Rats fed only during the light period are resistant to stress-induced weight loss

Repeated restraint stress (3 h/day for 3 days) causes a chronic down-regulation of body weight in rats. This study determined whether weight loss was influenced by the time of day that rats had access to food or that stress was applied. Groups of male Sprague-Dawley rats were fed a 40% kcal fat diet with food given ad libitum, only during the light phase or only during the dark phase. After 2 weeks of adaptation, rats within each feeding treatment were divided into four groups. One was exposed to repeated restraint at the start of the light phase, another was restrained at the start of the dark phase and the remaining groups were nonstressed controls for restrained rats. Body weight was significantly reduced in ad libitum- and dark-fed restrained rats, compared with nonstressed controls, from Day 2 of restraint, regardless of the time of day that they were stressed. There was no significant effect of restraint on weight change of light-fed rats. Food intake was inhibited by stress in ad libitum- and dark-fed rats, but it was not changed in light-fed rats. Serum corticosterone was increased by restraint in all rats irrespective of feeding schedule. This study demonstrates that stress-induced weight loss only occurs when rats have food available during their normal feeding period (dark phase) and is not determined by increased corticosterone release.     

Bacterial clearance and cytokine profiles in a murine model of postsurgical nosocomial pneumonia

The development of a nosocomial pneumonia is facilitated by alterations in host innate pulmonary antibacterial defenses following surgical trauma, which can result in decreased pulmonary bacterial clearance and increased morbidity and mortality. In a murine model of postoperative nosocomial infection, surgical stress (laparotomy) decreased Escherichia coli clearance from the lungs of animals that underwent surgery. Consistent with previous studies, (i) pulmonary levels of tumor necrosis factor alpha at 6 h and of interleukin-1beta (IL-1beta), IL-6, and gamma interferon (IFN-gamma) at 24 h post-bacterial infection (PBI) were decreased in animals that underwent laparotomy 24 h prior to E. coli infection (LAP/E. coli) compared to animals that received E. coli only; (ii) KC and macrophage inhibitory protein 2 were elevated at 6 h PBI in LAP/E. coli animals compared to E. coli-only animals; however, at 24 h PBI, levels were higher in the E. coli-only group; (iii) at 24 h PBI, monocyte chemoattractant protein 1 was lower in the LAP/E. coli group compared to the E. coli-only group; (iv) IL-10 levels were unaffected at all time points evaluated; and (v) the total number of neutrophils present in the lungs of LAP/E. coli animals at 6 h PBI was decreased in comparison to that in E. coli-only animals, resulting in decreased bacterial clearance and increased mortality in LAP/E. coli animals by 24 h PBI. Similar changes in cytokine profiles, pulmonary bacterial clearance, and mortality were consistent with reported findings in patients following surgical trauma. This model, therefore, provides a clinically relevant system in which the molecular and cellular mechanisms that lead to the development of nosocomial pneumonia can be further explored.     

The distribution of neuropeptide Y-immunoreactive neurons and nerve fibers in the forebrain of the carp Cyprinus carpio L

The present study reports the distribution of Neuropeptide Y (NPY)-immunoreactive neurons and fibers in the forebrain of the adult carp Cyprinus carpio L. Serial Nissl-stained sections were used for cytoarchitecture and identification of anatomical structures. Immunostaining of NPY-containing neurons and fibers was used as neurochemical marker and tool for comparison with other species, including the goldfish.The general outline of the cytoarchitecture of the carp forebrain is similar to that of other Cypriniformes. However, using NPY immunohistochemistry, we found several specific differences with the goldfish, especially in the diencephalon. In the hypothalamus of the carp NPY-immunoreactive (NPYir) neurons were identified in the n. dorsolateralis thalami, and in the n. ventralis lateralis thalami. In the same location, we observed the n. anterior hypothalami and the n. preglomerulosus pars lateralis, described in the goldfish, as parts of n. prerotundus. However, in the carp we were not able to identify a n. preglomerulosus pars medialis, a n. preglomerulosus pars medialis commissuralis and a n. glomerulosus. We describe a n. rotundus, in which we did not find substructures typical of the goldfish.Further differences with the goldfish, trout and salmon were also noted.     

17q21-qter trisomy is an indicator of poor prognosis in acute myelogenous leukemia

A reciprocal translocation (9;11) is often found in acute myeloid leukemia (AML), mostly of the M5a type. We report a case of a child with AML, in whom t(9;11) was observed at diagnosis as the sole structural abnormality, together with trisomies 19 and 21. The diagnosis was AML evolving from a myelodysplastic syndrome (MDS), and the blast morphology was undifferentiated. Chemotherapy failed to induce morphological remission and the patient's condition soon worsened. A subclone appeared and expanded during the course of the disease, with an additional unbalanced translocation (1;17) leading to trisomy of the long arm of chromosome 17 (17q). The data available from the literature on acquired anomalies involving 17q and our observation led us to postulate a specific link between the gain of 17q and complete chemoresistance.     

Fully automatic quantification of microarray image data

DNA microarrays are now widely used to measure expression levels and DNA copy number in biological samples. Ratios of relative abundance of nucleic acids are derived from images of regular arrays of spots containing target genetic material to which fluorescently labeled samples are hybridized. Whereas there are a number of methods in use for the quantification of images, many of the software systems in wide use either encourage or require extensive human interaction at the level of individual spots on arrays. We present a fully automatic system for microarray image quantification. The system automatically locates both subarray grids and individual spots, requiring no user identification of any image coordinates. Ratios are computed based on explicit segmentation of each spot. On a typical image of 6000 spots, the entire process takes less than 20 sec. We present a quantitative assessment of performance on multiple replicates of genome-wide array-based comparative genomic hybridization experiments. By explicitly identifying the pixels in each spot, the system yields more accurate estimates of ratios than systems assuming spot circularity. The software, called, runs on Windows platforms and is available free of charge for academic use.     

Efficacy and safety of fluticasone propionate 250 microg administered once daily in patients with persistent asthma treated with or without inhaled corticosteroids.

BACKGROUND: Studies have shown fluticasone propionate (FP) 100, 200, and 500 microg administered once daily to be effective in the treatment of asthma. The efficacy of a once daily regimen of FP 250 microg has not been evaluated previously. OBJECTIVE: We sought to evaluate the efficacy and safety of inhaled FP 250 microg administered once daily in patients currently receiving inhaled short-acting beta-agonists (SABA) alone or inhaled corticosteroids (ICS). METHODS: In two separate studies, 408 patients in the SABA study and 401 patients in the ICS study were randomly assigned to receive FP 250 microg or placebo for 12 weeks through the Diskus device (GlaxoSmithKline, Research Triangle Park, NC) each morning. RESULTS: At the study endpoint, SABA patients treated with FP and placebo had mean increases in forced expiratory volume in 1 second from baseline of 0.23 +/- 0.03 L and 0.10 +/- 0.03 L, respectively (P < 0.001). ICS patients treated with FP had a mean increase of 0.08 +/- 0.02 L compared with a decrease in forced expiratory volume in 1 second of -0.08 +/- 0.03 L with placebo (P < 0.001). Changes of similar magnitude in morning peak expiratory flow rates were seen with FP in both the SABA and ICS studies. Fewer FP-treated ICS study patients were withdrawn from the study as a result of predetermined asthma stability criteria and, therefore, those patients had a greater probability of remaining in the study than placebo-treated patients (P < 0.001). CONCLUSIONS: FP 250 microg, once daily, produced greater improvements in pulmonary function and asthma symptom control than placebo. This new treatment regimen provides clinicians with an additional therapeutic option for patients with asthma previously treated with either beta2-agonists alone or ICS.     

Resident Enteric Bacteria Are Necessary for Development of Spontaneous Colitis and Immune System Activation in Interleukin-10-Deficient Mice

Mice with targeted deletion of the gene for interleukin-10 (IL-10) spontaneously develop enterocolitis when maintained in conventional conditions but develop only colitis when kept in specific-pathogen-free (SPF) environments. This study tested the hypothesis that enteric bacteria are necessary for the development of spontaneous colitis and immune system activation in IL-10-deficient mice. IL-10-deficient mice were maintained in either SPF conditions or germfree conditions or were populated with bacteria known to cause colitis in other rodent models. IL-10-deficient mice kept in SPF conditions developed colitis in all segments of the colon (cecum and proximal and distal colon). These mice exhibited immune system activation as evidenced by increased expression of CD44 on CD4⁺ T cells; increased mesenteric lymph node cell numbers; and increased production of immunoglobulin A (IgA), IgG1, and IL-12 p40 from colon fragment cultures. Mice populated with bacterial strains, including Bacteroides vulgatus, known to induce colitis in other rodent models had minimal colitis. Germfree IL-10-deficient mice had no evidence of colitis or immune system activation. We conclude therefore that resident enteric bacteria are necessary for the development of spontaneous colitis and immune system activation in IL-10-deficient mice.     

An ultrastructural study of normal human mammary epithelial cells in culture

The ultrastructure of normal human mammary cells cultured from post-weaning breast fluids is described. Cells from confluent monolayers in two week old cultures were studied. The epithelial nature of these cells was established by the demonstration of a well developed system of cell-to-cell interdigitation and numerous desmosomes. These cells also share with breast epithelial cells in vivo, polarity, with blunt short microvilli on the apical surface and an oriented arrangement of organelles in the basal and apical portions of the cells. The Golgi apparatus, which is the most highly developed organelle, is localized in the apical pole and contains substantial quantities of secretory material in the cisternae and vesicles. A variegated palisade of finely granular material mixed with tonofilaments is seen in the basal portion of the cells; many of these tonofilaments end in the terminal web of the desmosomes. The regular occurrence of these cells in breast fluids during the terminal phases of lactation suggests that their separation is a part of normal breast involution.     

Altered major histocompatibility complex-restricted antigen recognition by T cells from elderly humans.

Positive selection of T cells within the thymus gland leads to major histocompatibility complex (MHC)-restricted recognition of antigen by T lymphocytes. As the thymus gland involutes with age, altered MHC-restricted antigen recognition by T cells from elderly humans would be expected. We have tested this hypothesis by comparing the proliferative response of T cells and T cell clones from aged and young subjects to influenza determinants presented by autologous or allogeneic antigen-presenting cells (APC). Under conditions in which the allogeneic mixed lymphocyte reaction was minimal, T cells from six of seven aged donors but only one of seven young donors were stimulated by influenza vaccine presented by allogeneic APC. More importantly, one-half of the influenza-specific T cell clones derived from aged donors, but none of the clones derived from young donors, were activated by influenza vaccine presented by allogeneic APC. While 80% of the MHC-nonrestricted influenza-specific T cell clones expressed the gamma/delta T cell receptor, 20% of these clones expressed the alpha/beta T cell receptor. Thus, changes in MHC-restricted antigen recognition by T cells and in altered distribution of alpha/beta versus the gamma/delta T cell receptor bearing antigen-specific T cell clones occur with aging.     

Coping in chest pain patients with and without psychiatric disorders

We first examined relations between psychiatric disorder and coronary heart disease (CHD) in 77 patients presenting with chest pain. The coping profiles of chest pain patients with and without psychiatric disorder and CHD were then compared. Psychiatric patients with no medical illness (n = 129) were also studied. On the basis of previous research we hypothesized specific coping differences across the groups. As expected, chest pain patients without psychiatric disorder scored significantly higher on a problem-focused coping scale than chest pain patients with psychiatric disorder, who in scored higher on this scale than psychiatric patients with no medical illness. The opposite pattern occurred for a measure of wishful thinking. Scores of chest pain patients with psychiatric disorder were higher on a measure of avoidance and lower on a measure of seeking of social supports than those without psychiatric disorder. Scores on a self-blame measure were not different across the groups. The results are discussed in the context of illness behavior and somatization.