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Biomedical subjects

L Cheung

Publications and source records attributed to L Cheung.

7 recordsLinked to original sources
PubMed1992

Failure to detect vertical transmission of hepatitis C virus.

OBJECTIVE: To search for transmission of hepatitis C virus (HCV) from infected mothers to their infants. DESIGN: Prospective clinical, serologic, and molecular biologic follow-up (at least 3 months) of the infants of mothers with anti-HCV antibody. SETTING: A county hospital providing primary and referral care in high-risk obstetrics (perinatology). PATIENTS: Twenty-three mothers with anti-HCV antibody and their 24 infants. METHODS: An enzyme-linked immunosorbent assay (EIA) and a four-antigen recombinant immunoblot assay (RIBA) were used to test for anti-HCV antibody; serum HCV RNA was measured in two independent laboratories by reverse transcription and polymerase chain reaction (PCR) using nested primers in the 5'-noncoding region. Infant samples were tested for HCV RNA by PCR at delivery and after 3 to 6 months of follow-up. Each sample was tested at least four times in two independent laboratories. RESULTS: Twenty-nine of 648 mothers (4.5%; 95% Cl, 3.0% to 6.4%) had anti-HCV antibody; these women had 30 babies. Twenty-three mothers and their 24 babies were followed at least 3 months (mean follow-up, 52 weeks). Of the 23 mothers, 21 (91%; Cl, 72% to 99%) had a reactive RIBA; one woman had an indeterminate RIBA and was positive for HCV RNA by PCR. In 16 of 23 mothers (70%; Cl, 47% to 87%), PCR yielded a positive result in both laboratories. The mean maternal alanine aminotransferase (ALT) level was 1.6 times the normal value. All the babies had anti-HCV antibody in cord-blood samples, but antibody disappeared or diminished in strength in interval samples, and no infant had evidence of active production of anti-HCV antibody. Only 1 of 24 (4%; Cl, 0.1% to 21%) cord-blood samples was HCV RNA positive, and none of 24 (0%; Cl, 0% to 14%) follow-up samples was positive for HCV RNA by PCR in either laboratory. Four mothers and one baby had antibody to HIV. CONCLUSIONS: Infant anti-HCV antibody is most likely acquired passively in utero, and vertical transmission of HCV is uncommon.

Female↗
PubMed1991

Clinical pharmacology, metabolism, and tissue distribution of 90Y-labeled monoclonal antibody B72.3 after intraperitoneal administration.

B72.3 is a murine monoclonal antibody that recognizes a high-molecular-weight tumor-associated glycoprotein (TAG-72). Nine patients with TAG-72-positive ovarian carcinoma or papillary serous carcinoma of the peritoneum received an intraperitoneal infusion of 2, 4, or 10 mg B72.3 labeled with 0.5-1.2 (mean, 0.8) mCi 90Y. All patients had laparotomy, with multiple tissue and tumor samples removed 3-7 days later. The concentration of the total 90Y label in peritoneal fluid cleared with an extrapolated half-life of 68.6 +/- 4.5 hours. A low-molecular-weight 90Y-labeled species of metabolite was identified by high-performance liquid chromatography. The concentration of this low-molecular-weight species initially increased in the peritoneal fluid, with a half-life of 0.9 hour, and was rapidly cleared from the peritoneal cavity, with a half-life of 23.1 hours. Both the 90Y-labeled metabolite and the 90Y-labeled B72.3 were absorbed into the plasma, with half-lives of 16 +/- 2.2 hours and 25 +/- 5 hours, respectively. The clearance half-lives for these agents in plasma were 25 +/- 3 hours for the metabolite and 42 +/- 17 hours for B72.3. Approximately 8%-11% of the total injected 90Y label appeared in urine over 72 hours. Most of the label (about 70%) was present as the 90Y-labeled metabolite, but about 30% of the 90Y label in urine appeared identical to the authentic 90Y-labeled B72.3 standard when assayed by chromatography. Tissue distribution studies showed that normal tumor tissue and omentum contained the highest content of 90Y (about 0.017% of the injected dose per gram), followed in descending order by liver, normal lymph nodes, peritoneum, bone, and fascia. The lowest concentrations of 90Y were found in rectus abdominis muscle, bone marrow, and fat. There was substantial heterogeneity in the uptake of the 90Y label into tumor sites among patients and among different sites within the same patient. No correlation could be demonstrated between the TAG-72 content and the amount of 90Y label found in tumor sites. Preliminary radiation dosimetry estimates suggest that the tumor sites received about 82.8 cGy for each millicurie of 90Y administered. Thus, if an adequate total radiation dose can be achieved, 90Y-labeled B72.3 should be therapeutically useful for treating diffuse intraperitoneal disease.

Adult↗
PubMed1991

Decrease in serum hepatitis C viral RNA during alpha-interferon therapy for chronic hepatitis C.

OBJECTIVE: To assess the effect of alpha-interferon therapy on hepatitis C viral RNA in serum of patients with chronic hepatitis C. DESIGN: Retrospective testing for hepatitis C viral (HCV) RNA and antibody to the hepatitis C virus (anti-HCV) of stored serum samples from a randomized, double-blind, placebo-controlled trial of alpha-interferon therapy. SETTING: Warren Grant Magnuson Clinical Center of the National Institutes of Health, a tertiary referral center. PATIENTS: Forty-one patients with chronic non-A, non-B hepatitis were entered in this trial. INTERVENTIONS: Twenty-one patients were treated with alpha-interferon, and 20 patients were treated with placebo for 6 months. Seventeen placebo recipients were then treated with alpha-interferon for up to 1 year. METHODS: Samples were tested for anti-HCV by enzyme-linked immunosorbent assay. Hepatitis C viral RNA was detected in serum using the polymerase chain reaction. Titers of both antibody and RNA were determined by serial end-point dilution. MAIN RESULTS: At entry into the trial, 37 (90%) of 41 patients had anti-HCV and 39 (95%) had HCV RNA in serum. Anti-HCV titers decreased slightly with treatment. Serum levels of HCV RNA decreased in all patients who responded to alpha-interferon therapy with improvements in serum aminotransferases; in 17 of 21 responders (81%; 95% Cl, 58% to 95%) HCV RNA became undetectable. In contrast, in only 2 of 16 (12%; Cl, 2% to 38%) patients who did not respond to treatment did HCV RNA become undetectable. In 19 patients treated during the preliminary 6-month period with placebo, HCV RNA remained detectable. Finally, in the 11 patients who relapsed when treatment was stopped, HCV RNA reappeared in the serum, but in 4 of 7 patients with a sustained improvement in serum aminotransferases, HCV RNA remained undetectable. CONCLUSIONS: These results indicate that the clinical and serum biochemical response to alpha-interferon in chronic hepatitis C is associated with a loss of detectable HCV genome from serum.

Base Sequence↗
PubMed1991

A potent and specific immunotoxin for tumor cells expressing disialoganglioside GD2.

Monoclonal antibody 14G2a (anti-GD2) reacts with cell lines and tumor tissues of neuroectodermal origin that express disialoganglioside GD2. mAb 14G2a was coupled to the ribosome-inactivating plant toxin gelonin with the heterobifunctional cross-linking reagent N-succinimidyl-3(2-pyridyldithio)propionate. The activity of the immunotoxin was assessed by a cell-free translation assay that confirmed the presence of active gelonin coupled to 14G2a. Data from an enzyme-linked immunosorbent assay demonstrated the specificity and immunoreactivity of the 14G2a-gelonin immunotoxin, which was identical to that of native 14G2a. Assays for complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) revealed that these functional properties of the native 14G2a antibody were also preserved in the 14G2a-gelonin immunotoxin. The gelonin-14G2a immunotoxin was directly cytotoxic to human melanoma (A375-M and AAB-527) cells and was 1000-fold more active than native gelonin in inhibiting the growth of human melanoma cells in vitro. The augmentation of tumor cell killing of 14G2a-gelonin immunotoxin was examined with several lysosomotropic compounds. Chloroquine and monensin, when combined with 14G2a-gelonin immunotoxin, augmented its cytotoxicity more than 10-fold. Biological response modifiers such as tumor necrosis factor alpha and interferon alpha and chemotherapeutic agents such as cisplatinum and N,N'-bis(2-chloroethyl)-N-nitrosourea (carmustine) augmented the cytotoxicity of 14G2a-gelonin 4- to 5-fold. The results of these studies suggest that 14G2a-gelonin may operate directly by both cytotoxic efforts and indirectly by mediating both ADCC and CDC activity against tumor cells; thus it may prove useful in the future for therapy of human neuroectodermal tumors.

Antibodies, Monoclonal↗
PubMed1991

A specific and potent immunotoxin composed of antibody ZME-018 and the plant toxin gelonin.

Murine monoclonal antibody ZME-018 recognizes a 240 Kda glycoprotein present on the surface of most human melanoma cells and on over 80% of human biopsy specimens tested. Gelonin is a ribosome-inactivating plant toxin similar in nature and rivaling the activity of ricin A chain. ZME-018 was coupled to purified gelonin using the reagents SPDP and 2-iminothiolane. The ZME-gelonin conjugate was purified by S-300 Sephacryl and Blue Sepharose chromatography, removing unreacted gelonin and antibody, respectively. PAGE analysis showed that ZME was coupled to 1, 2, or 3 gelonin molecules. The ZME-gelonin conjugate was 10(6)-fold more active than gelonin itself in inhibiting the growth of log-phase human melanoma cells in culture. The immunoconjugate was not cytotoxic to antigen negative T-24 (human bladder carcinoma) cells. Treatment of melanoma cells with recombinant IFN-alpha or TNF substantially augmented the cytotoxicity of the immunoconjugate while treatment with IFN-gamma had a minor effect. Using the human tumor colony assay of melanoma cells obtained from fresh biopsy specimens, greater than 90% growth suppression was observed in 2 of 4 samples tested at a concentration of 250 ng/ml. In addition, 25% growth suppression was observed with a third sample tested, and no growth suppression was observed in 1 sample. Thus, clonogenic melanoma cells are sensitive in vitro to the cytotoxic activity of this immunotoxin at concentrations which we presume are pharmacologically relevant.

Antibodies, Neoplasm↗
PubMed1991

Antibody-mediated delivery of tumor necrosis factor (TNF-alpha): improvement of cytotoxicity and reduction of cellular resistance.

Recombinant human tumor necrosis factor-alpha (TNF-alpha) is a macrophage-derived, non-glycosylated (17 kDa) peptide that has a remarkably broad range of biological and immunological effects including antiviral action and cytotoxic and cytostatic effects. TNF-alpha was coupled to murine antibody ZME-018, which recognizes a 240 kDa glycoprotein present on over 80% of melanoma cells. The crosslinking was accomplished using the heterobifunctional crosslinking reagent, N-succimindyl 3-(2-pyridyldithio)proprionate (SPDP). After purification on gel-permeation and affinity columns, the resulting eluate was analyzed by non-reducing SDS-PAGE, which confirmed that the product was a mixture of ZME-018 coupled to one or two TNF-alpha molecules. The ZME-TNF conjugate was titered against murine L-929 cells to demonstrate the presence of active TNF. ELISA of the conjugate against target BRO human melanoma cells or non-target T-24 cells demonstrated specific binding only to target cells. Melanoma BRO cells were killed by the immunoconjugate (IC50 of 10 units/mL), whereas native TNF-alpha had no effect at concentrations greater than 50,000 units/mL. The immunoconjugate and TNF-alpha were inactive against T-24 non-target cells. These studies suggest that the sensitivity of cells to TNF was dramatically augmented by specific antibody mediated delivery to tumor cells.

Animals↗