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Results for “Biomarker variability”

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PubMed2001

Improved diagnostic classification of alcohol abusers by combining carbohydrate-deficient transferrin and gamma-glutamyltransferase.

BACKGROUND: Biochemical markers can provide objective evidence of high alcohol consumption. However, currently available markers have limitations in their diagnostic performance. METHODS: The diagnostic values of the most frequently used markers [carbohydrate-deficient transferrin (CDT), gamma-glutamyltransferase (GGT), aspartate aminotransferase, alanine aminotransferase, and mean corpuscular volume] were studied in an analysis of six different clinical studies (n = 1412) on alcohol abusers and social drinkers. The purpose of the analyses was to determine whether a combination of markers would improve the diagnosis of subjects. RESULTS: Discrimination between alcohol abusers and social drinkers, as measured by the areas under nonparametric ROC plots, was significantly better (P<0.001) for the new combined marker [gamma-CDT = 0.8. ln(GGT) + 1.3. ln(CDT)] than for any of the separate markers or combination of CDT or GGT with other markers. The cutoff values for gamma-CDT (6.5) can be taken to be the same among males and females. CONCLUSIONS: The combined variable gamma-CDT is a powerful tool to discriminate alcohol abusers from social drinkers and is recommended for clinical use.

Alcohol Drinking↗

PubMed2003

Maternal serum activin, inhibin, human chorionic gonadotrophin and alpha-fetoprotein as second trimester predictors of pre-eclampsia.

OBJECTIVE: To compare the serum levels of human chorionic gonadotrophin (hCG), alpha-fetoprotein, activin A, inhibin A and inhibin isoforms containing pro and alphaC in the second trimester serum of women who subsequently developed hypertensive disorders of pregnancy with those who remained normotensive throughout pregnancy. DESIGN: Retrospective case-control study of 15-20 week serum samples matched for duration of storage at -20 degrees C. SETTING: Antenatal clinics at a teaching hospital in Scotland. SAMPLE: Second trimester serum samples of 39 women who subsequently developed pre-eclampsia, 31 who subsequently developed pregnancy-induced hypertension and 155 women who remained normotensive throughout pregnancy. MAIN OUTCOME MEASURES: hCG, alpha-fetoprotein, activin A, inhibin A and inhibin pro-alphaC serum levels. RESULTS: Activin A levels in serum were significantly elevated in women who later developed pregnancy-induced hypertension (26% increase compared with controls) and hCG levels were significantly elevated in women who later developed pre-eclampsia (24% increase compared with controls). alpha-Fetoprotein, inhibin A and inhibin pro-alphaC levels were not significantly elevated in the patient groups compared with their controls. CONCLUSIONS: A combination of analyses including second trimester serum activin A and hCG may yet prove to be helpful predictors of women at risk of hypertensive disorders of pregnancy. While the results proved significant, the effects reported in this study are too modest compared with natural variability to be useful as screening tools on their own.

Activins↗

PubMed2003

Biochemical markers of bone metabolism: application to understanding bone remodeling in children and adolescents.

Markers of bone remodeling have been developed that provide biochemical indices that reflect changes in the rates of bone formation, resorption, and mineralization. These processes are important determinants of bone metabolism, and indicators that correspond to these processes can provide clinically relevant information. Until recently, the best way to measure parameters of bone metabolism was to perform a bone biopsy after administration of two courses of tetracycline. Bone markers offer significant potential advantages over bone biopsy. Some of these markers are protein fragments that are generated during metabolism of type I collagen, the major structural protein of bone, and are formed as this collagen is synthesized or degraded. Other markers, such as osteocalcin and alkaline phosphatase, are released from osteoblasts during bone formation. Although these markers have found significant utility in the evaluation of adults with metabolic bone diseases, their application in children has been limited due to great variability in normal ranges that reflect the changes in skeletal metabolism induced by age, growth rate, gender, and pubertal state.

Adolescent↗

PubMed1994

S-100 protein-negative malignant melanoma: fact or fiction? A light-microscopic and immunohistochemical study.

S-100 protein is considered a characteristic immunohistochemical marker for all nevomelanocytic lesions, in which it is expected to be present consistently. We reviewed 17 cases of malignant melanomas that previously tested negative for S-100 protein. They were reevaluated by light microscopy, a broad panel of immunohistochemical reagents including monoclonal and polyclonal antibodies to S-100 protein, and electron microscopy. On reexamination, five of the 17 cases were reclassified as non-melanoma tumors, and eight of the 17 cases were found to be positive for S-100 protein (six with monoclonal and eight with polyclonal antibodies) and HMB-45 antigen, consistent with melanoma. The remaining four cases repeatedly tested negative for S-100 protein despite various antigen enhancement methods, but they were positive for HMB-45 antigen and contained premelanosomes or melanosome-like structures by electron microscopy. Two of these repeatedly S-100 negative melanomas were acrally located; although the numbers are small, a possible relationship to a specific anatomic location cannot be excluded. These findings suggest that in a small subset of melanomas S-100 protein is either not fully expressed or is below the level that can be detected by routine immunohistochemistry. We also conclude that in the majority of the initially S-100-negative cases of melanomas, the misdiagnosis may occur due to the use of an incomplete immunohistochemical panel, technical reasons, or the inherent variability of tissue expression of S-100 protein.

Antigens, Neoplasm↗

PubMedDate not supplied

The prognostic significance of epidermal growth factor receptor (EGFR), C-erbB-2, Ki-67 and PCNA expression in breast cancer.

The evaluation of the immunohistochemical expression of epidermal growth factor receptor (EGFR), c-erbB-2 oncoprotein, proliferating indices Ki-67, and PCNA were determined on 68 primary breast carcinomas. These markers were correlated with each other and with other clinicopathological variables such as: age, tumor size? histotype, tumor grade and steroid receptors' content as well as nodal status. The monoclonal antibodies anti-human Epidermal Growth Factor Receptor (EGFR1), anti-human Ki67 (DAKO) and N13259 (Oncogene Science) were applied to paraffin and frozen tissue sections. All markers showed an heterogeneous pattern of staining. There was almost equally high staining intensity at the membranus for EGFR and c-erbB-2 in about 32% of the cases. The EGFR and c-erbB-2 positive cases were much less common in infiltrating lobular (2,2/13) rather than in ductal adenocarcinomas (21,20/55). The low grade carcinomas showed low expression of EGFR and c-erbB-2 oncoprotehl comparing with high grade ductal adenocarcinomas. A high index of Ki-67 was correlated with EGFR and c-erbB-2 membrane positivity. There was an inverse relationship between the expression of c-erbB-2 and EGFR, when compared with oestrogen receptors' content. A significant correlation was also demonstrated between EGFR and c-erbB-2 immunoreactivity with lymph node status. Our results provide evidence that the synchronous immunohistochemical detection of EGFR, c-erbB-2 and Ki-67 may be of useful significance in breast cancer patients, especially when combined with other clinicopathological variables. Furthermore the expression of EGFR and c-erbB-2 oncoprotein may affect the cell proliferation and differentiation.

Biomarkers, Tumor↗

PubMed1998

Carcinosarcoma of the parotid gland: report of a case with cytohistologic and immunohistochemical findings.

True malignant mixed tumors (carcinosarcomas) of salivary gland origin are exceedingly rare and demonstrate malignant epithelial and stromal components. We report a case of parotid gland carcinosarcoma that showed squamous cell carcinoma and malignant fibrous hystiocytoma without clinical or histologic evidence of a preexisting pleomorphic adenoma. This tumor consisted of 2 histologically different populations of cells without evidence of a common origin from the myoepithelial cell, which is the putative precursor cell of pleomorphic adenoma and its derived carcinosarcoma. In addition to supplementing the literature, this case report includes cytohistologic and immunohistochemical analyses that provide further insights into the variable histogenesis of this neoplasm and the distinction between de novo carcinosarcoma and carcinosarcoma originating from pleomorphic adenoma.

Aged↗

PubMedDate not supplied

Failure of platelet parameters and biomarkers to correlate platelet function to severity and etiology of heart failure in patients enrolled in the EPCOT trial. With special reference to the Hemodyne hemostatic analyzer. Whole Blood Impedance Aggregometry for the Assessment of Platelet Function in Patients with Congestive Heart Failure.

Data from small studies have suggested the presence of platelet abnormalities in patients with congestive heart failure (CHF). We sought to characterize the diagnostic utility of different platelet parameters and platelet-endothelial biomarkers in a random outpatient CHF population investigated in the EPCOT ('Whole Blood Impedance Aggregometry for the Assessment of Platelet Function in Patients with Congestive Heart Failure') Trial. Blood samples were obtained for measurement of platelet contractile force (PCF), whole blood aggregation, shear-induced closure time, expression of glycoprotein (GP) IIb/IIIa, and P-selectin in 100 consecutive patients with CHF. Substantial interindividual variability of platelet characteristics exists in patients with CHF. There were no statistically significant differences when patients were grouped according to incidence of vascular events, emergency revascularization needs, survival, or etiology of heart failure. Aspirin use did not affect instrument readings either. PCF correlates very poorly with whole blood aggregometry (r(2) = 0.023), closure time (r(2) = 0.028), platelet GP IIb/IIIa (r(2) = 0.0028), and P-selectin (r(2) = 0.002) expression. Furthermore, there was no correlation with brain natriuretic peptide concentrations, a marker of severity and prognosis in heart failure reflecting the neurohumoral status. Patients with heart failure enrolled in the EPCOT Trial exhibited a marginal, sometimes oppositely directed change in platelet function, challenging the diagnostic utility of these platelet parameters and biomarkers to serve as useful tools for the identification of platelet abnormalities, for predicting clinical outcomes, or for monitoring antiplatelet strategies in this population. The usefulness of these measurements for assessing platelets in the different clinical settings remains to be explored. Taken together, opposite to our expectations, major clinical characteristics of heart failure did not correlate well with the platelet characteristics investigated in this study.

Aged↗

PubMed2006

Identification of genes expressed differentially in an in vitro human lung carcinogenesis model.

Lung cancer is the deadliest among all cancers in the US for both men and women. Early detection of premalignant lesions or tumors appears to be a promising approach to reducing the morbidity and mortality from lung cancer because the survival of early stage lung cancer patients is better than that of patients with advanced cancers. We approached the identification of early biomarkers of human lung carcinogenesis, by combining the use of cDNA array and an in vitro human lung carcinogenesis model that consists of normal (NHBE), immortalized (BEAS-2B and 1799), transformed (1198) and tumorigenic (1170-I) human bronchial epithelial (HBE) cells. We hypothesized that certain genes that are expressed differentially among these cells can serve as both biomarkers for early detection and targets for intervention. Nineteen genes were downregulated and six were upregulated in tumorigenic 1170-I HBE cells compared to normal HBE cells (NHBE) using cDNA array. Downregulated genes encode cell-to-cell and cell-to-matrix adhesion-related proteins, calcium-binding proteins and some enzymes or growth factor-related proteins. The functions of upregulated gene were more variable. Similar expression of selected genes was found in different nonsmall cell lung cancer cell lines analyzed by Northern blotting. Furthermore, the differential expression of some genes was also observed by in silico analysis of database of human lung tumors. The differentially expressed genes encode calcium-binding proteins and cell-cell and cell-matrix adhesion proteins. Furthermore, Northern blotting analysis of RNA from different cell lines comprising an in vitro carcinogenesis model including normal, immortalized, transformed, and tumorigenic cells indicated that the expression of subsets of the identified genes changed at different stages of carcinogenesis. These data show that the in vitro carcinogenesis cell system could be useful for discovering potential biomarkers of early and late stages of lung carcinogenesis and targets for chemoprevention.

Carcinoma, Non-Small-Cell Lung↗

PubMed2006

Serial testing of B-type natriuretic peptide and NTpro-BNP for monitoring therapy of heart failure: the role of biologic variation in the interpretation of results.

BACKGROUND: B-Type natriuretic peptide (BNP) and NTpro-BNP are widely used for diagnosis and risk stratification of patients with heart failure (HF). Although not currently cleared by the Food and Drug Administration as a test indication, there is interest in using these biomarkers for monitoring the success of HF medications. An assessment of the analytical and biologic variations is necessary to interpret the results of serial testing. METHODS AND RESULTS: The intra-individual biologic variances and analytical assay variances of BNP and NT-proBNP from healthy subjects and those with stable HF were reviewed. The analytical variability of BNP and NT-proBNP assays was reported, as some have suggested that only the analytical variance is important in interpreting the results of tightly regulated hormones. The reference change values (RCV) for serial measurements were derived and used to interpret results of therapeutic studies whereby serial changes in BNP and NT-proBNP concentrations were obtained to evaluate the therapeutic success of short-term (inpatient) and long-term (outpatient) management. The use of RCV may also be important in studies comparing BNP-guided versus physician-guided HF drug therapy. CONCLUSIONS: Relative to the RCV, short-term therapeutic studies of inpatients have largely resulted in a statistically significant decline in BNP and NT-proBNP with clinical evidence of patient improvements. In contrast, many therapeutic studies involving long-term outpatient monitoring have produced changes in BNP/NT-proBNP that do not exceed the biologic variances. The value of BNP for monitoring therapeutic success can be questioned for trials that demonstrate clinical benefit without statistically significant decreases in biomarker levels.

Adult↗

PubMed1997

Biological indicators of survival in patients treated by surgery for squamous cell carcinoma of the oral cavity and oropharynx.

Squamous cell carcinomas of the head and neck are a heterogeneous group of tumours with regard to anatomical site, natural history and response to various treatments. Assessment of the role of biomarkers as indicators of prognosis or response to treatment is thus complex. In the last decade, different biomarkers have been investigated in the search for objective and reproducible indicators of prognosis. In 69 squamous cell carcinomas of the oral cavity or oropharynx from patients treated with radical surgery alone, we determined cell kinetics, evaluated as in vitro 3H-thymidine labelling index (TLI), p53, bcl-2 and glutathione S-transferase pi (GST pi) expression, by using immunohistochemical methods. The biological variables were unrelated to one another or to established clinical and pathological prognostic factors. Univariate analysis showed that a low proliferative activity was associated to a significantly higher risk of death than that observed in patients with a high TLI, whereas p53, bcl-2 and GST pi expression did not provide prognostic information. Multivariate analysis showed that cell proliferation, gender and nodal status retained their clinical relevance. In the subset of node-negative patients, TLI and p53 expression were indicators of survival. Moreover, the combined analysis of TLI and p53 expression identified a subgroup of node-negative patients with slowly proliferating and highly p53-expressing tumours who died within 1 year of radical surgery. These results indicate that in patients with operable oral cavity and oropharyngeal cancer, biomarkers can provide important information on clinical outcome.

Adult↗

PubMed1996

Association between human papillomavirus type and clonal status of cervical squamous intraepithelial lesions.

BACKGROUND: Lesions that are histologically classified as precursors of cervical cancer, which are often referred to as squamous intraepithelial lesions (SILs), represent a heterogeneous clinical entity that can be associated with many different types of human papillomaviruses (HPVs) and have a variable biologic behavior. Approximately one half of low-grade SILs behave as non-neoplastic, productive viral lesions that frequently regress spontaneously, whereas the other half behave as neoplasms and either persist or progress to a histologically higher grade lesion. Identification of biomarkers that reliably differentiate those low-grade SILs with the properties of a non-neoplastic viral infection from those with the properties of neoplasia would provide a more rational basis for decisions about disease management. Since monoclonality is a hallmark of neoplasia irrespective or organ site, clonal status might represent one such biomarker. PURPOSE: To better understand the pathobiology of SILs, we analyzed the clonality of low-grade and high-grade SILs and compared their clonal status with their associated HPV types. METHODS: One hundred forty formalin-fixed, paraffin-embedded cervical biospy and loop electrosurgical specimens, originally diagnosed as SILs, were obtained from the pathology archives of both the Columbia-Presbyterian Medical Center and Kyto Diagnostics in New York. Clonality was determined with the use of a polymerase chain reaction (PCR) based method that detects nonrandom X-chromosome inactivation. This PCR-method amplifies a polymorphic region of the androgen receptor gene that is flanked by several differentially methylated enzyme sites. The same tissue was also analyzed for HPV DNA with the use of PCR and both L1 and E6 "consensus" primers. RESULTS: All 25 evaluable cases of high-grade SILs were determined to be monoclonal. Although 54 (68%) of 79 evaluable low-grade SILs were monoclonal, 25 (32%) of 79 low-grade SILs were polyclonal. A strong association was observed between HPV type and clonal status, with a total of 71 (47 low-grade and 24 high-grade) SILs determined to be monoclonal and containing HPV types 16, 18, 31, 33, 35, 39, 45, 56, 58, or 65. In contrast, 22 (92%) of the 24 low-grade SILs that contained another type of HPV were polyclonal (Fisher's exact test, two-sided, P</-.001). CONCLUSIONS: Our findings suggest that the histopathologic entity termed low-grade SIL consists of two different types of lesions that are biologically distinct. One lesion is monoclonal and is associated with HPV types 16, 18, 31, 33, 35, 39, 45, 56, 58, or 65. The second types of low-grade SIL is polyclonal and is associated with other types of HPV.

Alleles↗

PubMed2006

Serum proteomic fingerprints of adult patients with severe acute respiratory syndrome.

BACKGROUND: Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a new coronavirus strain, SARS-CoV. Specific proteomic patterns might be present in serum in response to the infection and could be useful for early detection of the disease. METHODS: Using surface-enhanced laser desorption/ionization (SELDI) ProteinChip technology, we profiled and compared serum proteins of 39 patients with early-stage SARS infection and 39 non-SARS patients who were suspected cases during the SARS outbreak period. Proteomic patterns associated with SARS were identified by bioinformatic and biostatistical analyses. Features of interest were then purified and identified by tandem mass spectrometry. RESULTS: Twenty proteomic features were significantly different between the 2 groups. Fifteen were increased in the SARS group, and 5 were decreased. Their concentrations were correlated with 2 or more clinical and/or biochemical variables. Two were correlated with the SARS-CoV viral load. Hierarchical clustering analysis showed that a majority of the SARS patients (95%) had similar serum proteomic profiles and identified 2 subgroups with poor prognosis. ROC curve analysis identified individual features as potential biomarkers for SARS diagnosis (areas under ROC curves, 0.733-0.995). ROC curve areas were largest for an N-terminal fragment of complement C3c alpha chain (m/z 28 119) and an internal fragment of fibrinogen alpha-E chain (m/z 5908). Immunoglobulin kappa light chain (m/z 24 505) positively correlated with viral load. CONCLUSIONS: Specific proteomic fingerprints in the sera of adult SARS patients could be used to identify SARS cases early during onset with high specificity and sensitivity.

Adult↗

PubMed2003

Relation between lung function and RBC distribution width in a population-based study.

STUDY OBJECTIVES: Pulmonary function is dependent not only on smoking, but also on nutritional status. Since an increased RBC distribution width (RDW) has been associated with nutritional deficiencies, we postulated that RDW has an inverse relation to pulmonary function. The purpose of this study was to test this hypothesis. DESIGN AND SETTING: A cross-sectional study was conducted of a random sample of the general population in western New York. PARTICIPANTS: A total of 1,616 subjects of both genders who were aged 35 to 79 years and were free of respiratory disease. INTERVENTIONS: None. MEASUREMENTS: Pulmonary function was assessed from FEV(1), FVC, height, body weight, total pack-years of smoking, smoking status, hemoglobin concentration, and hematologic indexes, eosinophil count, education, and blood levels of retinol, beta-cryptoxanthin, and vitamin E. RESULTS: We found a direct relation between RDW and the number of pack-years of smoking and smoking status, and an inverse relation between FEV(1) and FVC with RDW, even when potentially confounding variables such as smoking were taken into account. When the variability of FEV(1) due to smoking was used for comparison, an additional 27% of that variability in FEV(1) was explained by variations in antioxidant vitamin levels, and another 24% by RDW. CONCLUSIONS: The results confirmed our hypothesis that there is an inverse relation between RDW and pulmonary function, and raise the possibility that RDW may be a biomarker for as-yet unidentified nutrients that affect pulmonary function.

Adult↗

PubMed1997

Prognostic factors in prostate cancer.

The clinical course of prostate cancer (PCa), the most common cancer in Swedish men, is highly variable and difficult to predict. Consequently, there is an urgent need to distinguish tumours with a high risk of progression from those with a low risk. To investigate the prognostic implications of proliferation and apoptosis, two important processes in tumor biology, immunoreactivity for biomarkers associated with these processes was assessed, quantified in indexes, and related to cause-specific survival (CSS). A consecutive series of 186 men presenting with voiding symptoms and PCa were treated with transurethral resection and deferred endocrine therapy. After 13-21 years follow-up, 43% of these men had died of prostate cancer. In a subgroup of men with localised disease at the time of diagnosis, 27% succumbed to the disease. Immunoreactivity for p53 protein, indicative of a defective p53 function, predicted shorter CSS in univariate (52 vs 123 months, p < 0.0001), but not in multivariate analysis. Mean index for the apoptosis blocking bcl-2 protein was higher in foci of prostatic intraepithelial neoplasia, a putative precursor to PCa, than in manifest cancer areas (79 vs 12, p < 0.0001). This indicates that bcl-2 may be involved in early tumourigenesis. No prognostic value was found for the bcl-2 index. A high index for the proliferation marker Ki-67 predicted shorter CSS in univariate (53 vs 132 months p < 0.0001) and in multivariate analysis. To test if p53 is predictive for clinical radioresistance, as suggested by experimental models, p53 immunoreactivity was investigated in biopsies obtained before radical radiotherapy in an unrelated series of 60 PCa patients. Patients with p53 reactive tumours had longer CSS, indicating that p53 is not treatment-predictive for radiotherapy in Pca. Core biopsies were obtained before and a week after castration therapy in patients with advanced PCa. According to the serum prostate specific antigen (PSA) level 3 months after therapy, 15 responding tumours and 13 non-responding tumours were selected. Regressive morphology was seen in 14/15 responders after castration therapy, compared with 4/13 non-responders. Median apoptotic index increased significantly after castration therapy for responders (from 2.6 to 3.5, p < 0.05) whereas it was 2.8 before and after therapy in non-responders. This indicates that subsequent clinical response can be predicted by the induction of regressive morphology and an increase in apoptotic index. In conclusion, immunoreactivity for Ki-67 appeared to be a putative prognostic factor in PCa, whereas the prognostic value of p53 and bcl-2 was dubious. p53 immunoreactivity did not appear to be predictive of radioresistance in PCa. Cellular response in biopsies shortly after castration therapy might be treatment-predictive.

Adult↗

PubMed1994

Cellular expression of bone-related proteins during in vitro osteogenesis in rat bone marrow stromal cell cultures.

Rat bone marrow stromal cells comprise a heterogeneous mixture of cell lineages including osteoblastic cells. When grown in the presence of ascorbic acid, beta-glycerophosphate and 10(-8) M dexamethasone, osteoprogenitor cells within the population divide and differentiate to form bone nodules (Maniatopoulos et al., 1988, Cell Tissue Res., 254:317-330; Aubin et al., 1990, J. Bone Miner. Res., 5:S81) providing a useful model to investigate temporal and spatial changes in expression of osteoblastic markers. Immunocytochemistry was combined with Northern blotting, enzymatic assay, and radioimmunoassay to analyze the expression of bone-related proteins during the growth and differentiation sequence. By mRNA levels, protein production and/or enzymatic activity, expression of osteocalcin, bone sialoprotein, and alkaline phosphatase increased concomitantly with the development of bone nodules, while osteopontin mRNA levels decreased and those of SPARC/osteonectin did not change significantly. In older cultures with mineralizing nodules, mRNA levels for alkaline phosphatase and bone sialoprotein, but not osteocalcin, declined. Immunolabeling revealed that cells in early cultures stained poorly for SPARC/osteonectin and strongly for thrombospondin. Later, SPARC/osteonectin staining increased in most cells, while thrombospondin staining could be seen in both matrix and in cells, but with marked intercellular variability in intensity. At all time points studied, osteoblasts within bone nodules stained homogeneously for thrombospondin and alkaline phosphatase, and with marked heterogeneity of intensity amongst cells for SPARC/osteonectin and osteocalcin. Labelling with RCC455.4, a monoclonal antibody raised against rat calvaria cells which intensely labels osteoblasts and osteocytes (Turksen et al., 1992, J. Histochem. Cytochem., 40:1339-1352), co-localized with osteocalcin. Alkaline phosphatase activity and the amount of osteocalcin determined by both radioimmunoassay and immunolabelling decreased in very late cultures, a time corresponding to appearance of fully mineralized nodules. These studies indicate that the bone marrow stromal cell system is a useful model to study the temporal and spatial expression of bone-related proteins during osteogenesis and formation, mineralization, and maturation of bone nodules. Further, immunolabelling at the individual cell and single bone nodule level allowed discrimination of marked variability of expression of osteoblast markers during the differentiation sequence.

Alkaline Phosphatase↗

PubMed2005

TNF-alpha levels and TNF-alpha gene polymorphism in type I Gaucher disease.

The objective of this pilot study was to determine the levels of Tumor Necrosis Factor (TNF)-alpha and TNF-alpha gene polymorphism as a marker of inflammation among patients with type I Gaucher disease as well as to ascertain the relationship between this cytokine and parameters of disease severity and other measures of inflammation. Levels of TNF-alpha and genotyping for the -308 G-->A polymorphism in the promoter of the TNF-alpha gene were performed in 17 patients with type I Gaucher disease. TNF-alpha levels were compared with the promoter gene polymorphism, and with hematological and other clinical parameters of Gaucher disease. Eight patients (47.1%) were homozygotes (A/A) for the TNF-alpha polymorphism, six patients (35.3%) had the wild type (G/G), and three patients (17.6%) were heterozygotes (G/A). A significant correlation was found between serum TNF-alpha levels and TNF-alpha genotypes for homozygotes versus heterozygotes patients (p = 0.02), with patients homozygous for the polymorphism having the lower levels of serum TNF-alpha relative to heterozygotes with the highest levels. No correlation was found between TNF-alpha genotypes and chitotriosidase levels, a putative biochemical marker for Gaucher disease severity. Because a significant correlation was found between homozygosity for a common promoter polymorphism of TNF-alpha and milder expression i.e. non-neuronopathic form, of Gaucher disease (versus the neuronopathic forms), this may be suggestive of an association between genetic variability in TNF-alpha and phenotypic expression in Gaucher disease. Larger studies will be required.

Adolescent↗

PubMed1998

Diagnostic subgrouping of depressed patients by principal component analysis and visualized pattern recognition.

A data-analytical method is described for identifying behavioral and biological variables in psychiatric patients with predictive value in defining clinical subgroups. The procedure, based on principal component analysis (PCA) and graphical analysis, was applied in a group of 28 depressed patients. The 28 depressed patients of unipolar type were observed for up to 15 years for re-evaluation of the diagnoses at the start of the study. Platelet monoamine oxidase activity, post-dexamethasone serum cortisol and serum melatonin predicted two main clinical subgroups as well as a smaller subgroup of bipolar patients. The selection procedure revealed which of several variables were predictive of subgroups that were not possible to identify by univariate methods. The three biological variables may thus be useful in further assessment of clinical subgroups of unipolar depressed patients studied by other research groups.

Adult↗

PubMed1998

Serum levels of cross-linked N-telopeptides and aminoterminal propeptides of type I collagen indicate low bone mineral density in elderly women.

Levels of aminoterminal propeptide (PINP) and the cross-linked carboxyterminal (ICTP) and aminoterminal (NTx) telopeptides of type I collagen were determined in the sera of 202 healthy women, 60-90 years of age, and correlated with densitometric measurements of their lumbar spine, femoral neck, and total body regions. Total skeleton bone mineral density (BMD) was associated most strongly with serum NTx levels (r = -0.51, p < 0.0001). Serum NTx and PINP levels correlated with BMD at all regions measured and were significantly increased in osteopenic women (16.0 vs. 13.3 nmol bone collagen equivalents/L for NTx, p = 0.0006 and 46.5 vs. 40.9 micrograms/L for PINP, p = 0.02). Elevations of NTx and PINP over a 3 year interval correlated with decreases in BMD measured at the femoral neck and to increases in serum concentration of alkaline phosphatase activity and ICTP. Serum levels of ICTP, NTx, PINP, ICTP, estrone, and alkaline phosphatase activity were correlated and serum NTx values were related to circulating thyroxine and intact parathyroid hormone levels. NTx and PINP levels were significantly decreased in the sera of women receiving estrogen replacement therapy (12.0 vs. 14.8 nmol bone collagen equivalents/L for NTx, and 35.5 vs. 45.2 micrograms/L for PINP, p < 0.001). Multiple regression analysis indicated that 42% of the variability observed in total skeletal BMD could be explained by age, weight, and serum levels of NTx and estrone. Within this model of covariance, the serum NTx level alone accounted for 10.1% of total body BMD variability.

Absorptiometry, Photon↗