CARMA1 is a critical lipid raft-associated regulator of TCR-induced NF-kappa B activation

CARMA1 is a lymphocyte-specific member of the membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins, which coordinate signaling pathways emanating from the plasma membrane. CARMA1 interacts with Bcl10 via its caspase-recruitment domain (CARD). Here we investigated the role of CARMA1 in T cell activation and found that T cell receptor (TCR) stimulation induced a physical association of CARMA1 with the TCR and Bcl10. We found that CARMA1 was constitutively associated with lipid rafts, whereas cytoplasmic Bcl10 translocated into lipid rafts upon TCR engagement. A CARMA1 mutant, defective for Bcl10 binding, had a dominant-negative (DN) effect on TCR-induced NF-kappa B activation and IL-2 production and on the c-Jun NH(2)-terminal kinase (Jnk) pathway when the TCR was coengaged with CD28. Together, our data show that CARMA1 is a critical lipid raft-associated regulator of TCR-induced NF-kappa B activation and CD28 costimulation-dependent Jnk activation.     

Striated intramural gallbladder lucencies on US studies: predictors of acute cholecystitis

Ultrasound scans of 51 consecutive patients with gallbladder wall thickening were reviewed, and specific sonographic features were correlated with surgical and clinical follow-up. Two patterns of thickening were identified as specific indicators of the presence or absence of acute cholecystitis. "Striated" wall thickening, consisting of several alternating, irregular, discontinuous, lucent and echogenic bands, was seen in eight of 13 patients (62%) with acute cholecystitis. This pattern was not encountered in any of the patients who did not have acute cholecystitis. Conversely, "three-layer" thickening, consisting of a single circumferential lucent zone between two relatively uniform echogenic layers, was seen in only one of 13 patients (8%) with acute cholecystitis but in 11 of 38 patients (29%) with other diagnoses. Other abnormalities, including the presence of intramural echogenic foci and wall irregularities, were more frequently seen in patients with acute cholecystitis but were not as helpful. Use of these features may suggest or help exclude a diagnosis of acute cholecystitis in those patients in whom the cause of gallbladder wall thickening is otherwise not apparent.     

The ability of PK 8165, a quinoline derivative, to reduce responses to a stressful situation in a double-blind study in man

A double-blind and cross-over study was carried out in order to explore the effects of PK 8165 (a quinoline derivative) on the heart rate, respiratory rate and motor reflex responses produced by an experimental model of stress in 8 healthy volunteers. The stress was induced by repetitive sequences of anticipation of pain (stressful stimulus: S) spaced by resting periods (R). In a control session, the cumulative effects of S resulted, in all subjects, in a progressive increase in heart and respiratory rates; 5 subjects showed a cumulative facilitation in the H reflex (motor reflex response) while the 3 others exhibited a cumulative depression in this motor parameter as a function of repetition of S during the session. The three doses (50, 100, 150 mg) of PK 8165 produced a very significant dose-dependent reduction in these responses during both stressful periods and resting sequences. Furthermore, the baseline values of respiratory and especially heart rate were also significantly reduced in a dose-dependent fashion by PK 8165. In contrast, the treatment with placebo did not significantly modify these parameters, compared to control values. The functional implications of these data are discussed in terms of stress-induced activation of some CNS structures and of the possible mechanisms of the "anti-stress" effect of PK 8165.     

Metastatic embryonal rhabdomyosarcoma of the breast: A case report and literature review

Rhabdomyosarcoma (RMS) is a common malignancy in children, but embryonal rhabdomyosarcoma (ERMS) deposits rarely occur in the breast in adults. Therefore, little is known about magnetic resonance imaging (MRI) features of breast metastases from RMS, especially the embryonal type. We reported a case of a 22-year-old woman who was diagnosed with ERMS at left foot 2 years ago and accepted operation and chemotherapy. She was confirmed to have breast metastases from the left foot. Successive imaging examinations were performed 3 months apart. Breast ultrasound indicated a benign lesion, and further examination did not reveal any bone metastases. However, predominant restricted diffusion and rim contrast enhancement on MRI combined with the patient's medical history suggested a malignancy of BI-RADS 5. After 3 months, breast ultrasound revealed masses detected last time became larger and lobulated. In addition, internal heterogeneous intensity and rim contrast enhancement with restricted diffusion were revealed on MRI. We speculated that typical MRI findings of breast metastases from RMS may include iso- to hypointensity on T1WI, heterogeneous hyperintensity on T2WI, and circular enhancement with restricted diffusion. Moreover, mild peritumoral edema, rapid expansion of necrosis, and ascending time-intensity curve detected on MRI may be features of the ERMS type.     

Laitinen's stereo-adapter: application to the fractionated cerebral irradiation under stereotaxic conditions

Radiosurgery is a technique which provides a single high dose of radiation very precisely to an intracranial lesion. The volume of tissue treated is small enough to avoid undue biological damage. This treatment requires very sophisticated apparatus and often considerable modifications in the treatment apparatus. The authors have closen to elaborate a system which makes it possible to deliver conventional fractionated irradiation, using a non-invasive stereotactic head frame called "Laitinen stereo-adapter". By fractionating the dose, most benign or low-grade malignant brain tumours can be treated, whatever their volume. The stereo-adapter and the target localization process are described. It can be used with C.T. scanning, angiography or M.R.I. The treatment apparatus is a linear accelerator delivering a 10 M.V. photon beam and treatment is made in the precise positioning of the target localization. The geometrical accuracy of the repeated mountings was studied in a preliminary study, showing a mean discrepancy of less than 1 mm in the three space planes. The geometrical accuracy of the radiation treatment was also studied on a phantom and the precision evaluated at less than 1 mm. The addition of extra collimators with a precollimation system decreased the lateral penumbra to 2-3 mm. Careful dosimetry was performed for each collimator. The use of non-coplanar arcs makes it possible to obtain a steep dose fall off outside the target volume. The dose planning calculations were compared to photodensitometry and thermoluminescent measurements, showing a good correlation. Each technical point will be discussed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Is the IV obstructed or infiltrated? A simple clinical test

Objective. The objective of our study was to determine if clinical observation of pressure-flow relationships (PFR) can differentiate between partial external obstruction (obstruction) and infiltration as a cause of poor performance of gravity-fed infusions.Methods. A total of 24 patients with functional intravenous cannulae in situ had obstruction simulated by the application of a tourniquet proximal to the cannula. The change in flow (F) for a discrete change in pressure (P) was determined in each case by counting drop rates at two different elevations of the fluid reservoir level, 10 cm apart. The same process was repeated in 15 patients in whom the cannula was in an extra vascular location (infiltration). Three sizes of cannula—16-gauge, 18-gauge, and 20-gauge—were examined, with equal distribution of sizes in each group. The effect on flow rates of inflating a blood pressure (BP) cuff proximally on the cannulated limb was assessed. The ratio P/F is the total resistance of the infusion system, and by subtracting known values for resistance of infusion tubing and cannula, the venous or tissue resistance was calculated.Results. There was a statistically significant difference between the change in flow for obstructed compared with infiltrated cannulae for the same change in pressure for each cannula size. The mean venous resistance was 23 mm Hg/L/hr, while that of tissue was 280 mm Hg/L/hr, with no overlap between groups. There was no effect on flow rate with blood pressure cuff inflation in the infiltrated group whereas flow progressively fell in the obstructed group.Conclusions. Clinical observation of PFRs in poorly functioning gravity-fed IV infusions can assist in detecting infiltration as a cause. Inflation of a blood pressure cuff will further impair flow where the cannula is intravascular, but will have no effect in an extravascular location.     

MRI dosimetry: a fast quantitative MRI method to determine 3D absorbed dose distributions

RATIONALE AND OBJECTIVES: Magnetic resonance imaging (MRI) techniques seem to be very promising for 3D dosimetry studies, but long imaging acquisition time limits their use. A new fast T1 mapping protocol, easy to implement on a conventional MR imager, has been used to determine dose distributions on Fricke gels. METHODS: The method has been tested on manganese chloride (MnCl2) doped ferrous gelatin gels. The T1 measuring times range from 1 minute 40 seconds to 3 minutes 30 seconds for a 256x256 matrix image. RESULTS: The two- and three-dimensional profiles agree with those obtained with conventional dosimetry techniques (ion chambers). The precision and the spatial resolution principally depend on the signal-to-noise ratio of the used imaging RF coil. For example, for a surface coil, the accuracy is about 2.5% with a 1.56 mm spatial resolution. CONCLUSION: These preliminary results support the feasibility of the proposed technique for accurate MRI dosimetry studies and also have potential for various clinical quantitative MRI applications.     

Pulmonary injury from proton and conventional radiotherapy as revealed by CT

OBJECTIVE: Although radiation therapy is used in early-stage inoperable lung cancer, it often results in injury to functional lung tissue. A study was undertaken to determine the frequency and severity of pulmonary injury revealed by CT in patients who had undergone conformal proton (to a limited volume) radiation therapy. We compared these findings with those from a group of patients who had undergone a combination of photon and conformal proton (to a larger volume) radiation therapy. CONCLUSION: Proton radiation therapy was associated with a lower frequency of pulmonary injury than the combined regimen. Injury correlated well with the volume of normal lung that was irradiated. Conformal proton radiation therapy appears to be able to reduce the incidence and severity of pulmonary injury revealed by CT.