Prevention of T cell anergy by signaling through the gamma c chain of the IL-2 receptor

When stimulated through their antigen receptor without requisite costimulation, T cells enter a state of antigen-specific unresponsiveness termed anergy. In this study, signaling through the common gamma chain of the interleukin-2 (IL-2), IL-4, and IL-7 receptors in the presence of antigen was found to be sufficient to prevent the induction of anergy. After culture with IL-2, IL-4, or IL-7, Jak3 kinase was tyrosine-phosphorylated, which correlated with the prevention of anergy. Therefore, a signal through the common gamma chain may regulate the decision of T cells to either clonally expand or enter a state of anergy.     

Early formation of sexually dimorphic glomeruli in the developing olfactory lobe of the brain of the moth Manduca sexta

The antennal lobes (ALs), the primary olfactory centers, of the moth Manduca sexta are sexually dimorphic. Only ALs of males possess the macroglomerular complex (MGC), the site of primary processing of information about the female's sex pheromone. To understand the development of identified, odor-specific olfactory glomeruli, we investigated the cellular events involved in the morphogenesis of the MGC by means of various fluorescence staining techniques and laser-scanning confocal microscopy. The MGC lies near the entrance of the antennal nerve into the AL of the adult male and comprises three glomeruli, the globular cumulus and two toroidal structures. The MGC forms during early stages of metamorphic adult development through a stereotyped sequence of coordinated changes in MGC-specific receptor axons, glial cells, and early-ingrowing projection neurons of the medial group of AL neurons. The MGC divisions are the earliest glomeruli to form in the male AL, and their basic organization is established within about 3 days after ingrowth of the first sensory axons. Despite their special anatomical features, the MGC glomeruli develop in a manner similar to that of the ordinary glomeruli. Comparison of the ALs of males and females reveals that two relatively large and early-developing glomeruli that are situated dorsolaterally in the female AL appear to be female-specific. Development of the sexually dimorphic glomeruli diverges immediately after the ingrowth of the first olfactory receptor axons, resulting in the formation of these large glomeruli in females and the MGC in males.     

Imagined empathy and attributions concerning activity preferences of physically disabled college students.

Investigated 89 college students' attributions about the activity preferences of able-bodied vs physically disabled peers and evaluated the effects of imagined empathy on attributional patterns and attitudes toward disabled people. Ss were asked to predict the responses of either a male or a female able-bodied or wheelchair-user college student to items on a 20-item questionnaire offering choices between gregarious–nongregarious activities and between active–passive activities. Results indicate that there was considerable variability in able-bodied students' attributions about disabled peers' activity preferences. Previous contact with disabled people was unrelated either to attitudes toward disabled people or to activity preference attributions. Asking students to imagine empathy for a disabled peer was not an effective technique to change either attributional patterns or attitudes toward disabled people. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dosimetric analysis of chimeric monoclonal antibody cMOv18 IgG in ovarian carcinoma patients after intraperitoneal and intravenous administration

In this study the potential of intraperitoneal (i.p.) and intravenous (i.v.) administration of chimeric iodine-131-labelled MOv18 IgG for radioimmunotherapy was determined. The dosimetry associated with both routes of administration of cMOv18 IgG was studied in patients. Eight patients suspected of having ovarian carcinoma received 150 MBq 131I-cMOv18 IgG i.p. Blood and urine were collected and serial gamma camera images were acquired. Another group of four patients received 7.5 MBq 131I-cMOv18 IgG i.v. For all patients, tissue biopsies were obtained at surgery. Activity in the blood after i.p. administration was described by a bi-exponential curve with a mean uptake and elimination half-life of 6.9+/-3.2 h and 160+/-45 h, respectively. For i.v. infusion the mean half-life for the elimination phase was 103+/-12 h. Cumulative excretion in the urine was 17%+/-3% ID and 21%+/-7% ID in 96 h for i.p. and i.v. administration, respectively. Scintigraphic images after i.p. administration showed accumulation in ovarian cancer lesions, while all other tissues showed decreasing activity with time. Tumour uptake determined in the ovarian cancer tissue specimens ranged from 3.4% to 12.3% ID/kg for i.p. administration and from 3.6% to 5.4% ID/kg for i.v. administration. Dosimetric analysis of the data indicated that 1.7-4.3 mGy/MBq and 1.7-2.2 mGy/MBq can be guided to solid or ascites cells after i.p. and i.v. administration, respectively. Assuming that an absorbed dose to the bone marrow of 2 Gy will be dose limiting, a total activity of 4.1 GBq 131I-cMOv18 IgG can be administered safely via the i.p. route and 3.5 GBq via the i.v. route. At this maximal tolerated dose, a maximum absorbed dose to 1-g tumours in the peritoneal cavity of 18 and 8 Gy can be reached after i.p. and i.v. administration, respectively. For the i. p. route of administration, dose estimates for the tumour are even higher when the electron dose of the peritoneal activity is also taken into account: total doses to the tumour of 30 Gy and 22 Gy will be absorbed at the tumour surface and at 0.2 mm depth, respectively. In conclusion, therapeutic tumour doses can be achieved with 131I-cMOv18 IgG in patients with intraperitoneal ovarian cancer lesions with no normal organ toxicity. The i.p. route of administration seems to be preferable to i.v. administration.     

Visualization of specific B and T lymphocyte interactions in the lymph node

Early events in the humoral immune response were visualized in lymph nodes by simultaneous tracking of antigen-specific CD4 T and B cells after immunization. The T cells were initially activated in the T cell areas when the B cells were still randomly dispersed in the B cell-rich follicles. Both populations then migrated to the edges of the follicles and interacted there, resulting in CD154-dependent B cell proliferation and germinal center formation. These results provide visual documentation of cognate T-B cell interactions and localize them to the follicular border.     

Rectal hemorrhage as a first sign of renal cell adenocarcinoma

We present a 3-year-old patient with stenotic kinking of the left internal carotid artery (ICA) who developed an ischaemic infarction of the left brain hemisphere followed by severe neurological sequelae after a prolonged generalized seizure. At time of the seizure the boy was in biological remission of a nephrotic syndrome and received prednisolone and cyclosporin A (CsA) treatment. The haemodynamic consequences of inborn kinking of the ICA is discussed controversely in the literature. The presented case shows that stenotic kinking of the ICA may significantly impair the blood flow towards the homolateral hemisphere and therefore may result in an ischaemic infarction. The influence of CsA on seizure activity is discussed. CONCLUSION: This case provides clinical and radiological evidence supporting an association between stenotic kinking of the carotid artery and homolateral hemispheric brain infarction.     

Biodistribution of radiolabeled lipid-DNA complexes and DNA in mice

The tissue biodistribution and expression of [33P]DNA-1-[2-[9-(Z)-octadecenoyloxy]ethyl]]-2-[8](Z)-heptadece nyl]-3 -[hydroxyethyl]imidazolinium chloride (DOTIM):cholesterol complexes and 33P-radiolabeled DNA expressing chloramphenicol acetyl transferase (CAT; 4.7 kB) were studied after intravenous (iv) injection in ICR mice. Mice were injected with 200 microL of complex containing DNA at 3 mg/kg or DNA alone. One group received 8 microCi of radioactivity and were sacrificed at 5 and 20 min, and 1, 2, 4 and 24 h post-dose (n = 4/time point). A second group received the equivalent of 3.9 microCi of radioactivity and were sacrificed at 20 min, and 2 and 24 h for subsequent whole body autoradiographic analysis (WBA; n = 2/time point). The tissue distribution of intact DNA was assessed by Southern blot at 24 h post-dose, whereas the integrity of complexes and DNA incubated in heparinized whole blood was studied separately. In further studies, the time course of expression in lung tissue over a 48-h period was examined, and the relative lung-expression of purified open circular (OC) versus supercoiled (SC) DNA at 24 h was evaluated. Approximately 42% of the radioactivity was found in the lungs 5 min after injection and about half this percentage was found in the liver. By 2 h, only 5% remained in the lungs, but 48% was present in the liver. No other tissue accumulated >5% of the dose throughout the duration of the study. WBA radiograms confirmed the tissue distribution results and highlighted significant accumulation of radioactivity in bone over time. Southern Blot analysis demonstrated intact DNA in many tissues 24 h after dosing. In contrast, the majority of DNA incubated in blood was degraded within 2 h, although the complexes afforded some protection relative to DNA alone. The OC DNA expressed equivalently to SC DNA in lung tissue (OC = 1035 +/- 183 pg; SC = 856 +/- 257 pg/mg soluble protein, n = 6, mean +/- SEM) at 24 h, and detectable levels of CAT were present within 2 h of dosing (21.3 +/- 7.2 pg, n >/= 8, mean +/- SD). The results confirm that DNA-DOTIM:cholesterol complexes are initially deposited in the lungs after iv administration.