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Biomedical subjects

M H Collie

Publications and source records attributed to M H Collie.

8 recordsLinked to original sources

The localization of influenza virus in the respiratory tract of ferrets: susceptible nasal mucosa cells produce and release more virus than susceptible lung cells.

Infectious virus production by ferret nasal mucosa and lung organ cultures has been monitored in both tissue pieces and medium over 24 h following inoculation with an Asian (H2N2) strain of influenza virus. Freshly prepared cultures of nasal mucosa produced approx. 10-fold more virus per cell than fresh lung cultures. Also the nasal mucosa cells liberated into the medium a greater proportion (mean 31%) of the total virus produced than did fresh lung (mean 6%). Maintenance of lung explants for 24 h prior to inoculation resulted in a 20- to 100-fold increase in the amount of virus released. However, total virus production by fresh and maintained lung was similar. Trypsin did not increase the infectivity of virus released from any of the cultures, indicating that the haemagglutinin in the virus particles was cleaved. Similar results were obtained with a Hong Kong (H3N2) virus strain. Hence, one factor operating in the lower susceptibility of the lung compared with the nasal mucosa in vivo may be a lower capacity of lung cells both to produce and release influenza virus.

Animals

Association of foetal wastage with influenza infection during ferret pregnancy.

Inoculation of influenza virus into pregnant ferrets during the late gestational period was investigated. Foetal resorption followed intracardial inoculation of a large dose of influenza virus (10(9.4) EBID50) and a 100-fold lower dose caused lower litter sizes at birth. The possible role of fever in foetal resorptions was largely discounted by 2 observations: a non-pyrexic dose inoculated intracardially into the pregnant ferret still had detrimental effects on foetal viability; influenza virus inoculated intranasally caused a pyrexia but did not affect the progeny. The potential of the ferret as a model for studying the possible adverse effects of influenza during pregnancy is discussed.

Animals

Sensitivity to pyrexial temperatures: a factor contributing to virulence differences between two clones of influenza virus.

The influence of pyrexia on the differential persistence of a virulent and an attenuated clone of influenza virus in the respiratory tract of ferrets has been further studied. Clone 64d, an attenuated clone of a recombinant virus (A/PR/8/34-A/England/939/69 (H3N2)) grown in organ cultures of ferret nasal turbinates, was inactivated at pyrexial temperatures more readily than a virulent Clone 7a. In addition, replication of Clone 64d was restricted at pyrexial temperatures to a greater extent than that of Clone 7a in organ cultures of both ferret nasal turbinate and lung tissue. The greater adverse effects of pyrexial temperatures on Clone 64d appears to explain the earlier reduction of upper respiratory tract infection seen in ferrets infected with this attenuated clone. Also, the differential influence of pyrexial temperatures may be the reason for the virtual lack of lung infection with Clone 64d in vivo in contrast to the consistent infection found with Clone 7a. The relevance of these findings to human infection and to markers of attenuation of influenza virus is discussed.

Animals

The pregnant guinea-pig as a model for studying influenza virus infection in utero: infection of foetal tissues in organ culture and in vivo.

Organ cultures of guinea-pig foetal tissues showed a similar pattern of susceptibility to influenza virus to that already observed for human (Rosztoczy et al., 1975) and ferret (Sweet, Toms and Smith, 1977) foetal tissues. Respiratory, alimentary and urogenital tract tissues were susceptible whereas neural and lymphopoietic tissues were insusceptible. However, of the foetal membranes (amnion, chorion, umbilical cord and placenta) only the chorion was susceptible, in contrast to the corresponding ferret tissues, all of which were susceptible. The insusceptibility of the placenta paralleled that of human placenta which is similarly haemomonochorial in structure. Following intracardial inoculation of high titre virus (ca 10(9-4) EBID50) into pregnant guinea-pigs virus was isolated from all foetal membranes (amnion, chorion, umbilical cord and placenta), but in low titre. Although sporadic isolations were made from foetal tissues (intestine, kidney, heart, liver and spleen) there was no evidence for viral replication in these tissues. These results are discussed in relation to possible infection of the human foetus in utero with influenza virus.

Animals

Antibody production to lipopolysaccharide in thymectomized Xenopus.

Xenopus toadlets, some of which had been thymectomized as larvae, were immunized with E. coli lipopolysaccharide. Antibody titers were similar in thymectomized and intact toadlets. Antibody was exclusively IgM. The results suggest that a division into thymus-dependent and thymus-independent anti-body responses extends at least as far back in phylogeny as the amphibians.

Animals

Influence of antigen dose on antibody production of intact and splenectomised Xenopus laevis.

Antigen persistence and serum antibody production in intact Xenopus were monitored using human gamma globulin (HGG), in adjuvant, in various immunisation schedules. Retention of HGG in spleen and serum was directly related to the quantity injected. However, antibody responses to a dose range between 1 mu-g-6 mg antigen were similar in intensity. These were detected in the serum two weeks after injection and at this stage were exclusively mercapto-ethanol (ME) sensitive; ME-resistant antibodies had appeared by four weeks. No antibodies were detected below a dose of 100 ng HGG. The effect of splenectomy on antibody levels was tested using HGG/adjuvant or sheep erythrocytes (SRBC) in saline. Splenectomised toads showed impairment of antibody responses only to threshold doses of HGG (100 ng) but to a wider range of SRBC doses.

Animals