Neuroendocrine tumor of the bladder

Small cell carcinoma (SCC) of the bladder is a rare and aggressive tumor associated with a poor prognosis. It often presents at a later stage than urothelial carcinoma of the bladder, and comprises less than 1% of bladder malignancies. A number of treatment algorithms have been used to treat bladder SCC, including cystectomy, partial cystectomy, radiotherapy, chemoradiotherapy, chemotherapy alone, and neoadjuvant/adjuvant chemotherapy. Presented is a case of SCC of the bladder, and the epidemiology, prognosis, and current treatment algorithms for patients with bladder SCC are reviewed.     

Evidence for cryptic speciation of Leucocytozoon spp. (Haemosporida, Leucocytozoidae) in diurnal raptors

Species of Leucocytozoon (Haemosporida, Leucocytozoidae) traditionally have been described based on morphological characters of their blood stages and host cells, with limited information on their avian host specificity. Based on the current taxonomy, Leucocytozoon toddi is the sole valid species of leucocytozoids parasitizing falconiform birds. Using a nested polymerase chain reaction protocol, we determined the prevalence of Leucocytozoon infection in 5 species of diurnal raptors from California. Of 591 birds tested, 177 (29.9%) were infected with Leucocytozoon toddi. Subsequent phylogenetic analysis of the cytochrome b gene revealed that distinct haplotypes are present in hawks of these genera. Haplotypes present in Buteo spp. are not found in Accipiter spp., and there is a 10.9% sequence divergence between the 2 lineage clades. In addition, Leucocytozoon sp. from Accipiter spp. from Europe group more closely with parasites found in Accipiter spp. from California than the same California Accipiter species do with their sympatric Buteo spp. Similarly, a Leucocytozoon haplotype from a Common Buzzard (Buteo buteo) from Kazakhstan forms a monophyletic lineage with a parasite from B. jamaicensis from California. These results suggest that Leucocytozoon toddi is most likely a group of cryptic species, with 1 species infecting Buteo spp. and 1 or more species, or subspecies, infecting Accipiter spp.     

Blood parasites of chickens in Uganda and Cameroon with molecular descriptions of Leucocytozoon schoutedeni and Trypanosoma gallinarum

Using microscopy and PCR, we determined the prevalence of blood parasites in village chickens in Uganda and Cameroon. Of 148 individuals tested, 18.3% were infected with Leucocytozoon schoutedeni (Haemosporida, Leucocytozoidae) and 4.1% were infected with Trypanosoma gallinarum (Kinetoplastida, Trypanosomatidae). No other blood parasites were detected. Subsequent phylogenetic analysis of the cytochrome b gene of L. schoutedeni identified 2 distinct lineages that were found at all 3 sampling locations in Uganda. The sequence divergence between these 2 lineages is 1.5%. One of these lineages was also found in chickens in Cameroon, nearly 2,000 km distant. There are no morphological differences between blood stages of the parasites represented by the 2 different lineages, suggesting that cytochrome b gene sequence divergence can be as high as 1.5% within a single well-defined morphospecies of Leucocytozoon. We sequenced a portion of the small subunit ribosomal RNA gene (SSU rRNA) of T. gallinarum, and redescribe T. gallinarum for the first time since its discovery in 1911. These are the first assignments of DNA sequence data to these morphospecies of Leucocytozoon and Trypanosoma and may represent an example of intraspecific sequence divergence.     

ADAMTS-12 associates with and degrades cartilage oligomeric matrix protein

Loss of articular cartilage because of extracellular matrix breakdown is the hallmark of arthritis. Degradative fragments of cartilage oligomeric matrix protein (COMP), a prominent noncollagenous matrix component in articular cartilage, have been observed in the cartilage, synovial fluid, and serum of arthritis patients. The molecular mechanism of COMP degradation and the enzyme(s) responsible for it, however, remain largely unknown. ADAMTS-12 (a disintegrin and metalloprotease with thrombospondin motifs) was shown to associate with COMP both in vitro and in vivo. ADAMTS-12 selectively binds to only the epidermal growth factor-like repeat domain of COMP of the four functional domains tested. The four C-terminal TSP-1-like repeats of ADAMTS-12 are shown to be necessary and sufficient for its interaction with COMP. Recombinant ADAMTS-12 is capable of digesting COMP in vitro. The COMP-degrading activity of ADAMTS-12 requires the presence of Zn2+ and appropriate pH (7.5-9.5), and the level of ADAMTS-12 in the cartilage and synovium of patients with both osteoarthritis and rheumatoid arthritis is significantly higher than in normal cartilage and synovium. Together, these findings indicate that ADAMTS-12 is a new COMP-interacting and -degrading enzyme and thus may play an important role in the COMP degradation in the initiation and progression of arthritis.     

Structure-function studies of the functional and binding epitope of the human 37 kDa laminin receptor precursor protein.

Expression of the 37 kDa laminin receptor precursor protein (37LRP) correlates directly with increased invasiveness and the metastatic potential of tumors. The 37LRP matures to a 67 kDa protein which facilitates the binding of cancer cells to basement membranes. The palindrome peptide sequence LMWWML, corresponding to the 173-178-residue stretch of the human 37LRP sequence, has been identified as the laminin-1-binding site. Peptides from 37LRP of species that contain this palindrome-bind laminin-1 with high affinity. Nuclear magnetic resonance (NMR) conformational studies have been undertaken on a synthetic 15-residue peptide (KGAHSVGLMWWMLAR) containing the palindrome to establish the structural basis of this activity. To further correlate the structural data with laminin-1-binding function, analogous structural studies were conducted for a similar peptide (RGKHSIGLIWYLLAR) lacking the palindrome, originating from 37LRP sequence of Saccharomyces cerevisiae and exhibiting low laminin-1-binding affinity. Finally, in vitro cell invasion assays were performed to investigate the possibility that the laminin-1-binding affinity of the peptides influences their inhibitory activity.     

Retrieval with gene queries

Background  

Accuracy of document retrieval from MEDLINE for gene queries is crucially important for many applications in bioinformatics. We explore five information retrieval-based methods to rank documents retrieved by PubMed gene queries for the human genome. The aim is to rank relevant documents higher in the retrieved list. We address the special challenges faced due to ambiguity in gene nomenclature: gene terms that refer to multiple genes, gene terms that are also English words, and gene terms that have other biological meanings.     

Age trends in pre‐cancerous and cancerous lesions of the uterine cervix in a cytology screening programme: what should be the target age group for a major thrust of screening in resource‐limited settings?

Objective:  To identify the target age group where screening efforts may be concentrated in order to reduce the incidence of cervical cancer in resource-limited countries.
Study design:  The results of cyto-screening in a hospital-based screening programme for early detection of cervical cancer were analysed retrospectively. The frequency of epithelial cell abnormalities (ECAs) was computed in different age groups.
Observations and results:  A total of 5.6% ECAs were detected on cyto-screening. The peak age incidence for squamous intraepithelial lesions (SILs) was in the 30–39 age group while that for malignancies was age >60 years. The mean ages for LSIL, HSIL and cancer were 34.7, 37.7 and 51.8 years respectively. Around 43% LSILs and 48% HSILs presented in the fourth decade. If both fourth and fifth decade are covered by screening we could detect almost two-thirds of SILs.
Conclusions:  A distinct latent period of more than a decade between the onset of SIL and development of frank cancer provides us with ample opportunity to prevent cervical cancer through screening. Our data validate the WHO recommendation of once in a lifetime screening of women in their fourth decade, for low-resource settings. If resources permit, screening can be extended to include women in the fifth decade. This approach would enable us to pick up maximum SILs within the available resources and prevent their progression to cancer.