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Biomedical subjects

D D Heath

Publications and source records attributed to D D Heath.

At least 37 records · Page 2Linked to original sources
PubMed2000

Assessment of protective immune responses against hydatid disease in sheep by immunization with synthetic peptide antigens.

Four synthetic peptides which comprise the immunodominant linear epitopes of the EG95 recombinant protein, were investigated for their ability to induce host-protective immunity against Echinococcus granulosus in sheep. Sheep were immunized with either free peptide or peptide conjugated to diphtheria toxoid and challenge infected with E. granulosus eggs. All of the peptides elicited specific antibody, but these did not kill the parasite in in vitro culture assays, nor did the peptides induce protection against challenge infection. In contrast, anti-EG95 antibodies affinity purified against each of the 4 peptides were lethal to the parasite in in vitro culture. These affinity-purified antibodies were shown to contain specific antibody to both peptide and EG95. In in vitro inhibition assays, the peptides did not diminish anti-EG95 antibody binding to EG95 or parasite lysis in oncosphere killing assays. These results suggest that the fine specificities of antibodies raised against the recombinant protein are different to those raised against the peptide immunogens and that the majority of the antibody induced by vaccination with EG95 is raised against conformational determinants.

Animals↗
PubMed1999

Duration of immunity, efficacy and safety in sheep of a recombinant Taenia ovis vaccine formulated with saponin or selected adjuvants.

The efficacy and safety of a recombinant Taenia ovis protein was tested in sheep using 13 different adjuvant formulations, including oil adjuvants, aluminium salts, saponin, Iscoms and DEAE-dextran. The oil adjuvants, saponin and DEAE-dextran gave the highest antibody responses and greatest degree of protection against challenge infection with T. ovis eggs. Duration of immunity studies with a saponin based vaccine showed that highly significant protection (>90% reduction of cyst numbers) was achieved when sheep were challenge infected one month after immunisation. Significant protection (79%) was still present when sheep were challenged 6 months after immunisation. The optimum dose for this batch of saponin was 10 mg, which stimulated a peak antibody titre of 38,400, 4 weeks after immunisation and did not cause injection site reactions. Dialysed saponin was shown to retain its adjuvant properties and allowed an increase in dose to 30 mg without site reaction, resulting in a peak antibody titre of 51,200.

Adjuvants, Immunologic↗
PubMed1999

A phase II/pharmacokinetic trial of high-dose progesterone in combination with paclitaxel.

PURPOSE: The purpose of this study was to investigate the effect of high-dose progesterone, an inhibitor of P glycoprotein, on the pharmacokinetics and toxicity of paclitaxel. PATIENTS AND METHODS: A total of 29 patients with various tumors were treated with single-agent paclitaxel (125 mg/m2 administered over 3 h once every 3 weeks) until progression of disease, at which point high-dose progesterone (3 g administered i.v. over 24 h) was added to the paclitaxel treatment program in 20 patients (13 women, 7 men). Pharmacokinetic studies of paclitaxel administered alone and with progesterone were performed in eight patients. RESULTS: The pharmacokinetic parameters of paclitaxel were highly variable. High-dose progesterone increased the peak plasma levels (3.00 +/- 0.94 vs. 4.15 +/- 1.63 microM; P = 0.029; mean +/- SD) and the area under the curve (AUC; 14.3 +/- 4.75 vs. 17.3 +/- 5.59 microM x h; P = 0.006) of paclitaxel. The absolute neutrophil and platelet nadir counts did not differ significantly between the paclitaxel and the combined treatment cycles. Three of the 20 patients documented to have progressive disease on paclitaxel alone had partial responses when high-dose progesterone was added to the paclitaxel regimen. CONCLUSION: Progesterone had a statistically significant impact on the pharmacokinetics of paclitaxel. The addition of high-dose progesterone to paclitaxel is feasible, but the small number of patients prevents conclusions being drawn about the clinical efficacy of combined progesterone and paclitaxel.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Vaccination trials in Australia and Argentina confirm the effectiveness of the EG95 hydatid vaccine in sheep.

Experimental vaccine trials against hydatid disease have been undertaken in sheep using the EG95 recombinant vaccine. Challenge infection was with viable Echinococcus granulosus eggs obtained from a New Zealand isolate (dog/sheep cycle), an Australian isolate (dingo/wallaby cycle) and an Argentine isolate (dog/sheep cycle). Vaccination with EG95 conferred a high degree of protection against challenge with all three parasite isolates (protection range 96-100%). Taken together, the trials demonstrated that 86% of vaccinated sheep were completely free of viable hydatid cysts when examined approximately 1 year after challenge infection. Vaccination reduced the number of viable cysts by 99.3% compared with unvaccinated controls. These results suggest that the EG95 vaccine could have wide applicability as a new tool for use in hydatid control campaigns.

Animals↗
PubMed1998

Epitope specificities and antibody responses to the EG95 hydatid vaccine.

Antibody isotype and epitope specificities were examined in sheep immunized with EG95, a protective recombinant vaccine against hydatid disease. All sheep immunized with EG95 as a fusion protein with glutathione S-transferase (GST) produced prominent IgG antibodies against the EG95 portion of the protein. Linear, antibody-binding epitope specificities of EG95 were mapped using a series of 25 overlapping synthetic peptides. Three immunodominant regions were identified which generated specific IgG1 and IgG2 antibodies in the majority of vaccinated sheep. These regions corresponded to the EG95-derived sequences SLKAVNPSDPLVYKRQTAKF, DIETPRAGKKESTVMTSGSA and SALTSAIAGFVFSC. An additional immunogenic region was identified which induced almost exclusively IgG2 antibody. This epitope was located within the sequence TETPLRKHFNLTPV. The anti-parasitic, protective effects of the EG95 vaccine correlated with the detection of specific antibody to two or more of the four linear immunogenic regions. The identification of these immunogenic peptides of EG95 maybe useful in the development of a synthetic peptide vaccine as a derivative of the EG95 recombinant.

Amino Acid Sequence↗
PubMed1998

Mytilus protamine-like sperm-specific protein genes are multicopy, dispersed, and closely associated with hypervariable RFLP regions.

Protamine-like sperm packaging proteins replace somatic histones during spermatogenesis, and although the proteins have been well-characterized in many marine invertebrate species, little is known of the arrangement of the genes. The research described here was designed to determine the sequence and structure of the protamine-like PL-III (or "phi 1") gene in marine mussels (Mytilus spp). The PL-III sequence was found to be extremely variable not only among the closely related Mytilus species, but also within species and populations. The variation observed among eight PL-III sequences from a single individual indicated that PL-III was probably multiple-copied. Southern analysis confirmed that PL-III, and another protamine-like gene, (PL-II), were multicopy and dispersed, as well as associated with a hypervariable element. Some PL-III genes are also arranged in nontandem clusters, and the spacer regions are probably the source of the hypervariable nature of the Southern blots. The arrangement of the protamine-like genes in Mytilus appears to be closer to that reported for histones than protamines; however, their association with a hypervariable element is novel.

Amino Acid Sequence↗
PubMed1997

Vaccination against echinococcus in perspective.

Vaccination of intermediate hosts will effectively reduce the prevalence of human echinococcosis. The rate of progress can be enhanced by concurrent tactical treatment of definitive hosts. The oncosphere of Echinococcus granulosus contains a specific protein which when expressed on the oncosphere surface will combine with specific antibody In the presence of complement, damage is caused to the plasma membrane, resulting in failure of the oncosphere to develop into a metacestode. Immunisation of sheep with oncosphere secretions or with an oncosphere homogenate results in 99% resistance to a challenge infection of the sheep with E. granulosus eggs. Immunisation of sheep with the specific purified protein results in 92% resistance. The gene coding for the protein has been isolated from an E. granulosus oncosphere cDNA library and expressed in E.coli as a fusion protein with glutathione-S-transferase. A monoclonal antibody to an epitope on the E. granulosus portion of the molecule is able to bind to the surface of oncospheres and to prevent their development to metacestodes in vitro. Immunisation of sheep with the fusion protein has given 97 and 98% resistance to a challenge infection in two separate trials. The shelf-life of formulated vaccine is at least 12 months, and the immunity generated by two injections given 1 month apart persists for at least 12 months. A homologue of the gene has been identified in E. multilocularis. The vaccine has the potential to be used as a tool for control of transmission of E. granulosus through its natural intermediate hosts (particularly domestic ungulates) as part of hydatid control programmes. Traditional methods of hydatid control (anthelmintic treatment of dogs) require regular treatment within the prepatent period for prolonged periods (20-30 years) to achieve satisfactory control, and often sociological factors to do with dog-feeding, dog ownership and dog-control prevent such an achievement. By controlling the disease in both the definitive host and the intermediate host, the shortcomings of either procedure can be overcome, resulting in a cost-effective desired result within a practical time period.

Animals↗
PubMed1997

Pathological studies of wobbly possum disease in New Zealand brushtail possums (Trichosurus vulpecula).

Following an outbreak of wobbly possum disease in a colony of brush tail possums (Trichosurus vulpecula), the disease was established experimentally in captive possums by inoculating the animals intraperitoneally with tissue homogenates. Crude tissue homogenates of liver remained infectious after freezing at -75 degrees C or filtration through a 0.22 micron filter. The disease was characterised by docility, incoordination, loss of balance and wasting. Fifteen of 16 infected animals had to be euthanased owing to the severity of clinical signs. Cachexia was the only change observed postmortem. Histology revealed widespread perivascular infiltrations with plasma cells and lymphocytes which were severe in the liver and kidney and moderate to mild in a variety of other tissues, including skeletal and cardiac muscle. Changes in the brain consisted of a mild to moderate mononuclear perivascular cuffing. Most of the animals had small to large numbers of circulating nucleated red blood cells and eosinopenia when they were euthanased. There was a consistent decrease in serum albumin concentration and an increase in serum globulins, which resulted in a decreased albumin:globulin ratio. Virus-like particles were observed in preparations of liver from two animals; they appeared to be spherical or icosahedral and were 45 nm in diameter.

Animals↗
PubMed1997

The early stages of Echinococcus granulosus development.

The paper points out the essential aspects of host/parasite relationship during the development of oncospheres (ONC) of Echinococcus granulosus into an early cyst. Secretions of the penetration glands in the hatched ONC causes lysis of host tissue during penetration of the activated ONC. It also protects the parasite against the host's immune response while developing the laminated layer. The microvilli, compressed under the plasma membrane in the hatched ONC, are uplifted in the activated larvae; they increase in number and size and are substituted by short and truncated microtriches in metacestodes 3 days old. At that time appears the first lamination of the laminated layer that surrounds the metacestodes as an electron-dense matrix composed of fine microfibrillated material and remnants of sloughed microvilli. The second lamination appears by day 6-8 and is more electron-dense than the first one. The laminated layer is of parasite origin, formed of a series that emanates from the germinal membrane. It is suggested that Vg secretory vesicles, that are elaborated in the perikaryon of the germinal zone and continuously carried to the syncytium via the microtubular-cytoskeleton, are responsible for the laminated layer formation and are involved in initial evasion of the immune response of the host. The cyclical production of laminations could be necessary to create layers that can ultimately be sloughed off as the cyst grows and serve to divert the host cellular response to the parasite.

Animals↗
PubMed1997

Internal parasites of possums (Trichosurus vulpecula) from Kawau Island, Chatham Island and Stewart Island.

As part of a search for pathogens that might be useful agents for biological control of possums, the three largest offshore islands of New Zealand that still have possums were surveyed to determine the pathogens present in these isolated populations. Brushtail possums from Kawau Island (n = 158), Chatham Island (n = 214) and Stewart Island (n = 194) were examined for internal parasites. Possums from Kawau Island were infected with Eimeria spp. (16.7%), Bertiella trichosuri (5.2%) and Purustrongyloides trichosuri (15.5%). No Paraustrostrongylus trichosuri or Trichostrongylus spp. were found. Possums from Chatham Island were infected with Eimeria spp. (10.9%). Bertiella trichosuri (3.6%), T colubriformis (6.6%), T retortaeformis (1%) and T. vitrinus (0.5%). No Parastrongyloides or Paraustrostrongylus spp. were found. Possums from Stewart Island were infected only with Eimeria spp. (4.6%). Because of their paucity of some parasites, the opportunity exists to use these offshore islands to study the introduction and spread of a parasite into a possum population, and what technology would be required to bring it to hyperendemicity.

Journal Article↗
PubMed1997

Endoparasites of brushtail possums (Trichosurus vulpecula) from the South Island, New Zealand.

As part of a study to assess whether endoparasites could assist in the biological control of brushtail possums in New Zealand, we investigated the composition and distribution of possum endoparasites in the South Island. Possums were collected near five of the original release areas in the South Island : Banks Peninsula, Hokitika, Nelson, Dunedin and Invercargill. Among the nematodes, those most frequently encountered were Trichostrongylus spp., which were present in possums from all five study areas. Trichostrongylus species from possums in the Invercargill area comprised 4.5% T. colubriformis, 0.9% T. vitrinus and 11.3% T. retortaeformis. Paraustrostnmgylus trichosuri and Parastrongyloides trichosuri were found only in the Invercargill area, where they infected 1.4% and 14% of possums respectively. The cestode Bertiella trichosuri was present in possums from all locations except Dunedin. The protozoan Eimeria spp. occurred in all areas. These are the first records of Parastrongyloides trichosuri, Paraustrostrongylus trichosuri, T. vitrinus, T. retortaeformis and Eimeria spp. in South Island possums. The prevalence of endoparasites and the intensity of infection was very low compared to the lower North Island of New Zealand. Endoparasites at the existing levels in the South Island probably have very little effect on possum populations.

Journal Article↗
PubMed1996

Identification and cDNA cloning of two novel low molecular weight host-protective antigens from Taenia ovis oncospheres.

Oncosphere antigens of Taenia ovis were solubilised in sodium dodecyl sulphate and separated by electrophoresis in polyacrylamide gels (SDS-PAGE). Antigen-containing gel fractions cut from the region covering 18-12 kDa were shown to be highly immunogenic in sheep challenge experiments. Specific antisera against 2 candidate antigens at 18 and 16 kDa were used to screen a cDNA library prepared from T. ovis oncosphere mRNA. Recombinant proteins selected with antibody to the 16 and 18 kDa native antigens were expressed as GST fusion proteins. Vaccination trials using either of the 2 fusion proteins To16.17-GST and To18-GST, revealed that each was capable of inducing high levels of immunity in sheep against challenge infection with T. ovis eggs. Antibodies induced by vaccination with the recombinant antigens reacted specifically with their respective 18 or 16 kDa native oncosphere antigens. There was no apparent homology between the T. ovis cDNA coding for To18 and To16.17, or with another host-protective antigen, To45W, described previously. These additional host-protective antigens should prove a valuable adjunct to To45W and permit the development of effective vaccination strategies.

Amino Acid Sequence↗
PubMed1996

Neurological complications of ankle arthroscopy.

A retrospective review of the first 612 patients undergoing consecutive ankle arthroscopy in the practices of two experienced arthroscopists was under-taken. All inpatient records, outpatient charts, and operative reports were reviewed. Indications for surgery included pain, swelling, locking, and instability that failed to respond to nonoperative management. The results of our investigation revealed an overall complication rate of 9.0% (55 complications). There were 27 neurological complications (4.4% of all arthroscopies) accounting for 49.1% of the complications noted. Specifically, the superficial peroneal nerve was injured in 15 cases, the sural nerve in 6, the saphenous nerve in 5, and the deep peroneal nerve in 1. All nerve injuries occurred through direct injury by portal or distractor pin placement. No cases of neurological injury caused by tourniquet compression or compartment syndrome were seen. Also, 1 case of reflex sympathetic dystrophy was identified.

Adolescent↗
PubMed1996

Antigenic polypeptides of Echinococcus granulosus oncospheres and definition of protective molecules.

Immunoblotting and in vitro oncosphere-killing were used to identify a putative protective molecule in Echinococcus granulosus mature oncospheres. A range of sera from sheep that had been shown to be protected against E. granulosus, and from those that were not, were tested. The sera used were obtained from sheep hyperimmunized with E. granulosus oncospheres, or immunized with oncosphere non-denatured extract, with immature oncosphere extract or with denatured extracts of oncospheres. Results indicated the involvement of native antigens of 23, 25, 30, 34 and 40 kDa in the protective response to E. granulosus infection. The rapid appearance of antibodies to the 23, 25 kDa antigens, their association with early onset of protection and in vitro oncosphere lysis by affinity-purified antibodies obtained from these fractions, indicated that these antigens contained protective epitopes. Final confirmation was provided by immunization of sheep with fractions prepared by preparative SDS/PAGE, and challenge infection. Only the fraction containing the 23 and 25 kDa molecules was able to stimulate protection. Antisera against this pair of molecules should provide a useful probe for screening an E. granulosus oncosphere cDNA library to identify clones expressing protective molecules.

Animals↗
PubMed1996

Immune responses associated with protection in sheep vaccinated with a recombinant antigen from Taenia ovis.

This paper describes the evaluation of the protective antibody response of sheep to vaccination against Taenia ovis infection with a defined recombinant antigen (45W). Sera from 181 vaccinated sheep, collected prior to experimental challenge with T.ovis, were assessed for 45W specific IgA, IgG, IgG1, IgG2 and IgM levels and these results correlated with protection data. There were significant relationships (P < 0.001) between IgG, IgG1 and IgG2 titres and protection. Serum IgA levels did not correlate with protection and there were no significant levels of 45W specific IgM detected. Killing of several other taeniid cestodes has been shown to be complement mediated and the findings in this study are consistent with the involvement of this immune mechanism in 45W vaccinated sheep. A comparison of the adjuvants used in this study (saponin and oil in water) demonstrated that whereas both adjuvants stimulated the production of similar levels of 45W specific IgG1, the IgG2 response was significantly higher in sheep vaccinated with oil adjuvant.

Adjuvants, Immunologic↗
PubMed1996

Pilot field trial of a recombinant Taenia ovis vaccine in lambs exposed to natural infection.

Previous trials of an experimental Taenia ovis vaccine using the recombinant antigen GST--45W(B/X) established that it was possible to achieve >90% protection against a single artificial challenge of T. ovis eggs. This trial was undertaken to assess vaccine efficacy against artificial challenge and natural infection acquired by lambs grazing contaminated pasture. Two hundred Romney lambs were vaccinated at 6 and 12 weeks of age. One hundred control lambs were not vaccinated but were allowed to run with the vaccinated mob. At 15 weeks of age, 10 controls and 18 vaccinated lambs were artificially challenged with 2000 T. ovis eggs. The remaining control and vaccinated lambs were allowed to graze contaminated pasture for 3 weeks and were then moved to clean pasture for 5 months. The artificially challenged lambs plus 24 of the field-infected lambs were slaughtered and the carcasses dissected to obtain cyst counts. The remaining field-infected lambs were slaughtered at a commercial processing plant and the carcasses examined by conventional meat inspection. The results showed that the vaccine provided a high level of protection against artificial challenge (92%) and natural infection (98%) when assessed by carcass dissection. The data from commercial meat inspection showed that vaccination provided 89% efficacy against downgrading or condemnation compared to non-vaccinated control lambs. The average difference in carcass values between vaccinated and non-vaccinated groups was 4.36 dollars, representing a 35% loss in value due to T.ovis infection in non-vaccinated lambs.

Journal Article↗
PubMed1996

The serological response of dogs to Taenia ovis.

The effect of 4-weekly anthelmintic dosing and other treatment regimes on the serological response of dogs to Taenia ovis was examined. Most dogs which were frequently fed infected meat and dosed with a cestocidal anthelmintic at 4-week intervals eventually showed a positive ELISA absorbance. The absence of dosing, or intermittent dosing, of repeatedly infected dogs raised ELISA absorbances to very high levels in most dogs and these absorbances took an increasingly longer time to fall after each new infection. The feeding of large numbers of frozen, dead cysts to sensitised dogs raised absorbance levels. The serological test for T. ovis infections in dogs does not detect false positives. Positive tests result from the dog being exposed to T. ovis scolex secretory antigen.

Journal Article↗