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Biomedical subjects

V L Ng

Publications and source records attributed to V L Ng.

At least 19 recordsLinked to original sources
PubMed2000

Reversal of human immunodeficiency virus type 1-associated hematosuppression by effective antiretroviral therapy.

The immunodeficiency of human immunodeficiency virus type 1 (HIV-1) disease may be due to accelerated destruction of mature CD4+ T cells and/or impaired differentiation of progenitors of CD4+ T cells. HIV-1 infection may also inhibit the production of other hematopoietic lineages, by directly or indirectly suppressing the maturation of multilineage and/or lineage-restricted hematopoietic progenitor cells. To test this hypothesis, the effects of durable viral suppression on multilineage hematopoiesis in 66 HIV-1-seropositive patients were evaluated. Administration of effective antiretroviral therapy resulted in an increase in circulating CD4+ T cell counts and statistically significant increases in circulating levels of other hematopoietic lineages, including total white blood cells, lymphocytes, polymorphonuclear leukocytes, and platelets. These results suggest that a significant lesion in untreated HIV-1 disease may lie at the level of cell production from hematopoietic progenitors.

Adult↗
PubMed2000

Long-term outcome after partial external biliary diversion for intractable pruritus in patients with intrahepatic cholestasis.

BACKGROUND: Chronic intrahepatic cholestasis is associated with severe pruritus that is often refractory to maximal medical management and leads to significantly impaired quality of life. The hypothesis in this study was that partial external biliary diversion (PEBD) can substantially improve intractable pruritus secondary to intrahepatic cholestasis with subsequent improvement of functional quality of life. METHODS: Parents' and/or patients' clinical rating of pruritus, growth percentiles, biochemical parameters, and liver biopsies performed before and after surgery were compared in a retrospective medical record review. RESULTS: Eight children underwent PEBD from 1990 through 1997. Complete follow-up data were available for seven patients. Before surgery, all patients had intense pruritus, which was not responsive to maximal medical therapy. Specimens obtained in preoperative liver biopsies showed moderate (n = 1), minimal (n = 6), or no (n = 1) portal fibrosis. After PEBD, all patients received ursodeoxycholic acid (10-15 mg/kg/dose two to three times daily) until resolution of pruritus. Of the seven patients with complete follow-up data, six had complete resolution of pruritus and sustained resolution up to 8 years after surgery. The patient with mild to moderate residual pruritus was the youngest to undergo PEBD. Growth improved from below the 5th percentile before surgery to the 5th through the 25th percentiles for five of six patients with more than 6 years' follow-up. All families reported improved quality of life, defined by school attendance and ability to resume normal activity with peers. There has been no clinical evidence of progression of liver disease. CONCLUSION: Partial external biliary diversion is effective in the long-term treatment of pruritus refractory to medical therapy and provides a favorable outcome in a select group of patients with chronic intrahepatic cholestasis without cirrhosis.

Bile Acids and Salts↗
PubMed2000

Comparative genomic analyses of primary effusion lymphoma.

BACKGROUND: A rare subset of human immunodeficiency virus (HIV) lymphomas, known as primary effusion lymphomas (PELs), are high-grade tumors carrying human herpes virus 8. Mechanisms postulated to contribute to lymphomagenesis include impaired immune surveillance, alterations in hemopoietic regulatory pathways due to expressed viral genes, and acquisition of genomic alterations in regions of the genome that contain regulatory genes. In PEL, limited information exists about the nature of genome-wide aberrations in these rare lymphomas. METHODS: We used comparative genomic hybridization to detect regions of sequence gain and loss throughout the genome of 8 PEL cases. Regions of DNA sequence loss or gain were confirmed using forward and reverse hybridization and t-statistic analyses. RESULTS: Genomic aberrations were identified in 6 of 8 cases, including recurrent gain of sequence in chromosomes 12 [ish enh (12q22;12q23, 12q12;12q23)] in 3 of 8 cases and X [ish enh (X, Xp)] in 2 of 8 cases. CONCLUSIONS: DNA copy number changes occurred in a majority of PEL cases and are consistent with changes observed in other HIV lymphomas. These observations suggest that common genetic events may occur in HIV-associated lymphoid malignancies, but they probably do not contribute to the unique markers and morphology of PEL. Although individual genetic loci have been evaluated previously in a few PEL cases, to our knowledge this study represents the first reported genome-wide scan of copy number changes in these rare HIV-associated tumors.

Chromosome Aberrations↗
PubMed1998

Highly sensitive thromboplastins do not improve INR precision.

For determination of the international normalized ratio (INR), it has been suggested that "highly sensitive" thromboplastin reagents (International Sensitivity Index [ISI] < or = 1.2) provide the most consistent performance and minimize interlaboratory variability. We compared the INR values obtained from 69 specimens drawn from patients receiving long-term oral anticoagulant therapy, using four thromboplastin preparations (manufacturer-assigned ISI range of 0.96-1.10) and two automated photo-optical analyzers. Multivariate analysis of the INR response matrix (552 INR values) indicated that the eight reagent-coagulometer combinations did not produce equivalent INR values. Similar analysis indicated that INR values were not normalized when uncorrected prothrombin ratios or INR values, calculated after assignment of "local ISI values" to each thromboplastin reagent, were compared. The INR differences also seemed to be clinically significant because 17% to 29% of paired thromboplastin values were discordant when all INR values were assigned to one of four therapeutic categories used in oral anticoagulant therapy (< 2.0; 2.0-3.0; 3.0-4.5; or > 4.5). These differences in INR values obtained with two photo-optical coagulometers and four highly sensitive thromboplastin reagents suggest that the existing INR system has not achieved the goal of standardized prothrombin time values and does not support the recommendation to use only highly sensitive reagents for the regulation of oral anticoagulant therapy.

Anticoagulants↗
PubMed1998

Prolonged prothrombin time and activated partial thromboplastin time due to underfilled specimen tubes with 109 mmol/L (3.2%) citrate anticoagulant.

Underfilling of specimen tubes containing 129 mmol/L (3.8%) buffered citrate prolongs prothrombin time (PT) and activated partial thromboplastin time (APTT) values. We studied this phenomenon by using 109 mmol/L (3.2%) buffered citrate as the anticoagulant, anticipating some increase in tolerance to underfilling. Venous blood drawn from 12 healthy subjects and 30 patients receiving long-term oral warfarin therapy was mixed with 109 mmol/L buffered citrate solution in proportions equivalent to filling the collection tubes from 52% to 100% of capacity. Accurate PT values were obtained from normal specimens if the tubes were filled to 65% or more of capacity. Accurate PT results in the therapeutic range were obtained only with filling to 80% or more of capacity (using a "moderately sensitive" thromboplastin reagent, International Sensitivity Index [ISI] = 2.06) or 90% or more of capacity (using a "highly sensitive" thromboplastin reagent, ISI = 1.01). In contrast, APTT was much less tolerant to underfilling, with prolonged values observed in most specimens filled to less than 90% of capacity. No false low values were observed. Specimen tubes should be filled to at least 90% of capacity to avoid falsely elevated PT or APTT results, but values within the reference range may be acceptable even from underfilled tubes.

Adult↗
PubMed1998

The immunology of AIDS-associated lymphomas.

Lymphomas that occur in patients with human immunodeficiency virus (HIV) infection are predominantly of B-cell origin and subsets show evidence for Epstein-Barr virus (EBV) infection or chromosomal translocations in the c-myc locus. The only subset of lymphoma clearly related to the immunodeficiency caused by HIV infection (similar to transplantation-associated lymphomas) is the EBV+ primary central nervous system lymphoma. The systemic AIDS-related lymphomas (ARLs) represent a complex set of disease processes histologically categorized as large cell or small non-cleaved (Burkitt's-like) lymphomas. Molecular analyses of the ARLs have demonstrated polyclonal lymphomas as likely early representatives of monoclonal immunoglobulin (Ig)-expressing B-cell lymphomas. Variable region analysis of lymphoma-associated Ig has shown evidence for extensive somatic mutation with little evidence for appropriate affinity maturation. These observations suggest that abnormal control of B-cell maturation in response to polyclonal antigenic stimulation may play a central role in the pathogenesis of ARL. The recent finding of clonal HIV integrated within macrophages in a subset of early lymphomas also provides evidence for abnormalities outside the B-cell compartment playing roles in this disease. Overall, ARLs generally appear to be outgrowths of antigen-driven B-cells with significant growth control influence provided by abnormal T-cell and antigen-presenting cell processes.

Cell Transformation, Neoplastic↗
PubMed1997

VH gene use by HIV type 1-associated lymphoproliferations.

The pathogenesis of polyclonal HIV-associated lymphomas lacking traditional B cell cofactors (i.e., Epstein-Barr virus [EBV] infection, c-myc translocations) is poorly understood. A multistep pathogenesis model has been proposed in which polyclonal lymphomas represent an earlier stage in HIV-associated lymphomagenesis before the emergence of a dominant malignant clone. Chronically present antigens have been proposed as a likely stimulus for polyclonal B cell proliferation; if so, polyclonal lymphoma-associated immunoglobulins (Igs) should have molecular evidence of somatic hypermutation, a process by which antibody affinity maturation in response to chronic antigenic stimulation occurs. Molecular analyses of Ig heavy chain variable (V(H)) gene use by B cells in a polyclonal HIV-associated large cell lymphoma lacking EBV and c-myc rearrangement was undertaken. Eighteen randomly selected clones generated from RT-PCR yielded 15 unique V(H) sequences, all of which were most homologous to only three previously identified germline V(H)1 genes. Two sets of clones (consisting of three and two clones, respectively) had identical V(H) gene sequences, and one pair of clones had identical third complementarity determining regions (CDR3s) but different V(H) gene sequences; eight clones were <95% homologous to their most related germline V(H)1 genes. We compared these results with Ig V(H)1 gene use by B cells present in a reactive hyperplastic lymph node obtained from an HIV-1-infected individual. Fifteen clones randomly selected from RT-PCRs yielded 15 unique V(H)1 sequences, all of which were most homologous to 5 previously identified germline V(H)1 genes; 10 clones were <95% homologous to their most related germline gene. Binomial probability analysis revealed that only 1 of the 15 unique V(H)1 sequences derived from the polyclonal lymphoma (i.e., 7%), as compared with 5 of 15 unique V(H)1 sequences derived from the reactive lymph node (i.e., 33%), had a low probability of occurrence by random chance (p < 0.05). These data provide molecular evidence of polyclonality in an HIV-associated polyclonal lymphoma, demonstrate a qualitative difference in somatic hypermutations of Ig V(H) genes associated with malignant versus reactive B cell lymphoproliferations, and support an antigen-mediated multistep pathogenesis model of HIV-1-associated lymphomagenesis.

Amino Acid Sequence↗
PubMed1997

Extrapulmonary pneumocystosis.

Extrapulmonary pneumocystosis is an exceedingly rare complication of Pneumocystis carinii pneumonia (PCP). Prior to the advent of the human immunodeficiency virus type 1 (HIV-1) epidemic, only 16 cases of extrapulmonary pneumocystosis in individuals who were immunocompromised by a variety of underlying diseases had been reported. Since the beginning of the HIV-1 and related PCP epidemic, at least 90 cases of extrapulmonary pneumocystosis have been reported. This review briefly presents a history of the discovery of P. carinii and its recognition as a human pathogen, the controversy regarding its taxonomy, and the epidemiology of this organism. A more detailed analysis of the incidence of extrapulmonary pneumocystosis in HIV-1-infected individuals and its occurrence despite widespread prophylaxis for PCP with either aerosolized pentamidine or systemic dapsone-trimethoprim is presented. The clinical features of published cases of extrapulmonary pneumocystosis in non-HIV-1-infected individuals are summarized and contrasted with those in HIV-1 infected individuals. The diagnosis of extrapulmonary pneumocystosis is discussed, and because clinical microbiologists and pathologists are the key individuals in establishing the diagnosis, the characteristic microscopic morphology of P. carinii as its appears when stained with a variety of stains is presented and reviewed. The review concludes with a brief discussion of treatments for extrapulmonary pneumocystosis.

Classification↗
PubMed1996

Evidence for early B-cell activation preceding the development of Epstein-Barr virus-negative acquired immunodeficiency syndrome-related lymphoma.

To investigate the origin and pathogenesis of acquired immunodeficiency syndrome (AIDS)-related lymphoma (ARL), we studied 14 cases in which Epstein-Barr virus (EBV) infection was not an etiologic factor. By histology, 8 of the specimens were of the small noncleaved cell type and 6 consisted of the large diffuse cell type. Southern analysis using a J(H) probe was consistent with a monoclonal B-cell tumor in 13 cases. To characterize the expressed Ig genes, we performed reverse transcriptase-polymerase chain reaction (RT-PCR) and direct sequencing of PCR products. Eight cases expressed IgM and 1 case expressed IgG. V(H)3 genes were found in 5 cases, V(H)4 genes in 3 cases, V(H)1 genes in 2 cases, and a V(H)7 gene in 1 case. The nucleotide homology to known germline V(H) genes ranged from 80% to 97%, suggesting significant somatic diversification of expressed V(H) genes. The large proportion of V(H)3-expressing lymphomas in this series corresponds to the frequency of V(H)3-expressing B cells in the peripheral blood from healthy and (recent) human immunodeficiency virus (HIV)-seropositve individuals and contrasts with the V(H)3 clonal deficit observed in late stages of HIV infection. Similar to the Ig heavy chain genes, the corresponding Ig light chain genes showed significant deviation from known germline gene sequences. The large proportion of V(H)3-expressing lymphomas as well as the high degree of somatic deviation from germline suggest that these EBV-negative lymphomas might arise from antigen-selected expanded B-cell clones before transformation. Further support for this hypothesis is provided by sequential Ig sequence analysis in 1 patient with large-cell lymphoma. It was shown that 3 years before the diagnosis of axillary lymphoma, there existed several B-cell clones in this patient's bone marrow. One of these clones present in the bone marrow expressed the same rearranged V(H) gene as the axillary lymphoma. Taken together, the current findings from Ig gene analyses suggest that activation of B cells in the early phase of HIV infection may be a predisposing factor for subsequent B-cell transformation.

Amino Acid Sequence↗
PubMed1996

The natural history and molecular heterogeneity of HIV-associated primary malignant lymphomatous effusions.

Primary malignant lymphomatous effusions arising in individuals infected with the human immunodeficiency virus, type 1 (HIV-1) represent a rare subset of HIV-associated lymphomas. Previous studies have demonstrated that the malignant cells are monoclonal (as defined by rearrangement of the immunoglobulin gene), express cell surface CD38, and are infected with Epstein-Barr virus (EBV) and human herpes virus, type 8 (HHV-8). Despite these detailed molecular and immunophenotypic studies, clinical information on this disease entity is scant, prompting us to review the clinical features of eight cases seen at our institutions. All eight patients had total peripheral CD4+ lymphocytes < 200/microliter and presented with complaints related to body cavity distension. Routine laboratory values were nondiagnostic and yielded no prognostic information. Only two patients could tolerate and thus received chemotherapy with no obvious impact on their clinical course. The mean overall survival after diagnosis was 60 days (range 6-166 days). Four patients were examined at autopsy. The primary malignant lymphomatous effusion either was the immediate cause of death or contributed significantly to the death of only two. All four patients examined post mortem, however, had lymphomatous infiltration of serosal surfaces adjacent to the site of the primary malignant effusion. Molecular and immunologic studies performed on the malignant cells and effusion fluids revealed universal expression of cell surface CD38 and the presence of HHV-8 gene sequences, but in contrast with previous studies, only four had rearranged immunoglobulin genes or EBV present: IL-6 and IL-10 levels in the malignant effusion fluids were markedly elevated. In summary, this rare subset of HIV-associated lymphomas in our eight patients arose late in the course of HIV-associated disease, had a rapid clinical course, and was molecularly heterogeneous. A pathogenetic role for HHV-8 alone in this disease process is strengthened by our observation of four cases lacking EBV but containing HHV-8.

ADP-ribosyl Cyclase↗
PubMed1995

Cytokine expression in large cell lymphoma associated with acquired immunodeficiency syndrome.

Cytokine expression was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) in a retrospective sampling of 16 AIDS-associated large cell lymphomas (LCL). IL-6 receptor (IL-6R) and IL-10 expression was detected in a majority of the tumor specimens tested, IL-6 expression was detected in 5 of 16 lymphomas that also expressed IL-6R, suggestive of an autocrine mechanism of disease. A subset of tumor samples described as mixed immunophenotype contained large numbers of infiltrating T lymphocytes and macrophages. Immunoperoxidase staining of a representative tumor of mixed immunophenotype demonstrated the presence of HIV-infected macrophages that also stained with anti-IL-6. This finding suggests that IL-6 produced by nonlymphoid cells may act as a paracrine growth factor for tumor cells that express IL-6R. Although earlier studies of AIDs burkitt's lymphoma cell lines suggested that IL-10 expression required EBV infection, 7 of 12 AIDS LCLs that expressed IL-10 did so in the absence of EBV by EBER in situ hybridization. Because AIDS LCLs frequently express cell surface CD5, we speculate that IL-10 may act as an autocrine or paracrine growth factor for this class of lymphoma. These studies suggest that IL-6 and IL-10 are involved in the pathogenesis of AIDS-associated large cell and mixed immunophenotype lymphoma.

Base Sequence↗
PubMed1994

IgMs produced by two acquired immune deficiency syndrome lymphoma cell lines: Ig binding specificity and VH-gene putative somatic mutation analysis.

Two B-cell lines, 2F7 and 10C9, were established by single cell cloning from biopsies obtained from two acquired immune deficiency syndrome patients with Burkitt's lymphoma. Representation of the original tumors was verified by demonstration of (1) identical biallelic rearrangement of Ig genes for 2F7 and (2) shared idiotype for 10C9. Both cell lines displayed cell-surface Ig and secreted Ig (IgM lambda for 2F7, IgM kappa for 10C9). IgMs from both cell lines immunoprecipitated actin; in addition, 2F7 IgM lambda immunoprecipitated recombinant human immunodeficiency virus type 1 (HIV-1) gp 160. 2F7 IgM lambda did not react with other autoantigens (double-stranded and single-stranded DNA, actin, bovine serum albumin, IgG), whereas 10C9 IgM kappa reacted with human IgG. The 2F7 IgM heavy-chain variable region (VH) showed a 95% nucleotide homology with a previously sequenced VHIII germline gene, hv3019b9, whereas the 10C9 IgM VH showed a 95% homology with a previously sequenced VHIV germline gene, VH4.21. Use of minimally modified VH genes and demonstration of reactivity with chronically present antigens (ie, actin, HIV-1 gp 160, or human IgG) suggests that B cells in HIV-1-infected individuals proliferating in response to chronic antigenic stimulation may be at increased risk for lymphomagenesis.

Amino Acid Sequence↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗