Both the lymphotoxin and tumor necrosis factor pathways are involved in experimental murine models of colitis

BACKGROUND & AIMS: Membrane lymphotoxin (LT) alpha/beta, a member of the tumor necrosis factor (TNF) family of immune regulatory molecules, is involved both in the development of secondary lymphoid tissues and the maintenance of organized lymphoid tissues in the adult. Defects observed in the mucosal immune system in animals with a genetically disrupted LTalpha/beta pathway coupled with the expression of LTalpha/beta in activated T cells motivated an examination of the importance of this pathway in experimental colitis. METHODS: Soluble LTbeta receptor (LTbetaR) immunoglobulin fusion protein was used to inhibit the LTalpha/beta/light axis in two independent rodent models of colitis: CD45RBhi CD4(+)-reconstituted SCID mice and bone marrow-transplanted tg26 mice (BM --> tg26). RESULTS: Treatment with LTbetaR immunoglobulin attenuated the development of both the clinical and histological manifestations of the disease in these two murine models of colitis. Given the success of TNF inhibitors in the treatment of human Crohn's disease, the effects of LTbetaR immunoglobulin have been compared with antibody to TNF in the BM --> tg26 model, and both treatments were equally efficacious. CONCLUSIONS: The LT pathway plays a role in the development of colitis as important as that of the TNF system and, therefore, represents a potential novel intervention point for the treatment of inflammatory bowel disease.     

Transient hemifacial spasm associated with subarachnoid brainstem cysticercosis: a case report

The vestibulo-ocular reflex (VOR) and angular displacement perception were measured in 25 healthy humans in darkness before and after exposure to incoherent visual-vestibular stimulation (VVS): 45 min of repeated passive 180 degrees whole-body rotations around the vertical axis concurrent with only 90 degrees rotation in a visual virtual square room. Large inter-individual variability was observed for both VOR gain and turning estimates. The individual VOR gains were not correlated with perceived angles of rotation either before or after VVS. After VVS, the angular displacement perception decreased by 24+/-16% while the VOR gain did not change significantly. The results suggest that adaptive plasticity in turning perception and adaptive plasticity in VOR might be independent of one another.     

Surgical pathology of submandibular gland. Experience in La Rioja community

The AA. had work through medical histories of 44 patients operated for inflammatory and tumoral pathology of submandibular gland. Between inflammatory diseases they emphasize sialolithiasis (45%), acute submaxillaritis (18%) and Kuttner's tumor (11%). Pleomorphic adenoma accounted for the 50% of tumors. Diagnosis was based on each peculiar history sheet, on imaging procedures (simple X-ray plate, echography, sialography, TC) and extemporaneous biopsy. In all cases a complete exeresis of the gland was performed. In malignoma cases the procedure was completed with a prophylactic neck dissection. Incidence of lasting paralysis of the ramus marginalis mandibulae accounted for 6.8%.     

Intrauterine cortisol, aldosterone, and corticosteroid binding globulin-like activity during early porcine pregnancy and the estrous cycle

Studies were conducted to determine whether the corticosteroids cortisol and aldosterone, and corticosteroid-binding globulin (CBG) were present in the porcine early-embryonic environment. Cortisol was measured in uterine flushings from white crossbred gilts at Days 7, 10, 13, and 16 of the estrous cycle and pregnancy. Total content of cortisol increased (p < 0.01) between Days 13 and 16, and immunoreactive CBG (ir-CBG) increased (p < 0.01) between Days 10 and 13, in both cyclic and pregnant gilts. In a separate study with Chinese Meishan gilts, total cortisol and aldosterone content of uterine flushings increased (p < 0.02) between Days 10 and 15 of the estrous cycle and pregnancy. In another study with white crossbred gilts, CBG-like binding activity in uterine flushings was low at Day 10, then increased over 100-fold at Day 15 (p < 0.01). However, levels of CBG-like binding activity on Day 15 were 100-fold lower than those of ir-CBG measured in the previous study and could bind less than 4% of the uterine luminal cortisol. Differences between ir-CBG and CBG binding might be due to the ability of the CBG antibody to recognize either biologically inactive CBG or structurally similar molecules. CBG-like binding activity, which appeared unrelated to glucocorticoid receptors, was also present in the endometrial cytosol of white crossbred gilts. Concentrations (fmol/mg protein) of endometrial CBG-like activity decreased (p = 0.03) between Days 10 and 15 of the estrous cycle and pregnancy, did not differ with reproductive status, and on Day 15 were comparable to concentrations in uterine flushings but threefold lower (p < 0.01) than those in the serum. Equilibrium dissociation constants for CBG-like binding activities were comparable among the three locations. These studies indicate that corticosteroids are present-primarily in the free form-within the porcine uterine lumen and could influence early porcine conceptus development. Endometrial CBG-like binding activity could mediate actions of cortisol or progesterone on uterine function.     

Structurally related but functionally distinct yeast Sm D core small nuclear ribonucleoprotein particle proteins

Spliceosome assembly during pre-mRNA splicing requires the correct positioning of the U1, U2, U4/U6, and U5 small nuclear ribonucleoprotein particles (snRNPs) on the precursor mRNA. The structure and integrity of these snRNPs are maintained in part by the association of the snRNAs with core snRNP (Sm) proteins. The Sm proteins also play a pivotal role in metazoan snRNP biogenesis. We have characterized a Saccharomyces cerevisiae gene, SMD3, that encodes the core snRNP protein Smd3. The Smd3 protein is required for pre-mRNA splicing in vivo. Depletion of this protein from yeast cells affects the levels of U snRNAs and their cap modification, indicating that Smd3 is required for snRNP biogenesis. Smd3 is structurally and functionally distinct from the previously described yeast core polypeptide Smd1. Although Smd3 and Smd1 are both associated with the spliceosomal snRNPs, overexpression of one cannot compensate for the loss of the other. Thus, these two proteins have distinct functions. A pool of Smd3 exists in the yeast cytoplasm. This is consistent with the possibility that snRNP assembly in S. cerevisiae, as in metazoans, is initiated in the cytoplasm from a pool of RNA-free core snRNP protein complexes.     

Effect of levamisole on pokeweed mitogen stimulation of immunoglobulin production in vitro

The effects of levamisole (LMS) on immunoglobulin (Ig) production were studied in vitro using peripheral blood lymphocytes from normal subjects stimulated with pokeweed mitogen (PWM). Cells were cultured for 9 days with varying concentrations of LMS and PWM, and immunoglobulin secretion in the supernatants was quantified by solid phase radioimmunoassay. The results showed that 1) the effect of LMS in vitro depends upon the degree of lymphocyte stimulation by PWM. When PWM stimulation is optimal, typical pharmacologic concentrations of LMS (0.5 micro/ml) decrease both IgM and IgG production by 50%. However, at lower suboptimal doses of PWM, LMS, at similar concentrations, enhances immunoglobulin production by 24% (p less than 0.01). Unstimulated lymphocytes are not affected by LMS. 2) The target cell upon which LMS acts is present among a T subpopulation that lacks the Fc receptor for aggregated rabbit IgG (T gamma -negative). We suggest that the diverse effects of LMS on autoimmune disease in vivo may depend upon both the size and degree of activation of the T gamma -negative lymphocyte pool.