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Biomedical subjects

S Quan

Publications and source records attributed to S Quan.

At least 73 records · Page 4Linked to original sources
PubMed1993

Deficient expression of a B cell cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia.

We describe a novel cytoplasmic tyrosine kinase, termed BPK (B cell progenitor kinase), which is expressed in all stages of the B lineage and in myeloid cells. BPK has classic SH1, SH2, and SH3 domains, but lacks myristylation signals and a regulatory phosphorylation site corresponding to tyrosine 527 of c-src. BPK has a long, basic amino-terminal region upstream of the SH3 domain. BPK was evaluated as a candidate for human X-linked agammaglobulinemia (XLA), an inherited immunodeficiency characterized by a severe deficit of B and plasma cells and profound hypogammaglobulinemia. BPK mapped to within 100 kb of a probe defining the polymorphism most closely linked to XLA at DXS178. Reduction in or the absence of BPK mRNA, protein expression, and kinase activity was observed in XLA pre-B and B cell lines. BPK is likely the XLA gene and functions in pathways critical to B cell expansion.

Agammaglobulinemia↗
PubMed1993

Nocardioform arsenic resistance plasmid characterization and improved Rhodococcus cloning vectors.

A representative of a group of related Rhodococcus arsenic resistance plasmids was characterized, locating the resistance genes and regions influencing host range and controlling copy number. This information, together with identification of antibiotic resistance determinants to replace the arsenic marker was used to construct Rhodococcus-Escherichia coli positive selection shuttle plasmids which, compared with those previously constructed, had half the size, a much higher copy number, and chloramphenicol rather than arsenic as selectable marker.

Arsenic↗
PubMed1993

Relevance of anti-HCV reactivity in patients with alcoholic hepatitis. VA cooperative Study Group #275.

From 8 Department of Veterans Affairs Medical Centers, 296 patients with varying degrees of alcoholic liver disease were tested for hepatitis C (HCV) infection using an EIA and RIBA 2. A high frequency of positive response was observed with 13.9% reactive to both and an additional 4.4% positive only to RIBA 2 (total 18.3%). An evaluation of known risk factors (injection drug use and prior blood transfusions) failed to account for the mode of transmission in 42.6% of the HCV+ patients. The clinical severity of the liver disease and degree of liver pathology were nearly identical in HCV+ vs. HCV- patients. However, the process was accelerated in the HCV+ patients occurring at a 12.8% younger age (p < 0.0001) with a 43% increase in ALT (p = 0.05). The most striking differences were observed in immune parameters. In peripheral blood, total lymphocyte counts were increased 20% (p = 0.01) accompanied by a 56% increase in B cells (p = 0.01) and a 35% elevation of IgG levels (p = 0.0001) in HCV+ patients. T cell changes consisted of a 50% increase in CD8 cells (p = 0.047). However, lymphocyte infiltration into liver was not significantly different (HCV+ vs. HCV-) for any of the subsets studied (CD4, CD8, B cells, NK cells). The combined presence of HCV and alcohol injury did not significantly increase mortality but did significantly increase the number of hospitalizations from 2.4 to 4.0 per year (p = 0.0005).

Hepacivirus↗
PubMed1993

Hepatitis C virus infection in kidney transplant recipients.

To determine the prevalence and significance of hepatitis C virus infection in kidney transplant recipients, paired serum samples collected from 100 renal allograft recipients on admission for kidney transplantation and 1 yr after transplantation were tested for antibody to hepatitis C virus with second-generation enzyme immunoassay and recombinant immunoblot assay and for hepatitis C virus RNA with reverse transcription-polymerase chain reaction. Before kidney transplantation, hepatitis C virus antibody was detected with second-generation enzyme immunoassay in 18 patients (12 second-generation recombinant immunoblot assay-positive, 6 second-generation recombinant immunoblot assay-indeterminate). Nine of 12 second-generation recombinant immunoblot assay-positive and 2 of 6 second-generation recombinant immunoblot assay-indeterminate samples were hepatitis C virus RNA positive. In addition, 7 of 82 patients who had no detectable antibody on second-generation enzyme immunoassay or second-generation recombinant immunoblot assay were hepatitis C virus RNA positive. After kidney transplantation, hepatitis C virus antibody was detected in 19 patients (12 second-generation recombinant immunoblot assay-positive, 7 second-generation recombinant immunoblot assay-indeterminate, 14 seropositive for hepatitis C virus antibody). Eleven of 12 patients with second-generation recombinant immunoblot assay-positive results and 4 of 7 with second-generation recombinant immunoblot assay-indeterminate results were positive for hepatitis C virus RNA. Hepatitis C virus RNA was present in 28 patients 1 yr after kidney transplantation. Six patients appeared to have acquired active hepatitis C virus infection 1 yr after kidney transplantation (seroconverted to hepatitis C virus RNA positivity).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

A pattern of 5-1-1 and c100-3 only on hepatitis C virus (HCV) recombinant immunoblot assay does not reflect HCV infection in blood donors.

Current criteria for a reactive (positive) interpretation on hepatitis C virus (HCV) recombinant immunoblot assay (RIBA) require > or = 1+ reactivity to at least two of the four HCV antigens present in the assay. Given that 5-1-1 is a subcomponent of c100-3, there is concern that donor samples reacting only with these two antigens (and not with c22-3 or c33c) could be incorrectly classified as positive on the basis of limited reactivity to only one HCV gene product. It is determined that 0.23 to 0.44 percent of HCV enzyme immunoassay-repeatably reactive donor sera demonstrate a pattern of 5-1-1 and c100-3 only on RIBA. Evaluation of six such donor sera using peptide enzyme immunoassays spanning the c100-3 antigen showed highly restricted reactivity to the 5-1-1 N-terminal region of c100-3, in contrast to broad 5-1-1 and c100-3 C-terminal peptide reactivity observed in the majority of donor sera with other positive RIBA patterns. HCV polymerase chain reaction and follow-up serologic evaluations of four of these donors indicated the absence of viremia or evolving seroconversion in all cases. It is concluded that, in the blood donor setting, a pattern of only 5-1-1 and c100-3 reactivity is typically not indicative of HCV infection. To avoid overinterpretation, it is recommended that RIBA grading criteria be revised to require reactivity to two or more HCV-encoded gene products.

Amino Acid Sequence↗
PubMed1993

Hepatitis C virus antibodies in patients with chronic liver disease: ELISA and RIBA HCV strip immunoblot assay results.

In a study using the current first generation Ortho ELISA, a second generation Ortho ELISA, and the RIBA HCV strip immunoblot assay, all patients who were strongly positive for antihepatitis C virus (HCV) on ELISAs (OD490 > 3) were reactive to RIBA for multiple bands. While all ELISA false positive samples had low or intermediate OD490 values, RIBA confirmed HCV reactivity in 50% of the patients reactive to ELISA with a low suspicion of HCV infection, thus suggesting that RIBA HCV strip immunoblot assay will be most useful for patients who react weakly positive or intermediate to ELISA.

Chronic Disease↗
PubMed1993

Natural history of hepatitis C virus infection in multitransfused hemophiliacs: effect of coinfection with human immunodeficiency virus. The Multicenter Hemophilia Cohort Study.

The objective of this prospective cohort study was to describe the natural history of hepatitis C virus (HCV) infection and the effect of human immunodeficiency virus (HIV) on the clinical manifestations of HCV liver disease. Two hundred twenty-three hemophiliacs were followed in a comprehensive care setting with periodic clinical and laboratory evaluations. Dates of HIV seroconversion were determined retrospectively from frozen sera. HCV assays were performed by a "second generation" four-antigen recombinant immunoblot assay (RIBA 2). Liver failure was found after a latency period of 10 to 20 years in 9% of multitransfused HCV-positive/HIV-positive adult hemophiliacs without an AIDS-defining opportunistic infection or malignancy. Lymphocytopenia, decreased CD4 counts, and, possibly, thrombocytopenia were associated with liver failure which appeared to be accelerated by HIV disease and its treatment. This form of severe liver disease is being seen with increasing frequency among multi-transfused persons with hemophilia who are coinfected with HCV and HIV.

Adolescent↗
PubMed1993

Epidemiology of hepatitis C among veterans with alcoholic liver disease. The VA Cooperative Study Group 275.

Of 288 patients with alcoholism and various stages of alcoholic hepatitis, 18.4% (53 of 288) reacted serologically for hepatitis C (HCV). An evaluation of the risk factors associated with HCV indicated that parenteral drug use, even in the distant past, increased the risk for infection 10.1-fold (p = 0.0001). Ethnicity was also a significant, independent risk factor. Minorities (i.e., African-Americans or Hispanic-Americans) had a 2.4-fold increase (p = 0.038). Prior blood transfusions, even if multiple, showed only a tendency toward increased infections (p = 0.088) in this population. An interaction between age and contact with parenteral drug users was demonstrated such that the risk of HCV infection was increased by contact with drug users. This was further increased with increasing age (p = 0.006). There was no relationship between HCV reactivity and the severity of the liver disease; however, the liver injury appeared to be accelerated since it occurred at a younger age (p = 0.0001) and was associated with more frequent hospitalizations (p = 0.0005).

Hepatitis C↗
PubMed1993

Non-A, non-B posttransfusion hepatitis: comparing C and non-C hepatitis.

Using assays to detect antibodies against antigens (C-100, 5-1-1, C-22 and C-33) of the hepatitis C virus, we tested stored sera from 40 patients prospectively identified as having non-A, non-B posttransfusion hepatitis. The 28 patients who demonstrated seroconversion ("documented hepatitis C") had more severe initial disease; all 20 cases of chronic hepatitis occurred in this subgroup. Only 2 of the 12 patients who did not demonstrate such seroconversion even had symptoms. In the group of patients with documented hepatitis C, chronic hepatitis was more commonly seen in men (89%) than in women (40%). The patients in whom antibody to the C-100 antigen developed were younger and had received more blood than had those patients who had hepatitis C diagnosed by demonstration of antibodies to the 5-1-1, C-22 or C-33 antigen (or all three). The proportion of cases of posttransfusion hepatitis that could be associated with antibody sero-conversion decreased around the time that blood banks switched to an all-volunteer system. The hepatitis seen in patients who failed to demonstrate serological evidence of hepatitis C virus exposure was usually clinically unimportant; it may or may not have been due to viral infection.

Acute Disease↗
PubMed1992

Prevalence of hepatitis C virus RNA in organ donors positive for hepatitis C antibody and in the recipients of their organs.

BACKGROUND: There is a high prevalence of liver disease among the recipients of organs from donors with antibodies to hepatitis C virus (HCV). We undertook a study to determine the frequency of persistent HCV infection, as indicated by the presence of HCV RNA, among both cadaveric organ donors positive for antibodies to HCV (anti-HCV) and the recipients or organs from these donors. METHODS: Serum samples from donors and recipients were tested for HCV RNA with the reverse transcriptase polymerase chain reaction, with use of primers from the 5' untranslated region of the HCV genome, and for anti-HCV with the first-generation enzyme-linked immunosorbent assay (ELISA) and two second-generation tests. RESULTS: HCV RNA was detected in 9 of the 11 organ donors (82 percent) with a positive first-generation ELISA for anti-HCV. Among the organ recipients, the prevalence of HCV RNA increased after transplantation: 7 of 26 patients (27 percent) had positive samples before transplantation, as compared with 23 of 24 patients (96 percent) after transplantation (P less than 0.001). Among 13 recipients who were HCV RNA-negative before receiving organs from the nine HCV RNA-positive donors, HCV infection was detected in all 13 after transplantation, and anti-HCV developed in 8 (62 percent). On the basis of a positive test for HCV RNA, the maximal sensitivity of the three anti-HCV tests was 57 percent (positive in 4 of 7 patients with end-stage organ failure) before transplantation and 70 percent (positive in 16 of 23 patients) after transplantation. CONCLUSIONS: Nearly all the recipients of organs from anti-HCV-positive donors become infected with HCV. The current tests for anti-HCV antibodies underestimate the incidence of transmission and the prevalence of HCV infection among immunosuppressed organ recipients.

Base Sequence↗
PubMed1992

Detection of hepatitis C virus infection among cadaver organ donors: evidence for low transmission of disease.

OBJECTIVE: To determine the prevalence of antibodies to hepatitis C virus (anti-HCV) and HCV RNA among cadaver organ donors and to correlate these results with donor liver histologic abnormalities and evidence for transmission of disease through organ transplantation. DESIGN: Retrospective testing of stored serum samples from cadaver organ donors for anti-HCV and HCV RNA. SETTING: Transplantation service of the University of Miami/Jackson Memorial Medical Center and other cooperative medical centers furnishing follow-up data. SUBJECTS: Of 1096 cadaver organ donors harvested between 1 January 1979 and 28 February 1991, 484 had stored serum samples available for analysis. Recipients of organs from recombinant immunoblot assay (RIBA)-positive donors for whom adequate follow-up was available were also included in the analysis. MEASUREMENTS: Samples were tested for anti-HCV by enzyme-linked immunosorbent assay (ELISA). Confirmatory testing was done using a second-generation RIBA. Hepatitis C viral RNA was detected in serum using the polymerase chain reaction. Liver biopsies were obtained from the organ donor and interpreted blindly by a pathologist unaware of the clinical data. Liver chemistry profiles and serum sample analysis for HCV RNA were done for transplant recipients. RESULTS: From the 484 cadaver organ donors, 89 samples (18%; 95% Cl, 15% to 21%) were reactive by ELISA. Of these, 33 (6.8%; Cl, 4.6% to 9%) were RIBA seropositive. Hepatitis C viral RNA sequences were detected in 50% of the RIBA-positive serum samples tested. Liver tissue was available from 24 of the 33 RIBA-positive donors and showed chronic active hepatitis in 16, chronic persistent hepatitis in 2, and no abnormality in 6. Among the 46 recipients of a kidney from a RIBA-positive donor, 13 (28%; Cl, 15% to 41%) developed post-transplant liver disease, of which only 4 cases were highly suggestive of viral transmission from the donor. Little morbidity and no mortality could be attributed to liver disease in this cohort of recipients. CONCLUSIONS: These data suggest that HCV transmission by organ transplantation is low and that the consequences of infection are small. If the medical condition of the potential recipient is so serious that other options no longer exist, the use of an organ from an anti-HCV-seropositive donor should be considered.

Adult↗
PubMed1992

Propagation of human blastic myeloid leukemias in the SCID mouse.

Existing in vitro culture technology does not permit the routine propagation of most human myeloid leukemias. Previous work has shown the usefulness of mice with severe combined immunodeficiency (SCID) for the growth of human lymphoblastic leukemia. We show here that human myeloid cell lines and bone marrow samples from patients with acute myeloid leukemia (AML) and blast crisis of chronic myeloid leukemia (CML) also grow in SCID mice. Human AML or CML cell lines (three of three lines tested) grew in the bone marrow and peripheral blood of the mice after intravenous (IV) inoculation in a pattern closely resembling human AML. To define the best conditions for the growth of primary human myeloid leukemia cells, samples were transplanted into mice at several alternative sites. Using flow cytometry and Southern analysis, mice were analyzed at defined intervals up to 36 weeks after transplantation for the presence of human cells in various tissues. For four of four patients with AML and two of two patients with blast crisis of CML, myeloblasts grew locally at the site of implantation and were detected in the murine hematopoietic tissues. In contrast, marrow implants from patients in the chronic phase of CML (six patients) showed infrequent and limited myeloid growth in the mice. These findings demonstrate that the SCID mouse is a reproducible system for the propagation of blastic human myeloid leukemias. The differential growth of early- versus late-phase CML suggests that the SCID mouse may be a useful assay for identifying biologically aggressive leukemias early in their clinical presentation.

Acute Disease↗
PubMed1992

Production of granulocyte-macrophage colony-stimulating factor in two patients with lung cancer, leukocytosis, and eosinophilia.

Leukocytosis in association with malignancy has been well described, but the cause is not known. One potential explanation is production of a colony-stimulating factor by the tumor, and this has been demonstrated in vitro. The authors report two patients with lung cancer, leukocytosis, and eosinophilia. The pleural fluid of both patients contained malignant cells and biologically active granulocyte-macrophage colony-stimulating factor (GM-CSF), as demonstrated by radioimmunoassay, enzyme-linked immunosorbent assay (ELISA), and colony-forming unit-granulocyte-macrophage (CFU-GM) assay. To determine whether GM-CSF is normally detectable in pleural fluid, the authors performed assays on an additional 11 patients with pleural effusions of various origins but without peripheral blood leukocytosis and eosinophilia; only 1 patient had a detectable level of GM-CSF (i.e., greater than or equal to 0.1 ng/ml). Because GM-CSF usually is not present in pleural fluid, the authors postulate that the high levels of GM-CSF found in the pleural fluid of these two patients was produced by their tumors, and production of GM-CSF by their lung cancers likely caused the leukocytosis with eosinophilia.

Adenocarcinoma↗
PubMed1992

Improved detection of antibodies to hepatitis C virus using a second generation ELISA.

A screening assay for the detection of antibodies to hepatitis C virus (HCV); ORTHO HCV ELISA Test System, Second Generation, was compared with the currently licensed c100-3 based test (ORTHO HCV ELISA Test System). The second generation ELISA differs from the c100-3 based assay in that it detects circulating antibodies to both structural (nucleocapsid) and non-structural (NS3/NS4) HCV proteins. Specimens tested consisted of a cohort of 35 patients diagnosed with non-A, non-B hepatitis (NANBH) and 3971 presumably healthy volunteer blood donors. Second generation ELISA demonstrated significantly greater clinical sensitivity in patients with acute phase NANBH (80% vs. 60%) as well as chronic disease (88% vs. 72%). Additional specimens reactive only in second generation ELISA, demonstrated reactivity to HCV antigens c33c and/or c22-3 in supplemental testing by the Chiron HCV RIBA Assay System. The second generation ELISA also detected additional RIBA reactive volunteer blood donors (0.18% of the population tested) that were nonreactive in first generation ELISA. This data indicated that second generation ELISA would detect approximately 2 additional anti-HCV reactive donors per 1,000 screened. Specificities obtained with this low risk population were 99.6% for first generation and 99.7% for second generation ELISA.

Blood Donors↗
PubMed1992

Comparative evaluation of supplemental hepatitis C virus antibody test systems.

Implementation of routine blood donor screening using anti-hepatitis C virus (HCV) enzyme immunoassay (EIA) has resulted in an urgent need for well-characterized supplemental assays to confirm the presence of HCV antibodies. A comparative study of four commercially available supplemental assays is reported here: first- and second-generation versions of a strip recombinant immunoblot assay (RIBA-1 and RIBA-2), an HCV neutralization EIA, and HCV neutralization plus synthetic peptide EIA. Three hundred sixty-seven blood donor specimens that were repeatedly reactive on HCV EIA were studied. Most specimens (93%) were also evaluated by radioimmunoassay (RIA) with a six-antigen panel, and 60 selected specimens were tested for HCV RNA by the polymerase chain reaction (PCR). RIBA-1 and RIBA-2 gave concordant results with 86 percent of specimens, while an additional 13 percent were correctly classified by RIBA-2 but not RIBA-1. Neutralization EIA alone correctly identified 94 percent of the study group, while the remaining 6 percent required the peptide EIA or the combined neutralization-peptide assay system for correct classification. The RIBA-2 and neutralization-peptide assay system for correct classification. The RIBA-2 and neutralization-peptide assay systems yielded identical results for 86 percent of specimens, and these results were supported by RIA and selected PCR testing. Only 2 specimens (0.5%) were frankly discrepant, while 51 specimens were indeterminate on either (47) or both (4) assays. When either the RIBA-2 or neutralization-peptide assay yielded an indeterminate interpretation, the other system correctly classified the specimen (based on concordance with RIA and PCR data) in a high proportion (92%) of cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Viral↗
PubMed1992

Early antihepatitis C virus response with second-generation C200/C22 ELISA.

Detection of early antibody to hepatitis C virus (HCV) by a new second-generation C200/C22 anti-HCV enzyme-linked immunosorbent assay (ELISA) and a four-antigen recombinant immunoblot assay (4-RIBA) was compared with the first-generation anti-HCV C100 ELISA using sequential serum samples of 9 recipients who were infected with HCV, as detected by polymerase chain reaction after transfusion of blood products. Within 26 weeks after transfusion, 9/9 (100%) recipients seroconverted with C200/22 ELISA, and 6/9 (67%) seroconverted with C100 ELISA. Compared with C100 ELISA, C200/C22 ELISA seroconversion occurred simultaneously in 3 cases, 5-6 weeks earlier in 3 other cases, and 20 weeks earlier in 1 case. Seven of 9 (78%) recipients became positive, and 2/9 (22%) became indeterminate with 4-RIBA. In 8 cases with clinical posttransfusion hepatitis non-A, non-B (PTH-NANB), anti-HCV C200/C22 ELISA seroconversion occurred 2-17 (mean 6) weeks after the onset of hepatitis. In 6 cases of PTH-NANB, anti-HCV C100 ELISA seroconversion occurred 2-26 (mean 9) weeks after the onset of hepatitis. It is concluded that the second-generation C200/C22 ELISA is more sensitive than the C100 ELISA for the detection of antibody during early HCV infection. Indeterminate 4-RIBA results are found in the early phase of HCV infection.

Enzyme-Linked Immunosorbent Assay↗