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Biomedical subjects

V L Ng

Publications and source records attributed to V L Ng.

At least 37 records · Page 2Linked to original sources

Seroprevalence of human T-lymphotropic virus, hepatitis C virus, and human immunodeficiency virus in Asian American potential bone marrow donors.

BACKGROUND: Asian Americans are generally underrepresented both as volunteer blood and bone marrow donors. STUDY DESIGN AND METHODS: To investigate the risk of transfusion transmission of viruses that is associated with increasing participation by Asian American donors, antibodies to human T-lymphotropic virus (HTLV), hepatitis C, and human immunodeficiency virus in Asian American volunteers recruited as potential bone marrow donors were measured. A total of 1354 Asian Americans were enrolled in the study, of whom 54 percent were Chinese, 26 percent Japanese, 9 percent Filipino, 4 percent Korean, 3 percent Indian, and 5 percent of other Asian or mixed Asian and other ethnicity. The majority of the study population was aged 20 through 49 and of high socioeconomic status, as indicated by education and income. Viral antibodies were measured with both screening enzyme-linked immunosorbent assays and supplemental testing, and polymerase chain reaction was used to resolve discrepant HTLV results. RESULTS: Confirmed seroprevalence rates for HTLV were 0.15 percent with one manufacturer's Western blot and 0.3 percent with the other; however, no sample was positive for HTLV types I or II in polymerase chain reaction. Confirmed seroprevalence to hepatitis C virus was 0.5 percent. No subject was seropositive for human immunodeficiency virus. CONCLUSION: On the basis of the moderate size and high education level of this study population, it is concluded that Asian American volunteer bone marrow donors do not pose a greater risk for transmission of HTLV type I or II, human immunodeficiency virus, or hepatitis C virus than does the average American blood donor.

Adolescent↗

Failure of the International Normalized Ratio to generate consistent results within a local medical community.

Use of the International Normalized Ratio (INR) has been recommended as a means of standardizing prothrombin time (PT) results for management of oral anticoagulant therapy. During the evaluation of a new lot of thromboplastin reagent, however, INR values were obtained that were inconsistent with results obtained with the prior lot of reagent from the same manufacturer. A local normalized ratio (LNR) was substituted for the INR for the new reagent, based on a calculated local sensitivity index (LSI). Validation of the LSI was performed at the three hospitals in the medical community by testing an identical panel of aliquots from 64 plasmas obtained from patients who were chronically receiving oral anticoagulants. Each test result was classified according to the INR value as low, low therapeutic, high therapeutic, or high. Local normalized ratio values obtained at one hospital in the community were in reasonable agreement with INR determinations in the other two hospital laboratories. Classification mismatches occurred using the INR, however, in 84 of 280 (30%) of the paired samples. Thus, the inability to generate consistent INR values within a local medical community raises serious concern about the reliability of the INR concept in its current form.

Anticoagulants↗

Evaluation of an enzyme immunoassay for detection of cryptococcal capsular polysaccharide antigen in serum and cerebrospinal fluid.

The Premier enzyme immunoassay (Meridian Diagnostics, Inc., Cincinnati, Ohio) was compared with a latex agglutination assay (CALAS; Meridian) for the ability to detect cryptococcal capsular polysaccharide antigen (CrAg) in serum and cerebrospinal fluid (CSF). A total of 594 specimens (471 serum samples and 123 CSF samples) obtained from 430 patients, most of whom were at risk for or had AIDS, were tested in parallel by both systems. Both tests were independently evaluated for their ability to (i) detect CrAg when used as a screening test and (ii) quantitate the CrAg present when used as a titration assay. Chart review to assess clinical outcome after the time of specimen collection was conducted for all patients. When both assays were used as screening assays, 103 serum samples and 18 CSF samples were positive and 356 serum samples and 104 CSF specimens were negative by both assays (97.8% concordance). Thirteen specimens (12 serum samples, 1 CSF sample) gave discrepant screening results. When the tests were used as semiquantitative assays for titer determinations, the CrAg titers determined by the enzyme immunoassay were generally higher than those obtained with the latex agglutination assay. In summary, results obtained with the enzyme immunoassay correlated well with those obtained with the latex agglutination test for screening for the presence of CrAg and for determining the titer of CrAg in serum or CSF.

Acquired Immunodeficiency Syndrome↗

Lack of effect of prophylactic aerosolized pentamidine on the detection of Pneumocystis carinii in induced sputum or bronchoalveolar lavage specimens.

Two independent studies were undertaken to determine the effect of prophylactic treatment with aerosolized pentamidine on the laboratory diagnosis of Pneumocystis carinii pneumonia in individuals at risk for or with the acquired immunodeficiency syndrome. The first study was a retrospective analysis to determine the effect of prophylactic treatment with aerosolized pentamidine on the diagnostic yield and sensitivity of detection of P carinii in induced sputum specimens. The results of examinations of 110 induced sputum specimens from patients who had not received aerosolized pentamidine were compared with the findings in 57 specimens from patients who had. There was no statistically significant difference between the two groups for the diagnostic yield in induced sputum specimens (48% vs 47%) or in bronchoalveolar lavage fluid specimens subsequently obtained from patients with nondiagnostic induced sputum examinations (33% vs 37%). The sensitivity of induced sputum specimens for identifying P carinii was 76% to 78% for patients who had not received aerosolized pentamidine and 71% to 75% for patients who had received the drug. The second study was a prospective comparison of 118 bronchoalveolar lavage fluid specimens to determine the effect of prophylactic treatment with aerosolized pentamidine on the number of organisms present. One hundred eighteen bronchoalveolar lavage fluid specimens were quantitatively examined and scored according to the number of clumps of P carinii present. No statistically significant difference was seen in the number of clumps of P carinii found in specimens from patients who had received aerosolized pentamidine vs the number of clumps found in specimens from patients who had not. In conclusion, prophylactic treatment with aerosolized pentamidine had no effect on (1) the diagnostic yield and sensitivity of detection of P carinii in induced sputum specimens or (2) the number of organisms detected in bronchoalveolar lavage fluid specimens obtained from individuals at risk for or with the acquired immunodeficiency syndrome.

AIDS-Related Opportunistic Infections↗

Use of DNA probes to detect Mycobacterium intracellulare and "X" mycobacteria among clinical isolates of Mycobacterium avium complex.

A mycobacterial DNA probe (designated X) was recently developed to help identify Mycobacterium avium complex (MAC) isolates that are nonreactive with probes specific for M. avium or Mycobacterium intracellulare. The prevalence of X probe-positive mycobacteria in clinical specimens and their role in causing disease is unknown. Using a DNA probe kit that includes the X probe, we characterized 100 consecutive clinical MAC isolates as M. avium, M. intracellulare, or X. Lysates from 81 of the isolates reacted with the M. avium probe, 13 with the M. intracellulare probe, 3 with the X probe, and 3 failed to hybridize with any of the probes. All three X-positive isolates were recovered from sputa of patients who were recent immigrants to the United States and who presented with hemoptysis. One isolate was from a Hispanic man infected with human immunodeficiency virus type 1 (HIV-1) and the other 2 were from Filipino patients with no HIV-1 risk factors. This study also showed a higher than expected number of M. intracellulare isolates from blood and cerebrospinal fluid of HIV-1-infected patients.

Acquired Immunodeficiency Syndrome↗

Clofazimine crystals in alveolar macrophages from a patient with the acquired immunodeficiency syndrome.

An induced sputum specimen from a 35-year-old patient with the acquired immunodeficiency syndrome (AIDS) contained numerous bright orange-red needle-shaped crystal inclusions in his alveolar macrophages. Careful questioning revealed that he recently had been treated for 7 months with clofazimine (200 mg/d) for persistent Mycobacterium avium complex bacteremia. The striking cytologic finding observed is diagnosed easily if the characteristic morphologic appearance of the crystals and their location within the cytoplasm of macrophages and cells of the reticuloendothelial system is appreciated. Although this is the first observation at San Francisco (Calif) General Hospital of clofazimine crystals in a respiratory specimen from a patient with AIDS, the potential of more widespread therapy with clofazimine in patients with AIDS who are infected with M avium complex makes it imperative that the microscopic appearance of these crystals be recognized.

Acquired Immunodeficiency Syndrome↗

Rapid detection of Pneumocystis carinii using a direct fluorescent monoclonal antibody stain.

A collaborative study was undertaken at two institutions to assess the performance of a direct fluorescent-antibody stain for the detection of Pneumocystis carinii in respiratory specimens from patients with known or suspected human immunodeficiency virus type 1 infections. A total of 163 specimens (125 induced sputa, 37 bronchoalveolar lavage fluids, and 1 tracheal aspirate) from 124 patients were examined by using modified Giemsa (Diff-Quik; Baxter American Scientific Products, Chicago, Ill.) and direct fluorescent-antibody stains. A total of 73 specimens contained P. carinii, which was detected in 66 (92%) of the specimens by using the modified Giemsa and in 71 (97%) of the specimens by using the fluorescent-antibody stain. One bronchoalveolar lavage fluid specimen in which P. carinii was detected only with the fluorescent-antibody stain was determined to be a false-positive based on subsequent clinical evaluation of the patient. Although the overall time for processing and examining specimens stained with either stain was not significantly different for those specimens containing P. carinii, considerably less time was required for microscopic examination of those fluorescent-antibody-stained specimens lacking P. carinii.

Antibodies, Monoclonal↗

Evaluation of an indirect fluorescent-antibody stain for detection of Pneumocystis carinii in respiratory specimens.

Two prospective studies were undertaken to evaluate a commercial indirect fluorescent-antibody (IFA) stain for the detection of Pneumocystis carinii in respiratory specimens from individuals at risk for or with the acquired immunodeficiency syndrome. The first study compared IFA with Diff-Quik (DQ; a rapid Giemsa-like stain) for detecting P. carinii in 95 induced sputa obtained from 77 asymptomatic patients who had survived one previous episode of P. carinii pneumonia and who were being treated prophylactically with aerosolized pentamidine. Only one induced sputum specimen was found to contain P. carinii; organisms were detected by both stains. The second study compared the performance of the IFA stain versus DQ, modified toluidine blue O, and Gomori methenamine silver stains for detecting P. carinii in symptomatic individuals at risk for or with acquired immunodeficiency syndrome. Of 182 specimens examined, P. carinii was detected in 105 by one or more stains; the DQ stain detected 73 (70%), the modified toluidine blue O stain detected 75 (71%), the Gomori methenamine silver stain detected 76 (72%), and the IFA stain detected 95 (90%). The IFA stain was more sensitive (P less than 0.01) than the other traditional stains for detecting P. carinii; however, a subsequent clinical evaluation revealed that a subset of IFA-positive-only specimens were from patients whose clinical symptoms resolved without specific anti-P. carinii therapy.

Diagnostic Errors↗

The clinical significance of human immunodeficiency virus type 1-associated paraproteins.

We observed and characterized paraproteins present in the serum of seven human immunodeficiency virus type 1 (HIV-1)-infected individuals. Immunoglobulin (Ig) subclass typing performed on these paraproteins identified five as IgG1 kappa, one as an IgG3 lambda, and one as an IgA lambda. The IgG1 kappa paraproteins, purified by high-pressure liquid chromatography, contained the majority of anti-HIV-1 antibody reactivity present in the five serum specimens (ranging from 1:5,000 to 1:500,000) as demonstrated by immunoblot. All five IgG1 paraproteins had at least two light chain species as demonstrated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and the antibodies were reactive with multiple HIV-1 viral antigens. In contrast, the electrophoretically purified IgG3 lambda and IgA lambda paraproteins did not react with HIV-1 antigens and only one light chain species was detected by SDS-PAGE. The subsequent clinical evaluation of these patients following the initial observation of paraproteinemias failed to correlate the presence of paraproteins with the development of lymphoma over a 2 to 3 year period. These data support the hypothesis that IgG1 paraproteins present in the sera of HIV-1 infected individuals reflect a normal albeit exuberant polyclonal immune response to HIV-1 viral antigens. In contrast, the clinical significance of an IgG3 lambda or an IgA lambda paraprotein is unclear at present.

Antibody Specificity↗

IgM secreted by human T lymphoma virus-I-infected and transformed human B cell clones recognize a 66-kilodalton host-encoded protein.

It has previously been determined that transformed human B cells may be infected by and retain integrated human T cell lymphotropic virus, type I (HTLV-I). Although HTLV-I is primarily associated with transformation of human T lymphocytes, immortalized B cell populations have arisen after cocultivation of normal B cells and irradiated HTLV-I-infected T cells. To test whether HTLV-I infection might be involved in this B cell transformation process, we characterized five independent HTLV-I-infected and -immortalized human B cell clones. All five clones contained clonal HTLV-I integrations, expressed cell surface IgM, and secreted IgM in quantities varying from 0.1 to 4.0 micrograms/ml. Immunoblotting and immunoprecipitation of metabolically labeled cell lysates failed to detect synthesis of HTLV-I gag, env, or tat gene products, and cellular RNA dot blot analysis detected varying levels of HTLV-I gene transcripts in only three of the five clones. The secreted IgM from culture supernatants were affinity purified, and were found to selectively immunoprecipitate an acidic protein (isoelectric point = 5.0) of 66,000 m.w. (p66) from purified radioiodinated HTLV-I virions. This p66 copurified with metabolically labelled HTLV-I-infected B cell IgM from HKA-3 cells. Although HTLV-I RNA transcripts were present at low levels, the absence of HTLV-I proteins in HKA-3 cells made it unlikely that p66 was related to the major HTLV-I envelope glycoprotein, gp62. Anti-idiotypic mAb directed against the IgM produced by one B cell clone (HKA-3), as well as purified HTLV-I virions (containing p66), stimulated HKA-3 cell proliferation. Preincubating the anti-Id antibody or HTLV-I with excess HKA-3 IgM abolished the binding of either to HKA-3 cells. These data suggest that HTLV-I infected cells produce a cellular protein (p66), which is incorporated into and copurifies with HTLV-I virions, and which in at least one case (HKA-3) may act as a mitogenic stimulus, potentially contributing to the HTLV-I mediated transformation process.

Antibodies, Anti-Idiotypic↗

GLQ223: an inhibitor of human immunodeficiency virus replication in acutely and chronically infected cells of lymphocyte and mononuclear phagocyte lineage.

GLQ223 is a highly purified, formulated preparation of trichosanthin, a 26-kDa plant-derived ribosome-inactivating protein with potent inhibitory activity against human immunodeficiency virus (HIV) in vitro. The compound produced concentration-dependent inhibition of HIV replication in acutely infected cultures of T-lymphoblastoid cells (VB cell line). Treatment with GLQ223 selectively reduced levels of detectable viral proteins compared to total cellular protein synthesis and produced a selective decrease in levels of viral RNA relative to total cellular RNA in acutely infected cells. Substantial inhibition of viral replication was observed at concentrations of GLQ223 that showed little inhibition of parallel uninfected cultures. Selective anti-HIV activity was also observed in cultures of primary monocyte/macrophages chronically infected with HIV in vitro. When freshly drawn blood samples from HIV-infected patients were treated with a single 3-hr exposure to GLQ223. HIV replication was blocked for at least 5 days in subsequently cultured monocyte/macrophages, without further treatment. The anti-HIV activity of GLQ223 in both acutely and chronically infected cells and its activity in cells of both lymphoid and mononuclear phagocytic lineage make it an interesting candidate as a potential therapeutic agent in HIV infection and AIDS.

Antigens, Viral↗

Comparative recovery of cytomegalovirus from saliva, mucolysed induced sputum, and bronchoalveolar lavage fluid from patients at risk for or with acquired immunodeficiency syndrome.

The recovery rates of cytomegalovirus from mucolysed induced sputum samples and bronchoalveolar lavage fluid obtained from individuals at risk for or with acquired immunodeficiency syndrome were compared. It was demonstrated that cytomegalovirus could be reliably recovered from mucolysed induced sputum, and such recovery was highly predictive of recovery from bronchoalveolar lavage samples obtained from the same individual.

Acquired Immunodeficiency Syndrome↗

Unexpected isolation of Bordetella pertussis from patients with acquired immunodeficiency syndrome.

We isolated Bordetella pertussis from three patients with acquired immunodeficiency syndrome who underwent diagnostic bronchoscopy for evaluation of respiratory symptoms. The B. pertussis isolates were recovered from medium (charcoal-yeast extract agar) formulated to enhance recovery of Legionella spp., and one of the isolates stained positively with antisera directed against Legionella spp.

Acquired Immunodeficiency Syndrome↗