Experimental models of colorectal cancer

PURPOSE: A review of in vivo and in vitro models of colorectal cancer is presented. METHODS: A retrospective literature review was performed with reference to CD-ROM Medline and Index Medicus. RESULTS: A comparison of the advantages and disadvantages of the models is presented in addition to a summary of individual model methodology and applications. CONCLUSIONS: Such models are a useful adjunct for surgical research in colorectal oncology.     

Experimental models of torsade de pointes

Torsade de pointes is a potentially life threatening form of polymorphic ventricular tachycardia typically seen in the setting of congenital and acquired abnormal QT-prolongation. Numerous in vitro studies have investigated basic ionic mechanisms underlying delayed repolarization. The role of different ion channels and the induction of early afterdepolarizations have been studied in various cardiac cells including M cells. In addition, isolated heart models with and without electrical stimulation and/or the use of drugs which prolong repolarization have been developed in recent years. Some of these models have simulated conditions likely to exist in the clinical setting of torsade de pointes, such as bradycardia and hypokalemia. In in vivo canine and rabbit models, torsade-like polymorphic ventricular tachyarrhythmias have been induced by the administration of different agents such as cesium, neurotoxins, e.g., anthopleurin or various class III drugs under conditions designed to mimic the clinical situation. In the context of recent advances in the molecular genetics of long QT syndrome, those models which have used sodium or potassium channel blockers have gained particular interest. Based on all experimental studies it seems probable that the first beats of torsade occur due to early afterdepolarizations and triggered activity. The development of subsequent beats is less clear. Reentry based on inhomogeneity of refractoriness has been suggested as the underlying mechanism.     

Connectionist and diffusion models of reaction time.

Two connectionist frameworks, GRAIN (J. L. McClelland, 1993) and brain-state-in-a-box (J. A. Anderson, 1991), and R. Ratcliff's (1978) diffusion model were evaluated using data from a signal detection task. Dependent variables included response probabilities, reaction times (RTs) for correct and error responses, and shapes of RT distributions. The diffusion model accounted for all aspects of the data, including error RTs that had previously been a problem for all response-time models. The connectionist models accounted for many aspects of the data adequately, but each failed to a greater or lesser degree in important ways except for one model that was similar to the diffusion model. The findings advance the development of the diffusion model and show that the long tradition of RT research and theory is a fertile domain for development and testing of connectionist assumptions about how decisions are generated over time. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Experimental infection of dogs with the nasal mite Pneumonyssoides caninum

Cisplatin (CP) has been reported to activate murine macrophages to tumoricidal state, however, its mechanism of action is not known. In the present study it is reported that the production of: (a) interleukin-1 (IL-1); (b) tumor necrosis factor (TNF); (c) nitric oxide (NO); and (d) macrophage-mediated cytotoxicity by cisplatin-treated bone marrow-derived macrophages were inhibited by PKC inhibitors H-7 and chelerythrine chloride. Also, it was observed that treatment of macrophages with CP resulted in the translocation of PKC from the cytosol to the membrane fraction. These findings suggest the involvement of PKC in the activation of bone marrow-derived macrophages with cisplatin.     

Pathogenesis of neuroimmunologic diseases. Experimental models

Development of the retina, like that of other tissues, occurs via an orderly sequence of cell division and differentiation, producing the functional retina. In teleost fish, however, cell division and differentiation in the retina continue throughout the life of the animal in two distinct ways. Stem cells in a circumferential germinal zone at the periphery of the retina give rise to all retinal cell types and progenitor cells located throughout the retina in the outer nuclear layer (ONL) produce new rod photoreceptors. These processes in adult retina recapitulate in space the embryonic events responsible for forming the retina. Analysis of these events in an African cichlid fish, Haplochromis burtoni, confirmed that cone photoreceptors differentiate first, followed by rod photoreceptors. Correspondingly, at the margin of the eye, cone photoreceptors differentiate nearer to the margin than do rods. Control of photoreceptor production is not understood. Here we present the time of appearance and distribution pattern of GABA and vimentin which are candidates for the control of retinal cell division and differentiation. Antibody staining reveals that both GABA and vimentin exhibit unique patterns of expression during embryonic retinal development. Vimentin immunoreactivity is evident throughout the retina in a spoke-like pattern between developmental Days 4 and 7, as both cone and rod photoreceptors are being formed. GABA is expressed in horizontal cells between Days 5 and 7, corresponding to the onset of rod differentiation in time and in position within the retina. Moreover, the wave of GABAergic staining in the horizontal cells parallels the wave of rod differentiation across the embryonic retina of H. burtoni. Thus, GABA may play a role in the development of rod photoreceptors.     

Experimental animal models in cerebral ischemia

This paper describes the potential markers of cell death and connective tissue degradation which might serve as markers of periodontal disease activity. The first section deals with enzymes released by dead and degenerating cells. Firstly, it describes how these pass from the periodontal tissues into gingival crevicular fluid (GCF) and explains that these enzymes have been used as markers of cell death in medicine for several decades. It then discusses the main enzymes in this group, aspartate amino transferase (AST) and lactate dehydrogenase (LDH) and reviews those studies which have attempted to relate these enzymes to periodontal disease severity and activity. Secondly, it describes the potential markers of connective tissue degradation, fibronectin, hydroxyproline-containing peptides and glycosaminoglycans (GAGs) and explains how these are produced. Finally, it describes the only commercial test kit for markers in this group (GCF-AST).     

Experimental evaluation of three single-particle dissolution models

The dissolution of the 60-85-mesh fraction os recording, flow-through dissolution apparatus equipped with a dissolution cell; it was particularly suitable for kinetic analysis of multiparticulate systems. By using a time-scaling approach, experimental data are compared with theoretical calculations to evaluate, quantitatively, which of three single-particle dissolution models best describes the data and how well the multiparticulate kinetics can be explained mathematically. The nonspherical tolbutamide particles are replaced in the calculations by a hypothetical system of spherical particles that appears to be log-normally distributed. This procedure permits the calculation of the intrinsic dissolution profile, considering both size distribution and particle shape effects.     

Psychophysically principled models of visual simple reaction time.

Visual psychophysics has shown that the perceptual representation of a stimulus has complex time-varying properties that depend on the response characteristics of the channel on which it is encoded. A fundamental expression of these properties is the distinction between sustained and transient processing channels. A theoretical and mathematical framework is introduced that allows such properties to be incorporated into fully stochastic models of simple reaction time (RT). These models, the multichannel leaky stochastic integrators, combine a linear filter model of stimulus encoding with an accumulative decision process and yield a stimulus representation described by a time-inhomogeneous Ornstein-Uhlenbeck diffusion process. Methods for obtaining RT distributions for these models are described, together with comparative fits to luminance-increment data obtained under conditions of channel pooling and channel independence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The reaction of the nasal mucosa in allergic rhinitis to cold saline stimulus

To clarify the nature of the reaction pattern of the nasal mucosa in allergic rhinitis, nasal lavage using a cold saline solution of 4 degrees C and a warm saline solution was attempted in 8 patients with nasal allergy to the pollen of the Japanese cedar and cypress in a non-scatter season, and the concentration of protein contents in the nasal washings was determined. The concentrations of total protein, albumin and 26 kD protein were higher in cold saline than in the warm saline lavage. In particular, the concentration of 26 kD protein was 5.3 times higher. However, the concentration was not very high compared with the value obtained by warm saline lavage in the scatter season. These findings indicate that the nasal mucosa of patients with allergic rhinitis is reactive to cold saline stimuli even in the non-scatter season.     

Experimental headache models in animals and humans

Using multiple regression analysis, six MR parameters were correlated with three histological grades among 43 proven adult supratentorial astrocytic gliomas to ascertain important MR parameters and their optimal contributions. Analysis revealed that two parameters, border definition and tumor hemorrhage, were unreliable. Using the remaining four parameters an equation was derived: Tumor grade = 0.32 (ring enhancement) +0.29 (degree of contrast enhancement) +0.13 (heterogeneity) +0.12 (edema) +0.41. Ring enhancement was the most reliable predictor of tumor grade, followed by degree of contrast enhancement. The maximum accuracies of the "semi-automatic" approach using this equation for predicting low-grade astrocytomas, anaplastic astrocytomas, and glioblastoma multiforme were 91%, 83%, and 88%, respectively. Although "semi-automatic" grading provided relatively high accuracy, possible sampling errors and some atypical cases reduced such accuracy.     

Experimental models of atrial fibrillation--what have we learned?

The first pubovaginal fascial sling was reported in 1907, however, until recently this procedure was rarely utilized except after other incontinence procedures had failed. Currently, a pubovaginal sling is indicated as the primary incontinence procedure if intrinsic sphincter deficiency or coexisting intrinsic sphincter deficiency and urethral hypermobility are diagnosed preoperatively. Additionally, incontinence secondary to urethral hypermobility should be treated with a pubovaginal sling if the patient has a high risk of postoperative failure due to obesity, chronic cough, or repetitive strenuous activity. Pubovaginal slings are relatively easy to perform and yield reliably good results with minimal morbidity. We describe our current technique and results using pubovaginal slings for stress incontinence in women.     

Experimental animal models and complications of transluminal coronary angioplasty

Serial changes in the endometrial levels of estrogen and progesterone receptors (ER and PR) were measured in 50 women from days 2 to 14 of missed menses and correlated with the plasma concentrations of hCG, progesterone and 17 beta-estradiol. Both ER and PR of nuclei were higher than cytosolic proteins, with a shift in the ratio of nER/nPR to nPR from 4th day after missed menses. On Scatchard analysis of the cytosolic and nuclear binding proteins, two classes of proteins, corresponding to Type I and II, were found. While the increasing levels of hCG maintained luteal secretion of progesterone and 17 beta-estradiol at normal mid-luteal phase levels, a gradual increase in 17 beta estradiol from 9th day of missed menses was noted. This delicate balance between circulating levels of progesterone and 17 beta-estradiol and their nuclear receptors at early stages of pregnancy may be of significance.     

Experimental models and treatment trials for cerebral infarction

Recent progress in both experimental and clinical studies of cerebral infarction is outlined, and research on delayed neuronal death and ischemic penumbra is described. Development of animal models to study clinical pathophysiology is reviewed, and our focal cerebral ischemia model which has been used for many years is introduced. With elucidation of the pathophysiology of cerebral ischemia, various pharmaceutical agents have appeared recently in the clinical setting and our experimental trials on the treatment of cerebral ischemia are also introduced. From the clinical aspect, practical methods of treatment including antiplatelet therapy are explained. Cerebrovascular dementia and its prevention are also described.     

Cloning of genes by mRNA differential display induced during the hypersensitive reaction of soybean after inoculation with Pseudomonas syringae pv. glycinea

Soybean (Glycine max [L.] Merr.) cell suspension cultures (cv. Williams 82) inoculated with the pathogenic bacteria Pseudomonas syringae pv. glycinea respond with a hypersensitive reaction (HR) when the bacteria express the avirulence gene avrA. A mRNA differential display was established for this system to allow the identification of genes induced during the HR. Six PCR-fragments (DD1-DD6) from the differential display analysis were identified, which are induced during the HR. Database searches revealed that the fragment DD1 encodes chalcone isomerase and DD2 was identified as ubiquitin. The fragment DD3 shares significant homology to the signalling molecule 14-3-3. The partial DD4 product is homologous to the enhancer of rudimentary from Drosophila and an uncharacterized homologue of it from Arabidopsis. The fragment DD5 is similar to glucose-6-phosphate dehydrogenase which provides NADPH to the cell. The PCR-product DD6 seems to be a new leucine-rich-repeat disease resistance gene from soybean, which is significantly induced during the HR. All of the identified genes are clearly induced during a HR in infected plants of the same cultivar, indicating that results from the cell culture model system can be transferred to intact plants. These studies show that complex mRNA differential display is a powerful tool to identify new induced gene in plant-pathogen interactions.