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Shc associates with the IL-3 receptor beta subunit, SHIP and Gab2 following IL-3 stimulation. Contribution of Shc PTB and SH2 domains.

p46(Shc) and p52(Shc) become heavily tyrosine phosphorylated in response to interleukin 3 (IL-3) treatment. We have investigated the potential of Shc to integrate IL-3 signalling pathways and demonstrate that Shc associates with the beta subunits of the human (betac) and murine (Aic2A) IL-3 receptors, SHIP and Gab2 following IL-3 stimulation. The interaction between Shc and the IL-3 receptor beta chains was direct, mediated by both the SH2 and PTB domains. Interaction with SHIP was via the Shc PTB domain and the Shc SH2 domain mediated the interaction with Gab2. Phosphopeptide competition studies suggest that the SH2 domain interacts primarily with tyrosine 612 of betac (610 of Aic2A), and the PTB domain with tyrosine 577 of betac (575 of Aic2A). PTB binding to IL-3R beta chains was of highest affinity, and appeared to play the primary role in binding. These findings suggest that Shc may play an important role in coordinately integrating IL-3 signalling pathways.

Adaptor Proteins, Signal Transducing↗

Decoding protein-protein interactions through combinatorial chemistry: sequence specificity of SHP-1, SHP-2, and SHIP SH2 domains.

A general, combinatorial library method for the rapid identification of high-affinity peptide ligands of protein modular domains is reported. The validity of this method has been demonstrated by determining the sequence specificity of four Src homology 2 (SH2) domains derived from protein tyrosine phosphatase SHP-1 and SHP-2 and inositol phosphatase SHIP. A phosphotyrosyl (pY) peptide library was screened against the SH2 domains, and the beads that carry high-affinity ligands of the SH2 domains were identified and peptides were sequenced by partial Edman degradation and mass spectrometry. The results reveal that the N-terminal SH2 domain of SHP-2 is capable of recognizing four different classes of pY peptides. Binding competition studies suggest that the four classes of pY peptides all bind to the same site on the SH2 domain surface. The C-terminal SH2 domains of SHP-1 and SHP-2 and the SHIP SH2 domain each bind to pY peptides of a single consensus sequence. Database searches using the consensus sequences identified most of the known as well as many potential interacting proteins of SHP-1 and/or SHP-2. Several proteins are found to bind to the SH2 domains of SHP-1 and SHP-2 through a new, nonclassical ITIM motif, (V/I/L)XpY(M/L/F)XP, which corresponds to the class IV peptides selected from the pY library. The combinatorial library method should be generally applicable to other protein domains.

Amino Acid Sequence↗

The NCI Drug Information System. 4. Inventory and Shipping Modules.

The Inventory/Shipping package of the NCI Drug Information System (DIS) is designed to support all inventory and shipping operations associated with the testing by the NCI of large numbers of chemicals for anticancer activity. Two major databases, an Inventory database and a Shipping History database, contain all of the data associated with these operations. Software that supports the operations in an online interactive manner also provides for the accessing and updating of these databases as necessary. Special hardware in the form of barcode reader/printers and digital balances is also interfaced to the system to improve the efficiency of the operations.

Antineoplastic Agents↗

Pesticide extraction efficiency of two solid phase disk types after shipping.

An interlaboratory study was conducted to compare pesticide recovery from Empore C(18) and Speedisks C(18)XF solid phase extraction disks after shipping. Four pesticides were used for the comparison of the two disk extraction materials: atrazine, diazinon, metolachlor, and tebuconazole. These pesticides were chosen to provide a range of physiochemical properties. Water samples were extracted onto the disk types and shipped to a cooperating laboratory for elution and analysis. The mean recoveries from Empore disks were atrazine, 95%; diazinon, 91%; metolachlor, 92%; and tebuconazole, 83%. The recoveries from Speedisks C(18)XF were atrazine, 89%; diazinon, 87%; metolachlor, 86%; and tebuconazole, 79%. Means for each of the pesticides using the different disk types were not statistically different (alpha = 0.05), but results were more variable when using Speedisks C(18)XF as compared to Empore disks. Reasons for the increased variability are discussed, but overall results indicate that Speedisks C(18)XF could be used as an alternative to Empore disks. Speedisks C(18)XF are enclosed in a plastic housing, so they can be used more easily in remote sampling sites without the possibility of glassware breakage, no prefiltration of samples is needed, and there are realignment problems that can be associated with the Empore disks.

Acetamides↗

Laboratory and field evaluation of predator odors as repellents for kiore (Rattus exulans) and ship rats (R. rattus).

Predator odors may serve to stop rats from entering conservation areas or to decrease predation, food consumption, and other damage by rats in areas tainted with predator odor. We compared the efficacy of real predator odors and synthetic odors (derived from the urine and feces of carnivores) as rat repellents with real herbivore odors as controls in a Y maze. We tested six predator odors: cat (Felis catus) urine and feces, mongoose (Herpestes auropunctatus) feces, n-propylthietane, S-methyl, methyl butanol, and isopentyl-methyl sulphide. The herbivore odors we used were: red deer (Cervus elaphus) urine, guinea pig (Cavia porcellus) feces, and white rabbit (Oryctolagus cuniculus) urine. Ship rats (Rattus rattus) and kiore or Polynesian rats (R. exulans) showed no aversion to any of the six predator odors when compared with herbivore odors. Ship rats, however, may have avoided synthesized odors more than real ones. We applied two odors (S-methyl, methyl butanol and n-propylthietane) to purpose-built feeders in native forest but recorded no change in either visitation rate or duration of visits for rodents [rats and mice (Mus musculus)] or possums (Trichosurus vulpecula). The consumption of maize at feeders was correlated with the number and duration of possum visits, but only weakly correlated with the number of visits by rodents. Consumption of maize was unaffected by the odor associated with the feeder. It is unlikely that the odors we tested will be useful in deterring rodents or possums from areas where they have been removed for economic, public health or conservation reasons.

Animals↗

Bilevel control of B-cell activation by the inositol 5-phosphatase SHIP.

The balanced interplay between positive and negative signals pathways emanating from surface receptors has emerged as a common paradigm for regulation of cell function and the immune response. Here, we will review the recent progress in analysis of signaling pathways initiated upon antigen receptor (BCR) aggregation, and co-aggregation with the inhibitory IgG receptor FcgammaRIIB. Particular attention is paid to the function of the inositol 5-phosphatase SHIP and its effector p62i(Dok), a RasGAP adapter protein. SHIP and Dok function in FcgammaRIIB-mediated inhibition as well as in feedback regulation of signals generated through the BCR. These inhibitory molecules may play critical roles in the prevention of immune system hyperactivity and resulting autoimmunity.

Animals↗

Role of the inositol phosphatase SHIP in negative regulation of the immune system by the receptor Fc(gamma)RIIB.

Immune complexes are potent activators of inflammatory cells, triggering effector responses through the crosslinking of Fc receptors (FcRs) such as Fc(epsilon)RI or Fc(gamma)RIII. On B cells and mast cells, immune complexes are also negative regulators of activation triggered by antigen and Fc receptors, a consequence of coligation of the B-cell antigen receptor or Fc(epsilon)RI, respectively, and the inhibitory receptor Fc(gamma)RIIB. Here we show that inhibitory signalling by Fc(gamma)RIIB does not require the SH2-domain-containing protein tyrosine phosphatase, SHP-1, in mast cells and results in the recruitment of the SH2-domain-containing inositol polyphosphate 5-phosphatase, SHIP, to the tyrosine-phosphorylated 13-amino-acid inhibitory motif of Fc(gamma)RIIB in both B cells and mast cells. SHIP, by hydrolysing the 5-phosphate of phosphatidylinositol(3,4,5)P3 and inositol(1,3,4,5)P4, suggests a mechanism by which Fc(gamma)RIIB can inhibit calcium influx and downstream responses triggered by immune receptors.

Amino Acid Sequence↗

FcgammaRIIB-mediated inhibition of T-cell receptor signal transduction involves the phosphorylation of SH2-containing inositol 5-phosphatase (SHIP), dephosphorylation of the linker of activated T-cells (LAT) and inhibition of calcium mobilization.

The low-affinity receptor for immunoglobulin G, FcgammaRIIB, is expressed on most B-cells and on immature and activated mature T-cells. Co-aggregation of FcgammaRIIB with the B-cell antigen receptor (BCR) leads to attenuation of BCR-induced blastogenesis and cell proliferation via inhibition of p21(ras), phosphatidylinositol 3-kinase (PI3-K) and phospholipase Cgamma (PLCgamma) activation. These effects are mediated, at least in part, by the recruitment of SH2-containing protein tyrosine phosphatase-1 (SHP-1) and -2 (SHP-2) and SH2-containing inositol 5-phosphatase (SHIP). In this report, we demonstrate that FcgammaRIIB co-aggregation with the T-cell antigen receptor (TCR), which may occur when T-cells recognize antibody-coated target cells, leads to inhibition of TCR-induced phosphorylation of the linker of activated T-cells (LAT). When phosphorylated, LAT functions as an adapter molecule and recruits PI3-K. Additionally, we demonstrate that PI3-K is required for TCR-induced Ca(2+) mobilization. Together, these data suggest that FcgammaRIIB may inhibit TCR-mediated Ca(2+) mobilization, in part via inhibition of LAT phosphorylation and subsequent inhibition of PI3-K activation. A similar mechanism has been described in B-cells, where FcgammaRIIB co-aggregation with the BCR leads to inhibition of PI3-K activity via dephosphorylation of CD19. It is likely that, in both cell types, levels of PtdIns(3,4,5)P(3) are additionally modulated via the enzymic activity of SHIP.

Adaptor Proteins, Signal Transducing↗

Effects of low-dose alcohol exposure on simulated merchant ship handling power plant operation by maritime cadets.

AIMS: Under current US Department of Transportation (DOT) regulations, some commercial vehicle operators are subject to sanctions for having > or = 00.04 g% blood alcohol concentrations (BACs) on the job. This study investigated the effects of alcohol (between 0.04 and 0.05 g% BAC) on the simulated operation of a commercial ship's power plant. DESIGN: A balanced placebo design was used in which alcohol administration was fully crossed with expectancy that alcohol was administrated. SETTING: The study was conducted at the Massachusetts Maritime Academy, Buzzards Bay, MA, USA. PARTICIPANTS: Participants were 18 volunteer engineering students in their senior year, at least 21 years of age, with previous experience on the diesel simulator. INTERVENTION: Following a baseline trial on day 1, on day 2 participants were randomized to expectancy (told alcohol or placebo) and beverage (receive alcohol or placebo). The dosage was 0.6 g/kg for males and 0.5 g/kg for females. In both baseline and performance days, participants were randomized to one of four diesel simulator scenarios, each replicating a system failure in a power plant subsystem (e.g. main propulsion, electrical generating). MEASUREMENT: Performance was measured by time required for problem identification and remediation. FINDINGS: A main effect for alcohol administration was found. In the alcohol condition, simulator performance time was almost twice as long (351 sec) as on the placebo condition (186 sec). The expectancy effect was not significant. CONCLUSION: These findings support the current federal policy on the hazards of this low alcohol level within the context of commercial shipping.

Adult↗

Development and evaluation of a shipping system for platelet components.

BACKGROUND: Platelet concentrates and apheresis platelets must be maintained at a temperature as close as possible to 20 to 24 degrees C during transport. To improve temperature control, ensure component quality, and meet handling and freight carrier needs, a new insulated shipping container system was developed and evaluated. STUDY DESIGN AND METHODS: Molded polyurethane-insulated shipping containers were loaded with different payloads of simulated platelet components, with or without gel-based temperature stabilizing packs (TSPs). The containers were subjected to constant ambient temperature of 37, 4 or -10 degrees C. Payload temperatures were continuously monitored, in situ, for 24 hours. RESULTS: Temperature data are reported as the mean number of hours needed for components to warm or cool by 1 degree C. The temperature of payloads exposed to a constant 37 degrees C ambient temperature increased by 1 degree C in 2.5 to 3.8 hours when no TSPs were included in the shipment and in 6.1 to 6.9 hours when TSPs were used. Exposure to a constant 4 degrees C ambient temperature resulted in a 1 degree C temperature decrease in 1.8 to 3.4 hours without TSPs and in 4.6 to 5.6 hours with TSPs. At a -10 degrees C ambient temperature, there was a 1 degree C drop within 1.0 to 1.6 hours without TSPs and within 2.7 to 2.9 hours with TSPs. CONCLUSION: The container and packing methods described moderate the rate of change in the temperature of platelet components during their exposure to challenging ambient conditions. The use of TSPs substantially improves the performance of the system. In addition, the system meets freight carrier requirements and is easy to use, environmentally friendly, and durable.

Blood Preservation↗

[Methods for quality assurance of medical examination in epidemiological field studies: the "Study of Health in Pomerania" (SHIP)].

The aims of the population-based, cross-sectional survey "Study of Health in Pomerania" (SHIP) are to describe prevalences and distributions of a broad range of diseases, as well as environmental and behavioural risk factors in the region of Pomerania (North-eastern Germany). The examinations are performed in two study units by different physicians, technicians and interviewers and laboratory analyses in two separate laboratories. In addition, the study will take at least 3 years and approximately 7000 persons will be examined. Because of the design of the study a special concept of quality assurance is indispensable. In the present paper methods are presented for quality assurance and control in anthropometry, ECG, echocardiography, abdominal sonography, carotid ultrasound, sonography of the thyroid gland, blood pressure measurements as well as clinical laboratory analyses. The technical control protocols, the training programmes of the observers and methods to establish observer and method variabilities are presented by means of typical examples. The logistic, personal and technical measures for quality assurance and control require appropriate attention. The methods and procedures presented here are expected to provide an effective instrument to continually monitor the quality of medical examinations in the SHIP study.

Adult↗

A comparison of the survival of shipped and locally transplanted cadaveric renal allografts.

BACKGROUND: The effect on allograft survival of the shipment of cadaveric renal allografts from one organ-procurement organization to another is uncertain. METHODS: Using data from the Organ Procurement and Transplantation Network of the United Network for Organ Sharing, we identified 5446 pairs of cadaveric kidneys (10,892 allografts) in which one kidney was shipped and the other was transplanted locally. We compared the risk of graft failure using statistical models that accounted for confounding variables, including the degree of HLA mismatching. RESULTS: After adjustment for the degree of HLA mismatching, shipped organs had a significantly higher rate of allograft failure than locally transplanted organs in the first year after transplantation (adjusted hazard ratio, 1.17; 95 percent confidence interval, 1.05 to 1.31; P=0.004), but not thereafter. An association between the shipment of organs with no HLA mismatches and allograft failure was not confirmed. CONCLUSIONS: The shipment of cadaveric renal allografts increases the risk of failure of HLA-mismatched grafts during the first year after transplantation.

Acute Disease↗

Homoclinic connections and period doublings of a ship advancing in quartering waves.

The large-amplitude motions of a ship running in waves are analyzed with a mathematical model reduced to a system of eight coupled nonlinear ordinary differential equations. Bifurcation analysis in relation to the surf-riding condition, with control parameter the angle of the rudder, shows the existence of a region of oscillatory behavior, containing also a chaotic domain. This region ends with a homoclinic connection and a dangerous jump toward the overtaking-wave mode, which can incur ship capsize. Addition of linear control removes the chaotic domain while giving rise to new regions of oscillation. (c) 1996 American Institute of Physics.

Journal Article↗

Association of tyrosine phosphatases SHP-1 and SHP-2, inositol 5-phosphatase SHIP with gp49B1, and chromosomal assignment of the gene.

We have analyzed the molecules participating in the inhibitory function of gp49B1, a murine type I transmembrane glycoprotein expressed on mast cells and natural killer cells, as well as the chromosomal location of its gene. As assessed by SDS-polyacrylamide gel electrophoresis and immunoblot analysis, tyrosine-phosphorylated, but not nonphosphorylated, synthetic peptides matching each of the two immunoreceptor tyrosine-based inhibitory motif (ITIM)-like sequences found in the cytoplasmic portion of gp49B1 associated with the approximately 65-kDa tyrosine phosphatase SHP-1 and approximately 70-kDa SHP-2 derived from RBL-2H3 cells. In addition, the phosphotyrosyl peptide matching the second ITIM-like sequence also bound the approximately 145-kDa inositol polyphosphate 5-phosphatase SHIP. Thus, it has been strongly suggested that the inhibitory nature of gp49B involves the recruitment of SHP-1, SHP-2, and SHIP for the delivery of inhibitory signal to the cell interior upon phosphorylation of tyrosine residues in their ITIMs. The gp49B gene has been found to be in the juxtaposition of its cognate gene, gp49A. The gene pair was shown to locate in the B4 band of mouse chromosome 10. In this region, no conserved linkage homology to human chromosome 19, where the genes for killer cell inhibitory receptors are found, has been identified.

Animals↗

An influenza outbreak due to A/USSR/77-like (H1N1) virus aboard a US Navy ship.

An explosive outbreak of influenza caused by an A/USSR/77-like (H1N1) virus occurred aboard a US Navy ship in December 1977 and January 1978. Two hundred volunteers aboard the ship were studied. Virus was isolated from 36 of 57 patients from whom isolation was attempted. Among virologically confirmed patients, headache (97%), chills (92%), malaise (86%), and cough (75%) were the most frequent symptoms. There were two virologically confirmed cases with complications: one with collapsed lung and the other with pneumonitis. The study subjects were 25 years of age or less, but there was little influenza-like disease in members of the crew greater than 25 years of age. Prior vaccination with bivalent vaccine, containing A/NJ/76 (Hsw1N1) virus, did not offer significant protection against disease caused by A/USSR/77-like virus. Serologic tests, either or both complement fixation and hemagglutination inhibition, were positive in only 14 of 22 virologically confirmed cases, indicating a poor serologic response to primary infection with this strain of virus. These findings prevented calculation of meaningful disease to infection ratios. However, inapparent infection occurred in 3 of 19 (16%) individuals who denied having illness during the outbreak yet had serologic evidence of recent influenza infection.

Adolescent↗

Island colonization and founder effects: the invasion of the Guadeloupe islands by ship rats (Rattus rattus).

The stepwise colonization of islands within an archipelago is typically punctuated by successive founder effects, with each newly founded population being a subsample of the gene pool of the source island. Thus, the genetic signature of successive bottlenecks should be detected when analysing the genetic structure between islands of an archipelago. To test this prediction, we investigated introduced ship rat populations, Rattus rattus (Linnaeus, 1758), in the Guadeloupe Archipelago. Three different methods, commonly named the heterozygosity excess, the mode-shift indicator and the M ratio method, were used to detect bottlenecks from genetic data obtained with eight microsatellite markers on Guadeloupe and two neighbouring islands, Petite-Terre and Fajou. Moreover, a recent eradication failure on Fajou allowed us to test the accuracy of the methods in an 'experimental-like' situation. The results indicate that rats were introduced on Guadeloupe first, which then became the source population for independent secondary colonization of Fajou and Petite-Terre. Moreover, the heterozygosity excess and the mode-shift indicator only detected bottlenecks for the recent colonization of Petite-Terre and the eradication failure on Fajou. However, bottlenecks were detected for all the populations using the M ratio method. This could be interpreted as the remaining signature of the early introduction of the ship rat in the archipelago.

Alleles↗

Geoacoustic inversion with ships as sources.

Estimation of geoacoustic parameters using acoustic data from a surface ship was performed for a shallow water region in the Gulf of Mexico. The data were recorded from hydrophones in a bottom mounted, horizontal line array (HLA). The techniques developed to produce the geoacoustic inversion are described, and an efficient method for geoacoustic inversion with broadband beam cross-spectral data is demonstrated. The performance of cost functions that involve coherent or incoherent sums over frequency and one or multiple time segments is discussed. Successful inversions for the first sediment layer sound speed and thickness and some of the parameters for the deeper layers were obtained with the surface ship at nominal ranges of 20, 30, or 50 water depths. The data for these inversions were beam cross-spectra from four subapertures of the HLA spanning a little more than two water depths. The subaperture beams included ten frequencies equally spaced in the 120-200 Hz band. The values of the geoacoustic parameters from the inversions are validated by comparisons with geophysical observations and with the parameter values from previous inversions by other invesigators, and by comparing transmission loss (TL) measured in the experiment with modeled TL based on the inverted geoacoustic parameters.

Journal Article↗

Coronavirus and Pasteurella infections in bovine shipping fever pneumonia and Evans' criteria for causation.

Respiratory tract infections with viruses and Pasteurella spp. were determined sequentially among 26 cattle that died during two severe epizootics of shipping fever pneumonia. Nasal swab and serum samples were collected prior to onset of the epizootics, during disease progression, and after death, when necropsies were performed and lung samples were collected. Eighteen normal control cattle also were sampled at the beginning of the epizootics as well as at weekly intervals for 4 weeks. Respiratory bovine coronaviruses (RBCV) were isolated from nasal secretions of 21 and 25 cattle before and after transport. Two and 17 cattle nasally shed Pasteurella spp. before and after transport, respectively. RBCV were isolated at titers of 1 x 10(3) to 1.2 x 10(7) PFU per g of lung tissue from 18 cattle that died within 7 days of the epizootics, but not from the lungs of the remaining cattle that died on days 9 to 36. Twenty-five of the 26 lung samples were positive for Pasteurella spp., and their CFU ranged between 4.0 x 10(5) and 2.3 x 10(9) per g. Acute and subacute exudative, necrotizing lobar pneumonia characterized the lung lesions of these cattle with a majority of pneumonic lung lobes exhibiting fibronecrotic and exudative changes typical of pneumonic pasteurellosis, but other lung lobules had histological changes consisting of bronchiolitis and alveolitis typical of virus-induced changes. These cattle were immunologically naive to both infectious agents at the onset of the epizootics, but those that died after day 7 had rising antibody titers against RBCV and Pasteurella haemolytica. In contrast, the 18 clinically normal and RBCV isolation-negative cattle had high hemagglutinin inhibition antibody titers to RBCV from the beginning, while their antibody responses to P. haemolytica antigens were delayed. Evans' criteria for causation were applied to our findings because of the multifactorial nature of shipping fever pneumonia. This analysis identified RBCV as the primary inciting cause in these two epizootics. These viruses were previously not recognized as a causative agent in this complex respiratory tract disease of cattle.

Animals↗