Association of a 70-kDa tyrosine phosphoprotein with the CD16:ζ:γ complex expressed in human natural killer cells

The CD16: ζ: γ receptor complex allows natural killer (NK) cells to recognize and eliminate antibody-coated target cells. Whereas the ectodomain of CD16 is the receptor for Fcγ domains of immunoglobulins, disulfide-linked homo- and heterodimers composed of ζ and γ are required for the cell surface expression, and signal transduction properties of the complex. Engagement of CD16 activates the tyrosine kinase pathway, which induces the tyrosine phosphorylation of several substrates, including the ζ subunit and the phospholipase C γ-1 and γ-2 isoforms. Here we show that CD 16 stimulation of either peripheral blood NK cells, leukemic NK cells, or Jurkat transformants expressing a CD16:ζ:γ receptor complex, results in the tyrosine phosphorylation of a 70 kDa ζ-associated protein (pp70). Similarly, a 70-kDa ζ-associated phosphoprotein in T cells has been shown to be a tyrosine kinase (ZAP-70). Peptide mapping analysis indicates that the 70-kDa ζ-associated phosphoproteins from T cells and NK cells are structurally indistinguishable. We conclude that the CD16:ζ:γ complex may use a ZAP-70-related non-receptor tyrosine kinase, in the CD16 signaling cascade leading to NK cell activation.     

Responses of tonically discharging neurons in the monkey striatum to primary rewards delivered during different behavioral states

In the primate striatum, the tonically discharging neurons respond to conditioned stimuli associated with reward. We investigated whether these neurons respond to the reward itself and how changes in the behavioral context in which the reward is delivered might influence their responsiveness. A total of 286 neurons in the caudate nucleus and putamen were studied in two awake macaque monkeys while liquid reward was delivered in three behavioral situations: (1) an instrumental task, in which reward was delivered upon execution of a visually triggered arm movement; (2) a classically conditioned task, in which reward was delivered 1 s after a visual signal; (3) a free reward situation, in which reward was delivered at irregular time intervals outside of any conditioning task. The monkeys′ uncertainty about the time at which reward will be delivered was assessed by monitoring their mouth movements. A larger proportion of neurons responsive to reward was observed in the free reward situation (86%) than in the classically conditioned (57%) and instrumental tasks (37%). Among the neurons tested in all situations (n = 78), 24% responded to reward regardless of the situation and 65% in only one or two situations. Responses selective for one particular situation occurred exclusively in the free reward situation. When the reward was delivered immediately after the visual signal in the classically conditioned task, most of the neurons reduced or completely lost their responses to reward, and other neurons remained responsive. Conversely, neuronal responses invariably persisted when reward was delivered later than 1 s after the visual signal. This is the first report that tonic striatal neurons might display responses directly to primary rewards. The neuronal responses were strongly influenced by the behavioral context in which the animals received the reward. An important factor appears to be the timing of reward. These neurons might therefore contribute to a general aspect of behavioral reactivity of the subject to relevant stimuli. Received: 16 September 1996 / Accepted: 1 April 1997     

Comparison of Two Formulations of Nifedipine During 24-Hour Ambulatory Blood Pressure Monitoring

Study Objective . To determine if one commercial extended-release formulation of nifedipine (Adalat CC) is as effective as another (Procardia XL) in controlling blood pressure over 24 hours. Design . Open-label, randomized, crossover study. Setting . University-affiliated family medicine clinic. Patients . Fifteen patients with stage 1–4 primary hypertension. Interventions . Procardia XL or Adalat CC once/day was titrated to achieve blood pressure control. The effective dose was continued for 4 weeks, washed out for 1 week, and reinstituted with other study drug. Measurements and Main Results . Twenty-four-hour ambulatory blood pressure was recorded the conclusion of each treatment phase. Treatment phases were compared for mean 24-hour blood pressure, mean daytime (6:00 a.m.–10:00 p.m.) and mean nighttime blood pressure, and mean blood pressure load (percentage of blood pressure measurements < 140/90 mm Hg daytime and > 120/80 mm Hg nighttime). Thirteen patients completed the study. No statistically significant difference was seen in mean 24-hour blood pressure (138/86 mm Hg for Procardia XL vs 137/85 mm Hg for Adalat CC), daytime or nighttime blood pressure, or blood pressure load. Two patients experienced clinically significant adverse effects while taking Adalat CC. Conclusions . In these patients with primary hypertension, Adalat CC was as effective as Procardia XL at controlling blood pressure for 24 hours. Blood pressure, heart rate, and adverse effects should be monitored 2–4 weeks after any exchange of Adalat CC for Procardia XL.     

Neuronal dysfunction in heart failure assessed by cardiac 123-iodine metaiodobenzylguanidine scintigraphy

In patients with chronic heart failure, increased sympathetic activity and cardiac sympathetic neuronal dysfunction are present and have been related to unfavourable clinical outcome. Modification of these alterations with the objective to improve prognosis has become an important aim of pharmacological therapy for these patients. A noninvasive technique to assess sympathetic neuronal function at the cardiac level may be valuable in evaluating newly developed therapeutic strategies. 123-iodine metaiodobenzylguanidine can be used visualize cardiac sympathetic nerve function and activity. Single photon emission computerized tomographic is preferred to planar scintigraphy since it does not depend on superposition of other anatomical structures and may allow assessment of regional cardiac 123-iodine metaiodobenzylguanidine uptake. Although the quantitation of cardiac uptake in these tomographic images has several limitations, the use of the left ventricular cavity as a reference, calibrated by the 123-iodine activity in a blood sample drawn at the time of acquisition, may have clinical applications, with respect to the evaluation of therapeutical intervention in patients with heart failure.Abbreviations BS blood sample - CD count density - dP/dt change in pressure over time - [¹²³I] 123-iodine - K_m affinity constant - MIBG metaiodobenzylguanidine - MB_q mega Bequerel - SPECT single photon emission computerized tomography - V_m capacity constant     

Disarticulation resections of the mandible: a prospective review of 16 cases.

PURPOSE: This article provides a review of the disarticulation resection of the mandible for various benign and malignant tumors and non-neoplastic processes. In so doing, the author proposes a classification to describe extension of pathology into the condylar region, thereby requiring its sacrifice. Recommendations are also proposed for preservation versus sacrifice of the meniscus when performing a disarticulation resection of the mandible. Finally, complications are evaluated in this type of mandibular resection. PATIENTS AND METHODS: This review is based on the author's accumulated clinical data obtained from performing disarticulation resections on 16 patients who presented with 10 different pathologic diagnoses. Disarticulation resections are performed for 3 different patterns of extension of pathologic processes into the condylar region, designated as type I, type II, and type III by the author. These designations reflect the radiographic involvement of the condyle or subcondylar region of the mandible by the pathologic entity. The designations of type II and type III extensions are diagnosis dependent, whereas type I extension is independent of diagnosis. RESULTS: Five patients in this series presented with type I condylar extension, 2 patients presented with type II condylar extension, and 9 patients presented with type III condylar extension. The meniscus required sacrifice in 3 of the 16 patients. Complications occurred in 3 of 16 patients and included 1 dislocation of the plate into the middle cranial fossa, 1 dislocation of the plate inferiorly and posteriorly to the mastoid process, and 1 cutaneous exposure of the plate. CONCLUSIONS: Disarticulation resections are rarely required variants of segmental resection of the mandible, and they are required by a variety of pathologic processes of the jaws and contiguous structures. The placement of a reconstruction bone plate with an affixed condylar prosthesis is well tolerated by patients and is associated with few complications. These reconstruction bone plates favorably support facial form, symmetry, and occlusion such that many patients delay their definitive bony reconstruction. Because these condyles are temporary prostheses, the surgeon should consider their removal with bony reconstruction of the disarticulation defect as soon as possible after the ablative surgery.     

Rapidly enhancing hepatic hemangiomas at MRI: Distinction from malignancies with T2-weighted images

The purpose of this study is to describe a subset of atypical hepatic hemangiomas that enhance rapidly and diffusely and to determine whether heavily T2-weighted images could distinguish between atypically enhancing liver hemangiomas and hypervascular malignancies. A retrospective search of MR records identified seven patients with liver hemangiomas that demonstrated diffuse early enhancement and 23 patients with biopsy-proven malignant liver lesions that were hypervascular on dynamic gadolinium-enhanced MR images. Quantitative analysis of signal intensity measurements was performed on the T2-weighted images, heavily T2-weighted (TE < 140), and dynamic gadolinium-enhanced images. Blinded reader comparison of the T2-weighted images and gadolinium-enhanced images was performed. Hypervascular hemangiomas enhanced to a greater degree than hypervascular malignant liver lesions on the early phase gadolinium-enhanced images. Perilesional parenchymal enhancement was demonstrated in five cases of rapidly enhancing hemangiomas. Signal intensity and contrast-to-noise ratios on the heavily T2-weighted images of the hemangiomas were significantly greater than that of the hypervascular malignant lesions (P < .05). Hemangiomas were differentiated from the hypervascular malignant liver lesions with high accuracy (97–100%) by three blinded readers based on the T2-weighted images. A subset of hemangiomas have atypical rapid diffuse enhancement on dynamic gadolinium-enhanced images. These atypical hemangiomas can be distinguished from hypervascular malignant liver lesions on T2-weighted MR images.     

Individualized versus standardized therapy: A comparative evaluation with obsessive-compulsive patients

The aim of this study was to investigate whether individualized tailor-made behavioural treatment based upon a problem analysis of each case was more effective than a standardized behavioural treatment protocol. Twenty-two obsessive-compulsive patients were randomly assigned to two treatment conditions: (1) tailor-made cognitive behavioural therapy and (2) standardized exposure in vivo therapy. Treatment in both conditions led to significant improvements on obsessive-compulsive targets and on the Maudsley Obsessional-Compulsive Inventory. Improvement generalized to general levels of psychopathology, depressed mood and social anxiety. Contrary to expectations the individualized treatment was not more effective than the standardized exposure therapy.