Showing papers by "Gary A. Silverman published in 1995"
TL;DR: The cloning of the SCCA gene from normal genomic DNA found two genes that suggested that the neutral form of the protein was encoded by SCC a1 and the acidic form was encode by S CCA2, and further characterization of the region should determine whether the differential expression of theSCCA genes plays a causal role in development of more aggressive squamous cell carcinomas.
Abstract: The squamous cell carcinoma antigen (SCCA) is a member of the ovalbumin family of serine proteinase inhibitors (serpins). A neutral form of the protein is found in normal and some malignant squamous cells, whereas an acidic form is detected exclusively in tumor cells and in the circulation of patients with squamous cell tumors. In this report, we describe the cloning of the SCCA gene from normal genomic DNA. Surprisingly, two genes were found. They were tandemly arrayed and flanked by two other closely related serpins, plasminogen activator inhibitor type 2 (PAI2) and maspin at 18q21.3. The genomic structure of the two genes, SCCA1 and SCCA2, was highly conserved. The predicted amino acid sequences were 92% identical and suggested that the neutral form of the protein was encoded by SCCA1 and the acidic form was encoded by SCCA2. Further characterization of the region should determine whether the differential expression of the SCCA genes plays a causal role in development of more aggressive squamous cell carcinomas.
262 citations
TL;DR: Human macrophage metalloelastase (HME) is a recent addition to the matrix metalloproteinase (MMP) family that was initially found to be expressed in alveolar macrophages of cigarette smokers and analysis of the structure and location of the gene was performed to understand more about HME expression.
156 citations
Journal Article•
TL;DR: The results suggest that the variability in clinical phenotype may be more representative of a contiguous-gene syndrome with a baseline deficit of 18q22.2-qter than of the loss of a single critical region within 18q21.3.
Abstract: The 18q- syndrome is one of several terminal deletion disorders that occur in humans. Previous G-banding studies suggest that the loss of a critical band, 18q21.3, results in mental retardation, craniofacial anomalies, and metabolic defects. However, it is difficult to reconcile the consistent loss of a single region with the large variability in clinical phenotype. The purpose of this study was to reassess the extent of chromosomal loss in a cohort of 17 18q- syndrome patients by using fluorescent-activated chromosome sorting, PCR, and FISH. Bivariate flow karyotypes revealed heterogeneity among the deletions; they ranged in size from 9 to 26 Mb. To confirm this heterogeneity at a molecular level, deleted and normal chromosomes 18 of six patients were collected by flow sorting, preamplified by random priming, and assayed for marker content by the PCR. This analysis defined five unique breakpoints among the six patients. We conclude that the terminal deletions in the 18q- syndrome occur over a broad region spanning the interval from 18q21.2 to 18q22.2. Our results suggest that the variability in clinical phenotype may be more representative of a contiguous-gene syndrome with a baseline deficit of 18q22.2-qter than of the loss of a single critical region within 18q21.3.
44 citations
TL;DR: There have been concerted efforts in the past 5 years to create a high-resolution genetic map for all of the human chromosomes that contain markers that can be analyzed using the polymerase chain reaction technique, but most published genetic maps contain minimal information about the physical location of the markers.
9 citations
TL;DR: Whether the sensitivity of the PCR could be used to detect sequences specific to chromosomes discriminated and purified by flow cytometry was determined and the random amplification scheme provided enough template DNA from a single sort to perform > 1000 PCR assays.
3 citations
TL;DR: Two protocols for carrying out homologous recombination in Saccharomyces cerevisiae are described; one relies on the meiotic phase of the yeast cycle, while the other utilizes the mitotic phase ofThe yeast life cycle.
Abstract: Despite the relatively large cloning capacity of YACs, many genomic regions or individual genes are not cloned intact, but are represented as a collection of overlapping clones or contigs. Fortunately, the relatively high frequency and fidelity of homologous recombination in Saccharomyces cerevisiae can be used to reconstruct intact genes within a single clone by splicing together overlapping DNA segments. This unit describes two protocols for carrying out such homologous recombination; one relies on the meiotic phase of the yeast cycle, while the other utilizes the mitotic phase of the yeast life cycle. Despite the relatively large cloning capacity of YACs, many genomic regions or individual genes are not cloned intact.