Detection of HCV core antigen in HCV RNA positive, anti-HCV negative blood donations from Polish blood donors.
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Biomedical subjects
Publications and source records attributed to J E Peterson.
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This report documents the removal of a large mobile serpiginous right atrial thrombus using percutaneous intravascular techniques with fluoroscopic and transesophageal echocardiographic guidance. Technical aspects and potential complications are discussed.
A highly specific, human IgG mAb, F223, which reacts with both HIV-1-infected cells and uninfected lymphoid cells, has been derived. F223 reacts with gp120 but fails to neutralize viral infection. The antibody does enhance HIV-1 infection in a complement-dependent manner. The autoantigen recognized by F223 is expressed on a small percentage of T cells and NK cells and the majority of B cells. Immunoprecipitation demonstrates F223 reactivity with an as of yet unidentified 159-kDa protein in uninfected lymphoid cells. This reactivity with uninfected cells is inhibited by free gp120 demonstrating the cross-reactive nature of this antibody. The F223 light chain demonstrates strong homology to VLlambda2 family genes whereas the heavy chain is most homologous (84%) to the germline gene VH3-H.11. In vivo usage of VH3 family genes by F223 and an anti-HIV-1 (gp41) human mAb, 3D6, with related autoreactivity, suggests that VH3 sequences may be important components of potentially pathogenic human anti-HIV-1 envelope autoantibodies. F223 was isolated from an HIV-1 infected individual with lymphoma and in vitro F223 significantly enhances EBV transformation of normal B cells and increases immunoglobulin production without affecting B cell proliferation. Characterization of this antibody response may provide important insights and mechanistic information on HIV pathogenesis.
BACKGROUND: The search for the cause of chronic hepatitis among individuals with non-A to G hepatitis has led to the discovery of a post-transfusion hepatitis-related DNA virus, designated TT virus (TTV), which, based on viral sequences, belongs to a new virus family. The principal modes of infection with TTV are poorly understood, and its role in human immunodeficiency virus type 1 (HIV-1) infection is unclear. OBJECTIVE: To determine if injection drug use (IDU) and high-risk heterosexual activity (HRHA), principal modes of acquiring HIV-1 infection, place individuals at greater risk of acquiring TTV. METHODS: The authors analyzed DNA, extracted from sera or filter paper-blotted whole blood, obtained during August 1997 and June 1998 from 324 Vietnamese (148 male; 176 female), for TTV sequences by hot-start, heminested polymerase chain reaction. RESULTS: Prevalence of TTV viremia was similar among individuals engaging in IDU or HRHA (23.4% vs. 20.2%; P > 0.5), with no age- or gender-specific differences. No association was found between TTV viremia and co-infection with HIV-1 or hepatitis C virus (HCV). Phylogenetic analysis of 30 TTV sequences revealed two distinct genotypes and four subtypes that did not segregate according to gender, HIV-1 and HCV risk behaviors, or geographic residence. CONCLUSIONS: Among HIV-1- or HCV-infected Vietnamese, who presumably acquired their infection by either the parenteral or nonparenteral route, the data indicate no clear association between acquisition of TTV infection and risk behavior for HIV-1 or HCV infection, suggesting that the usual route of TTV transmission in Vietnam is other than parenteral or sexual.
Immunoglobulin G reactive with primary isolate virions was detected in 36% of serum samples from individuals infected with human immunodeficiency virus type 1. Of these individuals, serum samples from only 7% captured significant quantities of virus. Virion-specific antibody correlated with CD4 counts and, of more significance, primary isolate neutralization. Further dissection of this response should lead to the identification of antibodies and antigenic epitopes for vaccine purposes.
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PURPOSE: A T1-weighted multishot inversion-recovery (IR) echo-planar MR imaging (EPI) sequence was developed to improve intracranial tissue differentiation; its diagnostic utility was compared with that of conventional axial T1-weighted spin-echo and axial T2-weighted turbo spin-echo sequences. METHODS: Eighteen patients with known or suspected primary or metastatic brain neoplasia were imaged in a 1.5-T unit with IR-EPI sequences. Three observers measured gray/white matter contrast-to-noise ratios and subjectively compared IR-EPI sequences with T1-weighted spin-echo and T2-weighted turbo spin-echo sequences for gray/white matter discrimination, visibility of intracranial and vascular structures, overall lesion conspicuity, size of lesion(s), and presence and severity of artifacts. RESULTS: Twenty-four lesions (including neoplasia, infarction, treatment-associated encephalomalacia, nonneoplastic white matter signal abnormalities, and basilar artery dolichoectasia) were detected in 12 patients. Basilar artery dolichoectasia was not included in subsequent statistical analysis. Pulsatile flow artifacts were markedly reduced on IR-EPI sequences relative to those on T1-weighted spin-echo sequences. Gray/white matter contrast was greater on IR-EPI images than on T1-weighted spin-echo images. Periaqueductal gray matter, basal ganglia, optic tracts, cranial nerve V, and claustrum were seen better or as well on IR-EPI images as compared with T1-weighted spin-echo images. IR-EPI was more sensitive to magnetic sensitivity effects, with resultant decreased visibility of cranial nerves VII and VIII and the orbital portion of the optic nerves. For noncontrast sequences, lesion conspicuity was better on IR-EPI images than on T1-weighted spin-echo images in 16 (70%) of 23 lesions and was equal on the two sequences in seven (30%) of 23 lesions. Lesion size, including surrounding edema, was greater on IR-EPI images than on T2-weighted turbo spin-echo images in two (9%) of 23 cases and equal in 21 (91%) of 23 cases. Hyperintense foci of methemoglobin were more conspicuous on T1-weighted spin-echo images. CONCLUSION: Multishot IR-EPI is superior to conventional T1-weighted spin-echo imaging for parenchymal tissue contrast and lesion conspicuity, and is equal to T2-weighted turbo spin-echo imaging in sensitivity to pathologic entities.
GB virus C/hepatitis G virus (GBV-C/HGV) is a positive-sense, single-stranded RNA virus belonging to the family Flaviviridae and is distantly related to hepatitis C virus (HCV). GBV-C/HGV can be transmitted by the parenteral and the sexual route. Among individuals infected with human immunodeficiency virus type 1 (HIV-1) by the sexual route, we and others have demonstrated a high prevalence of GBV-C/HGV infection. Recently, Woolley and colleagues reported that AIDS patients co-infected with GBV-C/HGV had a significantly lower mean CD4 cell count than AIDS patients without GBV-C/HGV infection, suggesting that GBV-C/HGV antibody may be lost with progression to AIDS. To our knowledge no data are available on the loss of antibody against GBV-C/HGV in AIDS patients. We now report on an HIV-infected patient who exhibited gradual loss of IgG antibodies against GBV-C/HGV, as well as HCV, with progression of HIV disease.
The insulin-like growth factor type I (IGF-I) receptor can become tyrosine phosphorylated and enzymatically activated either in response to ligand or because of the activity of the Src tyrosine kinase (Peterson, J. E., Jelinek, T., Kaleko, M., Siddle, K., and Weber, M. J. (1994) J. Biol. Chem. 269, 27315-27321). The goal of the present study was to analyze the mechanistic basis and functional significance of the Src-induced phosphorylation and activation of the IGF-I receptor. 1) We mapped the sites of IGF-I receptor autophosphorylation to peptides representing three different receptor domains: tyrosines 943 and 950 in the juxtamembrane region; tyrosines 1131, 1135, and 1136 within the kinase domain; and tyrosine 1316 in the carboxyl-terminal domain. The juxtamembrane and kinase-domain peptides were phosphorylated both in vivo and in vitro. The carboxyl-terminal site, although phosphorylated in vitro and in src-transformed cells, was not a major site of ligand-induced phosphorylation in vivo. 2) We determined that the sites of Src-induced phosphorylation of the IGF-I receptor are the same as the ligand-induced autophosphorylation sites and that the Src kinase can catalyze these phosphorylations directly. 3) We showed that cells cultured from mice in which the IGF-I receptor has been knocked out by homologous recombination are defective for morphological transformation by src. Thus, the Src kinase can substitute for the receptor kinase in phosphorylating and activating the IGF-I receptor, and this receptor phosphorylation and activation are essential for transformation by src.
Class II malocclusion is a commonly observed problem, occurring in about one third of the United States population. The numerous treatment approaches that have been advocated to treat this malocclusion presumably produce differing treatment effects within the skeletal, dentoalveolar, and soft tissue components of the face. In the first section of this article, the three-dimensional components of Class II malocclusion are described, with transverse maxillary discrepancy, mandibular skeletal retrusion, and increased lower anterior facial height observed as common findings in a mixed dentition sample of Class II subjects. Second, the literature concerning two seemingly diverse treatment methods (extraoral traction and functional jaw orthopedics) is reviewed in detail. Last, cephalometric data are presented from a retrospective clinical study and is used to evaluate the treatment effects produced by cervical traction and the FR-2 appliance of Fränkel in comparison with an untreated sample of mixed dentition Class II patients. The results of this study indicated that although both skeletal and dentoalveolar components of Class II, Division 1 malocclusion were altered in the Class I direction by either a facebow or a Fränkel appliance, these two appliance systems accomplished the correction in dramatically differing ways. Cervical traction affected the skeletal and dentoalveolar components of the maxilla and mandible, whereas the FR-2 appliance had less of an effect on maxillary and dentoalveolar components and a greater effect on mandibular length. Thus, these two treatment modalities produce decidedly different treatment effects in patients with Class II malocclusions.
Mammography was done with a conventional molybdenum anode/filter combination and either a molybdenum/rhodium (Mo/Rh) or rhodium/rhodium (Rh/Rh) combination to compare the contrast characteristics and penetrating ability of the different techniques. Each pair was rated as being equal, one slightly better than the other, or one much better than the other. The "preferred" image was also selected. The entrance surface exposure and the mean glandular dose were determined for each exposure. Mo/Mo was compared with Mo/Rh in 26 patients and to Rh/Rh in 23. Mo/Mo was judged to produce better or equal contrast and penetration in all cases except one using the Mo/Rh combination. Mo/Rh was the preferred image only once and Rh/Rh not at all. In comparison to the conventional Mo/Mo technique, the average dose was reduced by approximately 25% with Mo/Rh and by 50% with Rh/Rh.
Using a panel of src mutants partially defective for malignant transformation, our laboratory has previously identified the insulin-like growth factor (IGF-I) receptor as a protein whose tyrosine phosphorylation correlates with transformation by src in embryonic chick cells (Kozma et al., 1990; Kozma and Weber, 1990). It has not been clear, however, whether src-induced phosphorylation altered the enzymatic or signaling properties of the IGF-I receptor and thus whether the IGF-I receptor could be a functionally significant target for pp60v-src. To examine the effect of src expression on the activity of the IGF-I receptor, the human IGF-I receptor was expressed in Rat-1 fibroblasts co-expressing the temperature-sensitive v-src mutant, tsLA29. The IGF-I receptor exhibited an elevated level of tyrosine phosphorylation in src transformed cells even in the absence of IGF-I treatment. Increased receptor phosphorylation occurred rapidly when cells expressing a temperature-conditional src mutant were shifted from the restrictive to the permissive temperature. Src-induced phosphorylation of the receptor was correlated with an increase in the in vitro tyrosine kinase activity of the receptor, both toward itself and exogenous substrates. The src-induced increase in receptor activity was shown to be dependent on tyrosine phosphorylation, as treatment with a tyrosine-specific phosphatase lowered receptor activity. A kinase-defective mutant of the IGF-I receptor also became constitutively phosphorylated in src-transformed cells, ruling out a possible autocrine mechanism for this phosphorylation. Collectively these data indicate that pp60v-src induces ligand-independent phosphorylation and activation of the IGF-I receptor by an intracellular mechanism, consistent with the possibility that receptor phosphorylation could contribute to the genesis of the transformed phenotype.
Although hypertrophic cardiomyopathy (HC) is believed to be a relatively uncommon cardiac disease, the frequency with which it occurs in the general or cardiac population has not been defined. To address this issue, the patient population of a community-based echocardiography laboratory was used to assess the prevalence of HC in 714 consecutively studied outpatients with (or suspected of having) heart disease. The most common cardiac disease identified was mitral valve prolapse (73 patients [10%]), and HC was present in 4 patients (0.5%). Ages were 50 to 69 years. Maximal left ventricular wall thicknessess were 15 to 22 mm (mean 19); only 1 had evidence of obstruction to left ventricular outflow by virtue of marked mitral valve systolic anterior motion. Before echocardiographic study, each of the 4 patients with HC had signs or symptoms of cardiac disease, but the correct diagnosis had not been suspected. Of 11 other patients who were referred for echocardiographic study because of a clinical suspicion of HC, none proved to have this disease. The present study demonstrates that HC is a particularly uncommon disease entity occurring in about 0.5% of an unselected outpatient population referred for echocardiographic study.
Primary cultures of embryonic chick skeletal myogenic cells were used as an experimental model to examine the possible role of mono(ADP-ribosyl)ation reactions in myogenic differentiation. Initial studies demonstrated arginine-specific mono(ADP-ribosyl)transferase activity in the myogenic cell cultures. We then examined the effect of a novel inhibitor of cellular arginine-specific mono(ADP-ribosyl)transferases, meta-iodobenzylguanidine (MIBG), on differentiation of cultured embryonic chick skeletal myoblasts. MIBG reversibly inhibited both proliferation and differentiation of embryonic chick myoblasts grown in culture. Micromolar (15-60 microM) concentrations of MIBG blocked myoblast fusion, the differentiation-specific increase in creatine phosphokinase activity, and both DNA and protein accumulation in myogenic cell cultures. Meta-iodobenzylamine, an analog of MIBG missing the guanidine group, had no effect. Low concentrations of methylglyoxal bis-guanylhydrazone, a substrate for cholera toxin with a higher Km than MIBG, also had no effect, but higher concentrations reversibly inhibited fusion. These findings suggest a possible role for mono(ADP-ribosyl)ation reactions in myogenesis. In addition, the total arginine-specific mono(ADP-ribosyl)transferase activity increased with differentiation in the myogenic cell cultures, and this increase was also blocked by MIBG treatment. Because high levels of activity were found in the membrane fraction derived from later, myotube cultures, the membrane fraction from 96-h cultures was incubated with [32P]NAD+ and subjected to electrophoresis and autoradiography. Three proteins, migrating at 21, 20, and 17 kDa, that were ADP-ribosylated in the absence, but not the presence, of MIBG were identified. These proteins may be endogenous substrates for this enzyme.
Analysis of the kinds of data used for the derivation of ambient air quality standards (AAQSs) for carbon monoxide and ozone shows that these values are based on the toxicology of the materials and thus are suitable for evaluating potential health effects of indoor environments, especially on the very young, the aged, and the infirm. A similar analysis shows that the AAQSs for suspended particulate matter, nitrogen dioxide, and sulfur dioxide are strictly empirical and that they should not be used for any but their first, intended purpose. The AAQSs for non-methane hydrocarbons are based on photochemical smog production, not injury of any kind, and have no utility for indoor environment evaluation.
In a field experiment in the Mallee district of Victoria, Merlno xBorder Leicester ewes and wethers grazed Heliotropium europaeum (heliotrope) over periods of 3 to 4 months in 4 successive years. By the end of the second year 12% (14 of 120) of the sheep had died; after 4 years the loss attributable to heliotrope was between 18% and 35%. Mortality was not affected by intraruminal treatment with cobalt or antimethanogen. At the end of the experiment the highest concentration of copper in the liver was 1.95 mmol/kg wet weight (approximately 413 micrograms/g dry weight). The relatively low mortality from primary heliotrope poisoning and the low concentration of copper in the liver of sheep grazing the plant are discussed in relation to the contrasting situation that prevails in the Riverina area of New South Wales. The importance of local environmental factors in the management of heliotrope grazing by sheep is emphasised, particularly in relation to the number of seasons in which the plant may be a major component of the diet.
The state legislature is comprised of a mixture of personalities and viewpoints. In this first of a series of three interviews with members of the general assembly, Senators John Peterson and J. Doyle Corman talk about life in rural Pennsylvania, what physicians can do to be more involved in the political process, and a number of other issues.