[Giant cutaneous squamous cell carcinoma of the nose with subsequent brain extension]. / Carcinome épidermoïde cutané géant du nez avec extension cérébrale secondaire.

INTRODUCTION: Cutaneous squamous cell carcinoma is an invasive and destructive tumor, and may cause death by local extension or because of metastasis. We report the case of a patient with a giant squamous cell carcinoma of the nose and extension to the brain and discuss the main risk factors from this extension. OBSERVATION: Resection of a giant squamous cell carcinoma was performed of the nose in a 45 year-old man after debulking radiotherapy. Histological examination disclosed a well-differentiated tumor and perineural involvement, with at least a 6 mm margin. A first relapse occurred on the orbital edge of the initial resection, the lesion was removed revealing an involvement of the infra-orbital nerve. Whilst the patient was receiving chemotherapy, a second relapse occurred responsible for ophthalmoplegia and loss of vision, with involvement of the left orbital apex, cavernous sinus and temporal lobe. The patient died from grand mal seizures. DISCUSSION: Brain extension of cutaneous squamous cell carcinoma of the head is rare. It develops along the anatomic pathways, especially perineural spread. Main risk factors for such a poor course are discussed, including the size of tumor, the anatomic site, the depth and perineural invasion.

Superoxide prevents nitric oxide-mediated suppression of helper T lymphocytes: decreased autoimmune encephalomyelitis in nicotinamide adenine dinucleotide phosphate oxidase knockout mice.

NO, which suppresses T cell proliferation, may be inactivated by superoxide (O2-) due to their strong mutual affinity. To examine this possibility, preactivated Th clones were cocultured with stimulated macrophages. PMA neutralized the inhibitory activity of NO, which was dependent on extracellular O2- production. In contrast, macrophages from p47phox -/- (pKO) mice, which lack functional NADPH oxidase, retained their NO-dependent inhibition of T cell proliferation upon stimulation with PMA, indicating that NADPH oxidase is the major source of NO-inactivating O2- in this system. To examine the NO-O2- interaction in vivo, the role of NADPH oxidase in experimental autoimmune encephalomyelitis was studied in pKO mice. No clinical or histological signs were observed in the pKO mice. Neither a bias in Th subsets nor a reduced intensity of T cell responses could account for the disease resistance. Although spleen cells from pKO mice proliferated poorly in response to the immunogen, inhibition of NO synthase uncovered a normal proliferative response. These results indicate that NO activity may play a critical role in T cell responses in pKO mice and that in normal spleens inhibition of T cell proliferation by NO may be prevented by simultaneous NADPH oxidase activity.

Antigen presentation to Th1 but not Th2 cells by macrophages results in nitric oxide production and inhibition of T cell proliferation: interferon-gamma is essential but insufficient.

The induction and role of nitric oxide (NO) during antigen presentation by macrophages to T helper (Th) cell subsets was examined. When cultured with Th1 clones, macrophage APC produced NO only in the presence of cognate Ag, which in turn suppressed T cell proliferation. IFN-gamma production by the activated Th1 cells was essential for the induction of NO. Th2 cells presented with the same cognate Ag did not induce NO production and proliferated uninhibited. Coactivation of Th1 and Th2 cells specific for the same Ag indicated that Th2 cells did not inhibit NO production, but were sensitive to NO induced by stimulated Th1 cells. Antigenic activation of Th2 cells in the presence of rIFN-gamma resulted in NO-mediated inhibition of proliferation. Th2 cells provided only a cell-associated cofactor, whereas Th1 cells secreted a soluble cofactor for IFN-gamma as well, i.e., TNF-alpha. Finally, a role for IFN-gamma and NO during immune responses was studied in spleen cells obtained from immunized IFN-gamma(-/-) mice. NO production and subsequent inhibition of Ag-specific proliferation ex vivo was observed only after the addition of rIFN-gamma. These studies suggest an IFN-gamma-dependent regulatory role for NO during Ag-specific Th cell activation involving macrophages, with obvious implications for Th subset-dependent immune responses in general.

Nitric oxide inhibits the proliferation of T-helper 1 and 2 lymphocytes without reduction in cytokine secretion.

To study the effect of nitric oxide (NO) on the activity of Th subsets, cloned Th1 and Th2 lymphocytes were stimulated in the presence of an NO donor. NO, when present from the start of incubation, inhibited the proliferation of both Th subsets dose-dependently, achieving complete inhibition at a relatively low level. The addition of NO 24 h after the onset of T cell stimulation also resulted in reduced proliferation of both Th subsets, suggesting that NO affects a late process during T cell activation. Stimulation of T cells in the presence of NO did not induce apoptosis at the concentrations that completely inhibited proliferation, although apoptosis became evident at higher NO concentrations. The secretion of several cytokines (i.e., IFN-gamma, IL-4, and IL-5) was slightly upregulated, while IL-2 production was modestly inhibited in the presence of NO. However, exogenous IL-2 did not reverse the NO-induced inhibition of T cell proliferation, nor did additional stimulation with phorbol esters. Finally, expression of IL-2R was modestly decreased in the presence of NO, although TCR expression was not affected. These studies demonstrate that relatively low concentrations of NO induce a strong and specific inhibition of T cell proliferation in both Th subsets, suggesting that local NO production may regulate Th-mediated tissue inflammation.

An injury profile of elite ironman competitors.

An injury questionnaire was administered to the 30 elite ironman competitors (mean age = 25.7 +/- 4.6 yrs) participating in a commercially sponsored seven race national series. Responses provided retrospective data from the preceding three years indicating the type, location, frequency, cause and severity of injuries sustained by ironmen, and associated these injuries with particular race components (run, swim, board, ski). Twenty self-reported questionnaires were returned for analysis that described a total of 67 injuries incurred by 19 subjects. Results indicated the following: (i) the most frequently injured body parts were the knee (n = 18) and shoulder (n = 14) with the lower extremity accounting for 55% of all injuries reported; (ii) knee, shin and calf injuries had a significant association with the run component and upper extremity injuries had a significant association with the swim component; (iii) running was perceived to be the most injurious race component in terms of the frequency and severity of injury; (iv) overtraining was perceived to be the main cause of injury; (v) tendinitis was perceived to be the main type of injury; (vi) athletes adjusted their training mode to accommodate injury so that total training volume could be maintained; and (vii) injury did not result in withdrawal from competition. Further research investigating the techniques used in the ironman event and their relationship to injury is recommended.

Athletes and pain tolerance.

Athletes' attitudes towards pain, and the cognitive strategies they use while experiencing pain, may be reflected in their pain tolerance levels and their performance and adherence to sport injury rehabilitation. Association and dissociation are 2 of the more popular cognitive strategies, and most research has found that these strategies increase pain tolerance and performance. It has not clearly been established how these results are transferred to athletes overcoming the pain associated with injury rehabilitation. The major limitation of most of these pain induction techniques is that they are inherently safe, and individuals know that the induced pain can be terminated at any time. Not only will the stressor be terminated, but the pain experienced will also decline because the pain is due to the stimulation. Thus, it is possible that pain tolerance and performance levels are higher in experimental settings than would normally be in real-life situations. However, exercise-induced muscle soreness is one pain induction technique which attempts to alleviate this limitation and therefore provide more realistic levels of pain to tolerate. The pain, stiffness, prolonged reduction in muscle strength, and decreased range-of-motion that appear 24 to 48 hours after strenuous eccentric exercise does not fully subside until 8 to 10 days after the initial bout of exercise. Study participants experience long-lasting, real-life pain. Thus, it is worthwhile for those involved in sport injury rehabilitation to be aware of the effectiveness of these cognitive strategies that may assist athletes to overcome the pain associated with exercise-induced muscle soreness, and how this relates to rehabilitation.

[Anti-atherosclerotic properties of some components of food (a clinico-experimental study)]. / Antiateroskleroticheskie svoistva nekotorykh komponentov pishchi (kliniko-éksperimental'noe issledovanie).

Platelet lysosomal proteinase and phospholipase activity, cholesterol content in the blood serum and circulating immune complexes, as well as blood serum atherogenic potential were studied with the use of human aortal intima atherosclerotic cell culture in patients with postinfarction cardiosclerosis (males aged from 45 to 62 years), 1-3 h before and 2-6 h after a single intake of one of the following products (50 g): sunflower oil, butter, cod fat, glucose, fructose, starch, dried milk protein, or 22 g of soybean protein isolate 500 U. The total data obtained have evidenced that the soybean protein isolate produces hypolipidemic and hypocholesterolemic effects, as well as possesses pronounced anti-atherosclerotic properties.

Measurement of the concentration of murine IgG monoclonal antibody in hybridoma supernatants and ascites in absolute units by sensitive and reliable enzyme-linked immunosorbent assays (ELISA).

We have investigated an enzyme-linked immunosorbent assay (ELISA) for mouse IgG using affinity-purified goat anti-mouse antibodies for capture and detection. This assay was used to measure the absolute or weight/volume concentration of murine monoclonal antibody in hybridoma supernatants. Bovine or subclasses except IgG3 in the 1-20 ng/ml range. Antibody capture was essentially complete in the optimized assay. In combination with an antigen-dependent ELISA, the assay allowed estimation of the absolute concentration of specific monoclonal antibody in ascites. These rapid and relatively simple assays may be applicable in many situations in which a practical means of measuring murine monoclonal antibodies in weight/volume units is needed.