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Circulating bcr-abl-specific CD8+ T cells in chronic myeloid leukemia patients and healthy subjects.

BACKGROUND AND OBJECTIVES: The fusion oncoprotein bcr-abl that characterizes chronic myeloid leukemia (CML) is a leukemia-specific antigen, which may be immunogenic in vivo. KQSSKALQR and GFKQSSKAL, peptide sequences spanning the b3a2 bcr-abl junction, have affinity for HLA-A3 and HLA-B8, respectively, and we have shown the presence of KQSSKALQR on the surface of CML cells. We analyzed the existence of bcr-abl-specific T cells in vivo and correlated their presence to contemporary disease burden. DESIGN AND METHODS: We investigated circulating CD8+ T lymphocytes directed against the bcr-abl junction, using fluorochrome-labeled tetramers of HLA-A3 with KQSSKALQR and of HLA-B8 with GFKQSSKAL, and flow cytometry analysis. Using chromium-release assays and interferon-g ELISPOT assays, we also studied the functionality of these expanded T cells. RESULTS: Eight of 12 b3a2+ HLA-A3+ and/or HLA-B8+ CML patients studied serially on at least three occasions had bcr-abl junction-specific CD8+ T cells. Specific T cells were more likely to be found in patients with a low leukemic burden (p=0.03). Three of 18 HLA-A3+ and/or HLA-B8+ healthy donors had bcr-abl junction-specific T cells, though these were not detected in any of 13 subjects who were HLA-A3- and HLA-B8-. Bcr-abl-specific T cells were expandable in vitro in three of seven healthy donors and five of seven CML patients. INTERPRETATION AND CONCLUSIONS: Bcr-abl-specific T cells are detectable in CML patients, and might contribute to leukemic control. The occurrence of specific CD8+ T cells in some healthy donors might represent an immune response to occult BCR-ABL rearrangements.

Adult↗

Comparative clinical and physiological features of Maori, Pacific Islanders and Europeans with sleep related breathing disorders.

UNLABELLED: Recent studies have suggested that there is a familial association of sleep apnoea syndrome and that this is not entirely explained by inheritance of known risk factors. Maori (M) and Pacific Islanders (PI) have many of the body habitus features associated with sleep apnoea and therefore might be expected to exhibit more severe disease than Europeans (E). OBJECTIVE: To compare the clinical and physiological characteristics of the different ethnic groups and to determine if race was an independent predictor of severity of sleep apnoea. METHODOLOGY: A prospective evaluation of patients attending the Sleep Disordered Breathing Clinic which serves the whole of Auckland (population 1.1 million), New Zealand was conducted for the period July 1994 to August 1995. The evaluation included history including a 26 question questionnaire, Epworth sleepiness score, examination, and where indicated, full polysomnography. RESULTS: A total of 233 patients (154 E, 48 M and 33 PI), underwent full polysomnography. Forty-one (85%) of the M and 31 (94%) of PI had obstructive or mixed sleep apnoea compared with only 74 (49%) of the E (P < 0.0001; chi 2). There were few racial differences in the responses to the sleep questionnaire. M and PI were shown to have much greater neck and waist circumference and body mass indices. Severity parameters (apnoea-hypopnoea index, wake and minimum oxygen saturation, and apnoea duration) were greater for both M and PI compared with E (P < 0.001; Mann-Whitney U-test). Stepwise regression identified neck size, body mass index and age as independent predictors of severity. CONCLUSION: When other factors were controlled for, race was not an important independent predictor of severity of sleep apnoea.

Adult↗

An outbreak of Norwalk-like gastroenteritis associated with contaminated drinking water at a caravan park.

During the 1989 Christmas holiday period, a large outbreak of gastroenteritis occurred among persons staying at a caravan park in southern New South Wales. Review of local hospital records found that 77 per cent of patients presenting with infective diarrhoea between 29 December and 3 January had stayed at the caravan park. In a retrospective cohort study we compared rates of illness among caravan park patrons exposed to different water sources. Stools were tested for pathogens and convalescent sera for viral antibodies. Rain and reticulated river water sampled from the caravan park were tested for bacteria and viruses. Of 351 persons interviewed at the caravan park, 305 (87 per cent) reported an illness characterised by diarrhoea, vomiting and abdominal pain. Of 196 persons who used reticulated river water for drinking or ablutions, 175 (89 per cent) became ill compared with 47 of 72 persons (65 per cent) who did not use this water (relative risk 1.4, 95 per cent confidence interval 1.2 to 1.6). The outbreak was probably caused by a 27-28 nm small round structured virus found in the stool from one ill person. High levels of faecal coliforms in the reticulated river water and enterovirus in sediment samples suggest that the outbreak was caused by sewage contaminating the reticulated river water through a break in the pipe directly over the underground water tanks. To prevent such outbreaks, poor water and sewerage system layouts should be avoided and nonpotable water should be clearly labelled. Where feasible, all camping-ground water should stem from town supplies.

Abdominal Pain↗

Leptographium wingfieldii introduced into North America and found associated with exotic Tomicus piniperda and native bark beetles.

Leptographium wingfieldii is a well-known fungal associate of the pine shoot beetle, Tomicus piniperda, in Europe. This fungus is pathogenic to pines and is an important cause of blue-stain in the sapwood of infested trees. Tomicus piniperda was first found in a Christmas tree plantation in Ohio, USA, 1992, but isolation of the fungi associated with these intercepted insects was not attempted. Fungal strains resembling L. wingfieldii were recently isolated from pines attacked by T. piniperda, Dendroctonus valens and Ips pini in the northeastern United States. These strains were morphologically similar to the ex-type and other reference strains of L. wingfieldii. Strains were also compared based on sequences of the partial ITS ribosomal DNA operon, beta-tubulin and elongation factor 1-alpha (EF-1alpha) genes. Based on these DNA sequence comparisons, reference strains of European L. wingfieldii were conspecific with North American strains from pines attacked by T. piniperda, D. valens and I. pini. A single strain from Canada, collected in 1993 near the Ontario border with the USA, shortly after the discovery of T. piniperda in that area and tentatively identified as L. wingfieldii, was also included in this study. Its identification was confirmed, suggesting that L. wingfieldii has been present in this region and probably over the whole range of the insect's distribution for at least a decade. This represents the first record of L. wingfieldii associated with the introduced and damaging pine shoot beetle T. piniperda in North America. It shows that the fungus is well established and can become associated with other native bark beetles that attack stressed and/or dying trees. The occurrence and spread of this highly pathogenic fungus associated with North American bark beetles should be monitored.

Animals↗