Abstract: A system, composition and method for the stabilization of biological specimens, which employs a chemical fixative.

Abstract: An apparatus and method for producing tissue slides is disclosed. The apparatus includes a holding assembly for manipulating the sample block, a blade assembly for preparing a thin section from the sample block, and a transfer roller mechanism for transferring the thin section to a receiving medium. The apparatus further includes a controller that may track the sample block and thin section. The method includes the steps of first locating a sample embedded within a support medium, which may be paraffin or a similar medium. Next, the embedded sample is oriented in such a way that its working surface is presented. This orientation may entail determining the orientation of the embedded sample with respect to the blade that will produce the largest cross-sectional area. Next, a slice of the sample from said embedded sample is removed and subsequently transferred to a suitable receiving medium, which may include a microscope slide.

Abstract: The invention concerns a method whereby a tissue is fixed by a liquid fixative, dehydrated by a liquid dehydrating agent, and infiltrated/embedded in a molten compound having a melting point higher than room temperature, wherein the method comprises the steps of fixing the tissue in a liquid fixative comprising at least a soluble zinc salt, in an aqueous buffer solution, dehydrating the fixed tissue in a liquid consisting essentially of acetone, embedding and infiltrating the dehydrated fixed tissue with a resin essentially soluble in acetone.

Abstract: A system for developing diagnostic assays, useful in determining whether a particular therapeutic agent will benefit an individual, comprises a continuum of processes that advance diagnostic development while concomitantly benefiting development of the therapeutic agent. This continuum of processes that are dual use, in promoting both diagnostic and drug development, is highly economical and efficient, and creates synergy between pharmaceutical and diagnostic companies.

Abstract: A method for preparing an organic sample for cutting and subsequent examination, involving immersing the sample in a composition containing: an infiltrating substance; an embedding substance, which can be the same or different from the infiltrating substance; and a stain that chemically associates with the organic sample, wherein the stain exhibits different detectable properties when associated and not associated with the sample.

Abstract: A composition and treatment method for fixating cells and for preparing them for examination. In particular, the invention contemplates compositions effective in inhibiting crystal formation in the cell sample and effective in enhancing cell adherence to examination slides.

Abstract: A process and apparatus for cell purification and ablation is disclosed. The present invention comprises a laser system which directs radiant energy at computer or manually selected individual cells thereby disrupting DNA, RNA and protein structure in those cells. The present invention produces a purified tissue section containing relatively intact DNA, RNA or protein from only the untreated cells. This purified sample is suitable for amplification of material by PCR or other techniques for the analysis of molecular genetic features in the selected cells of interest.

Abstract: In vivo assays for selecting candidate therapeutics for inhibiting amyloidoses, such as congophilic and fibrillar &bgr;/A4 amyloid deposition in brain. A candidate reagent is administered to a first rat in a first infusate comprising &bgr;/A4 peptide and perlecan by continuous infusion for at least one week into hippocampus. The candidate reagent is selected as a candidate therapeutic for inhibiting congophilic and fibrillar &bgr;/A4 amyloid deposition in brain if the first infusate diminishes congo red and thioflavin S staining indicative of amyloid deposition adjacent to the infusion site, as compared with a second rat receiving a second infusate consisting essentially of &bgr;/A4 peptide and perlecan.

Abstract: A system, composition and method for the stabilization of biological specimens, which employs a chemical fixative.

Abstract: The invention provides monoclonal antibodies and other binding agents to human cytochrome P450 1A2 having advantageous properties, including capacity substantially to inhibit enzyme activity of human cytochrome P450 1A2 and lack of specific binding to other human cytochromes P450. The binding agents of the invention are useful inter alia in methods for screening drugs for metabolism by cytochrome P450 1A2, and in methods of measuring p450 1A2 levels in individuals relative to p450 1A2 levels in a control population.

Abstract: The present invention relates to methods of tyramide coating live cells for flow cytometry, using catalyzed reporter deposition and serial amplification staining. A catalyzed reporter deposition or an analyte dependent enzyme activation system is described for detecting and/or quantitating an analyte of interest on the surface of a cell by flow cytometry. Also described is a method for serial amplification staining by tyramide coating cells which possess an analyte of interest or a solid phase to which an analyte is bound.

Abstract: The invention provides monoclonal antibodies and other binding agents to human cytochrome P450 2A6 having advantageous properties, including capacity substantially to inhibit enzyme activity of human cytochrome P450 2A6 and lack of specific binding to other human cytochromes P450. The binding agents of the invention are useful inter alia in methods for screening drugs for metabolism by cytochrome P450 2A6, and in methods of measuring p450 2A6 levels in an individual relative to p450 2A6 levels in a control population.

Abstract: A method and composition for quenching formaldehyde fixation of cell and tissue specimens. The composition includes a formaldehyde-reactive agent. The formaldehyde-reactive agent reacts with the formaldehyde to quench the fixation of the cell or tissue specimen. The method involves contacting a formaldehyde fixative solution with the composition.

Abstract: A method for determining the shortest distance between the periphery of a lesion and the cut edge of the tissue specimen utilizing a cylindrical tissue specimen. The cylindrical tissue specimen is placed inside a fixative transmitting cylindrical canister for fixation. After the tissue specimen has been fixed and embedded, it is cross-section sliced in planar slices that are perpendicular to the longitudinal axis of the fixed cylindrical tissue specimen. The slicing can be performed with the tissue specimen remaining inside the cylindrical canister or the tissue specimen can be removed from the canister prior to slicing. The tissue slices are mounted on slides and the slides are evaluated to select the slide showing the lesion periphery nearest to the cut edge of the specimen. The shortest distance between the periphery of the lesion and the cut edge of the specimen is measured. Preferably, the measured distance is adjusted for artifacts in the fixation, mounting, embedding and slicing processes.

Abstract: Methods of fixing and processing tissue and samples on a membrane by using ultrasound radiation as a part of the method are presented. Ultrasound of a frequency in the range of 0.1-50 MHz is used and the sample or tissue receives 0.1-200 W/cm2 of ultrasound intensity. The use of ultrasound allows much shorter times in the methods. Also presented are apparati comprising transducers of one or of multiple heads for producing the ultrasound radiation and further comprising a central processing unit and optionally comprising one or more sensors. Sensors can include those to measure and monitor ultrasound and temperature. This monitoring system allows one to achieve accurate and optimum tissue fixation and processing without overfixation and tissue damage. The system also allows the performance of antigen-antibody reactions or nucleic acid hybridizations to be completed in a very short time while being highly specific and with a very low or no background.

Abstract: A sample of an epithelial lesion which may be keratinized is disclosed in which an analytical system including an imaging system is provided to detect precancerous and cancerous cells. A transepithelial non-lacerational brush produces sufficient cells from all three layers of the epithelium so that an analytical system comprising a programmed computer can detect which cells exhibit abnormal keratinization and require further examination because of a likely suspicion of said pre-cancerous and cancerous conditions. The method and system can apply to the diagnosis non-cancerous conditions as well.

Abstract: Fluorescent monomethine cyanine complexes rigidized a two-carbon alkyl group between the nitrogen's of the cyanine's heterocycles are provided and having the structure wherein R1 through R7 represent various selected groups or ring structures that may be chosen to provide desired solubility, reactive, or spectral properties.

Abstract: Tissue cells are preserved for infrared spectroscopic analysis by soaking a fresh cellular specimen in a 0.5 to 3.0% concentration inorganic salt solution, removing excess salt solution by centrifuging, placing the remaining damp specimen on an infrared optical window and then drying the specimen in a flow of room temperature air such that a dried, spectrally preserved specimen is obtained within 2 minutes. Alternatively, a cellular specimen in wet and fresh form is placed on the surface of a crystal water-soluble inorganic salt in the form of an infrared window to dissolve some of the salt and thereby cover the specimen with the dissolved salt solution and then drying the specimen as described above in less than 2 minutes. In both cases, the drying results in the formation of a salt crystal film covering the surface of the cells for spectral preservation.

Abstract: A diagnostic method and screening test for atherosclerosis and analogous diseases involving activated phagocytes and/or inflammation is provided which comprises determining the presence of 3-chlorotyrosine in a test sample of a body fluid or tissue at a level which is elevated relative to the level in a normal patient.

Abstract: Methods are disclosed for rapid, reliable and simple isolation of RNA from formalin-fixed paraffin-embedded tissue samples. RNA purified in this manner can be used to monitor gene expression levels. The tissue sample can be a tumor or other pathological tissue.

Abstract: Methods for detecting if a subject with tumor cells is at increased risk of developing tumor progression. The method involves determining the frequency of endoapoptosis in a sample of tumor tissue taken from the subject. The frequency of endoapoptosis in the tissue sample indicates whether the subject is at increased risk of developing tumor progression. Method for screening chemical agents for anti-tumor effects.

Abstract: The present invention relates to an action between an inhibitor of apoptosis (IAP) protein and members of the caspase family of cell death proteases, for example, an interaction of the X chromosome linked IAP (XIAP) and caspase-3, caspase-7 or caspase-9, wherein the IAP regulates the activity of the caspases. The invention provides screening assays for identifying agents that alter the specific association of an IAP such as XIAP, c-IAP-1 or c-IAP-2 and a caspase such as caspase-3 or caspase-7. The invention also provides screening assays for identifying agents that alter the specific association of an IAP such as XIAP, c-IAP-1 or c-IAP-2 and a pro-caspase such as pro-caspase-9. In addition, the invention also provides methods for identifying agents that modulate the activity of a caspase in the presence of an IAP and that regulate the activation of a pro-caspase by an IAP.

Abstract: Primary screening for cervical dysplasia is effected by measuring a biochemical marker of apoptosis and/or angiogenesis in each of a population of cells derived from convenient, superficial swabbing, sponging, scraping or lavage of superficial epithelial cells from the cervix, wherein the marker indicates the presence of cervical dysplasia in the sample, and scoring the results of the measuring step for cervical dysplasia (i.e. ascertaining whether or not the marker is present) in the patient in the absence of any cytological examination.

Abstract: A process and apparatus for rapid, continuous flow histological processing of tissues is disclosed. The steps of fixation, dehydration, clearing and impregnation are performed in less than one hour; this allows a pathologist to evaluate samples shortly after receipt, perhaps while the patient is still in the operating room. Rapid and continuous processing is accomplished by decreasing the thickness of tissue sections, use of non-aqueous solutions composed of admixtures of solutions, solution exchange at elevated temperature and with agitation, and impregnation under vacuum pressure. The patient in surgery is thus provided with point-of-care surgical pathology.

Abstract: Testing methods are provided for determining whether given candidate compounds are effective for regulating NF-&kgr;B, JNK and apoptosis cell activities. The methods involve forming a mixture including a compound such as a proteinaceous specie containing two death effector domains (DEDs) or structural or functional homologs and analogs thereof, the candidate compound and a binding target capable of specifically binding to at least one of the DEDs. This mixture is incubated under conditions such that, but for the presence of the candidate compound, the cell activity takes place to a determinable extent. After incubation, the activity is determined and is compared with the determinable extent thereof in the absence of the candidate compound. The assays may be carried out intracellularly or in a cell-free assay.

Abstract: A method for determining the immunocompetence of a mammal is described. Bodily fluid having T cell receptor complexes from a mammal is provided. Expression of a first component and a second component of the T cell receptor complexes is evaluated. An abnormal ratio of the number of cells expressing the first component as compared to the number of cells expressing the second component indicates altered immunocompetence in the mammal.

Abstract: The system provides frame means, mechanical loading means, electronic control means and perfusion chamber means in which an accurately cut human or animal trabecular bone sample can be maintained in a viable state for an extended period. A chamber is provided which permits perfusion of the trabecular bone sample with suitable media. Mechanical means are provided for loading of the sample under controlled specified conditions. Second messenger and growth factors may be collected from the perfusion chamber effluent to enable study of samples under a wide variety of perfusion and loading conditions. The system allows viability of the sample to be maintained for in excess of 14 days and permits the study of rate of bone formation and the rate of resorption of trabecular bone.