Abstract: A histological specimen cassette for use in connection with a larger histological specimen cassette, wherein each histological specimen cassette has an internal chamber that includes a receptacle and a lid, the receptacle having a bottom wall, opposite side walls, opposite front and back walls, and an internal chamber or cavity, where the internal chamber or cavity is positioned between the sidewalls, the front and back walls and partially bound by the bottom wall, having a plurality of apertures that extend through the bottom wall and that create fluid passageways into the cavity, the lid having a plurality of apertures that extend through the lid and that create additional fluid passageways into the cavity, the histological specimen cassette being dimensioned such that the histological specimen cassette can fit entirely within the void of the larger histological specimen cassette when the lid is in the closed position.

Abstract: A system for making cell blocks includes a cell block cassette and processing station, the cassette including a main body having a having a collection aperture formed therein and a filter assembly removably attached to the main body, the filter assembly defining a collection well in communication with the collection aperture, and having a filter positioned across a bottom surface of the collection well, the filter configured to retain cellular matter carried in a fluid that is dispensed into the collection well and flows across the filter. The cell block processor has a cassette interface removably seating the cell block cassette, and a sensor positioned or positionable to detect and monitor a fluid level in the collection well.

Abstract: A microdissection method for separating and taking a target zone of a biological preparation, disposed on a carrier device with a laser light-absorbent incisable layer and a carrier means, comprises cutting the preparation and the incisable layer along an edge segment of the target zone and removing of a non-excised segment of the incisable layer from the carrier means.

Abstract: In a wide variety of human solid tumors, an aggressive, metastatic phenotype and poor clinical prognosis are associated with expression of the receptor tyrosine kinase Met. Disclosed herein are (a) a monoclonal antibody named Met4, which antibody is specific for Met, and (b) a hybridoma cell line that produces Met4. The Met4 antibody is particularly useful for detecting Met in formalin-fixed tissue. Methods of using the Met4 antibody for detection, diagnosis, prognosis, and evaluating therapeutic efficacy are provided.

Abstract: The present invention relates generally to kits that provide reagent mixes and instructions for the use thereof, in performing high-throughput assay methods that determine the proliferative status of isolated target cell populations. The methods measure the luminescent output derived from the intracellular ATP content of incubated target cells, and correlate the luminescence with the proliferative status of the cells. The present invention further relates to kits that provide reagent mixes and instructions for high-throughput assays methods for screening compounds that may modulate the proliferative status of a target cell population. The kits of the present invention and methods therein described may be used for determining the proliferative status of any isolated cell line or type. The kits and methods of the present invention address the need for rapid assays that determine the proliferative status of isolated hematopoietic stem and progenitor cells and of subpopulations of differentiated cells thereof.

Abstract: This application includes description of antibodies for specifically detecting prions of human origin and methods for detecting pathogenic prions. In some embodiments, the antibodies bind to an epitope characteristic of a human prion protein which is not found in the prion proteins of other species. In some embodiments, the antibodies are not cross-reactive with cow, Syrian Gold hamster, mouse, or rat prions. The application also includes a conformation-dependent immunoassay method for detecting pathogenic prions in a sample containing a prion (PrP) protein. The PrP protein may be present in a first conformation and a second conformation, such as PrPc and PrPSc in which the two conformations have different binding affinity for the antibody used to detect them.

Abstract: Provided is a tissue piece treating apparatus comprising an automatic controlling means for feeding back the temperature of the treatment liquid or molten paraffin in the bath inside detected by a temperature sensor to switch a heating mode and a cooling mode alternately to control the temperature; a heating means for turning OFF in an air-cooling fan of the ultrasonic vibrator and ON in a plane heater at the heating mode, thereby transferring the heat generated by the ultrasonic vibrator and the plane heater; and, a cooling means for turning ON in the air-cooling fan of the ultrasonic vibrator and OFF in the plane heater at the cooling mode, thereby blocking the heat transfer from the ultrasonic vibrator and the plane heater to the bath inside. These means can suppress the excessive heating of a tissue piece so that they can suppress the heating modification of the tissue piece.

Abstract: An antibody which reacts with N-acetylheparosan and heparan sulfate that is derived from bovine kidney but does not substantially react with heparan sulfate derived from a murine Engelbreath-Holm-Swarn tumor tissue, the antibody being produced with a hybridoma which is prepared using a substance composed of a protein and N-acetylheparosan bound to the protein.

Abstract: The present invention provides methods and compositions for treatment, screening, diagnosis and prognosis of breast cancer, colorectal cancer, gastric cancer, hepatocellular carcinoma, lung cancer and pancreatic cancer, for monitoring the effectiveness of breast cancer, colorectal cancer, gastric cancer, hepatocellular carcinoma, lung cancer and pancreatic cancer treatment, and for drug development.

Abstract: A thin-section slide-sample manufacturing apparatus and a method for manufacturing a thin-section slide sample by cutting out a thin section from an embedded block, transporting the thin section on a conveyor unit, transferring and mounting the thin section on a substrate, the thin-section slide-sample manufacturing apparatus including: a relay having a fixing plane onto which the thin section is fixed detachable; a rotating transportation unit which moves the relay between the conveyor unit and the substrate; and a control unit which moves the relay to the conveyor unit by using the rotating transportation unit, which moves the relay to the substrate where the thin section is detached and transferred to the substrate; wherein, the control unit rotates the relay according to the preliminarily set fixing plane and the relative position of the thin section around a rotation axis provided orthogonal to the fixing plane by using the rotating transportation unit.

Abstract: The histochemical and biomarker for liver fibrosis is a technique for determining the existence and extent of liver fibrosis by evaluating the extent of peptidylarginine deiminase (PAD) activity by immunological methods. The method is illustrated using liver biopsy. A small section of tissue from a liver biopsy is incubated overnight with a monoclonal antibody specific to PAD, stained, and examined microscopically. The number of hepatocytes that positively express PAD activity per one hundred hepatocytes is counted and expressed as a percentage. The percentage of PAD activity is then correlated with a METAVIR fibrosis score according to results from a statistically significant reference population. The degree of liver fibrosis and an appropriate treatment regimen may then be determined.

Abstract: Imaging specimen such as biological tissue is facilitated. According to an example embodiment of the present invention, a relatively thin, surface portion of a specimen is stained and imaged. The thin portion is removed, exposing a new portion of the specimen. The newly-exposed portion is stained and imaged. Subsequent new surface portions (newly exposed) are similarly stained and imaged, with multiple images obtained from the specimen in an automated fashion. Some applications are directed to the distinct imaging of specimen characteristics having relatively small vertical separation (e.g., less than about 40 nanometers), with an upper characteristic imaged, removed, and the lower characteristic subsequently imaged.

Abstract: A multilayer label comprising a polymeric film or cloth, e.g., a polyester film or a polyester woven cloth, having opposing facial surfaces, one facial surface of which is in intimate contact with a xylene-resistant, water-based topcoat and the other facial surface of which is in intimate contact with a pressure sensitive adhesive (PSA) if the other facial surface is a cloth, or a water-based, melted wax-resistant PSA if the other facial surface is a film.

Abstract: Tissue orientation devices include a perforated tissue support with at least one perforated channel for receiving a tissue sample, and a plurality of tabs configured to extend along and into the channel to retain the tissue sample during processing and embedding. Tissue orientation devices include elongated legs coupled together for holding one or more biopsy tissue samples therebetween. Associated methods include using the cassettes and orientation devices to hold and orient tissue samples for processing, embedding and microtome sectioning.

Abstract: A biological reaction apparatus for receiving at least one substrate having a sample located in a sample region, and a separate cover, such that a reaction chamber is formed between the cover and substrate over the sample region, wherein the apparatus includes a locating means to locate the substrate; a cover locating means for locating and moving the cover with respect to the substrate; a fluid dispensing means for dispensing fluid into the reaction chamber; and a draining mechanism; wherein the draining mechanism includes wicking means.

Abstract: A cassette for fixing, embedding and slicing biological tissues includes a base sheet and a lid sheet formed of an elongated plastic sheet which is sliceable and has not less than predetermined strength. The base sheet has grooves as biological tissue receiving portions. The base plate and the lid sheet are formed by folding the plastic sheet along a fold line so that the lid sheet can be selectively opened and closed. Biological tissues are pressed against the bottoms of the grooves with pressing/retaining sponge members secured to the lid sheet at its portions corresponding to the respective grooves. In this state, the biological tissues are fixed by a fixing agent, and the cassette is dehydrated, infiltrated with paraffin as an embedding agent to embed the cassette, thereby forming a block including an embedding frame. The block is then sliced with a microtome to provide good biological tissue specimens.

Abstract: A method for aiding in the determination of whether a living or deceased human is afflicted with or will likely have atherosclerosis respectfully, the method comprising determining the level of SPRR3 protein in a intimae or body fluid sample by using molecular localization analysis technique comparing the determined level of SPRR3 protein in the biological sample obtained from said individual with a range of SPRR3 levels previously defined as characteristic for humans having atherosclerosis, concluding from the comparison that the person is likely suffering from atherosclerosis when a SPRR3 level is in the range previously defined as characteristic for the presence of atherosclerosis as an indication that the individual is suffering from or has suffered from atherosclerosis.

Abstract: A tissue embedder comprising a transport mechanism for an input member, the input member adapted to hold a plurality of tissue supports, with each tissue support associated with a mould, a wax bath and a cooling station wherein the transport mechanism moves the input member from a wax bath to a cooling station.

Abstract: A method is disclosed for reversing fixation-induced cross-linking in tissue specimens that have been preserved for histological examination. The method involves placing the fixed tissue in a liquid under elevated temperature and pressure conditions that are sufficient to reverse the fixation-induced cross-linking, restore antigenicity to proteins, and permit improved molecular and proteomic analysis of the preserved tissue specimen. Methods are also disclosed for processing tissues for histological examination under elevated pressure conditions that enhance the perfusion of liquid reagents into the tissue and reduce overall processing times.

Abstract: A cell colonies dissecting and transplanting apparatus comprises: a base, a platform, a feeding mechanism having at least three axis feeding means, a movable holder, a cutting means, a transplanting means, and a CCD image capturing means. The platform having the CCD image capturing means therebottom is disposed onto the base, and on the platform is defined with the holder for receiving a plurality of loading trays, so as to the original cell colonies and a plurality of media boards of subculture can be placed on the loading trays of holder, the holder can displace from a first axis feeding means and a second axis feeding means of feeding mechanism to moveably align with a first axis and a second axis.

Abstract: A specimen holder (10) is proposed in order to create a capability for preparing, in a cutting device, in particular a microtome or ultramicrotome, a specimen that is to examined in an AFM. The specimen holder (10) is embodied in several parts. It comprises an insert (12) in which the specimen is secured. Also provided is a receiving ring (14) in which the insert (12) can be received. The insert together with the receiving ring (14) is mounted, in particular thread-joined, on a base element (16). As a result of the mounting of the receiving ring (14) on the base element (16), the insert together with the specimen is fixed in its position.

Abstract: An automated machine for handling and embedding tissue samples contained on microtome sectionable supports. The machine includes an input member configured to hold a plurality of the microtome sectionable supports prior to a tissue embedding operation. An output member is configured to hold a plurality of the microtome sectionable supports after the tissue embedding operation. A cooling unit is configured to hold at least one of the microtome sectionable supports during the tissue embedding operation. A motorized carrier assembly is mounted for movement and configured to hold at least one of the microtome sectionable supports. The carrier assembly moves the support from the input member to the cooling unit and, finally, to the output member. A dispensing device dispenses an embedding material onto the microtome sectionable support and at least one tissue sample carried by the microtome sectionable support during the embedding operation.

Abstract: For successful wound healing to occur, the newly formed skin must generate tensile strength through collagen deposition. Measurement of collagen in the granulating wound bed may be predictive of successful wound healing. Existing methods for collagen measurement either require specialized equipment, or do not allow for discrimination of potential interfering molecules. Herein described is an accurate, specific and reliable method to extract and quantify collagen from tissue utilizing high pressure liquid chromatography techniques. The method is sensitive enough to measure the small amounts of collagen found in newly healing wounds.

Abstract: Methods and compositions for preventing artifacts in tissue samples fixed with an aldehyde-based fixative are described. The methods include fixing a tissue sample with an aldehyde-based fixative, such as a formalin fixative agent. After fixation, the tissue sample can be contacted with separate solutions that each contain an artifact preventing composition or a tissue stain. However, because the artifact preventing composition may increase the stain's shelf-life, the stain and the composition are preferably mixed before being added to the sample. The artifact preventing composition can include one or more amino acids, polyamines, and/or Schiff-base-forming compounds. The components of the composition can bind to or react with free fixative to prevent fixative artifacts.

Abstract: A process for maintaining 3 dimensional orientation between a tissue specimen and images of the area of investigation, to register histopathologic diagnoses of multiple locations within the specimen with corresponding locations on the surface of said area of investigation, by marking at least two fiduciary lines on the area of investigation; acquiring a fiduciary image of the tissue with the fiduciary lines; excising the tissue to form a tissue specimen; inserting at least two parallel needles through said specimen; acquiring a specimen image of the specimen with inserted needles over an alignment grid; fixing the specimen by immersing the specimen; acquiring a fixed image of the fixed specimen with the inserted needles over the alignment grid; forming a paraffin mold containing the fixed specimen and inserted needles; injecting different colored inks through the needles while withdrawing them from the fixed specimen, so that different colored needle tracks are formed in the specimen; sectioning the specimen

Abstract: Methods and apparatus for providing and processing serial tissue sections. In one example, an “automatic tape collecting lathe ultramicrotome” (ATLUM) slices a block of tissue sample having various geometries into a continuous ribbon of thin tissue, or multiple thin tissue sections, and disposes the sliced thin tissue on an appropriate substrate to facilitate subsequent imaging of the sliced thin tissue. Closed-loop control of section thickness of the sliced thin tissue sections or ribbons is implemented to produce thinner sliced tissue sections or ribbons and tightly regulate thickness. Thin tissue sections or ribbons may be particularly processed/prepared to facilitate imaging with a scanning electron microscope (SEM). Collected thin tissue sections or ribbons may be used to create UltraThin Section Libraries (UTSLs) that allow for fully automated, time-efficient imaging in the SEM to facilitate expansive tissue studies.

Abstract: An apparatus and method for tagging a specimen slide are described. The apparatus comprises a receiving region for receiving at least one cassette magazine, a reading unit for reading the machine-readable coded information of a cassette identifier of a cassette, and a tagging unit for generating a machine-readable coded information for tagging the specimen slide with a specimen slide identifier that depends on the cassette identifier. Data are transferred from the microtome to the apparatus via the data transfer path as soon as the cassette is inserted into the microtome, and only then can the machine-readable coded information for tagging the specimen slide be applied onto the specimen slide by the tagging unit.

Abstract: The present invention concerns a method and an apparatus for automatic staining of at least one tissue sample accommodated on a slide by applying reagents. The system may include at least one slide provided in a slide rack, a fluid containment element, a slide holder, a vertical slide positioner to pivot the slides to a vertical position, and a slide immerser element to immerse the vertical slide into a fluid containment element or even a dip tank. By pivoting the slides from a horizontal to a vertical position, an automated method and apparatus for carrying out a pretreatment in an automated staining apparatus may be provided. The pivoting of slides may ensure an appropriate orientation of the slides for both the pretreatment and the staining processes.

Abstract: This application relates to a newly identified animal cell structure, the midbody scar. This structure is a remnant of the midbody that is retained by one daughter cell following cytokinesis and persists through multiple subsequent cell cycles. The midbody scar can be useful as a marker of dividing cells or of a cell's replicative age.

Abstract: [Problems] It is intended to provide a storing device which is convenient in preserving a slice of a pathological tissue or the like over a long time and by which a required number of slices can be quickly provided without waste. It is also intended to provide an instrument for microscopic observation which is equipped with this storing device and a transparent plate having an adhesive layer formed thereon. [Means for Solving Problems] A device comprising: a piece of a resin film on which a slice having been excised from a sample block or a cell block slice is adhered and fixed via an adhesive layer provided on the surface thereof; and a holder on the surface of which the back face of the film piece is detachably adhered and fixed via a pressure-sensitive adhesive layer. An instrument for microscopic observation which comprises the storing device and a transparent plate for adhering and fixing the film piece having been peeled off from the storing device.

Abstract: The present invention relates generally to assays, methods, and kits that provide reagent mixes and instructions for determining the proliferative status of isolated target cell populations. The methods measure the luminescent output derived from the intracellular ATP content of incubated target cells, and correlate the luminescence with the proliferative status of the cells.

Abstract: A mobile intra-operative microscopic diagnosis laboratory capable of analyzing fresh tissue specimens and providing intra-operative consultation within 20 minutes is described. The mobile laboratory is preferably a van and contains a cryostat for freezing the fresh tissue specimens and a means for cutting the specimens. In addition, it also contains the means for reading the slides to make microscopic diagnosis and a means for handling for fresh tissue and a means for indicating various locations in the specimen, preferably by inking them. It preferably contains a stainer for staining the samples and an intercom for communicating the microscopic diagnosis back to the operating room.

Abstract: A method for determining a volume of ablated tissue is provided. The method includes the steps of: supplying energy to tissue to create an ablation volume therein; excising one or more slices of the tissue having a portion of the ablation volume therein; and subjecting at least a portion of the slice to a first contrast agent for a predetermined period of time, wherein the contrast agent is configured to color dead cells within the ablation volume.

Abstract: The present disclosure provides methods and compositions to facilitate prediction of the likelihood of responsiveness of cancer patients to treatment including a taxane and/or a cyclophosphamide.

Abstract: The invention is directed to novel compositions of matter and methods of detecting in situ an immunohistochemical epitope or nucleic acid sequence of interest in a biological sample comprising binding an enzyme-labeled conjugate molecule to the epitope or sequence of interest in the presence of a redox-inactive reductive species and a soluble metal ion, thereby facilitating the reduction of the metal ion to a metal atom at or about the point where the enzyme is anchored. Novel phosphate derivatives of reducing agents are described that when exposed to a phosphatase are activated to their reducing form, thereby reducing metal ions to insoluble metal.

Abstract: Provided is a system and method for staining of one or more samples, including providing one or more self-contained sample processing receptacles, each of the one or more self-contained sample processing receptacles configured to be inserted into an auto-staining instrument; and enabling one of one or more staining procedures appropriate for the one or more samples as a function of a choice of self-contained sample processing receptacle, each of the one or more self-contained sample processing receptacles configured to process each inserted sample of the one or more samples within the self-contained sample processing receptacle.

Abstract: A method for presenting at least one structure of a histological specimen. The method comprises providing a plurality of images of a plurality of sections of a single histological specimen having a plurality of structures, segmenting a plurality of segments of the plurality of structures in each the image, associating among respective the segments of a common structure of the plurality of structures, and presenting the association in relation to at least some of the plurality of images.

Abstract: A method for processing biological tissue used in biological prostheses includes providing a tissue procurement solution formed from a phosphate buffered saline (PBS) solution and a chelating agent. The tissue is transferred from the tissue procurement solution and undergoes chemical fixation. The fixed tissue is then immersed in a series of fresh bioburden reduction process (BRP) solutions to extract phospholipids. The tissue procurement solution reduces the bioburden on the stored tissue and preserves tissue architecture by minimizing tissue swelling. The tissue procurement solution further reduces calcium from the incoming water and/or tissue, and inhibits enzymes that digest the collagen matrix. The serial immersion of the tissue in the fresh bioburden solutions ensures optimal extraction of phospholipids thereby mitigating subsequent calcification of the tissue.

Abstract: A microarrayer apparatus for constructing arrays of biological material from donor cores obtained from at least one donor block and placing the donor cores in an embedding medium carried by at least one recipient block. The apparatus includes a donor punch, a recipient punch, and a stylus mounted for independent coaxial movement along a common punch axis. The recipient punch cooperates with the stylus when ejecting a donor core from the donor punch to minimize deformation of the donor core.

Abstract: The invention relates to the processing of a biological sample for histological analysis. In particular, it relates to a rapid automated processing system that can be operated with continuous throughput and that eliminates the use of toxic solvents such as xylene. Provided is a method for processing a biological sample for histological analysis, comprising contacting the sample with a composition comprising a supercritical or near supercritical fluid followed by impregnating the sample under a pressure of more than 1 bar with an embedding medium, preferably paraffin.

Abstract: Methods that combine processing and staining of tissue samples such that the processed tissue is stained and ready for histological evaluation prior to embedding and sectioning, and separate staining of the sectioned tissue is not required. The method may be used with chemical and/or mechanical/thermal tissue penetrant enhancers in an automated tissue processing system.

Abstract: The present invention is directed to a method for processing a tissue specimen in situ prior to histological examination by providing a tissue specimen having a predetermined examination face, disposing the specimen on a tissue positioning member for removably maintaining the tissue specimen with the examination face in a desired orientation thereon, processing the tissue specimen while maintaining the examination face in the desired orientation on the positioning member throughout processing, separating the tissue specimen from the tissue positioning member by application of a separation force, and maintaining the orientation of the examination face after the specimen is removed from the tissue positioning member wherein processing of the specimen includes contacting the specimen with fluids for dehydrating and clearing the specimen and subsequent casting of the specimen in an embedding material for forming a specimen-containing mold portion having the tissue specimen contained therein in desired orientation

Abstract: Systems and methods allowing for the automatic control and scheduling of a staining apparatus for biological samples on slides present within the apparatus are provided. In some embodiments, the actions of a robot coupled to the staining apparatus, which performs some of the staining tasks on the individual slides in accordance with their respective protocols, may be prioritized and scheduled. In some embodiments, the scheduling may result in increasing or maximizing the throughput of slides. In some embodiments, robot scheduling ensures that the individual slides are processed substantially within the tolerances specified by their respective protocols. In some embodiments, the robot scheduler may respond to spontaneous user actions and adaptively schedule or re-schedule robot actions.

Abstract: The present invention provides a non-destructive macromolecules extraction (NDME) device for extracting high quantity of biological molecules (including, but not limited to, proteins, DNA, and/or RNA) from tissue specimens (including, but not limited to, fresh or fixed tissue sections, homogenized tissues, and cell cultures), while preserving the morphology and antigenicity of the tissue. The device contains a base, a slide cover, and a thermal control device. The tissue specimen is placed onto the base. The slide cover is mounted to the base to form a space where an extraction solution can be added. The device optionally contains a chamber cover over the slide cover. The chamber cover and the slide cover forms a reaction chamber where a steam is infused to maintain the humidity of the tissue. The extraction solution contains a detergent. The present invention also provides a method for extracting the same.

Abstract: Disclosed are methods and systems that include: (a) fixing a tissue sample in a bath of fixing solution by directing ultrasonic waves to be incident on the tissue sample; (b) sectioning the tissue sample to produce a tissue section; (c) applying one or more stains to the tissue section; and (d) obtaining one or more images of the stained tissue section.

Abstract: Irradiation methods and apparatus configured to deliver power, via electromagnetic fields at a variety of frequencies and power levels, in a localized fashion to a target area. In one example, an electromagnetic field generator is disposed on a substrate and configured to deliver power via electromagnetic energy to a thin region proximate to (above) a surface of the substrate, wherein electromagnetic field intensity decreases significantly beyond the thin region. Such methods and apparatus are particularly useful in a wide variety of processes involving chemical and/or physical interactions in connection with a sample of interest located in the thin region. In different aspects, irradiator apparatus may be configured as disposable devices, and/or used in combination with one or more microfluidic or sensing components, for a variety of medical/laboratory/diagnostic methods and instrumentation implementations.

Abstract: Systems and methods allowing for the automatic control and scheduling of a staining apparatus for biological samples on slides present within the apparatus. In some embodiments, the actions of a robot coupled to the staining apparatus, which performs some of the staining tasks on the individual slides in accordance with their respective protocols, may be prioritized and scheduled. In some embodiments, the scheduling may result in increasing or maximizing the throughput of slides. In some embodiments, robot scheduling ensures that the individual slides are processed substantially within the tolerances specified by their respective protocols. In some embodiments, the robot scheduler may respond to spontaneous user actions and adaptively schedule or re-schedule robot actions.

Abstract: To preprocess a tissue sample, a first permeable mesh membrane is tautly stretched out over the tissue sample and overlaid on top of a flat surface. This covering sandwiches and secures the tissue sample in between the first permeable mesh membrane and the flat surface. If it is desired to reinforce the mechanical strength of the first permeable mesh membrane, a second permeable mesh membrane can be tautly stretched out and overlaid on top of the sandwich. Alternatively, the second permeable mesh membrane can be attached onto a third component, such as a disposable solvent resistant frame, to create a framed mesh. Thereafter, the first permeable mesh membrane may be attached to the framed mesh to create a compound framed mesh. The tissue sample may then be sandwiched and secured in between the compound framed mesh and the flat surface. To retain and flatten the tissue sample, gentle pressure may be uniformly applied.

Abstract: Mass-spectrometry based methods of analyzing estrogens and other steroids from biological tissue sections samples are disclosed herein. Methods of detecting a disease state or condition or elevated risk of a disease state or condition in a mammal from tissue sections are also disclosed.

Abstract: The invention provides methods for treating demyelinating inflammatory diseases by administering to the subject an effective amount of an agent that provides activated protein C activity, where the dose is effective to reduce the adverse clinical indicia of the disease. In some embodiments, the patient being treating is of the chronic active plaque type.