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Biomedical subjects

S A Campbell

Publications and source records attributed to S A Campbell.

At least 19 recordsLinked to original sources
PubMed2006

Enzymes of type II fatty acid synthesis and apicoplast differentiation and division in Eimeria tenella.

Apicomplexan parasites, Eimeria tenella, Plasmodium spp. and Toxoplasma gondii, possess a homologous plastid-like organelle termed the apicoplast, derived from the endosymbiotic enslavement of a photosynthetic alga. However, currently no eimerian nuclear encoded apicoplast targeted proteins have been identified, unlike in Plasmodium spp. and T. gondii. In this study, we demonstrate that nuclear encoded enoyl reductase of E. tenella (EtENR) has a predicted N-terminal bipartite transit sequence, typical of apicoplast-targeted proteins. Using a combination of immunocytochemistry and EM we demonstrate that this fatty acid biosynthesis protein is located in the apicoplast of E. tenella. Using the EtENR as a tool to mark apicoplast development during the Eimeria lifecycle, we demonstrate that nuclear and apicoplast division appear to be independent events, both organelles dividing prior to daughter cell formation, with each daughter cell possessing one to four apicoplasts. We believe this is the first report of multiple apicoplasts present in the infectious stage of an apicomplexan parasite. Furthermore, the microgametes lacked an identifiable apicoplast consistent with maternal inheritance via the macrogamete. It was found that the size of the organelle and the abundance of EtENR varied with developmental stage of the E. tenella lifecycle. The high levels of EtENR protein observed during asexual development and macrogametogony is potentially associated with the increased synthesis of fatty acids required for the rapid formation of numerous merozoites and for the extracellular development and survival of the oocyst. Taken together the data demonstrate that the E. tenella apicoplast participates in type II fatty acid biosynthesis with increased expression of ENR during parasite growth. Apicoplast division results in the simultaneous formation of multiple fragments. The division mechanism is unknown, but is independent of nuclear division and occurs prior to daughter formation.

Amino Acid Sequence↗
PubMed2006

A methodology for investigating new nonprecious metal catalysts for PEM fuel cells.

This paper reports an approach to investigate metal-chalcogen materials as catalysts for the oxygen reduction reaction (ORR) in proton exchange membrane (PEM) fuel cells. The methodology is illustrated with reference to Co-Se thin films prepared by magnetron sputtering onto a glassy-carbon substrate. Scanning Auger microscopy (SAM), X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD) have been used, in parallel with electrochemical activity and stability measurements, to assess how the electrochemical performance relates to chemical composition. It is shown that Co-Se thin films with varying Se are active for oxygen reduction, although the open circuit potential (OCP) is lower than for Pt. A kinetically controlled process is observed in the potential range 0.5-0.7 V (vs reversible hydrogen electrode) for the thin-film catalysts studied. An initial exposure of the thin-film samples to an acid environment served as a pretreatment, which modified surface composition prior to activity measurements with the rotating disk electrode (RDE) method. Based on the SAM characterization before and after electrochemical tests, all surfaces demonstrating activity are dominated by chalcogen. XRD shows that the thin films have nanocrystalline character that is based on a Co(1-x)Se phase. Parallel studies on Co-Se powder supported on XC72R carbon show comparable OCP, Tafel region, and structural phase as for the thin-film model catalysts. A comparison for ORR activity has also been made between this Co-Se powder and a commercial Pt catalyst.

Journal Article↗
PubMed2005

Two-cell to N-cell heterogeneous, inhibitory networks: precise linking of multistable and coherent properties.

Inhibitory networks are now recognized as being the controllers of several brain rhythms. However, experimental work with inhibitory cells is technically difficult not only because of their smaller percentage of the neuronal population, but also because of their diverse properties. As such, inhibitory network models with tight links to the experimental data are needed to understand their contributions to population rhythms. However, mathematical analyses of network models with more than two cells is challenging when the cellular models involve biophysical details. We use bifurcation analyses and simulations to show that two-cell analyses can quantitatively predict N-cell (N = 20, 50, 100) network dynamics for heterogeneous, inhibitory networks. Interestingly, multistable states in the two-cell system are manifest as different and distinct coherent network patterns in the N-cell networks for the same parameter sets.

Action Potentials↗
PubMed2004

Using heterogeneity to predict inhibitory network model characteristics.

From modeling studies it has been known for >10 years that purely inhibitory networks can produce synchronous output given appropriate balances of intrinsic and synaptic parameters. Several experimental studies indicate that synchronous activity produced by inhibitory networks is critical to the production of population rhythms associated with various behavioral states. Heterogeneity of inputs to inhibitory networks strongly affect their ability to synchronize. In this paper, we explore how the amount of input heterogeneity to two-cell inhibitory networks affects their dynamics. Using numerical simulations and bifurcation analyses, we find that the ability of inhibitory networks to synchronize in the face of heterogeneity depends nonmonotonically on each of the synaptic time constant, synaptic conductance and external drive parameters. Because of this, an optimal set of parameters for a given cellular model with various biophysical characteristics can be determined. We suggest that this could be a helpful approach to use in determining the importance of different, underlying biophysical details. We further find that two-cell coherence properties are maintained in larger 10-cell networks. As such, we think that a strategy of "embedding" small network dynamics in larger networks is a useful way to understand the contribution of biophysically derived parameters to population dynamics in large networks.

Biological Clocks↗
PubMed2004

A complete shikimate pathway in Toxoplasma gondii: an ancient eukaryotic innovation.

The shikimate pathway is essential for survival of the apicomplexan parasites Plasmodium falciparum, Toxoplasma gondii and Cryptosporidium parvum. As it is absent in mammals it is a promising therapeutic target. Herein, we describe the genes encoding the shikimate pathway enzymes in T. gondii. The molecular arrangement and phylogeny of the proteins suggests homology with the eukaryotic fungal enzymes, including a pentafunctional AROM. Current rooting of the eukaryotic evolutionary tree infers that the fungi and apicomplexan lineages diverged deeply, suggesting that the arom is an ancient supergene present in early eukaryotes and subsequently lost or replaced in a number of lineages.

Alcohol Oxidoreductases↗
PubMed2000

An acute hemolytic transfusion reaction due to anti-IH in a patient with sickle cell disease.

BACKGROUND: A hemolytic transfusion reaction (HTR) due to anti-IH is reported in a patient with sickle cell disease (SCD). CASE REPORT: An 18-year-old woman with SCD and a complete phenotype on file had been identified as group B-positive with negative antibody-screening tests and had received 1 unit of packed RBCs. Ten days later, she was readmitted in painful crisis with a Hb of 4.2 g per dL. Antibody-screening tests and panel cells were positive at all test phases with a negative autocontrol, which suggested alloantibodies. Phenotypically matched group O RBCs were issued emergently. After the transfusion of 100 mL, the patient had an HTR with chills, fever, and tachycardia and laboratory findings of hemoglobinemia, hemoglobinuria, and negative DATs. A high-titer, IgM anti-IH with a high thermal amplitude (reactive with group O, but not group B RBCs at 37 degrees C) was identified. Autologous RBCs appeared to have normal I antigen expression, but less H antigen than pooled group B RBCs. She was given group B RBCs, uneventfully, by use of a blood warmer. CONCLUSIONS: This is a rare case of anti-IH as the cause of a HTR, as a serologic problem that may be seen in SCD, and as an autoantibody that may mimic an alloantibody. Ironically, this HTR resulted from the effort to provide phenotypically matched RBCs, which necessitated the selection of group O RBCs.

Adolescent↗
PubMed2000

Crystallization and preliminary X-ray analysis of shikimate dehydrogenase from Escherichia coli.

Shikimate dehydrogenase from Escherichia coli has been crystallized by the vapour-diffusion method using ammonium sulfate as a precipitant. Mass spectrometry confirmed the purity of the enzyme and dynamic light scattering was used to find the appropriate additives to yield a monodisperse enzyme solution. The crystals are monoclinic, space group C2, with unit-cell parameters a = 110.0, b = 139.8, c = 102.6 A, beta = 122.2 degrees (at 100 K). Native crystals diffract to 2.3 A in-house on a rotating-anode X-ray source. The asymmetric unit is likely to contain four molecules, related by 222 symmetry, corresponding to a packing density of 2.86 A(3) Da(-1).

Alcohol Oxidoreductases↗
PubMed1999

Characterization of P1,P4-diadenosine 5'-tetraphosphate binding on bovine aortic endothelial cells.

In recent years it has become increasingly clear that alpha, omega-dinucleotides act as extracellular modulators of various biological processes. P1,P4-diadenosine 5'-tetraphosphate (Ap4A) is the best characterized alpha,omega-dinucleotides and acts as an extracellular signal molecule by inducing the release of nitric oxide (NO) from bovine aortic endothelial cells (BAEC) (R. H. Hilderman, and E. F. Christensen (1998) FEBS Lett. 407, 320-324). However, the characteristics of Ap4A binding to endothelial cells have not been determined. In this report we demonstrate that Ap4A binds to a heterogeneous population of receptors on BAEC. Competition ligand-binding studies using various adenosine dinucleotides, guanosine dinucleotides, adenosine/guanosine dinucleotides, and synthetic P2 purinoceptor agonists and antagonists demonstrate that Ap4A binds to a receptor on BAEC that has a high affinity for some of the adenosine dinucleotides. The apparent IC50 values for Ap4A, Ap2A, and Ap3A are between 12 and 15 microM, while the apparent IC50 values for Ap5A and Ap6A are greater than 500 microM. Evidence is also presented which suggests that this receptor can be classified as a putative P4 purinoceptor. Competition studies also demonstrate that Ap4A binds at a lower affinity to a second class of binding sites.

Adenosine Triphosphate↗
PubMed1998

A ca. 40 kDa maize (Zea mays L.) embryo dehydrin is encoded by the dhn2 locus on chromosome 9.

Dehydrins (LEA D11 proteins) are the products of multigene families in a number of higher plants. To date, however, only one dehydrin locus, dhn1 (a major embryo and drought-induced protein of ca. 18 kDa) has been placed on chromosome 6L of the genetic linkage map of maize. The presence of a larger, ca. 40 kDa embryo protein that is also specifically detected by anti-dehydrin antibodies had been observed in some maize inbreds, including B73, suggesting that other dhn loci may exist. The ca. 22 kDa and ca. 40 kDa immunopositive proteins were purified from B73 and their amino acid compositions determined. The two proteins' amino acid compositions are typical of dehydrins, yet they differ from each other, indicating that they are distinct dhn gene products. Different size alleles for both proteins, or presence/absence in the case of the ca. 40 kDa protein, were evident from comparisons of embryo proteins of various maize inbreds. Analysis of segregating F2 progeny derived from self-pollination of F1 hybrids from four crosses (B73 x OH43, Mo17 x A632, AHO x A632, Latente x A632) revealed that alleles of the two genes assort independently. Map positions of the two dhn loci were then determined using two maize recombinant inbred line (RIL) mapping populations. The predicted map position of the gene controlling production of the ca. 22 kDa protein confirmed that this protein is the product of the dhn1 gene. The gene encoding the ca. 40 kDa dehydrin-like protein maps to a new locus on chromosome 9S near wx1, which we have named dhn2.

Amino Acid Sequence↗
PubMed1998

Synergistic effects of feeding and dexamethasone on serum leptin levels.

The objectives of this study were to determine the time course of the stimulatory effect of dexamethasone on serum leptin and whether it depends on food intake. Dexamethasone (4mg) was administered I.V. over 1 minute to healthy human volunteers (n=8) under fasting and feeding conditions (2000 kcal given at three meals over 7 hours). At 10 hours, serum leptin levels were increased only in the fed subjects (delta leptin 10.6+/-1.6 vs -2.4+/-1.9 ng/ml, p=0.01, n=8). To assess the interactive effect of food and dexamethasone on serum leptin, a subgroup (n=4) was studied under 4 conditions: 1) dexamethasone/fast; 2) dexamethasone/food; 3) saline/fast; 4) saline/food. Serum leptin declined from baseline under the fasting conditions, with or without dexamethasone. Feeding prevented the drop in serum leptin. In the dexamethasone/food condition, leptin levels rose from baseline after 7 hours and doubled after 10 hours (p<0.05). The rise in serum leptin was significantly greater in the food/dexamethasone condition compared to all other conditions (p<0.05). In summary, dexamethasone has no independent effect on serum leptin in the absence of food intake. Rather, dexamethasone appears to potentiate the food-induced increase in serum leptin. This synergism may be mediated by insulin and/or other factors associated with food ingestion.

Adult↗
PubMed1995

Pregnancy outcome when both members of a couple have balanced translocations.

BACKGROUND: Couples in which one partner is the carrier of a balanced translocation have increased risks of infertility, recurrent abortion, and delivery of chromosomally abnormal offspring. Pregnancies in which both partners carry balanced translocations are uncommon; therefore, only limited information regarding risk figures is available. We present a couple in which both members had a balanced translocation and discuss their pregnancy outcomes. CASE: A couple had three first-trimester spontaneous abortions at 12, 10, and 8 weeks' gestation, respectively. Both partners were found to be carriers of balanced autosomal translocations. The mother had a Robertsonian translocation with the karyotype 45,XX,t(13q14q). The father had a reciprocal translocation with a 46,XY,t(1;4)(q32;q25) karyotype. There was no information regarding the karyotype of the patient's first-born child with a previous partner. The patient's first-born child with her current partner carried a double balanced translocation karyotype of 45,XX,t(13;14)t(1;4). Their second and third children both had a 45,XX,t(13q14q) karyotype. CONCLUSION: Couples in which both members have a balanced translocation are at increased risk for adverse pregnancy and fetal outcomes, but precise information regarding risk estimates for this rare circumstance is limited. Genetic counseling of such couples therefore presents a unique challenge.

Abortion, Habitual↗
PubMed1995

Management of small unilateral renal cell carcinomas: radical versus nephron-sparing surgery.

OBJECTIVES: There is controversy concerning the management of small unilateral renal cell carcinomas. The present study was undertaken to evaluate the relative efficacy of radical nephrectomy versus nephron-sparing surgery in such patients. METHODS: Patients with a single, small (less than 4 cm), localized, unilateral, sporadic renal cell carcinoma (RCC) were identified from an institutional registry. From 1975 to 1992, 88 patients fulfilling these criteria were treated with either radical nephrectomy (n = 42) or nephron-sparing surgery (n = 46). The mean postoperative follow-up interval is 48 +/- 29 months. RESULTS: The radical and nephron-sparing surgical groups were well matched for patient age, sex, renal function, diabetes, hypertension, tumor size, tumor location, and tumor stage. All patients in both groups had low pathologic stage RCC. There was no difference between the two groups in terms of the mean hospital stay, the requirement for blood transfusions, or the occurrence of surgical complications. There was no difference in the mean preoperative and postoperative serum creatinine levels for patients in the nephron-sparing surgery group. However, the mean postoperative serum creatinine levels were significantly higher than the mean preoperative levels for patients in the radical nephrectomy group (P < 0.001). A single patient in each group developed recurrent RCC postoperatively. The cancer-specific 5-year survival rate for patients in the radical and nephron-sparing surgical groups is 97% and 100%, respectively. CONCLUSIONS: Radical nephrectomy and nephron-sparing surgery each provide safe and effective curative treatment for patients with a single, small, unilateral localized RCC. The long-term renal functional advantage of nephron-sparing surgery in this setting is not established.

Aged↗
PubMed1994

Use of molybdenum telluride as a substrate for the imaging of biological molecules during scanning tunnelling microscopy.

Scanning tunnelling microscopy was used to image biological molecules including supercoiled deoxyribonacetic acid and specific retrovirus enzymes, the reverse transcriptases of the avian myeloblastosis virus, the moloney murine leukaemia virus and the human immunodeficiency virus. Measurements were carried out on graphite and Group VI transition metal dichalcogenide layered crystals. Images obtained with graphite could not be unequivocally interpreted and attachment appears to occur solely at surface defect sites. The layered crystal MoTe2 shows different imaging properties. The bimolecules are clearly visible, distributed over the semiconductor surface, and the molecular shapes and dimensions show good correlation with structure predictions.

DNA, Superhelical↗
PubMed1992

Scanning tunnelling microscopy observations of biomolecules on layered materials.

Scanning tunnelling microscopy (STM) has been performed on the reverse transcriptases of the human immunodeficiency virus (HIV-1) and the moloney murine leukaemia virus (MuLV). The biological molecules are adsorbed on n-type semiconducting MoTe2. The p66 (66 kD) subunit of the RT of HIV-1 is imaged by STM. Both STM and processed transmission electron microscopy (TEM) data show a spherical and horseshoe-like shape of external diameter ca. 65 A, depending on the angle of observation. The STM results show a larger diameter which is related to the curvature radius of the tip of the probing needle. The RTs of HIV-1 and MuLV exhibit a circular hole of ca. 20 A diameter in accordance with structure predictions and functioning considerations. The surface-molecule interaction is discussed in terms of the electronic properties of the semiconductor surface including the influence of small defect sites at the layered crystal surface.

Dialysis↗
PubMed1992

Direct observation of reverse transcriptases by scanning tunneling microscopy.

First images on a nanometer scale of reverse transcriptases (RT) of the human immunodeficiency virus (HIV-1) and of the Moloney murine leukemia virus (MuLV) obtained by scanning tunneling microscopy (STM) are reported. The common feature of the observed molecules is a ring-type or horseshoe shape with hole diameters of approximately 30 A. The STM images are compared with high resolution transmission electron microscopy (TEM) and existing structure predictions. The similarities of the structural data obtained by STM and TEM and their agreement with the structure prediction for the RT of HIV-1 shows the principal possibility to image such biomolecules by STM.

Crystallization↗
PubMed1991

Late effects of childhood malignancies seen in Western Australia.

Eighty-nine pediatric oncology patients, in remission and off treatment for at least 4 years, were reviewed annually in the Late Effects Clinic of Princess Margaret Hospital for Children in Perth, Western Australia. Interval from time of diagnosis to follow-up ranged from 4 to 23 years (mean 10.8 years). Acute lymphoblastic leukemia (ALL) (40%) and Wilms' tumor (27%) were the most common primary malignancies in this group. Late sequelae included musculoskeletal abnormalities (23 children), growth hormone deficiency (11), second tumors (9), learning difficulties (7), puberty and fertility problems (4), and hypothyroidism (4). These complications were most often related to radiation therapy. The need for prolonged, regular follow-up of survivors of childhood malignancy for early detection of late sequelae and subsequent intervention is stressed.

Adolescent↗
PubMed1990

Oral activity of the growth hormone releasing peptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 in rats, dogs and monkeys.

The purpose of this study was to evaluate the growth hormone (GH) releasing activity of orally administered His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6, SK&F 110679) in rats, dogs and monkeys. Rats were administered GHRP-6 orally by gavage or parenterally through femoral artery catheters. Blood was collected before and after GHRP-6 administration for estimation of plasma GH and comparison of GH changes resulting from enteral and parenteral administration of the peptide. GHRP-6 was administered to dogs intravenously (i.v.) through cephalic vein catheters, intragastrically (i.g.) through esophagostomy tubes or intraduodenally (i.d.) through vascular access ports, and blood was collected before and after peptide administration for estimation of plasma GH. Cynomolgus monkeys were administered GHRP-6 i.g., and blood was collected from abdominal aorta for estimation of changes in plasma GH. Enteral activity of GHRP-6 was observed in all 3 species tested. In rats, ED50's for enteral and parenteral administration of GHRP-6 were 4 mg/kg and 28 micrograms/kg, respectively. Thus in rats, enterally administered GHRP-6 was 0.7% as bioactive as the parenterally administered peptide. In dogs GHRP-6 was slightly less potent than in rats, with ED50's for i.g. and i.v. administration approximately 15 mg/kg and 125 micrograms/kg, respectively. However, enteral potency of GHRP-6 in dogs was 0.8% of parenteral potency, and thus, comparable to that in rats. Additionally, comparison of plasma GH levels following i.g. vs i.d. administration in dogs suggested greater activity by the i.d. route. Monkeys were the species most sensitive to enterally administered GHRP-6, with plasma GH increased in those receiving i.g. doses as low as 0.3 mg/kg and an ED50 of 0.75 mg/kg compared to 4 and 15 mg/kg in rats and dogs, respectively. The results of this study demonstrate that GHRP-6 releases GH when administered directly into the gastrointestinal tract. Although enteral activity is approximately 1% of parenteral activity, GHRP-6 is potent, especially in primates which require relatively low doses to provoke GH release. These data suggest that orally active GHRP-6 may provide a practical therapeutic alternative to parenterally administered peptides such as GHRH, especially if enteral activity is enhanced with appropriate formulation.

Administration, Oral↗