Transcription factor E2F controls the reversible gamma delta T cell growth arrest mediated through WC1

IL-2-stimulated expansion of T cells requires continued and sequential passage of the dividing cells through a major cell cycle check point in the G1 phase. We have previously shown that a gamma delta T cell-specific surface receptor, WC1, induces G0/G1 growth arrest, reversible with Con A, in proliferating IL-2-dependent gamma delta T cells. We now show that this reversible WC1-induced cell cycle arrest is correlated with induction of the cyclin kinase inhibitor p27kip1 and an associated down-regulation in cyclins A, D2, and D3 expression, along with dephosphorylation of pocket proteins p107, p130, and pRb. Together with diminished pocket protein phosphorylation, p107 expression levels are significantly down-regulated in response to WC1 stimulation. This coordinated sequence of signaling events is focused on E2F regulation so that, downstream of the pocket proteins, WC1 stimulation results in a diminished DNA binding activity for free E2F as a consequence of reduced E2F1 expression, whereas E2F4 expression is unaffected. Consistent with this interpretation, overexpression of E2F1 overcomes the growth-arresting effects induced by WC1 stimulation. Finally, in accordance with our previous observations at both the cellular and molecular level, subsequent mitogen stimulation can reverse all the above changes induced by WC1. These results, focused on E2F regulation, therefore provide a first insight into the effects of both positive (mitogen) and negative (anti-WC1) stimuli on cell cycle control in IL-2-dependent gamma delta T cells.     

Seroepidemiology of emerging tickborne infectious diseases in a Northern California community

A seroprevalence and risk factor study of emerging tickborne infectious diseases (Lyme disease, ehrlichiosis, and babesiosis) was conducted among 230 residents of a semirural community in Sonoma County, California. Over 50% of residents reported finding a tick on themselves in the preceding 12 months. Samples from 51(23%) residents were seroreactive to antigens from one or more tickborne disease agents: 1.4% to Borrelia burgdorferi, 0.4% to Ehrlichia equi, 4.6% to Ehrlichia chaffeensis, and 17.8% to the Babesia-like piroplasm WA1. Only 14 (27%) of these seroreactive residents reported one or more symptoms compatible with these diseases. Seroreactivity was significantly associated with younger age (<16 years), longer residence in the community (11-20 years), and having had a physician's diagnosis of Lyme disease. In northern California, the risk of infection with these emerging tickborne diseases, particularly in children, may be greater than previously recognized.     

Obituary: Julius Segal (1924–1994).

Memoralizes the life of J. Segal who authored and co-authored 8 books and approximately 500 articles, chapters, and magazine and newspaper features in the field of behavioral science and mental health. Shortly before his death, he co-authored the 8th edition of the widely used textbood, Psychology: An Introduction . Segal was the 1st psychologist to receive the American Psychological Foundation's Science Writer's Award. In the areas of stress and coping, Segal conducted the Department of Defense's official study of the American soldier who had been brainwashed during the Korean War. Segal is noted for possessing the rare capacity to present complex scientific and professional issues in understandable language, and his writing style was graceful, felicitious, and engaging. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Clinical feasibility of a free-weight strength-training program for older adults

In the present study the intergraft mRNA formation immediately before and after transplantation of human livers was investigated by semi-quantitative polymerase chain reaction. The analysis was carried out with mRNA isolated from biopsies routinely taken perioperatively and included the determination of the expression of tumour necrosis factor alpha (TNF-alpha), interleukin (IL-6), IL-8, IL-10, transforming growth factor beta (TGF-beta) and beta-actin. It was found that biopsies obtained 30-60 min after reperfusion of the liver graft contained significantly higher levels of mRNA for TNF-alpha, IL-6 and IL-8 than biopsies collected subsequently to cold preservation. No such differences were obtained for TGF-beta and IL-10 mRNA. Considerable interindivdual differences were observed concerning the degree of inducibility, in particular for IL-6 mRNA. Retrospective comparison with the clinical course of the individual patients revealed a close and statistically significant correlation between low IL-6 expression and the occurrence of acute rejection episodes within 30 postoperative days, while high IL-6 mRNA levels coincided with the absence of rejection signs. High values for TNF-alpha mRNA were associated with ensuing acute rejection episodes.     

Diagnosis and management of traumatic aorto-right ventricular fistulas

BACKGROUND: Traumatic aorto-right ventricular (Ao-RV) fistulas are rare lesions that result in congestive heart failure if left untreated. Early diagnosis and prompt surgical intervention are required to avoid the natural outcome of cardiac decompensation. METHODS: All cases of traumatic Ao-RV fistula described in the English literature since 1958 were reviewed. The clinical presentation, methods of diagnosis, and treatment strategies were assessed to determine the pathophysiology, natural history, and outcome of surgical intervention. RESULTS: Forty cases of traumatic Ao-RV fistulas were described in the English literature. There were 39 men and 1 woman, with a mean age of 28.3 years (range, 15 to 50 years). Twenty-two (55%) patients had isolated Ao-RV fistulas. Fourteen (35%) had Ao-RV fistulas with aortic insufficiency. Definitive surgical repair was performed in 38 patients. The associated aortic valve injuries were managed with repair techniques or replacement with prosthetic devices. The surgical outcomes in all patients were satisfactory. CONCLUSIONS: The pathophysiology and natural history of Ao-RV fistulas involves the development of congestive heart failure. Traumatic aortic insufficiency frequently is associated with this disorder. Early diagnosis and prompt treatment are necessary to avoid the natural outcome of cardiac decompensation. Definitive repair should be performed with the aid of cardiopulmonary bypass during the same hospitalization.     

The immune response of cattle, persistently infected with noncytopathic BVDV, after superinfection with antigenically semi-homologous cytopathic BVDV

The present study was undertaken to investigate firing patterns, locations, and projections to the phrenic motor nucleus of respiratory neurons in medullary raphe nuclei of rat. Experiments were performed on spontaneously breathing rats anesthetized with sodium pentobarbital. Extracellular spikes of single respiratory neurons were explored in midline medullary tegmentum. A total of 107 respiratory neurons was recorded in the raphe magnus, obscurus and pallidus. They were classified into the following eight types based on the relation of their firing patterns to the phase of respiration: (1) Inspiratory (I) throughout (n = 42); (2) I-late (n = 9); (3) I-decrementing (n = 1); (4) Pre-I (n = 2); (5) I-frequency modulated (n = 13); (6) Post-I (n = 12); (7) Expiratory (E) (n = 23) and (8) E-frequency modulated neurons (n = 5). Twenty of the 45 respiratory neurons examined were antidromically activated from the phrenic motor nucleus at the C4 spinal level with thresholds of 2-58 microA and latencies of 0.4-2.4 ms. Among the 20 neurons, 11 neurons were I-throughout, five were I-frequency modulated and four were E neurons. These results suggest that there is a population of neurons in the medullary raphe nuclei that projects to the phrenic motor nucleus at the C4 spinal level. It is possible that this projection may, in part, mediate the control of the diaphragmatic muscle motor neurons located in the C4 segments.     

Polyneuropathy: diagnosis and management

A polyneuropathy is characterized by a symmetrical distribution of sensory or motor abnormalities, more pronounced distally than proximally and usually more evident in the lower than in the upper limbs. Polyneuropathies may be classified on the basis of (a) clinical picture: acute/subacute/chronic, sensory/motor/autonomous, axonal degeneration/segmental demyelinization, and (b) cause: metabolic disorder, deficiency, infection, auto(dys)immunity, hereditary and toxic/iatrogenic polyneuropathy, with idiopathic polyneuropathy as the remaining group. Damaged nerves may recover as the result of spontaneous remyelinization and axonal regeneration. Treatment is particularly successful in immunomediated neuropathies. Withdrawal is often successful in intoxications and suppletion in deficiencies. Even if no treatment is possible, the diagnosis is important: the patient can be taught to accept his disease and the prognosis can be determined, in connection with possible handicaps.     

Knowledge-based modeling of a legume lectin and docking of the carbohydrate ligand: the Ulex europaeus lectin I and its interaction with fucose

Ulex europaeus isolectin I is specific for fucose-containing oligosaccharide such as H type 2 trisaccharide alpha-L-Fuc (1-->2) beta-D-Gal (1-->4) beta-D-GlcNAc. Several legume lectins have been crystallized and modeled, but no structural data are available concerning such fucose-binding lectin. The three-dimensional structure of Ulex europaeus isolectin I has been constructed using seven legume lectins for which high-resolution crystal structures were available. Some conserved water molecules, as well as the structural cations, were taken into account for building the model. In the predicted binding site, the most probable locations of the secondary hydroxyl groups were determined using the GRID method. Several possible orientations could be determined for a fucose residue. All of the four possible conformations compatible with energy calculations display several hydrogen bonds with Asp-87 and Ser-132 and a stacking interaction with Tyr-220 and Phe-136. In two orientations, the O-3 and O-4 hydroxyl groups of fucose are the most buried ones, whereas two other, the O-2 and O-3 hydroxyl groups are at the bottom of the site. Possible docking modes are also studied by analysis of the hydrophobic and hydrophilic surfaces for both the ligand and the protein. The SCORE method allows for a quantitative evaluation of the complementarity of these surfaces, on the basis of molecular lipophilicity calculations. The predictions presented here are compared with known biochemical data.