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Biomedical subjects

P J Brown

Publications and source records attributed to P J Brown.

At least 19 recordsLinked to original sources

A novel explosive process is required for the gamma-ray burst GRB 060614.

Over the past decade, our physical understanding of gamma-ray bursts (GRBs) has progressed rapidly, thanks to the discovery and observation of their long-lived afterglow emission. Long-duration (> 2 s) GRBs are associated with the explosive deaths of massive stars ('collapsars', ref. 1), which produce accompanying supernovae; the short-duration (< or = 2 s) GRBs have a different origin, which has been argued to be the merger of two compact objects. Here we report optical observations of GRB 060614 (duration approximately 100 s, ref. 10) that rule out the presence of an associated supernova. This would seem to require a new explosive process: either a massive collapsar that powers a GRB without any associated supernova, or a new type of 'engine', as long-lived as the collapsar but without a massive star. We also show that the properties of the host galaxy (redshift z = 0.125) distinguish it from other long-duration GRB hosts and suggest that an entirely new type of GRB progenitor may be required.

Journal Article↗

Inheritance of inflorescence architecture in sorghum.

The grass inflorescence is the primary food source for humanity, and has been repeatedly shaped by human selection during the domestication of different cereal crops. Of all major cultivated cereals, sorghum [Sorghum bicolor (L.) Moench] shows the most striking variation in inflorescence architecture traits such as branch number and branch length, but the genetic basis of this variation is little understood. To study the inheritance of inflorescence architecture in sorghum, 119 recombinant inbred lines from an elite by exotic cross were grown in three environments and measured for 15 traits, including primary, secondary, and tertiary inflorescence branching. Eight characterized genes that are known to control inflorescence architecture in maize (Zea mays L.) and other grasses were mapped in sorghum. Two of these candidate genes, Dw3 and the sorghum ortholog of ramosa2, co-localized precisely with QTL of large effect for relevant traits. These results demonstrate the feasibility of using genomic and mutant resources from maize and rice (Oryza sativa L.) to investigate the inheritance of complex traits in related cereals.

Chromosome Mapping↗

Alignment of genetic maps and QTLs between inter- and intra-specific sorghum populations.

To increase the value of associated molecular tools and also to begin to explore the degree to which interspecific and intraspecific genetic variation in Sorghum is attributable to corresponding genetic loci, we have aligned genetic maps derived from two sorghum populations that share one common parent (Sorghum bicolor L. Moench accession BTx623) but differ in morphological and evolutionarily distant alternate parents (S. propinquum or S. bicolor accession IS3620C). A total of 106 well-distributed DNA markers provide for map alignment, revealing only six nominal differences in marker order that are readily explained by sampling variation or mapping of paralogous loci. We also report a total of 61 new QTLs detected from 17 traits in these crosses. Among eight corresponding traits (some new, some previously published) that could be directly compared between the two maps, QTLs for two (tiller height and tiller number) were found to correspond in a non-random manner (P<0.05). For several other traits, correspondence of subsets of QTLs narrowly missed statistical significance. In particular, several QTLs for leaf senescence were near loci previously mapped for 'stay-green' that have been implicated by others in drought tolerance. These data provide strong validation for the value of molecular tools developed in the interspecific cross for utilization in cultivated sorghum, and begin to separate QTLs that distinguish among Sorghum species from those that are informative within the cultigen (S. bicolor).

Chromosome Mapping↗

A case of invertebral disc degeneration and prolapse with Schmorl's node formation in a sheep.

A Schmorl's node is the herniation of nucleus pulposus through the cartilaginous end plate of the vertebral disc into the body of the adjacent vertebra. Their formation is relatively common in people, and they may be symptomatic or asymptomatic. In contrast, there are few reported cases of Schmorl's nodes in non-human animals. This report describes a case of thoracic intervertebral disc degeneration, with Schmorl's node formation in a sheep.

Animals↗

Ultrasonographic evaluation of the thickness of the small intestinal wall in dogs with inflammatory bowel disease.

OBJECTIVES: To establish whether the intestinal wall thickness, as measured ultrasonographically, is significantly increased in dogs with inflammatory bowel disease (IBD). The results would provide the information necessary to decide whether measurement of ultrasonographic wall thickness can predict IBD in dogs. METHODS: The intestinal wall thickness of 75 dogs with idiopathic IBD, as measured by ultrasonography, was compared with recently published normal values. IBD was either confirmed histologically (n = 54) or suspected (n = 21). In all cases there was a positive response to immunosuppressive treatment. RESULTS: A positive association between intestinal wall thickness in dogs and either the histological diagnosis or the response to treatment was not found. Ultrasonographic intestinal wall measurements do not appear to be able to establish a diagnosis of intestinal inflammation and may result in a false negative diagnosis in cases of IBD. CLINICAL SIGNIFICANCE: The same 'grey zone' of between 4 and 6 mm used in humans can be used in the canine duodenum to distinguish the normal range, reserving the term 'abnormal' for an intestinal measurement greater than 6 mm in the duodenum and greater than 4.7 mm in the jejunum.

Animals↗

A novel diffuse large B-cell lymphoma-associated cancer testis antigen encoding a PAS domain protein.

Here we report that the OX-TES-1 SEREX antigen, which showed immunological reactivity with serum from four out of 10 diffuse large B-cell lymphoma (DLBCL) patients, is encoded by a novel gene, PAS domain containing 1 (PASD1). PASD1_v1 cDNA encodes a 639 amino-acid (aa) protein product, while an alternatively spliced variant (PASD1_v2), lacking intron 14, encodes a 773 aa protein, the first 638 aa of which are common to both proteins. The PASD1-predicted protein contains a PAS domain that, together with a putative leucine zipper and nuclear localisation signal, suggests it encodes a transcription factor. The expression of PASD1_v1 mRNA was confirmed by RT-PCR in seven DLBCL-derived cell lines, while PASD1_v2 mRNA appears to be preferentially expressed in cell lines derived from non-germinal centre DLBCL. Immunophenotyping studies of de novo DLBCL patients' tumours with antibodies to CD10, BCL-6 and MUM1 indicated that two patients mounting an immune response to PASD1 were of a poor prognosis non-germinal centre subtype. Expression of PASD1 mRNA was restricted to normal testis, while frequent expression was observed in solid tumours (25 out of 68), thus fulfilling the criteria for a novel cancer testis antigen. PASD1 has potential for lymphoma vaccine development that may also be widely applicable to other tumour types.

Amino Acid Sequence↗

Toxicological and biochemical responses of the earthworm Lumbricus rubellus to pyrene, a non-carcinogenic polycyclic aromatic hydrocarbon.

The effects of the polycyclic aromatic hydrocarbon (PAH) pyrene on earthworms were investigated in contact and soil tests. In addition to measuring toxic effects on survival and reproduction, Ethoxyresorufin-o-deethylase (EROD) activity and catalase activity were also studied as possible biomarkers of toxic stress. The survival data indicated that LC50 values were 0.0068 mg/ml for the contact test, and 283 mg/kg in the soil test. Cocoon production rate was significantly reduced compared to controls at 160, 640 and 2560 mg/kg in the soil test. No EROD activity could be detected in preliminary studies using control and exposed animals from the contact test, so this assay was not used to the soil test. Catalase activity was shown to be significantly lower at 640 mg/kg in the soil test compared to all other treatments and the control. When compared to toxicological data for other soil invertebrates, Lumbricus rubellus has an intermediate sensitivity in respects of survival and a lower sensitivity for reproductive effects, although the soil used in this study had a higher organic content than previous studies, meaning that the sensitivity of this species may be underestimated in comparison to previous published data for other soil invertebrates.

Animals↗

Feline necrotising sialometaplasia: a report of two cases.

Unilateral swelling of submandibular salivary gland in two cats was diagnosed as necrotising sialometaplasia. Histological features that differentiate the disease from other salivary gland lesions, particularly neoplasia are: lobular necrosis of salivary tissue; squamous metaplasia conforming to duct and/or acinar outlines; preservation of salivary lobular morphology; and variable inflammation and granulation tissue.

Animals↗

Slipped capital femoral epiphysis in dogs.

In a retrospective review of 43 femoral fractures, three dogs had separation of the femoral capital epiphysis from the metaphysis in the absence of trauma. Two of these dogs also had evidence of pathology in the contralateral femoral neck including, in one dog, displacement of the capital epiphysis in relation to the metaphysis without actual separation. The case histories, radiographic features and histopathological findings of these cases were reviewed and compared with previous cases of slipped capital femoral epiphysis (SCFE) reported in dogs and also with SCFE in children. Pre-slip, acute, chronic and acute-on-chronic slips were Identified. Based on the cases reviewed, the authors advise internal fixation of stable slipped epiphyses in dogs. This may also be appropriate for unstable separations, although resorption of the femoral neck may preclude stable fixation and necessitate femoral head and neck excision.

Animals↗

Salivary gland basal cell adenocarcinoma: a report of cases in a cat and two dogs.

Basal cell adenocarcinoma of the salivary gland is described in a cat and two dogs; tumour tissue was characterized by cords and islands of epithelial cells with a distinct basal layer. The tumours were stained by various immunohistochemical methods. In addition to positive staining with cytokeratin 14 and pancytokeratin (CKs 5, 6, 8, 17 and 19), there was also staining with Jack bean agglutinin A (ConA) and soya bean agglutinin (SBA); this occurs in many other types of salivary gland tumours and is a feature of normal salivary gland acinar cells. In one dog there was also staining with SBA. This is the first report of this tumour in domestic animals; the immunohistochemical characteristics did not distinguish it from other salivary gland tumours.

Adenocarcinoma↗

Immunohistochemical characteristics of canine aortic and carotid body tumours.

In an immunohistochemical study of 25 canine chemodectomas, 17 tumours were stained with antisera to neurone specific enolase and the same number were stained for synaptophysin; a single tumour was stained for S100. Staining for Ki-67 occurred in 18 cases; the Ki-67-labelling index and the intensity of immunostaining was increased in more pleomorphic and malignant tumours, as assessed on histological grounds. Immunohistochemistry did not aid in recognition of less well-differentiated tumours.

Animals↗

Polyomavirus infection in hamsters and trichoepitheliomas/cutaneous adnexal tumours.

Multiple skin nodules, with histological features of adnexal tumours consistent with trichoepithelioma, were observed on the head and trunk of Syrian hamsters. Skin biopsies from 20 hamsters from five different colonies were affected, and two of the affected hamsters also had lymphoma. Two owners reported that 16 of 70 hamsters and 50 of 100 hamsters in their colonies had similar skin lesions. These tumours have previously been associated in laboratory colonies with hamster polyomavirus (HaPV) infection. Examination of skin tissues by electron microscopy failed to reveal intranuclear virus particles. Using recombinant major capsid protein VP1 of HaPV, VP1-specific antibodies were detected in sera from 12 of 12 affected hamsters and in four of four unaffected in-contact hamsters, by ELISA. The ELISA data were verified by immunoblot analysis. Eleven of 13 serum samples contained antibodies which reacted with at least one recombinant structural HaPV protein (VP2), including samples from three in-contact unaffected hamsters. Nine of the 11 anti-VP2-positive samples also reacted with recombinant VP3 of HaPV, and six reacted with VP1. Amplification by PCR and sequencing detected VP1 -encoding sequences showing a high degree of homology with HaPV. The findings suggest a possible infection by HaPV or a HaPV-like virus and it is likely that such an infection was enzootic within the affected colonies.

Animals↗

Sebaceous carcinoma of the salivary gland in a cat.

Sebaceous carcinoma of the submandibular salivary gland is described in a cat, tumour cells were characterized histologically by moderate amounts of pale eosinophilic or vacuolated cytoplasm. Tumour cells were stained with antibody to cytokeratins (CKs 5. 6, 8, 17 and 19) and with lectins Con A and wheat germ agglutinin (WGA); this occurs in many other types of salivary gland tumour and is a feature of normal salivary gland acinar cells.

Adenocarcinoma, Sebaceous↗

Nomenclature of magnetic, incommensurate, composition-changed morphotropic, polytype, transient-structural and quasicrystalline phases undergoing phase transitions. II. Report of an IUCr Working Group on Phase Transition Nomenclature.

A general nomenclature applicable to the phases that form in any sequence of transitions in the solid state has been recommended by an IUCr Working Group [Acta Cryst. (1998). A54, 1028-1033]. The six-field notation of the first Report, hereafter I, was applied to the case of structural phase transitions, i.e. to transformations resulting from temperature and/or pressure changes between two crystalline (strictly periodic) phases involving modifications to the atomic arrangement. Extensive examples that illustrate the recommendations were provided. This second Report considers, within the framework of a similar six-field notation, the more complex nomenclature of transitions involving magnetic phases, incommensurate phases and transitions that occur as a function of composition change. Extension of the nomenclature to the case of phases with less clearly established relevance to standard schemes of transition in equilibrium systems, namely polytype phases, radiation-induced and other transient phases, quasicrystalline phases and their transitions is recommended more tentatively. A uniform notation for the translational periodicity, propagation vector or wavevector for magnetic and/or incommensurate substances is specified. The notation adopted for incommensurate phases, relying partly on the existence of an average structure, is also consistent with that for commensurate phases in a sequence. The sixth field of the nomenclature is used to emphasize the special features of polytypes and transient phases. As in I, illustrative examples are provided for each category of phase sequence.

Journal Article↗

A low-temperature neutron diffraction study of Mn12-acetate.

In the low-temperature region, where the dodecanuclear mixed-valence manganese carboxylate hexadecaacetatotetraaquadodecaoxododecamanganese bis(acetic acid) tetrahydrate, [Mn(12)O(12)(C(2)D(3)O(2))(16)(H(2)O)(4)].2C(2)HD(3)O(2).4H(2)O, displays unusual magnetic properties, its structure is similar to that previously determined at room temperature [Lis (1980). Acta Cryst. B36, 2042-2046], differing only by a small change in the configuration of one of the coordinated acetate groups, related to the formation of additional hydrogen bonds, and by the orientation of the methyl groups. Since most of the magnetization density of this system resides on the Mn atoms, the consequences of these rearrangements for the magnetic properties of the compound are small.

Journal Article↗

Domains of invasion organelle proteins from apicomplexan parasites are homologous with the Apple domains of blood coagulation factor XI and plasma pre-kallikrein and are members of the PAN module superfamily.

Micronemes are specialised organelles, found in all apicomplexan parasites, which secrete molecules that are essential for parasite attachment to and invasion of host cells. Regions of several microneme proteins have sequence similarity to the Apple domains (A-domains) of blood coagulation factor XI (FXI) and plasma pre-kallikrein (PK). We have used mass spectrometry on a recombinant-expressed, putative A-domain from the microneme protein EtMIC5 from Eimeria tenella, to demonstrate that three intramolecular disulphide bridges are formed. These bridges are analogous to those that stabilise A-domains in FXI and PK. The data confirm that the apicomplexan domains are structural homologues of A-domains and are therefore novel members of the PAN module superfamily, which also includes the N-terminal domains of members of the plasminogen/hepatocyte growth factor family. The role of A-domains/PAN modules in apicomplexan parasites is not known, but their presence in the microneme suggests that they may be important for mediating protein-protein or protein-carbohydrate interactions during parasite attachment and host cell invasion.

Amino Acid Motifs↗