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PubMed1987

Studies on cell adhesion and concanavalin A-induced agglutination of Candida albicans after mannan extraction.

Candida albicans cells were treated with alkali and acid to extract preferentially the cell wall alpha-mannan. Cells were recovered at three stages, as extraction proceeded from mild to more extensive: Alk-1, Alk-2 and Alk + Acid. Yeast adhesion to human epithelial cells was then examined with an in-vitro adherence assay. Yeasts from all three stages of extraction adhered in significantly lower numbers to buccal mucosal cells than did unextracted yeasts. Adhesion was as low for Alk-1 cells as for those submitted to more complete mannan extraction. When yeast cells from all three stages were treated with Concanavalin A (Con A), a lectin probe with strong affinity for yeast alpha-mannans, and then subjected to the adherence assay, there was no significant change in adhesion. When yeast agglutinability by Con A was examined in tests with treated and untreated yeast cells, abundant agglutination occurred only with the untreated cells. However, Alk-1 cells, though lacking in adhesive capacity towards mucosal cells, showed significant agglutination. The results suggest that candidal adhesion is mediated by an alkali-soluble, mannan-containing moiety(ies) which appears to be lost early in the extraction process. Blockage of this moiety by Con A inhibits the adhesion of unextracted cells. Extracted cells lack this moiety but still possess enough structural mannan for Con A recognition and agglutination.

Agglutination↗
PubMed2005

High expression of calcium-binding proteins, S100A10, S100A11 and CALM2 in anaplastic large cell lymphoma.

Anaplastic large cell lymphomas (ALCL) are characterised by the presence of CD30-positive large cells, which usually are of T-cell type. Based on the presence or absence of translocations involving the anaplastic lymphoma kinase (ALK) locus, ALCL cases can be divided into two groups. To gain more insight in the biology of ALCL, we applied serial analysis of gene expression (SAGE) on the Karpas299 cell line and identified 25 up- and 19 downregulated genes. Comparison of the differentially expressed genes with DNA copy number changes in Karpas299 revealed that two overexpressed genes, S100A10 and S100A11, were located in an amplicon suggesting that the increased mRNA levels were caused by DNA amplification. Quantitative reverse transcription polymerase chain reaction on 5 ALCL cell lines and 12 ALCL tissues confirmed the SAGE data for 13 out of 14 up- and one out of four downregulated genes. Immunohistochemical staining confirmed the presence of S100A10, a calcium-binding protein, in three out of five ALK+ and all 7 ALK- ALCL cases. S100A11 staining was confirmed in all ALK+ and six of seven ALK- ALCL cases. Three of the upregulated genes represented calcium-binding proteins, which suggest that altered intracellular signaling might be associated with the oncogenesis of ALCL.

Annexin A2↗
PubMed1985

The use of a reference allergenic extract in the evaluation of allergen products.

Two commercially available mugwort (Artemisia vulgaris (Av] pollen extracts Av-ALK and Av-PS were compared with a dialysed reference mugwort pollen extract (Av-REF) by means of crossed immunoelectrophoresis (CIE), crossed radio immunoelectrophoresis (CRIE), RAST-inhibition, RAST-screening and skin prick test. Av-ALK and Av-PS both contained approximately half the number of precipitation arcs detectable in Av-REF, and Av-PS seemed to lack two intermediate allergens and two minor allergens, while Av-ALK seemed to lack one minor allergen. The RAST-inhibition curve obtained for Av-PS did not parallel the curves obtained for Av-ALK and Av-REF, indicating that the allergen composition of Av-PS differs from that of the others. Further, RAST-screening experiments support the CIE observation that Av-PS seemed to lack two of the intermediate allergens. The HEP values determined for Av-ALK and Av-PS diverge considerably from those stated by the manufacturers. The results obtained demonstrate that the outcome of a comparison between a reference allergenic extract and allergenic products depends very much on the method employed.

Allergens↗
PubMed1996

Overproduction of a foreign membrane protein in Escherichia coli stimulates and depends on phospholipid synthesis.

When the Pseudomonas oleovorans alk system, consisting of the alkBFGHJKL and alkST genes, is expressed in Escherichia coli W3110, significant changes in phospholipid metabolism of the host are observed. A major role seems to be played by the cytoplasmic membrane protein alkane hydroxylase (AlkB), which is synthesized as up to 10-15% of the total protein in this strain [Nieboer, M., Kingma, J. & Witholt, B. (1993) The alkane oxidation system of Pseudomonas oleovorans: induction of the alk genes in Escherichia coli W3110[pGEc47] affects membrane biogenesis and results in overexpression of alkane hydroxylase in a distinct cytoplasmic membrane subfraction, Mol. Microbiol. 8, 1039-1051]. In the present paper, we have studied the link between synthesis of the membrane protein and the synthesis of phospholipids and fatty acids by examining the kinetics of these processes. Using [35S]methionine labeling, it was shown that induction of AlkB was maximal within 30-60 min after addition of inducer, when up to 15% of all newly synthesized protein is AlkB. Phospholipid synthesis was followed by measuring the incorporation of 14C-labeled acetate and 33P-labeled phosphoric acid into phospholipids. Despite a negative effect of the inducer on the growth rate of W3110[pGEc47], net phospholipid synthesis was significantly enhanced as a result of the expression of alkB. Synthesis of all three major phospholipids were stimulated to comparable extents by the induction of alkB. Induction did not increase 33P incorporation into lipids in the control recombinant alk+ strain which lacked alkB. Simultaneous with AlkB synthesis, the conversion of unsaturated 9-hexadecenoic acid (C16:1) into 9,10-methylene hexadecanoic acid (C17:ocyc) was reduced in the alk+ recombinant. Overall, these data show that the production of a foreign membrane protein in E. coli can engender a response of the phospholipid-synthesizing system of the host. In the absence of such a response, induction of the alk system would be much more toxic to the cells. Apparently, the increased phospholipid synthesis plays an important role in enabling the AlkB overproducing strain to grow.

Bacterial Proteins↗
PubMed1977

Fractionation of inducible alkane hydroxylase activity in Pseudomonas putida and characterization of hydroxylase-negative plasmid mutations.

The plasmid-determined inducible alkane hydroxylase of Pseudomonas putida resolved into particulate and soluble fractions. Spinach reductase and spinach ferredoxin could replace the soluble hydroxylase component. Two alkane hydroxylase mutants show in vitro complementation (S. Benson and J. Shapiro, J. Bacteriol., 123: 759-760, 1975): one, alk-7, lacks an active soluble component and the other, alk-181, lacks an active particulate component. Together with previous results on a particulate alcohol dehydrogenase enzyme (Benson and Shapiro, J. Bacteriol., 126: 794-798, 1976), these results allowed us to assay three plasmid-determined inducible activities: soluble alkane hydroxylase (alkA+), particulate alkane hydroxylase (alkB+), and particulate alcohol dehydrogenase (alkC+). Growth tests and in vitro complementation assays revealed three groups of plasmid mutations that block expression of alkane hydroxylase activity: alkA, which so far includes only the alk-7 mutation; alkB, which includes alk-181 and 11 other mutations; and a pleiotropic-negative class, which includes nine mutations that lead to loss of alkA+, alkB+, and alkC+ activities. Thus, the alk+ gene cluster found on IncP-2 plasmids contains at least four cistrons. We believe it is significant that two of these determined the presence of membrane proteins. The accompanying paper shows that these loci are part of a single regulon.

Alkanes↗
PubMed2000

An n-alkane-responsive promoter element found in the gene encoding the peroxisomal protein of Candida tropicalis does not contain a C(6) zinc cluster DNA-binding motif.

When an asporogenic diploid yeast, Candida tropicalis, is cultivated on n-alkane, the expression of the genes encoding enzymes of the peroxisomal beta-oxidation pathway is highly induced. An upstream activation sequence (UAS) which can induce transcription in response to n-alkane (UAS(ALK)) was identified on the promoter region of the peroxisomal 3-ketoacyl coenzyme A (CoA) thiolase gene of C. tropicalis (CT-T3A). The 29-bp region (from -289 to -261) present upstream of the TATA sequence was sufficient to induce n-alkane-dependent expression of a reporter gene. Besides n-alkane, UAS(ALK)-dependent gene expression also occurred in the cells grown on oleic acid. Several kinds of mutant UAS(ALK) were constructed and tested for their UAS activity. It was clarified that the important nucleotides for UAS(ALK) activity were located within 10-bp region from -273 to -264 (5'-TCCTGCACAC-3'). This region did not contain a CGG triplet and therefore differed from the sequence of the oleate-response element (ORE), which is a UAS found on the promoter region of 3-ketoacyl-CoA thiolase gene of Saccharomyces cerevisiae. Similar sequences to UAS(ALK) were also found on several peroxisomal enzyme-encoding genes of C. tropicalis.

Acetyl-CoA C-Acyltransferase↗
PubMed1984

Renal handling of phosphate during acute respiratory acidosis and alkalosis in the rat.

Clearance experiments were performed in acutely thyroparathyroidectomized rats to evaluate the renal handling of phosphate during respiratory acidosis (R ACID) and alkalosis (R ALK) in rats fed either a normal (0.7%) or low (0.07%) phosphate diet for 4 days. Different acid-base states were achieved by varying the mixture of carbon dioxide in the inspired air. Each group received graded infusions of phosphate to control for differences in plasma phosphate (PPi) and to determine the maximum transport capacity of phosphate reabsorption (TmPi/GFR). In rats fed a normal phosphate diet, PPi and the fractional excretion of phosphate (FEPi) were significantly greater in R ACID than in R ALK. However, there were no differences between R ACID and R ALK when FEPi was evaluated as a function of the PPi, and values for TmPi/GFR during R ACID were not different from those during R ALK. In rats fed low phosphate diet, PPi during R ACID was significantly greater than during R ALK, yet FEPi was less than 1% in all groups due to an adaptive increase in TmPi/GFR. Further, the TmPi/GFR was similar irrespective of the acid-base state. We conclude that acute respiratory acid-base changes do not alter the intrinsic capacity of the kidney to reabsorb phosphate.

Acidosis, Respiratory↗
PubMed1997

Differential expression of transforming growth factor-beta receptors in rat kidney development.

Transforming growth factor-beta 1 (TGF-beta 1) is strongly expressed during embryogenesis and in sites undergoing intense development and morphogenesis. Two receptor serine/threonine kinases (types I and II) have been identified as signal-transducing TGF-beta receptors. This study was undertaken to further explore the role of the distinct TGF-beta receptors during kidney development. The species-specific sequence information for the two T beta R-I, namely, activin receptor-like kinase-5 (ALK-5) and Tsk7L, in the rat was sought. Two full-length T beta R-I cDNAs were cloned from a neonatal rat kidney and lung libraries, and sequencing revealed that they were the rat homologs of human ALK-5 and murine Tsk7L. Both types I and II TGF-beta receptors are expressed in the kidney as determined by Northern blot analysis. T beta R-II mRNA abundance was significantly greater in the neonatal rat kidney compared with the adult rat kidney. Similarly, ALK-5 mRNA was more highly expressed in the fetal and neonatal rat kidney than the adult rat kidney. In contrast, there was no significant difference in Tsk7L mRNA abundance among the fetal, neonatal, and adult rat kidney. Thus, based on these findings, both T beta R-II and ALK-5 are developmentally regulated in the kidney. Increased expression of T beta R-II and ALK-5 proteins in the developing kidney was confirmed by immunohistochemistry. Interestingly, the two TGF-beta receptors did not entirely colocalize, raising the intriguing possibility that other TGF-beta signaling receptors may be involved.

Activin Receptors, Type I↗
PubMed1994

Effect of acid-base balance on the growth hormone response to acute high-intensity cycle exercise.

To investigate the effect of acid-base balance on serum human growth hormone (hGH) concentration after an acute high-intensity anaerobic exercise bout, 10 untrained but normally active men [age, 24.6 +/- 1.5 (SE) yr] participated in a randomized double-blind counterbalanced experiment. Each subject reported in a fasted state at the same time of day for two experimental sessions separated by 1 wk. For each session, subjects were administered a decaffeinated tea solution containing either 0.3 g NaHCO3/kg body wt [alkalosis (ALK)] or 0.04 g NaCl/kg body wt [control (CTRL)] over a 45-min ingestion period. Venous blood samples were obtained before [baseline (BL)] and 75 min after the ingestion period, as well as postexercise at 0, 5, 10, 15, 20, and 30 min. The exercise task immediately followed the preexercise blood draw and consisted of 90 s of maximal-effort cycle ergometry against an opposing force of 0.49 N (0.05 kg)/kg body wt. There were no differences between the ALK and CTRL conditions in mean or peak power output or total work during the exercise task. Whole blood pH was significantly (P < or = 0.05) elevated in ALK above CTRL at all time points except BL. Postexercise serum hGH concentration significantly increased above BL at 10, 15, 20, and 30 min in CTRL and at 20 and 30 min in ALK. The hGH concentration was significantly lower in ALK than in CTRL at 15, 20, and 30 min postexercise. These data indicate that an increase in blood hydrogen ion concentration may be partly responsible for the hGH response to acute high-intensity anaerobic exercise.

Acid-Base Equilibrium↗
PubMed2002

Immunohistochemical localization of osteogenetic protein (OP-1) and its receptors in rabbit articular cartilage.

We assessed the distribution and relative immunohistochemical staining intensity of the bone morphogenetic protein-7, osteogenic protein-1 (OP-1), in its pro- and mature forms, and four of its receptors, type I (ALK-2, ALK-3, and ALK-6) and type II in normal adolescent New Zealand White rabbit articular cartilage. Expression of the protein and its receptors was also examined in cartilage from joints that had been previously subjected to cartilage matrix degradation. Pro-OP-1 was moderately expressed in chondrocytes of the superficial, middle, and deep cartilage zones and in the osteocytes. The expression of mature OP-1 was similar, with the exception of less staining in the superficial zone of cartilage. Expression of these two forms of OP-1 was enhanced in the middle and deep cartilage zones after catabolic challenge. The type I receptor, ALK-6, displayed the strongest staining of the receptors in both cartilage and bone, whereas ALK-2 displayed the weakest staining. No differences were observed in the receptor staining levels after catabolic challenge. This study shows that OP-1 and its receptors have been identified in rabbit articular cartilage and bone, suggesting a possible role for this pathway in cartilage and bone homeostasis.

Activin Receptors, Type I↗
PubMed1995

Myofibrillar ATPase activity of feline muscle fibers expressing slow and fast myosin heavy chains.

The interrelationships among myofibrillar ATPase activity (Quant-mATPase), qualitative myofibrillar ATPase staining after acid (Acid-mATPase) and alkaline (Alk-mATPase) preincubations, and myosin heavy chain (MHC) composition were determined in frozen sections of soleus (Sol) and medial gastrocnemius (MG) muscle fibers from adult control cats and cats 6 months after complete spinal cord transection (Sp). Fibers were categorized as either fast, slow, or fast and slow (Fast-Slow) based on monoclonal antibody labeling. Slow fibers had low Quant-mATPase activity and stained lightly with Alk-mATPase and darkly with Acid-mATPase. Fast fibers had high Quant-mATPase activity (approximately twice that of slow fibers) and stained darkly with Alk-mATPase and lightly with Acid-mATPase. Fast-Slow fibers had intermediate Quant-mATPase activity and stained intermediately for Acid-mATPase and darkly for Alk-mATPase. There was a positive linear relationship between Alk-mATPase and Quant-mATPase for all fibers of Sol and MG from control and Sp cats. There was a negative linear relationship between Acid-mATPase and Quant-mATPase for all fibers of Sol and MG. However, within the fast fiber population of the MG there was a positive relationship between these two measures of mATPase. In summary, quantitative and qualitative measures of mATPase are highly correlated with the types of MHC expressed by single fibers from control and Sp cat muscles.

Animals↗
PubMed2005

Activation of alpha-diacylglycerol kinase is critical for the mitogenic properties of anaplastic lymphoma kinase.

Oncogenic rearrangements of the tyrosine kinase receptor anaplastic lymphoma kinase (ALK), most commonly represented by the nucleophosmin/ALK fusion protein (NPM/ALK), are involved in the pathogenesis of anaplastic large-cell lymphomas (ALCLs). In an effort to identify new intracellular transducers operative in ALK-positive malignancies, we have investigated the potential involvement of diacylglycerol kinase (DGK). Here we show that alphaDGK is constitutively activated in the NPM/ALK-positive ALCL-derived cell line Karpas 299 and in NPM/ALK-infected 32D hematopoietic cells. These results were further validated in fibroblastic NIH-3T3 cells expressing a previously described chimeric epidermal growth factor receptor (EGFR)/ALK molecule that allows dissection of ALK enzymatic function under conditions of controlled ligand-induced activation. In this cell system, we also show that ALK-mediated alphaDGK activation is dependent on p60src tyrosine kinase, with which alphaDGK forms a complex. The specific inhibition of alphaDGK, obtained by cell treatment with R59949, significantly reduced cellular growth in all cell lines. This result was further confirmed in Karpas 299 cells following specific down-regulation of alphaDGK by RNA interference. Overall, our data indicate that alphaDGK activation is involved in the control of ALK-mediated mitogenic properties.

Anaplastic Lymphoma Kinase↗
PubMed2001

Unusual childhood extramedullary hematologic malignancy with natural killer cell properties that contains tropomyosin 4--anaplastic lymphoma kinase gene fusion.

This report describes an unusual extramedullary hematologic malignancy in an 18-month-old child who presented with a capillary leak syndrome that evolved into hyperleukocytosis with malignant cells. The circulating tumor cells did not express an antigen profile typical of any subtype of leukemia commonly observed in children. Tumor cells were CD3(-)/CD56(+); had germline TCR genes; and strongly expressed CD30, epithelial membrane antigen, and anaplastic lymphoma kinase (ALK) consistent with a null cell anaplastic large cell lymphoma (ALCL). The malignant cells contained a t(2;19)(p23;p13.1) that interrupted ALK and translocated it to the der(19). Reverse transcriptase-polymerase chain reaction and nucleotide sequence analysis revealed fusion of ALK to tropomyosin 4, an ALK fusion partner not described previously in hematologic malignancies. The clinical presentation and phenotypic features of this malignancy were not typical for ALCL because tumor cells expressed both myeloid (CD13, CD33, HLA-DR) and natural killer (NK) cell antigens. The neoplastic cells most resembled NK cells because in addition to being CD3(-)/CD56(+) with germline TCR genes, these cells were CD25(+)/CD122(+)/granzyme B(+) and possessed the functional properties of immature NK cells. The unusual clinical presentation, immunophenotype, and functional properties of these neoplastic cells suggest that this malignancy may be derived from the putative myeloid-NK precursor cell. Furthermore co-expression of NK and ALCL features supports the concept that a minority of null-ALCL may be derived from NK cells and expands the spectrum of phenotypes that can be seen in tumors produced by ALK fusion proteins. (Blood. 2001;98:1209-1216)

Anaplastic Lymphoma Kinase↗
PubMed2002

Expression levels of apoptosis-related proteins predict clinical outcome in anaplastic large cell lymphoma.

In vitro studies suggest that resistance to chemotherapy-induced apoptosis might explain poor response to therapy in fatal cases. Actual execution of apoptosis depends on proper functioning of effector caspases, particularly caspase 3, and on the expression levels of apoptosis-regulating proteins, including Bcl-2 and the recently identified granzyme B- specific protease inhibitor 9 (PI9). Thus, high levels of caspase 3 activation should reflect proper functioning of the apoptosis pathways, resulting in chemotherapy-sensitive neoplastic cells and a favorable prognosis. We tested this hypothesis by quantifying numbers of tumor cells positive for active caspase 3, Bcl-2, and PI9, respectively, in pretreatment biopsies of systemic anaplastic large cell lymphoma (ALCL) patients and by comparing these numbers with clinical outcome. Activation of caspase 3 in more than 5% of the tumor cells was strongly correlated with a highly favorable outcome. High numbers of Bcl-2- and PI9-positive tumor cells were found to predict unfavorable prognosis. This prognostic effect was strongly related to anaplastic lymphoma kinase (ALK) status: ALK-positive ALCL had significantly higher levels of active caspase 3, while high expression of the antiapoptotic proteins Bcl-2 and PI9 was almost completely restricted to ALK-negative cases. In conclusion, high numbers of active caspase 3-positive tumor cells predict a highly favorable prognosis in systemic ALCL patients. Poor prognosis is strongly related to high numbers of Bcl-2- and PI9-positive neoplastic cells. These data support the notion that a favorable response to chemotherapy depends on an intact apoptosis cascade. Moreover, these data indicate that differences in prognosis between ALK-positive and ALK-negative ALCL might be explained by differences in expression of apoptosis-inhibiting proteins.

Adult↗
PubMed1999

Characterization of bone morphogenetic protein-6 signaling pathways in osteoblast differentiation.

Bone morphogenetic protein (BMP)-6 is a member of the transforming growth factor (TGF)-(&bgr;) superfamily, and is most similar to BMP-5, osteogenic protein (OP)-1/BMP-7, and OP-2/BMP-8. In the present study, we characterized the endogenous BMP-6 signaling pathway during osteoblast differentiation. BMP-6 strongly induced alkaline phosphatase (ALP) activity in cells of osteoblast lineage, including C2C12 cells, MC3T3-E1 cells, and ROB-C26 cells. The profile of binding of BMP-6 to type I and type II receptors was similar to that of OP-1/BMP-7 in C2C12 cells and MC3T3-E1 cells; BMP-6 strongly bound to activin receptor-like kinase (ALK)-2 (also termed ActR-I), together with type II receptors, i.e. BMP type II receptor (BMPR-II) and activin type II receptor (ActR-II). In addition, BMP-6 weakly bound to BMPR-IA (ALK-3), to which BMP-2 also bound. In contrast, binding of BMP-6 to BMPR-IB (ALK-6), and less efficiently to ALK-2 and BMPR-IA, together with BMPR-II was detected in ROB-C26 cells. Intracellular signalling was further studied using C2C12 and MC3T3-E1 cells. Among the receptor-regulated Smads activated by BMP receptors, BMP-6 strongly induced phosphorylation and nuclear accumulation of Smad5, and less efficiently those of Smad1. However, Smad8 was constitutively phosphorylated, and no further phosphorylation or nuclear accumulation of Smad8 by BMP-6 was observed. These findings indicate that in the process of differentiation to osteoblasts, BMP-6 binds to ALK-2 as well as other type I receptors, and transduces signals mainly through Smad5 and possibly through Smad1.

3T3 Cells↗
PubMed1999

TGF-(beta) type I receptor/ALK-5 and Smad proteins mediate epithelial to mesenchymal transdifferentiation in NMuMG breast epithelial cells.

The capacities of different transforming growth factor-(beta) (TGF-(beta)) superfamily members to drive epithelial to mesenchymal transdifferentiation of the murine mammary epithelial cell line NMuMG were investigated. TGF-(beta)1, but not activin A or osteogenic protein-1 (OP-1)/bone morphogenetic protein-7 (BMP-7), was able to induce morphological transformation of NMuMG cells as shown by reorganisation of the actin cytoskeleton and relocalisation/downregulation of E-cadherin and (beta)-catenin, an effect that was abrogated by the more general serine/threonine kinase and protein kinase C inhibitor, staurosporine. TGF-(beta)1 bound to TGF-(beta) type I receptor (T(beta)R-I)/ALK-5 and T(beta)R-II, but not to activin type I receptor (ActR-I)/ALK-2. Activin A bound to ActR-IB/ALK-4 and ActR-II, and BMP-7 bound to ActR-I/ALK-2, BMP type I receptor (BMPR-I)/ALK-3, ActR-II and BMPR-II. TGF-(beta)1 and BMP-7 activated the Smad-binding element (SBE)(4) promoter with equal potency, whereas activin A had no effect. Transfection of constitutively active (CA)-ALK-4 activated the 3TP promoter to the same extent as TGF-(beta)1 and CA-ALK-5 indicating that activin signalling downstream of type I receptors was functional in NMuMG cells. In agreement with this, activin A induced low levels of plasminogen activator inhibitor I expression compared to the high induction by TGF-(beta)1. In contrast to activin A and BMP-7, TGF-(beta)1 strongly induced Smad2 phosphorylation. Consistent with these findings, TGF-(beta)1 induced the nuclear accumulation of Smad2 and/or Smad3. In addition, NMuMG cells transiently infected with adenoviral vectors expressing high level CA-ALK-5 exhibited full transdifferentiation. On the other hand, infections with low level CA-ALK-5, which alone did not result in transdifferentiation, together with Smad2 and Smad4, or with Smad3 and Smad4 led to transdifferentiation. In conclusion, TGF-(beta)1 signals potently and passes the activation threshold to evoke NMuMG cell transdifferentiation. The TGF-(beta) type I receptor (ALK-5) and its effector Smad proteins mediate the epithelial to mesenchymal transition. Activin A does not induce mesenchymal transformation, presumably because the number of activin receptors is limited, while BMP-7-initiated signalling cannot mediate transdifferentiation.

Activin Receptors, Type I↗
PubMed2006

Sodium bicarbonate ingestion alters the slow but not the fast phase of VO2 kinetics.

PURPOSE: The influence of metabolic alkalosis (ALK) on pulmonary O2 uptake (pVO2) kinetics during high-intensity cycle exercise is controversial. The purpose of this study was to examine the influence of ALK induced by sodium bicarbonate (NaHCO3) ingestion on pVO2 kinetics, using a sufficient number of repeat-step transitions to provide high confidence in the results obtained. METHODS: Seven healthy males completed step tests to a work rate requiring 80% pVO2max on six separate occasions: three times after ingestion of 0.3 g x kg(-1) body mass NaHCO3 in 1 L of fluid, and three times after ingestion of a placebo (CON). Blood samples were taken to assess changes in acid-base balance, and pVO2 was measured breath-by-breath. RESULTS: NaHCO3 ingestion significantly increased blood pH and [bicarbonate] both before and during exercise relative to the control condition (P < 0.001). The time constant of the phase II pVO2 response was not different between conditions (CON: 29 +/- 6 vs ALK: 32 +/- 7 s; P = 0.21). However, the onset of the pVO2 slow component was delayed by NaHCO3 ingestion (CON: 120 +/- 19 vs ALK: 147 +/- 34 s; P < 0.01), resulting in a significantly reduced end-exercise pVO2 (CON: 2.88 +/- 0.19 vs ALK: 2.79 +/- 0.23 L x min(-1); P < 0.05). CONCLUSIONS: Metabolic alkalosis has no effect on phase II pVO2 kinetics but alters the pVO2 slow-component response, possibly as a result of the effects of NaHCO3 ingestion on muscle pH.

Acid-Base Imbalance↗
PubMed2002

Clusterin is widely expressed in systemic anaplastic large cell lymphoma but fails to differentiate primary from secondary cutaneous anaplastic large cell lymphoma.

A recent study by Wellmann et al (Blood. 2000;96:398-404) detected clusterin expression in all 36 systemic anaplastic large cell lymphomas (ALCLs) tested, but not in any of 9 primary cutaneous ALCLs. Our purpose was to confirm the diagnostic usefulness of clusterin in systemic ALCL and to evaluate its efficacy in distinguishing primary cutaneous ALCL from secondary skin involvement by systemic ALCL. We examined clusterin expression by paraffin immunohistochemical analysis in 41 systemic ALCLs (18 ALK-1+ and 23 ALK-1-), 9 primary cutaneous ALCLs, and 4 secondary cutaneous ALCLs. Clusterin was positive in 95% of systemic ALCLs (39/41), including 100% (18/18) of the ALK-1+ cases and 91% (21/23) of the ALK-1- cases. Five (56%) of 9 primary and 3 (75%) of 4 secondary cutaneous ALCLs were positive for clusterin. Our observations confirm the diagnostic usefulness of clusterin in systemic ALCL, especially in the ALK-1- cases. However, our data fail to demonstrate its value in distinguishing primary from secondary cutaneous ALCL.

Anaplastic Lymphoma Kinase↗