene near or in the galactose operon.6. The existence of a regulator gene mglR which is different from galR, melR l a d , araC or pts could be demonstrated. The mutation mglR was found to be located between the origin of two Hfr strains, AB313 and KL16, i.e. between 56 and 74 min on the linkage map of E . coli.7. Mutants defective in enzyme I activity of the phosphoenolpyruvate-dependent phosphotransferase system exhibit unimpaired /?-methylgalactoside transport activity excluding any function of the /?-methylgalactoside permease aa a specific enzyme I1 of the phosphotransferase system.Since the classical work of Rickenberg et al.[l] which combined kinetic measurements and genetic methods in the study of sugar transport phenomena in bacteria, several attempts have been made to isolate components of these transport systems. A membrane bound protein, the "M' protein, has been isolated and identified as the product of the lacy gene, a gene known to be essential for the transport of Unusual Abbreviations. MeGal, methyl-8-D-galactopyranoside; MeSGal, methyl-l-thio$-D-galactopyranoside. All sugars mentioned in the text have the n-configuration except L-arabinose. P-Pyruvate, phosphoenolpyruvate. The present paper is concerned with the galactose binding protein [7,8] and its possible function in a galactose-specific transport system, the ,%methyl-galactoside transport system as well as genetic [13] data point to a close relationship between this binding protein and the transport system, I n order to obtain additional evidence for this relationship, we studied the regulation of both, the methyl galactoside (MeGal) transport system and the galactose binding protein. Enzymes. ATP : D-galactose-l-phosphotransferase (ki-naseThe study of galactose transport in E . coli is complicated by the existence of several sugar transport systems reported to be specific for galactose [9, lo]. Criteria for their distinction are...