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PubMed1996

Phenotypic expression of marrow cells when grown on various substrata.

Our aim was to study the role of various extracellular matrices (ECM) on growth and differentiation of marrow stromal cells in vitro. Morphology changes, gene expression, and enzymatic activities were monitored in stromal osteoblastic MBA-15 and adipocytic 14F1.1 cells. These stromal cells were plated on dishes precoated with different substrata, such as matrigel (basement membrane), collagen type I, and endothelial ECM, and compared with cells plated on protein-free dishes. Striking morphological differences were observed when the cells grew on these different substrata. Changes in cell shape and growth also led to differential mRNA expression and enzymatic activities. When MBA-15 cells were plated on collagen, there was a decrease in mRNA for alkaline phosphatase (ALK-P), osteopontin (OP), and osteonectin (ON), and an increase in mRNA for procollagen (I). A differential effect was noted on 14F1.1 cells, the mRNA for ALK-P increased, the expressions of OP and ON lowered, and no expression for procollagen (I) was monitored. MBA-15 cells cultured on matrigel had decreased mRNA for ALK-P and OP, while they had increased ON mRNA expression and remained unchanged for procollagen I. No change in mRNA expression by 14F1.1 cells was monitored when cultured on matrigel. Functional enzymatic activities of ALK-P markedly decreased in MBA-15 cells cultured on various substrata, and increased or were unchanged in 14F1.1 cells. An additional enzyme, neutral endopeptidase (CD10/NEP), altered differentially in both cell types; this enzymatic activity increased or was unchanged when cells were cultured on these matrices. The results indicate a specific role for different ECM on various stromal cell types and their function.

Adipocytes↗
PubMed1999

Anaplastic large cell lymphoma: a clinicopathologic analysis.

The clinicopathologic features of anaplastic large cell lymphoma (ALCL) are reviewed. ALCL is a heterogeneous group of tumours, and histologic examination alone is not adequate in providing useful prognostic information. However, using a combination of clinical, phenotypic, and genotypic features, several distinct clinicopathologic entities have been identified. A subset of ALCL as presently defined is characterized by a balanced translocation, t(2;5)(p23;q35), resulting in a novel fusion protein (NPM-ALK) that can be readily detected by immunohistochemical methods using antibodies against the ALK protein. Detection of ALK protein, along with other methods for demonstrating the t(2;5), has assisted in identifying a distinct biologic entity within the heterogeneous group of ALCL with significant prognostic implications. It is important to separate these from cases of ALK-negative ALCL, which have a poorer prognosis, and cases of primary cutaneous ALCL, which have an excellent prognosis.

Adolescent↗
PubMed2004

Selective inhibition of activin receptor-like kinase 5 signaling blocks profibrotic transforming growth factor beta responses in skin fibroblasts.

OBJECTIVE: Members of the transforming growth factor beta (TGFbeta) cytokine superfamily play critical roles in both homeostasis and disease. In light of their profibrotic effects, these molecules are implicated in the pathogenesis of fibrosis. In fibroblasts, TGFbeta signals through the activin receptor-like kinase 5 (ALK-5) type I TGFbeta and triggers Smad and MAP kinase signaling pathways. Because targeting of TGFbeta signaling represents a potential approach to the treatment of systemic sclerosis (SSc) and other fibrotic disorders, we investigated the modulation of intracellular TGFbeta signal transduction by SB431542, the first small-molecule inhibitor of ALK-5 to be described. METHODS: Ligand-induced activation of the Smad signaling pathway in human dermal fibroblasts was examined by Western blot analysis and confocal immunocytochemistry. Modulation of profibrotic gene expression was investigated using Northern blot analysis, transient transfection assays, and confocal microscopy. Induction of TGFbeta production was evaluated by enzyme-linked immunosorbent assay. RESULTS: SB431542 abrogated TGFbeta-induced phosphorylation and nuclear importation of endogenous Smad2/3 and Smad4, and inhibited Smad3- and Smad2-dependent gene transcription. Treatment with SB431542 prevented TGFbeta-induced stimulation of collagen, fibronectin, plasminogen activator inhibitor 1, and connective tissue growth factor gene expression, TGFbeta autoinduction, and myofibroblast transdifferentiation, and it could reverse stimulation even when added to the cultures after TGFbeta. In contrast, STAT-6-mediated stimulation of collagen gene expression induced by interleukin-13 was not prevented by SB431542, indicating the specificity of blockade for ALK-5-dependent signaling. Furthermore, in contrast to its effects on receptor-activated Smad activation, SB431542 failed to prevent TGFbeta-induced activation of MAP kinases. CONCLUSION: The results indicate that SB431542 is a potent inhibitor of intracellular TGFbeta signaling in normal fibroblasts through selective interference with ALK-5-mediated Smad activation and Smad-dependent transcriptional responses. Therefore, SB431542 is useful as a novel experimental tool for gaining a detailed understanding of normal and aberrant TGFbeta signaling in SSc. Furthermore, as an anti-TGFbeta agent, SB431542 may represent a potential new approach to the treatment of fibrosis.

Activin Receptors, Type I↗
PubMed2003

Cytologic and immunocytochemical findings of anaplastic large cell lymphoma: analysis of ten fine-needle aspiration specimens over a 9-year period.

BACKGROUND: Anaplastic large cell lymphoma (ALCL) has raised much controversy in the field of hematolymphoid pathology. Its nature is becoming better characterized with recent advances in molecular genetics. However, to the authors' knowledge, a detailed description of the fine-needle aspiration (FNA) cytology of ALCL is lacking and the application of immunocytochemical study, including immunostaining for anaplastic lymphoma kinase (ALK) protein, to cytology samples has not been studied to date. METHODS: The authors reviewed 10 FNA specimens of ALCL from 8 patients encountered at Pamela Youde Nethersole Eastern Hospital and Queen Mary Hospital in Hong Kong over a 9-year period from early 1993 to the end of 2001. The cytologic and immunocytochemical findings (including ALK protein overexpression) of the specimens were correlated with histologic and immunohistochemical findings of surgical biopsy specimens. RESULTS: Six of the eight patients had ALCL of the common variant, whereas the remaining two patients had ALCL of the small cell variant. FNA specimens of ALCL of the common variant yielded many loosely dispersed "hallmark" cells that contained eccentric kidney-shaped or embryo-like nuclei, several prominent rod-shaped or angulated basophilic nucleoli, and abundant amphophilic cytoplasm. "Doughnut" cells, tumor cells with multilobated nuclei, and multinucleated giant cells with a wreath-like arrangement of nuclei occasionally were found. A small number of "plasmacytoid" tumor cells, nondescript small round tumor cells, and reactive polymorphs also was present. In contrast, "plasmacytoid" cells and nondescript small to medium-sized tumor cells represented the predominant cell population in ALCL of the small cell variant. The "plasmacytoid" appearance was exaggerated further in air-dried smears. In air-dried smears, small intracytoplasmic vacuoles and scanty azurophilic granules also were noted. On immunocytochemical study performed using the cell block materials, the majority of tumor cells demonstrated membranous and paranuclear "dot-like" positivity for CD30. The staining for epithelial membrane antigen, leukocyte common antigen, and T-cell markers was variable. Positive staining for ALK protein was demonstrated beautifully in two of the cases. CONCLUSIONS: Despite the wide morphologic spectrum of ALCL, a definitive diagnosis on the basis of FNA cytology is possible on careful interpretation of the cytologic features and a high index of suspicion. The cytologic diagnosis can be confirmed further with proper application of immunostaining to cell block sections. Immunocytochemical study for ALK protein, which provides useful prognostic information, also can be demonstrated satisfactorily using cytology samples.

Adolescent↗
PubMed2006

Proteomic analysis of anaplastic lymphoma cell lines: identification of potential tumour markers.

Anaplastic large-cell lymphomas (ALCL) are high grade lymphomas of T or null phenotype often associated with the t(2;5) translocation leading to the expression of a chimeric protein consisting of the N-terminal portion of nucleophosmin (NPM) and the intracellular domain of the anaplastic lymphoma kinase (ALK). Although ALCL are recognized as distinct clinical, biological and cytogenetic entities, heterogeneities persist in this group of tumours, which exhibit a broad spectrum of morphological features. Particularly, the common type tumour consisting in large cells contrast with the small cell variant that is sometimes associated with a leukemic phase. The ALK-negative ALCL is often associated with a poor prognosis. Here, we investigated the proteome of these subtypes of tumours using patient-derived cell lines. We compared the proteome of the cytosolic fraction of NPM-ALK-positive versus NPM-ALK-negative cells on one hand, and the proteome of common cell type versus small cell variant on the other hand. The identification of a set of proteins differentially expressed in the subtypes of ALCL points to new diagnosis/prognosis markers. This study also provides interesting information on the molecular mechanisms responsible for the different subtypes of ALCL.

Anaplastic Lymphoma Kinase↗
PubMed1996

Truncated activin type II receptors inhibit bioactivity by the formation of heteromeric complexes with activin type I. receptors.

Truncated activin type II receptors have been reported to inhibit activin receptor signaling in Xenopus embryos, although the mechanism of action for this effect has not been fully understood. In the present study we demonstrate that in P19 embryonal carcinoma cells both the induction of the activin responsive 3TP-lux reporter construct and the inhibition of retinoic acid-induced neuronal differentiation by activin are blocked by expression of a truncated activin receptor. To reveal the mechanism of action of truncated activin receptors, the interaction between different activin receptors has been investigated upon coexpression in COS cells followed by cross-linking of 125I-activin A and subsequent immunoprecipitation. Complexes between a truncated activin type IIA receptor and activin type IA and type IB receptors can be formed, as demonstrated by coimmunoprecipitation of these type I receptors with the truncated activin type IIA receptor. Other type I receptors known as ALK-1 and ALK-6 also coimmunoprecipitate with the truncated type IIA receptor, whereas ALK-3 and ALK-5 do not. Furthermore, the activin type IIB2 receptor does not coimmunoprecipitate with the truncated type IIA receptor, but decreases activin binding to the truncated type IIA receptor. In double immunoprecipitation experiments with cell lysates from COS cells, in which full-length activin type IIA and type IIB2 receptors were cotransfected, no interaction between these receptors was found. In contrast, homomeric complexes of full-length activin type IIA receptors were detected. These results implicate that truncated activin receptors can interfere with activin signaling by interacting with activin type I receptors. Additionally, truncated activin type IIB2 receptors might also interfere with type IIA receptor signaling by decreasing activin binding to the type IIA receptor and therefore might be more potent in inhibiting activin signal transduction. Furthermore, our data indicate that truncated type IIA receptors can interact with other type I receptors and as such might inhibit signal transduction by type I receptors other than activin type IA and type IB receptors.

Activin Receptors↗
PubMed1997

Thermophilic biodegradation of BTEX by two consortia of anaerobic bacteria.

Two thermophilic anaerobic bacterial consortia (ALK-1 and LLNL-1), capable of degrading the aromatic fuel hydrocarbons, benzene, toluene, ethylbenzene, and the xylenes (BTEX compounds), were developed at 60 degrees C from the produced water of ARCO'S Kuparuk oil field at Alaska and the subsurface water at the Lawrence Livermore National Laboratory gasoline-spill site, respectively. Both consortia were found to grow at 45-75 degrees C on BTEX compounds as their sole carbon and energy sources with 50 degrees C being the optimal temperature. With 3.5 mg total BTEX added to sealed 50-ml serum bottles, which contained 30 ml mineral salts medium and the consortium, benzene, toluene, ethylbenze, m-xylene, and an unresolved mixture of o- and p-xylenes were biodegraded by 22%, 38%, 42%, 40%, and 38%, respectively, by ALK-1 after 14 days of incubation at 50 degrees C. Somewhat lower, but significant, percentages of the BTEX compounds also were biodegraded at 60 degrees C and 70 degrees C. The extent of biodegradation of these BTEX compounds by LLNL-1 at each of these three temperatures was slightly less than that achieved by ALK-1. Use of [ring-14C]toluene in the BTEX mixture incubated at 50 degrees C verified that 41% and 31% of the biodegraded toluene was metabolized within 14 days to water-soluble products by ALK-1 and LLNL-1, respectively. A small fraction of it was mineralized to 14CO2. The use of [U-14C]benzene revealed that 2.6%-4.3% of the biodegraded benzene was metabolized at 50 degrees C to water-soluble products by the two consortia; however, no mineralization of the degraded [U-14C]benzene to 14CO2 was observed. The biodegradation of BTEX at all three temperatures by both consortia was tightly coupled to sulfate reduction as well as H2S generation. None was observed when sulfate was omitted from the serum bottles. This suggests that sulfate-reducing bacteria are most likely responsible for the observed thermophilic biodegradation of BTEX in both consortial cultures.

Bacteria, Anaerobic↗
PubMed1999

[Long-term stability of astigmatism outcome after arcuate lamellar keratotomy. 3-year results of a prospective study].

INTRODUCTION: The correction of low to moderate astigmatism is possible today by means of photoablation (PRK), while the treatment of moderate and higher astigmatism still involves refractive keratotomy. Experience has shown that cataract surgery, using modern tunnel techniques with self-healing incisions, results in earlier stability in both the refractive outcome and wound healing. In this study, we attempted to combine the advantages of lamellar keratotomy with those of a pair-wise T-incision as arcuate lamellar keratotomy (ALK). PATIENTS AND METHODS: The clinical outcome of 41 patients who underwent ALK was investigate in a prospective study over a period of 3 years. The pre- and postoperative investigations undertaken included the measurement of astigmatism using a Zeiss keratometer, uncorrected visual acuity, and corrected glare vision using a Humphrey autorefractor. All patients had astigmatism between 2.0 and 7.0 D. Together with a uniform arcuate incision, we used 7 mm (n = 26) and 8 mm (n = 15) mm zones for correction. RESULTS: The average preoperative astigmatism was 4.01 +/- 1.90 (median, 3.50) D. After a 3-year follow-up the average postoperative astigmatism was 1.59 +/- 1.29 (median, 1.38) D. The astigmatic change induced (Jaffé) after 3 years was about 3.23 +/- 2.23 (median, 3.16) D. The average uncorrected visual acuity (log MAR) before ALK was 0.20 +/- 0.12 (median, 0.22) and after follow-up, 0.41 +/- 0.14 (median, 0.39). Corrected glare vision before surgery was 0.23 +/- 0.19 (median, 0.10) and afterwards, 0.25 +/- 0.22 (median, 0.14). CONCLUSIONS: Arcuate lamellar keratomy (ALK) stood the test as a routine clinical procedure for correction of moderate astigmatism with stable postoperative functional outcomes. We did not find impairment of glare vision following this procedure.

Aged↗
PubMed2004

Primary anaplastic large cell lymphoma of the testis.

Anaplastic large cell lymphoma (ALCL) was first described by Stein et al. in 1985, at that time neoplastic cells were labeled by the monoclonal antibody CD30. ALCL was included as a differentiate entity in the reviewed Kiel and REAL classification. ALCL carries the t (2; 5) (p23; q35) translocation; the absence of ALK kinase from normal lymphoid cells indicates that immunohistochemical expression of ALK is specific for the (2; 5) translocation. This disease is characterized by a diffuse proliferation of large anaplastic cells with kidney-shaped/horse-shoe nuclei. A distinguishing feature is a perinuclear eosinophilic region that represents a prominent Golgi apparatus. These cells are named hallmark-cells being almost pathognomonic. Immunohistochemically the most important features are that tumor cells consistently express CD30 and EMA on the cell membrane and in the Golgi region, while ALK immunostaining is usually both, cytoplasmic and nuclear. To our knowledge only two cases of primary ALCL of the testis have been reported. Hereby we present a case of a typical ALCL expressing ALK and CD30, which presented with subcutaneous nodules and bilateral testicular mass, without systemic involvement.

Adult↗
PubMed1986

Plasmalogen biosynthesis in Madin-Darby canine kidney cells: selectivity in the acylation of 1-alkyl-2-lyso-sn-glycero-3-phosphoethanolamine and the subsequent desaturation step.

Acyl group specificity in the acylation of 1-alkyl-2-lyso-sn-glycero-3-phosphoethanolamine (1-alkyl-2-lyso-GroPEtn) to form 1-alkyl-2-acyl-sn-glycero-3-phosphoethanolamine (1-alkyl-2-acyl-GroPEtn) and the subsequent desaturation of 1-alkyl-2-acyl-GroPEtn to form plasmalogens (1-alk-1'-enyl-2-acyl-sn-glycero-3-phosphoethanolamine, i.e., 1-alk-1'-enyl-2-acyl-GroPEtn) was investigated in intact Madin-Darby canine kidney (MDCK) cells and cell-free membrane preparations. We found 1-[3H]alkyl-2-lyso-GroPEtn was selectively acylated with polyunsaturated fatty acids in the order 20:4 greater than 20:5 greater than 20:3 (n-9) greater than 22:6 by cell-free membrane preparations of MDCK cells. The same pattern of acyl specificity was seen in intact MDCK cells, although the intact cells produced significantly larger amounts of 1-[3H]alkyl-2-acyl-GroPEtn containing oleic acid. There was an increased desaturation of the 1-[3H]alkyl-2-acyl-GroPEtn species containing docosahexaenoic acid to plasmalogens (1-[3H]alk-1'-enyl-2-acyl-GroPEtn) by both intact MDCK cells and the cell-free membrane preparations. The relatively rapid disappearance of the 1-[3H]alk-1'-enyl-2-docosahexaenoyl-GroPEtn species during a 20-h incubation of prelabeled intact MDCK cells suggests a more rapid turnover of this molecular species. Our results indicate there is a high selectivity in the final acylation and desaturation steps of the biosynthetic pathway for plasmalogens.

Acylation↗
PubMed1982

Ether-linked lipids of Balb/c3T3, SV3T3 and concanavalin A-selected SV3T3 revertant cells.

Ether-linked lipids were analyzed in Balb/c3T3, SV3T3 and Concanavalin A-selected SV3T3 revertant cells. The three cell lines were found to contain significant quantities of alk-1-enyl- and alkyl-linked phosphatidylethanolamine (PE) and phosphatidylcholine (PC) and small amounts of alkyldiacylglycerols. Compared to 3T3 cells, SV3T3 cells contain a higher amount of alk-1-enyl-linked PC, while in SV3T3 revertant cells the concentrations of the various ether lipids are similar to those of 3T3 cells. The major difference in the composition of ether groups of SV3T3 cells, compared to 3T3 cells, is an increase of 18:0 accompanied by a decrease of 18:1 in the alk-1-enyl-linked PE and PC. Alk-1-enyl-linked PC of SV3T3 revertant cells also shows an increase of 18:0, while the decrease of 18:1 was not statistically significant.

Alcohols↗
PubMed1982

Transfer of 2H atoms to molecular species of ether analogues of hepatic phosphatidylcholines and phosphatidylethanolamines during metabolism of [l,l-2H2]ethanol in rats.

Rats were given [1,1-2H2]ethanol once every hour for 3-48 h and the concentrations of and deuterium incorporation into individual molecular species of either analogues of phosphatidylcholines and phosphatidylethanolamines were determined. The concentration of 1-alkyl-2-acyl-sn-glycero-3-phosphocholines increased 50-100%. The total amount of 1-alk-1'enyl-2-acyl-sn-glycero-3-phosphocholines was relatively constant but the percentage of 1-hexadec-1'-enyl-2-palmitoyl-sn-glycero-3-phosphocholine decreased throughout the experiment. A small increase of 1-alk-1'-enyl-2-sn-glycero-3-phosphoethanolamines was observed. The total deuterium content at C-2 and C-3 of the glycerol moiety of 1-alkyl-2-acyl- and 1-alk-1'-enyl-2-acyl-sn-glycero-3-phosphocholines was 2.7-4.4 atom% and 0.3-0.8 atom%, respectively, after 48 h of [1,1-2H2]ethanol administration. The corresponding values for 1-alk-1'-enyl-2-acyl-sn-glycero-3-phosphoethanolamines were 1.2-2.9 atom%. The deuterium content at C-1 of the alkyl group of 1-alkyl-2-acyl-sn-glycero-3-phosphocholines was low. The results are compatible with formation of ether lipids from alkyl dihydroxyacetone phosphate followed by reduction with NADPH with low labelling, but argue strongly against participation of alcohol dehydrogenase in the formation of the fatty alcohol.

Animals↗
PubMed1995

The CoA-independent transacylase in PAF biosynthesis: tissue distribution and molecular species selectivity.

Microsomal membranes from six different rat tissues (spleen, lung, kidney, brain, testis, and liver) were found to possess CoA-independent transacylase activity that could both acylate lyso-[3H]PAF (1-[3H]hexadecyl-2-lyso-sn-glycero-3-phosphocholine) and then deacylate the 1-[3H]hexadecyl-2-acyl-sn-glycero-3-phosphocholine product via the transacylation of added exogenous 1-alk-1'-enyl-2-lyso-sn-glycero-3-phosphoethanolamine. Platelet-activating factor (1-[3H]hexadecyl-2-acetyl-sn-glycero-3-phosphocholine) was produced when acetyl-CoA was added to the spleen microsomes during generation of lyso-[3H]PAF by the transacylases. More extensive studies with subcellular fractions from spleen revealed that, in addition to microsomes, the transacylase activities were also present in the 15,000 x g membrane fraction but not in the cytosol. Analysis of molecular species of 1-[3H]hexadecyl-2-acyl-sn-glycero-3-phosphocholine before and after addition of 1-alk-1'-enyl-2-lyso-sn-glycero-3-phosphoethanolamine as the acyl acceptor demonstrated a high selectivity for polyunsaturated fatty acids (> 3 double bonds/acyl group) in both the acylation and deacylation processes that occurred in testicular microsomal membranes. The transfer of acyl groups by the transacylase appeared to be equally effective for either arachidonic or docosapentaenoic(n - 6) fatty acids, whereas linoleic and oleic fatty acids were not transferred from 1-[3H]hexadecyl-2-acyl-sn-glycero-3-phosphocholine following the addition of 1-alk-1'-enyl-2-lyso-sn-glycero-3-phosphoethanolamine. Similar experiments with the membrane fraction of undifferentiated HL-60 cells showed that arachidonic acid supplementation of intact cells enhanced both the CoA-independent transacylation of lyso-[3H]PAF and the subsequent deacylation of 1-[3H]hexadecyl-2-acyl-sn-glycero-3-phosphocholine caused by addition of 1-alk-1'-enyl-2-acyl-sn-glycero-3-phosphoethanolamine. Differentiation of the HL-60 cells into a neutrophil-like form had no effect on the transacylase activity. Our results indicate the PAF-related transacylase is widely distributed among tissues and, although highly selective for polyunsaturated acyl groups, does not discriminate selectively among the polyunsaturates.

Acyltransferases↗
PubMed2005

Functional roles of the bone morphogenetic protein system in thyrotropin signaling in porcine thyroid cells.

We uncovered a new regulation of thyrocyte function by bone morphogenetic protein (BMP) under the influence of thyrotropin (TSH) using primary culture of porcine thyrocytes. The BMP type I receptors, ALK-2 (ActRIA), -3 (BMPRIA), and -6 (BMPRIB), were expressed in porcine thyrocytes, while ALK-6 was not detected in human thyroid. Treatment with BMP-2, -4, -6, -7, and TGF-beta1 exhibited a dose-dependent suppression of DNA synthesis by porcine thyrocytes. BMP-2, -4, -6, -7, and TGF-beta1 suppressed TSH receptor mRNA expression on thyrocytes, which was consistent with their suppressive effect on TSH-induced cAMP synthesis and TSH-induced insulin-like growth factor-1 expression. Activin exhibited minimal suppression of thyrocyte DNA synthesis and did not exhibit suppressive effects on TSH receptor mRNA expression. Phosphorylated Smad1/5/8 was detected in the lysates of porcine thyrocytes treated with BMP-2, -4, -6, and -7. However, in the presence of TSH, BMP-6 and -7 failed to activate Smad1/5/8 phosphorylation and 3TP-reporter activity, whereas BMP-2 and -4 maintained clear activation of the BMP signaling regardless of the presence of TSH. This diverged regulation of thyroid BMP system by TSH is most likely due to the reduction of ALK-6 expression caused by TSH. Thus, the thyroid BMP system is functionally linked to TSH actions through modulating TSH receptor expression and TSH, in turn, selectively inhibits BMP signaling. Given that BMP system is present in human thyroid and the expression pattern of ALK-2 and BMPRII is different between follicular adenomas and normal thyroid tissues, the endogenous BMP system may be involved in regulating thyrocyte growth and TSH sensitivity of human thyroid adenomas.

Adult↗
PubMed2002

A comparison of two skin test methodologies and allergens from two different manufacturers.

BACKGROUND: Skin prick tests (SPTs) are a frequently used method for evaluation of atopy. A variety of standard allergen preparations are available, together with a number of different methods of application. OBJECTIVE: The objective of this study was to compare SPT reactivity 1) using Soluprick SQ allergens (ALK Allergologisk Laboratorium A/S, Hørsholm, Denmark) and Bayer allergens [Bayer Corporation, West Haven, CT], and 2) using two common methods of application, a standard prick lancet and a Quintest, both produced by Bayer. METHODS: SPTs were undertaken on 22 adult volunteers (mean age 40 years, 17 female, 5 male). Wheal size was recorded as mean diameters (mm) and area (mm2). RESULTS: Bayer allergens produced larger mean diameters and areas to dust mites than ALK allergens, with the differences significant when allergens were applied with the lancet. There was a tendency for the ALK cat allergen to produce larger reactions than the Bayer product. The method of application also influenced the wheal size, with the lancet producing significantly larger mean diameters than the Quintest for the histamine and allergens from both manufacturers, except the ALK cat allergen. There were similar differences between methods of application for reactions measured as an area. CONCLUSIONS: SPTs that use different allergens or different methods of application will not provide comparable assessments of atopy.

Adult↗
PubMed2001

Catalytic and immunochemical properties of hepatic cytochrome P450 1A in three avian species treated with beta-naphthoflavone or isosafrole.

Induction of cytochrome P450 1A (CYP1A) can be used as a biomarker of exposure to planar halogenated aromatic hydrocarbons (PHAHs). Our objective was to characterize the induction of CYP1A activity and protein in three avian species following in vivo treatment with beta-naphthoflavone (BNF) and/or isosafrole. Alkoxyresorufin-O-dealkylase (alk-ROD) activities of hepatic microsomes from Herring Gulls (Larus argentatus) (HGs), Double-crested Cormorants (Phalacrocorax auritus) (DCCs) and chickens (Gallus domesticus) were measured using ethoxy-, methoxy-, pentoxy- and benzyloxy-resorufin, in the presence and absence of the inhibitors ellipticine or furafylline. Immunoreactivity of microsomal proteins with antibodies to several CYP1A proteins was investigated. CYP1A protein and alk-ROD activities of HGs and DCCs, but not chickens, were induced by isosafrole. Ellipticine was a potent and non-selective inhibitor of alk-ROD activity in all three species, while furafylline inhibition of alk-ROD activities varied among species and treatments. In all three species, BNF induced a protein immunoreactive with monoclonal antibody to CYP1A1 from the marine fish Stenotomus chrysops (scup), but a CYP1A2-like protein was not detected in avian microsomes probed with polyclonal antibodies to mouse CYP1A2. Variations in responses among avian species indicate that CYP1A proteins and substrate specificities should be characterized for each species used in PHAH biomonitoring programs.

Animals↗
PubMed2005

Contents of phenolic acids, alkyl- and alkenylresorcinols, and avenanthramides in commercial grain products.

The contents of free and total phenolic acids and alk(en)ylresorcinols were analyzed in commercial products of eight grains: oat (Avena sativa), wheat (Triticum spp.), rye (Secale cerale), barley (Hordeum vulgare), buckwheat (Fagopyrum esculentum), millet (Panicum miliaceum), rice (Oryza sativa), and corn (Zea mays). Avenanthramides were determined in three oat products. Free phenolic acids, alk(en)ylresorcinols, and avenanthramides were extracted with methanolic acetic acid, 100% methanol, and 80% methanol, respectively, and quantified by HPLC. The contents of total phenolic acids were quantified by HPLC analysis after alkaline and acid hydrolyses. The highest contents of total phenolic acids were in brans of wheat (4527 mg/kg) and rye (4190 mg/kg) and in whole-grain flours of these grains (1342 and 1366 mg/kg, respectively). In other products, the contents varied from 111 mg/kg (white wheat bread) to 765 mg/kg (whole-grain rye bread). Common phenolic acids found in the grain products were ferulic acid (most abundant), ferulic acid dehydrodimers, sinapic acid, and p-coumaric acid. The grain products were found to contain either none or only low amounts of free phenolic acids. The content of avenanthramides in oat flakes (26-27 mg/kg) was about double that found in oat bran (13 mg/kg). The highest contents of alk(en)ylresorcinols were observed in brans of rye (4108 mg/kg) and wheat (3225 mg/kg). In addition, whole-grain rye products (rye bread, rye flour, and whole-wheat flour) contained considerable levels of alk(en)ylresorcinols (524, 927, and 759 mg/kg, respectively).

Amides↗
PubMed2007

Electrophilic reactions of skin-sensitizing sultones.

Reactions of the strong skin sensitizer hexadec-1-ene-1,3-sultone with sodium hydroxide, sodium methoxide, sodium metabisulfite, sodium butanethiolate, n-butylamine, and aniline have been investigated, and the reaction products have been identified. Most of the nucleophiles studied react by nucleophilic addition (Michael type addition) to the double bond at the 2-position, although in most cases the final products result from further reactions of the initital adducts. The findings are considered together with those reported by Meschkat, Barratt, and Lepoittevin for reactions of hex-1-ene-1,3-sultone and hexane-1,3-sultone, and the implications of the two sets of findings for the mechanism of skin-sensitizing action are discussed. It is concluded that nucleophilic attack at the 3-position of the alk-1-ene-1,3-sultones occurs only with those nucleophiles, which either have very low reactivity in nucleophilic addition or are unable to give rise to thermodynamically stable products via initial reaction at the 2-position. It is further concluded that the observed differences in electrophilic reactivity between alk-1-ene-1,3-sultones and alkane-1,3-sultones are not large enough to rationalize the differences in skin sensitization properties between the two types of sultone. It is suggested that the differences in specificity arise because the alk-1-ene-1,3-sultones act as Michael type electrophiles whereas the alkane sultones act as SN2 electrophiles. It is suggested that the reason for the greater potency of the alk-1-ene-1,3-sultones may be the ability of the initial C2 adducts with protein to undergo further reactions by substitution at C3, leading to cross-linking and consequent perturbation to the protein tertiary structure.

Butylamines↗