Coding assignments of Drosophila X virus genome segments: in vitro translation of native and denatured virion dsRNA

Both dsRNA genome segments of Drosophila X virus (DXV) were denatured and translated in vitro using nuclease-treated rabbit reticulocyte lysates. The synthesis of all four primary gene products was detected by polyacrylamide gel electrophoresis and autoradiography. Genome segment A (mol wt 2.3 X 10(6)) encoded polypeptides with molecular weights of 67,000 (67K), 34K, and 27K, whereas segment B (mol wt 22 X 10(6)) encoded the 110K polypeptide. The proteolytic processing of 67K which generates a 49K polypeptide in infected cells was also observed in vitro. Pulse-chase experiments indicated that synthesis of the three polypeptides encoded by genome segment A initiated independently and simultaneously, suggesting that segment A is polycistronic. Native (undenatured) DXV dsRNA could also be translated with high fidelity (vitro). The messenger activity of native dsRNA was abolished by S1 nuclease treatment but completely restored on subsequent denaturation. In vitro "pulse-chase" experiments using native dsRNA as messenger, indicated that the order of translation of polypeptides on genome segment A was 5'-67K-27K-34K-3'.     

Circulating immune complexes during immunotherapy.

Chronic immunization may lead to the production of circulating immune complexes (CICs). This study was undertaken to determine the presence of circulating IgG immune complexes in 95 subjects with allergic rhinitis/asthma receiving immunotherapy, 46 individuals with similar diagnosis but not on immunotherapy, and 64 healthy controls. Modified Raji cell and murine leukemia cell (L-1210) assays, selected for a high density of Fc receptors and devoid of Epstein-Barr virus membrane antigen, were used. Other immunological parameters such as immunologlobulins G, A, M, E, and rheumatoid factor activity were also studied. The CIC concentrations in the treated group did not differ significantly from the untreated group, although both groups did have a significantly higher concentration than the healthy controls. The presence of CICs has no relationship with age or sex of patients, dosage of allergen administered, number and nature of allergens received, period between the time of last injection and the blood sampling, and the duration of immunotherapy. Serum IgG, IgA, IgM, and rheumatoid factor activity did not differ between the treated and untreated groups. IgE was significantly higher in the treated group when compared with the untreated, and IgE levels in treated patients with elevated CICs were significantly increased compared with CIC-negative treated patients. These data suggest that CICs are present in serum of atopic diseases such as allergic rhinitis/asthma. Significantly, an association of elevation of CICs with immunotherapy could not be demonstrated.     

Familial renal carcinoma

Renal carcinoma developed in two or more members of nine families. Multiple generations were affected in five kindreds, and siblings in four. The median age at cancer diagnosis was a decade earlier than usual, and individual patients had bilateral or multifocal lesions; these are features of hereditary forms of diverse cancers. No patient had von Hippel-Lindau disease or other predisposing genetic syndromes. Karyotypes of the peripheral blood of nine persons showed no instance of a 3;8 chromosome translocation as recently reported in association with renal carcinoma in ten members of one family. The findings show that familial renal cancer is more common than previously reported in the literature.     

Accessibility, clinical effectiveness, and practice costs of providing a telephone option for routine asthma reviews: phase IV controlled implementation study.

BACKGROUND: Attendance for routine asthma reviews is poor. A recent randomised controlled trial found that telephone consultations can cost-effectively and safely enhance asthma review rates; however, concerns have been expressed about the generalisability and implementation of the trial's findings. AIM: To evaluate the effectiveness of a telephone option as part of a routine structured asthma review service. DESIGN OF STUDY: Phase IV controlled before-and-after implementation study. SETTING: A large UK general practice. METHOD: Using existing administrative groups, all patients with active asthma (n = 1809) received one of three asthma review services: structured recall with a telephone-option for reviews versus structured recall with face-to-face-only reviews, or usual-care (to assess secular trends). Main outcome measures were: proportion of patients with active asthma reviewed within the previous 15 months (Quality and Outcomes Framework target), mode of review, enablement, morbidity, and costs to the practice. RESULTS: A routine asthma review was provided for 397/598 (66.4%) patients in the telephone-option group compared with 352/654 (53.8%) in the face-to-face-only review group: risk difference 12.6% (95% confidence interval [CI] = 7.2 to 17.9, P<0.001). The usual-care group achieved a review rate of 282/557 (50.6%). Morbidity was equivalent in the three groups; however, enablement (P = 0.03) and confidence (P = 0.007) in asthma management were greater in the telephone-option versus face-to-face-only group. The cost per review achieved by providing the telephone-option service was lower than the face-to-face-only service (10.03 pounds versus 12.74 pounds, mean difference 2.71 pounds; 95% CI = 1.92 to 3.50, P<0.001); usual-care costs were 11.85 pounds per review achieved. CONCLUSION: Routinely offering telephone reviews cost-effectively increased asthma review rates, enhancing patient enablement and confidence with management, with no detriment to asthma morbidity. Practices should consider a telephone option for their asthma review service.     

Identification of epididymis-specific antigens using neonatal tolerization

PROBLEM: Conventional immunization using whole sperm containing multiple antigens as the immunogen followed by hybridoma technology usually gives antibodies to antigens invariably of testicular origin, probably because of the strong immunogenic nature of these antigens. Therefore, an alternate approach of neonatal tolerization or subtractive immunization has been utilized to raise antibodies specific to epididymis by suppressing immune response to testicular antigens. METHOD OF STUDY: Neonatal mice were tolerized with testicular sperm proteins on days 0 and 5. These animals were then immunized with epididymal sperm proteins on day 21, followed by two boosters at biweekly intervals. Sera from these mice were used to localize epididymis-specific antigens. RESULTS: Sera from mice that were tolerized to testicular sperm proteins and later immunized with epididymal sperm proteins reacted only with epididymal proteins. CONCLUSION: The results of this study demonstrate that neonatal tolerization with testicular sperm proteins, followed by immunization with epididymal sperm proteins, enhances the production of antibodies to proteins exclusively of epididymal origin.     

In vivo and in vitro correlates of food allergy.

Sera of 86 patients clinically sensitive to foods were tested by passive sensitization of human and/or monkey lung (127 tests) and the radioallergosorbent test (RAST) (72 tests), using whole-food antigens; the results were compared with skin (prick) testing. Results of the prick test correlated with history in 76% of cases; lung sensitization correlated with history in 37% and with prick test in 57%; and RAST correlated with history in 54% and prick test in 72%. It is concluded that a very large percentage of adverse reactions to foods are IgE-mediated. The prick test is of use in diagnosis, particularly when combined with RAST; the lung sensitization test is technically impractical and not a reliable indicator. The best diagnostic method is careful history with food challenge and withdrawal and rechallenge; the latter is safe except in patients with a history of violent reaction.     

Relations between various fiber groups of vagal and splanchnic nerves and gastric motility in rats

Gastric motility changes evoked in rats by electrical stimulation of centrally transected vagal and splanchnic B and C fibers were investigated. Gastric motility was slightly facilitated by repetitive stimulation of vagal B fibers and was greatly facilitated by similar stimulation of the C fibers. In addition, vagal C fiber stimulation evoked a transient, initial inhibition of motility. Splanchnic C fiber stimulation inhibited gastric motility, but the B fiber contribution to inhibition was much greater.     

Karyotypic evolution in Ph-positive chronic myeloid leukemia in relation to management and disease progression

In a prospective study of 32 patients with chronic myeloid leukemia the frequency of chromosome abnormalities in addition to the Philadelphia chromosome (Ph) increased when the disease progressed. Before metamorphosis, 10 patients (31%) had developed additional abnormalities. Such abnormalities were present in three of them at the time of diagnosis; in the other seven, they were detected late in the chronic phase. New clonal abnormalities heralded or accompanied a more malignant phase of the disorder, usually a blastic leukemia. During metamorphosis, 78% of the patients had additional abnormalities, which in 68% of these cases comprised at least one of +8, +22q- or i(17q). Clones with additional abnormalities disappeared in eight cases, either spontaneously or in association with cytostatic therapy during the chronic or blastic phase. Involvement of chromosome #8, usually in the form of a trisomy, was found in 7 of 12 patients treated with busulfan, but was not found in any of the 10 hydroxyurea-treated patients, of whom 8 were splenectomized early during the chronic phase. Cells from the spleen, obtained by fine needle aspiration or splenectomy were cytogenetically examined in 18 cases during the chronic phase, but abnormalities in addition to the Ph were noted in only one patient, who was examined in the late chronic phase. The same abnormalities were present in bone marrow cells of this patient.     

Constitutional C-band pattern in patients with adenomatosis of the colon and rectum

The pattern of polymorphism in the C-band-positive constitutive heterochromatin of chromosomes #1, #9, and #16 was studied in fibroblasts from 23 unrelated patients with adenomatosis of the colon and rectum and in peripheral lymphocytes from 78 control persons. The parameters of the heterochromatic regions analyzed were relative size, symmetry-asymmetry within homologous chromosome pairs, and frequency of inversions. The polyposis coli patients had a significantly higher frequency (p less than 0.05) of partial and total heterochromatin inversion on chromosome #9 than the control group (37.0% compared with 21.8%). In the other parameters studied, no significant differences were found between patients and controls.