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Biomedical subjects

D L Barnard

Publications and source records attributed to D L Barnard.

At least 19 recordsLinked to original sources
PubMed1992

Topographical analysis of the G virion of Aleutian mink disease parvovirus with monoclonal antibodies.

The topography of the Aleutian mink disease parvovirus (ADV) G virion was analyzed with monoclonal antibodies and polyclonal antiserum. There was homology between the two major structural proteins as others have previously reported. Trypsin treatment of the virion with subsequent immunoblotting revealed that VP2 represents the main peptide on the exterior of virion and that VP1 is probably embedded within the capsid. Additional analyses of the trypsin-treated virions showed that VP2 is responsible for binding complement and that it also represents the structural part of the virion that binds to cellular receptors. A third protein, p34, was detected that might represent a third structural polypeptide because of its many unique epitopes relative to the other peptides detected.

Aleutian Mink Disease Virus↗
PubMed1992

Appearance of Ph negative recipient clones in chronic myeloid leukemia patients following bone marrow transplantation.

Seven patients were studied following bone marrow transplantation for chronic myeloid leukemia. Cytogenetic heteromorphisms were used to determine the origin of cells present post-BMT. Differences were found between results from blood and bone marrow samples, and between karyotype and interphase Y-body studies on the same samples. Philadelphia negative (Ph-) hematopoietic chimerism was found in 6 of 7 patients, all of whom had been Ph+ before BMT. One patient also demonstrated hematopoietic chimerism with Ph+ recipient cells following clinical evidence of relapse. In two patients who had received T-cell depleted grafts, cytogenetically rearranged Ph- clones of recipient cells were prominent in PHA-stimulated blood. In one case two clones had appeared only 1 month post BMT. The appearance of these clones so soon after transplant suggests very rapid clonal expansion, or that they were already present pre-BMT but at levels too low to have been detected. In the second patient, clones were not observed until more than 12 months post-BMT, after which four were found. These collectively expanded to occupy an increasing proportion of the total cells. These two patients with clones both remain in good health 44 and 51 months post-BMT. Further studies are needed to determine the true frequency and the significance of such findings.

Adult↗
PubMed1992

Selective inhibition of arthropod-borne and arenaviruses in vitro by 3'-fluoro-3'-deoxyadenosine.

A novel nucleoside analog, 3'-fluoro-3'-deoxyadenosine (3'F3'dAdo), was evaluated for antiviral activity against several arthropod-borne and arenaviruses in Vero cell culture. The following 50% inhibitory concentrations (EC50) of virus plaque formation were obtained against the test viruses: Semliki Forest (10.3 microM) and Venezuelan equine encephalitis (5.3 microM) alphaviruses, lymphocytic choriomeningitis (7.7 microM) and Pichinde (greater than 32 microM) arenaviruses, Punta Toro (greater than 32 microM) and San Angelo (1.6 microM) bunyaviruses, banzi flavivirus (4.0 microM), and Colorado tick fever orbivirus (0.6 microM). By comparison, the broad-spectrum antiviral agent ribavirin was active against lymphocytic choriomeningitis (18 microM), Pichinde (24 microM), Punta Toro (114 microM), and San Angelo (99 microM) viruses, but was less active against the other 4 viruses (greater than 200 microM). Vero cell proliferation and thymidine and uridine incorporation into replicating Vero cells were inhibited by 50% with 3'F3'dAdo concentrations of 36, 45, and 32 microM, respectively. In virus yield reduction assays, increasing the multiplicity of infections of Semliki Forest and Venezuelan equine encephalitis viruses reduced the inhibitory activity of 3'F3'dAdo. Using the same assay, 3'F3'dAdo was found to enhance Punta Toro virus replication up to 5-fold relative to the untreated control. By adding the nucleoside transport inhibitor nitrobenzylthioinosine (100 microM) to the culture medium, antiviral activity against the two alphaviruses was eliminated, indicating that 3'F3'dAdo uses the nucleoside transport system for cell entry. When actinomycin D (5 microM) was used to greatly suppress cellular RNA synthesis in Semliki Forest virus-infected and uninfected cells, 3'F3'dAdo preferentially inhibited viral RNA synthesis. The results of these studies indicate 3'F3'dAdo is a selective inhibitor of most of the viruses tested and should be a promising candidate for in vivo evaluations.

Animals↗
PubMed1992

Evaluation of the antiviral activity of anthraquinones, anthrones and anthraquinone derivatives against human cytomegalovirus.

A number of anthraquinones, anthrones and anthraquinone derivatives were evaluated for antiviral activity against human cytomegalovirus (HCMV) as well as for cytotoxicity. Of those compounds evaluated, quinalizarin, emodin, rhein, hypericin, protohypericin, alizarin, emodin bianthrone and emodin anthrone showed antiviral activity against a normal laboratory HCMV strain, AD-169. When tested against a ganciclovir-resistant strain of HCMV, the EC50 values for quinalizarin, rhein and alizarin were superior to the values obtained for the AD-169 strain of HCMV. These results suggest that these compounds will be useful as prototypes for synthesizing a class of anti-HCMV drugs that are effective against ganciclovir-sensitive and -resistant strains of HCMV.

Anthracenes↗
PubMed1991

Thalidomide treatment for chronic graft-versus-host disease.

The treatment of chronic graft-versus-host disease (GVHD) may present a difficult therapeutic problem. We used thalidomide to treat six patients with severe chronic GVHD who failed to respond to standard immunosuppressive agents. Four of the six patients showed a clear response to thalidomide, with the fifth patient showing a partial response. The best results were seen in patients with chronic cutaneous GVHD. Two of the patients developed neurophysiological evidence of a peripheral neuropathy, associated with clinical signs in one patient. Measurement of thalidomide plasma levels and pharmacokinetic curves showed a significant inter-patient variation. Peak plasma levels varied from 0.47 to 1.46 micrograms/ml. Thalidomide has a role to play in the management of chronic GVHD and further studies are needed.

Adolescent↗
PubMed1991

Changes in serum erythropoietin levels during allogeneic bone marrow transplantation.

Serial serum erythropoietin levels were measured in 10 consecutive patients undergoing allogeneic bone marrow transplantation. Observed erythropoietin levels are compared with those predicted from a large control population of anaemic patients not receiving chemotherapy. There was an initial acute rise in serum erythropoietin, peaking between days 1 and 4 after marrow transfusion, which was unrelated to changes in haemoglobin concentration. Patients maintained serum erythropoietin concentrations at around twice the predicted level for the first 2 weeks following transplantation, with a gradual fall into the expected range by wk 3. Erythropoietin levels did not change with episodes of bacterial infection or acute graft-versus-host disease. A patient with severe aplastic anaemia had initial successful engraftment with normalisation of erythropoietin levels, but showed a marked and amplified rise in erythropoietin 2 wk before falling peripheral blood counts indicated failure of the bone marrow graft.

Adolescent↗
PubMed1988

Effects of ribamidine, a 3-carboxamidine derivative of ribavirin, on experimentally induced Phlebovirus infections.

Ribamidine (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamidine) was inhibitory in rhesus monkey kidney (LLC-MK2 derivative) cells to Adames and Balliet strains of Punta Toro virus (PTV), a Phlebovirus related to Rift Valley fever and sandfly fever viruses. The 50% effective dose was 8 and 12 micrograms/ml against each respective virus strain; the 50% cytotoxic dose was 320 micrograms/ml, giving selectivity indices of 40 and 27 against each virus strain. The virus ratings were 1.2 and 1.0, respectively. In radiolabel uptake studies, ribamidine had a moderate effect on [3H]leucine uptake at dosages down to 1 microgram/ml, but [3H]thymidine, [32P], and [3H]uridine were inhibited at high (100-1000 micrograms/ml) doses only. Subcutaneous (s.c.) and oral treatments of Adames PTV-infected mice were equally highly effective, as evidenced particularly by 100% survivors. Reduced hepatic icterus, serum oxalic acid transaminase, serum glutamic pyruvic acid transaminase, and recoverable virus titers from livers and sera of infected mice were also seen as a result of ribamidine treatment. Twice daily treatment for 5 days could be started as late as 72 h post-virus inoculation (p.v.i.) with significant inhibition of PTV infection seen. Single s.c. treatments administered as late as 48 h p.v.i. were similarly effective. Using the chronic therapy schedule, the maximum tolerated dose was 1000 mg/kg/day and the minimum effective dose was 31.3 to 62.5 mg/kg/day. Using single treatment, a maximum tolerated dose was greater than 1000 mg/kg, and the minimum effective dose was 125 mg/kg. Ribamidine s.c. treatment of mice infected intracerebrally with the Balliet strain of PTV resulted in a moderate infection-inhibitory effect, seen especially by reduced virus titers in the brains of the infected, treated mice.

Administration, Oral↗
PubMed1987

Vitamin B12 absorption after allogeneic bone marrow transplantation.

The B12 absorption test (Schilling test) with intrinsic factor was used to examine ileal B12 absorption in 26 patients after allogeneic transplantation. The test was well tolerated and showed a profound fall in B12 absorption, which was maximal at two weeks after transplantation and recovered by eight weeks. The predominant influence on absorption at this stage was probably the conditioning schedule, and the presence of acute graft versus host disease (GVHD) was not associated with a further impairment of absorption. Six patients with chronic GVHD were studied. When compared with nine patients without GVHD there was a significant (p less than 0.005) reduction of B12 absorption. These findings suggest that the B12 absorption test may be a useful non-invasive method of studying bowel function after bone marrow transplantation.

Adolescent↗
PubMed1986

Suitability of new chlamydia transport medium for transport of herpes simplex virus.

A new chlamydia transport medium (ChlamydiaPort; Scott Laboratories, Inc., Fiskeville, R.I.) was evaluated for its suitability as a transport medium for herpes simplex virus (HSV). Two laboratory HSV strains (McIntyre and 333) and two clinical isolates (AO218 and AO301) were suspended in ChlamydiaPort, ViraPort (Scott Laboratories), and cell culture medium and maintained at 2 and 22 degrees C. Samples were tested at various time intervals to determine surviving virus. The range of half-lives of the HSV strains held at 2 degrees C in ChlamydiaPort medium was from 3.5 to 10 days, while virus stability was greater in ViraPort and less in cell culture medium. These HSV strains held at 22 degrees C in ChlamydiaPort had half-lives from 1.5 to 6 days, which were significantly greater than the half-lives of the viruses held in either tissue culture medium or ViraPort. Clinical specimens were tested for virus by using the Selecticult-HSV (Scott Laboratories) system to determine the performance of the transport medium under field conditions. Clinical specimens maintained up to 5 days at ambient temperatures in ChlamydiaPort medium appeared suitable for diagnostic testing without detectable loss of positive specimens. In addition, there was a significant decrease in the average time required for diagnosis when compared with a standard transport system, Virocult (Microdiagnostics, Cleveland, Ohio). These results show that HSV infections can be successfully diagnosed in distant virology laboratories by shipping specimens in ChlamydiaPort transport medium at ambient temperatures.

Chlamydia↗
PubMed1985

Comparison of an avidin-biotin immunoassay with three commercially available immunofluorescence kits for typing of herpes simplex virus.

An avidin-biotin complex system was compared with three commercially available immunofluorescence kits for serotyping herpes simplex virus isolates from clinical specimens. Sensitivity values showed that the Electro-Nucleonics and Immulok reagents were useful in detecting the presence of virus, whereas the predictive values showed that the Syva and Immulok reagents possessed adequate discrimination between the herpes simplex virus serotypes. The avidin-biotin complex system was equal or superior to the immunofluorescence reagents tested both in detecting herpes simplex virus antigens in cell culture and in serotyping herpes simplex virus isolates.

Antigens, Viral↗
PubMed1983

A retrospective evaluation of mediastinal tomograms, isotope liver scans, and isotope bone scans in the staging and management of patients with lymphoma.

The influence of mediastinal tomograms and isotope scans of liver and bone on the initial staging and management of patients with lymphoma has been studied. There appears to be only a small role for these investigative procedures, and it is suggested that considerable savings in time and money can be made by a more judicious use of these techniques.

Adolescent↗
PubMed1983

A pilot study of cyclical chemotherapy with high-dose methotrexate and CHOP (MTX-CHOP) in poor-prognosis non-Hodgkin's lymphoma (NHL).

In a pilot study of cyclical chemotherapy in patients with poor-prognosis non-Hodgkin's lymphoma (NHL), high-dose methotrexate (MTX) 1 g/m2 with folinic acid rescue was given as initial treatment and then between cycles of a single-arm CHOP combination administered every 4 weeks. Of 21 patients with previously untreated or minimally treated grade 2 (high-grade) histology stage II/III/IV NHL, 13 (62%) achieved complete remission (CR); the CR rate for stage III/IV patients was 56%. Of all 25 patients with grade 2 stage II/III/IV NHL, including previously treated patients, 16 (64%) achieved CR. The median follow-up of patients who completed treatment is currently 22 months and only 1 relapse has been recorded in the CR group. Only five of 24 grade 2 patients given the initial 'test' MTX failed to show any response, and eight patients achieved partial remission (PR) as a result of this single treatment. The response to MTX-CHOP in nine patients with grade 1 (low-grade) histology NHL was poor; only two achieved CR. These findings lend support to other data which indicate a useful role for MTX in the induction chemotherapy of advanced high-grade NHL, though the optimum dosage and drug sequence have yet to be determined.

Adolescent↗