Production and characterization of monoclonal antibody against colon cancer associated antigen in Chinese]

Although many monoclonal antibodies have been made in human colon cancer, none of them are from the Chinese species. Recently, a colon cancer cell line CC-M2 established from a Chinese patient has been completely characterized and used as immunogen to produce monoclonal antibodies. Monoclonal antibodies were produced by standard hybridoma technique. The fusion rate was 95.8%. An isotype IgG1 of high proliferation named as Sam-2 was used in this study. The titers were measured around 10(4). Further studies on MoAb Sam-2 through indirect immunofluorescent and immunoperoxidase tests revealed its good specificity and sensitivity in colorectal cancer tissue. In CEA study, the result indicated that Sam-2 may react on a non-CEA related antigen. For further clinical application, the antigen was identified as a glycoprotein by chemical resistant test. In preliminary studies using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting techniques, Sam-2 could recognize two closed antigens or a dimer antigen with molecular weight 25.2 and 27 Kd respectively.     

In vivo induction of CD4+ T cell responses by antigens covalently linked to synthetic microspheres does not require adjuvant

Macrophages, dendritic cells or B lymphocytes have been shownto play a major role in the presentation of soluble antigensto CD4⁺ T cells. In contrast, the capacity of these cells topresent particulate antigens such as bacterial or parasiticantigens to T cells remains controversial. To investigate thisquestion, well defined particulate antigens were prepared bycovalent linkage of proteins or peptides to 1 µm in diametersynthetic microspheres. The T cell immunogenicity of such particulateantigens was analyzed in vitro and in vivo. In vitro, a solubleprotein such as hen egg lysozyme (HEL) coupled to beads stimulateda strong proliferative T cell response of lymph node cells fromHEL-primed mice or of specific T cell hybridomas. HEL coupledto beads was presented to the specific T cell hybridomas bysplenocytes or by peritoneal macrophages, but not by lymphomaB cells. Immunization of mice with several different proteinantigens or with a synthetic peptide covalently linked to beadsinduced strong CD4⁺ T cell responses in the absence of adjuvant.The strong in vivo immunogenicity of proteins coupled to beadsdid not result from a non-specific adjuvant effect of beadssince covalent linkage of the antigen to beads was strictlyrequired to induce T cell responses in the absence of adjuvant.In vivo treatment by carrageenan showed that macrophages arerequired for the in vivo stimulation of T cell responses bythese particulate antigens. Thus, these results demonstratedthe role of phagocytic cells, especially macrophages, for invivo presentation of particulate antigens. These particulateantigens represent an interesting approach for the developmentof new vaccines, and for the in vivo analysis of the role ofvarious antigen presenting cells in T cell activation and differentiation.     

The bioavailability and nonlinear pharmacokinetics of MK-679 in humans

MK-679 (R(?)-3-((3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)(3-(dimethylamino)-3-oxopropyl)thio)methyl)thio(propanoic acid) is a potent and specific LTD₄-receptor antagonist. The disposition of MK-679 was investigated in a three-way crossover study in 12 healthy males receiving single intravenous doses of 75, 250, and 500 mg of MK-679. A greater than proportional increase in the area under the plasma concentration—time curve of MK-679 was observed with increase in dose. The plasma concentration data for each subject fitted well to the differential equations for a two-compartment model with linear tissue distribution and Michaelis-Menten elimination from the central compartment, indicating that the elimination of MK-679 in humans is saturable. In a previous study, the disposition of MK-679 in humans was also dose-dependent when given together with its S(+)-isomer, L-668,018. Thus, the disposition of MK-679 in humans is dose-dependent regardless of the presence of its stereoisomer. Also, the bioavailability of MK-679 was determined in six healthy males receiving simultaneously an oral dose of 250 mg of MK-679 and intravenous infusion of 1 mg ¹⁴C-MK-679. Results of this study indicate that the oral bioavailability of MK-679 is nearly quantitative.     

Akathisia as a side effect of antipsychotic treatment with quetiapine in a patient with Parkinson's disease.

Due to its low profile for extrapyramidal side-effects, quetiapine has become an alternative to clozapine in the treatment of dopamimetic psychosis in patients with Parkinson's disease (PD). We describe the case of a patient with PD who developed severe akathisia, a common complication with classical antipsychotics, with quetiapine.     

Carotid-cavernous sinus fistula associated with a primitive trigeminal artery

Carotid-cavernous sinus fistulas are not rare, but they have never been reported in association with persistent primitive trigeminal artery. We recently encountered such a case. The Jaeger-Hamby procedure was employed, with mandatory occlusion of the primitive trigeminal artery.