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David G Grenache

Publications and source records attributed to David G Grenache.

13 recordsLinked to original sources
PubMed2006

Wound healing in the alpha2beta1 integrin-deficient mouse: altered keratinocyte biology and dysregulated matrix metalloproteinase expression.

The alpha2beta1 integrin, a collagen/laminin receptor, is expressed at high level in the basal cell layer of the epidermis. To define the role of the alpha2beta1 integrin in wound healing, wound repair was extensively evaluated in wild-type and alpha2-null mice in vivo. In addition, the impact of alpha2beta1 integrin-deficiency on the function of primary murine keratinocytes in vitro was analyzed. Our in vivo findings demonstrate that genetic deletion of the alpha2beta1 integrin does not significantly alter the rate of re-epithelialization, collagen deposition, or tensile strength during wound closure in mice. In marked contrast to the observed similarities in wound healing, deletion of the alpha2beta1 integrin resulted in a dramatic increase in neoangiogenesis in the wound microenvironment. In contrast to in vivo studies, primary keratinocytes from alpha2-null mice adhered poorly and displayed impaired migration on type I collagen in vitro. We demonstrate that alpha2beta1 integrin-ligation negatively regulates expression of genes including matrix metalloproteinases both in vivo and in vitro. Furthermore, the changes in gene expression could potentially account for relatively normal wound healing in the alpha2-deficient mouse and our recent observation that suggests an antiangiogenic role for the alpha2beta1 integrin in vivo.

Animals↗
PubMed2006

Integrated and automatic mixing of whole blood: an evaluation of a novel blood gas analyzer.

BACKGROUND: A homogeneous whole blood specimen is essential to produce quality results from blood gas analysis, however achieving an adequately mixed specimen can be difficult due to the absence of any dead space in a blood gas syringe. This study evaluated the efficacy of an automatic mixing feature incorporated into the ABL800 FLEX blood gas analyzer and estimated the systematic error in tests performed by the instrument. METHODS: Quantitative measurements of pH, PCO(2), PO(2), Na(+), K(+), Ca(+), glucose, lactate, and total hemoglobin were performed on 388 whole blood specimens collected into standard blood gas syringes or specific syringes designed to work in conjunction with the ABL800 FLEX. One hundred eighty specimens were manually or automatically mixed following horizontal storage for 10, 20, or 30 min and total hemoglobin was used as in indicator of specimen homogeneity. Two hundred eight specimens were used to estimate the systematic error of tests performed by the ABL800 FLEX. RESULTS: Manual mixing produced significantly more variation in paired hemoglobin measurements compared to automatic mixing at all three time points (p<0.0001). All estimates of systematic error were very low and clinically insignificant. Quantitative results showed excellent agreement with a reference analyzer. CONCLUSIONS: In contrast to manual mixing, automatic mixing by the ABL800 FLEX consistently produces a homogeneous specimen.

Adult↗
PubMed2006

Immunofixation reveals an apparent alpha heavy chain caused by precipitation of fibrinogen with IgA antiserum.

BACKGROUND: Fibrinogen present in serum specimens can interfere with the interpretation of serum protein electrophoresis. We report here the unexpected precipitation of fibrinogen by an IgA antiserum used in immunofixation electrophoresis. METHODS: Immunofixation electrophoresis of plasma combined with ethanol precipitation, serial dilution of plasma, and fibrinogen adsorption of the antiserum were used to investigate the apparent immunoreactivity of a commercial source of IgA antiserum to fibrinogen. RESULTS: Fibrinogen immunoreactivity by IgA antiserum was observed at fibrinogen concentrations > or =0.93 g/l. Ethanol precipitation of plasma removed fibrinogen and prevented the immunofixation of the protein by the IgA antiserum. Adsorption of the IgA antiserum with human fibrinogen removed its ability to precipitate fibrinogen, demonstrating cross-reactivity between the IgA antiserum and fibrinogen. CONCLUSIONS: Commercial sources of antiserum used for immunofixation electrophoresis may contain antibodies with specificity towards proteins typically absent from serum such as fibrinogen and can produce clinically misleading results.

Female↗
PubMed2005

Fetal lung maturity.

Respiratory distress syndrome of the newborn infant caused by immaturity of the fetal lung continues to be a clinical problem. Measurement of pulmonary surfactant production is the most effective way to evaluate pulmonary maturity. Since the first fetal lung maturity test was described more than two decades ago, advances in methodology have produced diagnostically sensitive tests that are both rapid and precise. Unfortunately, currently available tests continue to demonstrate low diagnostic specificity and remain poor predictors of fetal lung immaturity. We review the background, methodology, pre-analytical and analytical concerns, and clinical performance of various fetal lung maturity assays, and discuss the appropriate use and interpretation of these tests.

Fetal Organ Maturity↗
PubMed2005

Diagnostic considerations in the measurement of human chorionic gonadotropin in aging women.

BACKGROUND: Human chorionic gondadotropin (hCG) screening tests are performed on nearly all female patients of childbearing age before any medical intervention. Although older women usually have negative hCG test results, positive results do occur and may cause clinical confusion. We examined changes with age in serum hCG concentrations in nonpregnant women and investigated the use of serum follicle-stimulating hormone (FSH) measurements as an aid to interpreting higher than expected ("positive") hCG results. METHODS: We used 240 serum specimens for each of 4 female cohorts: pregnant, > or =18 years; nonpregnant, 18-40 years (premenopausal); nonpregnant, 41-55 years (perimenopausal); and nonpregnant, >55 years (postmenopausal). Patients were excluded if they had an ectopic pregnancy, a history of trophoblastic disease or a germ-cell tumor, or if no chart was available for review. Quantitative hCG and FSH tests were performed on each specimen. RESULTS: Serum hCG concentrations in nonpregnant women increased with the age of the women. hCG results were higher and significantly different (P < 0.0001) for nonpregnant women >55 years (<2.0 to 13.1 IU/L) compared with nonpregnant women 18-40 years (<2.0 to 4.6 IU/L) and 41-55 years (<2.0 to 7.7 IU/L). Nineteen nonpregnant women >40 years of age had hCG concentrations > or = 5.0 IU/L, all with an FSH concentration >32.4 IU/L. The highest FSH concentration in pregnancy was 7.3 IU/L. CONCLUSIONS: Serum hCG increases with age in nonpregnant women. A cutoff of 14.0 IU/L should be used when interpreting hCG results in women >55 years of age. Pregnancy is unlikely in perimenopausal women 41-55 years of age with an hCG between 5.0 and 14.0 IU/L if serum FSH is >20.0 IU/L.

Adolescent↗
PubMed2005

Effect of anemia on plasma concentrations of NT-proBNP.

BACKGROUND: Concentrations of the amino-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) are increased in the blood of patients with heart failure. Understanding the variables that influence the concentrations of NT-proBNP is required to refine its clinical use criteria. The effect of anemia on plasma concentrations of NT-proBNP was investigated. METHODS: Hemoglobin and NT-proBNP were measured in blood specimens collected from 209 adult patients without heart failure or renal disease. RESULTS: The median NT-proBNP concentration of patients with anemia was significantly higher than in those without anemia (82 vs. 232 ng/l, p<0.0001). Anemic patients were also 3 times more likely to have an NT-proBNP concentration that exceeded age-specific cutoffs recommended by the assay manufacturer (odds ratio 3.1, 95% CI 1.7 to 5.4, p<0.0001). CONCLUSIONS: Decreased concentrations of hemoglobin are sufficient to produce serum concentrations of NT-proBNP above diagnostic cutoffs in anemic patients without heart failure independent of gender, body mass index, glomerular filtration rate, left ventricular hypertrophy, and valve disease. The impact of this finding on the clinical use and interpretation of the test needs to be examined.

Adolescent↗
PubMed2004

Endometrial adenocarcinoma associated with elevated serum concentrations of the free beta subunit of human chorionic gonadotropin.

We report a case of a histologic grade II endometrial adenocarcinoma without trophoblastic differentiation in a 24-year-old woman with an elevated serum concentration of human chorionic gonadotropin (hCG) and with no evidence of pregnancy. Serum and urine specimens were used to study the hCG immunoreactivity. Qualitative tests performed on serum and urine using 5 different assays produced conflicting results. The hCG concentration in serum and urine was quantified using assays designed to detect different molecular forms of the molecule; analysis revealed that serum hCG immunoreactivity was due entirely to the presence of the free beta subunit. Immunohistochemical analysis performed on tissue samples showed strong cytoplasmic staining for hCG. While hCG is a well-recognized tumor marker in gynecologic malignant neoplasms, immunoreactivity most often is due to the presence of both intact molecule and the free beta subunit. To our knowledge, this is the first report of an endometrial adenocarcinoma producing only the free beta subunit of hCG.

Adult↗
PubMed2003

Alpha2beta1 integrin and development of atherosclerosis in a mouse model: assessment of risk.

OBJECTIVE: The alpha2beta1 integrin serves as a collagen or collagen/laminin receptor on many cell types, including endothelial cells and platelets. Many studies indicate that the alpha2beta1 integrin is a critical mediator of platelet adhesion to collagen. Epidemiologic studies suggest a direct correlation between the genetically determined platelet surface density of the alpha2beta1 integrin and the risk of thrombotic diseases, such as myocardial infarction and stroke, in the young, which are well-established complications of atherosclerosis. We have now used the alpha2beta1 integrin-deficient mouse to evaluate the contributions of the alpha2beta1 integrin to the development of atherosclerosis. METHODS AND RESULTS: We generated wild-type (alpha2+/+) or alpha2beta1 integrin-deficient (alpha2-/-) mice that were also deficient in the apolipoprotein E (ApoE) gene (ApoE-/-) and compared atherosclerotic lesion development in alpha2+/+ ApoE-/- and alpha2-/- ApoE-/- mice that were fed a high-fat, cholesterol-containing diet for 6 or 15 weeks. Total lesional area did not differ significantly between the alpha2-null animals and the wild-type animals at either 6 or 15 weeks. CONCLUSIONS: Our results suggest that risk for arterial thrombotic disease associated with high-level alpha2beta1 integrin expression is not attributable to enhanced development of atherosclerosis per se but may rather be a consequence of thrombotic complications at the plaques.

Animals↗
PubMed2003

The contributions of the alpha 2 beta 1 integrin to vascular thrombosis in vivo.

The alpha 2 beta 1 integrin serves as a receptor for collagens, laminin, and several other nonmatrix ligands. Many studies have suggested that the alpha 2 beta 1 integrin is a critical mediator of platelet adhesion to collagen within the vessel wall after vascular injury and that the interactions of the platelet alpha 2 beta 1 integrin with subendothelial collagen after vascular injury are required for proper hemostasis. We have used the alpha 2 beta 1 integrin-deficient mouse to evaluate the contributions of the alpha 2 beta 1 integrin in 2 in vivo models of thrombosis. Studies using a model of endothelial injury to the carotid artery reveal that the alpha 2 beta 1 integrin plays a critical role in vascular thrombosis at the blood-vessel wall interface under flow conditions. In contrast, the alpha 2 beta 1 integrin is not required for the formation of thrombi and pulmonary emboli following intravascular injection of collagen. Our results are the first to document a critical in vivo role for the alpha 2 beta 1 integrin in thrombus formation at the vessel wall under conditions of shear following vascular injury.

Animals↗
PubMed2003

Preanalytical factors that influence the Abbott TDx Fetal Lung Maturity II assay.

BACKGROUND: The TDx Fetal Lung Maturity II (FLM II) assay uses amniotic fluid to assess lung maturity of the unborn infant. We investigated common preanalytical factors that influence FLM results, including centrifugation, sample storage, and contamination by whole blood. METHODS: We tested 18 specimens after centrifugation and after resuspension by vortex-mixing. We also analyzed 23 specimens stored at -20 degrees C for up to 448 days and then thawed (duplicate measurements), 20 specimens stored at 4 degrees C, and 24 specimens stored at room temperature. In addition, we evaluated the effects of whole blood diluted into 19 different specimens. RESULTS: Centrifugation significantly decreased FLM II results from baseline (P <0.0001), and resuspension returned results to baseline values (P = 0.286). Storage at -20 degrees C produced highly variable results that demonstrated a nonsignificant negative trend associated with storage time. Specimens were stable for 24 h when stored at 4 degrees C and 16 h at room temperature. Blood contamination produced significantly positive differences in results only in specimens with baseline values < or =39 mg/g with a 5.8 mg/g increase in FLM II for every 0.1 x 10(12)/L increase in the erythrocyte count (slope = 58.4). CONCLUSIONS: Resuspension of centrifuged specimens produces clinically valid FLM II results. Results from specimens stored at -20 degrees C can be highly variable and decrease over time. Results from specimens stored at 4 degrees C and at room temperature are stable for 24 and 16 h, respectively. Blood contamination up to 0.03 x 10(12) erythrocytes/L is acceptable for FLM II analysis.

Albumins↗
PubMed2002

The alpha(2) integrin subunit-deficient mouse: a multifaceted phenotype including defects of branching morphogenesis and hemostasis.

The alpha(2)beta(1) integrin is a collagen/laminin receptor expressed on platelets, endothelial cells, fibroblasts, and epithelial cells. To define the role of the alpha(2)beta(1) integrin in vivo, we created a genetically engineered mouse in which expression of the alpha(2)beta(1) integrin was completely eliminated. Mice deficient in the alpha(2)beta(1) integrin are viable, fertile, and develop normally with no excess lethality of homozygotes. Both alpha(2)beta(1)-integrin protein and alpha(2) mRNA were undetectable in the alpha(2)-null mice. Gross and histological evaluation of the heart, lungs, kidneys, gastrointestinal tract, pancreas, skin, and reproductive tracts revealed no abnormalities. However, quantitative analysis of mammary gland branching morphogenesis demonstrated that branching complexity is markedly diminished in the alpha(2)-deficient animals. Studies in the alpha(2)-deficient animals do not support the proposed roles for the alpha(2)beta(1) integrin on fibroblasts and keratinocytes in wound healing. When compared to platelets from wild-type littermates, platelets from alpha(2)-null mice failed to adhere to type I collagen under either static or shear-stress conditions. Although platelets from alpha(2)-deficient animals aggregated in response to collagen, they did so with prolonged lag time and lessened intensity. The alpha(2)beta(1) integrin-null mouse thus exhibits diverse, sometimes subtle, phenotypes consistent with the widespread pattern of alpha(2)beta(1) integrin expression.

Animals↗