Aizen J. Marrogi

Role of Borrelia burgdorferi in the pathogenesis of morphea/scleroderma and lichen sclerosus et atrophicus: a PCR study of thirty‐five cases

Morphea (localized scleroderma), and lichen sclerosus et atrophicus (LSA) share common features with acrodermatitis chronica atrophicans (ACA), a known chronic form of borreliosis. These include similar histologic findings such as diffuse dermal fibrosis. These observations have led several investigators to consider the possibility of Borrelia burgdorferi (Bb) as a common etiologic factor among all of these diseases.

Epidermal Growth Factor Receptor Expression by Acoustic Neuromas

Antibodies directed against epidermal growth factor receptor (EGFr) impede proliferation and induce differentiation of EGFr‐positive cancers. To explore the effectiveness of anti‐EGFr monoclonal antibodies on acoustic neuromas (ANs), we first sought to evaluate EGFr expression by ANs. The records of all patients with the diagnosis of AN at our institution from January 1989 to July 1994 were reviewed.

Gene therapy : clinical potential and relationships to drug treatment

Gene therapy has been defined as the alteration of the genetic material of a cell with resultant benefit to a patient. Since its first clinical application in 1989, gene therapy has become a standard experimental approach for a number of diseases that have no alternative treatment. Gene therapy trials have been separated into 2 broad categories: therapeutic trials, in which the goal is to treat a disease; and marking trials, in which the goal is to transfer a gene to label a cell type to determine the fate of a cell or the marker gene. Clinical trials are ongoing in 5 different general areas, which will be discussed. Before a clinical trial begins in the US, the protocol must undergo review by both the National Institutes of Health Recombinant DNA Advisory Committee (RAC), if the protocol has received federal funding, and the US Food and Drug Administration. For each section, a general overview of the basic science background for each application is outlined, along with the current clinical protocoL The focus of this article is on the utility of gene transfer as a drug delivery system, and both therapeutic and marking trials are discussed.

Atypical cutaneous lymphocytic infiltrate and a role for quantitative immunohistochemistry and gene rearrangement studies.

Aim To help clarify the significance of the T‐cell receptor (TCR) gene rearrangement and its relationship to the immunophenotyping of histologically atypical cutaneous T‐cell lymphoid infiltrates (ACLIs).

DNA ploidy and proliferating cell nuclear antigen image analysis of peritoneal and pleural effusions. A possible diagnostic role.

OBJECTIVE To determine the role of DNA and proliferating cell nuclear antigen (PCNA) image analysis (IA) in enhancing the diagnostic sensitivity of conventional cytology (CC). STUDY DESIGN The histopathologic and clinical data on 87 consecutive pleural and peritoneal effusions were used to evaluate the accuracy of CC and DNA IA results. RESULTS CC showed a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 65%, 100%, 100% and 62%, respectively. Aneuploidy peaks were seen in 49 cases; 47 of them were true positives. Thirty of 38 diploid cases were true negatives. The sensitivity, specificity, PPV and NPV were 85%, 94%, 96% and 80%, respectively. There were positive correlations between DNA ploidy profile and PCNA proliferative index (PI), (R = .697) and significant differences in PCNA PI between malignant and benign effusions (P < .001). CONCLUSION The DNA IA PI by PCNA can be used as a complementary diagnostic tool with CC in cytologically inconclusive cases.

AN IMMUNOHISTOCHEMICAL STUDY OF LEU 7 AND PCNA EXPRESSION IN THYROID NEOPLASMS

Monoclonal Antibody (MoAb) HNK, or anti-leu-7, is reactive with several neuroendocrine and nonneuroendocrine tumors. The aim of this study is to examine anti-leu-7 reactivity in thyroid neoplasms and its relationship to cellular proliferation as determined by anti-PCNA reactivity. The expression of anti-leu-7 in 56 thyroid neoplasms (24 papillary carcinomas, 14 follicular carcinomas, two medullary carcinomas and 16 follicular adenomas) was examined immunohistochemically. Papillary and follicular thyroid carcinomas reacted with anti-leu-7 in a membranous and cytoplasmic pattern in 88% and 93% of cases, respectively. The adjacent benign tissues were nonreactive. Only eight cases diagnosed as follicular adenomas were reactive with anti-leu-7. Furthermore, the mean proliferative index (PI), as measured by the percentage of nuclei immunoreactive with anti-PCNA, was greater than 30% in all thyroid neoplasms reactive with anti-leu-7. The PI was 58% for papillary carcinomas and 68% and 48% for follicular carcinomas, and follicular adenomas, respectively. Lesions originally classified as follicular adenomas that were nonreactive with anti-leu-7 had a PI of 24% and were reclassified as hyperplastic nodules. These data suggest that anti-leu-7 may be useful for characterizing thyroid neoplasia.

Clinical Approaches to Cancer Gene Therapy

Despite significant advances in standard therapy, many types of cancer currently have no effective treatment. The search for therapies that will be effective against tumors that are unresponsive to surgical removal, chemotherapy, and radiation therapy has led to a number of innovative approaches, including gene therapy, a form of cancer biotherapy. Many gene therapies have been designed to eliminate tumors through tumor-specific properties that are different from those targeted by conventional therapy. Thus, tumors that are resistant to conventional agents could be treatable through a separate mechanism. In addition, some types of gene therapies have been shown to enhance the effects of chemotherapy and other biotherapies such that they might serve as adjunct treatment in diseases for which no one therapy is curative. Clinical trials employing gene transfer for the treatment of cancer have been underway since 1989, when the first phase 1 trial was initiated [1].

The Role of the Blood Bank in Human Gene Therapy Trials

Molecular biology has developed over the last two decades as the structure and function of many genes and their regulation have begun to be elucidated. This basic understanding of gene expression in cells led to studies to genetically transfer genes into cells. Initial studies in gene transfer for gene therapy purposes focused on diseases in which the gene of interest is mutated and thus led to treatment of a genetic disease resulting from the dysfunction of a single gene (e.g., Lesch-Nyhan Syndrome) [1,2]. The mutated gene leads to a dysfunctional protein or unexpressed gene. The early studies for gene therapy focused on these genetic diseases since it was hypothesized that replacing a single gene defect would be the easiest and most ethical approach to the first clinical gene therapy trial [3]. In order to genetically modify a renewable population of cells so that the gene would be expressed for the lifetime of an individual, gene transfer into haematopoietic stem cells to correct a lymphocyte defect, adenosine deaminase deficiency (ADA), seemed the most likely approach. Currently, there are six main groups of target diseases for stem cell gene transfer. Disease affecting red blood cells, such as sickle cell anaemia and thalassaemia, could be cured by insertion of a normal globin gene into stem cells. Neutrophil deficiencies that are caused by an enzyme defect (e.g., chronic granulomatous disease) lead to chronic infections, and can be corrected by insertion of the normal gene that corrects the oxidative pathway [4]. Storage disease can be corrected through stem cell gene transfer, which would correct the genetic defect within the monocyte cell population.