Global phase diagram for the quantum Hall effect: An experimental picture.
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Biomedical subjects
Publications and source records attributed to W Mason.
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OBJECTIVE: To compare the safety and efficacy of various intravenously administered immune globulin (IVGG) products in patients with Kawasaki disease. METHODS: We performed a retrospective matched-pair study of 45 pairs of patients, matched by age, gender, hospital, and illness day when IVGG therapy was initiated. All patients received aspirin, 80 to 100 mg/kg per day; one of each pair received Venoglobulin, 2 gm/kg (product A), and the other received Iveegam, 2 gm/kg (product B). Safety was assessed during and after IVGG infusion by recording rigors, pruritus, hypotension, urticaria, and nausea. Treatment efficacy was evaluated by posttreatment height and duration of fever, and subsequent echocardiographic changes. RESULTS: Untoward reactions during infusions occurred more often with product A (25%) than with product B (2%) (p < 0.025); most reactions were rigors (18% vs 2%) (p < 0.05). Therapy was completed in all patients. Height of fever and proportion of patients febrile each day after product A or B did not differ significantly. No differences were found in the frequency of coronary artery abnormalities 1 year after illness. CONCLUSIONS: No significant differences in efficacy appeared between the two IVGG products, but they differed significantly in non-life-threatening adverse reactions, especially infusion-related rigors. Other IVGG products should be evaluated in a similar fashion.
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The experiments compare intracellular changes in porcine eggs induced by electrical activation with those induced by sperm penetration. Adequate electrostimulation induces changes in both cortical granule exocytosis and protein synthesis similar to those induced by sperm during fertilization. However, ionic changes induced by electrostimulation differ markedly from those initiated at fertilization. Thus, dynamic video imaging using Fura-2 as a Ca2+ probe provides evidence that parthenogenetic activation induced by electrostimulation is initiated by a single sharp rise in the concentration of intracellular free calcium ([Ca2+]i) in the egg. The intracellular Ca2+ transient increase is triggered by an influx of extracellular Ca2+ immediately after electrostimulation. The amplitude of the intracellular Ca2+ transient increase is a function both of the extracellular Ca2+ concentration and of electric field parameters (field strength and pulse duration). Imaging demonstrates further that a single electrical pulse can only induce a single Ca2+ transient which usually lasts three to five minutes; no further Ca2+ transients are observed unless additional electrical stimuli are applied. By contrast, sperm-induced activation is characterised by a series of Ca2+ spikes which continue for at least 3 hours after sperm-egg fusion. The pattern of Ca2+ spiking after fertilization is not consistent during this period but changes both in frequency and amplitude. Overall, the results demonstrate that, although electrostimulation induces both cortical granule exocytosis and protein reprogramming in porcine eggs, it does not reproduce the pattern of [Ca2+]i changes induced by sperm entry at fertilization.
The core gene promoter of duck hepatitis B virus (DHBV) has been localized and an enhancer element has been found in a region of the DHBV genome immediately upstream of the core promoter. This enhancer was able to activate expression from both the core promoter and the S promoter of DHBV, as well as from the heterologous thymidine kinase and simian virus 40 early promoters, but not from the DHBV PreS promoter, which was active both in the absence and in the presence of the enhancer. The activity of the enhancer showed a preference for cell cultures of hepatic origin, suggesting a possible tissue preference in vivo.
Duck hepatitis B virus mutants containing frameshift or stop codon mutations in a portion of the viral pol gene separating the terminal protein and reverse transcriptase domains had a leaky phenotype and, depending on the location and type of mutation, synthesized up to 10% as much viral DNA as did the wild type. This region of the pol gene had previously been reported to be refractory to missense mutations; in fact, the leakiness of most of our mutants appeared attributable to translational suppression, which would also be expected to introduce amino acid changes. However, at least one mutant (pH1093 + 2), which was ca. 10% as active as the wild type, appeared to use a novel pathway to express the viral pol gene. Our analyses indicated that pH1093 + 2 synthesized the viral reverse transcriptase as a fusion protein with the amino-terminal portion of the pre-S envelope protein. Thus, in this case, the products of the terminal-protein and reverse transcriptase domains of the pol gene would function as separate protein species, though perhaps noncovalently joined in a dimeric structure during assembly of DNA replication complexes. Evidence was also obtained that was consistent with the idea that the wild-type pol gene may, at least in certain instances, be expressed as functional, subgenic polypeptides.
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Previous studies have demonstrated circulating immune complexes (CICs) in sera of 70% of Kawasaki syndrome (KS) patients but the pathogenic role of these complexes in the illness is unknown. Infusions of gamma-globulin (GG) have been shown recently to reduce the prevalence of coronary artery aneurysms in KS patients. One of the proposed mechanisms of action of GG therapy is through an effect on CICs. We analyzed paired sera for CICs from 29 patients with KS, 19 of whom were treated with aspirin and GG and 10 of whom received aspirin only. Assay systems used for CIC detection were Raji-mu enzyme immunoassay, C1q solid phase assay-enzyme immunoassay and F(ab')2-anti-C3-mu enzyme immunoassay. Overall 20 of 29 patients had CICs detected by at least two of three assays used. Of the 19 GG-treated patients 14 had CICs detected: 5 in both paired sera; 2 in pretherapy sera; and 7 posttherapy specimens. There was no correlation between duration of fever, presence of myocarditis or the development of coronary artery aneurysms and the presence of CICs in the serum of KS patients. Although CICs can be found frequently in the sera of KS patients there seems to be no association between the presence of CICs and the duration of fever or the development of coronary artery aneurysms.
cDNA prepared from the single-stranded circular RNA genome of hepatitis delta virus was cloned in lambda gt11 by using RNA from the liver of an infected woodchuck. From the sequence of overlapping clones, we assembled the full sequence of 1,679 nucleotides. The sequence indicated an exceptional ability for intramolecular base pairing, yielding a rod structure with at least 70% of the bases paired and a predicted free energy of -805 kcal (-3,368 kJ)/mol. Three of the lambda clones contained sequences that were not only expressed as fusion proteins with beta-galactosidase but were recognized by human hepatitis delta virus-specific antibody. These clones were sequenced so as to establish the reading frame of the delta antigen on the antigenomic strand. The fusion protein produced by one clone was purified by immunoaffinity chromatography and then was used to raise rabbit antibodies specific for the delta antigen.
Home sleep recordings were done on 358 randomly selected elderly volunteers (mean age 72.4). When men and women were combined, 62 (17%) had predominantly obstructive sleep apnea, 21 (6%) had predominantly central sleep apnea, and 3 (1%) had mixed sleep apnea. Although the prevalence of sleep apnea in women does increase after menopause, sleep apnea was still significantly more common in older men (31%) than in older women (19%). There were no significant differences in age among groups with different types of apnea. There was a significant correlation of age with increasing apnea index within the obstructive sleep apnea group. Elderly volunteers with central sleep apnea had more midsleep awakenings. Elderly volunteers with obstructive sleep apnea had longer apneas. Unlike previous studies, we found many similarities and only modest differences in the presentations of central and obstructive sleep apnea.
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We obtained two lines of evidence that monolayer cultures of primary woodchuck hepatocytes support replication of the genome of human hepatitis delta virus (HDV). (i) From a Northern (RNA blot) analysis of the HDV-related RNA in infected cultures, both genomic and antigenomic 1.7-kilobase RNA species were detected at 11 days after infection. The ratio of genomic RNA to antigenomic RNA was 2:1 to 10:1, comparable to that previously reported in studies of experimentally infected chimpanzees and woodchucks. (ii) Replication in culture was also demonstrated by in situ hybridization with a strand-specific probe. Such studies showed that only a small fraction of the cultured cells supported replication and that in such cells the relative and absolute levels of the HDV RNAs were comparable to those in liver cells infected in vivo. Furthermore, as with the in vivo studies, the HDV RNAs were predominantly localized to the nucleus. In summary, we demonstrated that cultured cells supported both the early events of HDV adsorption and penetration and the intermediate events of genome replication.
Coronary aneurysms were demonstrated echocardiographically in 34 of 186 patients who presented with Kawasaki syndrome between 1979 and 1983. The aneurysms were confirmed by selective coronary angiography in 27 patients and by postmortem examination in one. The 27 surviving patients with proven aneurysms were followed for 2 to 40 months (mean 15), during which they received low dose (5 to 10 mg/kg) aspirin daily. Progressive improvement and resolution of aneurysms were observed by serial echocardiography in 18 patients and confirmed by angiography in 14. Coronary aneurysms persisted, however, in nine other patients for 14 to 40 months (mean 25.7). The incidence of aneurysm resolution was higher in children less than 1 year of age at the onset of the illness than in patients older than 1 year (100% vs 50%; p less than .001). Aneurysms were more likely to resolve in girls than in boys (100% vs 42%; p less than .001). Fusiform aneurysms tended to resolve more frequently than saccular lesions (80% vs 18%; p less than .025). Aneurysms located distally in the coronary arteries appear to regress more rapidly than proximal ones. We conclude that an age of less than 1 year at the onset of Kawasaki syndrome, female sex, and fusiform aneurysm morphology are significant factors that favor resolution of coronary artery aneurysms. However, important questions remain with regard to the long-term fate and functional capabilities of these healed lesions.
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The hepatitis delta virus can be found in the serum and liver of some hepatitis B virus patients. We now report that the RNA genome of serum-derived delta virus is single-stranded and circular. Livers of infected chimpanzees or woodchucks contained as many as 300,000 copies of genomic strand RNA per average cell, and at least some of this RNA had a circular conformation. Also present in the livers were RNA species complementary to the virion RNA. The genomic RNA was 5-22 times more abundant than this antigenomic strand. Some of the antigenomic RNA was complexed with genomic RNA, as evidenced by the fact that at least 34% of the antigenomic RNA was resistant to digestion with either RNase A in 0.3 M NaCl or S1 nuclease. Some of the antigenomic RNA was in a circular conformation. These and other findings showed that the structure and replication of hepatitis delta virus are in many ways similar to those of the previously described plant viroids, virusoids, and satellite RNAs.