Biomedical subjects

B Holcman

Publications and source records attributed to B Holcman.

4 recordsLinked to original sources

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

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↗

PubMed1994

Ultrastructure of oncosphere and early stages of metacestode development of Echinococcus granulosus.

The ultrastructure of the oncospheres and developing metacestodes in vitro of Echinococcus granulosus was studied with emphasis on the origin of the laminated layer. The activated oncospheres measured 28 microns (S.D. = 1.83), and by day 5 of in vitro culture the metacestodes attained diameters up to 52 microns (S.D. = 2.66). The oncospheral plasma membrane of the tegument appeared to be formed by a microtubular cytoskeleton arranged in a predetermined pattern. By day 2 there were three main types of vesicles in the perikaryon: Vd, Vg1 and Vg2. Vesicles appeared to be synthesized in the perikaryon and continuously transported to the periphery, where the Vd vesicles could contribute to the ground substance of the syncytial tegument. We suggest that the Vg1 and Vg2 vesicles contribute to the laminated layer where, by day 5, they were seen in increased density and forming aggregations on the outer border.

Animals↗

PubMed1994

Echinococcus granulosus: the mechanism of oncosphere lysis by sheep complement and antibody.

A heat-labile component of normal sheep serum (56 degrees C for 30 min but not 50 degrees C for 30 min) was able to lyse oncospheres in vitro. The degree of effect, and the proportion of oncospheres lysed, was related to the concentration of normal unheated sheep serum complement, or other sources of complement (rabbit, mouse) in the culture. Lower concentrations were required for lysis if the culture serum was obtained from sheep immune to E. granulosus infection. Heat inactivation of normal or immune sheep serum removed any lytic ability. No lysis occurred in any concentration of unheated foetal lamb serum. However, unheated foetal lamb serum was able to restore the lytic effect to heated normal or immune serum. This suggests that lysis in both immune and normal serum is antibody-dependent and complement-mediated. The lysis in normal serum would appear to be due to natural cross-reacting antibodies that can fix complement at the oncosphere surface. The complement lesion resulted in damage to the plasma membrane. This then peeled back, predisposing the oncosphere to osmotic destruction. The use of bleach to dissolve the embryophore caused damage to the plasma membrane similar to that caused by complement. Developing metacestodes at 3 days of age in vitro in immune serum were susceptible to the addition of complement at that time.

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