Multiple Myeloma Includes Phenotypically Defined Subsets of Clonotypic CD20+ B Cells that Persist During Treatment with Rituximab

Potential progenitor B cell compartments in multiple myeloma (MM) are clinically important. MM B cells and some circulating MM plasma cells express CD20, predicting their clearance by treatment with anti-CD20. Here we describe two types of clonotypic CD20+ B cell in peripheral blood of myeloma patients, identified by their expression of CD19 and CD20 epitopes, their expression of CD45RA and their light scatter properties. Thus, the circulating component of the MM clone includes at least two distinct CD19+ CD20+ B cell compartments, as well as CD138+ CD20+ plasma cells. To determine whether either or both B cell subsets and the CD20+ plasma cell subset were depleted by anti-CD20 therapy, they were evaluated before, during and after treatment of patients with rituximab (anti-CD20), followed by quantifying B cell subsets over a 5 month period during and after treatment. Overall, all three types of circulating B lineage cells persist despite treatment with rituximab. The inability of rituximab to prolong survival in MM may result from this failure to deplete CD20+ B and plasma cells in MM

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Engineering antibodies for use in leukemia and lymphoma therapy / Penelope Jane Adamson.

Bibliography : leaves 224-256.xxii, 256 leaves : ill. (chiefly col.) ; 30 cm.Thesis (Ph.D.)--University of Adelaide, Dept. of Paediatrics, 200

Diversity in Glycosaminoglycan Binding Amongst hMPV G Protein Lineages

We have previously shown that hMPV G protein (B2 lineage) interacts with cellular glycosaminoglycans (GAGs). In this study we examined subtypes A1, A2 and B1 for this interaction. GAG-dependent infectivity of available hMPV strains was demonstrated using GAG-deficient cells and heparin competition. We expressed the G protein ectodomains from all strains and analysed these by heparin affinity chromatography. In contrast to the B2 lineage, neither the A2 or B1 G proteins bound to heparin. Sequence analysis of these strains indicated that although there was some homology with the B2 heparin-binding domains, there were less positively charged residues, providing a likely explanation for the lack of binding. Although sequence analysis did not demonstrate well defined positively charged domains in G protein of the A1 strain, this protein was able to bind heparin, albeit with a lower affinity than G protein of the B2 strain. These results indicate diversity in GAG interactions between G proteins of different lineages and suggest that the GAG-dependency of all strains may be mediated by interaction with an alternative surface protein, most probably the conserved fusion (F) protein. Analysis of both native and recombinant F protein confirmed that F protein binds heparin, supporting this conclusion

Prevalence of macrolide-resistant Mycoplasma pneumoniae in South Australia

Mycoplasma pneumoniae remains a common cause of community acquired respiratory tract infections in adults and children. To provide empirical coverage against M. pneumoniae, doxycycline or a macrolide combined with a β-lactam is considered the most appropriate therapy for patients with community acquired pneumonia in Australia.1 Documented outbreaks of macrolide-resistant M. pneumoniae (MRMP) have occurred in several countries, including China2 and Japan3 with resistance also being reported in Europe,4,5 North America6 and South Korea.7 Rates of resistance amongst paediatric populations with lower respiratory tract infections and community acquired pneumonia have been reported to be up to 30% in Japan8 and as high as 90% in China.9 Despite Australia's relatively close proximity to countries with high rates of MRMP, there has only been a single case recorded in Australia10 and the overall prevalence of resistance remains unknown. In this study we utilised polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and high resolution melt analysis (HRMA) to determine the prevalence of common point mutations responsible for encoding high-level macrolide resistance in confirmed M. pneumoniae samples from South Australia

hMPV Lineage Nomenclature and Heparin Binding

Human metapneumovirus (hMPV), first described in 2001 [1], is responsible for causing serious respiratory illness in young children, the elderly and immunocompromised patients. Four distinct lineages of hMPV have been identified with the original nomenclature for these subgroups (A1, A2, B1 and B2), reported by van den Hoogen et al. [2], utilised by many. An alternate terminology (1A, 1B, 2A and 2B) was also published by Ishiguro et al. in 2004 [3] which has been adopted by others. However, this has caused some confusion in the interpretation of publication results as the terminology is similar yet describes different subtypes. As a result, a number of investigators have made a submission to the International Committee on Taxonomy of Viruses (ICTV, ICTV taxonomic proposal 2012.012V) for the official adoption of the original terminology as an approved nomenclature for hMPV [4]. We welcome this officially approved nomenclature which should provide clarification of these subtypes in future. Therefore to assist with the interpretation of our recently published research in the 2012 special issue of Viruses: Pneumoviruses and Metapneumoviruses entitled “Diversity in Glycosaminoglycan Binding Amongst hMPV G Protein Lineages” [5] we have updated the Figure 3 in this letter (see Figure 1), showing the proposed ICTV terminology compared to the Ishiguro classification (used in our publication). Note that in the original publication the alphanumeric order for the Ishiguro classification was transposed (e.g., 1A was referred to as A1)

Multilocus sequence typing of Campylobacter jejuni isolates from New South Wales, Australia

Aims: Multilocus sequence typing (MLST) was used to examine the diversity and population structure of Campylobacter jejuni isolates associated with sporadic cases of gastroenteritis in Australia, and to compare these isolates with those from elsewhere. Methods and Results: A total of 153 Camp. jejuni isolates were genotyped. Forty sequence types (STs) were found, 19 of which were previously undescribed and 21 identified in other countries. The 19 newly described STs accounted for 43% of isolates, 16 of which were assigned to known clonal complexes. Eighty-eight percent of isolates were assigned to a total of 15 clonal complexes. Of these, four clonal complexes accounted for 60% of isolates. Three STs accounted for nearly 40% of all isolates and appeared to be endemic, while 21 STs were represented by more than one isolate. Seven infections were acquired during international travel, and the associated isolates all had different STs, three of which were exclusive to the travel-acquired cases. Comparison of serotypes among isolates from clonal complexes revealed further diversity. Eight serotypes were identified among isolates from more than one clonal complex, while isolates from six clonal complexes displayed serotypes not previously associated with those clonal complexes. Conclusions: Multilocus sequence typing is a useful tool for the discrimination of subtypes and examination of the population structure of Camp. jejuni associated with sporadic infections. Significance and Impact of the Study: This study highlights the genotypic diversity of Camp. jejuni in Australia, demonstrating that STs causing disease have both a global and a local distribution evident from the typing of domestically and internationally acquired Camp. jejuni isolates