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M McKnight

Publications and source records attributed to M McKnight.

At least 19 recordsLinked to original sources

Identification of the immunoreactive peptide sequence for AgSK1, an adenocarcinoma-restricted antigen.

SK1, a human immunoglobulin M (IgM) monoclonal antibody was derived from regional nodal lymphocytes of a Dukes B colon carcinoma patient. The antigen recognized by the human monoclonal antibody (HuMab) SK1, termed AgSK1, was shown to be a two-chain glycoprotein with an apparent molecular weight range of 42-46 kDa and preferentially expressed by human adenocarcinomas, particularly human gastrointestinal malignancies. To identify the gene encoding the AgSK1 antigenic epitope, a cDNA expression library constructed in lambda gt22A using mRNA from the colon carcinoma cell line HT29 was screened and one of the isolated clones encoding a 1.5-kb cDNA, which showed strong immunoreactivity with HuMab SK1, was selected for further analysis. This clone consisted of an amino terminal open reading frame of 54 amino acids and the carboxyl terminal 20 amino acids of this protein coding region contained the antigenic epitope recognized by HuMab SK1.

Adenocarcinoma↗

Lithium dosage and leukocyte counts in psychiatric patients.

OBJECTIVE: To evaluate differences in leukocyte counts among patients treated with either lithium alone, antipsychotic medications alone, or a combination of both. DESIGN: Retrospective study. SETTING: Long-stay psychiatric hospital. PATIENTS: Patients admitted between 1990 and 1993, and treated with lithium for at least 1 week and/or with antipsychotic medication for at least 2 weeks. Excluded from the study were those patients for whom complete blood counts at baseline and during therapy were not available, and those patients whose blood picture could primarily be accounted for by extraneous factors. Included in the study were 38 patients treated with lithium alone, 207 patients receiving antipsychotic medications alone, and 71 patients receiving both. OUTCOME MEASURES: Leukocyte, lymphocyte and granulocyte counts. RESULTS: Patients treated with lithium alone had significantly higher mean leukocyte and granulocyte counts than those treated with antipsychotic medication alone (analysis of variance, p < 0.05). None of the patients receiving lithium alone showed leukopenia. The dosage of lithium was significantly correlated with leukocyte count (r = 0.25, 95% confidence interval [CI] 0.14 to 0.35, p < 0.001,) and granulocyte count (r = 0.27, 95% CI 0.16 to 0.38, p < 0.001), but not with lymphocyte count (r = 0.06, p = 0.286, 95% CI -0.05 to 0.17). CONCLUSIONS: Lithium therapy is associated with higher leukocyte and granulocyte levels in psychiatric patients. This leukocytotic effect of lithium may be dose dependent.

Adult↗

Characterization of human IgG1 monoclonal antibody against gangliosides expressed on tumor cells.

A human IgG1.k monoclonal antibody (MAb) designated GMA1 was developed by fusing pooled lymph node lymphocytes from cancer patients with the human lymphoblastoid cell line, SHFP-1. The GMA1 MAb reacted with several melanoma and neuroblastoma cell lines. Normal tissue derived from human brain and tumor-cell lines derived from colon, ovary, and breast were not reactive. FACS analysis performed using live cells demonstrated that the antibody recognizes a cell-surface antigen. Enzyme immunoassay (EIA) and thin layer chromatography (TLC) immunostaining with purified gangliosides indicated that the antibody has specificity for the major tumor associated gangliosides GD3, GM3, and GD2. GMA1 heavy and light chain genes were isolated by RT-PCR and a recombinant derivative of this human antibody was expressed in Chinese hamster ovary (CHO) cells. High-level antibody synthesis and secretion was achieved using a vector designed to maximize expression. FACS analysis and TLC immunostaining indicated recombinant GMA1 reacted with human tumor cell lines and gangliosides GD3, GM3, GD2 in a manner similar to the antibody produced by the hybridoma cell line, demonstrating that the specificity of the antibody was not altered during molecular cloning.

Amino Acid Sequence↗

Cloning and expression of the human tumor-specific antibody GM4.

The human monoclonal antibody GM4 was generated by fusing pooled lymphocytes from cancer patients with the lymphoblastoid cell line SHFP-1. Immunohistochemical staining of tumor and normal tissue indicated that this human IgG4 antibody preferentially reacted with melanomas and neuroblastomas. In this study, we demonstrate that GM4 recognizes a "vimentin-like" peptide sequence that we have termed AgGM4. To generate a recombinant derivative of this human antibody, we isolated and expressed the complete heavy and light chain genes. The entire coding sequence for both the heavy and light chains was isolated by RT-PCR using a set of degenerate 5' signal sequence specific primers and a 3' constant region primer. High level antibody synthesis and secretion was achieved in Chinese hamster ovary (CHO) cells using a vector designed to maximize expression. Western blot and FACS analysis indicated recombinant GM4 reacted with human tumor cell lines and AgGM4 in a manner similar to the antibody produced by the hybridoma cell line, demonstrating that the specificity of the antibody was not altered during molecular cloning.

Amino Acid Sequence↗

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Communication↗