Biomedical subjects

R Jennings

Publications and source records attributed to R Jennings.

At least 19 recordsLinked to original sources

PubMed1992

The IgA and subclass IgG responses and protection in mice immunised with influenza antigens administered as ISCOMS, with FCA, ALH or as infectious virus.

Comparative studies on the local IgA, and circulating IgG subclass antibody responses of mice to A/Sichuan/2/87 (H3N2) influenza virus surface antigens administered with different carrier or delivery systems by the parenteral route, were carried out. The results obtained were compared with the responses observed following live influenza virus infection, and the protection afforded to these animals by these various preparations determined. Infection with live virus elicited early and high levels of protection against homologous virus challenge and this correlated with both local IgA and circulating IgG2a antibody levels. When incorporated into immunostimulating complexes (ISCOMS), A/Sichuan surface antigens promoted high levels of local IgA and circulating IgG1 antibody, and achieved a more rapid and more solid immunity against homologous virus challenge infection, than that elicited by the same surface antigens administered alone or together with Freund's complete adjuvant or alhydrogel.

Aluminum Hydroxide↗

PubMed1992

Acute and latent infection of mice immunised with HSV-1 ISCOM vaccine.

The effect of immunisation with an HSV-1 antigen preparation (containing at least 6 viral glycoproteins) on primary infection with HSV and the establishment of latency, was assessed in two mouse models (involving either skin or corneal challenge with virus). The vaccine preparation, given either with Freund's complete adjuvant or aluminium hydroxide gel or in the form of immunostimulating complexes (ISCOMS), induced high ELISA antibody responses (highest with HSV as the ISCOM preparation) and low levels of neutralising antibody. In both models, immunisation with the HSV ISCOM preparation significantly reduced the incidence of zosteriform spread of virus and the severity of disease and, in some cases, the incidence of latent infection in sensory ganglia. In the eye model it was possible to show that immunisation with the HSV ISCOMS restricted the establishment of latency almost entirely to the ophthalmic part of the trigeminal ganglion. Protection from establishment of latency correlated with prechallenge antibody levels.

Acute Disease↗

PubMed1992

Liposomes enhance the immunogenicity of reconstituted influenza virus A/PR/8 envelopes and the formation of protective antibody by influenza virus A/Sichuan/87 (H3N2) surface antigen.

Reconstituted influenza virus (A/PR/8 strain) envelopes (RIVE) and influenza virus (A/Sichuan/87 (H3N2) strain) surface antigens were entrapped in dehydration-rehydration vesicles (DRV liposomes) composed of egg phosphatidylcholine (PC) or distearoyl phosphatidylcholine (DSPC DRV) and equimolar (32 mumol) cholesterol. Entrapment values for RIVE were 31.2 (PC) and 29.4% (DSPC DRV) of the material used. Corresponding entrapment values for the A/Sichuan/87 strain antigens were 40.7 and 39.3%. Balb/c mice injected intramuscularly with PC or DSPC DRV liposomes containing 0.1 and 1.0 microgram RIVE exhibited primary (higher dose only) and secondary responses (IgG1) which were significantly higher than those obtained in mice injected with identical amounts of non-entrapped RIVE. Significantly higher secondary responses were also observed for the IgG2a and IgG2b subclasses. In experiments designed to assess the effectiveness of DRV liposomes as a carrier of influenza virus antigens in a potential vaccine, hamsters were immunized intramuscularly with 0.1, 0.5 and 5.0 micrograms of free or liposome-entrapped influenza A/Sichuan/87 surface antigens. Results showed increased haemagglutination inhibition (HI) antibody levels in terms of both primary (0.5 and 5.0 micrograms doses) and secondary (all doses) responses in the sera of animals treated with the liposomal formulations. DSPC compared with PC DRV exhibited greater adjuvanticity when the lower doses of antigens were used.

Adjuvants, Immunologic↗

PubMed1992

Longitudinal study of Toxoplasma seroprevalence in South Yorkshire.

Serum samples collected from individuals of a wide range of ages in South Yorkshire between 1969 and 1990 provided the basis for a longitudinal seroprevalence survey of Toxoplasma gondii antibodies. Sera numbering 3868 were screened for T. gondii specific antibodies using a commercial latex agglutination test. The resultant temporal series of serological profiles revealed a rise, with age, in seroprevalence, the rate of which showed a decrease through time. A plateau of around 40-50% prevalence was attained by the 41- to 45-year age-class in 1969 which was not approached until the 66- to 70-year class in the 1988-90 data set. This trend for decline in seroprevalence was confirmed by statistical analysis for the age range 21-60 years. These results may be indicative of a decrease in the rate of toxoplasma exposure in this study community over the 20-year period. The survey of 1988-90 provides a base-line profile of present-day seroprevalence in which 11% of individuals in the age range 16-45 years (roughly corresponding to the childbearing age-range) show evidence of past infection. The representative nature of the serum collection and public-health implications of these results are discussed.

Adolescent↗

PubMed1991

Biochemical characterization of herpes simplex virus type-1-immunostimulating complexes (ISCMOs): a multi-glycoprotein structure.

The preparation and characterization of an immunostimulating complex (ISCOM) preparation containing several HSV-1 glycoproteins, including the major glycoproteins B and D is described. The multi-glycoprotein HSV-1 ISCOM preparation was obtained from a gradient-purified aqueous HSV-1 antigen preparation following extraction from infected cells using a zwitterionic detergent. With polyclonal and monoclonal antibodies to HSV-1 glycoproteins in enzyme-linked immunosorbent assay, SDS-polyacrylamide gel electrophoresis and radioimmunoprecipitation techniques, the HSV-1 ISCOM preparation was shown to contain glycoproteins B, C, D, E, H and I, although further, additional proteins were also present. The DNA content of HSV-1 ISCOMs was determined using a 3H-thymidine labelling method. The protein and DNA contents of the HSV-1 ISCOM preparation are discussed with reference to the potentialities of the preparation as a vaccine for use in human beings.

DNA, Viral↗

PubMed1991

Efficacy of HSV-1 ISCOM vaccine in the guinea-pig model of HSV-2 infection.

The capability of a herpes simplex virus (HSV)-1 ISCOM vaccine to protect against intravaginal HSV-2 challenge infection in guinea-pigs is described. The protective efficacy of the HSV-1 ISCOM vaccine is compared with that of a purified, aqueous HSV-1 antigen preparation administered using a similar immunization schedule. The results show that female guinea-pigs immunized with two doses of HSV-1 ISCOM vaccine, each consisting of 20 micrograms of protein given 2 weeks apart responded with high ELISA and neutralization antibody titres, and are almost completely protected against the clinical effects of intravaginal challenge with 10(5.2) TCID50 of HSV-2. This cross-protection is significantly greater than that observed in guinea-pigs immunized with a single dose of HSV-1 ISCOM vaccine, two doses of aqueous HSV-1 antigen preparation or two doses of a mock ISCOM vaccine. However, none of the vaccine preparations completely prevented HSV-2 replication following challenge. Western blot and radioimmunoprecipitation of sera from immunized guinea-pigs show the HSV-1 ISCOM vaccine preparation to contain the major HSV-1 glycoproteins. These findings are discussed in relation to the value and potential use of HSV-1 ISCOM vaccine in humans.

Animals↗

PubMed1990

Comparative studies of HSV-1 antigens solubilised from infected cells by using non-ionic or zwitterionic detergents.

HSV-1 antigen preparations solubilised from Vero cells by using either the non-ionic detergent Nonidet P40 or the zwitterionic detergent Empigen BB, and purified on sucrose density gradients or over a sucrose cushion, were tested by ELISA with anti-HSV-1 glycoprotein monoclonal antibodies and by radioimmunoprecipitation (RIP) with polyclonal HSV-1 antiserum. Amongst several proteins detected in these preparations, the four major HSV-1 glycoproteins, gB, gC, gD, and gE, were found to be present. Differences between NP40 or Empigen-solubilised HSV-1 antigen preparations with respect to two of these glycoproteins, gB and gE, were detected by using a small panel of monoclonal antibodies. Comparative studies in mice showed the Empigen-solubilised HSV-1 antigen preparations elicited greater antibody responses and greater protection against lethal HSV-1 challenge infection than the NP40-solubilised preparation.

Animals↗

PubMed1990

Pulmonary vascular resistance in neonatal swine: response to right pulmonary artery occlusion, isoproterenol, and prostaglandin E1.

The pulmonary physiological response of adults to unilateral pulmonary artery (PA) occlusion has been well-characterized as resulting in a decrease in the pulmonary vascular resistance (PVR), in order to maintain the same PA pressure and accommodate the entire cardiac output (CO). We evaluated the response of the neonate to unilateral PA occlusion and how this response is altered by infusions of Isoproterenol (Isuprel) and prostaglandin E1 (PGE1) in the neonatal swine model. Twenty farm piglets (five at 1 day, three at 5 days, seven at 14 days, and five at 60 days as controls) underwent left lateral thoracotomy and measurement of PA and left atrial (LA) pressures, CO, and PVR with the right PA open and occluded. To determine if neonatal PVR could be influenced by a vasodilator (indicating the vascular capacity is not fixed) or by an inotrope (indicating the lung is not maximally recruited) this experiment was then repeated with infusions of PGE1 (a vasodilator) at doses of 0.1, 0.5, and 1.0 micrograms/kg/min and subsequently with Isuprel (an inotrope and vasodilator) at doses of 0.1, 0.5, 1.0 micrograms/kg/min. Control measurements taken without unilateral PA occlusion showed that PVR is high at 1 day of age but progressively decreases to a level 89% lower by 60 days of age. The vascular capacity of the neonatal lung is fixed and responds to unilateral PA occlusion with a dramatic increase in PVR. This response cannot be altered by either a vasodilator (PGE1) or an inotrope (Isuprel) thereby limiting the utility of these drugs in treating neonatal pulmonary hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗

PubMed1990

Surgical wound dressings as barriers to an enveloped virus.

To determine their efficacy as barriers to the passage of lipid-enveloped viruses, wound dressings were exposed to known concentrations of Semliki Forest virus (SFV) at their inner surfaces for varying periods of time. The dressings were tested such that their outer surfaces were maintained in either a dry or a wet environment. Out of a total of 120 dressings each tested at four time points under wet conditions, virus was found to have penetrated on only one occasion. Similarly, virus penetration was noted in only a single test out of 442 carried out on 59 dressings under dry conditions. The dressings under test thus proved highly effective barriers to passage of a lipid enveloped virus.

Evaluation Studies as Topic↗

PubMed1990

Nonfulminant herpes simplex encephalitis as a cause for mesial temporal sclerosis.

Although mesial temporal sclerosis has been recognized for more than 100 years, its etiology remains unknown. It is proposed that a common infectious agent, herpes simplex virus type-1, may cause this disorder by means of a nonfulminant infection of mesial temporal lobe structures, which is resolved by the immune system and becomes gliotic in the course of healing by the central nervous system. Brain sections from a long-term experiment in a model of herpes simplex encephalitis reveal such a scar, which shows a high concentration of glial fibrillary acidic protein, without any evidence of residual herpes antigen, by immunocytochemistry.

Animals↗

PubMed1990

Specificity and in vitro transfer of the immunosuppressive effect of detergent-disrupted influenza virus vaccine.

Primed murine splenocytes give an in vitro antibody response to influenza whole virus vaccine (WVV), as measured by enzyme immunoassay (EIA). When subunit vaccine (SV) of either influenza A or influenza B virus was added to in vitro splenocyte cultures stimulated with WVV, the EIA antibody response to homologous WVV was reduced. This reduction in antibody response was observed when SV was prepared using zwitterionic detergent (empigen BB), non-ionic detergent (triton-X-100) or cationic detergent cetyl-trimethyl ammonium bromide (CTAB); it was found to be effected only by SV of strains of the same virus subtype--when SVs prepared from a heterotypic (H3N2) strain, an H1N1 strain and an influenza B strain were added to splenocyte cultures in the presence of WVV. When splenocytes from immunologically naive mice, exposed in vitro to SV, were transferred to secondary cultures of primed splenocytes, the antibody response to WVV in the secondary cultures was also reduced. Mechanisms that may suppress the in vitro antibody response are discussed.

Animals↗

PubMed1990

Use of isolated cold stress testing in determining normal lower extremity thermoregulation.

Isolated cold stress testing was performed on 72 healthy subjects in order to evaluate the normal thermoregulatory potential of vessel beds in the acral areas of the lower extremity. Two patterns of response were demonstrated: a cool response in approximately 80% of subjects, and a warm pattern in approximately 20%. In the former, the responses to cold stress were more active and the temperatures lower; in the latter, there was little change in temperature in response to the cold stress. Both patterns correlated strongly with initial temperature, and neither pattern correlated with age, sex, or smoking habits. No subjects reported pain, numbness, or discomfort during the test. This study demonstrated that wide variations in thermoregulatory flow were possible without clinical symptoms, and suggested that nutritional blood flow was adequate to meet metabolic demands despite thermoregulatory modulation.

Adolescent↗

PubMed1989

Effect of influenza A on phagocytic cell function.

The effect of various strains of influenza virus on polymorphonuclear leucocyte (PMNL) function were studied by chemiluminescence (CL) and bacterial killing assays. All virus strains induced PMNL CL and peak CL correlated with haemagglutination (HA) but not neuraminidase (NA) activity of virus pools. Heat-treatment of virus pools generally had little effect on HA activity or ability to generate a PMN CL response but almost completely destroyed NA activity. Exposure of PMNL to each of the six virus strains resulted in loss of surface-associated sialic acid and a marked depression in both zymosan-induced PMNL CL and PMNL bactericidal capacity. However, there was no correlation between the degree of PMNL functional impairment and virus NA activity and, furthermore, heat treatment of virus pools removed NA activity but generally had little effect on their ability to reduce PMNL function. NA does not appear to play a primary role in impairment of PMNL function by influenza virus.

Adult↗

PubMed1989

Latent HSV-1 infection in mice immunized with a zwitterionic detergent-extracted HSV-1 antigen preparation.

A HSV-1 antigen preparation obtained by zwitterionic detergent-extraction of HSV-1 infected Vero cells was investigated for its ability to protect mice against establishment of latent infection in the trigeminal ganglion following HSV-1 challenge by ear scarification. The antigen preparation was shown to induce antibody production and correlation between pre-challenge antibody level and establishment of latency was found. Although immunization did not reduce the overall incidence of ear erythema following challenge the duration of erythema was significantly decreased. Latency in the trigeminal ganglion was also significantly reduced in vaccinated mice and in addition, a correlation was found between the duration of erythema and latency, there being significantly more latent infections in mice with erythema of three or more days duration, than in those with erythema lasting less than three days.

Animals↗

PubMed1989

Protection and serum antibody responses in guinea-pigs and mice immunized with HSV-1 antigen preparations obtained using different detergents.

Guinea-pigs immunized with a zwitterionic detergent-extracted HSV-1 antigen preparation responded with EIA and NT serum antibody titres that were significantly greater than those elicited by a non-ionic detergent-extracted antigen preparation inoculated using a similar dosage schedule. Following intravaginal challenge of the guinea-pigs with HSV-2 (strain SH/B), there was no statistically significant difference in the protection afforded to these animals by the two antigen preparations, although the results indicated the zwitterionic detergent-extracted HSV-1 antigen preparation to be slightly superior in this respect. In mice, the zwitterionic detergent-extracted HSV-1 antigen preparation elicited an EIA antibody response and partial protection against homologous virus challenge. The relevance of these animal models to determination of immunogenicity and efficacy of HSV vaccines prepared for use in man, and the reasons for the differences in immunogenicity of these HSV-1 antigen preparations in guinea-pigs, are discussed.

Animals↗

PubMed1989

Dose to the cardiac vascular and conduction systems in primary breast irradiation.

Using computerized tomography (CT) in which cardiac anatomy was defined, doses delivered to the cardiac compartments, vascular and conduction systems were assessed for various standard techniques of primary breast irradiation. Included in the analysis were 6 MV photon tangents (T) alone, or in conjunction with a separate internal mammary field (IMF). Beams evaluated in the IMF were 6 MV photons, 12 MeV electron beam, and mixed photon/electron beam; Cobalt 60 was also analyzed as an alternate photon beam. Treatment of the IMF with photons, either alone or in combination with electron beam, delivered doses ranging between 30 Gy to 50 Gy to all chambers of the heart, coronary arteries and branches of the conduction system. Complete sparing of the posterior cardiac structures and volume is accomplished with treatment plans using tangents alone or in combination with 12 MeV electron beam irradiation to the IMF. Sparing of the anterior wall of the left ventricle, Bundle of His and left anterior descending coronary artery is also achieved in treatment with tangents and 12 MeV electron beam IMF. Doses to this region with tangents alone ranged from 20 Gy to 45 Gy compared to 0 to 30 Gy with tangents and 12 MeV electron beam IMF. Clinical significance of these findings will be discussed.

Breast Neoplasms↗

PubMed1989

Antibody responses and protection in mice immunized with herpes simplex virus type 1 antigen immune-stimulating complex preparations.

The formation of immune-stimulating complexes (iscoms) obtained by mixing the glycoside Quil A with an antigen preparation derived from herpes simplex virus type 1 (HSV-1)-infected cell cultures using a zwitterionic detergent is described. The HSV-1 antigen preparation incorporated into iscoms elicited significantly greater antibody responses in mice than the same preparation administered together with aluminium hydroxide gel, and provided complete protection against HSV-1 or HSV-2 lethal, systemic challenge infection in animals given a single dose containing 5 micrograms of protein. The HSV-1 iscom preparation also provided significant protection in mice against local reactions following challenge with HSV-1 by skin scarification.

Adjuvants, Immunologic↗

PubMed1989

Behavioural consequences of hypertension: effects of age and type of antihypertensive agent.

In order to investigate the effects on behaviour of hypertension, age, and the types of antihypertensive agents, we have conducted a retrospective analysis in 100 hypertensive patients receiving chronic treatment in our Hypertension Clinic. A group of 80 normotensive subjects, matched for age, were included in the study. Half of the hypertensive patients were under the age of 50 (young group) and half were over the age of 50 yrs (old group). The antihypertensive agents had not been administered according to any specific protocol, but represented the choice of the individual clinicians treating the patients in the clinic. All patients had received treatment for at least one year, and usually for two years. The behavioural tests performed were designed to measure sensory-perceptive ability, cognitive ability and psychomotor function and were those employed and described in our previous studies. The results achieved were varied, but indicated that older age was associated with an impairment in performance as was blood pressure. Test performances in the young hypertensives were similar to those achieved by older normotensives. These results were more prominent in cognitive and psychomotor functions than in the sensory-perceptive tests. The antihypertensive drugs used also affected these results; the worst behavioural performances tended to be in patients receiving the central nervous system agonists (methyl-dopa and clonidine) and better performances in patients receiving beta-blockers alone when compared with the other groups. Surprisingly, patients receiving diuretics showed poorer performance levels, but these were better in patients who received a beta-blocker in combination with their diuretic.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗