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PubMed1994

Specific cellular and humoral reactions as markers of Listeria monocytogenes infections.

The purpose of the study was to test in experimental mouse model if some immunological parameters could be helpful in recognizing Listeria infections. Delayed type hypersensitivity (DTH) and ELISA tests carried out with soluble fractions of L. innocua (serotype 6a) or L. monocytogenes (serotype 4b) seem to be useful in detecting listeriosis at an early stage. Although crude antigen fractions were used in this study, very weak only nonspecific DTH reactions were observed in unifected animals and they could be easily distinguished from the DTH reactions developed by the animals infected with Listeria. However, genetic factors influenced specific anti-listerial reactivity and it was especially observed when DTH test was used as an indicator of Listeria infection. In contrast to DTH and ELISA tests, determination of antibodies active in agglutination or passive haemagglutination assay seem useless in detecting listeriosis at an early stage of infection.

Agglutination Tests↗
PubMed2003

Analysis of interleukin-1alpha (IL-1alpha) and interleukin-8 (IL-8) expression and release in in vitro reconstructed human epidermis for the prediction of in vivo skin irritation and/or sensitization.

In the present study, reconstructed human epidermis (RHE) was used as an in vitro model to discriminate 1-chloro-2,4-dinitrobenzene (DNCB), nickel sulfate (NiSO(4)), oxazolone (OXA), 2,4-dinitrofluorobenzene (DNFB) and 2,4,6-trinitrobenzenesulfonic acid (TNBS) as skin sensitizers from benzalkonium chloride (BC), benzoic acid (BA) and sodium lauryl sulfate (SLS) as skin irritants. Our criteria were (a) the differential IL-1alpha and IL-8 synthesis and release (b) cytotoxicity assessment by MTT assay. When the RHE are topically treated with the sensitizers, very low levels of extra- and intracellular IL-1alpha are observed although they induce significant cytotoxicity. In contrast, they exhibit a sharp maximum of IL-8 release. In the presence of the tested irritants, we observe the inverse cytokine release profile, although they induce dose-dependent cytotoxicity profiles similar to those observed with the sensitizers. Finally, IL-1alpha mRNA upregulation is observed after topical application of both sensitizers and irritants, but only the latter significantly increase extracellular IL-1alpha. In conclusion, our results suggest that the associated determination of IL-8, with IL-1alpha, and MTT conversion are at least necessary to discriminate and classify, in a single assay, irritant and sensitizing agents and represent a potential in vitro alternative to two classical in vivo assays.

Administration, Topical↗
PubMed2007

Early detection of head and neck cancer: development of a novel screening tool using multiplexed immunobead-based biomarker profiling.

Squamous cell carcinoma of the head and neck (SCCHN) is an aggressive disease that has been linked to altered immune, inflammatory, and angiogenesis responses. A better understanding of these aberrant responses might improve early detection and prognosis of SCCHN and provide novel therapeutic targets. Previous studies examined the role of multiplexed serum biomarkers in small cohorts or SCCHN sera. We hypothesized that an expanded panel comprised of multiple cytokines, chemokines, growth factors, and other tumor markers, which individually may show some promising correlation with disease status, might provide higher diagnostic power if used in combination. Thus, we evaluated a novel multianalyte LabMAP profiling technology that allows simultaneous measurement of multiple serum biomarkers. Concentrations of 60 cytokines, growth factors, and tumor antigens were measured in the sera of 116 SCCHN patients before treatment (active disease group), 103 patients who were successfully treated (no evidence of disease group), and 117 smoker controls without evidence of cancer. The multimarker panel offering the highest diagnostic power was comprised of 25 biomarkers, including epidermal growth factor, epidermal growth factor receptor, interleukin (IL)-8, tissue plasminogen activator inhibitor-1, alpha-fetoprotein, matrix metalloproteinase-2, matrix metalloproteinase-3, IFN-alpha, IFN-gamma, IFN-inducible protein-10, regulated on activation, normal T-cell expressed and secreted (RANTES), macrophage inflammatory protein-1alpha, IL-7, IL-17, IL-1 receptor-alpha, IL-2 receptor, granulocyte colony-stimulating factor, mesothelin, insulin-like growth factor binding protein 1, E-selectin, cytokeratin-19, vascular cell adhesion molecule, and cancer antigen-125. Statistical analysis using an ADE algorithm resulted in a sensitivity of 84.5%, specificity of 98%, and 92% of patients in the active disease group correctly classified from a cross-validation serum set. The data presented show that simultaneous testing using a multiplexed panel of serum biomarkers may present a promising new approach for the early detection of head and neck cancer.

Adult↗
PubMed1997

Urinary growth hormone following exercise to assess growth hormone production in adults.

OBJECTIVE: The insulin stress test (IST) is the most commonly used test to assess the GH reserve in children and adults. It is a time-consuming, expensive and potentially dangerous test. We investigated whether measurement of urinary growth hormone excretion following exercise would prove on reliable method to diagnose adult GH deficiency. DESIGN: Healthy volunteers underwent a standard IST to confirm GH secretion. Using a standardized exercise protocol on a treadmill, the urinary excretion of GH was measured. Three patients confirmed as GH deficient by an IST were exercised during the same exercise protocol and their urinary excretion of GH was measured. PATIENTS: Ten healthy volunteers and three patients with hypopituitarism were evaluated. MEASUREMENTS: A standard IST was performed on both healthy volunteers and patients, with measurements of plasma GH and plasma cortisol. Urinary growth hormone and urinary GH/creatinine (GH/CR) ratios were measured before and after IST. On a separate visit, healthy volunteers and patients were exercised on the treadmill with measurements of plasma GH and cortisol. Urinary GH and GH/CR ratios were measured before and after exercise. RESULTS: There was at least a two-fold increase in urinary GH and GH/CR ratios following exercise in all healthy adults. By contrast, patients with GH deficiency showed no rise in urinary GH or urinary GH/CR ratios following exercise. CONCLUSIONS: Measurements of urinary GH following exercise can distinguish between GH-deficient adults and healthy volunteers. Urinary GH excretion can be measured over a timed interval following exercise or can be expressed as the GH/CR ratio. This can be measured on a single sample following exercise and can be used to diagnose GH deficiency. The exercise test employed for this study is arduous. We are therefore performing further studies with a less strenuous exercise protocol with a view to designing a 'patient-friendly' exercise test for GH deficiency in adults.

Adult↗
PubMed2004

[Cuttoff values of biochemical tests on pleural fluid: their usefulness in differential diagnosis of 1,040 patients with pleural effusion].

OBJECTIVE: The aim of biochemical pleural fluid testing is to reach an etiological diagnosis of the pleural effusion. We assessed the utility of considering cuttoff points for the wide range of analytes used to investigate pleural fluid. PATIENTS AND METHODS: Among 1,040 patients with pleural effusion, we sought the etiologies of those fluids which showed any of the following characteristics: red blood cell count = 10 x 109/L, leukocytes = 10 x 109/L, percentage of neutrophils or lymphocytes >50%, protein = 50 g/L, glucose = 60 mg/dL, pH = 7.2, lactate dehydrogenase = 1,000 U/L, adenosine deaminase = 40 U/L, amylase = 100 U/L or cholesterol = 60 mg/dL. RESULTS: Some of the more prominent findings were: a) a sixth of transudates were blood-tinged or contained predominantly neutrophils; b) a groosly bloody fluid suggests malignant disease, trauma, or pulmonary embolization; c) nearly 90% of fluids containing = 10 x 10(9) leukocytes/L were parapneumonics; d) 73% of tuberculous pleural fluids had protein > or = 50 g/L, e) tuberculosis and parapneumonics explained more than 90% of fluids with high adenosine deaminase content; f) one third of amylase-rich pleural effusions were malignant; g) a low pleural glucose or pH levels indicate that patient probably has a parapneumonic, tuberculous or malignant etiology; y h) the diagnostic yield of pleural fluid cytology in malignant effusions was 57%, a percentage which raised to 94% in those with low glucose fluid level. CONCLUSIONS: Cuttof values of biochemical pleural fluid tests may greatly support particular causes of pleural effusions.

Biomarkers↗
PubMed2005

Biomarkers in molecular medicine: cancer detection and diagnosis.

In spite of advances in diagnostics and therapeutics, cancer remains the second leading cause of death in the U.S. Successful cancer treatment depends not only on better therapies but also on improved methods to assess an individual's risk of developing cancer and to detect cancers at early stages when they can be more effectively treated. Current cancer diagnostic imaging methods are labor-intensive and expensive, especially for screening large asymptomatic populations. Effective screening strategies depend on methods that are noninvasive and detect cancers in their early stages of development. There is increasing interest and enthusiasm in molecular markers as tools for cancer detection and prognosis. It is hoped that newly discovered cancer biomarkers and advances in high-throughput technologies would revolutionize cancer therapies by improving cancer risk assessment, early detection, diagnosis, prognosis, and monitoring therapeutic response. These biomarkers will be used either as stand-alone tests or to complement existing imaging methods.

Biomarkers, Tumor↗
PubMed2001

Carcinogen biomarkers for lung or oral cancer chemoprevention trials.

The potential applicability of specific carcinogen-derived biomarkers in chemoprevention trials against lung and oral cancer is discussed. At present, there are no examples of the use of these biomarkers in chemoprevention trials, but the principle has been established in chemoprevention trials directed at aflatoxin B1-induced liver cancer. Polycyclic aromatic hydrocarbons (PAHs) and tobacco-specific nitrosamines are among the most important carcinogens invoked as causes of lung and oral cancer. Biomarkers that are potentially practical for current application in chemoprevention trials are 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene-DNA adducts, as determined by HPLC with fluorescence detection, nitrosamino acids in urine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides in urine, nicotine metabolites in urine, and metabolites of cytochrome P450 substrates in urine. Biomarkers that need further development or exploration before application in trials include 7-methylguanine in DNA, tobacco-specific nitrosamine-DNA adducts, acrolein/crotonaldehyde-DNA adducts, PAH-protein adducts, acetaldehyde-protein adducts, pyrene metabolites in urine and benzo[a]pyrene metabolites in urine. Such carcinogen derived-biomarkers could be applied in chemoprevention trials to test the hypothesis that chemopreventive agents alter carcinogen metabolic activation and detoxification and, ultimately, risk for cancer.

Anticarcinogenic Agents↗
PubMed1990

Patterns of serum alkaline phosphatase activity in unilateral hepatic duct obstruction: a clinical and experimental study.

The levels of serum alkaline phosphatase (ALP) were measured in eight patients with bile duct obstruction limited to one lobe of the liver. Although an initial rise of enzyme concentration was documented in every patient, unrelieved biliary obstruction was associated with a gradual return of ALP to normal values. The return to normal levels coincided with the development of atrophy of that part of the liver deprived of its bile drainage. An animal model of experimental selective biliary obstruction supported a causative association between reduction of hepatocyte mass and a decrease in ALP activity. It appears that normal serum ALP levels can be expected with advanced obstructive biliary disease. Suspected lobar or segmental duct obstruction warrants investigation--even if liver function tests are normal.

Adult↗
PubMed2005

Allium cepa derived EROD as a potential biomarker for the presence of certain pesticides in water.

Allium cepa root length inhibition test is a well recommended bioassay for the evaluation of the toxicity of various polluted waters. The utility of EROD (7-ethoxy resorufin O-deethylase) as a potential biomarker of pesticide pollution was investigated using the Allium cepa system. Onion bulbs exposed to model water samples containing any of the six pesticides viz. 2,4-D, HCB, malathion, carbaryl, DDT and endosulphan were analyzed for EROD activity. The pesticide treatment resulted in the enhanced activity of the enzyme, with carbaryl and HCB causing 63- and 53-fold induction respectively with respect to the control at a dose of 1.2 ppb. The industrial wastewater samples from Ghaziabad city of Northern India resulted in about a 68-fold rise in the EROD activity, whereas the Aligarh samples did not exhibit any change within the statistical limit. These results suggest the presence of the test pesticides in the Ghaziabad sample and their absence in the Aligarh sample. Pesticide analysis in the test water samples by HPLC supported this to a large extent. Presence of cycloheximide in the test system brought down the EROD activity, equal to that of control, suggesting the de novo synthesis of the enzyme following the exposure of Allium cepa to pesticides. These studies suggest that the Allium cepa derived EROD can act as a potential biomarker of certain pesticides since even 1ppb of total/individual pesticides brought about >10-fold induction of EROD. We recommend the assay of EROD in the Allium cepa system as a presumptive test for the detection of these pesticides before using analytical techniques like HPLC.

Biomarkers↗
PubMed2003

Estradiol in premenstrual asthma: a double-blind, randomized, placebo-controlled, crossover study.

STUDY OBJECTIVES: To characterize asthma symptoms and pulmonary function throughout two menstrual cycles, with and without exogenous estradiol administration, in women with premenstrual asthma, and to determine the effect of estradiol administration on asthma symptoms, pulmonary function, quality of life, and biomarkers of airway inflammation. DESIGN: Double-blind, randomized, placebo-controlled, crossover study. SETTING: Respiratory clinic and clinical research center. SUBJECTS: Twelve women with documented premenstrual asthma (> or = 20% premenstrual worsening of asthma symptoms and/or of peak expiratory flow [PEF] during a 1-month screening phase). INTERVENTION: Each woman received either estradiol 2 mg or placebo orally between cycle days 23 and 28 (i.e., premenstrually, or before the onset of menses) in the first cycle and then crossed over to the other arm in the second cycle. Throughout both cycles, the women recorded daily morning and evening PEF readings and asthma symptoms. MEASUREMENTS AND MAIN RESULTS: Spirometry testing and measurement of serum estradiol and biomarkers of airway inflammation were performed on days 8 (follicular phase), 22 (luteal phase), and 28 (premenstrually) of both the estradiol and placebo cycles. During the two premenstrual visits, the Asthma Quality of Life Questionnaire was administered. No notable differences were observed between the estradiol and placebo cycles in daily PEF recordings or composite asthma symptoms scores. The area under the curve (AUC) for the composite asthma symptoms versus time profile was numerically, but not statistically, lower (denoting less severe symptoms) during the estradiol cycle than during the placebo cycle. Likewise, no significant difference in AUC values for morning PEF or evening PEF was found between the estradiol cycle and the placebo cycle. Despite differences (p<0.05) in day-28 estradiol concentrations for estradiol and placebo cycles, no significant differences were found in forced expiratory volume in 1 second, serum endothelin-1, serum and urine eosinophil protein X, urine leukotriene E4, or quality-of-life scores. CONCLUSION: Exogenously administered estradiol did not have a significant effect in women with premenstrual asthma whose asthma was classified predominantly as mild and under excellent control. As in the case of premenstrual syndrome, the placebo effect may be prominent in premenstrual asthma. Further trials, involving women with more severe asthma under poorer control, are warranted to discern underlying mechanisms for the worsening of asthma in relation to menstruation.

Adult↗
PubMed2002

Biomarkers of oxidative stress after controlled human exposure to ozone.

This study was aimed at evaluating whether controlled short-term exposure to ozone (O(3)) induces changes in biomarkers of lung inflammation and oxidative stress in exhaled breath condensate (EBC) and blood of healthy subjects. Twenty-two volunteers were exposed to 0.1 ppm of O(3) for 2 h while performing moderate intermittent exercise. EBC and blood were collected before, immediately after and 18 h after exposure. Changes in biomarkers were measured both in EBC and blood, without significant alterations of lung function tests. Changes in EBC, but not in blood, were mainly accounted for by a subgroup of 'susceptible' individuals bearing the wild genotype for NAD(P)H:quinone oxidoreductase (NQO1) and the null genotype for glutathione-S-transferase M1 (GSTM1). Thus, a single 2-h exposure to 0.1 ppm of O(3) induces changes in biomarkers of inflammation and oxidative stress. Polymorphic NQO1 and GSTM1 act as modifier of the lung response to O(3).

Adult↗
PubMed2006

Application of the Mars Organic Analyzer to nucleobase and amine biomarker detection.

The Mars Organic Analyzer (MOA), a portable microfabricated capillary electrophoresis instrument being developed for planetary exploration, is used to analyze a wide variety of fluorescamine-labeled amine-containing biomarker compounds, including amino acids, mono and diaminoalkanes, amino sugars, nucleobases, and nucleobase degradation products. The nucleobases cytosine and adenine, which contain an exocyclic primary amine, were effectively labeled, separated, and detected at concentrations <500 nM. To test the general applicability of the MOA for biomarker detection, amino acids and mono- and diamines were extracted from bacterial cells using both hydrolysis and sublimation followed by analysis. The extrapolated limit of detection provided by the valine biomarker was approximately 4 x 10(3) cells per sample. Products of an NH(4)CN polymerization that simulate a prebiotic synthesis were also successfully isolated via sublimation and analyzed. Adenine and alanine/serine were detected with no additional sample cleanup at 120 +/- 13 microM and 4.1 +/- 1 microM, respectively, corresponding to a reaction yield of 0.04% and 0.0003%, respectively. This study demonstrates that the MOA provides sensitive detection and analysis of low levels of a wide variety of amine-containing organic compounds from both biological and abiotic sources.

Adenine↗
PubMed2026

Prion disease mimicking rapidly progressive Alzheimer disease: case series and systematic review.

BACKGROUND: Prion disease and Alzheimer disease (AD) are common causes of rapidly progressive dementia (RPD). Although most patients with prion disease are distinguished by MRI and CSF findings, selected cases mimic rapidly progressive AD. We characterized AD-prion disease mimics within a prospective cohort and the extant literature to identify the clinical features and tests that support accurate diagnoses in these patients. METHODS: Patients with prion disease initially diagnosed as rapidly progressive AD were identified from a prospective cohort study at Mayo Clinic (February 2020-June 2026) and through systematic review of MEDLINE and Embase. RESULTS: Of 204 patients with RPD, five (2.5%) were initially diagnosed with clinically probable AD but ultimately determined to have prion disease. Systematic review identified 10 additional cases (n=15, median age-at-onset, 59&#xa0;years; 67% male). Presentations reproduced amnestic (53%), dysexecutive (27%), primary progressive aphasia (13%), and posterior cortical atrophy (7%) AD phenotypes; median time from AD diagnosis to consideration of prion disease was 2&#xa0;months. Diffusion-weighted MRI abnormalities were absent in Mayo Clinic cases and absent/equivocal (n=2) or overlooked (n=8) in published cases. CSF biomarkers were consistent with AD in 6/9 tested patients, with elevated total tau levels in 11/13 patients and total-tau/p hosphorylated-tau181 ratios in 5/9 patients. Real-time quaking-induced conversion assays for prions were positive in the CSF of 9/12 patients. Prion disease was confirmed by neuropathology (n=7), genetics (n=2), or real-time quaking-induced conversion (n=6) assays. CONCLUSIONS: Prion disease may rarely mimic rapidly progressive AD. Disproportionate elevations in CSF total-tau levels or total-tau/p hosphorylated-tau181 ratios should prompt consideration of prion disease.

Humans↗
PubMed2006

Altered expression and localization of creatine kinase B, heterogeneous nuclear ribonucleoprotein F, and high mobility group box 1 protein in the nuclear matrix associated with colon cancer.

Identification of biomarkers could lead to the development of effective screening tests for colorectal cancer. A previous study from our laboratory showed specific alterations of nuclear structure in colon cancer. In an effort to characterize these biomarkers, protein spots were selected from separations made by two-dimensional gel electrophoresis, which were analyzed by mass spectrometry. The sequences obtained from the isolated spots revealed that they have close similarity to creatine kinase B (CKB) isoforms, heterogeneous nuclear ribonucleoprotein F (hnRNP F) and high mobility group box 1 protein (HMGB1) isoforms. To determine the expression of these proteins in colon cancer, expression was studied in 9 tumor and matched adjacent normal pairs, 5 donor colons, 16 polyps, 4 metastatic liver lesions and matched adjacent normal pairs, and 3 liver donors. CKB and hnRNP F were expressed in 78% and 89% of colon tumors, respectively. hnRNP F had a higher frequency of expression than CKB in premalignant polyps. With the establishment of differential expression of the proteins in colon cancer, their subcellular localization was analyzed. The subcellular fractions studied both showed high protein levels of hnRNP F in colon tumors compared with normal colon tissues. Surprisingly, subcellular levels of CKB were decreased in colon tumors, suggesting that the observed high CKB levels in nuclear matrix extracts are caused by the enhanced localization of CKB to the nuclear matrix during colon tumorigenesis. These results suggest an involvement of hnRNP F and CKB in colorectal cancer. Additionally, they suggest that hnRNP F is a potential marker for colorectal cancer progression.

Adenocarcinoma↗