Dermatan sulfate in tunicate phylogeny: Order-specific sulfation pattern and the effect of [→4IdoA(2-Sulfate)β-1→3GalNAc(4-Sulfate)β-1→] motifs in dermatan sulfate on heparin cofactor II activity

After the publication of the work entitled "Dermatan sulfate in tunicate phylogeny: Order-specific sulfation pattern and the effect of [→4IdoA(2-Sulfate)β-1→3GalNAc(4-Sulfate)β-1→] motifs in dermatan sulfate on heparin cofactor II activity", by Kozlowski et al., BMC Biochemistry 2011, 12:29, we found that the legends to Figures 2 to 5 contain serious mistakes that compromise the comprehension of the work. This correction article contains the correct text of the legends to Figures 2 to 5

Biodiversity of CS-proteoglycan sulphation motifs: chemical messenger recognition modules with roles in information transfer, control of cellular behaviour and tissue morphogenesis

Chondroitin sulphate glycosaminoglycan chains on cell and ECM proteoglycans can no longer be regarded as merely hydrodynamic space fillers. Overwhelming evidence over recent years indicates that sulphation motif sequences within the chondroitin sulphate chain structure are a source of significant biological information to cells and their surrounding environment. Chondroitin sulphate sulphation motifs have been shown to interact with a wide variety of bioactive molecules e.g. cytokines, growth factors, chemokines, morphogenetic proteins, enzymes and enzyme inhibitors, as well as structural components within the extracellular milieu. They are therefore capable of modulating a panoply of signalling pathways thus controlling diverse cellular behaviours including proliferation, differentiation, migration and matrix synthesis. Consequently, through these motifs, chondroitin sulphate proteoglycans play significant roles in the maintenance of tissue homeostasis, morphogenesis, development, growth and disease. Here we review (i) the biodiversity of chondroitin sulphate proteoglycans and their sulphation motif sequences and (ii) the current understanding of the signalling roles they play in regulating cellular behaviour during tissue development, growth, disease and repai

Prevalence of Antimicrobial Resistance in Haemophilus influenzae and Streptococcus pneumoniae : Comparison of Clinical Isolates of Japan and The Philippines

For clinical isolates of Haemophilus influenzae and Streptococcus pneumoniae in Japan (356 and 179 strains, respectively) and in the Philippines (98 and 59 strains, respectively), minimum inhibitory concentrations (MICs) of ampicillin, cefazolin, cefotiam, ceftizoxim, ofloxacin, erythromycin, and minocycline were examined. The rates of β-lactamase producing H. influenzae were 17.7% (63/356) in Japan and 2.0% (2/98) in the Philippines, and all of these strains were ampicillin MICs 〓1.56 ugml^. In addition, 5 strains in Japan that lacked β-lactamase activity were also less susceptible to ampicillin. Among the antimicrobials tested, ceftizoxim was the most active against H. influenzae in both countries (MICs 〓0.2 ugml^). Five strains of S. pneumoniae in Japan were relatively resistant to ampicillin (MIC=0.1 ugml^), whereas there were no such strains among isolates in the Philippines. Forty strains (22.3%) and 108 strains (60.3%) among S. pneumoniae in Japan exhibited erythromycin MICs 〓0.2 ugml^ and minocycline MICs 〓1.56 ugml^, respectively. In contrast, all isolates in the Philippines were erythromycin MICs 〓0.05 ugml^ and minocycline MICs 〓0.39 ugml^. Present study indicates that H. influenzae and S. pneumoniae in the Philippines remained still susceptible to the antimicrobials tested except for 2 β-lactamase-positive, ampicillin-resistant H. influenzae, whereas ampicillin-resistant H. influenzae mediated by β-lactamase or non-β-lactamase mechanisms and ampicillin-, erythromycin- or minocycline-resistant S. pneumoniae were included among isolates in Japan

Diagnostic Validity of Combining HTLV-1 Serology and Immunophenotyping in Adult T-Cell Leukemia

Adult T-cell leukemia (ATL) is heterogeneous and sometimes equivocal to other T-cell neoplasms. Detecting anti- HTLV-1 antibodies is significant for a first screening not only for HTLV-1 infection but also for the HTLV-1-related disorders of ATL and TSP/HAM. The purpose of the present study was to investigate the diagnostic validity of HTLV-1 serology in ATL. The serologic results by a gelatin particle agglutination (PA) assay were highly sensitive (100%) and specific (99.5%) for the results of polymerase chain reaction (PCR) assay in 666 healthy blood donors who live in an area endemic for the HTLV-1 virus. Of 7,536 hospitalized patients, 189 patients with ATL were serologically screened. There were 1,140 patients (15.2%) infected by chance with HTLV-1, showing specificity, sensitivity, positive predictive value (PV), and negative PV of 84.3%, 100%, 14.2%, and 100%, respectively. Since the low positive PV (14.2%) was useless, we tried combining the anti-HTLV-1 assay with the immunophenotyping necessary for the diagnosis of lymphoid neoplasms. This combination gave nearly 100% positive and negative PV, and could prove to be useful in diagnosing ATL with the probability of 98%, especially for epidemiologic studies

Impaired proteoglycan glycosylation, elevated TGF-β signaling, and abnormal osteoblast differentiation as the basis for bone fragility in a mouse model for gerodermia osteodysplastica

<div><p>Gerodermia osteodysplastica (GO) is characterized by skin laxity and early-onset osteoporosis. <i>GORAB</i>, the responsible disease gene, encodes a small Golgi protein of poorly characterized function. To circumvent neonatal lethality of the <i>Gorab</i>^<i>Null</i> full knockout, <i>Gorab</i> was conditionally inactivated in mesenchymal progenitor cells (Prx1-cre), pre-osteoblasts (Runx2-cre), and late osteoblasts/osteocytes (Dmp1-cre), respectively. While in all three lines a reduction in trabecular bone density was evident, only <i>Gorab</i>^Prx1 and <i>Gorab</i>^Runx2 mutants showed dramatically thinned, porous cortical bone and spontaneous fractures. Collagen fibrils in the skin of <i>Gorab</i>^<i>Null</i> mutants and in bone of <i>Gorab</i>^Prx1 mutants were disorganized, which was also seen in a bone biopsy from a GO patient. Measurement of glycosaminoglycan contents revealed a reduction of dermatan sulfate levels in skin and cartilage from <i>Gorab</i>^<i>Null</i> mutants. In bone from <i>Gorab</i>^Prx1 mutants total glycosaminoglycan levels and the relative percentage of dermatan sulfate were both strongly diminished. Accordingly, the proteoglycans biglycan and decorin showed reduced glycanation. Also in cultured <i>GORAB</i>-deficient fibroblasts reduced decorin glycanation was evident. The Golgi compartment of these cells showed an accumulation of decorin, but reduced signals for dermatan sulfate. Moreover, we found elevated activation of TGF-β in <i>Gorab</i>^Prx1 bone tissue leading to enhanced downstream signalling, which was reproduced in <i>GORAB</i>-deficient fibroblasts. Our data suggest that the loss of <i>Gorab</i> primarily perturbs pre-osteoblasts. GO may be regarded as a congenital disorder of glycosylation affecting proteoglycan synthesis due to delayed transport and impaired posttranslational modification in the Golgi compartment.</p></div

The trail of my studies on glycoproteins from enterokinase to tumor markers

This review describes the results of the author’s studies on glycoproteins which have been carried out for more than 50 years. Starting from the elucidation of basic structures of glycoproteins, i.e. the structure of the linkage between an amino acid and a sugar and the occurrence of the β-mannosidic linkage as the common structure of glycoproteins, the author became interested in the cell membrane glycoproteins focused on the comparison of cancer cells versus normal cells. These studies were then extended to the establishment of sugar-directed and cancer-associated monoclonal antibodies. Some of the monoclonal antibodies are useful for cancer diagnosis

Functional validation of novel compound heterozygous variants in B3GAT3 resulting in severe osteopenia and fractures: expanding the disease phenotype

Background A new disease class of syndromes, described as linkeropathies, which are derived from defects in the glycosaminoglycan-linker region as well as glycosaminoglycan-side chains of proteoglycans is increasingly being recognized as a cause of human disease. Proteoglycans are an essential component of the extracellular matrix. Defects in the enzymatic process of proteoglycan synthesis broadly occur due to the incorrect addition of side chains. Previously, homozygous missense variants within the B3GAT3 gene encoding beta 1,3 glucuronyltransferase 3(GlcAT-I) responsible for the biosynthesis of glycosaminoglycans have been described in 7 individuals. Case presentation In this study, a 4-year-old patient with a severe phenotype of osteoporosis, hypotonia, joint laxity, fractures, scoliosis, biscuspid aortic valve and myopia was referred for next generation sequencing after extensive negative clinical testing. Whole exome sequencing was performed on the proband and his unaffected parents to identify the molecular basis of his disease. Sequencing revealed compound heterozygous variants in B3GAT3: c.1A > G (p.Met1?) and c.671 T > A (p.L224Q). Clinical and in vitro functional studies were then completed to verify the pathogenicity of the genotype and further characterize the functional basis of the patient’s disease demonstrating the patient had a decrease both in the protein level of B3GAT3 and in the glucuronyltransferase activity when compared to control samples. Independent in vitro assessment of each variant confirmed the B3GAT3: c.1A > G (p.Met1?) variant is functionally null and the c.671 T > A (p.L224Q) missense variant has significantly reduced glucuronyltransferase activity (~3% of control). Conclusions This is the first report of a patient with compound heterozygosity for a null variant in trans with a missense in B3GAT3 resulting in a severe phenotype, expanding both the genotypic and phenotypic spectrum of B3GAT3-related disease