Motomu Shimaoka

NITRIC OXIDE INDUCES APOPTOSIS IN MOUSE SPLENIC T LYMPHOCYTES

The cytotoxic effect of nitric oxide (NO) on mouse T lymphocytes was investigated. Freshly isolated T lymphocytes from mouse spleen were incubated with NOR, a novel NO releasing agent, at different doses. After incubation for 4 h, apoptotic cell death was observed in both NOR-treated T lymphocytes and controls as judged by the appearance of DNA laddering in agarose gel electrophoresis, but a quantitative analysis by flow cytometry indicated that the high level of exogenous NO (500 micrograms ml of NOR) could promote apoptosis in T lymphocytes as compared with controls (30% vs. 8%). After 8 h, NO promoted apoptosis of T lymphocytes in a dose-dependent manner. This study indicated that NO might be one of the factors which regulate this life of T lymphocytes in vivo.

Circadian secretion patterns of melatonin after major surgery

Abstract: Biorhythms, such as regular variation in core body temperature and the pattern of the secretion of melatonin, are thought to be mediated by the same biological clock. Core body temperature is affected by the inflammatory response to major surgery. Apart from the well‐known inhibitory effect of bright light on its secretion, melatonin is an exceedingly good marker of one of the central generating systems of circadian rhythms. We sequentially measured the plasma melatonin concentration pattern in patients who had undergone esophagectomy with thoracotomy to elucidate the circadian rhythm after major surgery. From seven patients who had received esophagectomy with thoracotomy for esophageal cancer, plasma concentrations of melatonin were measured using an RIA method. Blood samples were collected via each patients arterial line at 00.00, 02.00, 04.00, 06.00, 08.00, 12.00, 16.00, 20.00, and 24.00 hr on the first postoperative day for six of the patients, and, for one patient, every 2 hr until the third postoperative day and every 4 hr thereafter until the sixth postoperative day. Four patients out of seven had melatonin concentrations of over 30 pg/ml (mean 34 pg/ml) at 24.00 hr on the first postoperative day. Five patients showed circadian secretion patterns of melatonin during the first postoperative day. One patient whose melatonin concentrations were measured consecutively for 6 days showed a regular circadian secretion pattern through the 6 days of the study. Even the stress caused by extremely invasive surgery did not significantly disturb the melatonin secretion pattern.

Up-regulation of Fas ligand (FasL) mRNA expression in peripheral blood mononuclear cells (PBMC) after major surgery

FasL, which is expressed mainly on activated lymphocytes, can induce apoptosis (programmed cell death) of cells which express Fas. Fas/FasL interaction is primarily beneficial in maintaining immunological and physiological homeostasis by eliminating unnecessary cells. Dysregulation of the interaction, however, leads to tissue damage. We investigated how Fas/FasL levels changed after major surgery. The major aim of this study was to elucidate the involvement of the Fas/FasL system in postoperative inflammation. The investigation involved 10 patients admitted to the intensive care unit after surgery. Although the percentage of Fas+ cells and the amount of Fas expression tended to increase, there was no significant difference between pre‐ and post‐operative samples. In contrast, the levels of FasL mRNA were dramatically up‐regulated after operation. Post‐operative C‐reactive protein (CRP) levels increased and correlated well with FasL levels (ru2003=u20030.91, Pu2003<u20030.01). Lymphocyte counts decreased after operation and were inversely proportional to FasL levels (ru2003=u20030.58, Pu2003<u20030.05). These results suggest that the enhanced FasL expression is likely to be related to systemic inflammatory responses induced during the perioperative period. FasL up‐regulation may be involved in the aggravation of tissue damage, including lymphocytopenia, in the early post‐operative period.

Orally administered cholera toxin prevents murine intestinal T cells from staphylococcal enterotoxin B-induced anergy

BACKGROUND & AIMSnCholera toxin (CT) has been shown to be a strong mucosal adjuvant for the induction of antigen-specific secretory immunoglobulin A (IgA). The mechanism of adjuvant activity of CT is still unknown. The aim of this study was to examine the immunomodulatory function of CT on mucosal T cells using staphylococcal enterotoxin B (SEB) as coadministered oral antigen, because SEB has been shown to directly regulate alpha beta T-cell responses.nnnMETHODSnC3H/HeN mice were orally or systemically immunized with SEB and/or CT. The levels of SEB-specific antibodies and frequencies of CD4(+)Vbeta8(+) T cells were analyzed. SEB-specific T-cell proliferation and cytokine production were also determined.nnnRESULTSnNeither SEB-specific IgA nor IgG antibodies were induced in feces when SEB was administered alone. This was a result of the clonal deletion and partial unresponsiveness of CD4(+)Vbeta8(+)T cells in Peyers patches. On the other hand, SEB-specific antibodies were induced by oral immunization with SEB and CT. Although some degree of clonal deletion was induced by oral immunization with SEB and CT, coadministered CT prevented the induction of anergy for CD4(+)Vbeta8(+) T cells in Peyers patches.nnnCONCLUSIONSnCT is a powerful immunomodulatory molecule that prevents mucosal T cells from SEB-induced anergy.

Lymphocyte activation is attenuated by stellate ganglion block

BACKGROUND AND OBJECTIVESnClinical evidence suggests that stellate ganglion block (SGB) might modulate the immune system. Little is known, however, about the immunologic effects of SGB. We examined how SGB affected immune functions by analyzing the activation response of lymphocytes during SGB.nnnMETHODSnTwenty-four volunteers were randomly subdivided into three groups. The SGB group (SGB; n = 9) received 6 mL 1% lidocaine at the sixth cervical vertebra (C6) transverse process and showed Horners sign and elevation of ipsilateral facial and upper limb temperature. The lidocaine group (n = 7) had 6 mL 1% lidocaine injected into subcutaneous tissue at the neck and showed no remarkable clinical effects. The saline group (placebo; n = 8) received 6 mL saline solution injected at approximately the C6 transverse process and showed no remarkable clinical effects. Peripheral blood samples were drawn before and 30 minutes after drug administration. Samples were incubated for 4 hours under the stimulation of mitogen. Using flow cytometry, we measured the de novo expression of CD69, which is one of the initial markers of lymphocyte activation and which reflects the cell activation process. The changes in pre- and post-values were calculated and compared among the three groups.nnnRESULTSnIn only the SGB group, the helper T-cell activation was significantly reduced, and the cytotoxic T-cell activation also tended to decrease after SGB.nnnCONCLUSIONSnSGB may depress immune system activity for a short time, as reflected in the T-cell activation response.

A case of multiple aneurysms of the vein of Galen with heart failure due to persistent fetal circulation

Vein of Galen aneurysm (VGA), first mentioned in the literature in 1937 [1], has a high mortality rate in spite of the development of therapeutic strategies. Mortality rates as high as 91.4% have been reported for a total of 80 neonates [2]. VGA frequently accompanies congestive heart failure, which is the major cause of mortality and morbidity [3], and neonates with this disease present the most severe challenges to physicians. We report a patient with huge multiple aneurysms with persistent fetal circulation, which were treated by embolization with direct injection of coils into the aneurysms under craniotomy.