Health test for a broad spectrum of health problems

Abstract

Provided herein are methods and devices for the detection of conditions or disorders by detecting altered levels of stress response pathway biomarkers. Also provided are methods and reagents for identifying panels of biomarkers associated with a condition or disorder.

What is claimed is: 
     
         1 . A device for detecting at least one stress response biomarker in a test sample comprising:
 (a) a disposable module for uptake of a test sample and reagent storage, wherein the module comprises reagents for assaying for at least one stress response biomarker; and   (b) a reusable module for signal detection and result display; wherein the reusable module displays a signal that indicates the presence of the at least one stress response biomarker in the test sample.   
     
     
         2 . The device of  claim 1  wherein the signal provides a digital readout of a percentage above a baseline representing the presence of the at least one stress response biomarker in the test sample. 
     
     
         3 . The device of  claim 1  wherein the signal provides a visual indication representing the presence of the at least one stress response biomarker in the test sample. 
     
     
         4 . The device of  claim 3  wherein the visual indication is a color indication. 
     
     
         5 . The device of  claim 1  wherein the test sample is selected from the group containing breath air, saliva, urine, sweat, tears, blood, serum, stool, phlegm, bone marrow, cerebrospinal fluid, seminal fluid, vaginal fluid, amniotic fluid, skin, breast milk, tissue, plant sap, an egg, microbial body, cells suspension or a combination thereof. 
     
     
         6 . The device of  claim 1  wherein the at least one stress response biomarker is selected from the group consisting of aldose reductase, apoptosis signal-regulating kinase 1, aquaporin 5, beta-endorphin, betaine GABA transporter, caspase recruitment domain protein 9, caspase 8, cyclin D, cyclooxygenase 2, cytochrome P450, cytochrome c, c-fos, c-jun, epidermal growth factor receptor, ferritin, glucocorticoid receptor, glucose regulated protein 58, glucose regulated protein 75, glutathione S-transferase p, GroEL, heat shock protein 25/27, heat shock protein 40, heat shock protein 60, heat shock protein 70, heat shock protein 90, heat shock transcription factor-1, heme oxygenase-1, interleukin 1β, interleukin 6, interleukin 8, interleukin 10, interleukin 12, laminin, leptin receptor, matrix metalloproteinase 9, metallothionein, Mek-1, Mekk-1, inducible nitric oxide synthase, peripheral benzodiazepine receptor, p38 MAPK, salivary alpha amylase, SAPK, serotonin, serotonin receptor, substance P, superoxide dismutase Mn, superoxide dismutase Cu/Zn, superoxide dismutase EC, transforming growth factor β, tumor suppressor p53, and vasoactive intestinal peptide. 
     
     
         7 . The device of  claim 1 , wherein the at least one stress biomarker is associated with dehydration. 
     
     
         8 . The device of  claim 1 , wherein the at least one stress biomarker is associated with AIDS progression. 
     
     
         9 . The device of  claim 1  wherein the device further comprises a means for accessing a database, wherein the database provides a correlation between the presence of the at least one stress biomarker molecule in the test sample and (i) the presence, absence, or severity, if present, of a particular disease state; or (ii) the likelihood that an organism from which the test sample was obtained will contract or be subject to a particular disease state. 
     
     
         10 . A method for detecting a condition or disorder associated with a stress response in a subject comprising:
 detecting an altered level of at least one biomarkers in an stress response biomarker panel in a sample comprising salivary cells from a subject, as compared to a corresponding sample from a normal subject, wherein the panel comprises at least two biomarkers, and wherein further an alteration in the level of biomarker is indicative of a stress response associated with the condition or disorder, thereby detecting the condition or disorder in the subject.   
     
     
         11 . The method of  claim 10 , wherein the at least one stress response biomarker is selected from the group consisting of aldose reductase, apoptosis signal-regulating kinase 1, aquaporin 5, beta-endorphin, betaine GABA transporter, caspase recruitment domain protein 9, caspase 8, cyclin D, cyclooxygenase 2, cytochrome P450, cytochrome c, c-fos, c-jun, epidermal growth factor receptor, ferritin, glucocorticoid receptor, glucose regulated protein 58, glucose regulated protein 75, glutathione S-transferase p, GroEL, heat shock protein 25/27, heat shock protein 40, heat shock protein 60, heat shock protein 70, heat shock protein 90, heat shock transcription factor-1, heme oxygenase-1, interleukin 1β, interleukin 6, interleukin 8, interleukin 10, interleukin 12, laminin, leptin receptor, matrix metalloproteinase 9, metallothionein, Mek-1, Mekk-1, inducible nitric oxide synthase, peripheral benzodiazepine receptor, p38 MAPK, salivary alpha amylase, SAPK, serotonin, serotonin receptor, substance P, superoxide dismutase Mn, superoxide dismutase Cu/Zn, superoxide dismutase EC, transforming growth factor β, tumor suppressor p53, and vasoactive intestinal peptide. 
     
     
         12 . The method of  claim 10 , wherein the at least one stress biomarker is associated with dehydration. 
     
     
         13 . The method of  claim 10 , wherein the at least one stress biomarker is associated with AIDS progression. 
     
     
         14 . The method of  claim 10 , wherein the levels of the at least one biomarker are detected by analysis of biomarker protein or nucleic acid in the sample comprising the salivary cells. 
     
     
         15 . The method of  claim 14 , wherein the analysis of biomarker protein includes detection with an antibody. 
     
     
         16 . The method of  claim 15 , wherein the salivary cells are lysed prior to analysis with the antibody. 
     
     
         17 . The method of  claim 16 , wherein the analysis is by ELISA. 
     
     
         18 . The method of  claim 15 , wherein the sample comprising the salivary cells is analyzed on microscope slide. 
     
     
         19 . The method of  claim 14 , wherein the analysis of biomarker nucleic acid comprises isolation of salivary cell nucleic acid. 
     
     
         20 . The method of  claim 19 , wherein the biomarker nucleic acid is detected in the isolated salivary cell nucleic acid by nucleic acid hybridization or PCR amplification. 
     
     
         21 . A method of processing a salivary cell sample for biomarker analysis comprising:
 (a) applying a sample of saliva or salivary cells to a substrate;   (b) fixing the cells;   (c) incubating the cells in low pH citrate buffer at 37° C.;   (d) contacting the cells with serum;   (e) applying a primary antibody for each of biomarker of a biomarker panel; and   (f) detecting the binding of the primary antibody using a secondary antibody having a detectable label, wherein the label is detected optically using a computerized image analysis.   
     
     
         22 . The method of  claim 21 , wherein the salivary cells are collected using an oral brush. 
     
     
         23 . The method of  claim 21 , wherein the biomarker panel comprises at least one biomarker selected from the group consisting of aldose reductase, apoptosis signal-regulating kinase 1, aquaporin 5, beta-endorphin, betaine GABA transporter, caspase recruitment domain protein 9, caspase 8, cyclin D, cyclooxygenase 2, cytochrome P450, cytochrome c, c-fos, c-jun, epidermal growth factor receptor, ferritin, glucocorticoid receptor, glucose regulated protein 58, glucose regulated protein 75, glutathione S-transferase p, GroEL, heat shock protein 25/27, heat shock protein 40, heat shock protein 60, heat shock protein 70, heat shock protein 90, heat shock transcription factor-1, heme oxygenase-1, interleukin 1β, interleukin 6, interleukin 8, interleukin 10, interleukin 12, laminin, leptin receptor, matrix metalloproteinase 9, metallothionein, Mek-1, Mekk-1, inducible nitric oxide synthase, peripheral benzodiazepine receptor, p38 MAPK, salivary alpha amylase, SAPK, serotonin, serotonin receptor, substance P, superoxide dismutase Mn, superoxide dismutase Cu/Zn, superoxide dismutase EC, transforming growth factor β, tumor suppressor p53, and vasoactive intestinal peptide. 
     
     
         24 . A method for constructing a biomarker panel for detecting a stress response in a cultured cell comprising:
 (a) detecting the level of one or more biomarkers from a panel of biomarkers in cultured cells subjected to a treatment that induces cellular stress;   (b) comparing the level of the biomarkers from the treated cells to the level of the biomarker from a corresponding sample of cultured cells that have not been subjected to the treatment that induces cellular stress, wherein biomarkers having a difference level in the treated cells as compared to the untreated cells are included in an SR biomarker panel for a stress response.   
     
     
         25 . The method of  claim 24 , wherein the treatment that induces cellular stress is a stressor selected from the group consisting of heat shock, freeze/thaw cycling, hypersalinity, dehydration, and oxidative stress. 
     
     
         26 . The method of  claim 24 , wherein the cultured cells are salivary cells, peripheral blood mononuclear cells, or cells from organ cultures of tonsil, skin, gut or lung. 
     
     
         27 . The method of  claim 24 , wherein the cells are animal cells. 
     
     
         28 . The method of  claim 24 , wherein the cells are human cells. 
     
     
         29 . A method for detecting a condition or disorder associated with a stress response in a subject comprising:
 detecting an altered level of at least one biomarkers in an stress response biomarker panel in a sample comprising salivary cells from a subject, as compared to a corresponding sample from a normal subject, wherein the panel comprises at least two biomarkers, and wherein further an alteration in the level of biomarker is indicative of a stress response associated with the condition or disorder, wherein the altered levels of the at least one or more biomarkers are detected using a device of  claim 1 , thereby detecting the condition or disorder in the subject.