Alternative magnetic field exposure metrics: relationship to TWA, appliance use, and demographic characteristics of children in a leukemia survival study.

The ongoing Childhood Leukemia Survival Study is examining the possible association between magnetic field exposure and survival of children with newly diagnosed acute lymphocytic leukemia (ALL). We report the results of the first year 24 h personal magnetic field monitoring for 356 US and Canadian children by time weighted average TWA and alternative exposure metrics. The mean TWA of 0.12 microT was similar to earlier personal exposure studies involving children. A high correlation was found between 24 h TWA and alternative metrics: 12 h day TWA, 12 night TWA, geometric mean, 95th percentile value, percentage time over 0.2 and 0.3 microT, and an estimate of field stability (Constant Field Metric). Two measures of field intermittency, rate of change metric (RCM) and standardized rate of change metric (RCMS), were not highly correlated with TWA. The strongest predictor of TWA was location of residence, with highest TWAs associated with urban areas. Residence in an apartment, lower paternal educational level, and residential mobility were also associated with higher TWAs. There were no significant differences in the appliance use patterns of children with higher TWA values. Children with the highest field intermittency (high RCM) were more likely to sit within 3 feet of a video game attached to the TV. Our results suggest that 24 h TWA is a representative metric for certain patterns of exposure, but is not highly correlated with two metrics that estimate field intermittency.

The New Zealand cataract and refractive surgery survey 1997/1998.

BACKGROUND: This study documents the current practice for cataract and refractive surgery in New Zealand. METHOD: A postal questionnaire was distributed in late 1997 to all consultant members of the Ophthalmological Society of New Zealand that were resident in the country at that time. Most questions were identical to the 1997 survey of the American Society of Cataract and Refraction Surgeons (ASCRS) to enable a comparison. RESULTS: There were 98 returns from 101 surveys distributed. Of the returns, 72 performed cataract surgery, 23 performed PRK and 11 performed LASIK. ASCRS members did more refractive surgery than did New Zealanders: 28 versus 1% of 1-5 RK per month, 7 versus 1% of 1-2 clear lens extractions per month and 85 versus 51% had access to an excimer laser. For cataract surgery, ASCRS members used more topical anaesthesia (30 vs 5.5%), used no sutures more often (73 vs 51%), used more preoperative antibiotics (76 vs 26%) and used fewer injections of antibiotic/steroids (38 vs 61%). Otherwise the two groups were broadly similar.

Cell surface organization of the erythropoietin receptor complex differs depending on its mode of activation.

During erythroid development erythropoietin (EPO) binds specifically to a receptor primarily present on committed erythroid progenitors, stimulating mitogenic, survival, and differentiative growth response pathways. Other modes of erythropoietin receptor (EPO-R) activation, such as interaction with the env gene Friend virus envelope glycoprotein (F-gp55) of spleen focus-forming virus or specific mutations in the extracellular domain of the EPO-R, give rise to pathological consequences, in vivo and EPO-independent proliferation and differentiation of cultured cells. Activating extracellular receptor mutations result in covalently linked receptor homodimers. These observations and others have led to the proposal that EPO activates the EPO-R by inducing dimer formation on the cell surface. It has been assumed that F-gp55 also induces dimer formation of the EPO-R; however, clear evidence of this is lacking. In addition, EPO and F-gp55 stimulation of the EPO-R elicit different biological responses. To probe whether the cell surface EPO-R is structurally different with these activators, we contrasted the cell surface EPO-R complex formed following receptor activation by EPO, F-gp55, and mutations in the extracellular domain of the receptor. Our results indicate that cell surface forms of activated EPO-R differ, as judged by their differential association with F-gp55 and pattern of associated cell surface proteins. Interestingly, we find that the env gene of an anemic strain of Friend virus, Rauscher virus envelope glycoprotein, does not interact with the EPO-R at the cell surface. Thus, the mode of Rauscher virus envelope glycoprotein-induced erythroblastosis may be distinct from F-gp55-induced erythroblastosis and possibly not involve the EPO-R.

Growth signal transduction by the human interleukin-2 receptor requires cytoplasmic tyrosines of the beta chain and non-tyrosine residues of the gamma c chain.

To evaluate the possible role for receptor-based tyrosine phosphorylation in growth signaling induced by interleukin-2 (IL-2), a series of substitution tyrosine mutants of the IL-2 receptor beta and gamma c chains was prepared and analyzed. Concurrent mutation of all six of the cytoplasmic tyrosines present in the beta chain markedly inhibited IL-2-induced growth signaling in both pro-B and T cell lines. Growth signaling in a pro-B cell line was substantially reconstituted when either of the two distal tyrosines (Tyr-392, Tyr-510) was selectively restored in the tyrosine-negative beta mutant, whereas reconstitution of the proximal tyrosines (Tyr-338, Tyr-355, Tyr-358, Tyr-361) did not restore this signaling function. Furthermore, at least one of the two cytoplasmic tyrosines that is required for beta chain function was found to serve as a phosphate acceptor site upon induction with IL-2. Studies employing a chimeric receptor system revealed that tyrosine residues of the beta chain likewise were important for growth signaling in T cells. In contrast, although the gamma c subunits is a target for tyrosine phosphorylation in vivo, concurrent substitution of all four cytoplasmic tyrosines of this chain produced no significant effect on growth signaling by chimeric IL-2 receptors. However, deletion of either the Box 1, Box 2, or intervening (V-Box) regions of gamma c abrogated receptor function. Therefore, tyrosine residues of beta but not of gamma c appear to play a pivotal role in regulating growth signal transduction through the IL-2 receptor, either by influencing cytoplasmic domain folding or by serving as sites for phosphorylation and subsequent association with signaling intermediates. These findings thus highlight a fundamental difference in the structural requirements for IL-2R beta and gamma c in receptor-mediated signal transduction.

Endoprosthetic insertion for malignant obstructive jaundice: a retrospective review.

We reviewed 13 cases of biliary endoprosthetic insertion for malignant obstructive jaundice from August 1983 to May 1987, and recorded (1) location and etiology of the obstruction, (2) length of time the endoprosthesis remained functional, and (3) complications related to the endoprosthesis, its insertion, or its long-term function. Of the 13 patients, 3 had pancreatic carcinoma, 3 had cholangiocarcinoma, and 3 had metastatic disease to the porta hepatis. The underlying malignancy was not histologically proved in four patients despite evidence of neoplasm by percutaneous cholangiography and computerized tomography. These four patients were not considered good surgical risks and were referred for percutaneous therapy. The longest endoprosthetic patency was 3.5 years. Three patients experienced obstruction of the endoprosthesis at 3, 4, and 9 months after insertion, respectively. Two of the endoprostheses were subsequently removed endoscopically, while the third was extracted through a new percutaneous tract with use of a balloon angioplasty catheter. Complications related to endoprosthetic insertion included bilous hydro pneumothorax (1 patient), subcutaneous and subcapsular liver abscess (1 patient), postinsertion cholangitis (4 patients), and reflex ileus (1 patient).

Predilection of a nasopharyngeal carcinoma-derived isolate of Epstein-Barr virus for infection of specific subsets of B lymphocytes.

It is important to know whether there are variants of Epstein-Barr virus (EBV) with biological properties that are different from the prototype viruses that have been studied in detail, such as P3HR-1 and B95-8. We have studied an EBV isolate derived from a nasopharyngeal carcinoma (NPC) tumor, designated NPC-EBV. We have examined the target B lymphocytes infected and growth-transformed with NPC-EBV as compared with two common EBV isolates, B95-8 and AG876 EBV, for stage of maturation using antibodies to several immunoglobulin chains. Typing of the NPC-EBV transformed lymphoblastoid cell lines revealed the predilection of the NPC-EBV isolate to infect immature B lymphocytes. This was not the case for the B95-8 and AG876 isolates. The reason for the predilection of NPC-EBV for immature B lymphocytes remains to be explored further. However, these results may be important in understanding the pathophysiology of EBV-associated diseases.

The transforming prototype of Epstein-Barr virus (B95-8) is also a lytic virus.

The B95-8 isolate of the Epstein-Barr virus (EBV) has been described as a non-lytic transforming virus. We have performed experiments in order to determine if the B95-8 EBV is capable of super-infecting and replicating in EBV-genome-positive non-producer lymphoblastoid cells. Using concentrates of B95-8 EBV, prepared from 6 different B95-8 cell lines treated with 12-O-tetradecanoylphorbol-13-acetate (TPA), we demonstrated that virus concentrates could transform human or cotton-top tamarin B-lymphocytes and also lytically replicate in Raji cells, inducing EBV antigens and infectious virus. While the virus obtained from B95-8 super-infected Raji cells was able to transform cord-blood lymphocytes (CBLs) and super-infect Raji cells, transformation was abortive, with cell cultures only growing for up to 6 weeks. Transformation titers of the B95-8 virus concentrates ranged from 10(5) to greater than 10(8) transforming units/ml; early antigen (EA) induction ranged from 1% to 50% after superinfection of Raji cells, depending on the virus stock used, as determined by immunofluorescence. Southern blot analysis was carried out on the DNA prepared from B95-8 cells and virion DNA. The results were consistent with the published EcoRI restriction pattern for B95-8 EBV. The issue of whether the B95-8 cells produce virions with a dual biological phenotype or, rather, 2 biologically distinct viruses, is addressed.

Retinopathy of prematurity: review of a five-year period, examination techniques and recommendations for screening.

The reported resurgence of retinopathy of prematurity prompted analysis of the prevalence of retinopathy among premature infants born at Christchurch Women's Hospital over a five-year period. Of the 129 surviving very-low-birthweight infants, 65 (50.4%) underwent ocular screening during the review period. Retinopathy was detected in 17.1% (22/129) of surviving infants, or 34% (22/65) of selected infants referred by paediatricians for ocular screening. Five infants had severe or blinding retinopathy and these premature infants were of significantly lower birthweight and born after shorter gestation periods than those found to have no retinopathy. Examination techniques for eyes of premature infants are discussed, and recommendations for screening for retinopathy of prematurity made.

Modulation of cellular immunity in medical students.

This study assessed the psychosocial modulation of cellular immunity in 34 medical-student volunteers. The first blood sample was obtained 1 month before examinations, and the second on the day of examinations. There were significant declines in the percentage of helper/inducer T-lymphocytes, in the helper/inducer-suppressor/cytotoxic-cell ratio, and in natural killer-cell activity in the blood samples obtained on the day of examinations. Half of the subjects were randomly assigned to a relaxation group which met between sample points; the frequency of relaxation practice was a significant predictor of the percentages of helper/inducer cells in the examination sample. Three biochemical nutritional assays (albumin, transferrin, and total iron-binding protein) were within normal limits on both samples. Data from the Brief Symptom Inventory showed significantly increased global self-rated distress associated with examinations in the no-intervention group, compared to nonsignificant change in the relaxation group. Clinical and theoretical implications are discussed.

Stress-related impairments in cellular immunity.

The percentages of total T-lymphocytes (OKT-3+), helper T-cells (OKT-4+), and suppressor T-cells (OKT-8+) were significantly lower in blood samples obtained from 40 medical students during examinations, compared to baseline values obtained 6 weeks earlier. In addition, the response of T-lymphocytes to stimulation by phytohemagglutinin and concanavilin A was also significantly lower during examinations, compared to baseline. Self-report data documented significantly greater distress associated with examinations. The data have implications for immunosuppressive disorders and stress-related illnesses.

Changes in Epstein-Barr virus antibody titers associated with aging.

Antibody titers to the Epstein-Barr virus (EBV), early antigen (EA) IgG, and virus capsid antigen (VCA) IgG and IgA, were measured in 44 geriatric subjects to determine if the depression in cellular immunity known to be associated with aging affects the expression of latent EBV. Similar assays were performed on plasma obtained from a young adult (medical student) population as a control group. We found that 89% of the geriatric samples were positive for EA IgG, and 83% of the plasma obtained from medical students were positive for EA IgG. One hundred percent of the geriatric subjects were positive for VCA IgG, and 87% of the medical students were positive for VCA IgG. Seven percent of the medical student blood samples were positive for VCA IgA; in contrast, 36% of the blood samples obtained from the geriatrics subjects were positive. Significant differences were also found in the geometric mean titers (GMT) of antibodies to EBV antigens; the GMT to EBV EA and VCA were significantly higher in the geriatric group. The data suggest that there may be some loss of control over latent EBV by the cellular immune response in geriatric individuals.

Effects of stress on methyltransferase synthesis: an important DNA repair enzyme.

The enhancement of tumor development following acute stress has been demonstrated in some animal studies. This study was designed to explore mechanisms that would account in part for the relationship between stress and tumor development at the level of DNA repair, using a rat model. Forty-four rats were given the carcinogen dimethylnitrosamine in their drinking water, and half were randomly assigned to a rotational stress condition. The levels of methyltransferase, a DNA repair enzyme induced in response to carcinogen damage, were significantly lower in spleens from the stressed animals. These data suggest that stress may impair DNA repair.