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The process of lymphocyte differentiation involves structural alterations of specific genes including those for the immunoglobulin (Ig) and T-cell receptor (TCR) antigen genes. This process occurs very early in the differentiation of B- and T-lymphocytes and involves an ordered pr ...

Molecular methods have proven extremely useful for the detection of occult tumor cells and can yield valuable clinical information as well as a better understanding of the mechanisms of metastasis and relapse of cancer (1). In the case of many hematopoietic malignancies, the presence of a uni ...

Molecular methods permit the detection of cells too few in number to be detected by light microscopy, immunohistochemistry, or flow cytometry (1–5). Numerous investigators are therefore developing sensitive and specific reverse transcriptase polymerase chain reaction (RT-P ...

The identification and study of nonrandom recurrent chromosomal translocations has substantially increased our understanding of the non-Hodgkin lymphomas. Cytogenetic and molecular genetic data now form an integral part of current lymphoma classifications (1) and provi ...

RNA can be isolated from fresh or frozen tissue, then purified and quantified for subsequent molecular analysis. RNA is quite labile compared to DNA for good reason: RNA is the transient message that transmits information from activated genes. Once gene transcription is turned off, no more RNA is ...

The TP53 tumor suppressor gene coding for a nuclear phosphoprotein involved in cellular stress responses is the most frequently mutated gene in human cancers described so far (1–4). Mutations are found throughout the gene but most frequently within the highly conserved middle region (ex ...

The onset of human cancer typically requires numerous genetic mutations, generally specific for the tissue type from which the cancer originates. Thus, it has been difficult to screen all tumor types for a single mutation. In recent years, telomerase activity has been associated with at least ...

In 1993, three groups independently discovered that the lengths of microsatellites in tumors could vary from the normally constant pattern defined at birth (5–5) (see review in ref. 4). This discovery has been designated either microsatellite instability (MSI) or replication errors (R ...

During embryogenesis in females, in each cell either the paternal or the maternal X chromosome is randomly inactivated through methylation (1 2). This event is stably inherited by daughter progeny of each cell. Therefore, in adult women, polyclonal cell populations will comprise a random mi ...

In situ hybridization was first described in the late 1960s by Pardue and Gall (1), who hybridized mouse ribosomal DNA sequences to a mouse chromosome spread. The technique came into broader use with the description of DNA probes for various viral sequences, and in the late 1980s with the publicatio ...

Neurodegenerative conditions are increasing in prevalence as the average human life expectancy rises. Alzheimer’s disease (AD) is the fourth commonest cause of death in the United States; the recent outbreak of new variant Creutzfeldt-Jakob disease (nvCJD) has raised the specter of a la ...

The infectious cause of the transmissible spongiform encephalopathies (TSEs), or prion diseases, is not yet clearly defined. Although minorities of researchers cling tenaciously to the virus hypothesis, the prion or protein-only hypothesis is now widely accepted by most scientis ...

It was believed that only proteins could carry out enzymatic reactions, and only nucleic acids could mediate inheritance. In recent years, the work of Cech and Altman and others has shown that nucleic acids can catalyze reactions. Now it has been shown that, in yeast, proteins can mediate inheritan ...

“Science is nothing but trained and organized common sense, differing from the latter only as a veteran may differ from a raw recruit.”a Prion disease is a disease of the second half of the twentieth century, but the scientific method that has elucidated this fascinating group of diseases is much olde ...

Various approaches have been taken to study the function of prion proteins. Biochemical methods were applied to search for a binding partner of PrPC which is attached to the cell surface by a glycosylphosphatidylinositol GPI anchor (1). The glial fibrillary acidic protein was one of the first p ...

Protein function is often observed directly following protein isolation, or is deduced by loss of function following gene knockout or by analogy with proteins of known function and similar amino acid sequence. None of these is true in the case of prion proteins because aside from the association ...

The fundamental problem in addressing prion diseases, or the transmissible spongiform encephalopathies, is finding an explanation for the massive neuronal death that occurs. Although some understanding of the mechanism by which neuronal death occurs comes from studies with scr ...

In the past two decades, thoroughly standardized mouse incubation time and brain lesion profile scoring assays have been developed to discriminate between prion strains. However, in these mouse infection experiments, large numbers of animals (about 20 mice/line) from three differe ...

A basic principle of microbiology that applies to all conventional infectious pathogens is that the disease phenotype is a function of both the infecting agent and the host’s response to it. All evidence indicates that this principle is also true for diseases acquired by infection with prions, ...

The prion hypothesis states that the partially protease-resistant and detergent-insoluble prion protein (PrPSc) is identical with the infectious agent, and lacks any detectable nucleic acids. Since the latter discovery, transgenic mice have contributed many important insig ...