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Biomedical subjects

J Gibson

Publications and source records attributed to J Gibson.

At least 19 recordsLinked to original sources
PubMed1997

Results of transplanting bone marrow from genetically identical twins into patients with aplastic anemia.

BACKGROUND: Aplastic anemia is caused by several diverse factors, including a lack of or defective hematopoietic stem cells, immune abnormalities, and disorders of the bone marrow microenvironment. The outcome of transplanting bone marrow from genetically identical twins into patients with aplastic anemia may help define how frequently these factors play a role in this condition. OBJECTIVE: To determine the outcome of transplanting bone marrow from genetically identical twins into patients with aplastic anemia. DESIGN: Observational study. SETTING: 31 centers participating in the international Bone Marrow Transplant Registry. PATIENTS: 40 patients with aplastic anemia who received bone marrow transplants from their genetically identical twins between 1964 and 1992. INTERVENTION: 23 patients received their first bone marrow transplant without pretransplantation conditioning; 17 received it after pretransplantation conditioning with cyclophosphamide alone or combined with other drugs or radiation. Six patients received post-transplantation immunosuppressive therapy with methotrexate, cyclosporine, and corticosteroids, alone or in combination. MEASUREMENTS: Outcomes of transplantation, including hematologic recovery and survival. RESULTS: Seven of 23 patients who received their first transplant without receiving conditioning had sustained complete hematologic recovery. One of 16 patients who did not have complete recovery after the first transplantation recovered after a second transplantation, which was not preceded by conditioning. The other 15 patients had two to five transplantations that were preceded by conditioning; in 13 patients, sustained bone marrow function was recovered. Twelve of 17 patients whose first transplantation was preceded by conditioning had sustained complete hematologic recovery. The likelihood of hematologic recovery was greater in patients who had conditioning before the first transplantation (P = 0.033). The actuarial 10-year survival rate for the 40 patients was 78% (95% CI, 59% to 92%). The survival rate was higher in patients who did not have conditioning before the first transplantation (patients without conditioning, 87% [range, 65% to 99%]; patients with conditioning, 70% [range, 47% to 89%]; P = 0.037). CONCLUSIONS: Most patients with aplastic anemia recover bone marrow function after receiving a transplant from a genetically identical twin. Pretransplantation conditioning may increase the chance of bone marrow recovery but does not seem to improve survival.

Adolescent↗
PubMed1997

Application of the Mast resistotyping scheme to Campylobacter jejuni and C. coli.

The Mast resistotyping scheme was assessed with 228 strains of Campylobacter jejuni and C. coli from enteric infections in man and from a diverse selection of other sources (livestock, chickens and river water). Most (153 of 158) C. jejuni examined were of the three most common Penner (heat stable, HS) serotypes, HS1, HS2 and HS4 complex. Fourteen resistotypes were identified in the 158 strains of C. jejuni and 16 in the 70 isolates of C. coli. The predominant codes were 00 (44% of C. jejuni; 33% of C. coli) and 40 (21% of both species). The scheme was simple to use but reproducibility and interpretation of sensitivity zones--notably for fluorouracil, triphenyltetrazolium chloride and metronidazole--was occasionally problematic. Overall, resistotypes did not correlate with Penner HS serotypes or with three key genomic markers (ribotype, PFGE macrorestriction-type and fla-type). Although resistotyping offers a rapid means for distinguishing between some strains of C. jejuni and C. coli, discrimination for common resistotypes can be achieved only in combination with other typing methods.

Animals↗
PubMed1997

4-hydroxybenzoyl coenzyme A reductase (dehydroxylating) is required for anaerobic degradation of 4-hydroxybenzoate by Rhodopseudomonas palustris and shares features with molybdenum-containing hydroxylases.

The anaerobic degradation of 4-hydroxybenzoate is initiated by the formation of 4-hydroxybenzoyl coenzyme A, with the next step proposed to be a dehydroxylation to benzoyl coenzyme A, the starting compound for a central pathway of aromatic compound ring reduction and cleavage. Three open reading frames, divergently transcribed from the 4-hydroxybenzoate coenzyme A ligase gene, hbaA, were identified and sequenced from the phototrophic bacterium Rhodopseudomonas palustris. These genes, named hbaBCD, specify polypeptides of 17.5, 82.6, and 34.5 kDa, respectively. The deduced amino acid sequences show considerable similarities to a group of hydroxylating enzymes involved in CO, xanthine, and nicotine metabolism that have conserved binding sites for [2Fe-2S] clusters and a molybdenum cofactor. Cassette disruption of the hbaB gene yielded a mutant that was unable to grow anaerobically on 4-hydroxybenzoate but grew normally on benzoate. The hbaB mutant cells did not accumulate [14C]benzoyl coenzyme A during short-term uptake of [14C]4-hydroxybenzoate, but benzoyl coenzyme A was the major radioactive metabolite formed by the wild type. In addition, crude extracts of the mutant failed to convert 4-hydroxybenzoyl coenzyme A to benzoyl coenzyme A. This evidence indicates that the hbaBCD genes encode the subunits of a 4-hydroxybenzoyl coenzyme A reductase (dehydroxylating). The sizes of the specified polypeptides are similar to those reported for 4-hydroxybenzoyl coenzyme A reductase isolated from the denitrifying bacterium Thauera aromatica. The amino acid consensus sequence for a molybdenum cofactor binding site is in HbaC. This cofactor appears to be an essential component because anaerobic growth of R. palustris on 4-hydroxybenzoate, but not on benzoate, was retarded unless 0.1 microM molybdate was added to the medium. Neither tungstate nor vanadate replaced molybdate, and tungstate competitively inhibited growth stimulation by molybdate.

Amino Acid Sequence↗
PubMed1996

The Ontario trial of active compression-decompression cardiopulmonary resuscitation for in-hospital and prehospital cardiac arrest.

OBJECTIVE: To compare the impact of active compression-decompression (ACD) cardiopulmonary resuscitation (CPR) and standard CPR on the outcomes of in-hospital and prehospital victims of cardiac arrest. DESIGN: Randomized controlled trial with blinding of allocation using a sealed container. SETTINGS: (1) Emergency departments, wards, and intensive care units of 5 university hospitals and (2) all locations outside hospitals in 2 midsized cities. PATIENTS: A total of 1784 adults who had cardiac arrest. INTERVENTION: Patients received either standard or ACD CPR throughout resuscitation. MAIN OUTCOME MEASURES: Survival for 1 hour and to hospital discharge and the modified Mini-Mental State Examination (MMSE). RESULTS: All characteristics were similar in the standard and ACD CPR groups for the 773 in-hospital patients and the 1011 prehospital patients. For in-hospital patients, there were no significant differences between the standard (n = 368) and ACD (n = 405) CPR groups in survival for 1 hour (35.1% vs 34.6%; P = .89), in survival until hospital discharge (11.4% vs 10.4%; P = .64), or in the median MMSE score of survivors (37 in both groups). For patients who collapsed outside the hospital, there were also no significant differences between the standard (n = 510) and ACD (n = 501) CPR groups in survival for 1 hour (16.5% vs 18.2%; P = .48), in survival to hospital discharge (3.7% vs 4.6%; P = .49), or in the median MMSE score of survivors (35 in both groups). Exploration of clinically important subgroups failed to identify any patients who appeared to benefit from ACD CPR. CONCLUSIONS: ACD CPR did not improve survival or neurologic outcomes in any group of patients with cardiac arrest.

Adolescent↗
PubMed1996

The labelling index of primitive plasma cells determines the clinical behaviour of patients with myelomatosis.

For patients with multiple myeloma the most important laboratory correlate of prognosis and disease activity is the bromodeoxyuridine (BrdUrd) plasma cell labelling index (LI). However, the traditional immunofluorescent microscope LI technique, like other manual enumeration assays, can suffer from poor precision and accuracy. In this study the LI of different subpopulations of plasma cells (CD38++) as determined by flow cytometry was correlated with disease state. The mean LI of the total CD38++ population was significantly higher (2.7 +/- 0.4%) than the LI determined by the traditional slide technique (0.6 +/- 0.1%) for 65 samples tested. Primitive plasma cells (CD38++, CD45++) had a higher labelling index than mature plasma cells (CD38++, CD45-) (7.0 +/- 1.3% v 1.8% +/- 0.3%) and in one patient the LI of the primitive plasma cells was 46%. In addition, the LI of the mature plasma cells was lower than the total plasma cell population. As expected, there was a significant difference between the LI of patients in plateau phase and progressive disease but this difference was greatest when the LI of the primitive plasma cells was studied (9.2 +/- 2.9% v 2.2 +/- 0.7%; z = 19.9, P < 0.001). This study has raised some concerns about the sensitivity and accuracy of the traditional labelling index and has shown that the increased LI associated with progressive disease is almost entirely attributable to an increase in the LI of the primitive plasma cell subpopulation and that the LI of primitive plasma cells provides a more clinically significant correlation with disease status than the traditional assay.

ADP-ribosyl Cyclase↗
PubMed1996

Rapid quantitation of mixed red cell populations using flow cytometry.

Methods are described for the identification and quantitation of mixed red cell populations using flow cytometry. Antibodies specific for a wide range of blood group antigens have been used and examples are given in which these analyses have proved to be of clinical use. These examples include monitoring of erythropoiesis following engraftment in allogeneic bone marrow transplant recipients and the detection of chimaeric states months or years after transplantation. The techniques involved are fast, simple and inexpensive.

Bone Marrow Transplantation↗
PubMed1996

Nucleoside transporters, bcl-2 and apoptosis in CLL cells exposed to nucleoside analogues in vitro.

The purine nucleoside analogues fludarabine (F1) and chlorodeoxyadenosine (2-CdA) are considered to be cell cycle specific agents which require DNA synthesis for cytotoxicity. However, their efficacy in the treatment of CLL, an indolent lymphoid malignancy suggests additional mechanisms of action. Like cytosine arabinoside (AraC), F1 and 2-CdA gain access to the cell via a specific nucleoside transporter (NST) protein. To investigate the mode of action of these drugs in CLL, we used a fluorescent ligand for the NST (5'-(SAENTA- x8)-fluorescein) and 3-colour flow cytometry to determine NST expression on CD5+/CD19+ B-cells from the peripheral blood (PB) of patients with CLL. NST levels on these cells was found to be not significantly different from normal control lymphocytes (mean = 485 +/- 425) vs. (mean = 553 +/- 178). Exposure to varying concentrations (0, 3 microM and 30 microM) of F1 and 2-CdA, however, resulted in an upregulation of NST (mean = 1552 +/- 775 with 30 microM FL; mean = 3392 +/- 2197 with 30 microM 2-CdA) after 48. "Large" lymphoid cells (not present in normal PB) were found to express significantly more NST (mean = 2540 +/- 2861) and have a higher proliferative capacity than "small" cells (mean = 357 +/- 517 NST/cell). Incubation of CLL cells with F1 (n = 6) and 2-CdA (n = 8) in vitro over 48 h also resulted in an increase in the proportion of cells in S-phase (0 microM = 0.2 + 2 - 0.1; 30 microM FL = 2.4 +/- 2.0; 30 microM 2-CdA = 3.3 +/- 1.3) and a significant increase in morphologically identifiable apoptosis. Apoptosis was confirmed by flow cytometric DNA analysis (0 microM = 13 +/- 8%; 30 microM FL = 40 +/- 20%; 30 microM 2-CdA = 48 +/- 11%). In situ hybridization using a biotinylated cDNA bcl-2 probe demonstrated that bcl-2 mRNA expression was markedly decreased in treated cells after 24 h. These studies have demonstrated that: (1) NST expression on CLL lymphocytes is low; (2) in vitro exposure to the analogues increases both the level of NST expression and the % cells in S-phase; (3) exposure to the analogues downregulates bcl-2 expression and increases apoptosis.

Antigens, CD19↗
PubMed1996

Botulinum toxin type A in the treatment of upper extremity spasticity: a randomized, double-blind, placebo-controlled trial.

Spasticity is a disorder of excess muscle tone associated with CNS disease. We hypothesized that botulinum toxin, a neuromuscular blocking agent, would reduce tone in spastic muscles after stroke. This randomized, double-blind, placebo-controlled, multicenter clinical trial evaluated the safety and efficacy of botulinum toxin type A (BTXA) in the treatment of chronic upper limb spasticity after stroke. Thirty-nine patients received IM injections of a total dose of either 75, 150, or 300 units of BTXA or placebo into the biceps, flexor carpi radialis, and flexor carpi ulnaris muscles. At baseline, patients demonstrated a mean wrist flexor tone of 2.9 and elbow flexor tone of 2.6 on the Ashworth Scale (0 to 4). Treatment with the 300-unit BTXA dose resulted in a statistically and clinically significant mean decrease in wrist flexor tone of 1.2 (p = 0.028), 1.1 (p = 0.044), and 1.2 (p = 0.026) points and elbow flexor tone of 1.2 (p = 0.024), 1.2 (p = 0.028), and 1.1 (p = 0.199) at weeks 2, 4, and 6 postinjection. In the placebo group, tone reduction at the wrist was 0.3, 0.2, and 0.0 and at the elbow was 0.3, 0.3, and 0.6 at weeks 2, 4, and 6 postinjection. BTXA groups reported significant improvement on the physician and patient Global Assessment of Response to Treatment at weeks 4 and 6 postinjection. There were no serious adverse effects. In this 3-month study, BTXA safely reduced upper extremity muscle tone in patients with chronic spasticity after stroke.

Adult↗
PubMed1996

Autologous red cell recovery and relapse of multiple myeloma after bone marrow transplantation: is this a graft-versus-myeloma effect?

We report a patient who, following an allogeneic bone marrow transplant for multiple myeloma, recovered autologous erythropoiesis which was rapidly followed by relapse of her multiple myeloma. We postulate that the loss of the graft (as demonstrated by loss of donor erythropoiesis) and subsequent relapse of the multiple myeloma may be support for the existence of a graft-versus-myeloma effect.

Adult↗
PubMed1995

Safety, pharmacokinetics, and antiviral response of CD4-immunoglobulin G by intravenous bolus in AIDS and AIDS-related complex.

To assess the safety, pharmacokinetics, and antiviral effects of intravenous recombinant CD4 immunoglobulin G (CD4-IgG), a 12-week Phase One study with an optional maintenance phase was performed. Twenty-two subjects with advanced human immunodeficiency virus (HIV) infection were enrolled; 15 subjects completed the initial 12 weeks. CD4-IgG doses were 30, 100, or 300 micrograms/kg weekly; 1,000 micrograms/kg once, twice, or three times per week; or 3,000 micrograms/kg twice weekly. Serum concentrations of CD4-IgG increased linearly with dose, with average peak serum concentrations of 22 micrograms/ml with 1,000 micrograms/kg. CD4-IgG was well tolerated; one patient had self-limited tachycardia and flushing associated with CD4-IgG therapy. No changes were seen in CD4 cell counts, hematologic or coagulation studies, serum chemistries, HIV p24 antigen titers, or plasma HIV titers. No subject developed anti-CD4 antibodies. HIV isolates from five patients had IC90 values that were higher than the peak concentrations of CD4-IgG achieved in those patients. Additional studies that achieve higher CD4-IgG concentrations are necessary to evaluate the antiviral activity of this compound.

AIDS-Related Complex↗