An Automated Self‐Similarity Analysis of the Pulmonary Tree of the Sprague–Dawley Rat

We present the results of an automated analysis of the morphometry of the pulmonary airway trees of the Sprague–Dawley rat. Our work is motivated by a need to inform lower‐dimensional mathematical models to prescribe realistic boundary conditions for multiscale hybrid models of rat lung mechanics. Silicone casts were made from three age‐matched, male Sprague–Dawley rats, immersed in a gel containing a contrast agent and subsequently imaged with magnetic resonance (MR). From a segmentation of this data, we extracted a connected graph, representing the airway centerline. Segment statistics (lengths and diameters) were derived from this graph. To validate this MR imaging/digital analysis method, airway segment measurements were compared with nearly 1,000 measurements collected by hand using an optical microscope from one of the rat lung casts. To evaluate the reproducibility of the MR imaging/digital analysis method, two lung casts were each imaged three times with randomized orientations in the MR bore. Diameters and lengths of randomly selected airways were compared among each of the repeated imaging datasets to estimate the variability. Finally, we analyzed the morphometry of the airway tree by assembling individual airway segments into structures that span multiple generations, which we call branches. We show that branches not segments are the fundamental repeating unit in the rat lung and develop simple mathematical relationships describing these structures for the entire lung. Our analysis shows that airway diameters and lengths have both a deterministic and stochastic character. Anat Rec, 2008. © 2008 Wiley‐Liss, Inc.     

Effects of a diet rich in Q-3 fatty acids on left ventricular geometry and dynamics in spontaneously hypertensive rats

Summary The aim of the present study was to investigate the chronic effects of a dietetic antihypertensive treatment on blood pressure, ventricular dynamics and geometry of the pressure loaded heart. Spontaneously hypertensive rats (SHR) received a standard diet enriched with 10% mackerel oil, containing 30% polyunsaturated Q-3 fatty acids, over a period of 70 days. As described previously the diet reduced blood pressure permanently by 40-50 mm Hg. Despite this reduction, the degree of left ventricular hypertrophy was only slightly (statistically insignificantly) reduced. This was probably a result of an increase in sympathetic tone as indicated by a raised pulse rate. On the other hand, the treatment prevented the development of eccentric hypertrophy, typical to the SHR, without changing the elastic material properties of the myocardium. Since the age-matched controls did not show significant degenerative alterations, protective effects at the level of myocardial tissue could not be demonstrated. Furthermore, future investigations need to investigate why myocardial contractility of the treated animals diminishes as observed in this study.     

Effects of local nerve cooling on conduction in vagal fibres shed light upon respiratory reflexes in the rabbit

In ten vagus nerves the effect of local cooling on the compound action potential was studied in the temperature range of 34 to 0 °C in spontaneously breathing, anaesthetized rabbits. The mean temperature at which the myelinated (A) fibres were completely blocked, was 10.2±2.4 °C (mean ± S.D.). In nine nerves, local vagus cooling to 0 °C failed to block all non-myelinated (C) fibres. In one nerve, total blocking occurred at 2.0 °C. We conclude that in the rabbit, the earlier found increase in tonic activity of the diaphragm following lung inflation or deflation during bilateral local vagus cooling to a temperature between 8 and 0 °C is due to afferent impulses in vagal C fibres.     

The outcome of T-cell costimulation through intercellular adhesion molecule-1 differs from costimulation through leucocyte function-associated antigen-1

Optimal T-cell activation requires both an antigen-specific and a costimulatory signal. The outcome of T-cell activation can be influenced by the nature of the costimulatory signal the T cell receives. We recently demonstrated the ability of stimulation through intercellular adhesion molecule-1 (ICAM-1), resident on the T-cell surface, to provide a second signal for T-cell activation, and have extended that work here to begin an examination of the functional outcome of this set of signals. Costimulation through ICAM-1 resulted in a greater percentage of cells having undergone more than three divisions when compared to costimulation through leucocyte function-associated antigen-1 (LFA-1). Costimulation through ICAM-1 also had an effect similar to costimulation through CD28 in its ability to down-regulate the cyclin dependent kinase inhibitor p27kip1. Costimulation through ICAM-1 provided greater protection from apoptosis than costimulation through LFA-1, especially in cells having divided more than three times. This was supported by the ability of costimulation through ICAM-1 to up-regulate the anti-apoptotic protein Bcl-2. Finally, costimulation through ICAM-1 or CD28 produced a greater number of T cells with a memory phenotype than costimulation through LFA-1.     

Human Exposure to a Granulocytic Ehrlichia and Other Tick-Borne Agents in Connecticut

Indirect fluorescent-antibody (IFA) staining methods with Ehrlichia equi (MRK or BDS strains) and Western blot analyses containing a human granulocytic ehrlichiosis (HGE) agent (NCH-1 strain) were used to confirm probable human cases of infection in Connecticut during 1995 and 1996. Also included were other tests for Ehrlichia chaffeensis, the agent of human monocytic ehrlichiosis (HME), Babesia microti, and Borrelia burgdorferi. Thirty-three (8.8%) of 375 patients who had fever accompanied by marked leukopenia or thrombocytopenia were serologically confirmed as having HGE. Western blot analyses of a subset of positive sera confirmed the results of the IFA staining methods for 15 (78.9%) of 19 seropositive specimens obtained from different persons. There was frequent detection of antibodies to a 44-kDa protein of the HGE agent. Serologic testing also revealed possible cases of Lyme borreliosis (n = 142), babesiosis (n = 41), and HME (n = 21). Forty-seven (26.1%) of 180 patients had antibodies to two or more tick-borne agents. Therefore, when one of these diseases is clinically suspected or diagnosed, clinicians should consider the possibility of other current or past tick-borne infections.     

Idiotypes of monoclonal anti-DNA antibodies produced in autoimmune B/W mice are expressed in normal mice.

An anti-idiotypic antiserum was prepared in a rabbit immunized against a pool of six monoclonal anti-DNA antibodies generated in B/W mice. This antiserum detected idiotypic determinants in four of the six monoclonal anti-DNA antibodies but also in the serum of several non autoimmune strains (BALB/c, NZB X BALB/c) F1 hybrids & CBA/LH). The antiserum also reacted, but only to a weak degree, with B/W mouse sera. These results indicate that some idiotypes of anti-DNA antibodies produced by autoimmune B/W mice are present in normal mouse sera.     

Heat Shock Protein 70 of the Agent of Human Granulocytic Ehrlichiosis Binds to Borrelia burgdorferi Antibodies

We describe a patient with human granulocytic ehrlichiosis (HGE), a diagnosis confirmed by PCR and immunoblot analysis. Unexpectedly, immunoglobulin G (IgG) directed towards an 80-kDa ehrlichial antigen (without detectable IgM) was present in the patient’s serum in the first week of illness. Lyme disease immunoblots were reactive for IgG (but not IgM), a result indicative of prior exposure to the Lyme disease spirochete. Amino-terminal sequencing revealed that the 80-kDa ehrlichial antigen was an HSP-70 homolog similar to Borrelia burgdorferi HSP-70. We conclude that antibodies against B. burgdorferi HSP-70 may cross-react with the ehrlichial heat shock protein and that this possibility must be considered when serologic test results for HGE and Lyme disease are interpreted.     

SGK1, a potential regulator of <Emphasis Type="Italic">c-fms</Emphasis> related breast cancer aggressiveness

The aggressive behavior of breast cancer cells can at times be modulated by hormonal mechanisms. Exposure to glucocorticoids (GC) has been shown to stimulate the invasiveness, motility and adhesiveness of breast cancer cells containing the glucocorticoid receptor. This is largely explained by GC-associated overexpression of the c-fms proto-oncogene, which encodes the receptor for the colony stimulating factor-1 (CSF-1). Our objective is to investigate additional GC-associated genetic alterations that could modulate c-fms related malignant behavior in breast cancer cells. A microarray technique using an oligonucleotide array representing 16,700 known expressed human genes was used to analyze the gene expression profile of breast cancer cells exposed to dexamethasone (Dex) or vehicle. Results were confirmed by western blot analysis. Six genes were found to be consistently differentially overexpressed in the Dex-exposed cells compared to control. We focused on serum-glucose kinase 1 (SGK1), a serine-threonine kinase known to be involved in intracellular signal transduction pathways and induced by GC and serum. An adhesion assay was performed on extracellular matrix after exposing the breast cancer cells to Dex, CSF-1 or to Dex or CSF-1 plus LY294002, a functional inhibitor of SGK1 action. Exposure to LY294002 significantly decreased both CSF-1 and Dex-induced adhesiveness to the level of control cells. SGK1 may act as a downstream intracellular regulator of c-fms, particularly of c-fms-induced adhesiveness of breast cancer cells after exposure to GC or CSF-1. This finding may have implications for potential therapeutic interventions aimed at decreasing the aggressiveness of breast cancer cells. This revised version was published online in July 2006 with corrections to the Cover Date.     

Comparative recombination rates in the rat, mouse, and human genomes

Levels of recombination vary among species, among chromosomes within species, and among regions within chromosomes in mammals. This heterogeneity may affect levels of diversity, efficiency of selection, and genome composition, as well as have practical consequences for the genetic mapping of traits. We compared the genetic maps to the genome sequence assemblies of rat, mouse, and human to estimate local recombination rates across these genomes. Humans have greater overall levels of recombination, as well as greater variance. In rat and mouse, the size of the chromosome and proximity to telomere have less effect on local recombination rate than in human. At the chromosome level, rat and mouse X chromosomes have the lowest recombination rates, whereas human chromosome X does not show the same pattern. In all species, local recombination rate is significantly correlated with several sequence variables, including GC%, CpG density, repetitive elements, and the neutral mutation rate, with some pronounced differences between species. Recombination rate in one species is not strongly correlated with the rate in another, when comparing homologous syntenic blocks of the genome. This comparative approach provides additional insight into the causes and consequences of genomic heterogeneity in recombination.