Lymphokine-activated killer cell function of peripheral blood mononuclear cells, spleen cells and regional lymph node cells in gastric cancer patients.

Lymphokine-activated killer (LAK) cells generated by culture of peripheral blood mononuclear cells (PBMC), spleen cells (SPC) and regional lymph node cells (LNC) with IL-2 for 4 days were examined for their functional capabilities in 29 patients with gastric carcinoma. The cytotoxic activity of LAK cells induced from LNC was significantly lower than that from either PBMC or SPC, although there was no difference between PBMC or SPC. The induction of mRNA of interferon-gamma (IFN-gamma) or tumour necrosis factor-alpha (TNF-alpha) and the production of these cytokines in the non-adherent LAK cells from LNC were also significantly reduced compared with those from PBMC or SPC. Further, the LAK cells from LNC secreted significantly lower levels of these cytokines when stimulated with tumour target, Raji cells, although the production of these cytokines was markedly increased by stimulation with the targets in all three cell populations. Phenotypic analysis of each cell population revealed a decreased proportion of the cells mediating natural killer (NK) activity, including CD16+, CD56+, and CD57+ cells in LNC either before or after culture, although OKIa1+ and CD25+ cells were uniformly increased in all cell populations after culture. Changes in subpopulations of CD4+ and CD8+ cells in LNC were not apparently different from PBMC or SPC. These results indicated the differential reactivity of each lymphocyte population to IL-2 and the reduced LAK cell function of LNC compared with PBMC or SPC in patients with gastric carcinoma.     

Thermal regulatory responses to submaximal cycling following lower-body cooling in humans

This study compared the effects of pre-exercise cooling with control water immersions on exercise-induced thermal loads derived from steady-state submaximal exercise. Eight healthy male participants [mean (SEM) age 29 (1) years, maximal oxygen uptake 3.81 (0.74) l·min^–1, and body surface area 1.85 (0.11) m²] took part in experiments that included 30 min of baseline data collection [ambient temperature 21.3 (0.2°C)], 30 min of immersion in water to the level of the supra-iliac crest [water temperatures of 35.1 (0.3)°C for thermoneutral and 17.7 (0.5)°C for precooled treatments], and 60 min of cycling exercise at 60% of maximal oxygen uptake. No significant differences were noted during exercise in net mechanical efficiency, metabolic rate, O₂ pulse, or ratings of perceived exertion between the two treatments. Precooling resulted in a significant negative body heat storage during immersion and allowed greater heat storage during exercise. However, net body heat storage for the entire protocol was no different between treatments. Cooling significantly lowered rectal, mean skin, and mean body temperatures as well as more than doubling the exercise time until a 0.5°C rectal temperature increase was observed. The cooling trial significantly delayed onset of sweating by 19.62 min and decreased sweat rate by 255 ml·h^–1 compared to control. Thermal and sweat sensation scores were lower after the cooling treatment compared to control. These data suggest that lower-body precooling is effective at decreasing body heat storage prior to exercise and decreases reliance on heat dissipation mechanisms during exercise. Therefore, this unique, well-tolerated cooling treatment should have a broader application than other precooling treatments. Electronic Publication     

The role of central parts of the brain in the control of sound production during courtship in Drosophila melanogaster

The question of the roles of the two main parts of the insect brain, the mushroom bodies and the central complex, in controlling motor coordination and triggering a variety of behavioral programs, including sound production, remains controversial. With the aim of improving our understanding of this question, we studied the parameters of songs used by five-day-old males during courtship for fertilized wild-type females (Canton-S, C-S) over 5-min periods at 25°C; males were of two wild-type Drosophila Melanogaster lines (Berlin and C-S). Berlin males lacking mushroom bodies because of treatment with hydroxyurea during development (chemical removal of the mushroom bodies) were used, along with two mutants with defects in the mushroom bodies (mbm ¹ and mud ¹), two mutants with defects in the central complex (ccb ^KS127 and cex ^KS181), and mutant cxb ^N71 with defects in both the mushroom bodies and the central complex. The experiments reported here showed that courtship songs in males lacking mushroom bodies were virtually identical to those of wild-type males. The main parameters of pulsatile song in mutants mbm ¹ and mud ¹ (interpulse interval and train duration) were insignificantly different from those of the songs of wild-type flies, though the stability of the pulse oscillator was the same. Flies of these lines were no different from wild-type flies in terms of courtship success (percentage of copulating pairs in 10-min tests). Conversely, the songs of mutants with defects in the central complex differed from those of wild-type males. Firstly, there was degradation of the stability of the pulse oscillator and interpulse intervals were very variable. In addition, pulses were often significantly longer and appeared multicyclic, as in the well-known cacophony mutant, while the mean train duration was significantly shorter. Males of the line cex ^KS181 usually courted very intensely, though abnormal sounds were generally emitted. Mutants cex ^KS181 and ccb ^KS127 were significantly less successful in courtship than wild-type flies. These data show that the central complex appears to play a very important role in controlling song, while the mushroom bodies are not related to this function.     

Production of immunoglobulins by human sIgD+ and sIgD- human blood B lymphocytes in response to stimulation with activated T cells and agonistic antibodies; effect of IL-10, IL-2 and mode of activation of T cells.

Production of IgM, IgG and IgA was induced from human blood B lymphocytes by culturing with a CD40 MoAb and IL-2 for 9 days. Replacement of IL-2 by IL-10 markedly enhanced production of all three isotypes. High levels of immunoglobulin production also occurred when activated irradiated autologous T cells replaced the CD40 MoAb, and when IL-10 replaced IL-2 in these cultures a spectacular increase in IgG production occurred. The effectiveness of the T cell stimulus depended on the mode of purification of the T cells and the nature of the stimulant used to activate them. Differences in the kinetics and level of expression of CD40L on the various T cell preparations were observed, but did not account for variations in immunoglobulin-inducing efficiency. Immunoglobulin production from sIgD+ and sIgD- B cells was investigated. IgG and IgA were found in sIgD+ cultures, indicating that some isotype switching had occurred, but the major part of the IgG and IgA secreted was from cells already committed to these isotypes. Anti-IgD or anti-IgM MoAbs enhanced the proliferation of B cells induced by anti-CD40 antibody, but immunoglobulin production was not enhanced. Factors affecting the balance of proliferation and differentiation are discussed.     

An Epstein-Barr virus-producer line Akata: Establishment of the cell line and analysis of viral DNA

An Epstein-Barr virus (EBV)-producer line, designated Akata, was established from a Japanese patient with Burkitt's lymphoma. The Akata line possessed the Burkitt's-type chromosome translocation, t(8q-; 14q+), and was derived from the tumor cell. Akata cells produced a large quantity of transforming virus upon treatment of cells with anti-immunoglobulin antibodies (Takada, 1984). Southern blot analysis of viral DNA indicated that the Akata EBV is nondefective and more representative of wild-type viruses. Akata cells should be useful as a source of EBV.     

Effect of endurance and sprint exercise on the sensitivity of glucose metabolism to insulin in the epitrochlearis muscle of sedentary and trained rats

Summary The effects of two types of acute exercise (1 h treadmill running at 20 m· min^–1, or 6 × 10-s periods at 43 m · min^–1, 0° inclination), as well as two training regimes (endurance and sprint) on the sensitivity of epitrochlearis muscle [fast twitch (FT) fibres] to insulin were measured in vitro in rats. The hormone concentration in the incubation medium producing the half maximal stimulation of lactate (la) production and glycogen synthesis was determined and used as an index of the muscle insulin sensitivity. A single period of moderate endurance as well as the sprint-type exercise increased the sensitivity of la production to insulin although the rate of la production enhanced markedly only after sprint exercise at 10 and 100 U· ml^–1 of insulin. These effects persisted for up to 2 h after the termination of exercise. Both types of exercise significantly decreased the muscle glycogen content, causing a moderate enhancement in the insulin-stimulated rates of glycogen synthesis in vitro for up to 2 h after exercise. However, a significant increase in the sensitivity of this process to insulin was found only in the muscle removed 0.25 h after the sprint effort. Training of the sprint and endurance types increased insulin-stimulated rates of glycolysis 24 h after the last period of exercise. The sensitivity of this process to insulin was also increased at this instant. Both types of training increased the basal and maximal rates of glycogen snythesis, as well as the sensitivity of this process to insulin at the 24^th following the last training session. It was concluded that in the epitrochlearis muscle, containing mainly FT fibres, both moderate and intensive exercise (acute and repeated) were effective in increasing sensitivity of glucose utilization to insulin. Thus, the response in this muscle type to increased physical activity differs from that reported previously in the soleus muscle, representing the slow-twitch, oxidative fibres in which sprint exercise did not produce any changes in the muscle insulin sensitivity.     

Slow event-related brain activity of aphasic patients and controls in word comprehension and rhyming tasks

Slow event-related potentials (ERP) were examined in healthy and aphasic subjects in two-stimulus designs comprising a word comprehension and a rhyming task. Aphasics, though selected to perform above chance level, made significantly more errors and responded more slowly than controls, although canonical correlations did not indicate a statistical relationship between performance measures and ERP amplitudes. A discriminant analysis of ERP amplitudes distinguished the groups for the slow wave (SW; 0.5-1.0 s post-S1 onset) in the word comprehension, for the SW and the initial contingent negative variation (iCNV; 1.0-2.0 s post-S1 onset) in the rhyming task. Similarly for both tasks, ERP topography showed left-anterior predominance of the negative SW and iCNV in controls, whereas participants with aphasia showed smaller anterior and larger left-posterior amplitudes. The centroparietal terminal CNV (tCNV; 1 s pre-S2) was smaller in participants with aphasia than in controls, but similar in topography. Results suggest left-anterior activation for those language processes that were presumably provoked in the present tasks, like lexical access, or phonological encoding. The pattern of participants with aphasia may indicate effects of language impairment and recovery, but also consequences of the brain damage.     

The soluble tumor necrosis factor receptor I is an early predictor of local infective complications after colorectal surgery

The clinical implications of increased cytokine levels after major surgery remain unclear. In this study, systemic concentration of a spectrum of cytokines, including interleukins IL-6, IL-8, IL-10, IL-1ra, and soluble tumor necrosis factor receptor-I (sTNF-RI) was examined in patients with and without postoperative septic complications following colorectal surgery. Although there were no significant changes in IL-1, TNF-, and IL-8 serum levels during the observation period, there was a significant rise in IL-6, IL-1ra, and sTNF-RI concentrations in the entire group of patients between postoperative day 1 and 14. There were no differences between the group without and with local complications when IL-6, IL-1ra, and IL-10 were examined. The serum levels of sTNF-RI, IL-1ra, and IL-6 were found to be sensitive indicators of the pro- and anti-inflammatory response to the surgical trauma, but only sTNF-RI turned out to be a sensitive early marker of local septic postoperative complications in patients with colorectal carcinoma.     

T cell activation correlates with an increased proportion of antigen among the materials acquired from target cells

We have investigated the density of peptides required to elicit different biological responses in cytotoxic T lymphocytes (CTL), including trogocytosis (i.e., the phenomenon whereby the lymphocytes actively capture fragments of plasma membrane from those cells with which they establish an immune synapse). We have used two separate mouse models of CTL recognising defined peptides presented by MHC class I molecules. In both systems, triggering of cytotoxicity and capture of membrane components reached saturation with low densities of ligand. On the other hand, down-modulation of cell-surface levels of TCR, induction of IFN-gamma production and detection of peptide captured required much higher ligand densities. Interestingly, fratricide (i.e., killing between CTL sharing the same specificity), a mechanism proposed to account for CTL exhaustion, was detected only at antigen concentrations still well above that second threshold leading to full blown activation. Taken together, our results show that the different thresholds that govern the elicitation of different CTL functions correlate with different proportions of antigen among the target cell components being captured via trogocytosis.     

The significance of argyrophilia in human breast carcinomas

Summary The significance of demonstrating argyrophilia in human breast carcinomas is a complex issue, although there is general agreement that true carcinoid tumours of the breast are rare.A predominantly unselected series of breast carcinomas has been investigated for evidence of argyrophilia using the Churukian Schenk method (Churukian and Schenk 1979), alpha lactalbumin and prealbumin, a marker of neuroendocrine cells.Argyrophilia has been detected in 25% of carcinomas, including all of mucinous types. However, only 4 of the 68 tumours had a diffuse cytoplasmic reaction typical of that seen in neuroendocrine cells. The others showed a focal or subluminal/ peripheral reaction. Those argyrophilic carcinomas with demonstrable alpha lactalbumin had this latter pattern of reactivity, although the milk protein was always detected in lesser amounts by comparison. Prealbumin was only found to varying degrees in eight tumours and the majority of these had a diffuse or focal cytoplasmic argyrophilic reaction.It would appear that in only a small number of breast carcinomas, approximately six percent, does the presence of argyrophilia probably represent neuroendocrine differentiation, whilst in others it is related to the secretory nature of the tumour cells.