Biomedical subjects
Publications and source records attributed to D J Demetrick.
We describe a case of a 68-yr-old man who died as a consequence of a massive bleed from esophageal varices. At autopsy, a pancreatic pseudocyst that communicated directly with the splenic vein was found. Histology confirmed that material from the pseudocyst had embolized to the peripheral portal veins, occluding many of them.
Murine monoclonal antibodies (MAbs) were produced with reactivity to human malignant melanoma. Six MAbs, 3 of the IgGI (LS113, LS140, LS152) and 3 of the IgG2a (LS59, LS62, LS76) subclasses, were selected for their binding, with an identical pattern of reactivity, to a novel melanoma-associated antigen. As characterized by the enzyme-linked immunosorbent assay (ELISA), these MAbs were found to be positive on n-octyl-beta-D-glucopyranoside extracts of all 10 melanoma cell lines tested and on extracts of 22 metastatic melanoma tumors. The antibodies had minimal reaction with a panel of 14 normal adult tissue extracts. A degree of cross-reactivity was observed with 50% of 39 non-melanoma tumor extracts. The results obtained with the ELISA on cell line and tissue extracts were duplicated using the ABC method of peroxidase staining. The pattern of cross-reactivity, as demonstrated by the intense staining of paraffin-embedded and frozen tissue sections of normal, benign and malignant tissues, defines the recognized protein as a neuroglandular antigen (NGA). Immunoadsorbents made with the antibodies were used to purify the antigen shed from cultured melanomas. All 6 MAbs recognized this purified antigen while 5 other antimelanoma antibodies did not react with it. On gel electrophoresis this antigen is a highly glycosylated glycoprotein with a protein core of 21 kDa.
We have previously examined a case of varicella embryopathy (VE) occurring in a 41-week gestational age infant, showing some of the most severe lesions reported to be associated with the syndrome to date. A previous survey of the postmortem tissue with two anti-varicella zoster antibodies was negative. It was hypothesized that if varicella-zoster virus (VZV) was associated with VE, a latent viral infection might be expected, similar to that occurring in adults infected with VZV. Subsequently, an attempt was made to identify DNA encoding three separate and specific VZV genes using the highly sensitive polymerase chain reaction from formalin-fixed tissues of the central nervous system including cerebral cortex, cerebellum, and brainstem, in addition to frozen tissue of liver, adrenal, and thymus. Although amplifications utilizing primers for a normal human DNA sequence (ME491) demonstrated the ability of the samples to serve as a target for the PCR, none of the samples contained amplifiable VZV DNA. Substitution of biotin 11-dUTP in the PCR and subsequent detection of the biotinylated amplimers resulted in a large increase of the sensitivity of the PCR amplimer detection, but still failed to detect the presence of VZV DNA in the samples. The most likely explanation for these findings suggests a complete destruction of fetal tissue tropic for VZV with a subsequent inability for a latent VZV infection to be established.
Recent advances in the knowledge of molecular events of cell growth and differentiation have provided considerable gains to the understanding of neoplasia. Along with this understanding, molecular biology has yielded many new techniques of great potential for diagnostic use. This review illustrates, in general terms, current models of gene regulation, intracellular signal transduction, and the regulation of cell division that are relevant to pediatric pathologists. These concepts are used to examine the molecular pathology of three pediatric tumors: retinoblastoma, Wilms' tumor, and neuroblastoma. In addition, molecular biology techniques potentially useful to pediatric pathologists are discussed, with examples of some possible applications of these techniques. Hopefully, this review portrays the relevance of molecular biology to pediatric pathologists and serves as a useful guide to the interpretation of the molecular pathology literature.