Leukemia clusters around nuclear facilities in Britain

He bas been retained for the defense by British Nuclear Fuelsplc in two suits in which leukemia and non-Hodgkin's lymphoma have been alleged to result from radiation exposures due to the operation of the nuclear reprocessing plant at Sellafield. This paper has been sent to the senior authors of the papers reporting clusters of leukemia or other malignancy in the vicinity of nuclear facilities in Britain and their comments invited. Subject to considerations of space and CCC style, these comments will be published as submited.     

A mutation in codon 717 of the CHO-K1 elongation factor 2 gene prevents the first step in the biosynthesis of diphthamide

The histidine residue at position 715 of elongation factor 2 (EF-2) is posttranslationally modified in a series of enzymatic reactions to 2-[3-carboxyamido-3-(trimethylammonio)-propyl]histidine, which has been given the trivial name diphthamide. The diphthamide residue of EF-2 is the target site for ADP ribosylation by diphtheria toxin and Pseudomonas exotoxin A. ADP-ribosylated EF-2 does not function in protein synthesis. EF-2 that has not been posttranslationally modified at histidine 715 is resistant to ADP ribosylation by these toxins. In this report we show that a G-to-A transition in the first position of codon 717 of the EF-2 gene results in substitution of arginine for glycine and prevents addition of the side chain of diphthamide to histidine 715 of EF-2. EF-2 produced by the mutant gene is fully functional in protein synthesis.This work was supported by Public Health Service grant AI-09100 from the National Institute of Allergy and Infectious Diseases and by Biomedical Research Support Grant PHS07RR05429-27. Brian Foley is supported by a Cancer Biology Training Grant T32Ca-09286 from the National Cancer Institute.     

Early gamma interferon responses in lethal and nonlethal murine blood-stage malaria.

This study was undertaken to explore early differences in cytokine production during nonlethal and lethal blood-stage murine malaria infections. Cytokine analysis of spleens during these infections showed that the principal difference between two nonlethal and two lethal Plasmodium species was the production of gamma interferon 24 h after infection with nonlethal parasites. In contrast, no increases in interleukin-4 production were observed in the first 24 h and tumor necrosis factor alpha levels increased equally in both nonlethal and lethal infections. During the later phase of infection with nonlethal parasites, both gamma interferon and interleukin-4 levels increased markedly a few days before parasite clearance. Early increases in gamma interferon production in nonlethal infections of Plasmodium yoelii and Plasmodium chabaudi were dose related and increased significantly with the size of the inoculum. Studies with the nonlethal P. yoelii suggest that the early gamma interferon response is mediated by T cells and natural killer cells, as it was reduced in athymic mice and in mice depleted of their natural killer cells by treatment with specific antiserum. Infecting mice with increasing numbers of lethal P. yoelii and Plasmodium berghei parasites did not increase the amount of gamma interferon, interleukin-4, and tumor necrosis factor alpha produced in a dose-dependent fashion. We conclude that one consequence of the early production of gamma interferon and tumor necrosis factor-alpha, particularly after nonlethal P. yoelii infection, may be to adjust the balance of T-helper cell subset activation, and probably that of other immune responses, so as to enhance the mechanisms that are essential for elimination of the parasites. This suggests that a successful vaccine should contain antigens capable of inducing such responses.     

Visual function in Huntington's disease patients and presymptomatic gene carriers.

Disturbances of visual cognition, visuomotor performance, and visual memory have been described frequently in Huntington's disease (HD). Early stage visual abnormalities could contribute to these deficits. We evaluated visual processing in 20 control subjects who were non-gene carriers at risk for HD, nine presymptomatic gene-positive subjects, and eight subjects with a recent diagnosis of Huntington's disease. Visual perceptual tests of contrast sensitivity and motion discrimination were used to probe early stage visual processing. Extraocular movements were evaluated in a neurologic examination, and the Digit Symbol test was used to test visual motor performance. Contrast sensitivity did not differ among the three groups. Motion discrimination was impaired in HD subjects but not in the presymptomatic gene carriers when compared to gene noncarriers. Among gene carriers, impaired motion discrimination performance was associated with poorer Digit Symbol performance and extraocular abnormalities. These findings suggest that the early stages of HD are associated with disturbances of motion perception as well as disruptions of visual motor and ocular motor performance.     

Comparison of stress-only vs. stress/rest with technetium-99m methoxyisobutylisonitrile myocardial perfusion imaging

Unlike conventional thallium-201 myocardial imaging, technetium-99m methoxyisobutylisonitrile (MIBI) requires separate stress and rest injections. We prospectively studied 148 consecutive patients referred for myocardial perfusion studies to determine the diagnostic value of rest images once normal exercise or dipyridamole tomographic images had been obtained. In patients referred with no history of previous myocardial infarction in whom the diagnosis of coronary artery disease was suspected, 45 of 109 (41%) patients had normal stress tomographic images. Obtaining rest images did not alter the final interpretation in any of these cases. From this we infer that in patients with normal images after exercise or dipyridamole administration and no past history of myocardial infarction, ^99mTc-MIBI rest images are not required. This provides several advantages including increased speed of diagnosis, decreased patient radiation exposure, improved cost efficiency and decreased demand on tomographic camera time. Offprint requests to: A.Y. Fung