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J Gibson

Publications and source records attributed to J Gibson.

At least 55 records · Page 3Linked to original sources

The efficacy of oral vaccination of mice with alginate encapsulated outer membrane proteins of Pasteurella haemolytica and One-Shot.

The goal of this study was to examine the efficacy of oral delivery of alginate encapsulated outer membrane proteins (OMP) of Pasteurella haemolytica and a commercial One-Shot vaccine in inducing protection in mice against lethal challenge with virulent P. haemolytica. We examined two alginate microsphere formulations and compared them with oral unencapsulated and subcutaneously administered vaccines. Alginate microspheres were made by the emulsion-cross-linking technique. They were examined for size, hydrophobicity, and antigen loading efficiency before they were used in the study. Mice were vaccinated by administering 200 microg of antigens in 200 microl of microspheres suspension orally or subcutaneously. One group of mice received blank microspheres and a second group was given unencapsulated antigen orally. A third and a fourth group received different formulations of alginate encapsulated antigens by oral administration. Three groups received subcutaneous inoculations (alginate encapsulated, non-adjuvanted and unencapsulated antigens, and adjuvanted One-Shot), and one group received water (naïve group). Mice were vaccinated orally for four consecutive days and challenged with P. haemolytica 5 weeks after the first vaccination. Weekly serum and feces samples were assayed for antigen specific antibodies. The number of dead mice in each group 4 days post challenge was used to compare the efficacy of the various vaccination groups. The mean volume sizes of blank alginate microsphere formulations A, and AA were 15.9, 16 and 9.2 microm, respectively. Hydrophobicity of the microspheres was evaluated by measuring contact angle on a glass slide coated with the microspheres. The contact angles on A and AA were 37.8 and 74.3 degrees, respectively. Antigen concentration in a 1:1 w/w suspension of microspheres in water was 0.9 mg/ml. Rate of death for the blank group was 42.8% whereas for groups vaccinated with antigens encapsulated in A and AA the death rates were 40 and 33.33%, respectively. The death rate in mice vaccinated with unencapsulated antigens was 55.6%. Groups vaccinated by subcutaneous inoculation showed the lowest death rate. These results show that encapsulating OMP and One-Shot in alginate microspheres improves their performance as an oral vaccine.

Administration, Oral↗

Illegitimate switch recombinations are present in approximately half of primary myeloma tumors, but do not relate to known prognostic indicators or survival.

The myeloma plasma cell is a postgerminal center, isotype-switched B cell. Chromosomal translocations into immunoglobulin heavy chain (IgH) switch regions, recombination sites in isotype switching, were initially demonstrated in myeloma cell lines but only a limited number of primary tumors. Molecular cytogenetics have since been applied to a series of primary tumors, in which IgH translocations accounted for many recurrent aberrations, among numerous nonrecurrent changes of unknown significance. This study, therefore, examined primary myeloma for IgH switch translocations using an established Southern blot assay that detected illegitimate switch recombinations. Sensitivity of the method was established by confining the analysis to 21 samples (4 stable, 17 progressive disease) with demonstrable legitimate isotype switches, of a total of 60 samples. Illegitimate recombinations were found in 12 or 57% (1 stable, 11 progressive) of 21 samples, comparable with estimates by molecular cytogenetics. The presence of switch translocations was supported by demonstrating up-regulated expression in myeloma marrow of cyclin D1 and fibroblast growth factor receptor 3 (FGFR3), candidate oncogenes on chromosomes 11q13 and 4p16, respectively. Illegitimate switches were detected most frequently in Smu, with more than one region involved in 6 cases. Although these results confirmed the presence of switch translocations in primary myeloma, their absence in 43% of cases may imply heterogeneity of pathogenesis. In progressive disease, there was no significant difference between patients with and without illegitimate switches in survival, nor the prognostic indicators of beta(2) microglobulin (beta(2)m) and serum thymidine kinase (STK). Hence IgH switch translocations as a single entity are unlikely to be a feature of disease progression or have prognostic significance.

Adult↗

An outcome study of breast reconstruction: presurgical identification of risk factors for complications.

BACKGROUND: Breast reconstruction following mastectomy has been shown to have a salutary effect on the overall psychological well-being of women being treated for breast cancer. Unfortunately, however, not every patient is an ideal candidate for reconstruction. Complications stemming from reconstructive surgery can cause significant morbidity, the most important of which may be the delay of subsequent adjuvant antineoplastic therapies, and therefore may not be in the best interests of the patient. METHODS: A retrospective study was performed on a consecutive series of 123 breast reconstructions in 98 patients, performed by one of two plastic surgeons, in a university setting over a 5-year period, for all surgical outcomes. Specifically, wound-healing complications, infections, and reoperations leading to the potential delay of subsequent chemotherapy or radiotherapy were recorded, and possible risk factors leading to these were sought. RESULTS: Three presurgical risk factors were found to have a statistically significant influence on the development of complications following breast reconstruction. These were: (1) increasing obesity, defined by the body mass index, (2) an active or recent (<5 year) history of cigarette smoking, and (3) a history of previous radiation exposure. Odds ratios were used to describe the magnitude of the effect of each factor for the development of complications. An ordinal regression analysis was used to create a nomogram based on this information that can be used to calculate any individual patient's presurgical risk for developing major complications following breast reconstruction, based on the presence of these factors. CONCLUSIONS: It is possible, based on the presence of specific presurgical risk factors, to predict the probability of developing major complications following breast reconstruction. This information can be useful to the referring physician and plastic surgeon alike in determining which patients are the best candidates for breast reconstruction and which type of reconstruction would be best suited for each individual patient.

Adult↗

Oxidation of galactose by galactose-1-phosphate uridyltransferase-deficient lymphoblasts.

The ability of EB virus-transformed lymphoblasts with undetectable galactose-1-phosphate uridyltransferase (GALT) from 15 galactosaemic patients to oxidize [1-(14)C]galactose to 14CO2 was compared to that of cells from 7 normal subjects. The oxidation of galactose but not of glucose was markedly diminished by cells from Q188R homozygous galactosaemic patients but was not absent. After 2.5 h these cells liberated 14CO2 at nearly 3% and at 5 h up to 9% of normal. Cells from patients homozygous for the S135L mutation produced much larger amounts of 14CO2 (15-17% of normal) and were distinguishable from the Q188R homozygous cells. A cell line with a homozygous deletion of the GALT gene oxidized galactose at 7% of the normal rate, suggesting that pathways(s) other than GALT exist in these cells as well as Q188R homozygous cells for oxidation of galactose to CO2. Concentration dependence studies are consistent with the presence of a pathway that is unsaturable or has a very high Km The ability of 10(7) lymphoblasts with the S135L genotype to oxidize more than 7% of the sugar to 14CO2 in 5 h suggests the presence of residual GALT despite the inability to detect the activity by enzymatic analysis.

Adolescent↗

Neonatal hypoglycaemia in severe succinyl-CoA: 3-oxoacid CoA-transferase deficiency.

Succinyl-CoA: 3-oxoacid CoA-transferase (SCOT) deficiency is an inborn error of ketone body utilization, characterized by intermittent ketoacidotic crises and persistent ketosis. The diagnosis was suspected in a patient who presented with hypoglycaemia, ketoacidosis and coma at 4 days of age. The hypoglycaemic tendency was only observed during the first month of life. A novel macromolecular labelling assay in cultured skin fibroblasts using D-3-hydroxy[3-14C]butyrate supported the diagnosis. Subsequently, 9% residual SCOT activity and undetectable cross-reactive protein were noted in fibroblasts and the patient was found to be homozygous for the G324E SCOT gene mutation. By 7 years of age, recurrent episodes of ketoacidosis superimposed on persistent hyperketonaemia had resulted in over 25 hospitalizations requiring intravenous fluid, glucose and sodium bicarbonate therapy. He has had normal growth but developmental delay and attention deficit-hyperactivity disorder. A continuous intravenous glucose infusion at 38 microlmol (6.8 mg)/kg per min reduced plasma total ketone levels from greater than 1.5 mmol/L to less than 0.5 mmol/L after 48 h. This indicates that patients with SCOT deficiency do not always manifest ketosis with administration of a sufficient amount of carbohydrates, but that even under such conditions hyperketonaemia is difficult to eliminate completely. The presence of hypoglycaemia does not exclude the diagnosis of SCOT deficiency in infancy.

Attention Deficit Disorder with Hyperactivity↗

Autotransplants for Hodgkin's disease in first relapse or second remission: a report from the autologous blood and marrow transplant registry (ABMTR).

Although patients with relapsed Hodgkin's disease have a poor prognosis with conventional therapies, high-dose chemotherapy and autologous hematopoietic stem cell transplantation (autotransplantation) may provide long-term progression-free survival. We reviewed data from the Autologous Blood and Marrow Transplant Registry (ABMTR) to determine relapse, disease-free survival, overall survival, and prognostic factors in this group of patients. Detailed records from the ABMTR on 414 patients with Hodgkin's disease in first relapse (n = 295) or second complete remission (CR) (n = 119) receiving an autotransplant from 1989 to 1995 were reviewed. Median age was 29 (range, 7-64) years. Median time from diagnosis to relapse was 18 (range, 6-219) months; median time from relapse to transplant was 5 (range, <1-215) months. Most patients received high-dose chemotherapy without total body irradiation for conditioning (n = 370). The most frequently used high-dose regimen was cyclophosphamide, BCNU, VP-16 (CBV) (n = 240). The graft consisted of bone marrow (n = 246), blood stem cells (n = 112), or both (n = 56). Median follow-up was 46 (range, 5-96) months. One hundred-day mortality (95% confidence interval) was 7 (5-9)%. One hundred and sixty-five of 295 patients (56%) transplanted in relapse achieved CR after autotransplantation. Of these, 61 (37%) recurred. Twenty-four of 119 patients (20%) transplanted in CR recurred. The probability of disease-free survival at 3 years was 46 (40-52)% for transplants in first relapse and 64 (53-72)% for those in second remission (P < 0.001). Overall survival at 3 years was 58 (52-64)% after transplantation in first relapse and 75 (66-83)% after transplantation in second CR (P < 0.001). In multivariate analysis, Karnofsky performance score <90% at transplant, abnormal serum LDH at transplant, and chemotherapy resistance were adverse prognostic factors for outcome. Progression of Hodgkin's disease accounted for 69% of all deaths. Autotransplantation should be considered for patients with Hodgkin's disease in first relapse or second remission. Future investigations should focus on strategies designed to decrease relapse after autotransplantation, particularly in patients at high risk for relapse.

Adolescent↗

Allogeneic haemopoietic cell transplants in Australia, 1996--a multi-centre retrospective comparison of the use of peripheral blood stem cells with bone marrow.

A retrospective comparison was carried out on adult patients receiving HLA-identical allogeneic haemopoietic stem cell transplants from siblings in Australia in 1996, comparing bone marrow with G-CSF-mobilised peripheral blood stem cells. A total of 131 transplant recipients from nine centres were included in this study, of whom 79 received bone marrow, 44 blood stem cells and eight both. All but three of the 131 patients had cyclosporin and methotrexate as graft-versus-host disease prophylaxis. The minimum follow-up time for surviving patients is 27 months. Comparisons were carried out between the BM and PBSC groups. There were no significant differences between groups in age, sex, diagnosis, donor characteristics or pretransplant conditioning. Median time to neutrophil recovery of 0.5 x 10(9)/l was 14 days for PBSC recipients, compared to 19 days for marrow recipients (P < 0.0005). median time to platelet recovery of 20 x 10(9)/l was 17 days for PBSC recipients, compared to 28 days for marrow recipients (P < 0.0005). there were no significantly increased risks of either acute or chronic GVHD in the PBSC recipients. there were no significant differences between the groups in the incidence of major transplant-related complications, disease-free survival or overall survival.

Adolescent↗

Amplified fragment length polymorphism genotyping of metronidazole-resistant Helicobacter pylori infecting dyspeptics in England.

OBJECTIVE: Intra-specific diversity of Helicobacter pylori infecting stomachs of different individuals was investigated by numerical analysis of amplified fragment length polymorphisms (AFLP), to determine the existence of clones within the strain population and the effect that antibiotic treatment, particularly with metronidazole (Mtz), had on the balance of types/subtypes present before and after treatment. METHODS: The 92 cultures studied comprised 89 single or multiple (pre- and post-treatment) isolates from gastric biopsies from 35 dyspeptic patients at two geographical locations in England, and three reference strains. HindIII restriction fragments tagged with specific adaptors were used as template DNA for AFLP. Patterns were coded in binary format according to deduced sizes of amplified fragments, and numerical analysis was performed. RESULTS: H. pylori isolated from different individuals were highly diverse (43 AFLP types) with a continuum of similarities that included three putative strain clusters at the 55% similarity level. Twelve sets each comprised identical isolates but subclonal variants with similarities of 82-99% coexisted in isolate sets from 19 patients. Seven sets contained strains with different AFLP types which for several corresponded with vacA/cagA genotypic differences. Mtz resistance was a feature of clonal as well as unrelated isolates. CONCLUSIONS: AFLP profiling was a robust, reproducible and highly discriminatory means of indexing H. pylori strain diversity, and the numerical analysis enabled clonal/subclonal variants infecting an individual to be defined and contrasted with the general species diversity. The majority (65%) of patients had co-infections with different strain types/subtypes but antibiotic treatment apparently did not markedly modify H. pylori population diversity in individual stomachs. Mtz sensitivity was generally associated with greater strain diversity as several subtypes often coexisted in sensitive pretreatment strain sets. In contrast, Mtz-resistant strain populations were less diverse, which was attributed to selection by previous exposure to nitroimidazoles in the same or a different host.

Anti-Bacterial Agents↗

Living with rheumatoid arthritis: the role of daily spirituality and daily religious and spiritual coping.

The objective of this preliminary study was to evaluate more fully the role of daily spiritual experiences and daily religious/spiritual coping in the experience of individuals with pain due to rheumatoid arthritis (RA). Thirty-five individuals with RA were asked to keep a structured daily diary for 30 consecutive days. The diary included standardized measures designed to assess spiritual experiences, religious and spiritual pain coping, salience of religion in coping, religious/spiritual coping efficacy, pain, mood, and perceived social support. The participants in this study reported having spiritual experiences, such as feeling touched by the beauty of creation or feeling a desire to be closer or in union with God, on a relatively frequent basis. These participants also reported using positive religious and spiritual coping strategies much more frequently than negative religious and spiritual coping strategies. Although most of the variance in these measures was due to differences between persons, each measure also displayed a significant variability in scores from day to day. Indeed, there was just as much (or more) variability in these measures over time as there was variability in pain. Individuals who reported frequent daily spiritual experiences had higher levels of positive mood, lower levels of daily negative mood, and higher levels of each of the social support domains. Individuals who reported that religion was very salient in their coping with pain reported much higher levels of instrumental, emotional, arthritis-related, and general social support. Coping efficacy was significantly related to pain, mood, and social support in that on days that participants rated their ability to control pain and decrease pain using spiritual/religious coping methods as high, they were much less likely to have joint pain and negative mood and much more likely to have positive mood and higher levels of general social support. Taken together, these results suggest that daily spiritual experiences and daily religious/spiritual coping variables are important in understanding the experience of persons who have RA. They also suggest that newly developed daily diary methods may provide a useful methodology for studying religious and spiritual dimensions of living with arthritis.

Journal Article↗

Intraoperative plateletpheresis and autologous platelet gel do not reduce chest tube drainage or allogeneic blood transfusion after reoperative coronary artery bypass graft.

Platelet-rich plasma (PRP) is postulated to decrease postoperative mediastinal chest tube drainage (MCTD) and allogeneic blood transfusions (ABT) after surgery with cardiopulmonary bypass. However, recent metaanalysis of the literature reveals that few good quality (therapeutic yield) trials that show a benefit have been published. The potential hemodynamic instability caused by plateletpheresis has not been emphasized. We studied the effect of plateletpheresis on MCTD, ABT, and hemodynamic stability in reoperative coronary artery bypass graft patients, a group perceived to be at high risk for ABT. Ninety patients were randomly assigned to Pheresis or Control groups. epsilon-Aminocaproic acid was given to all patients. Hemodynamic instability was assessed by degree of volume and inotrope resuscitation required. Part of the sequestered platelet volume was used to make autologous platelet gel, which was applied as a wound sealant. Mean pheresis yield was 30% +/- 7% of the circulating platelet mass or 6.4 +/- 2.2 allogeneic platelet unit equivalents. Total MCTD did not differ between the groups. There were no differences in mean packed red blood cell, platelet, and plasma transfusion rates. Overall, 52% of the Pheresis group received ABT, versus 55% of the Control group. Fifty-three percent of the Pheresis group patients exhibited significant hemodynamic instability, versus 27% of the Control group (P < 0.05). This study was unable to show any reduction in MCTD or ABT, although the plateletpheresis technique may offset platelet dysfunction caused by aspirin or increased blood exposure to nonbiologic surfaces, or it may compensate for lack of antifibrinolytic use. The significantly increased incidence of hemodynamic instability in the Pheresis group means that the risk/benefit ratio must be determined for individual cardiac surgical units.

Aged↗

Reductive, coenzyme A-mediated pathway for 3-chlorobenzoate degradation in the phototrophic bacterium Rhodopseudomonas palustris.

We isolated a strain of Rhodopseudomonas palustris (RCB100) by selective enrichment in light on 3-chlorobenzoate to investigate the steps that it uses to accomplish anaerobic dechlorination. Analyses of metabolite pools as well as enzyme assays suggest that R. palustris grows on 3-chlorobenzoate by (i) converting it to 3-chlorobenzoyl coenzyme A (3-chlorobenzoyl-CoA), (ii) reductively dehalogenating 3-chlorobenzoyl-CoA to benzoyl-CoA, and (iii) degrading benzoyl-CoA to acetyl-CoA and carbon dioxide. R. palustris uses 3-chlorobenzoate only as a carbon source and thus incorporates the acetyl-CoA that is produced into cell material. The reductive dechlorination route used by R. palustris for 3-chlorobenzoate degradation differs from those previously described in that a CoA thioester, rather than an unmodified aromatic acid, is the substrate for complete dehalogenation.

Biodegradation, Environmental↗

Relating palliative care principles to the promotion of undisturbed sleep in a hospice setting.

Nurses working at night have a specific role in supporting sleep and promoting rest and comfort. Sometimes the role of the night duty nurse in promoting sleep and comfort is taken for granted. One author's experience of working as a night duty nurse led to reflection on her responsibilities in improving practice and addressing the sleep-related needs of patients in a palliative care setting. Following a literature review, it was clear that there are very few publications on sleep disturbance in palliative care. Using the four principles of palliative care (Aranda, 1998a), the authors construct a series of strategies to prevent and manage sleep issues.

Health Facility Environment↗

Induction of mucosal and systemic antibody specific for SeMF3 of Streptococcus equi by intranasal vaccination using a sucrose acetate isobutyrate based delivery system.

Streptococcus equi causes equine strangles, a highly contagious disease of the upper respiratory tract. The antiphagocytic surface protein SeM is strongly immunogenic and evokes mucosal and systemic antibodies during convalescence. The present study investigated the potential of sucrose acetate isobutyrate (SAIB); a high viscosity excipient that provides controlled release of biologically active substances, to enhance antibody responses following intranasal immunization of horses with a 108 a.a. peptide of SeM (SeMF3). SeMF3-SAIB was administered intranasally to each of the 11 adult horses on days 0 and 28. A second group of seven horses was vaccinated with SeMF3 alone. SAIB enhanced the mucosal and systemic immunogenicity of SeMF3, whereas SeMF3 by itself stimulated only a shortlived mucosal IgA and no systemic response. Moreover, nasal mucosal responses of horses immunized with SeMF3-SAIB were qualitatively and quantitatively similar to those observed in convalescent horses and involved similar linear epitopes of SeM. Epitope analysis also suggested that the nasal response was different from that observed in serum. A booster response was obtained after the second vaccination. These results suggest that SAIB has potential as a vehicle for intranasal immunization of horses with antigenic peptides.

Administration, Intranasal↗

B7-2-positive myeloma: incidence, clinical characteristics, prognostic significance, and implications for tumor immunotherapy.

Deficiencies in B7:CD28 costimulation are considered to be one of the major causes of the failure to generate a tumor-specific immune response. Up-regulating the expression of the B7 molecules on malignant B cells has been shown to stimulate cytotoxic T cells. Plasma cells from patients with myeloma express a tumor-specific idiotype but lack CD80 (B7-1) and have a variable expression of CD86 (B7-2). This study has identified the incidence and clinical significance of high CD86 expression on plasma cells at diagnosis and studied the ability of trimeric human CD40 ligand (huCD40LT) to up-regulate the expression of the B7 family on malignant plasma cells. CD86 expression on plasma cells was increased in 54% of the patients studied at diagnosis (n = 35) and was associated with a significantly shorter survival (median, 28 versus 57 months; chi(2) = 4.6; P =.03) and a higher tumor load (patients with more than 50% bone marrow plasma cells, 47% versus 6%; chi(2) = 7.2; P =.005). CD86 expression was highest on immature and primitive plasma cells (CD38(++), CD45(+)) of both patients and controls and was associated with a CD40(+), CD20(+), CD19(-), CD138(+) phenotype. The shortened survival was associated with high CD86 only on mature (CD38(++), CD45(-)) plasma cells (chi(2) = 7.6; P =.006). There was no significant correlation between high CD86 and other known prognostic markers, including serum beta(2)-microglobulin, serum thymidine kinase, and labeling index. The addition of huCD40LT to short-term cultures up-regulated both CD80 and CD86 expression on B cells (CD19(+)) and CD80 on plasma cells (CD38(++)), but did not up-regulate CD86 expression on plasma cells. Thus, B7-2-positive myeloma consists of a subgroup of patients with a relatively poor prognosis, and CD40LT may be useful in immunotherapy protocols because it up-regulates CD80 expression on malignant plasma cells without inducing B7-2-positive myeloma. (Blood. 2000;96:1274-1279)

Adult↗

Monoalleleic transcription of the insulin-like growth factor-II gene (Igf2) in chick embryos.

A polymorphism in the igf2 gene of chickens was identified using NlaIII (GenBank accession number AF218827). In some embryos, the igf2 alleles were expressed monoallelically from either maternal or paternal alleles. These data demonstrate that genomic imprinting is not confined to mammalian vertebrates and suggest that genomic imprinting evolved at an early stage of vertebrate evolution. The observations that the igf2 gene is imprinted in a minority of embryos suggest that the imprinting in birds is unrelated to embryonic growth. Genome imprinting may provide opportunities for evolution of genes in a nonexpressed state. In poultry breeding, the presence of imprinted genes may make a major contribution to unequal performance in reciprocal matings between commercial lines.

Alleles↗

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Journal Article↗

CD34+ selection of autologous peripheral blood stem cells for transplantation following sequential cycles of high-dose therapy and mobilization in multiple myeloma.

A potential problem of autologous transplantation in the treatment of multiple myeloma (MM) is the infusion of tumor cells. CD34+ selection has been used to purge autografts in MM and it is also possible to reduce tumour cell contamination of autografts by cytotoxic drug therapy prior to peripheral blood stem cell (PBSC) collection. To evaluate the effectiveness of a protocol combining multiple cycles of high-dose therapy and CD34+ selection to reduce tumour contamination of PBSC autografts, 34 MM patients were entered on a treatment schedule comprising two sequential cycles of mobilisation, CD34+ selection, and transplantation following high-dose therapy. In the second cycle of mobilisation there was a five-fold reduction in tumour contamination of the stem cell harvest (0.5 x 106/kg) compared with the first cycle (2.5 x 106/kg). In the 97 CD34+ selection procedures performed a median of 185 x 108 mononuclear cells (MNC) were processed yielding a median of 0.98 x 108 CD34+-enriched cells. CD34+ cells were enriched 68-fold from 1. 3% to 88.6%. The median yield of CD34+ cells was 42.2%. Following CD34+ selection the tumour cell contamination of the leukapheresis product was reduced by a median of 2.7 logs. This study demonstrates that in multiple myeloma a significant reduction in the malignant contamination of stem cell autografts can be achieved by combining the in vivo purging effect of cytotoxic therapy with in vitro purging by CD34+ selection.

Adult↗