Massachusetts Institute of Technology

Northeastern University

William G Thilly

Elena Viktorovna Gostjeva

Daniel I Wang

David W Levine

Charles L Crespi

Jason S Wong

Thomas R Skopek

Barry L Karger

Roger W Giese

Aharon S Cohen

Frantisek Foret

Henry Hoppe, Iv

Howard L Liber

Xiao-Cheng Li-Sucholeiki

Phouthone Keohavong

Phouthone Koehavong

Konstaintin Khrapko

Bruce W Penman

Elena V Gost Jeva

The invention provides, inter alia, methods of treating a disorder characterized by excessive metakaryotic stem cell growth by a combination metakaryocidal therapy. Also encompassed by the present invention are preventative methods comprising the administration of a metakaryocidal or metakayrostatic therapeutic agent.

Metakaryocidal treatments

The invention provides methods of identifying wound healing metakaryotic stem cells, identifying molecules to modulate proliferation and/or migration of metakaryotic stem cells and molecules to treat wound healing disorders, such as blood vessel wound healing disorders, including restenosis. The invention also provides methods of diagnosing and treating wound healing disorders, such as blood vessel wound healing disorders and also of treating wounds by the use of metakaryotic stem cell transplant(s).

Wound healing metakaryotic stem cells and methods of use thereof

Methods are disclosed for the characterization of the stage of development or pathology of a tissue sample, and for identifying pluripotent metakaryotic stem cells, comprising detecting fluorescence of cells and syncytia in fixed samples treated with a non-fluorescent Schiff's base reagent in the absence of extraneous or exogenously added fluorescent dyes.

Methods for identifying stem cells by detecting fluorescence of cells and syncytia

Methods for identifying stem cells and other cells specific to embryogenesis and carcinogenesis, classifying tissue samples, diagnosing precancerous and cancerous or atherosclerotic lesions, testing the value of anticancer agents, discovering macromolecules specifically expressed in particular cell types, using stem cells in restorative tissue therapy as well as methods for preparing tissue samples so heteromorphic nuclear morphotypes remain intact are disclosed.

Methods for identifying stem cells based on nuclear morphotypes

Methods for identifying candidate anti-tumorigenic agents

Methods for detecting low frequency nuclear mutations in a target sequence from a genomic DNA sequence are disclosed.

Methods for detecting rare polymorphic variants in genomic DNA sequences

The invention relates to a method for identifying inherited point mutations in a targeted region of the genome in a large population of individuals and determining which inherited point mutations are deleterious, harmful or beneficial. Deleterious mutation are identified directly by a method of recognition using the set of point mutations observed in a large population of juveniles. Harmful mutations are identified by comparison of the set of point mutation observed in a large set of juveniles and a large set of aged individuals of the same population. Beneficial mutations are similarly identified.

Methods of identifying point mutations in a genome

The present invention pertains to a line of human blood cells which have high levels of oxidative activity (such as oxygenase, oxidase, peroxidase, and hydroxylase activity). Such cells grow in suspension culture, and are useful to determine the mutagenicity of xenobiotic substances that are metabolized into toxic or mutagenic substances. The invention also includes mutation assays using these cells, and other cells with similar characteristics.

Mutation assays involving blood cells that metabolize toxic substances

The disclosure relates to a method for resolving double-stranded DNA species differing by at least one base pair. Each of the species is characterized by an iso-melting domain with a unique melting temperature contiguous with a melting domain of higher thermal stability.

Electrophoretic detection and separation of mutant DNA using replaceable

A method of resolving (physically separating) mutant DNA from nonmutant DNA and a method of defining or establishing a mutational spectrum or profile of alterations present in nucleic acid sequences from a sample to be analyzed, such as a tissue or body fluid. The present method is based on the fact that it is possible, through the use of DGGE, to separate nucleic acid sequences which differ by only a single base change and on the ability to detect the separate mutant molecules. The present invention, in another aspect, relates to a method for determining a mutational spectrum in a DNA sequence of interest present in a population of cells. The method of the present invention is useful as a diagnostic or analytical tool in forensic science in assessing environmental and/or occupational exposures to potentially genetically toxic materials (also referred to as potential mutagens); in biotechnology, particularly in the study of the relationship between the amino acid sequence of enzymes and other biologically-active proteins or protein-containing substances and their respective functions; and in determining the effects of drugs, cosmetics and other chemicals for which toxicity data must be obtained.

Determination of a mutational spectrum

A line of human blood cells which have high levels of oxidative activity (such as oxygenase, oxidase, peroxidase, and hydroxylase activity) is disclosed. Such cells grow in suspension culture, and are useful to determine the mutagenicity of xenobiotic substances that are metabolized into toxic or mutagenic substances. Mutation assays using these cells, and other cells with similar characteristics, are also disclosed.

An assay is disclosed for determining mutagenic damage caused by the administration of a known or suspected mutagen to diploid human lymphoblastoid cell lines. The gene locus employed for this assay is the gene for thymidine kinase, uridine kinase, or cytidine deaminase. Since human lymphoblastoid cells contain two genes for these enzymes, heterozygotes of human lymphoblastoid cells are used in this assay.

Assay for mutagenesis in heterozygous diploid human lymphoblasts

An assay is disclosed for determining mutagenic damage caused by the administration of a known or suspected mutagen to bacterial cells such as Salmonella typhimurium. After administration of or exposure to a mutagenic agent, the bacterial cells are plated in the presence of a purine analog and resistance to purine analogs is used as the genetic marker. This bioassay system can be used by genetic toxicologists to determine the potential genetic hazards from the use of a variety of suspected or known mutagens, including newly-developed chemicals.

Assay for mutagenesis in bacterial cells

Improved cell culture microcarriers, and methods for their production and use, are disclosed herein. These improved microcarriers have positive charge capacities adjusted and/or controlled within a range suitable for good cell growth. One method for producing such improved microcarriers is by treating beads formed from polymers containing pendant hydroxy groups, such as dextran beads, with an aqueous solution of an alkaline material and a chloro- or bromo-substituted tertiary amine under precisely controlled conditions to produce the desired exchange capacity. The resultant positively charged microcarriers have been used in microcarrier cultures to produce outstanding growth of anchorage-dependent cells. Such cells can be harvested, or used for the production of viruses, vaccines, hormones, interferon or other cellular growth by-products.

Growing community of inventors

Winchester, MA, United States of America

William G Thilly