Protection from Shigella sonnei infection by immunisation of rabbits with Plesiomonas shigelloides (SVC 01).

Plesiomonas shigelloides, an organism commonly found in water, is only rarely associated with diarrhoea in man. P. shigelloides serotype O:17 (SVC O1), which is antigenically similar to Shigella sonnei, was found to be neither virulent nor toxic for rabbits. Rabbits immunised by feeding with P. shigelloides (SVC O1) were completely protected against an oral challenge with 10(10) cells of S. sonnei but non-immunised rabbits were not. P. shigelloides (SVC O1) may be a useful vaccine strain for shigellosis.     

Radioresponsiveness, sublethal damage repair and stem cell rate in spheroids from three human tumor lines: comparison with xenograft data.

Dose-control curves after fractionated irradiation were generated for small oxic spheroids from the two human glioma cell lines, U87 and A7, as well as the squamous cell carcinoma line FaDu. These data were fitted by the linear quadratic model assuming Poisson statistics. The alpha/beta values of A7, U87, and FaDu spheroids, respectively were 10.3 (8.1-12.9) Gy, 17.8 (15.1-21.1) Gy, and 37.9 (29.1-51.5) Gy. These data were compared with those previously published by Suit et al. (31) and Zietman et al. (40) for 6 mm xenografts of U87 and FaDu after fractionated irradiation and for A7 after single dose irradiation under clamped conditions. A good agreement in the alpha/beta values was observed for U87 and Fadu xenografts and spheroids assuming an oxygen enhancement ratio (OER) of 2.7. In addition, the ranking according to the single doses needed to control 50% of the tumors agreed for xenografts and spheroids from the three cell lines. U87 was the most resistant line in both model systems, followed by A7 and FaDu. However, the absolute values of alpha and beta, obtained from the direct fit to the dose-control data were only about half as high for U87 and FaDu xenografts than for the spheroids. Monte Carlo simulations showed that this discrepancy can be explained by a greater tumor heterogeneity of the xenografts. While the number of critical stem cells or spheroid rescuing units equaled the number of cells per spheroid for the three cell lines, the percentage of tumor rescuing units for Fadu and U87 xenografts was estimated to be below 1%. In a next step, survival curves were generated for exponentially growing cells of the three lines. A7 cells were significantly more radioresistant when plated on tissue plastic than in soft agar. Using the most resistance-promoting colony assay conditions for each cell line, a good agreement was observed for the alpha and SF2Gy values calculated from the colony and spheroid control data. This study shows that the spheroid model can quantitatively predict the repair capacity of sublethal damage as well as the rank order of radiation sensitivity of in vivo tumors.     

Neuroendocrine response to 5-hydroxytryptophan in seasonal affective disorder

A double-blind random-ordered comparison of the effects of placebo and 5-hydroxytryptophan (200 mg, orally) in ten depressed patients with seasonal affective disorder (SAD) and ten controls disclosed slightly but significantly higher basal levels of serum prolactin and a trend toward higher basal levels of serum cortisol in the patients with SAD compared with controls. After administration of 5-HTP, the cortisol level significantly increased and the prolactin level significantly decreased in both patients and controls. No differences in the melatonin level, growth hormone level, blood pressure, or pulse rate and no side effects were noted between patients and controls in the two study conditions; the timing of basal and 5-hydroxytryptophan-stimulated hormonal secretions was similar for both groups. These results are discussed with reference to current hypotheses of the cause of SAD.