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Biomedical subjects

E Ng

Publications and source records attributed to E Ng.

46 records · Page 3Linked to original sources

Synergistic actions of picibanil (OK-432) on recombinant interleukin-2 induction of tumor-infiltrating lymphocyte expansion, cytotoxicity, and phenotypic differentiation.

Tumor-infiltrating lymphocytes (TILs) comprise a subpopulation of lymphoid cells that infiltrate into growing tumors. These cells can be activated in vitro with recombinant interleukin-2 (rIL-2) to become highly cytotoxic against fresh tumor targets in vitro and against a variety of systemic metastases in vivo. OK-432 is a well-known inducer of NK cells and immune effector T cells. This study was designed to evaluate the effects of OK-432 on (a) the generation and (b) the cytotoxic potential of rIL-2-induced TILs. When TILs obtained from a murine colon adenocarcinoma (the MC-38 tumor) were cultured in complete media supplemented with 100 U of rIL-2/ml and 1.0 microgram of OK-432/ml, the number of TILs generated was greater than that seen with rIL-2 or OK-432 alone (number of TILs on day 15 of culture: 100 U of rIL-2/ml: 268 x 10(5) TILs; 1.0 microgram of OK-432/ml: 30 x 10(5) TILs; 100 U of rIL-2/ml + 1.0 microgram of OK-432/ml: 528 x 10(5) TILs). Higher concentrations of OK-432 had deleterious effects on TIL growth characteristics. TILs generated in 100 U of rIL-2 and 1.0 microgram of OK-432/ml of complete media demonstrated greater tumor lysis compared to rIL-2 alone (% lysis against MCA-102 target; 100 U of rIL-2/ml: 12%; 100 U of rIL-2/ml and 1.0 microgram of OK-432/ml: 50%; effector target ratio 20:1; p less than 0.001). Similar results were seen against the NK-sensitive YAC-1 lymphoma target.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Tumor-infiltrating lymphocytes cultured in recombinant interleukin-2: enhancement of growth, cytotoxicity, and phenotypic expression of cytotoxic T-cell antigens by cyclophosphamide given intravenously prior to tumor harvest.

Tumor-infiltrating lymphocytes (TILs) have potent antitumor effects in murine models of advanced disease. Although these cells are 50-100 times more potent than lymphokine-activated killer cells against micrometastases, their antitumor benefits are virtually nonexistent against large tumor burdens unless cyclophosphamide is added to the immunotherapy regimen. In an effort to determine the effects of cyclophosphamide on TILs obtained from tumor-bearing animals, we harvested tumors from animals having received either 0, 50, or 100 mg/kg cyclophosphamide intravenously and investigated the expansion, cytotoxicity, and phenotypic expression of these TILs co-cultured in vitro with recombinant interleukin-2. TILs obtained from animals given cyclophosphamide, demonstrated a greater fold expansion than TILs obtained from normal animals (mean fold expansion on day 59 of culture: 85, 400, and 150 for TILs obtained from animals given 0, 50, and 100 mg/kg cyclophosphamide, n = 3 consecutive experiments). In addition, these TILs demonstrated enhanced cytotoxicity compared to controls [effector to target ratio 4:1, day 16 TILs, % lysis: 24, 35, and 45%, cyclophosphamide 0, 50, and 100 mg/kg, respectively, against the MCA-102 sarcoma, natural killer (NK) insensitive tumor; 29, 38, and 56% against the YAC-1 lymphoma, NK sensitive tumor]. Similar results were seen with day 34 and day 59 TILs. When phenotypic analysis was performed, TILs obtained from animals given cyclophosphamide consistently demonstrated a greater percent expression of the Thy1.2 and Lyt-2 antigens up to day 59 of culture when the experiments were terminated. The NK cell marker 49H.8 was expressed on the majority of TILs and its expression did not change with respect to the cyclophosphamide concentration. The increase in TIL number and cytotoxicity seen with cyclophosphamide given intravenously before tumor harvest could have important ramifications for human immunotherapy with TILs.

Animals↗

Demonstration of Isospora belli by acid-fast stain in a patient with acquired immune deficiency syndrome.

Isospora belli, like Cryptosporidium sp., a sporozoan parasite of the small intestine, has been isolated from both immunodeficient and immunologically normal persons. In immunocompetent persons the infection may be asymptomatic; it frequently causes mild and self-limited diarrhea. The spectrum of the disease in persons with acquired immune deficiency syndrome is not well established. I. belli did not stain well with the methods usually used for intestinal protozoa and was difficult to see unstained. However, it stained well with the acid-fast technique used for Cryptosporidium sp. and was easily identified by such stains. A case of combined infection with Cryptosporidium sp. and I. belli is reported.

Acquired Immunodeficiency Syndrome↗

Renal puncture. A neglected aid in the diagnosis of renal masses.

Renal arteriography and nephrotomography are useful in distinguishing between renal neoplasmas and cysts. In the great majority of cases the well-vascularized neoplasm is readily identified. However, the arteriographic diagnosis of an "avascular lesion" is incomplete. These lesions make up a widely heterogeneous group, including the common simple renal cysts, avascular and degenerated neoplasms and congenital malformations. Percutaneous puncture of these "avascular" lesions under image-amplified fluoroscopy is a safe and simple means of obtaining further diagnostic information, often of decisive value.

Angiography↗

Efficacy and safety of adefovir dipivoxil with antiretroviral therapy: a randomized controlled trial.

CONTEXT: Adefovir dipivoxil is a nucleotide analog that has demonstrated effective antiretroviral activity against human immunodeficiency virus (HIV) with once-daily administration. OBJECTIVE: To determine if adefovir confers antiretroviral or immunologic benefit when added to stable antiretroviral therapy. DESIGN: Multicenter, 24-week, randomized, double-blind, placebo-controlled study. Enrollment was conducted from June 3, 1996, through May 6, 1997. SETTING: Thirty-three US HIV treatment centers. PARTICIPANTS: Of 1171 patients screened, 442 patients infected with HIV receiving stable antiretroviral therapy for at least 8 weeks with plasma HIV RNA greater than 2500 copies/mL and CD4+ cell count above 0.20 x 10(9)/L were randomized. INTERVENTION: Patients were randomized to receive either a single 120-mg/d dose of adefovir dipivoxil (n = 219) or an indistinguishable placebo (n = 223). All patients received L-carnitine, 500 mg/d. Open-label adefovir was offered after 24 weeks and was continued until the end of the study. MAIN OUTCOME MEASURES: Changes in HIV RNA from baseline, based on area under the curve and CD4+ cell levels, adverse events, and effect of baseline genotypic resistance on response to adefovir. RESULTS: Patients assigned to adefovir demonstrated a 0.4-log10 decline from baseline in HIV RNA compared with no change in the placebo group (P<.001), which continued through 48 weeks. CD4+ cell counts did not change. During the initial 24 weeks, elevated hepatic enzyme levels (P<.001), gastrointestinal tract complaints (P<.001), and weight loss (P<.001) were associated with use of adefovir. Between 24 weeks and 48 weeks elevations in serum creatinine occurred in 60% of patients, usually returning to baseline after discontinuation of adefovir. Patients with lamivudine or lamivudine and zidovudine resistance mutations demonstrated anti-HIV effects with adefovir (P< or =.01 vs placebo group). CONCLUSIONS: This study suggests that once-daily adefovir therapy reduces HIV RNA and is active against isolates resistant to lamivudine or lamivudine and zidovudine. Nephrotoxicity occurred when treatment extended beyond 24 weeks but was reversible.

Adenine↗

Orthodeoxia and platypnea secondary to a patent foramen ovale despite normal right-sided cardiac pressures.

Numerous cases of orthodeoxia and platypnea have been reported. Some have been found to be due to intracardiac shunts despite normal intracardiac pressures. In the case presented, a 79-year-old woman was noted to have orthodeoxia and platypnea secondary to a patent foramen ovale (PFO) despite normal intracardiac pressures. She recovered after closure of the PFO. The authors postulate that recent vertebral fractures and subsequent kyphosis, as well as a dilated thoracic aorta, altered intrathoracic relationships and may have led to a stream of venous return being directed across the PFO in the upright position, despite normal intracardiac pressures.

Aged↗

Immunohistochemical expression of p53 protein in invasive breast carcinoma: clinicopathologic correlations.

The results of immunohistochemical expression of p53 protein in 106 invasive breast cancers were correlated with conventional pathologic prognostic parameters. Archival formalin-fixed, paraffin-embedded tissue sections of these cases were stained with a monoclonal antibody (Ab-2), raised against p53 protein using a peroxidase-labelled streptavidin biotin kit. Fifty-six (53%) showed positive nuclear staining; 31 were considered weakly, 21 moderately and 4 strongly positive. Forty-three (77%) of these positive cases stained less than 50% of the tumor cells, with a significant association between intensity and proportion of nuclei stained (p<0. 05). p53 staining also correlated with histologic grade (p<0.005) but not with tumor size nor clinical stage (p>0.05). The follow-up data did not reveal any statistically significant survival advantage for patients with p53 negative tumors.

Biomarkers, Tumor↗