Elevated synaptophysin I in the prefrontal cortex of human chronic alcoholics

Convergent lines of evidence suggest potentiation of glutamatergic synapses after chronic ethanol exposure, and indicate that the presynaptic effect hereof is on modulators of synaptic strength rather than on executors of glutamate release. To address this hypothesis in the context of ethanol dependence in humans, we used semiquantitative immunoblotting to compare the immunoreactivities of synaptophysin I, syntaxin 1A, synaptosome-associated protein 25, and vesicle-associated membrane protein in the prefrontal and motor cortices between chronic alcoholics and control subjects. We found a region-specific elevation in synaptophysin I immunoreactivity in the prefrontal cortex of alcoholics, but detected no significant differences between the groups in the immunoreactivities of the other three proteins. Our findings are consistent with an effect of repeated ethanol exposure on modulators of synaptic strength but not on executors of glutamate release, and suggest a role for synaptophysin I in the enduring neuroplasticity in the prefrontal cortical glutamate circuitry that is associated with ethanol dependence.     

LRIG inhibitors of growth factor signalling – double-edged swords in human cancer?

The leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins are newly discovered negative regulators of growth factor signalling and proposed tumour suppressors. They antagonise signalling by interacting with growth factor receptors and by enhancing their ubiquitylation and degradation. Data on the expression of LRIG in human cancer have recently begun to accumulate; however, not all data appear consistent with the notion that the LRIG proteins always function as tumour suppressors. In the present review, we argue that the LRIG proteins could be double-edged swords, promoting or suppressing human cancer depending on cellular context.     

The adaptive response of skeletal muscle to increased use

Skeletal muscle undergoes profound changes in morphological, physiological, and biochemical character when subjected to prolonged periods of increased use. Although increased use may be brought about in a variety of ways, the results show consistent features. In particular, endurance exercise and chronic stimulation differ only in degree: the properties which change in response to exercise are also those which change at an early stage of stimulation; the properties which are resistant to change under exercise conditions change only after prolonged stimulation. There is therefore a hierarchy of stability in the properties of skeletal muscle which is revealed in its response to changing functional demands. The adaptive potential of muscle provedes a logical framework for understanding neural influences on the emergence of fiber types during muscle development. It is also relevant to the study of pathological conditions which may involve a sustained departure from normal postural and locomotor patterns of activity.     

LRIG1 expression in colorectal cancer

In the present study the expression of LRIG1 (leucine rich repeats and immunoglobin-like domains 1) and its relation to EGFR (epidermal growth factor receptor) was examined in tumour samples and adjacent non-neoplastic tissues from 30 patients with colorectal cancer. The LRIG1 gene, at chromosome 3p14, encodes an intergral membrane protein, which counteracts signalling by receptor tyrosine kinases belonging to the ERBB (epidermal growth factor receptor) family. LRIG1 is expressed in all tissues and organs analysed to date, including breast, brain, skin, kidney, spleen and colon. Overexpression of EGFR is seen in 70-90% of colorectal cancers, and is associated with a poor survival. Western blot analysis showed LRIG1 upregulation in 43% and downregulation in 43% of the colorectal cancers compared to adjacent non-neoplastic tissue. No correlation was evident between LRIG1, analysed by Western Blot and the expression of EGFR analysed by immunohistochemistry. FISH (fluoroscence in situ hybridisation) analysis showed increased LRIG1 copy number in one of nine tumours. Four colorectal cancer cell lines demonstrated two LRIG1 gene copies. In conclusion, there was a great heterogeneity in the expression of the LRIG1 protein in colorectal cancer, which was not related to gene dosage of the LRIG1 gene. Further studies can be of interest to evaluate whether alteration in LRIG1 expression in colorectal cancer is of biological or clinical significance.     

Landmark‐based software for anatomical measurements: A precision study

The aim of this study was to develop a software program, called Landmarker, which would aid studies of complex anatomical morphometry by simplifying the manual identification of landmarks in 3D images. We also tested its precision on routine magnetic resonance imaging (MRI) scans. To understand human biological variation, there is a need to identify morphological characteristics from the exterior and the interior of human anatomy. MRI, as opposed to other radiographic methods (mainly based on X‐ray techniques), supplies good soft tissue contrast, which allows for more complex assessments than what bony landmarks can provide. Because automation of this assessment is highly demanding, one of the primary goals for the new software was to enable more rapid identification of landmark sets in 3D image data. Repeat acquisition of head MRIs having a resolution of 0.94 × 0.94 × 1.20 mm³ were performed on 10 volunteers. Intra‐ and interoperator, as well as interacquisition variations of manual identification of exterior, craniofacial interior, and brain landmarks were studied. The average distances between landmarks were <1.8 mm, <2.3 mm, and <2.0 mm in the intra‐ and interoperator, and interacquisition evaluations, respectively. This study presents new software for time efficient identification of complex craniofacial landmarks in 3D MRI. To the best of our knowledge, no evaluation of software for rapid landmark‐based analysis of complex anatomies from 3D MR data has yet been presented. This software may also be useful for studies in other anatomical regions and for other types of image data. Clin. Anat. 22:456–462, 2009. © 2009 Wiley‐Liss, Inc.     

Effects of antimicrobial drugs on the cytotoxicity of epirubicin, bleomycin, estramustine and cisplatin.

The effect of concomitant treatment with different antibiotics on the cytotoxicity of epirubicin, bleomycin, estramustine and cisplatin was studied in vitro on fibroblasts (V79) and two cancer cell lines (colon cancer HT29 and lung cancer P31). The cell lines were propagated under standard tissue culture conditions and evaluated as the number of surviving cell clones in comparison to untreated controls. Fifteen commonly used antibiotics were tested and thirteen of these were found to modify the cytotoxic effect in one or several of the combinations tested. One antibiotic agent could affect the toxicity of different cytostatics in opposite directions and there were marked differences between the cell lines tested. Only in one of the situations, the combination of bleomycin and ceftazidim, did the antibiotic cause opposite effects on the toxicity of a cytostatic when comparing fibroblasts and carcinoma cells. A most impressive observation was the pronounced increase in cisplatin-induced cytotoxicity by amphotericin B. In conclusion, the results suggest that antibiotics can interact with the cytotoxicity of antitumoral drugs but that the feature of this interaction is seemingly an erratic phenomenon. Further studies are certainly justified, especially regarding the effects of amphotericin B and its mechanisms in enhancing the cytotoxicity of cisplatin.     

The major cysteine proteinase (cruzipain) from Trypanosoma cruzi is encoded by multiple polymorphic tandemly organized genes located on different chromosomes

We demonstrate that cruzipain, the major cysteine proteinase of Trypanosoma cruzi epimastigotes, is encoded by a large number of tandemly arranged genes. Restriction enzyme analysis of 20 clones containing complete repeat units of the gene, as well as sequencing of 2 of these clones, and comparison with previously published partial sequences, indicated that the sequence is conserved among the repeat units, although polymorphisms clearly exist. The repeat units contain an intergenic region of 528 bp and coding regions for pre- and pro-enzyme, a central domain and a C-terminal extension. The predicted amino acid sequences of these regions indicated a sequence identity of 30, 60, 70 and 36%, respectively, when the T. cruzi sequence was compared with the sequence of a similar cysteine proteinase from Trypanosoma brucei [14]. Studies by pulsed field gel electrophoresis, complemented with restriction analysis, indicated that the clusters are located on 2 4 different chromosomes in several parasite isolates.     

Beneficial effects of sucralphate in radiation induced diarrhea. An open randomized study in gynecological cancer patients

In an open randomized study including 51 consecutive patients with gynaecological malignancies sucralphate was daily administered to patients receiving pelvic irradiation. Sucralphate, an aluminium hydroxide complex of sulphated sucrose used in the treatment of gastric ulcer, seems to be of value in preventing radiation-induced bowel discomfort. The most objective parameter, frequency of diarrhoea was almost 50% less in the sucralphate groups as compared to the controls. The patients receiving sucralphate in general displayed only minor alterations in bowel habits even at the end of the radiation treatment. The number of patients requiring symptomatic therapy with loperamide were markedly lower in the sucralphate group. Subjective discomfort such as nausea, vomiting, loss of appetite were also less common. A reduction in acute reactions to irradiation increases the possibility of carrying through planned treatment and avoids unfavourable intermissions, and thus curing the patient with cancer in the pelvis by means of radiotherapy.