Rare C2 Research Articles

A rare case of large retropharyngeal pre-vertebral chordoma presented as oropharyngeal swelling

Posterior oropharyngeal swelling can result from various pathologies, including chordomas. Chordoma is a notochordal remnant origin tumor. It is a rare bone and central nervous system tumor, especially in the cervical region. Chordoma is a tumor with properties such as slowly growing and frequently recur in most patients. This case report aims to comprehensively understand the clinical presentation and radiological features of a rare C2 retropharyngeal pre-vertebral chordoma. A 24-year-old male with a two-year history of dysphagia presented with progressively worsening symptoms, including dyspnea, dysphonia, and weight loss. On examination, a large mass was observed in the posterior oropharynx. Radiologically, a large soft tissue mass involves the C2 vertebral body, extending into the pre-vertebral soft tissue and compromising the airway. The mass appears hypointense in T1 weighted images, heterogeneously hyperintense in T2, and shows heterogeneous contrast enhancement. The chordoma was confirmed through histopathological analysis, showing characteristic physaliferous cells within a myxoid stroma. Posterior oropharyngeal masses require prompt and accurate evaluation. Radiological evaluation is crucial in identifying the tumor's origin, extent, and vascularity, aiding in diagnosis and treatment planning. Surgical resection is the primary treatment, but chordomas have a high recurrence rate even after complete removal. Radiotherapy can improve survival and reduce recurrence. This case highlights the importance of multidisciplinary collaboration in providing individualized care for rare chordoma presentations.

Reactions of aluminium(i) with transition metal carbonyls: scope, mechanism and selectivity of CO homologation.

Over the past few decades, numerous model systems have been discovered that create carbon–carbon bonds from CO. These reactions are of potential relevance to the Fischer–Tropsch process, a technology that converts syngas (H2/CO) into mixtures of hydrocarbons. In this paper, a homogeneous model system that constructs carbon chains from CO is reported. The system exploits the cooperative effect of a transition metal complex and main group reductant. An entire reaction sequence from C1 → C2 → C3 → C4 has been synthetically verified. The scope of reactivity is broad and includes a variety of transition metals (M = Cr, Mo, W, Mn, Re, Co), including those found in industrial heterogeneous Fischer–Tropsch catalysts. Variation of the transition metal fragment impacts the relative rate of the steps of chain growth, allowing isolation and structural characterisation of a rare C2 intermediate. The selectivity of carbon chain growth is also impacted by this variable; two distinct isomers of the C3 carbon chain were observed to form in different ratios with different transition metal reagents. Based on a combination of experiments (isotope labelling studies, study of intermediates) and calculations (DFT, NBO, ETS-NOCV) we propose a complete mechanism for chain growth that involves defined reactivity at both transition metal and main group centres.

Genomic surveillance of Escherichia coli ST131 identifies local expansion and serial replacement of subclones.

Escherichia coli sequence type 131 (ST131) is a pandemic clone that is evolving rapidly with increasing levels of antimicrobial resistance. Here, we investigated an outbreak of E. coli ST131 producing extended spectrum β-lactamases (ESBLs) in a long-term care facility (LTCF) in Ireland by combining data from this LTCF (n=69) with other Irish (n=35) and global (n=690) ST131 genomes to reconstruct the evolutionary history and understand changes in population structure and genome architecture over time. This required a combination of short- and long-read genome sequencing, de novo assembly, read mapping, ESBL gene screening, plasmid alignment and temporal phylogenetics. We found that Clade C was the most prevalent (686 out of 794 isolates, 86 %) of the three major ST131 clades circulating worldwide (A with fimH41, B with fimH22, C with fimH30), and was associated with the presence of different ESBL alleles, diverse plasmids and transposable elements. Clade C was estimated to have emerged in c. 1985 and subsequently acquired different ESBL gene variants (bla CTX-M-14 vs bla CTX-M-15). An ISEcp1-mediated transposition of the bla CTX-M-15 gene further increased the diversity within Clade C. We discovered a local clonal expansion of a rare C2 lineage (C2_8) with a chromosomal insertion of bla CTX-M-15 at the mppA gene. This was acquired from an IncFIA plasmid. The C2_8 lineage clonally expanded in the Irish LTCF from 2006, displacing the existing C1 strain (C1_10), highlighting the potential for novel ESBL-producing ST131 with a distinct genetic profile to cause outbreaks strongly associated with specific healthcare environments.

Epoxynemanione A, nemanifuranones A–F, and nemanilactones A–C, from Nemania serpens, an endophytic fungus isolated from Riesling grapevines

Ten polyketide specialized metabolites, epoxynemanione A, nemanifuranones A–F, and nemanilactones A–C, were isolated from the culture filtrate of Nemania serpens (Pers.) Grey (1821), an endophytic fungus from a Riesling grapevine (Vitis vinifera) found in Canada's Niagara region. Additionally, four known metabolites 2-(hydroxymethyl)-3-methoxy-benzoic acid, phyllostine, 5-methylmellein and a nordammarane triterpenoid were isolated. A related known metabolite 2,3-dihydro-2-hydroxy-2,4-dimethyl-5-trans-propenylfuran-3-one has also been included for structural and biological comparison to the nemanifuranones. The latter was isolated from the culture filtrates of Mollisia nigrescens, an endophytic fungus from the leaves and stems of lowbush blueberry (Vaccinium angustifolium) found in the Acadian forest of Nova Scotia, Canada. Their structures were elucidated based on 1D and 2D NMR, HRESIMS measurements, X-ray crystallographic analysis of nemanifuranone A, the nordammarane triterpenoid and 2,3-dihydro-2-hydroxy-2,4-dimethyl-5-trans-propenylfuran-3-one compounds, and comparison of NOE and vicinal 1H-1H coupling constants to literature data for relative stereochemical assignments. Nemanifuranone A possesses a rare C2 hemiacetal and was active against both Gram-negative and Gram-positive bacteria.

RsaI but not DraI polymorphism in CYP2E1 gene increases the risk of gastrointestinal cancer in Malaysians: a case–control study

ObjectivesOur study aimed to investigate the association of CYP2E1 C-1019T RsaI and T7678A DraI polymorphisms and factors such as age, gender and ethnicity to the risk of gastrointestinal cancer (GIC)...

Allele and genotype frequencies of polymorphic cytochromes P4502D6, 2C19 and 2E1 in aborigines from western Australia.

The polymorphisms of the important xenobiotic metabolizing enzymes CYP2D6, CYP2C19 and CYP2E1 have been studied extensively in a large number of populations and show significant heterogeneity in the frequency of different alleles/genotypes and in the prevalence of the extensive and poor metabolizer phenotypes. Understanding of inter-ethnic differences in genotypes is important in prediction of either beneficial or adverse effects from therapeutic agents and other xenobiotics. Since no data were available for Australian Aborigines, we investigated the frequencies of alleles and genotypes for CYP2D6, CYP2C19 and CYP2E1 in a population living in the far north of Western Australia. Because of its geographical isolation, this population can serve as a model to study the impact of evolutionary forces on the distribution of different alleles for xenobiotic metabolizing enzymes. Twelve CYP2D6 alleles were analysed. The wild-type allele *1 was the most frequent (85.81%) and the non-functional alleles (*4, * 5, * 16) had an overall frequency of less than 10%. Only one subject (0.4%) was a poor metabolizer for CYP2D6 because of the genotype *5/*5. For CYP2C19, the frequencies of the *1 (wild-type) and the non-functional (*2 and *3) alleles were 50.2%, 35.5% and 14.3%, respectively. The combined CYP2C19 genotypes (*2/*2, *2/*3 or *3/*3) correspond to a predicted frequency of 25.6% for the CYP2C19 poor metabolizer phenotype. For CYP2EI, only one subject had the rare c2 allele giving an overall allele frequency of 0.2%. For CYP2D6 and CYP2C19, allele frequencies and predicted phenotypes differed significantly from those for Caucasians but were similar to those for Orientals indicating a close relationship to East Asian populations. Differences between Aborigines and Orientals in allele frequencies for CYP2D6* 10 and CYP2E1 c2 may have arisen through natural selection, or genetic drift, respectively.

The RsaI polymorphism of CYP2E1 and susceptibility to alcoholic liver disease in Caucasians: effect on age of presentation and dependence on alcohol dehydrogenase genotype.

Twin studies in Caucasians suggest that susceptibility to alcoholic liver disease is, in part, genetically determined. Because most of the deleterious effects of alcohol are caused by its metabolism, attention has focused upon genes encoding ethanol metabolizing enzymes. Caucasians are polymorphic at only two of these gene loci--cytochrome P450 2E1 (CYP2E1) and alcohol dehydrogenase 3 (ADH3). We examined the frequency of the RsaI polymorphism of CYP2E1 and ADH3 genotype in 264 patients with alcoholic liver disease and 121 local control individuals. There was a non-significant excess of the rare c2 CYP2E1 allele in patients with advanced liver disease compared with control individuals/patients with steatosis only (0.029 versus 0.017/0.00). However, patients with the c2 allele presented at a younger age compared with those with the wild type c1 allele only (42.3 +/- 1.6 years versus 49.0 +/- 0.6 years; P = 0.001) with at least as advanced histology (93% cirrhotic versus 74%). Male patients had a higher frequency of the ADH3*2/*2 genotype (which encodes the less active gamma2 subunit) than control individuals [odds ratio (OR) 2.04 (1.11-3.76)], however, ADH3 genotype did not differ with histological stage or with age of presentation. Patients with advanced disease possessing the c2 allele had a significantly higher frequency of the ADH3*2/*2 genotype compared with c1 homozygotes [OR 3.71 (1.24-11.09)]. This study demonstrates that, although rare in Caucasians, possession of the mutant c2 allele of CYP2E1 increases the risk of alcoholic liver disease at a given level of cumulative alcohol consumption. This risk appears to be particularly manifest in individuals carrying the ADH3*2 allele, presumably reflecting increased metabolism of ethanol by CYP2E1. In the absence of the c2 allele, ADH3 genotype does not influence the risk of advanced alcoholic liver disease but, in males at least, may influence the risk of alcoholism.

Decreased inhibition of immune precipitation by sera with the C2 B allotype

Complement-mediated precipitation inhibiting (CMPI) activity of sera of 5 individuals homozygous for C2 B was compared to that of sera of 20 individuals carrying the common C2 C allotype. Sera with the rare C2 B allotype had a depressed CMPI capacity in both the early (5 min) and the late (60 min) stages of the reaction. We have also compared the CMPI activity of seven homozygous C4A deficient ( C4A ∗Q0 ) and eight C4B deficient ( C4B ∗Q0 ) serum samples and did not find significant differences from the controls (no C4 null alleles) in any stage of the reaction. These results indicate that C2 is the critical component in the CMPI reaction of the two constituents of the classical pathway C3 convertase and that C2 B is less active than C2 C.

Individuals with IgA deficiency and common variable immunodeficiency share polymorphisms of major histocompatibility complex class III genes.

IgA deficiency and common variable immunodeficiency are heritable disorders that can occur within the same family. Both immunodeficiencies are characterized by arrests in B-cell differentiation that vary in the extent of the immunoglobulin isotypes involved. A high frequency of major histocompatibility complex supratypes associated with a null allele of the gene encoding the C4A isotype of complement component C4 has been observed in IgA-deficient individuals. In search of a genetic linkage between the two immunodeficiencies, we examined the major histocompatibility complex (MHC) class III genes encoding complement components C2, C4A, and C4B and steroid 21-hydroxylase in addition to the HLA serotypes in individuals with either common variable immunodeficiency or IgA deficiency. Twelve of 19 patients with common variable immunodeficiency (63%, P less than 0.001) and 9 of 16 patients with IgA deficiency (56%, P less than 0.01) had rare C2 alleles and/or C4A and 21-hydroxylase A deletions, whereas these gene features were seen in only 5 of 34 healthy individuals (15%) in the control group. Nine of 11 patients with C4A deletion had an HLA haplotype consistent with the MHC supratype HLA-A1, Cw7, B8, C4AQ0, C4B1, BfS, DR3 previously found to be associated with IgA deficiency. The data support the hypothesis that common variable immunodeficiency and IgA deficiency are related disorders, susceptibility to which is determined by a gene(s) within or near the MHC class III gene region on chromosome 6.

Complement C4 allotypes in congenital adrenal hyperplasia due to 21-hydroxylase deficiency: Further evidence for different allelic variants at the 21-hydroxylase locus

The gene frequencies and haplotype frequencies for the alleles of the C4A and C4B loci were determined in a population of 39 unrelated Italian patients with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase (21-OH) deficiency and compared with the frequencies of the C4 alleles and C4 haplotypes present on the normal parental HLA haplotypes (i.e., the parental HLA haplotypes which did not carry the 21-OH deficiency allele). There was a decrease in the C4A ∗QO (null) allele among the patients (uncorrected P < 0.05) and a slight but statistically insignificant increase among the patients of the C4A ∗4 allele. The gene frequencies of the C4B locus were similar in the two groups. The very rare C4B ∗3 allele occurred in one patient. Overall, the C4A;C4B haplotypes were very similar in the two groups. In the patient group there was a slight increase in the frequency of the C4A ∗3; B ∗QO haplotype and the C4A ∗4; B ∗2 haplotype, whereas the C4A ∗QO; B ∗1 and C4A ∗QO; B ∗2 haplotypes were decreased or absent. One patient had the very rare haplotype C4A ∗QO;B ∗3 , and was positive for the low frequency HLA-Bw47 determinant on the same haplotype. Seven patients with classical CAH and two patients with late onset 21-OH deficiency, who had the Bw47 antigen, were also found to have the unique complotype C4A ∗QO; B ∗3; BF ∗F: C2 ∗C . Eleven additional patients with the HLA-B14, DR1-associated disease variant late onset 21-OH deficiency and four individuals with cryptic, asymptomatic 21-OH deficiency were also typed for the C4 electrophoretic variants. The 19 haplotypes with B14;DR1 all had the complotype C4A ∗2;B ∗2;BF ∗S;C2 ∗C . The rare C2 ∗B allele of the C2 locus was found on 10 haplotype with 21-OH deficiency. The complotype on eight of these was C4A ∗4;B ∗2;BF ∗S; C2 ∗B . The C2 ∗B was found only once on the normal parental HLA haplotypes. This study provides additional evidence for the hypothesis that the mutation on the 21-OH locus associated with HLA-Bw47 is unique and different from the mutation on the 21-OH locus resulting in the late onset or cryptic 21-OH deficiency allele associated with B14. It is likely that many independent mutations have acted on the 21-OH locus and that the clinical and biochemical heterogeneity of the 21-OH deficiency syndromes reflect heterogeneity in the DNA assaults.

On the significance of C2, C4, and factor B polymorphisms in disease.

In this review article, recent evidence is presented that some diseases like insulin-dependent diabetes mellitus, multiple sclerosis, and idiopathic membranous nephropathy, which are primarily associated with HLA-D,DR, are also related to the rare C2, C4, and Factor B alleles. Circumstantial evidence is available that at least some of these rare variants may be functionally deficient. Based on the concept of functionally interacting gene clusters, mutant complement genes may lead to impaired effector mechanisms in virus neutralization or lysis of virus-infected cells. Other mechanisms such as alteration of vascular permeability may be involved in the development of proliferative retinopathy and familial hypertension. In lepromatous lepra, an impaired cell-mediated lysis of M. leprae may be related to the hemolytically inactive C4F1 allelic product.

Modification-deficient mutants of bacteriophage P1. I. Restriction by P1 cryptic lysogens.

The P1 restriction-modification system is responsible for the inefficient plating of c2 and c3 mutants of bacteriophage P1 on P1 cryptic lysogens. P1 cryptic is a defective prophage which does not express P1 immunity but which does express P1 modification and restriction. The rare c2 or c3 phage which do grow on the P1 cryptic lysogens [abbreviated (P1cry)], lose their ability to do so after growth on a nonlysogenic host. Temperature-sensitive c2 mutants grown on a nonlysogenic host at the permissive temperature plate efficiently on (P1cry). If grown at a nonpermissive temperature, however, the c2 ts mutants plate inefficiently on (P1cry). P1r−m+, a nonrestricting P1 phage, plates efficiently on (P1cry), but P1r−m−, which neither restricts nor modifies, plates inefficiently on (P1cry). These results are explained as follows: P1 DNA is itself a substrate for the P1 directed modification-restriction system. Normally, during lytic growth, P1 DNA is modified. However, P1r−m−, c2, the c3 mutants are modification-defective. Thus, when their unmodified DNA enters (P1cry), it is subject to P1 restriction. Direct evidence for this hypothesis was obtained from experiments in which the ability of P1 phage to modify λ was studied. P1r−m−, c2 and c3 mutants cannot modify λ whereas P1 wild type and P1r−m+ are able to do so. Furthermore, c2 and c3 mutants can complement each other to express P1 modification. P1r−m− is not complemented by either c2 or c3 mutants. It is concluded that c2 and c3 are two cistrons required for P1 modification. P1r−m− may be missing, or unable to transcribe, the c2 and c3 genes.