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Biomedical subjects

J Gibson

Publications and source records attributed to J Gibson.

At least 109 records · Page 6Linked to original sources
PubMed1998

Inhibition of delayed rectifier K+ channels by dexfenfluramine (Redux).

In light of recent reports linking K+ channel modulation with food intake and macronutrient preference, we investigated the effect of anorectic agent dexfenfluramine (d-FF), a 5-HT reuptake inhibitor and releasing agent, on the delayed rectifier K+ (DRK) channels in rat lingual taste cells using the patch-clamp technique in whole-cell configuration. In a concentration-dependent manner, d-FF caused a reduction of the DRK currents in taste cells with an IC50 of 30.5 microM. Other anorectics that promote 5-HT activity such as fenfluramine, sibutramine and m-chlorophenylpiperazine (a specific 5-HT2C receptor agonist) produced inhibition of DRK currents of a similar pattern with a respective IC50 of 69.0, 8.6 and 95.4 microM. The actions of all compounds had rapid onset and were readily reversible. The inhibitory effects were not secondary to their stimulation of 5-HT, because direct application of 5-HT up to 1 mM did not alter DRK current. In addition, d-FF-induced current reduction was not prevented by either the 5-HT synthesis inhibitor p-chlorophenylalanine or 5-HT receptor antagonist metergoline. d-FF was also tested in cardiac ventricular myocytes that are reportedly abundant in DRK channels and was found to depress the DRK currents concentration-dependently with an IC50 of 250.9 microM. These results indicate an important pharmacological role for d-FF as an inhibitor of the DRK channels. The common inhibitory effect on DRK channels in oral taste cells and cardiac cells by this class of compounds might contribute to the anorectic and some of the detrimental cardiovascular effect associated with long-term exposure.

Animals↗
PubMed1998

A flow-cytometric equivalent of the Kleihauer test.

BACKGROUND AND OBJECTIVES: The Kleihauer slide test is in general use to screen obstetric patients for possible fetomaternal haemorrhage. Since 1993, Rh(D)-negative patients have been tested in our laboratory by a flow-cytometric method detecting Rh(D)-positive fetal cells, a method which offers improved sensitivity and accuracy. We report another flow-cytometric method of broader application which quantitates cells according to haemoglobin F (HbF) content. MATERIALS AND METHODS: The red cells are fixed with glutaraldehyde and permeabilized by exposure to Triton X-100. A polyclonal sheep antibody to HbF is incubated with the cells followed by a fluorescein-labelled anti-sheep antibody. RESULTS: Quantitation of the percentage of fetal cells following a FMH can be achieved irrespective of the blood groups of either mother or infant, and the presence of maternal F cells need not interfere since the intensity of staining is usually less than that of fetal cells. Two of 19 transfusion-dependent patients with beta-thalassaemia have been found to have red cells indistinguishable from fetal cells on the basis of HbF content, but these patients also have been found to give positive results by the Kleihauer test. CONCLUSIONS: The flow-cytometric method may serve to replace the traditional Kleihauer test since it appears to offer improved accuracy and objectivity.

Erythrocytes↗
PubMed1997

A quantitative description of short-term plasticity at excitatory synapses in layer 2/3 of rat primary visual cortex.

Cortical synapses exhibit several forms of short-term plasticity, but the contribution of this plasticity to visual response dynamics is unknown. In part, this is because the simple patterns of stimulation used to probe plasticity in vitro do not correspond to patterns of activity that occur in vivo. We have developed a method of quantitatively characterizing short-term plasticity at cortical synapses that permits prediction of responses to arbitrary patterns of stimulation. Synaptic responses were recorded intracellularly as EPSCs and extracellularly as local field potentials in layer 2/3 of rat primary visual cortical slices during stimulation of layer 4 with trains of electrical stimuli containing random mixtures of frequencies. Responses exhibited complex dynamics that were well described by a simple three-component model consisting of facilitation and two forms of depression, a stronger form that decayed exponentially with a time constant of several hundred milliseconds and a weaker, but more persistent, form that decayed with a time constant of several seconds. Parameters obtained from fits to one train were used to predict accurately responses to other random and constant frequency trains. Control experiments revealed that depression was not caused by a decrease in the effectiveness of extracellular stimulation or by a buildup of inhibition. Pharmacological manipulations of transmitter release and postsynaptic sensitivity suggested that both forms of depression are mediated presynaptically. These results indicate that firing evoked by visual stimuli is likely to cause significant depression at cortical synapses. Hence synaptic depression may be an important determinant of the temporal features of visual cortical responses.

Animals↗
PubMed1997

A cluster of bacterial genes for anaerobic benzene ring biodegradation.

A reductive benzoate pathway is the central conduit for the anaerobic biodegradation of aromatic pollutants and lignin monomers. Benzene ring reduction requires a large input of energy and this metabolic capability has, so far, been reported only in bacteria. To determine the molecular basis for this environmentally important process, we cloned and analyzed genes required for the anaerobic degradation of benzoate and related compounds from the phototrophic bacterium, Rhodopseudomonas palustris. A cluster of 24 genes was identified that includes twelve genes likely to be involved in anaerobic benzoate degradation and additional genes that convert the related compounds 4-hydroxybenzoate and cyclohexanecarboxylate to benzoyl-CoA. Genes encoding benzoyl-CoA reductase, a novel enzyme able to overcome the resonance stability of the aromatic ring, were identified by directed mutagenesis. The gene encoding the ring-cleavage enzyme, 2-ketocyclohexanecarboxyl-CoA hydrolase, was identified by assaying the enzymatic activity of the protein expressed in Escherichia coli. Physiological data and DNA sequence analyses indicate that the benzoate pathway consists of unusual enzymes for ring reduction and cleavage interposed among enzymes homologous to those catalyzing fatty acid degradation. The cloned genes should be useful as probes to identify benzoate degradation genes from other metabolically distinct groups of anaerobic bacteria, such as denitrifying bacteria and sulfate-reducing bacteria.

Aerobiosis↗
PubMed1997

A 33.5-kDa heat- and protease-resistant NADH oxidase inhibited by capsaicin from sera of cancer patients.

Sera from patients with a variety of cancers, including solid carcinomas, leukemias, and lymphomas, contain a ca. 33.5-kDa protein absent from sera of healthy volunteers or patients not diagnosed as having cancer. The protein exhibits an NADH oxidase activity inhibited by 8-methyl-N-vanillyl-6-noneamide (capsaicin). The activity and the protein are resistant to digestion by proteases (trypsin, chymotrypsin, proteinase K, subtilisin) and to heat. Following protease digestion to reduce the content of major serum proteins, the 33.5-kDa protein could be detected on Western blots of SDS-PAGE transferred to nitrocellulose membranes using polyclonal antisera to a corresponding partially purified 33.5-kDa protein shed into culture media conditioned by growth of HeLa cells. No corresponding protein was seen with control sera. The findings confirm the capsaicin-inhibited NADH oxidase activity of cancer sera as a circulating marker potentially specific to sera of cancer patients and identify a ca. 33.5-kDa protein resistant to proteases and heat as the source of the circulating capsaicin-inhibited NADH oxidase activity.

Animals↗
PubMed1997

Pharmaceutical services in the United States Navy.

The status of pharmaceutical services in the United States Navy is described. In support of operational forces, pharmacists serve on hospital ships and in tent-based-fleet hospitals. The Navy has a long-term commitment to ensuring that its pharmacists receive postgraduate education and training; each year, pharmacists are selected for specific programs. Pharmacy technicians in the Navy have considerably more responsibility than their civilian counterparts; all complete a 23-week course, and many are board certified. Increasingly, Navy pharmacists provide pharmacokinetic services, counsel patients, serve as an information resource for provides, work in pharmacist-managed clinics, develop clinical pathways, and evaluate drug therapy. Automation and computerization are viewed as answers to challenges created by continued "rightsizing" of the staff and fiscal restraints. A project is under way that will consolidate historical and current patient information for improved clinical decision-making. The scope of Navy pharmacy practice is expanding dramatically.

Automation↗
PubMed1997

Reproductive measurements in Sinclair and NIH miniature pigs: a retrospective analysis.

The data presented here represent a retrospective analysis of information gathered while collecting data for other studies on miniature pigs. Two different breeds of miniature pigs, NIH and Sinclair, were used in this study. The NIH females were gilts, while Sinclair females included both gilts and sows. The pigs were checked twice a day for estrus and were mated at 12 and 24 h after the onset of estrus. One- and 2-cell stage embryos were collected on Day 2; while 4-cell, 8-cell, compact morula and blastocyst stage embryos were collected on Days 2.7, 3.5, 4.3 and 6.0, respectively. The percentage of recovery of these embryos was dependent upon the surgeon (P = 0.002) and the stage of development (P = 0.018). The number of ovulations was higher (P < 0.04) in the Sinclair sows (10.4 +/- 0.60) than in the Sinclair gilts (8.9 +/- 0.67) and in the NIH gilts (8.3 +/- 0.67). When the NIH gilts were divided into swine leukocyte antigen (SLA) haplotypes, it was found that SLA(dd) gilts (8.5 +/- 0.43) had more ovulations (P = 0.02) than SLA(ad) gilts (6.8 +/- 0.57). Some animals were treated with Regumate to synchronize estrus. The Sinclair gilts (7.8 +/- 0.28) and NIH gilts (7.7 +/- 0.27) took more days (P < 0.07) to show estrus than the Sinclair sows (6.3 +/- 0.58) after the removal of Regumate. Four of the animals had reproductive tract abnormalities; more specifically, a blind uterine horn or oviduct that was not patent with the other horn. All 4 were NIH gilts with the SLA(dd) haplotype.

Journal Article↗
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

Electromotive drug administration of lidocaine and dexamethasone followed by cystodistension in women with interstitial cystitis.

Electromotive drug administration (EMDA) involves the active transport of ionized drugs such as lidocaine by the application of an electric current. Twenty-one female subjects with interstitial cystitis were treated with EMDA of lidocaine and dexamethasone, followed by cystodistension. The procedure was convenient and well tolerated, with hospital attendance for 1 hour. Bladder anesthesia was excellent, with cystodistension from a discomfort level of 200 ml to a mean volume of 600 ml. Eighty-five percent had a good response (reduction in frequency and in pain score by 3 or more) at 2 weeks, with 63% still responding at 2 months. An excellent response (pain score of 0) was present in 25% of patients reviewed at 6 months. These results are comparable to the response following cystodistension under general anesthesia. There is a need for a randomized blinded comparison of lidocaine with and without EMDA. If proven to be of pharmacological efficacy, EMDA would have many applications in facilitating procedures previously requiring general anesthesia.

Administration, Intravesical↗
PubMed1997

Role of alpha interferon in multiple myeloma.

Interferons are soluble proteins produced by cells in response to viruses. Although they were first introduced as therapeutic agents for myeloma in 1979 their exact role in the management of myeloma remains to be precisely defined. Interferons have both anti-proliferative and immune regulation effects, but the predominant mode of action of interferons in myeloma is still unclear. Recombinant alpha interferon has been used in clinical trials as a single induction agent, co-induction agents with combination chemotherapy, as salvage therapy, and as therapy to maintain plateau phase after conventional chemotherapy or complete remission after auto or allogeneic transplantation. Interferon as a single induction or co-induction agent with other forms of chemotherapy appears to be of only minimal benefit in myeloma. However, its role as maintenance agent has received a great deal of interest and investigation. Its most beneficial role would appear to be in those patients who have had good responses to either conventional therapy or to bone marrow transplantation and the beneficial role of interferon in the maintenance of plateau phase is gaining credence. Its maximum advantage appears to be in patients with initial good response who have obtained plateau phase, or in patients who have developed complete remission after auto transplantation. It also has a role as salvage treatment in refractory patients with myeloma where the combination of interferon and dexamethazone may be a useful therapeutic modality.

Antineoplastic Agents↗
PubMed1997

Hemodialysis: an appropriate therapy in myeloma-induced renal failure.

To determine whether vigorous treatment with dialysis is of benefit to patients with myeloma-induced renal failure at presentation, we retrospectively reviewed outcomes in a group of patients diagnosed with multiple myeloma between January 1986 and September 1993. Increased age (P = 0.003), presence of renal impairment (P = 0.006), and failure to enter plateau phase (P < 0.001) were independently associated with shortened survival. However, there was no difference in outcome between patients with severe renal failure, those treated with dialysis, and those with milder renal impairment (median survival, 22 months in both groups), nor was reversibility of renal failure associated with any survival advantage. The lack of correlation between severity or reversibility of the renal failure and survival suggests that there may be characteristics of some patients or their underlying myeloma that are responsible both for renal impairment and for adverse prognosis. In this study, neither age, clinical stage, labeling index, nor response to treatment was able to account for the difference in outcome between patients with and without renal failure. The prolongation of life achieved in the dialysis patients such that their median survival was identical with that of the group with milder renal impairment was considered to represent a significant benefit to these patients and to justify the offer of dialysis to all patients requiring it.

Acute Kidney Injury↗
PubMed1997

Plasma cells in peripheral blood stem cell harvests from patients with multiple myeloma are predominantly polyclonal.

A flow cytometric technique has been developed to detect individual plasma cells in PBSC harvests and to establish light chain restriction as a surrogate marker of their clonality. Plasma cells were identified by high intensity CD38 (CD38++) and cytoplasmic immunoglobulin (cIg) expression. The ratio of cytoplasmic kappa to lambda expression was used to detect light chain restriction. All 25 PBSC harvests studied contained CD38++/cIg plasma cells (mean 0.7%, range 0.03-2%). Harvests from non-myeloma patients also contained plasma cells (mean 0.4%, range 0.01-1.5%). Most of the plasma cells detected in the harvests from myeloma patients were immature (CD45+/CD45++) rather than mature (CD45-). When the total plasma cell population was studied, definite isotype restriction could be detected in only 16% of harvests. Light chain restriction was found in 53% of harvests when the mature plasma cells (CD45-) were analysed but only in 9% of harvests when immature (CD45+/CD45++) plasma cells were analysed. Five percent of patients with myeloma had detectable light chain restriction in peripheral blood CD19+ cells. There was concordance between the ratio of malignant (CD19-/CD56+) to normal (CD19+/CD56-) plasma cells and light chain expression in 86% of patients studied. This study has demonstrated that the majority of plasma cells in PBSC harvests from patients with myeloma are not only immature but are also predominantly polyclonal and that monoclonality is best detected in mature plasma cells.

ADP-ribosyl Cyclase↗
PubMed1997

The prognostic significance of T cell receptor beta gene rearrangements and idiotype-reactive T cells in multiple myeloma.

Clonal T cell populations with idiotype specificity are present in the peripheral blood of a proportion of patients with multiple myeloma. We have identified the presence of both T cell subpopulations with a specificity for autologous immunoglobin fragments and T cell receptor beta gene rearrangements in peripheral blood samples of patients with myeloma. T cell receptor beta gene rearrangements were detected in 38 of 119 patient samples (32%) and were more common in progressive disease (70%), than at diagnosis (25%) or in stable disease (23%). The 38 patients who had T cell receptor beta gene rearrangements detected at any time had a better overall survival (median not yet achieved) than the patients who never had rearrangements detected (median 45 months, n = 49; chi2 = 6.2, P < 0.01). All 12 patients with T cell receptor beta gene rearrangements at diagnosis are still alive whereas the median survival for 28 patients with a germline configuration at diagnosis was 40 months (chi2 = 5.8, P > 0.01). The presence of T cell receptor beta gene rearrangements even conferred a survival advantage during progressive disease (median survival 44 months vs 19 months; chi2 = 8.7, P < 0.003). Two colour flow cytometry with biotinylated autologous immunoglobulin fragments demonstrated idiotype-reactive T cells in the peripheral blood of five out of 15 patients all of whom had T cell gene rearrangements. The remaining 10 patients had neither idiotype-reactive T cells nor a detectable T cell receptor beta gene rearrangement in concurrent samples. Thus in patients with myeloma there was a good correlation between the presence of T cell receptor beta gene rearrangements and idiotype-reactive T cells. Patients with a rearranged T cell receptor beta gene had a significantly better prognosis.

Aged↗
PubMed1997

Australian Leukaemia Study Group myeloma II: a randomized trial of intensive combination chemotherapy with or without interferon in patients with myeloma.

The Australian Leukaemia Study Group has performed a randomized trial of interferon alpha-2A (Roferon-A) as a co-induction agent together with intensive combination chemotherapy and as maintenance following completion of 12 cycles of induction treatment. When used as a co-induction agent, interferon-alpha did not improve response rates, time-to-treatment failure, or overall survival. Patients who had interferon together with intensive combination therapy (PCAB: prednisone 60 mg/m2 days 1-5, cyclophosphamide 600 mg/m2 day 1, BCNU 30 mg/m2 day 1, doxorubicin 30 mg/m2 day 1, repeated every 28 d for a total of 12 cycles) had more leucocyte and granulocyte toxicity and received a lower dose intensive of cytotoxic drugs than those patients who received PCAB without interferon. There was a trend towards prolongation of plateau phase which did not reach significance. Interferon, however, did improve the survival of patients who achieved plateau; for those patients interferon was associated with a 33% decrease in the rate of death after adjusting for initial beta-2 microglobulin level.

Activities of Daily Living↗
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

Lineages within Campylobacter jejuni defined by numerical analysis of pulsed-field gel electrophoretic DNA profiles.

Forty-seven Penner heat-stable (HS) serotype reference strains for Campylobacter jejuni and 47 serologically non-typable strains were examined by pulsed field gel electrophoresis (PFGE) DNA restriction analysis. The SmaI and KpnI digest profiles were compared by numerical analysis. Most strains grouped differently in the two analyses but strain lineages were inferred where the two agreed. Genetic relationships between reference strains in the cross-reacting HS4 complex were examined. Three clonal lines were evident and comprised: (i) HS4, HS13 and HS16; (ii) HS50 and HS65; (iii) HS43. The majority of those C. jejuni expressing HS antigens not recognised by currently available antisera had > 50% PFGE DNA digest similarity to one or more Penner scheme reference strain(s) and so did not necessarily represent distinct genetic lineages. PFGE analysis provided a high level of discrimination amongst strains of C. jejuni but overall similarity estimates for defining types must be based on the analysis of more than one restriction pattern.

Animals↗
PubMed1997

Antenatal screening for HPA-1a by flow cytometry.

Pregnant women who attended antenatal clinics at King George V Hospital, the Birth Centre or were referred by obstetricians from February 19 July, 1996 were screened for the platelet antigen HPA-1a by flow cytometry. Forty out of 2,300 (1.7%) were found to be negative for this antigen. Of the 28 women followed throughout their pregnancy, none developed antibody to HPA-1a. Platelet counts performed on samples from 17 babies born to 17 of these mothers were all normal. This study proves the simplicity and rapidity of flow cytometry for platelet antigen screening. The results were comparable with the Solid Phase Red Cell Adherence (SPRCA) method and with PCR. The lack of a plentiful supply of specific antibody and the rarity of fetomaternal alloimmune thrombocytopenia (FMAIT) argue against the introduction of routine screening for maternal HPA-1a status at the present time.

Adolescent↗