Community panel discussions: from research to community action.

HYPERTENSION AND CARDIOVASCULAR DISEASE are increasing among minorities. Participants at the workshop on the Epidemiology of Hypertension in Hispanic Americans, Native Americans, and Asian/Pacific Islander Americans voiced a need to intensify a systemic approach for community-based strategies to guide prevention, treatment, and control. To answer this need, a panel addressed recommended community-based strategies from inclusion of community members in the research process to implementation and application of findings for community action. Recommended strategies include encouraging close cooperation and data sharing between investigators and community groups; including differences in culture, heritage, and local influences in hypertension research; training and working with minority researchers and health care professionals; and intensifying comprehensive and culturally appropriate education programs that focus on prevention, treatment, and control of hypertension. This article contains a summary of key areas of emphasis, as well as implementation strategies to decrease hypertension and other cardiovascular diseases in specific ethnic groups.

Quantitation of reduced disulfide groups in monoclonal antibodies using 5-iodoacetamidofluorescein: a novel size exclusion-HPLC technique.

The interference of stannous in the quantitation of sulfhydryl in pretreated MAb using the Ellman's method is described. A HPLC method which effectively overcomes the interference by stannous ion in measuring sulfhydryls by the commonly used Ellman's technique has been developed. The method involves reacting the reduced monoclonal antibody with 0.1 M EDTA followed by the sulfhydryl specific reagent 5-iodoacetamidofluorescein and incubating the mixture at 37 degrees C for 1.0-1.5 h. The 5-IAF labeled protein is separated from the unbound free 5-IAF and its secondary degraded products by size exclusion HPLC using a TSK G3000 SWXL column. The method allows quantitation of MAb sulfhydryl present as monomeric MAb, aggregates and fragments and is a major improvement over the spectroscopic techniques.

Immunization of breast cancer patients using a synthetic sialyl-Tn glycoconjugate plus Detox adjuvant.

We have synthesized various formulations that have potential for active specific immunotherapy (ASI) of human cancers. Sialyl-Tn (STn) is a potentially important target structure for ASI because its expression on mucins is a strong, independent predictor of poor prognosis, suggesting that it may have functional significance in the metastatic process. In this first pilot study of synthetic sialyl-Tn hapten conjugated to keyhole limpet hemocyanin (STn-KLH), with Detox adjuvant, toxicity and humoral immunogenicity were assessed in 12 patients with metastatic breast cancer. Toxicity was minimal, restricted to local cutaneous reactions (apart from transient nausea and vomiting following single low-dose cyclophosphamide treatment). Using STn-conjugated human serum albumin in a solid-phase enzyme-linked immunosorbent assay, it was shown that all patients developed IgM and IgG specific for the synthetic STn hapten. Following immunization, most patients were shown to develop increased titres of complement-mediated cytotoxic antibodies, partially inhibited by synthetic STn hapten, but not by the related TF hapten. We also detected IgM and IgG antibodies reactive with natural STn determinants expressed on ovine submaxillary mucin, the STn specificity of this reactivity being confirmed by hapten inhibition. Evaluation of clinical efficacy in a small pilot study is difficult. Five patients are alive 12 or more months after entry, and another 4 patients are alive 6 or more months after entry into the study. All 3 patients with known widespread bulky disease progressed despite ASI, 2 having died from widespread cancer. Two patients had partial responses, each lasting 6 months. While several patients had disease stability for 3-10 months, 1 patient with pulmonary metastases remains stable 15 months after entry into the program.

Molecular characterization of three mutations in katG affecting the activity of hydroperoxidase I of Escherichia coli.

Hydroperoxidase I (HPI) of Escherichia coli is a bifunctional enzyme exhibiting both catalase and peroxidase activities. Mutants lacking appreciable HPI have been generated using nitrosoguanidine and the gene encoding HPI, katG, has been cloned from three of these mutants using either classical probing methods or polymerase chain reaction amplification. The mutant genes were sequenced and the changes from wild-type sequence identified. Two mutants contained G to A changes in the coding strand, resulting in glycine to aspartate changes at residues 119 (katG15) and 314 (katG16) in the deduced amino acid sequence of the protein. A third mutant contained a C to T change resulting in a leucine to phenylalanine change at residue 139 (katG14). The Phe139-, Asp119-, and Asp314-containing mutants exhibited 13, less than 1, and 18%, respectively, of the wild-type catalase specific activity and 43, 4, and 45% of the wild-type peroxidase specific activity. All mutant enzymes bound less protoheme IX than the wild-type enzyme. The sensitivities of the mutant enzymes to the inhibitors hydroxylamine, azide, and cyanide and the activators imidazole and Tris were similar to those of the wild-type enzyme. The mutant enzymes were more sensitive to high temperature and to beta-mercaptoethanol than the wild-type enzyme. The pH profiles of the mutant catalases were unchanged from the wild-type enzyme.

Equine parvovirus: initial isolation and partial characterization.

A viral agent was isolated from the fetal liver of an aborted equine fetus. The isolate hemagglutinated red blood cells from guinea pig, rhesus monkey and rooster. By hemagglutination inhibition tests, the isolate was shown to be antigenically distinct from parvoviruses of bovine and canine origin. Specific hemagglutination inhibiting antibody against the viral isolate was exhibited by 26 of 136 horse sera tested. The isolated virus showed properties compatible with those of an autonomous parvovirus including size, morphology, stability to ether treatment and heating to 56 degrees C, the presence of a 5300 base DNA genome, characteristic protein composition and density (1.405 g/mL). The virus was classified as an equine parvovirus.