Astrocyte expression of a dominant-negative interferon-gamma receptor

Interferon-gamma (IFN-gamma) is a major proinflammatory cytokine, and binding to its nearly ubiquitous receptor induces a wide variety of biological functions. To explore the role(s) of IFN-gamma signaling in astrocytes, transgenic mice (GFAP/IFN-gammaR1DeltaIC) expressing a dominant-negative IFN-gamma receptor alpha chain under control of the astrocyte-specific glial fibrillary acid protein (GFAP) promoter were generated. Transgenic mice developed normally, had normal astrocyte numbers and distribution, and exhibited no clinically overt phenotype. Transgene mRNA expression was detected only in the CNS, and the transgene-encoded IFN-gamma receptor 1 colocalized with GFAP, which is consistent with astrocyte expression. Astrocytes from transgenic mice exhibited reduced IFN-gamma-induced signaling as measured by major histocompatibility class II induction. Neither CNS inflammation nor perforin-mediated clearance of a neurotropic mouse hepatitis virus from astrocytes was impaired following infection. Transgenic mice with impaired astrocyte responsiveness to IFN-gamma provide a model for studying the selective astrocyte-dependent effects of this critical cytokine in CNS immunopathology.     

Expression of a dominant negative IFN-gammareceptor on mouse oligodendrocytes

The interferon-gamma (IFN-gamma) receptor is expressed by all nucleated cells, and binding of its cognate ligand, IFN-gamma, induces a wide variety of biological functions. Transgenic mice expressing a dominant negative IFN-gamma receptor 1 (IFN-gammaR1DeltaIC) on oligodendrocytes under control of the myelin proteolipid protein promoter are described. The mRNA encoding the transgene was only detected in the nervous system and protein expression was confirmed by immunohistochemistry. Transgenic receptor expression does not alter myelination and the mice exhibited no clinically apparent phenotype. Consistent with the restricted nervous system expression of the transgene, no alterations in peripheral immune responses were detected. Flow cytometric analysis demonstrated constitutive expression of both the IFN-gammaR1DeltaIC transgene and the endogenous IFN-gamma receptor 2 at high levels on oligodendrocytes derived from the transgenic mice. These oligodendrocytes also exhibited decreased STAT1 phosphorylation in response to IFN-gamma, confirming dominant negative transgene function. Transgenic mice in which oligodendrocytes have a diminished ability to respond to IFN-gamma showed delayed virus clearance from oligodendroglia compared with wild-type mice. This model will allow evaluation of oligodendrocyte responses to this critical cytokine during CNS inflammation.     

Variation of DaTSCAN quantification between different gamma camera types

OBJECTIVE: To acquire data from a 123I filled Alderson phantom on different gamma cameras types and compare the relative uptake results from processing using the QuantiSPECT program (GE Healthcare). METHODS: A DaTSCAN phantom was filled using the standard protocol and imaged on seven different gamma camera types and on two identical cameras of the same type. The standard GE Healthcare protocols for the given cameras were used. Aliquots of the striatum and brain background were counted in a gamma counter to determine variations in filling concentration. All the raw DaTSCAN SPECT data was imported into QuantiSPECT and processed by the three different algorithms (two box, three box and crescent) to determine the relative uptake in the striatum. Inter-operater and intra-operator variation was also determined. RESULTS: The 10% variation in filling concentration found across the sites was compensated for in the final results. There was a 5-15% variation between cameras depending on the processing algorithm used. There was an intra-operator variation of between 5 and 12% which reflected the proportion of operator intervention within the processing method. There was no statistical variation between operators. CONCLUSIONS: The transfer of a DaTSCAN database between camera types is feasible, but ideally all data would be acquired on a single camera type and phantom data used to normalize the database accordingly.     

Delivery and collection of radioactive packages to and from UK hospital nuclear medicine departments

Under radiation protection legislation in the UK, employers have a duty to maintain appropriate records to account for radioactive materials in their possession and to ensure security of these materials. This applies to radioactive packages, containing items such as technetium generators, which are regularly delivered to hospital nuclear medicine departments. It also applies to the collection of packages, such as those containing used generators for return to the supplier. This article has been written by the professional bodies representing nuclear medicine in the UK in order to provide guidance to hospitals on appropriate procedures that will comply with the legislation. General principles, which should be met by any acceptable protocol, are stated, and practical guidance on how these may be implemented is given. Some example scenarios are outlined.     

Predictors of Breastfeeding Intention Among Low-Income Women

OBJECTIVE: Breastfeeding rates are below the Healthy People 2010 goals despite recognized benefits of breastfeeding. This study determined factors that predict breastfeeding initiation among low-income pregnant women. METHODS: A self-administered closed-ended questionnaire was introduced to 694 pregnant women who were certified for WIC in Mississippi. The questionnaire collected data about demographics, breastfeeding intention, breastfeeding knowledge, self-efficacy, and three recognized barriers to breastfeeding: embarrassment, time and social constraints, and lack of social support. RESULTS: In bivariate analysis, women who intended to breastfeed were more often white and had at least some college education, higher income, a smaller family size, fewer children, and previous breastfeeding experience than women who did not intend to breastfeed. Intenders had higher levels of breastfeeding knowledge and self-efficacy and reported fewer barriers to breastfeeding than nonintenders. In multivariate logistic regression, fewer children, past breastfeeding experience, breastfeeding knowledge, self-efficacy, and perceived social support were independent predictors of breastfeeding intention. CONCLUSIONS: Women at high risk for not wanting to breastfeed can be identified for additional support. Interventions should focus on improving breastfeeding knowledge, enhancing confidence in one's ability to breastfeed, and overcoming barriers to breastfeeding, especially lack of social support, among low-income women.     

Olfactory-triggered panic attacks among Cambodian refugees attending a psychiatric clinic

Olfactory panic attacks have not been systematically assessed in a psychiatric population by any previous studies. Among Cambodian refugees attending a psychiatric clinic, the present investigation determines the following: (a) 1-month current prevalence of olfactory-triggered panic attacks, (b) associated psychopathology (Hopkins Symptom Checklist and the Structured Clinical Interview for DSM-IV-diagnosed posttraumatic stress disorder [PTSD]), and (c) frequency in events of olfactory panic of catastrophic cognitions (Panic Attack Cognitions Scale [PACQ]) and flashbacks (Clinician-Administered PTSD flashback scale). Forty-five percent of 100 consecutive psychiatric patients were found to have suffered an olfactory-triggered panic attack in the previous month; having current olfactory panic attacks was highly correlated with psychopathology (e.g., to PTSD diagnosis: and chi(2)=50.0; df=1; p<.001); and during olfactory-triggered panic attacks, catastrophic cognitions and flashbacks were common. Possible mechanisms for generation of high rates of olfactory-triggered panic attacks in this population are discussed (the "traumatic memory/catastrophic cognitions/interoceptive conditioning/escalating arousal" or "TCIE" model of panic generation) as are treatment implications.     

Olfactory-triggered panic attacks among Khmer refugees: a contextual approach

One hundred Khmer refugees attending a psychiatric clinic were surveyed to determine the prevalence of olfactory-triggered panic attacks as well as certain characteristics of the episodes, including trigger (i.e. type of odor), frequency, length, somatic symptoms, and the rate of associated flashbacks and catastrophic cognitions. Forty-five of the 100 patients had experienced an olfactory-triggered panic attack in the last month. Trauma associations and catastrophic cognitions (e.g. fears of a 'wind attack', 'weakness', and 'weak heart') were common during events of olfactory panic. Several case examples are presented. A multifactorial model of the generation of olfactory panic is adduced. The therapeutic implications of this model for the treatment of olfactory panic are discussed.