Antenatal diagnosis of non-previa placenta increta with histological confirmation.
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Adult↗
Biomedical subjects
K Burns
Publications and source records attributed to K Burns.
A case of uterine hematoma presenting as a transient vascular abnormality on ultrasonography.
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Female↗
Physical mapping of genes in the porcine ovarian transcriptome.
Reproductive efficiency and associated traits are of major economic importance to the swine industry and have been more difficult to improve genetically than other production traits. Integration of phenotypical data with gene mapping and expression studies provides a powerful approach for dissection of the genetic basis regulating complex traits. We developed a total of 101 polymerase chain reaction-based markers, representing 91 unique genes, for expressed sequence tags previously reported to be putatively differentially expressed in the porcine ovarian transcriptome of a swine line selected on an index of high ovulation rate and embryonic survival. These were subsequently used in physical mapping experiments with a porcine radiation hybrid and somatic cell hybrid panels. Our results increased the information content of the porcine physical map useful for comparative mapping by c. 10%. Moreover, the mapped genes are likely to be biologically relevant to the molecular mechanisms that control ovulation rate in the pig. A total of 12 differentially expressed genes were mapped to regions previously reported to contain quantitative trait loci affecting swine ovulation rate.
Animals↗
Preparation and characterization of a set of IAEA reference air filters for quality control in air-pollution studies.
Several sets of reference air filters were prepared as part of an IAEA evaluation of the performance of laboratories involved in air-pollution studies. Each set comprised three polycarbonate membrane filters, two of which were loaded with urban air particulate matter (APM) obtained in Vienna or Prague, and one unloaded filter. The filters were loaded by filtration of a suspension of the APM materials in water. The homogeneity both of bulk APM materials and of the loaded filters was evaluated and found suitable by determining several elements by instrumental neutron-activation analysis (INAA), proton-induced X-ray emission (PIXE), and micro-X-ray energy-dispersive fluorescence analysis (micro-EDXRF). After evaluation of the homogeneity, INAA, PIXE, EDXRF, atomic absorption spectrometry (AAS), inductively coupled plasma optical emission spectrometry (ICP-OES), and ICP mass spectrometry (ICP-MS) were used to characterize the filter materials and establish "target values" and their associated standard deviations for 15 elements. Problems encountered during the preparation of these unique, simulated air filters and the criteria for setting both the target values and standard deviations are presented.
Air Pollutants↗
Firearms risk management in psychiatric care.
OBJECTIVE: This study sought to assess the effectiveness of a firearms risk management program. METHODS: A firearms risk management program, which included multidisciplinary assessment, treatment, and discharge planning, was developed and implemented among 46 civilly committed psychiatric inpatients at the Twin Valley Psychiatric System, a behavioral health organization of the Ohio Department of Mental Health. RESULTS: The research sample comprised mainly men who had personality disorders and histories of substance abuse and who had expressed an intent to use a firearm to commit suicide. On discharge, none of the patients had access to a firearm. Of the 16 patients who were hospitalized during the next 24 months, only five were noted to have threatened to harm themselves or others with a firearm or to have access to a firearm. CONCLUSIONS: Multidisciplinary and focused assessment, treatment, and discharge planning can be effective in neutralizing the risk of firearms use among psychiatric patients.
Adolescent↗
FIST/HIPK3: a Fas/FADD-interacting serine/threonine kinase that induces FADD phosphorylation and inhibits fas-mediated Jun NH(2)-terminal kinase activation.
Fas is a cell surface death receptor that signals apoptosis. Several proteins have been identified that bind to the cytoplasmic death domain of Fas. Fas-associated death domain (FADD), which couples Fas to procaspase-8, and Daxx, which couples Fas to the Jun NH(2)-terminal kinase pathway, bind independently to the Fas death domain. We have identified a 130-kD kinase designated Fas-interacting serine/threonine kinase/homeodomain-interacting protein kinase (FIST/HIPK3) as a novel Fas-interacting protein. Binding to Fas is mediated by a conserved sequence in the COOH terminus of the protein. FIST/HIPK3 is widely expressed in mammalian tissues and is localized both in the nucleus and in the cytoplasm. In transfected cell lines, FIST/HIPK3 causes FADD phosphorylation, thereby promoting FIST/HIPK3-FADD-Fas interaction. Although Fas ligand-induced activation of Jun NH(2)-terminal kinase is impaired by overexpressed active FIST/HIPK3, cell death is not affected. These results suggest that Fas-associated FIST/HIPK3 modulates one of the two major signaling pathways of Fas.
Adaptor Proteins, Signal Transducing↗
Changes in endoplasmic reticulum luminal environment affect cell sensitivity to apoptosis.
To test the role of ER luminal environment in apoptosis, we generated HeLa cell lines inducible with respect to calreticulin and calnexin and investigated their sensitivity to drug-dependent apoptosis. Overexpression of calreticulin, an ER luminal protein, resulted in an increased sensitivity of the cells to both thapsigargin- and staurosporine-induced apoptosis. This correlated with an increased release of cytochrome c from the mitochondria. Overexpression of calnexin, an integral ER membrane protein, had no significant effect on drug-induced apoptosis. In contrast, calreticulin-deficient cells were significantly resistant to apoptosis and this resistance correlated with a decreased release of cytochrome c from mitochondria and low levels of caspase 3 activity. This work indicates that changes in the lumen of the ER amplify the release of cytochrome c from mitochondria, and increase caspase activity, during drug-induced apoptosis. There may be communication between the ER and mitochondria, which may involve Ca(2+) and play an important role in conferring cell sensitivity to apoptosis. Apoptosis may depend on both the presence of external apoptosis-activating signals, and, as shown in this study, on an internal factor represented by the ER.
Animals↗
The caspase-8 inhibitor FLIP promotes activation of NF-kappaB and Erk signaling pathways.
BACKGROUND: Activation of Fas (CD95) by its ligand (FasL) rapidly induces cell death through recruitment and activation of caspase-8 via the adaptor protein Fas-associated death domain protein (FADD). However, Fas signals do not always result in apoptosis but can also trigger a pathway that leads to proliferation. We investigated the level at which the two conflicting Fas signals diverge and the protein(s) that are implicated in switching the response. RESULTS: Under conditions in which proliferation of CD3-activated human T lymphocytes is increased by recombinant FasL, there was activation of the transcription factors NF-kappaB and AP-1 and recruitment of the caspase-8 inhibitor and FADD-interacting protein FLIP (FLICE-like inhibitory protein). Fas-recruited FLIP interacts with TNF-receptor associated factors 1 and 2, as well as with the kinases RIP and Raf-1, resulting in the activation of the NF-kappaB and extracellular signal regulated kinase (Erk) signaling pathways. In T cells these two signal pathways are critical for interleukin-2 production. Increased expression of FLIP in T cells resulted in increased production of interleukin-2. CONCLUSIONS: We provide evidence that FLIP is not simply an inhibitor of death-receptor-induced apoptosis but that it also mediates the activation of NF-kappaB and Erk by virtue of its capacity to recruit adaptor proteins involved in these signaling pathways.
Apoptosis↗
The psychological and physical health of hospice caregivers.
This study explores the psychological distress of caring for a dying family member and examines the differences in depression, anxiety, health, social and occupational functioning, and social support among hospice caregivers and community controls. It compares psychological functioning of spousal and adult child hospice caregivers. Caregivers of terminally ill hospice patients were assessed prior to death as a part of a longitudinal bereavement study. Caregivers reported experiencing higher levels of depression, anxiety, anger, and health problems than controls. Hospice caregiving was associated with deterioration in physical health and in social and occupational functioning. The comparisons between adult children and spouse caregivers revealed that levels of psychological and physical morbidity were very similar for the two generations of caregivers. An awareness of distress symptoms among hospice caregivers could lead to timely proactive clinical intervention that may prevent bereavement complications.
Adult↗
Development and preliminary validation of a brief broad-spectrum measure of trauma exposure: the Traumatic Life Events Questionnaire.
This article describes the development and preliminary validation of a brief questionnaire that assesses exposure to a broad range of potentially traumatic events. Items were generated from multiple sources of information. Events were described in behaviorally descriptive terms, consistent with Diagnostic and Statistical Manual of Mental Disorders IV posttraumatic stress disorder stressor criterion A1. When events were endorsed, respondents were asked if they experienced intense fear, helplessness, or horror (stressor criterion A2). In separate studies with college students, Vietnam veterans, battered women, and residents of a substance abuse program, most items possessed adequate to excellent temporal stability. In a study comparing questionnaire and structured-interview inquiries of trauma history, the 2 formats yielded similar rates of disclosure. Preliminary data on positive predictive power are also presented.
Adult↗
Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor.
Interleukin-1 (IL-1) is a proinflammatory cytokine that elicits its pleiotropic effects through activation of the transcription factors NF-kappaB and AP-1. Binding of IL-1 to its receptor results in rapid assembly of a membrane-proximal signalling complex that consists of two different receptor chains (IL-1Rs), IL-1RI and IL-1RAcP, the adaptor protein MyD88, the serine/threonine kinase IRAK and a new protein, which we have named Tollip. Here we show that, before IL-1beta treatment, Tollip is present in a complex with IRAK, and that recruitment of Tollip-IRAK complexes to the activated receptor complex occurs through association of Tollip with IL-1RAcP. Co-recruited MyD88 then triggers IRAK autophosphorylation, which in turn leads to rapid dissociation of IRAK from Tollip (and IL-1Rs). As overexpression of Tollip results in impaired NF-kappaB activation, we conclude that Tollip is an important constituent of the IL-1R signalling pathway.
Adaptor Proteins, Signal Transducing↗
Overexpression of an enzymically inactive interleukin-1-receptor-associated kinase activates nuclear factor-kappaB.
Upon interleukin 1 (IL-1) stimulation, the IL-1-receptor (IL-1R)-associated kinase (IRAK) is rapidly recruited to the IL-1R complex and undergoes phosphorylation. Here we demonstrate that recombinant wild-type IRAK (IRAK-WT), but not a kinase-defective mutant with Asp340 replaced by an asparagine residue (IRAK-Asp340Asn), is highly phosphorylated and is capable of auto-phosphorylation in vitro. Overexpression of both IRAK-WT and IRAK-Asp340Asn caused activation of nuclear factor kappaB, suggesting that the kinase activity of IRAK is not required outside of the IL-1R complex.
Amino Acid Sequence↗
Developmental intervention for preterm infants diagnosed with periventricular leukomalacia.
Preterm infants with periventricular leukomalacia (PVL) were evaluated to determine whether multi-sensory stimulation is safe and to assess whether it improved neurobehavior and neurodevelopment. Thirty preterm infants with documented PVL were randomly assigned to control (n= 15) or experimental (Group E) (n= 15) groups at 33 weeks post-conceptional age. Group E infants received 15 minutes of auditory, tactile, visual, and vestibular (ATVV) intervention twice a day, five days a week, for four weeks during hospitalization. Repeated measures ANOVA demonstrated that Group E infants experienced significant increases in heart and respiratory rate and a 0.72% drop in hemoglobin saturation, coinciding with a significant behavioral state shift from sleep to alertness during intervention. No differences were identified in neurobehavioral function and neurodevelopment, indicating that Group E suffered no injury. Group E had an average hospital stay nine days shorter than that of controls, with the associated cost savings of $213,840. The earlier hospital discharge indicates that ATVV intervention promotes alertness without compromising physiologic status in vulnerable infants.
Analysis of Variance↗
Ultrastructural distribution of the death-domain-containing MyD88 protein in HeLa cells.
MyD88, a protein implicated in interleukin-1 signaling, was localized in HeLa cells transiently transfected with an epitope-tagged (flag) version of MyD88. Overexpression of MyD88 can induce apoptosis. We have analyzed the fine structural intracellular distribution of MyD88 using immunoelectron microscopy. MyD88 is localized to the nucleus and to the cytoplasm as revealed by immunofluorescence visualization. Ultrastructural immunocytochemistry shows that, in the cytoplasm, this protein is associated with fibrillar aggregates containing beta-actin. In the nucleus, MyD88 was found in fibrillar domains present only in cells not yet displaying morphological signs of apoptosis. These domains are not derived from nucleoli and do not constitute an accumulation site of splicing factors. We suggest that such structures could be involved in the formation of the apoptotic bodies and/or in the modification of the nuclear structure and of nucleocytoplasmic trafficking during apoptosis.
Adaptor Proteins, Signal Transducing↗
Interaction between a Ca2+-binding protein calreticulin and perforin, a component of the cytotoxic T-cell granules.
Calreticulin is a component of cytotoxic T-lymphocyte and NK lymphocyte granules. We report here that granule-associated calreticulin terminates with the KDEL endoplasmic reticulum retrieval amino acid sequence and somehow escapes the KDEL retrieval system. In perforin knock-out mice calreticulin is still targeted into the granules. Thus, calreticulin will traffic without perforin to cytotoxic granules. In the granules, calreticulin and perforin are associated as documented by (i) copurification of calreticulin with perforin but not with granzymes and (ii) immunoprecipitation of a calreticulin-perforin complex using specific antibodies. By using calreticulin affinity chromatography and protein ligand blotting we show that perforin binds to calreticulin in the absence of Ca2+ and the two proteins dissociate upon exposure to 0.1 mM or higher Ca2+ concentration. Perforin interacts strongly with the P-domain of calreticulin (the domain which has high Ca2+-binding affinity and chaperone function) as revealed by direct protein-protein interaction, ligand blotting, and the yeast two-hybrid techniques. Our results suggest that calreticulin may act as Ca2+-regulated chaperone for perforin. This action will serve to protect the CTL during biogenesis of granules and may also serve to regulate perforin lytic action after release.
Amino Acid Sequence↗
Identification of CARDIAK, a RIP-like kinase that associates with caspase-1.
Members of the tumor necrosis factor receptor (TNFR) superfamily have an important role in the induction of cellular signals resulting in cell growth, differentiation and death. TNFR-1 recruits and assembles a signaling complex containing a number of death domain (DD)-containing proteins, including the adaptor protein TRADD and the serine/threonine kinase RIP, which mediates TNF-induced NF-kappa B activation. RIP also recruits caspase-2 to the TNFR-1 signaling complex via the adaptor protein RAIDD, which contains a DD and a caspase-recruiting domain (CARD). Here, we have identified a RIP-like kinase, termed CARDIAK (for CARD-containing interleukin (IL)-1 beta converting enzyme (ICE) associated kinase), which contains a serine/threonine kinase domain and a carboxy-terminal CARD. Overexpression of CARDIAK induced the activation of both NF-kappa B and Jun N-terminal kinase (JNK). CARDIAK interacted with the TNFR-associated factors TRAF-1 and TRAF-2, and a dominant-negative form of TRAF-2 inhibited CARDIAK-induced NF-kappa B activation. Interestingly, CARDIAK specifically interacted with the CARD of caspase-1 (previously known as ICE), and this interaction correlated with the processing of pro-caspase-1 and the formation of the active p20 subunit of caspase-1. Together, these data suggest that CARDIAK may be involved in NF-kappa B/JNK signaling and in the generation of the proinflammatory cytokine IL-1 beta through activation of caspase-1.
Amino Acid Sequence↗
MyD88, an adapter protein involved in interleukin-1 signaling.
MyD88 has a modular organization, an N-terminal death domain (DD) related to the cytoplasmic signaling domains found in many members of the tumor necrosis factor receptor (TNF-R) superfamily, and a C-terminal Toll domain similar to that found in the expanding family of Toll/interleukin-1-like receptors (IL-1R). This dual domain structure, together with the following observations, supports a role for MyD88 as an adapter in IL-1 signal transduction; MyD88 forms homodimers in vivo through DD-DD and Toll-Toll interactions. Overexpression of MyD88 induces activation of the c-Jun N-terminal kinase (JNK) and the transcription factor NF-kappaB through its DD. A point mutation in MyD88, MyD88-lpr (F56N), which prevents dimerization of the DD, also blocks induction of these activities. MyD88-induced NF-kappaB activation is inhibited by the dominant negative versions of TRAF6 and IRAK, which also inhibit IL-1-induced NF-kappaB activation. Overexpression of MyD88-lpr or MyD88-Toll (expressing only the Toll domain) acted to inhibit IL-1-induced NF-kappaB and JNK activation in a 293 cell line overexpressing the IL-1RI. MyD88 coimmunoprecipitates with the IL-1R signaling complex in an IL-1-dependent manner.
Adaptor Proteins, Signal Transducing↗
The reverse transcription polymerase chain reaction for the diagnosis of porcine reproductive and respiratory syndrome: comparison with virus isolation and serology.
A single-tube reverse transcription polymerase chain reaction (RT-PCR) assay for the detection of porcine reproductive and respiratory syndrome (PRRS) virus in blood samples from infected pigs was developed. This test was assessed for sensitivity and application as a rapid diagnostic tool by comparison with virus isolation and detection of PRRS virus antibody in blood. The RT-PCR test was slightly more sensitive than virus isolation for detection of virus in serum and markedly more sensitive than virus isolation from plasma from experimentally infected pigs. The RT-PCR test was also applicable when using whole blood-impregnated filter paper discs, with 94% of the specimens taken by this procedure being positive when compared to RT-PCR performed on serum. PRRS viral nucleic acid was detected in blood samples as early as 24 h after infection and persisted for some time, whereas circulating antibody to PRRS virus was not detected in the same animals until 9 days after infection. These results indicate that the RT-PCR may be an useful technique for the early identification of PRRS viral nucleic acid in blood samples of infected pigs.
Animals↗