Electromyography of oral-facial musculature in craniocarpaltarsal dysplasia (Freeman-Sheldon syndrome)

Electromyography and biopsy of the oral-facial musculature of a patient with craniocarpaltarsal dysplasia (Freeman-Sheldon syndrome) supports the thesis that facial muscle hypoplasia is a significant component of this evolving syndrome complex.     

Deconvoluting lung evolution using functional/comparative genomics

Parathyroid Hormone-related Protein (PTHrP) is a highly evolutionarily conserved, stretch-regulated gene that is necessary for the embryonic transition from branching morphogenesis to alveolization of the lung. It is expressed throughout vertebrate phylogeny, beginning with its expression in the fish swim bladder as an adaptation to gravity; microgravity downregulates the expression of PTHrP by alveolar type II cells, and by bones from rats exposed to 0 x g, suggesting that PTHrP signaling has been exploited for adaptation to 1 x g. PTHrP/PTHrP receptor signaling is upregulated by stretching alveolar type II cells and intersitial lung fibroblasts, whereas overdistension downregulates PTHrP and PTHrP receptor mRNA, further suggesting an evolutionary adaptation. Both surfactant homeostasis and alveolar capillary perfusion are under PTHrP control, indicating that alveolization and ventilation/perfusion matching may have evolved under the influence of PTHrP signaling. Phylogenetic analysis of lung evolution reflects the concomitant increases in alveolar surface area and surfactant production by "amplifying" the PTHrP pathway signal. This mechanism is discussed as a function of increased evolutionary respiratory demand to keep up with the increased metabolic demand for oxygen, and the role of the PTHrP signaling mechanism in leveraging this process.     

Blood and Marrow Transplant Clinical Trials Network State of the Science Symposium 2007.

Outcomes of hematopoietic cell transplantation are steadily improving. New techniques have reduced transplant toxicities, and there are new sources of hematopoietic stem cells from unrelated donors. In June 2007 the Blood and Marrow Transplant Clinical Trials Network convened a State of the Science Symposium of more than 200 participants in Ann Arbor to identify the most compelling clinical research opportunities in the field. This report summarizes the symposium's discussions and identifies eleven high priority clinical trials that the network plans to pursue over the course of the next several years.     

B cell early response gene expression coupled to B cell receptor,CD40 and interleukin-4 receptor co-stimulation: evidence for a role of the egr-2/krox20 transcription factor in B cell proliferation

B lymphocytes are activated following antigen stimulation of the B cell receptor but require co-stimulation with accessory molecules provided by interleukin (IL)-4/CD40 ligand for cell cycle progression and proliferation. By analyzing a panel of 11 early response genes induced by cross-linking of surface immunoglobulin, we show that CD40 signaling alone induces only 2 genes, c-myc together with an anonymous gene, 3L3, and that these are distinct from the set of genes induced in response to IL-4. Co-stimulation with the proliferative combination of anti-μ, IL-4 + CD40 signaling led to a fourfold enhancement of egr-2/krox20 expression over that seen with anti-μ alone. Egr-2 expression/activity was selectively inhibited by the immunosuppressive drug cyclosporin A, and antisense oligonucleotide blockade of Egr-2 activity elicited a dose-dependent inhibition of B cell proliferation. Taken together, these observations show that the early gene regulatory programs coupled to different surface receptors on B cells are largely distinct from each other, but that certain genes, exemplified by egr-2, may represent a point of convergence in the integration of different signaling pathways into the B cell proliferative response.     

Study of the HLA gene and antigen frequency from a Saudi Arabian hospital

The HLA-A, -B, -C and DR loci antigen frequencies were determined, respectively, on 1145, 558 and 352 healthy nonrelated Saudi family members. B21, CW4, CW7, and Dr7 showed the highest gene frequencies, of 14.6%, 28.3%, 7.4% and 19.5%, when compared to other populations. Haplotypes A2-B5, A32-B51, A26-B8, A2-B21, A28-B35, Aw19-B21 and B21-CW4 showed the highest frequencies when compared to other populations. Gene frequencies of 14.6% and 20.2% for B21 and Aw19 antigens, respectively, are highest among Middle East populations. Gene frequencies for A1 (10.5%), A2 (24.9%), A3 (8.9%), A9 (16.7%) and A28 (7.9%) are similar to the 10.1%, 24.9%, 8.3%, 16.8% and 7.7%, respectively, reported for the Turkish population. Also, gene frequencies for B5 (18.5%), B21 (14.6%) and B35 (10.2%) are very close to 17.1%, 14.0% and 10.2%, respectively, reported in the Yemenite population. The above results suggest some influence of other populations on the 'pure' Arab population.     

Long-term potentiation deficits and excitability changes following traumatic brain injury

The effects of traumatic brain injury (TBI) on hippocampal long-term potentiation (LTP) and cellular excitability were assessed at postinjury days 2, 7, and 15. TBI was induced using a well-characterized central fluid-percussion model. LTP of the Schaffer collateral/commissural system was assessed in vivo in urethane-anesthetized rats. Significant LTP of the population excitatory postsynaptic potential (EPSP) slope was found only in controls, and no recovery to control levels was observed for any postinjury time point. Four measurement parameters reflecting pyramidal cell discharges (population spike) indicated that TBI significantly increased cellular excitability at postinjury day 2: (1) pretetanus baseline recording showed that TBI reduced population spike threshold and latency; (2) tetanic stimulation (400 Hz) increased population spike amplitudes to a greater degree in injured animals than in control animals; (3) tetanus-induced population spike latency shifts were greater in injured cases; and (4) tetanic stimulation elevated EPSP to spike ratios (E-S potentiation) to a greater degree in injured animals. These parameters returned to control levels, as measured on postinjury days 7 and 15. These results suggest that TBI-induced excitability changes persist at least through 2 days postinjury and involve a differential impairment of mechanisms subserving LTP of synaptic efficacy and mechanisms related to action potential generation     

Differential regulation of IL-13 and IL-4 production by human CD8+ and CD4+ Th0, Th1 and Th2 T cell clones and EBV-transformed B cells

In the present study, the requirements and characteristics forthe production of IL-13 by human T cells, T cell clones andB cells were determined and compared with those of IL-4. IL-13was produced by human CD4⁺ and CD8⁺ T lymphocyte subsets isolatedfrom peripheral blood mononuclear cells and by CD4⁺ and CD8⁺T cell clones. CD4⁺ T cell clones belonging to T_h0, T_h1-likeand T_h2-like subsets produced IL-13 following antigen-specificor polyclonal activation. In addition, EBV-transformed B celllines expressed IL-13 mRNA and produced small amounts of IL-13protein. Expression of IL-13 mRNA and production of IL-13 proteinby peripheral blood T cells and T cell clones was induced rapidlyand was relatively long lasting, whereas IL-4 production bythese cells was transient In addition, IL-13 mRNA expressionwas induced by modes of activation that failed to induce IL-4mRNA expression. IL-13 shares many biological activities withIL-4 which Is compatible with the notion that the IL-13 andIL-4 receptors share a common component required for signaltransduction. However, IL-13 lacks the T cell-activating propertiesof IL-4. Here we have shown that this is related to the factthat T cells fall to bind radiolabeled IL-13 and do not expressthe IL-13-speclflc receptor component Taken together, theseresults indicate that the differences In expression and biologicalactivities of IL-4 and IL-13 on T cells may have consequencesfor the relative roles of these cytokines In the immune response.     

Isolation and Characterization of an Avian Adenovirus-Associated Virus

An 18- to 20-nm virus particle was isolated from the Olson strain of quail bronchitis, an avian adenovirus. On density gradient separation the small virions were primarily found at densities of 1.39 and 1.42 g/cm(3). The majority of the infectious particles were at the heavier density. The virus had a hexagonal outline and contained single-stranded deoxyribonucleic acid. It was resistant to heating at 56 C for more than an hour and was not inactivated by treatment with chloroform or low pH. Purified virus did not agglutinate erythrocytes of various avian and mammalian species. Replication of the small particles occurred either in chicken embryos or in cultures of embryo kidney cells coinfected with an adenovirus helper. Antigenically the virus was distinct from the adeno-associated viruses types 1, 2, 3, and 4. The virus is the avian equivalent of the adeno-associated viruses of primates and lower animals.     

Psychological functioning across stages of treatment for infertility

Psychological functioning was examined for a cross section of 104 couples in different stages of medical investigation for infertility. Couples were separated into three stages based upon the length of time they had been pursuing medical treatment for infertility: year 1, year 2, and year 3 and beyond. Emotional strain was moderately elevated during the first year, returned to more normal levels during the second year, and showed marked increases beyond year 3. Indices of marital adjustment and sexual satisfaction were stable across the first two stages but deteriorated after the third year. These data suggest that the stage of treatment may exert a major influence upon psychological functioning for infertile couples pursuing medical assistance. The results are consistent with a model of psychological strain that reflects an acute stress reaction to the initial diagnosis and treatment overlaid with a chronic strain response to longer-term treatment.Research was aided by a grant-in-aid of research from Sigma Xi, The Scientific Research Society, a research fellowship from the University of South Carolina, and NIMH Institutional Training Grant MH-15930.