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Biomedical subjects

K Piper

Publications and source records attributed to K Piper.

At least 19 recordsLinked to original sources
PubMed2004

CD23 expression in mediastinal large B-cell lymphomas.

AIMS: Mediastinal large B-cell lymphoma (MLBCL) is a subtype of diffuse large B-cell lymphoma (DLBCL) in the WHO classification with peculiar features, such as female prevalence, young patient age and bulky presentation. It shows a B-cell phenotype with variable expression of surface immunoglobulin, negative CD21 and CD10 and positive CD30 in a large number of cases. An origin from activated thymic B cells has been suggested in several studies. A subpopulation of large, dendritic cells (asteroid cells) strongly expressing CD23 has been identified amongst thymic B cells and these could represent the normal cellular counterpart for this type of primary mediastinal large cell lymphoma. METHODS AND RESULTS: To explore this possibility, we immunostained 24 cases of primary mediastinal lymphomas and 100 cases of non-mediastinal, nodal and extranodal, DLBCLs for CD23 in routinely processed paraffin-embedded tissues. CONCLUSIONS: Our results show that a vast majority (70%) of mediastinal lymphomas strongly express CD23 whilst the same antigen is expressed in only 15% of non-mediastinal nodal DLBCLs and 9% of non-mediastinal extranodal DLBCLs. These results support the hypothesis that most cases of MLBCL arise from activated dendritic thymic B cells. We also suggest that CD23 should be included in the panel of antibodies currently used to characterize this subtype of DLBCL.

Adolescent↗
PubMed2004

Beta cell differentiation during early human pancreas development.

Understanding gene expression profiles during early human pancreas development is limited by comparison to studies in rodents. In this study, from the inception of pancreatic formation, embryonic pancreatic epithelial cells, approximately half of which were proliferative, expressed nuclear PDX1 and cytoplasmic CK19. Later, in the fetal pancreas, insulin was the most abundant hormone detected during the first trimester in largely non-proliferative cells. At sequential stages of early fetal development, as the number of insulin-positive cell clusters increased, the detection of CK19 in these cells diminished. PDX1 remained expressed in fetal beta cells. Vascular structures were present within the loose stroma surrounding pancreatic epithelial cells during embryogenesis. At 10 weeks post-conception (w.p.c.), all clusters containing more than ten insulin-positive cells had developed an intimate relationship with these vessels, compared with the remainder of the developing pancreas. At 12-13 w.p.c., human fetal islets, penetrated by vasculature, contained cells independently immunoreactive for insulin, glucagon, somatostatin and pancreatic polypeptide (PP), coincident with the expression of maturity markers prohormone convertase 1/3 (PC1/3), islet amyloid polypeptide, Chromogranin A and, more weakly, GLUT2. These data support the function of fetal beta cells as true endocrine cells by the end of the first trimester of human pregnancy.

Animals↗
PubMed2002

Novel SOX9 expression during human pancreas development correlates to abnormalities in Campomelic dysplasia.

Haploinsufficiency of SOX9, which encodes a homeodomain transcription factor, results in Campomelic dysplasia. Classical features of this disorder (e.g. skeletal dysplasia and 46,XY sex reversal) are in concordance with SOX9 expression profiles during human embryonic development. We report the robust expression of SOX9 throughout the pancreas during human embryogenesis, at levels of detection equivalent to the developing skeleton and testis. In the early foetal period, SOX9 expression declines and, in particular, is not apparent within the pancreatic islets. In keeping with this profile, examination of three cases with Campomelic dysplasia revealed abnormal pancreatic morphology. Epithelial cells were less densely packed within the mesenchymal stroma and islets less clearly formed with variable expression of hormone and beta cell markers. Taken together, these data indicate a novel potential role for SOX9 in pancreas development during human embryogenesis and early foetal life.

Bone Diseases, Developmental↗
PubMed2000

The biopesticide Paenibacillus popilliae has a vancomycin resistance gene cluster homologous to the enterococcal VanA vancomycin resistance gene cluster.

We have previously identified, in Paenibacillus popilliae, a 708-bp sequence which has homology to the sequence of the enterococcal vanA gene. We have performed further studies revealing five genes encoding homologues of VanY, VanZ, VanH, VanA, and VanX in P. popilliae. The predicted amino acid sequences are similar to those in VanA vancomycin-resistant enterococci: 61% identity for VanY, 21% for VanZ, 74% for VanH, 77% for VanA, and 79% for VanX. The genes in P. popilliae may have been a precursor to or have had ancestral genes in common with vancomycin resistance genes in enterococci. The use of P. popilliae biopesticidal preparations in agricultural practice may have an impact on bacterial resistance in human pathogens.

Amino Acid Sequence↗
PubMed1999

Genetic control of schistosome infections by the SM1 locus of the 5q31-q33 region is linked to differentiation of type 2 helper T lymphocytes.

Human susceptibility to Schistosoma mansoni infections is controlled by the SM1 locus on chromosome 5 in q31-q33. This genetic region encodes cytokines which regulate the development of helper T lymphocytes. In the present work, a clonal analysis of CD4(+) T lymphocytes of homozygous resistant and homozygous susceptible subjects was undertaken to evaluate whether SM1 controls helper T-cell differentiation. Of 121 CD4(+) T-cell clones (TCC) from three susceptible (S) and three resistant (R) subjects, 68 proliferated when stimulated by parasite antigens. Parasite-specific TCC derived from susceptible subjects (33 STCC) produced 10- to 1,000-fold less interleukin-4 and -5 than TCC from resistant subjects (25 RTCC). Clones from both patient groups produced, however, the same amount of gamma interferon. Parasite-specific STCC were type 1 helper (Th1) or Th0/1, whereas RTCC were either Th2 or Th0/2. These results, together with the localization of SM1 in 5q31-q33, indicate that the SM1 locus controls the differentiation of Th2 lymphocytes.

Adolescent↗
PubMed1998

Outpatient costing and classification: are we any closer toa national standard for ambulatory classification systems?

The Outpatient Costing and Classification Study was commissioned by the Department of Health and Family Services to evaluate the suitability of the Developmental Ambulatory Classification System (DACS). Data on the full range of ambulatory services (outpatient clinics, emergency departments and allied health services) were collected prospectively from a stratified sample of 28 public hospitals. Patient encounters captured in the study represent 1% of the total ambulatory encounters in Australia in one year. Costing per encounter included time spent with the patient, cost of procedures, indirect costs (salaries and consumables), overhead costs and diagnostic costs. The most significant variable explaining cost variation was hospital type, followed by outpatient clinic type. Visit type and presence or absence of a procedure--major splits for the proposed DACS--did not produce splits that were consistent across all hospital strata. The study found that DACS is not an appropriate classification for hospital ambulatory services. A clinic-based structure for outpatients and allied health departments is recommended for classifying and funding ambulatory services in Australia.

Ambulatory Care↗
PubMed1998

Tuberculosis of the mandible in a child.

The incidence of notification of tuberculosis is increasing in the developed world. The disease has a variable mode of presentation and therefore diagnosis is not easy. We present an unusual case of tuberculosis involving the ramus of the mandible in a six-year-old boy and outline its management.

Child↗
PubMed1997

Characterization of a schistosome T cell-stimulating antigen (Sm10) associated with protective immunity in humans.

Parasite antigens that are strong T cell immunogens represent potential candidates for vaccines against pathogens susceptible to T cell-mediated immunity. We have previously shown that chromatographic fractions of schistosomula extracts contain components that are major T cell immunogen(s) in natural schistosome infections in humans and might contribute to the induction of human protective immunity against this parasite. In the present study, we report on the molecular cloning and on the biochemical characterization of the active components of these fractions. The screening of a schistosomula cDNA expression library with antibodies raised against the fractions allowed the cloning of a cDNA that hybridized to a 0.56-kb mRNA of schistosomula and adult worms. This cDNA contains an open reading frame of 267 base pairs (bp) which encodes a 10-kDa polypeptide. The analysis of the cDNA sequence revealed 70% homology with the sequences of previously reported proteins of unknown function. The native molecules in the active fractions were analyzed by mass spectrometry after additional purification by reverse phase high-performance liquid chromatography (HPLC). This procedure revealed two components in the fractions of molecular mass 10383 +/- 2 Da and 10401 +/- 9 Da. Both polypeptides stimulated immune T cells and yielded tryptic peptides whose sequences matched the sequence of the cloned molecule. These two polypeptides probably correspond to different post-translationally modified forms of the polypeptide encoded by the cloned cDNA.

Amino Acid Sequence↗
PubMed1997

Serum Lp(a) lipoprotein concentration is not associated with clinical and angiographic outcome five years after coronary artery bypass graft surgery.

OBJECTIVE: To examine the association between serum Lp(a) lipoprotein concentration and clinical and angiographic outcomes five years after coronary artery bypass graft (CABG) surgery. SETTING: A regional cardiothoracic centre, Freeman Hospital, and the University Clinical Investigation Unit, Royal Victoria Infirmary, Newcastle upon Tyne. PATIENTS AND DESIGN: 353 consecutive patients (56 female, 297 male, mean age 57-2 years) undergoing first time CABG surgery for stable angina were studied prospectively. MAIN OUTCOME MEASURES: Late cardiac death (beyond 30 days) and non-fatal myocardial infarction; prevalence of angina five years after surgery in 291 (94%) survivors and vein graft patency (evaluated by patient) in 118 survivors five years after surgery. Serum Lp(a) concentration and lipid profiles were measured before operation, and 3, 6, 12, and 60 months after surgery. Lipid profiles were also measured 24 months after surgery. RESULTS: Weighted Lp(a) concentration (by tertile) was not associated with late cardiac death or with the combination of late cardiac death and non-fatal myocardial infarction, with the presence of angina, or with vein graft occlusion. The association remained non-significant if analysis was restricted to the upper tertile of LDL cholesterol (> 4.1 mmol/l) or to patients under the age of 55 years at the time of surgery. CONCLUSIONS: Serum Lp(a) concentration did not predict late cardiac death, the combination of late cardiac death and non-fatal myocardial infarction, or the prevalence of angina or vein graft occlusion five years after CABG surgery.

Angina Pectoris↗
PubMed1996

The dnaB-pheA (256 degrees-240 degrees) region of the Bacillus subtilis chromosome containing genes responsible for stress responses, the utilization of plant cell walls and primary metabolism.

Within the framework of the international programme to sequence the genome of Bacillus subtilis strain 168, we were allocated the region between dnaB (256 degrees) and pheA (240 degrees). The sequencing of this region is now complete and we report our primary analysis of the 114 kb region containing 114 ORFs. In addition to previously characterized genes, we have identified genes involved in the utilization of plant cell wall polysaccharides, stress responses and the metabolism of amino acids, cell walls, DNA and fatty acids. We also discuss various structural and physical features, including the orientation of genes with respect to replication, putative start and stop codons, ribosome binding sites and rho-independent transcription terminators.

Bacillus subtilis↗
PubMed1996

Segregation analysis indicates a major gene in the control of interleukine-5 production in humans infected with Schistosoma mansoni.

The interleukine-5 (IL-5) is a hormone of the immune system that is the main regulator of eosinopoiesis, eosinophil maturation and activation, and immunoglobulin A production. Thus, IL-5 contributes in several ways to human immune defenses against various pathogens, including helminths and infectious agents of the digestive and respiratory tracts. On the other hand, the increase in eosinophil number and the activation of these cells, which both have been related to elevated IL-5 production, are the cause of severe pathological disorders, as in asthma or hypereosinophilic syndromes. Although the immunological pathways leading to IL-5 synthesis have been identified, the reasons for the large variability observed in IL-5 production among subjects exposed to comparable antigenic stimulation are unknown. To investigate the role of genetic factors in this variability, we conducted a segregation analysis in a Brazilian population infected by the helminth parasite Schistosoma mansoni. The analysis was performed on IL-5 levels produced by blood mononuclear cells of these subjects after in vitro restimulation with either parasite extracts (IL-5/schistosomula sonicates [SS] phenotype) or a T-lymphocyte mitogen (IL-5/phytohemagglutin [PHA]). The results provide clear evidence for the segregation of a codominant major gene controlling IL-5/SS and IL-5/PHA production and accounting for 70% and 73% of the phenotypic variance, respectively; the frequency of the allele predisposing to low IL-5 production was approximately .22 for both phenotypes. No significant relationship was found between these genes and the gene controlling infection intensities by S. mansoni detected in a previous study. Linkage studies are ongoing to locate those genes that would help to characterize the genetic factors involved in pathological conditions such as severe helminth infections and allergic diseases.

Adolescent↗
PubMed1995

Volumes of chick and rat osteoclasts cultured on glass.

We have examined the relationship between the number of nuclei of an osteoclast and its volume. Chick and rat cells were released from long bones by chopping the shafts and flushing the fragments in Eagle's Minimum Essential Medium with added 10% fetal calf serum. The bone cell suspension was seeded onto glass coverslips. In Experiment 1, rat and chick cells were allowed to settle for 15 minutes, more medium was then added, and the cells were cultured in 5% CO2 at 37 degrees C for 4 hours. In Experiment 2, only rat cells were used, and the cells were cultured in the presence or absence of 10(-6) M 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (APD) in the medium for 4 or 6 hours. The coverslips were washed in 37 degrees C phosphate-buffered saline and fixed for 24 hours in 2.5% glutaraldehyde in isotonic cacodylate buffer (initially 37 degrees C). The chick cells were critical point dried (CPD) or freeze dried (FD); all rat cells were FD. After drying, cells were coated with gold by vacuum evaporation. The volumes and areas of osteoclasts were measured using a video-rate, line-confocal reflection laser scanning microscope and the number of nuclei in each cell was counted. The volumes and volumes per nucleus of the FD cells were larger than those of the CPD cells but there was no significant difference in plan-areas. Rat osteoclasts were larger than chick cells in all the measured parameters except the mean number of nuclei/cell. The correlation coefficients for the areas, volumes, and the numbers of nuclei for rat and chick cells were all high (r > 0.725). The volumes and volumes per nucleus, but not the areas or areas per nucleus, of the osteoclasts cultured with APD were significantly smaller than control cells. We conclude that FD causes less shrinkage than CPD; chick osteoclasts are about two-thirds the size of rat osteoclasts; and 10(-6) M APD caused a reduction of rat osteoclast volume and volume per nucleus of 21%.

Animals↗
PubMed1994

The effect of 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (ADP) on the resorptive function of osteoclasts of known nuclear number.

Bisphosphonates (BP) are known to suppress osteoclastic resorption in vivo and in vitro, but doubt persists as to how, and the effect of BP on the resorptive capability of osteoclasts of known nuclear number is unknown. We aimed to find whether the addition of 3-amino-1-hydroxypropylidene-1,1- bisphosphonate (APD) changed the nuclear profile of an osteoclast population in vitro, and to measure the resorptive efficiency of individually characterized osteoclasts in the presence and absence of the BP. Prehatch chick bone cells were cultured for 24 hours on slices of dentine in medium with or without added APD at 10(-6) M or 10(-8) M, or in control medium on dentine presoaked with 10(-6) M APD for 48 hours. Total pit counts, and pit depths, areas and volumes for pits made by osteoclasts of known nuclear number, were found using confocal video-rate laser reflection microscopy and 3-D image analysis software. APD in the medium inhibited resorption and reduced the volume, area, and depth resorbed per nucleus per chick osteoclast. The nuclear number distribution did not shift significantly, suggesting that no preferential effect arose from the APD affecting one size of cell more than another. The large reduction found in pit numbers, depths, areas, and volumes in the APD dentine-pretreated group supports previous views that BP released during resorption act as metabolic inhibitors, altering protein synthesis by the cell. Larger cells made larger pits, but resorptive efficiency was similar for different cell sizes within the control or APD-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The relationship between the number of nuclei of an osteoclast and its resorptive capability in vitro.

This study examined the relationship between the number of nuclei in an osteoclast and its resorptive efficiency, as demonstrated by the size of the pit it can make in a mineralized tissue in 24 h in vitro. Osteoclasts released mechanically from prehatch chick long bones were cultured on dentine slices or on plastic dishes for periods of 6 or 24 h. The frequency distribution of the multinucleate tartrate-resistant acid phosphatase (TRAP)-positive cells with different numbers of nuclei was determined: the mean number of nuclei per cell was 6.92, with a mode of 4.47% had 5 or fewer nuclei and only 11% more than 10 nuclei. The pits associated with 292 osteoclasts with known numbers of nuclei were measured using a confocal laser light microscope (Lasertec) and dedicated image analysis system, and depths, plan areas and volumes determined. There was a positive correlation between the number of nuclei per osteoclast and the volume of the pit made, but a trend for the volume resorbed per nucleus to decrease with increase in the number of nuclei per osteoclast.

Animals↗
PubMed1991

Non-inpatient costing study.

Flinders Medical Centre, a University teaching hospital located in the south of Adelaide, spends approximately 27% of its annual budget in the treatment of ambulatory patients. In an attempt to gain a better appreciation of the profile of resource use by this group of patients, the hospital undertook a detailed cost survey. This study has made it possible to identify the cost impact of ambulatory attendances on each of the service areas of the hospital and compare variation in cost within and between specialist clinics.

Ambulatory Care↗