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PubMed1999

Some properties of alkaline DNases of tentacles of actinia Radianthus macrodactylus and their hemolytic activity.

Two alkaline DNases of tentacles of actinia Radianthus macrodactylus, referred to as alk DNase I and alk DNase II, respectively, have been purified up to apparent homogeneity with consecutive column ion exchange chromatography and gel filtration. Both enzymes have a lot of common properties, such as the ability to hydrolyze very effectively p-nitrophenyl-5'-TMP and heat-denatured DNA. They both have no preferential specificity to the sugar component of the nucleic acids and effectively digest ribopolymers. Their ability to hydrolyze supercoiled DNA of the pBR322 plasmid and linear DNA of the lambda phage by "miscellaneous" exo- and endonucleolytic types of attack and to produce nucleosides, nucleotides and short oligonucleotides suggests their similarity with phosphodiesterase I (5'-exonuclease, oligonucleate 5'-nucleotidohydrolase; E.C. 3.1.4.1), isolated from rattle snake Crotalus adamenteus venom. Alk DNase II has been revealed to have some uncommon properties, such as phosphomonoesterase and hemolytic activities. The protein causes a very potent lysis of human and rabbit erythrocytes. The ability of alk DNase II to precipitate some components of normal human and rabbit blood serum as well as the inhibition of this reaction by fucose but not by another monosaccharides suggest the enzyme to have a lectin-like activity. The appearance of only one protein band during electrophoresis of alk DNase II in denaturation conditions suggests that all activities are inherent to the same molecule of protein. The possible role of alkaline DNases in the toxic effect of burning by actinia tentacles is discussed.

Animals↗
PubMed1997

Ocular integrity after refractive procedures.

PURPOSE: The purpose of the study was to determine the integrity of human eyes after refractive procedures. METHODS: Whole human globes underwent either radial keratotomy (RK) with eight incisions, automated lamellar keratoplasty (ALK), photorefractive keratectomy (PRK), or excimer laser assisted in situ keratomileusis (LASIK). Eyes then were subjected to quantitatively increasing levels of trauma until rupture occurred. RESULTS: All eyes operated on required less energy to rupture as compared with that of control eyes. The mean number of trials required for rupture is as follows (energy doubled with each successive trial): normal, 4.29; LASIK, 3.80; ALK, 3.67; PRK, 3.60; and RK, 2.83. The level of energy required to rupture normal, ALK, PRK, and LASIK eyes was not significantly different. All RK eyes ruptured at incisions. Most ALK, PRK, and LASIK eyes ruptured near the flap edge or limbus. Most normal eyes ruptured with both corneal and scleral involvement. Age of tissue donors at the time of death and time elapsed between death and procedure were not significantly different between groups (P = 0.88 and 0.79, respectively). CONCLUSIONS: The energy required to rupture ALK, PRK, and LASIK eyes is not significantly different from that for normal eyes. The RK eyes ruptured with significantly less energy than did normal eyes. All RK eyes ruptured at incision sites.

Adult↗
PubMed1996

Automated keratomileusis in situ: clinical study of 142 eyes.

PURPOSE: To compare a modified automated lamellar keratoplasty (ALK) technique that uses two blades with the original technique, which uses one blade. SETTING: Buzard Eye Institute, Las Vegas, Nevada. METHODS: This study comprised 142 eyes of 85 patients who had ALK: 107 using the original one-blade technique (Group 1) and 35 eyes using the modified two-blade technique (Group 2). Mean follow-up was 11 months in Group 1 and 3 months in Group 2. RESULTS: Mean preoperative spherical equivalent was -8.93 diopters (D) +/- 2.80 (SD) in Group 1 and -8.33 +/- 2.80 D in Group 2. No patient had worse than 20/80 best corrected visual acuity preoperatively. Mean spherical equivalent at 1 month was -2.06 +/- 2.00 D in Group 1 and -0.79 +/- 1.20 D in Group 2 (P < .05). Mean postoperative spherical equivalent at last follow-up was -0.43 +/- 0.90 and -0.65 +/- 1.10 D, respectively. At last follow-up, 104 eyes (97%) in Group 1 and 34 (97%) in Group 2 had a spherical equivalent between +1.00 and -3.00 D, and 90 eyes (84%) in Group 1 and 27 (77%) in Group 2 had 20/40 uncorrected visual acuity. Seven eyes (7%) in Group 1 and 1 (3%) in Group 2 lost two or more lines of best corrected visual acuity at last follow-up. Three months after ALK (for equal comparison), 25 eyes (23%) in Group 1 and 3 (8%) in Group 2 required radial keratotomy; 20 (19%) and 2 (6%), respectively, needed ALK revision; and 45 eyes (42%) and 17 (47%) needed astigmatic keratotomy. CONCLUSIONS: The results suggest that ALK is capable of impressive myopic corrections across a broad range of refractive error. The procedure is not accurate enough with a single microkeratome pass and requires enhancement procedures including recuts of the bed with the microkeratome and astigmatic and radial keratotomies. Using two blades to achieve an even cut gives better spherical equivalent and best corrected visual acuity results and lower enhancement rates.

Adult↗
PubMed1997

Laser in situ keratomileusis after automated lamellar keratoplasty and penetrating keratoplasty.

We present three patients who had laser in situ keratomileusis (LASIK) after corneal surgery as follow: 15 months after automated lamellar keratoplasty (ALK) for hyperopia, 6 months after ALK for hyperopia, and 2 years after penetrating keratoplasty (PKP). Although the first case was uneventful, intraoperative complications arose in the second case because the connection of the ALK-related flap to its stromal bed was insufficient. In the third case, the refractive error caused by PKP was corrected as shown by corneal topography and visual acuity measurement. In conclusion, LASIK after PKP can be considered a precise and safe procedure if 2 to 3 years pass between the procedures. An interval of 6 months between ALK and LASIK was too short, whereas 15 months after ALK for hyperopia, LASIK was performed without problems and delivered a good result.

Adult↗
PubMed2001

Among diffuse large B-cell lymphomas, T-cell-rich/histiocyte-rich BCL and CD30+ anaplastic B-cell subtypes exhibit distinct clinical features.

BACKGROUND: The EORTC clinical trial 20901, activated in 1990, was designed to treat non-Hodgkin's lymphomas (NHL) of intermediate/high-grade malignancy according to the Working Formulation. Established in 1994, the R.E.A.L. Classification on NHL has now replaced all former classifications. PATIENTS AND METHODS: We reanalysed all cases (n = 273) documented by material available for review according to the R.E.A.L. Classification. In addition, we subdivided cases recognised as diffuse large B-cell lymphoma (DLBCL) into three morphologically distinct categories, namely, large cleaved DLBCL (LC-DLBCL), T-cell-rich/histiocyte-rich B-cell lymphoma (T-cell-rich/histiocyte-rich BCL) and CD30+ DLBCL with anaplastic cell features (CD30+ DLBCL). Finally, T/NULL anaplastic large-cell lymphoma (ALCL) cases were subdivided into ALK+ and ALK- lymphomas. Review was performed independently by two pathologists from two different centres. RESULTS: DLBCL (61%), T/NULL ALCL (15%) and mantle-cell lymphoma (MCL, 50%) were the main NHL categories represented in the study. Fifty-seven of one hundred sixty DLBCL cases were further subclassified as LC-DLBCL (33 cases), T-cell-rich/histiocyte-rich BCL (13 cases) or CD30+ DLBCL (11 cases). The remaining cases were indicated as unspecified DLBCL. A clinico-pathological correlation confirmed the findings of previous studies suggesting that MCL, DLBCL and ALCL represent distinct entities with MCL being characterised by a short survival, in contrast with the longer survival and less frequent progression typical of ALK+ compared to ALK- ALCL. Within DLBCL, T-cell-rich/histiocyte-rich BCL showed distinctive features at presentation whereas CD30+ DLBCL showed a trend towards a more favourable prognosis, that might be comparable to that of ALK+ ALCL. CONCLUSIONS: Our data further support the usefulness of the R.E.A.L. Classification and illustrate the feasibility of DLBCL subtyping. Moreover, our results demonstrate the distinct clinical characteristics of T-cell-rich/histiocyte-rich BCL and CD30+ DLBCL with anaplastic cell features suggesting that they may represent clinico-pathologic entities.

Adolescent↗
PubMed2006

Proteomic identification of oncogenic chromosomal translocation partners encoding chimeric anaplastic lymphoma kinase fusion proteins.

The anaplastic lymphoma kinase (ALK) on 2p23 is a tyrosine kinase that forms chimeric fusions with numerous translocation partners. We describe a mass spectrometry-based approach for the identification of ALK fusion partners. This approach accurately identified the nucleophosmin (NPM)-ALK fusion protein in an anaplastic large cell lymphoma (ALCL)-derived cell line carrying the t(2;5)(p23;q35), and the TPM3-ALK in a clinical biopsy of inflammatory myofibroblastic tumor (IMT) carrying the t(1;2)(q21;p23). This study shows the ability of mass spectrometry to identify oncogenic chimeric proteins resulting from chromosomal rearrangements. This strategy can be adapted for the identification of known and unknown translocation partners of chimeric ALK fusion proteins involved in oncogenesis.

Amino Acid Sequence↗
PubMed2000

Activation of anaplastic lymphoma kinase receptor tyrosine kinase induces neuronal differentiation through the mitogen-activated protein kinase pathway.

Anaplastic lymphoma kinase (ALK) is a novel neuronal orphan receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems, suggesting a role in its normal development and function. To determine whether ALK could play a role in neuronal differentiation, we established a model system that allowed us to mimic the normal activation of this receptor. We expressed, in PC12 cells, a chimeric protein in which the extracellular domain of the receptor was replaced by the mouse IgG 2b Fc domain. The Fc domain induced the dimerization and oligomerization of the chimeric protein leading to receptor phosphorylation and activation, thus mimicking the effect of ligand binding, whereas the wild type ALK remained as a monomeric nonphosphorylated protein. Expression of the chimera, but not that of the wild type ALK or of a kinase inactive form of the chimera, induced the differentiation of PC12 cells. Analysis of the signaling pathways involved in this process pointed to an essential role of the mitogen-activated protein kinase cascade. These results are consistent with a role for ALK in neuronal differentiation.

Anaplastic Lymphoma Kinase↗
PubMed2002

A ligand-inducible epidermal growth factor receptor/anaplastic lymphoma kinase chimera promotes mitogenesis and transforming properties in 3T3 cells.

Oncogenic rearrangements of the anaplastic lymphoma kinase (ALK) gene, encoding a receptor type tyrosine kinase, are frequently associated with anaplastic large cell lymphomas. Such rearrangements juxtapose the intracellular domain of ALK to 5'-end sequences belonging to different genes and create transforming fusion proteins. To understand how the oncogenic versions of ALK contribute to lymphomagenesis, it is important to analyze the biological effects and the biochemical properties of this receptor under controlled conditions of activation. To this aim, we constructed chimeric receptor molecules in which the extracellular domain of the ALK kinase is replaced by the extracellular, ligand-binding domain of the epidermal growth factor receptor (EGFR). Upon transfection in NIH 3T3 fibroblasts, the EGFR/ALK chimera was correctly synthesized and transported to the cell surface, where it was fully functional in forming high versus low affinity EGF-binding sites and transducing an EGF-dependent signal intracellularly. Overexpression of the EGFR/ALK chimera in NIH 3T3 was sufficient to induce the malignant phenotype; the appearance of the transformed phenotype was, however, conditionally dependent on the administration of EGF. Moreover, the EGFR/ALK chimera was significantly more active in inducing transformation and DNA synthesis than the wild type EGFR when either was expressed at similar levels in NIH 3T3 cells. Comparative analysis of the biochemical pathways implicated in the transduction of mitogenic signals did not show any increased ability of the EGFR/ALK to phosphorylate PLC-gamma and MAPK compared with the EGFR. On the contrary, EGFR/ALK showed to have a consistently greater effect on phosphatidylinositol 3-kinase activity compared with the EGFR, indicating that this enzyme plays a major role in mediating the mitogenic effects of ALK in NIH 3T3 cells.

3T3 Cells↗
PubMed2002

Anti-apoptotic signaling of pleiotrophin through its receptor, anaplastic lymphoma kinase.

The secreted growth factor pleiotrophin (PTN) can induce mitogenesis in cells that express the receptor for this growth factor, anaplastic lymphoma kinase (ALK). Here we examine the ability of PTN to produce anti-apoptotic signals. We demonstrate that PTN is a survival factor for SW-13 epithelial cells and show that ribozyme-mediated depletion of ALK from SW-13 cells abolishes this effect of PTN. Furthermore, in serum-starved NIH3T3 fibroblasts PTN prevents apoptosis (measured by annexin V staining) with an EC(50) of 0.2 ng/ml and induces cell growth at higher concentrations of PTN. A polyclonal antibody against the PTN ligand-binding domain of the ALK receptor (alpha-LBD) was a partial agonist for ALK in NIH3T3 cells. This alpha-LBD antibody showed high agonist activity for anti-apoptosis (56 +/- 9% relative to PTN), low agonist activity for cell growth (21 +/- 1% relative to PTN), and was an antagonist of PTN-induced cell growth (61 +/- 2% inhibition). Both MAP kinase and phosphatidylinositol (PI) 3-kinase cascades in NIH3T3 cells were activated by PTN, and this effect persisted for up to 3 h. Surprisingly, the anti-apoptotic effect of PTN was completely blocked by the MAP kinase inhibitor UO126, but was not affected by the PI 3-kinase inhibitor LY294002. In contrast, PTN-dependent cell growth required both MAPK and PI 3-kinase activity. We conclude that anti-apoptotic signaling of PTN through ALK in NIH3T3 fibroblasts is via the MAP kinase pathway.

3T3 Cells↗
PubMed2000

Reduced expression of BMP-3 due to mechanical loading: a link between mechanical stimuli and tissue differentiation.

Mechanical signaling and BMP expression appear to be involved in controlling the differentiation of cartilage in fracture repair, but the connection between mechanics and BMP signaling is not known. In this study of rats, we used a bone chamber to see how BMP gene expression was changed by a mechanical loading regime that induces cartilage formation in this model. We compared the still undifferentiated tissue in loaded and unloaded chambers in the same rat regarding the expression of TGFbeta-1, BMP-2, 3, 4, 5, 6, 7, CDMP-1, 2 and ALK-2 and 3 by using RT-PCR normalized against GAPDH. We found expression of TGFbeta-1, BMP-2 and 4 in all specimens, and BMP 5-7 and CDMPs in none. 1 week after loading started, BMP-3 was strongly expressed in the unloaded control specimens in 7 of 8 animals, but detectable in only I of the contralateral loaded ones. After 2 weeks of loading, the BMP-3 expression pattern was less clear, but with both time groups taken together, there was still less BMP-3 expression on the loaded side in 9 rats, more in 1 and no difference in 5 (p = 0.01). ALK-2 at 1 week was expressed in all specimens expressing BMP-3 and in none of the others. At 2 weeks, ALK-2 was expressed in all specimens. Thus, a loading regime, known to induce cartilage in this model, caused down-regulation of BMP-3 and ALK-2. The results are consistent with the view that BMP-3 inhibits differentiation, as recently described. This role appears to be linked to the ALK-2 receptor. Most importantly, the results indicate a link between mechanical signaling and BMP expression such that mechanically-induced down-regulation of the inhibiting BMP-3 enabled the induction of cartilage.

Activin Receptors, Type I↗
PubMed2004

Gene expression profiling in anaplastic large cell lymphoma and Hodgkin's disease.

Recent efforts have been made to isolate molecular targets that could explain different outcome between histological subtypes of lymphomas and to understand the molecular mechanisms underlying oncogenic events. Using the SSH technique, we compared the transcriptome of 2 cases of ALK+ and ALK- anaplastic large cell lymphoma (ALCL) and of 2 cases of classical Hodgkin's lymphoma (cHL) with opposite behavior. Regarding ALCL, we showed that ALK-positive tumors overexpressed genes involved in different signaling pathways such as activation or signaling of T-cells, regulation of apoptosis, phospholipase Cgamma and phosphatidyl inositol-3 Kinase. In addition, the characterization of a specific molecular signature may be of clinical relevance since ALK+ tumors generally have a better prognosis than ALK- ones. Similar problems of differential prognosis is observed in cases of cHL, which in addition, may be morphologically and immunologically indistinguishable. Therefore, we applied the same SSH technique to 2 cHL samples from patients with favorable and poor outcome, respectively. Forty-four cDNAs were significantly overexpressed in the poor outcome case. In addition to the defender against death cell 1 (DAD1) gene, overexpressed clones corresponded mostly to expressed sequence tags (ESTs). Interestingly, the present study identifies new genes which may be involved in the pathogenesis and/or clinical outcome of cHL and deserve further investigations.

Gene Expression Profiling↗
PubMed2006

In situ detection of hTERT variants in anaplastic large cell lymphoma.

The expression of hTERT and its isoforms is difficult to assess in lymphoma tissues with the commonly used reverse transcription-polymerase chain reaction (RT-PCR) methods, because non-neoplastic lymphocytes expressing hTERT are always present in the lymphomatous infiltrates. The present study aimed to investigate hTERT mRNA variants in anaplastic large cell lymphoma (ALCL) (n = 38) with in situ hybridization (ISH), along with the immunodetection of hTERT protein. Probes for the identification of mRNAs containing (Bplus) and lacking (Bdel) exons 7 and 8 of the hTERT mRNA were used. Normal lymphocyte populations equally expressed both Bplus and Bdel mRNAs. Although all ALCL examined were found positive for hTERT expression with RT-PCR, hTERT mRNAs were identified in 68% of these tumors with ISH, with a higher incidence in the group bearing ALK translocations (10 out of 11; 90.9%) compared to the ALK negative group (17 out of 27; 59.3%) (PPearson's = 0.002). The same results were obtained with immunohistochemistry for hTERT. In approximately 50% of cases, only Bplus positive cells were identified, again with a higher incidence in the ALK positive compared to the ALK negative group (PPearson's = 0.016). In conclusion, ISH for hTERT mRNAs appears to be a valuable tool for the investigation of hTERT expression in lymphomas. Aberrations in hTERT variant profiles and a decline in the expression of the B deleted isoform may be associated with the pathogenesis of ALCL, especially with respect to ALK positive tumors.

Adolescent↗
PubMed1997

The activin receptor-like kinase 1 gene: genomic structure and mutations in hereditary hemorrhagic telangiectasia type 2.

The activin receptor-like kinase 1 gene (ALK-1) is the second locus for the autosomal dominant vascular disease hereditary hemorrhagic telangiectasia (HHT). In this paper we present the genomic structure of the ALK-1 gene, a type I serine-threonine kinase receptor expressed predominantly in endothelial cells. The coding region is contained within nine exons, spanning < 15 kb of genomic DNA. All introns follow the GT-AG rule, except for intron 6, which has a TAG/gcaag 5' splice junction. The positions of introns in the intracellular domain are almost identical to those of the mouse serine-threonine kinase receptor TSK-7L. By sequencing ALK-1 from genomic DNA, mutations were found in six of six families with HHT either shown to link to chromosome 12q13 or in which linkage of HHT to chromosome 9q33 had been excluded. Mutations were also found in three of six patients from families in which available linkage data were insufficient to allow certainty with regard to the locus involved. The high rate of detection of mutations by genomic sequencing of ALK-1 suggests that this will be a useful diagnostic test for HHT2, particularly where preliminary linkage to chromosome 12q13 can be established. In two cases in which premature termination codons were found in genomic DNA, the mutant mRNA was either not present or present at barely detectable levels. These data suggest that mutations in ALK-1 are functionally null alleles.

Activin Receptors↗
PubMed1993

Sporicidal activity of chemical sterilants used in hospitals.

OBJECTIVE: The current study was designed to assess the sporicidal activity of chemical sterilants using the Association of Official Analytical Chemists (AOAC) sporicidal test. Chemical sterilants are used most commonly in the healthcare setting to disinfect medical instruments such as endoscopes. This study was undertaken to evaluate the efficacy of several newer formulations of glutaraldehydes and hydrogen peroxide as chemical sterilants. DESIGN: Using the AOAC test the following agents were tested: two 2% alkaline glutaraldehydes (2% Alk-Glut), 2% acid glutaraldehyde (2% Acid Glut), 2% glutaraldehyde-7.05% phenol-1.20% sodium phenate, 10% glutaraldehyde-0.5% phenylphenol-0.1% tertiary amylphenol, and 6% hydrogen peroxide (H2O2). Growth in > 1 of 60 seeded penicylinders is considered by the AOAC to indicate failure of sporicidal activity. RESULTS: Test results of the six disinfectants against Bacillus subtilis using the manufacturers' specified use-dilution and exposure time were: 0/60 with 2% Alk-Glut (product 1) at 10 hours, 0/60 with 2% Alk-Glut (product 2) at 8 hours, 0/60 with 2% Acid Glut at 10 hours, 2/60 with 2% glutaraldehyde-7.05% phenol-1.20% sodium phenate at 6.75 hours, 0/60 with a 1:5 dilution (2.0% Glut) of 10% glutaraldehyde-0.5% phenylphenol-0.1% amylphenol at 6 hours, 59/60 with a 1:20 dilution (0.5% Glut) of 10% glutaraldehyde-0.5% phenylphenol-0.1% tertiary amylphenol at 12 hours and 0/60 with 6% H2O2 at 6 hours. Test results against Clostridium sporogenes were: 2/60 with 2% Alk-Glut (product 1) at 10 hours, 1/60 with 2% Alk-Glut (product 2) at 8 hours, 1/60 with 2% Acid Glut at 10 hours, 2/60 with undiluted 2% glutaraldehyde-7.05% phenol-1.20% sodium phenate at 6.75 hours, 6/60 with a 1:5 dilution (2% Glut) of 10% glutaraldehyde-0.5% phenylphenol-0.1% amylpenol at 6 hours, 60/60 with a 1:20 dilution (0.5% Glut) of 10% glutaraldehyde-0.5% phenylphenol-0.1% amylpenol at 12 hours, and 0/60 with 6% H2O2 at 6 hours. Dilutions of 2% glutaraldehyde-7.05% phenol-1.20% sodium phenate yielded the following results against C sporogenes: 59/60 with a 1:8 dilution (0.25% Glut) at 6.75 hours, 60/60 with a 1:16 dilution (0.125% Glut) at 6.75 hours, 11/90 with a 1:8 (0.25% Glut) dilution at 12 hours, and 60/60 with a 1:16 dilution (0.125% Glut) at 12 hours. CONCLUSIONS: Both 2% acid and alkaline glutaraldehydes are effective chemical sterilants. Diluting glutaraldehyde-based sterilants below 2% glutaraldehyde resulted in failure to kill spores of B subtilis and C sporogenes.

Colony Count, Microbial↗
PubMed1999

Roles of bone morphogenetic protein type I receptors and Smad proteins in osteoblast and chondroblast differentiation.

The biological effects of type I serine/threonine kinase receptors and Smad proteins were examined using an adenovirus-based vector system. Constitutively active forms of bone morphogenetic protein (BMP) type I receptors (BMPR-IA and BMPR-IB; BMPR-I group) and those of activin receptor-like kinase (ALK)-1 and ALK-2 (ALK-1 group) induced alkaline phosphatase activity in C2C12 cells. Receptor-regulated Smads (R-Smads) that act in the BMP pathways, such as Smad1 and Smad5, also induced the alkaline phosphatase activity in C2C12 cells. BMP-6 dramatically enhanced alkaline phosphatase activity induced by Smad1 or Smad5, probably because of the nuclear translocation of R-Smads triggered by the ligand. Inhibitory Smads, i.e., Smad6 and Smad7, repressed the alkaline phosphatase activity induced by BMP-6 or the type I receptors. Chondrogenic differentiation of ATDC5 cells was induced by the receptors of the BMPR-I group but not by those of the ALK-1 group. However, kinase-inactive forms of the receptors of the ALK-1 and BMPR-I groups blocked chondrogenic differentiation. Although R-Smads failed to induce cartilage nodule formation, inhibitory Smads blocked it. Osteoblast differentiation induced by BMPs is thus mediated mainly via the Smad-signaling pathway, whereas chondrogenic differentiation may be transmitted by Smad-dependent and independent pathways.

Activin Receptors↗
PubMed2004

Biosynthesis of the flavour precursors of onion and garlic.

Onion (Allium cepa), garlic (A. sativum) and other Alliums are important because of the culinary value of their flavours and odours. These are characteristic of each species and are created by chemical transformation of a series of volatile sulphur compounds generated by cleavage of relatively stable, odourless, S-alk(en)yl cysteine sulphoxide flavour precursors by the enzymes alliinase and lachrymatory-factor synthase. These secondary metabolites are S-methyl cysteine sulphoxide (MCSO, methiin; present in most Alliums, some Brassicaceae), S-allyl cysteine sulphoxide (ACSO, alliin; characteristic of garlic), S-trans-prop-1-enyl cysteine sulphoxide (PECSO, isoalliin; characteristic of onion), and S-propyl cysteine sulphoxide (PCSO, propiin; in onion and related species). Information from studies of the transformation of putative biosynthetic intermediates, radiolabelling, and from measurements of sulphur compounds within onion and garlic have provided information to suggest a biosynthetic pathway. This may involve alk(en)ylation of the cysteine in glutathione, followed by cleavage and oxidation to form the alk(en)yl cysteine sulphoxide flavour precursors. There is also evidence that synthesis of the flavour precursors may involve (thio)alk(en)ylation of cysteine or a precursor such as O-acetyl serine. Both routes may occur depending on the physiological state of the tissue. There are indications from the effects of environmental factors, such as the availability of sulphur, that control of the biosynthesis of each flavour precursor may be different. Cysteine and glutathione metabolism are discussed to indicate parallels with Allium flavour precursor biosynthesis. Finally, possible avenues for exploration to determine the origin in planta of the alk(en)yl groups are suggested.

Cysteine↗
PubMed1998

Statistical evaluation of diagnostic and prognostic features of CD30+ cutaneous lymphoproliferative disorders: a clinicopathologic study of 65 cases.

Several clinical and histopathologic features of 65 CD30+ cutaneous lymphoproliferations were evaluated for their diagnostic value between CD30+ primary versus secondary cutaneous lymphomas and for their prognostic significance. Primary cutaneous disease, spontaneous regression, and absence of extracutaneous spreading (but not age < or =60 years) were associated with a better prognosis. Epithelial membrane antigen, BNH9, CD15 or CBF.78 antigen were expressed in all types of cutaneous lymphoproliferations. However, epithelial membrane antigen immunoreactivity was more frequently expressed in CD30+ secondary cutaneous large-cell lymphoma. Among CD30+ primary cutaneous large-cell lymphoma, CD15 expression was only seen in localized skin lesions. P53 expression was not associated with spontaneous regression, extracutaneous spreading, or survival. Nested reverse transcriptase-polymerase chain reaction allowed the detection of NPM-ALK transcripts in 10 of 26 CD30+ primary and in 3 of 11 secondary cutaneous large-cell lymphomas. The ALK protein was detected in only 1 of 50 primary and in 4 of 15 secondary cutaneous CD30+ lymphoproliferations. In CD30+ primary cutaneous lymphoproliferation, NPM-ALK transcripts might be expressed by very rare normal or tumoral cells that are undetectable by immunohistochemistry. However, the expression of either NPM-ALK transcripts or ALK-protein was not correlated with prognosis or age in CD30+ cutaneous lymphoproliferations.

Biomarkers, Tumor↗
PubMed1990

An effective technique for enrichment and isolation of Candida cloacae mutants defective in alkane catabolism.

Techniques are described which allow mutated populations of Candida cloacae to be enriched efficiently (up to 167-fold in one round of enrichment) for mutants deficient in the alkane degradation pathway (Alk-). Such mutants, as well as being of scientific importance in studies of the degradation pathway, are also of commercial interest because several of the degradative intermediates are of value to the chemical industry. The Alk- mutants were readily isolated by their inability to grow on agar plates supplied with hexadecane as sole carbon source. A total of 288 Alk- mutants were isolated from, effectively, 4 x 10(6) mutagen-treated cells. They were further characterized by replica-plating using palmitic acid (PA) or acetate (Ac) as sole carbon source. Preliminary screening studies showed that of the 84 Alk- PA- Ac+ mutants, most could accumulate dicarboxylic acids from hexadecane and palmitic acid and at least one mutant also produced 3-hydroxyhexadecanedioic acid. Of the 80 mutants characterized as Alk- PA+, 16 produced small amounts of hexadecanol.

Alkanes↗