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Biomedical subjects

R Jennings

Publications and source records attributed to R Jennings.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1988

Zwitterionic detergent solubilisation of HSV-1 surface antigens.

A preparation was obtained from herpes simplex virus type 1 (HSV-1)-infected cells using a zwitterionic detergent, Empigen BB. The preparation was partially-purified either by ultracentrifugation over a cusion of 20% sucrose or on a sucrose density gradient. Partial characterisation of these materials by ELISA, using both polyclonal and monoclonal antibodies showed them to contain at least four major HSV glycoproteins, gB, gC, gD and gE. Comparison of Empigen-extracted HSV-1 antigen preparations with preparations obtained using the non-ionic detergents Nonidet P40 or Triton-X-100 indicate that, using conventional procedures, separation of glycoproteins, B, C, D, and E from unwanted proteins may be facilitated using the former detergent. Immunization of mice with Empigen-extracted, partially-purified or gradient-purified antigen preparations elicited good levels of antibody detectable by ELISA and a high degree of protection against both HSV-1 and HSV-2 challenge infection. Such protection could be achieved using aqueous antigen preparations, but was augmented using aluminium hydroxide gel as an adjuvant. In general, Empigen-extracted HSV-1 antigen preparations elicited higher ELISA antibody levels and more complete protection against HSV challenge infection than NP40 or Triton-X-100-extracted preparations. The value and usefulness of the detergent Empigen for obtaining HSV surface antigen preparations and the role of these as potential vaccines against HSV infections, is discussed.

Animals↗
PubMed1987

Use of single radial haemolysis for assessing antibody response to influenza virus vaccines in animals.

The value of the single radial haemolysis (SRH) test as a possible replacement for the haemagglutination-inhibition (HAI) test for the estimation of antibodies against influenza was assessed in three animal models. The serum antibody response was measured by both assay systems; correlation of the two tests was assessed using regression analysis. The study showed that when the response to a single immunisation was determined, the ferret model gave satisfactory correlation of SRH and HAI, whilst in the mouse and hamster models poor correlation was observed. Correlation was only improved in the mouse model when an immunisation schedule that mimicked the human situation of a background exposure to different strains of influenza virus was used. Since influenza vaccine efficacy is usually assessed in animals using a single immunisation we suggest that the SRH is not acceptable for use in either hamsters or mice, but is acceptable where the ferret model is involved.

Animals↗
PubMed1987

Spontaneous natural killer cell activity in childhood acute lymphoblastic leukaemia.

Endogenous NK activity was measured in ALL patients and compared with child and adult control values. ALL children undergoing maintenance chemotherapy showed significantly lower NK activity than control groups; however, patients off treatment and in remission expressed cytotoxicity within the normal range of the control groups. The expression of the HNK-1 marker in the ALL children was not significantly different from child controls, although ALL patients failed to show the same correlation between cytotoxic activity and HNK-1 expression. The target binding capacity of PBLs from ALL children was significantly greater compared with controls but did not correlate with NK activity. In addition plasma from ALL patients was not inhibitory for NK cytolytic activity, suggesting an innate defect in cytotoxicity mediated by NK cells rather than a plasma inhibitory factor. Patients failing to display NK activity against K562 target cells appeared to mediate killing of measles virus infected (Raji) targets.

Adolescent↗
PubMed1987

Immunomodulation of natural killer activity in children with acute lymphoblastic leukaemia.

Modulation of NK activity of PBLs from ALL patients was studied following exposure to IFN-alpha, staphylococcal protein A and interleukin-2. Only 52% of ALL patients responded to IFN-alpha stimulation, where the majority of controls showed positive enhancement of NK activity. Protein A failed to cause a significant stimulation of ALL patient PBLs whereas all controls showed a positive response. The majority of ALL patient and child control PBLs were however able to produce significant levels of IFN-gamma (protein A stimulation) and IFN-alpha (Sendai virus stimulation), although significantly more of both types of interferon could be induced in adult PBL samples. The ability of IL-2 to activate NK activity of ALL PBL samples showed a similar trend to IFN-alpha stimulation; thus, not all ALL patients showed positive augmentation of NK activity upon IL-2 stimulation. It is clear from these results that interferons and IL-2 may not necessarily lead to activated NK cytolytic activity, and in the present study approx. 50% of ALL patients failed to respond to lymphokine stimulation.

Adolescent↗
PubMed1987

Sequential infection or immunization of ferrets with a series of influenza A (H3N2) strains (report to the Medical Research Council's Sub-Committee on influenza Vaccines (CDVIP/IV)).

Previous studies of boys at Christ's Hospital school have indicated that annual immunization with influenza virus vaccines did not significantly reduce the total incidence of influenza infection compared to unimmunized subjects. In view of the implications of this result, a similar study was conducted in ferrets to clarify these findings. Groups of ferrets were immunized or infected with a series of influenza A (H3N2) viruses over an 18-month period, and the immunity to subsequent live virus challenge was measured after each virus or vaccine exposure. The results indicated that live virus infection gave a more solid immunity than immunization with inactivated vaccine; and the serum haemagglutination-inhibiting antibody response was greater following immunization than following infection. In addition, differences in immunity could not be explained by measurements of cross-reacting and specific antibody, since the incidence of these antibodies was similar in both infected and immunized animals. The results do not suggest an explanation for the different levels of immunity induced following infection or immunization or the results obtained from the Christ's Hospital study. However, the relative contribution of various immune responses to virus or virus antigen is discussed, and it is suggested that the difference in immunity may lie in the ability of live virus infection to stimulate local antibody.

Animals↗
PubMed1987

Demonstration of an immunosuppressive action of detergent-disrupted influenza virus on the antibody response to inactivated whole virus vaccine.

In a series of experiments performed in hamsters and mice, administration of mixtures of detergent-disrupted (SV) influenza A X49 (H3N2) virus and inactivated X49 whole virus (WV) vaccine induced lower serum antibody titres than equivalent or lower doses of WV vaccine alone. This reduction in antibody titre was also observed using influenza A (H1N1) and influenza B (B/Hong Kong/8/73) SV and WV vaccine preparations. The results suggested that SV preparations can suppress the serum antibody response to WV vaccine. A suppressive effect of SV influenza virus on WV vaccine was also observed in an in vitro antibody-forming system, using primed mouse spleen cells. In this system, SV induced markedly lower IgG and IgM antibody responses than WV vaccine, and mixtures of SV with WV reproducibly resulted in lowered antibody responses compared to those elicited by WV alone. Possible reasons for these findings are discussed in the light of the known low immunogenicity observed for split and subunit influenza virus vaccine preparations in animals and in unprimed human populations.

Animals↗
PubMed1987

Infectivity and reactogenicity of reassortant cold-adapted influenza A/Korea/1/82 vaccines obtained from the USA and USSR.

The safety and immunogenicity of two live influenza A virus vaccine strains, the CR 59 and 17/25/1 cold-adapted (ca) reassortants, were evaluated in 170 healthy young adult volunteers. The vaccines were produced by recombining A/Korea/1/82 (H3N2) wild-type virus with either A/Ann Arbor/6/60 (H2N2) or A/Leningrad/134/17/57 (H2N2) ca donors of attenuation. Both vaccines were well tolerated in volunteers. The 17/25/1 strain, prepared from A/Leningrad, infected at least 70% of seronegative volunteers after the first dose and 84% after the second; the CR 59 strain infected 62% and 72% of volunteers after first and second doses, respectively. Among the vaccinees who were initially seropositive, 17/25/1 infected 66% after one dose and 85% after two, while CR 59 infected 62% and 71%, respectively. Despite differences in temperature sensitivity, genetic composition, and serological reactivity to monoclonal antibodies, both vaccines behaved almost identically in animal models and man. We conclude that both donors of attenuation may be of great potential value.

Adolescent↗
PubMed1986

Characterization and immunogenicity of HSV-1 antigens obtained following zwitterionic detergent treatment.

A preparation was obtained from herpesvirus hominis type 1 (HSV-1) infected cells using the zwitterionic detergent, Empigen BB. The preparation was partially purified by ultracentrifugation over a cushion of 20% sucrose. Serological characterization by ELISA and immuno double diffusion, using both polyclonal and monoclonal antibodies shows this preparation to contain HSV glycoproteins, including gC, gD and gE. Immunization of Balb/c mice elicited serum antibody responses against both HSV-1 and HSV-2 viruses, complete protection against HSV-1 (strain WAL) and partial protection against HSV-2 (strain 333).

Animals↗