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A Moseley

Publications and source records attributed to A Moseley.

At least 19 recordsLinked to original sources
PubMed2001

The large subunit of the mammalian mitochondrial ribosome. Analysis of the complement of ribosomal proteins present.

Identification of all the protein components of the large subunit (39 S) of the mammalian mitochondrial ribosome has been achieved by carrying out proteolytic digestions of whole 39 S subunits followed by analysis of the resultant peptides by liquid chromatography and mass spectrometry. Peptide sequence information was used to search the human EST data bases and complete coding sequences were assembled. The human mitochondrial 39 S subunit has 48 distinct proteins. Twenty eight of these are homologs of the Escherichia coli 50 S ribosomal proteins L1, L2, L3, L4, L7/L12, L9, L10, L11, L13, L14, L15, L16, L17, L18, L19, L20, L21, L22, L23, L24, L27, L28, L30, L32, L33, L34, L35, and L36. Almost all of these proteins have homologs in Drosophila melanogaster, Caenorhabditis elegans, and Saccharomyces cerevisiae mitochondrial ribosomes. No mitochondrial homologs to prokaryotic ribosomal proteins L5, L6, L25, L29, and L31 could be found either in the peptides obtained or by analysis of the available data bases. The remaining 20 proteins present in the 39 S subunits are specific to mitochondrial ribosomes. Proteins in this group have no apparent homologs in bacterial, chloroplast, archaebacterial, or cytosolic ribosomes. All but two of the proteins has a clear homolog in D. melanogaster while all can be found in the genome of C. elegans. Ten of the 20 mitochondrial specific 39 S proteins have homologs in S. cerevisiae. Homologs of 2 of these new classes of ribosomal proteins could be identified in the Arabidopsis thaliana genome.

Amino Acid Sequence↗
PubMed2001

Baboon mesenchymal stem cells can be genetically modified to secrete human erythropoietin in vivo.

Human mesenchymal stem cells (MSCs) are capable of differentiating into multiple mesenchymal lineages including chondrocytes, osteocytes, adipocytes, and marrow stromal cells. Using a nonhuman primate model, we evaluated nonhuman primate MSCs as targets for gene therapy. Baboon MSCs (bMSCs) cultured from bone marrow aspirates appeared as a homogeneous population of spindle-shaped cells. bMSCs were capable of differentiating into adipocytes and osteocytes in vitro and chondrocytes in vivo. bMSCs were genetically modified with a bicistronic vector encoding the human erythropoietin (hEPO) gene and the green fluorescent protein (GFP) gene. Transduction efficiencies ranged from 72 to 99% after incubation of MSCs with retroviral supernatant. Transduced cells produced from 1.83 x 10(5) to 7.12 x 10(5) mIU of hEPO per 10(6) cells per 24 hr in vitro before implantation. To determine the capacity of bMSCs to express hEPO in vivo, transduced bMSCs were injected intramuscularly in NOD/SCID mice. In a separate experiment, transduced bMSCs were loaded into immunoisolatory devices (IIDs) and surgically implanted into either autologous or allogeneic baboon recipients. Human EPO was detected in the serum of NOD/SCID mice for up to 28 days and in the serum of five baboons for between 9 and 137 days. NOD/SCID mice experienced sharp rises in hematocrit after intramuscular injection of hEPO-transduced bMSCs. The baboon that expressed hEPO for 137 days experienced a statistically significant (p < 0.04) rise in its hematocrit. These data demonstrate that nonhuman primate MSCs can be engineered to deliver a secreted and biologically active gene product. Therefore, human MSCs may be an effective target for future human gene therapy trials.

Adult↗
PubMed2001

A new face on apoptosis: death-associated protein 3 and PDCD9 are mitochondrial ribosomal proteins.

Two proteins known to be involved in promoting apoptosis in mammalian cells have been identified as components of the mammalian mitochondrial ribosome. Proteolytic digestion of whole mitochondrial ribosomal subunits followed by analysis of the peptides present using liquid chromatography-tandem mass spectrometry revealed that the proapoptotic proteins, death-associated protein 3 (DAP3) and the programmed cell death protein 9, are both components of the mitochondrial ribosome. DAP3 has motifs characteristic of guanine nucleotide binding proteins and is probably the protein that accounts for the nucleotide binding activity of mammalian mitochondrial ribosomes. The observations reported here implicate mitochondrial protein synthesis as a major component in cellular apoptotic signaling pathways.

Amino Acid Sequence↗
PubMed2001

The small subunit of the mammalian mitochondrial ribosome. Identification of the full complement of ribosomal proteins present.

Identification of all the protein components of the small subunit (28 S) of the mammalian mitochondrial ribosome has been achieved by carrying out proteolytic digestions of whole 28 S subunits followed by analysis of the resultant peptides by liquid chromatography and tandem mass spectrometry (LC/MS/MS). Peptide sequence information was used to search the human EST data bases and complete coding sequences of the proteins were assembled. The human mitochondrial ribosome has 29 distinct proteins in the small subunit. Fourteen of this group of proteins are homologs of the Escherichia coli 30 S ribosomal proteins S2, S5, S6, S7, S9, S10, S11, S12, S14, S15, S16, S17, S18, and S21. All of these proteins have homologs in Drosophila melanogaster, Caenorhabditis elegans, and Saccharomyces cerevisiae mitochondrial ribosomes. Surprisingly, three variants of ribosomal protein S18 are found in the mammalian and D. melanogaster mitochondrial ribosomes while C. elegans has two S18 homologs. The S18 homologs tend to be more closely related to chloroplast S18s than to prokaryotic S18s. No mitochondrial homologs to prokaryotic ribosomal proteins S1, S3, S4, S8, S13, S19, and S20 could be found in the peptides obtained from the whole 28 S subunit digests or by analysis of the available data bases. The remaining 15 proteins present in mammalian mitochondrial 28 S subunits (MRP-S22 through MRP-S36) are specific to mitochondrial ribosomes. Proteins in this group have no apparent homologs in bacterial, chloroplast, archaebacterial, or cytosolic ribosomes. All but two of these proteins have a clear homolog in D. melanogaster while all but three can be found in the genome of C. elegans. Five of the mitochondrial specific ribosomal proteins have homologs in S. cerevisiae.

Amino Acid Sequence↗
PubMed2001

Mesenchymal stem cells are capable of homing to the bone marrow of non-human primates following systemic infusion.

OBJECTIVE: The human bone marrow contains mesenchymal stem cells capable of differentiating along multiple mesenchymal cell lineages. Using a non-human primate model, we sought to determine whether the systemic infusion of baboon-derived mesenchymal stem cells was associated with toxicity and whether these cells were capable of homing to and persisting within the bone marrow. MATERIALS AND METHODS: Five baboons (Papio anubis) were administered lethal irradiation followed by intravenous autologous hematopoietic progenitor cells combined with either autologous (n = 3) or allogeneic (n = 2) mesenchymal stem cells that had been expanded in culture. In four of these baboons, the mesenchymal stem cells were genetically modified with a retroviral vector encoding either the enhanced green fluorescent protein gene (n = 3) or the human placental alkaline phosphatase gene (n = 1) for tracking purposes. A sixth animal received only intravenous gene marked autologous mesenchymal stem cells but no hematopoietic stem cells or conditioning irradiation. RESULTS: Following culture, baboon mesenchymal stem cells appeared morphologically as a homogeneous population of spindle-shaped cells that were identified by the monoclonal antibodies SH-3 and SH-4. These cells did not express the hematopoietic markers CD34 or CD45. Baboon mesenchymal stem cells isolated from primary culture were capable of differentiating along both adipogenic and osteogenic lineages. There was no acute or chronic toxicity associated with the intravenous infusion of mesenchymal stem cells. In all five recipients of gene marked mesenchymal stem cells, transgene was detected in post-transplant bone marrow biopsies. In two animals receiving autologous mesenchymal stem cells, including the one non-conditioned recipient, transgene could be detected over 1 year following infusion. In one recipient of allogeneic gene marked mesenchymal stem cells, transgene was detected in the bone marrow at 76 days following infusion. CONCLUSION: These data demonstrate that baboon mesenchymal stem cells: 1) are not associated with significant toxicity when administered intravenously, 2) are capable of homing to the bone marrow following intravenous infusion, and 3) have the capacity to establish residence within the bone marrow for an extended duration following systemic administration.

Alkaline Phosphatase↗
PubMed2001

Identification of four proteins from the small subunit of the mammalian mitochondrial ribosome using a proteomics approach.

Proteins in the small subunit of the mammalian mitochondrial ribosome were separated by two-dimensional polyacrylamide gel electrophoresis. Four individual proteins were subjected to in-gel Endoprotease Lys-C digestion. The sequences of selected proteolytic peptides were obtained by electrospray tandem mass spectrometry. Peptide sequences obtained from in-gel digestion of individual spots were used to screen human, mouse, and rat expressed sequence tag databases, and complete consensus cDNAs for these species were deduced in silico. The corresponding protein sequences were characterized by comparison to known ribosomal proteins in protein databases. Four different classes of mammalian mitochondrial small subunit ribosomal proteins were identified. Only two of these proteins have significant sequence similarities to ribosomal proteins from prokaryotes. These proteins are homologs to Escherichia coli S9 and S5 proteins. The presence of these newly identified mitochondrial ribosomal proteins are also investigated in the Drosophila melanogaster, Caenorhabditis elegans, and in the genomes of several fungi.

Amino Acid Sequence↗
PubMed2000

A proteomics approach to the identification of mammalian mitochondrial small subunit ribosomal proteins.

Mammalian mitochondrial small subunit ribosomal proteins were separated by two-dimensional polyacrylamide gel electrophoresis. The proteins in six individual spots were subjected to in-gel tryptic digestion. Peptides were separated by capillary liquid chromatography, and the sequences of selected peptides were obtained by electrospray tandem mass spectrometry. The peptide sequences obtained were used to screen human expressed sequence tag data bases, and complete consensus cDNAs were assembled. Mammalian mitochondrial small subunit ribosomal proteins from six different classes of ribosomal proteins were identified. Only two of these proteins have significant sequence similarities to ribosomal proteins from prokaryotes. These proteins correspond to Escherichia coli S10 and S14. Homologs of two human mitochondrial proteins not found in prokaryotes were observed in the genomes of Drosophila melanogaster and Caenorhabditis elegans. A homolog of one of these proteins was observed in D. melanogaster but not in C. elegans, while a homolog of the other was present in C. elegans but not in D. melanogaster. A homolog of one of the ribosomal proteins not found in prokaryotes was tentatively identified in the yeast genome. This latter protein is the first reported example of a ribosomal protein that is shared by mitochondrial ribosomes from lower and higher eukaryotes that does not have a homolog in prokaryotes.

Amino Acid Sequence↗
PubMed2000

In vivo exposure to bicarbonate/lactate- and bicarbonate-buffered peritoneal dialysis fluids improves ex vivo peritoneal macrophage function.

The impact on peritoneal macrophage (PMO) function of acidic lactate-buffered (Lac-PDF [PD4]; 40 mmol/L of lactate; pH 5.2) and neutral-pH, bicarbonate-buffered (TB; 38 mmol/L of bicarbonate; pH 7. 3) and bicarbonate/lactate-buffered (TBL; 25 mmol/L of bicarbonate/15 mmol/L of lactate; pH 7.3) peritoneal dialysis fluids (PDFs) was compared during a study of continuous therapy with PD4, TB, or TBL. During a run-in phase of 6 weeks when all patients (n = 15) were treated with their regular dialysis regimen with Lac-PDF, median PMO tumor necrosis factor alpha (TNFalpha) release values were 203.6, 89.9, and 115.5 pg TNFalpha/10(6) PMO in the patients subsequently randomized to the PD4, TB, and TBL treatment groups, respectively. Median stimulated TNFalpha values (serum-treated zymosan [STZ], 10 microgram/mL) were 1,894.6, 567.3, and 554.5 pg TNFalpha/10(6) PMO in the same groups, respectively. During the trial phase of 12 weeks, when the three groups of patients (n = 5 per group) were randomized to continuous treatment with PD4, TB, or TBL, median constitutive TNFalpha release values were 204.7, 131.4, and 155.4 pg TNFalpha/10(6) PMO, respectively. Stimulated TNFalpha values (STZ, 10 microgram/mL) were 1,911, 1,832, and 1,378 pg TNFalpha/10(6) PMO in the same groups, respectively. Repeated-measures analysis of variance comparing the run-in phase with the trial phase showed that PMO TNFalpha release was significantly elevated in patients treated with both TB (P = 0.040) and TBL (P = 0.014) but not in patients treated with Lac-PDF (P = 0. 795). These data suggest that patients continuously exposed to bicarbonate- and bicarbonate/lactate-buffered PDFs might have better preserved PMO function and thus improved host defense status.

Adult↗
PubMed2000

PEDro.

Explore the source record for details and available documents.

Academies and Institutes↗
PubMed1998

Bicarbonate/lactate- and bicarbonate-buffered peritoneal dialysis fluids improve ex vivo peritoneal macrophage TNFalpha secretion.

Peritoneal macrophage (PMO) function was examined ex vivo after their in vivo exposure to either acidic, lactate-buffered solutions (PD4; 40 mM lactate, pH 5.2), bicarbonate/lactate-buffered solution (TBL; 25 mM/15 mM bicarbonate/lactate, pH 7.3), or bicarbonate-buffered solution (TB; 38 mM bicarbonate, pH 7.3), containing either 1.36 or 3.86% glucose. Initial experiments demonstrated that tumor necrosis factor-alpha (TNFalpha) release (assessed by TNF-direct immunoassay [DIA]) from PMO isolated from the peritoneal cavities of patients exposed to conventional fluid (PD4 1.36% glucose) was lowest after 30 min of intraperitoneal dwell (3591+/-1200 versus 28,946+/-9359 for 240-min dwell [pg/ml], n=5, P < 0.05). Five patients were exposed on 3 successive days to PD4, TBL, and TB for 30-min acute dwells containing 1.36% glucose in the first week and 3.86% glucose during the second. PMO TNFalpha release was assessed after ex vitro exposure to lipopolysaccharide (LPS). Exposure of PMO to TBL or TB (1.36% glucose) resulted in a significant increase in the generation of TNFalpha (pg/2 X 10(6) PMO) compared with PD4. TBL: 68,659+/-35,633, TB: 53,682+/-26,536 versus PD4 17,107+/-8996 (LPS 1.0 ng/ml, n=5 patients, P=0.043 versus PD4 for both). PMO that were recovered from PD4 and TB dwells (3.86% glucose) showed no significant difference in TNFalpha secretion (21,661+/-6934 and 23,923+/-9147, respectively). In contrast, exposure to TBL resulted in a significant increase (41,846+/-11,471) compared with PD4 (LPS 1.0 ng/ml, n=5 patients, P=0.043). These data demonstrate enhanced PMO function after in vivo exposure to bicarbonate- and bicarbonate/lactate-buffered solutions. This response was sustained in TBL alone at the highest glucose concentrations. These results suggest that the newer solutions, and particularly bicarbonate/lactate, might improve host defense status in peritoneal dialysis patients.

Aged↗
PubMed1996

Bone marrow gene transfer in three patients with adenosine deaminase deficiency.

Adenosine deaminase (ADA) deficiency results in severe combined immune deficiency disease (SCID), which is fatal without treatment. Allogeneic bone marrow transplantation (BMT) is the treatment of choice if an HLA-identical sibling bone marrow donor is available, resulting in almost 100% cure rate. BMT-related mortality is high in patients lacking such a donor. For these patients, efficient transfer of a recombinant ADA gene into hematopoietic stem cells is a therapeutic option if it results in the outgrowth of a 'genetically repaired' lymphoid system. Based on successful gene transfer studies in monkeys, we performed retrovirus-mediated gene transfer into CD34+ bone marrow cells of three patients with ADA deficiency. Two patients received bovine ADA conjugated to polyethylene glycol (PEG-ADA); in the third patient, PEG-ADA was started 4 months after gene transfer. Gene transfer resulted in a 5-12% transduction frequency of in vitro colony forming cells (CFU-Cs). No toxicity was observed during and after infusion of the graft. Following infusion of the transduced CD34+ cells, transduced granulocytes and mononuclear cells persisted in the circulation for 3 months. In addition, the gene was present in the marrow of one of the patients at 6 months after gene transfer. Expression of the gene was not detected. After this period, the gene could not be detected. In monkey studies we showed that myeloablation, which was not performed in the patients, may enhance engraftment of genetically modified cells. We hypothesize that lack of myeloablation, administration of bovine ADA and low numbers of transduced progenitor cells all may have contributed to the relative low numbers of transduced cells in the patients. Under these conditions, no selective advantage of the genetically corrected progenitor cells was observed.

Adenosine Deaminase↗
PubMed1993

Direct isolation and expansion of human CD34+ hematopoietic stem cells.

The isolation and expansion of CD34+ cells has numerous applications as supportive therapy for cytopenias that occur postchemotherapy. In this report, we describe a simple system to directly isolate and culture human CD34+ cells. Using this system, CD34+ cells isolated from bone marrow were cultured in the presence of GM-CSF, G-CSF, erythropoietin, stem cell factor, IL-1, IL-3, and IL-6. Cell expansions up to 100-fold were noted during the first 2 weeks of culture with high maintenance of CD34+ cells during the first week of culture. Maximal expansions of progenitors were observed at one week of culture, with, on average, 20-fold increases in CFU-GM number. The results support the feasibility of CD34+ cell expansion for clinical application.

Antigens, CD↗
PubMed1990

Effect of feedback on learning a vertebral joint mobilization skill.

This study was designed to investigate whether concurrent quantitative feedback of performance could improve the learning of a joint mobilization technique. A group of 110 physical therapy students had been randomly divided into two groups for teaching purposes. All students had previously learned mobilization of peripheral joints and were currently learning spinal mobilization. From one of the groups, 22 students volunteered to comprise a control group, which was taught a spinal mobilization technique in the traditional way. Additional concurrent quantitative feedback of the level of force applied to the patient was given to 31 volunteers from the other group. These students formed the experimental group. A force plate was used for force measurement, and the feedback was given via an oscilloscope. The average force applied by the students' instructors was taken as an "ideal" force. The oscilloscope showed both the applied force and the "ideal" force. Consistency was measured by the variance of the group's performance. Accuracy was assessed by calculating the difference between the applied force and the "ideal" force. Results indicated that this feedback was associated with a significant improvement in accuracy and consistency in the application of the mobilizing force. This improvement was still present at a follow-up test conducted one week later. This result supports a greater use of such feedback in the teaching and practice of joint mobilization techniques, although the need for further research is emphasized.

Adult↗
PubMed1977

The significance of serial measurement of serum anti-native DNA antibodies and complement C3 and C4 components in the management of patients with systemic lupus erythematosus.

Serial measurements were made over a period of three years of serum DNA-binding capacity and complement C3 and C4 levels in parallel with documentation of clinical features of disease activity in Glasgow patients with SLE. Raised DNA-binding levels were noted in 27 of the 32 patients over this time period. High levels (over 80%) were found in patients with both renal and non-renal disease. In some patients increases in DNA-binding capacity and decreases in C3 levels were associated with changes in disease activity. This pattern was commonest in patients with renal SLE. In others DNA-binding capacity was elevated without any relationship to SLE disease activity. A fall in serum C3 levels was usually significant while serum C4 levels frequently fell without any change in clinical features of disease activity. Very low serum C4 levels (below 15 mg/dl), however, were usually of clinical relevance. The uses of immunological measurements in the differential diagnosis of a major illness in a patient with SLE are discussed. The finding of such an illness in a patient with normal serum DNA-binding levels made it unlikely that the illness was due to an exacerbation of the SLE and more likely that an alternative cause such as supervening bacteraemia was responsible.

Antibodies↗
PubMedDate not supplied

PEDro: a database of randomised controlled trials in physiotherapy.

PEDro is a database of clinical trials designed to assist the practice of evidence-based physiotherapy. When complete, it will contain bibliographic details, abstracts and quality assessment scores of all published randomised controlled trials in physiotherapy. Trials on the database will be rated on the basis of their methodological quality, so that users of the database can be guided to those trials which provide the most methodologically sound sources of evidence. The database has been made freely available on the world wide web, where it can be searched with a powerful and user-friendly search engine.

Australia↗