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Biomedical subjects

R Cappel

Publications and source records attributed to R Cappel.

At least 19 recordsLinked to original sources

Clinical efficacy of a herpes simplex subunit vaccine.

A DNA-free herpes simplex type 2 subunit vaccine was administered to 18 volunteers without past evidence of herpes simplex type 1 (HSV 1) or herpes simplex type 2 (HSV 2) infection, to 44 patients with severe recurrent genital HSV 2 infection, and to 15 patients with severe oral type 1 HSV recurrences. The vaccine elicited both humoral and cell-mediated immunity in 97% of the subjects without past HSV infections and boosted significantly the cell-mediated immunity and antibody titers in almost all the patients with recurrent HSV 1 or HSV 2. The vaccine elicited particularly the production of complement-dependent cytotoxic antibodies in 96% of the patients with recurrent HSV 2 infections. This might, at least partly, explain the clinical efficacy of the vaccine. Indeed, we observed a significant decrease (t test, p less than 0.01) in the attack rate of the recurrences and also a significant shortening of the time needed to complete healing of the lesions (t test, p less than 0.01).

Adult↗

Effect of thymopentin on the mortality and immune response after an experimental herpes simplex infection in mice.

The effect of thymopentin on the mortality rate of mice treated with lethal doses (LD90) of herpes virus 2 and on the cytotoxic T cell activity after sublethal doses (LD10) of herpes virus was investigated in two series of experiments. Doses of 1, 0.1 or 0.01 ng of thymopentin per g/mouse were administered i.p. in each experiment, either 3 days before, 3 days (66 h) after, or 3 and 6 days after the herpes virus infection. The cumulative mortality rate was evaluated 10 days after the infection. Cytotoxic T cell activity was measured 3, 7 and 14 days after the infection. The 0.1-ng dose of thymopentin reduced the mortality rate to less than 50% (p = 0.0000) if it was administered 3 days before the infection. A single injection of any dose after infection did not reduce the mortality at all, while two injections of 0.1 ng reduced it by about 25% (p = 0.0038). A 1-ng dose showed a mild but significant reduction (p = 0.0313) if it was applied 3 days before the infection. The cytotoxic T cell activity was either not influenced or significantly modified (p less than 0.05), i.e. increased or decreased as compared to the control, depending on the dose and timing of thymopentin. A correlation between increased cytotoxic T cell activity and protection against mortality can be demonstrated, while no protection was observed in dose regimens where the cytotoxic T cell activity became reduced. The results are discussed in connection with earlier clinical studies in which the beneficial effect of thymopentin has been demonstrated in frequently relapsing herpes labialis and herpes genitalis patients.

Adjuvants, Immunologic↗

Preliminary results of hepatitis B vaccination (HEVAC B) in healthy subjects and haemodialysis patients.

Hepatitis B vaccine (Hevac B, Pasteur) was assessed in 52 healthy and 25 haemodialysis individuals. The percentage of hepatitis B surface antibody seroconversion was 100% in the first group but only 57.7% in the other one. The mean levels of hepatitis B surface antibody, 3 months after the first injection were respectively 222 and 42 milli International Units per ml. Five health-care workers, who experienced an accidental exposure were protected by a combined passive-active immunization.

Adult↗

Creatine kinase activity in normal and Duchenne muscular dystrophy fibroblasts.

Cultured human skin fibroblasts from 9 patients with Duchenne muscular dystrophy (DMD) and 8 normal age- and sex-matched controls were examined for creatine kinase (CK) activity. Both the normal and the DMD fibroblasts were found to have significant levels of CK activity (approximately 10 x 10(-3) IU per milligram of fibroblast protein). The control cells had slightly higher CK activity than the DMD lines, but this difference was not significant (0.2 less than P less than 0.1). The MM (muscle) isozyme, the BB (brain) isozyme, and the MB (hybrid) isozyme, of CK were found to be present in fibroblasts. The isozymes were separated by electrophoresis and the relative amount of each was determined for both normal and DMD cells. In normal fibroblasts, approximately 48% of the total CK activity was of the MM type, 40% was of the BB type, and 12% was of the MB type with no significant differences apparent between normal and DMD groups. The presence in human fibroblasts of significant levels of CK activity with a characteristic isozyme profile is an important consideration for studies of this "marker" enzyme in the pseudohypertrophic muscle of DMD.

Adolescent↗

Immune response to a DNA free herpes simplex vaccine in man.

A DNA-free subunit herpes simplex virus (HSV) vaccine was administered to 15 volunteers without past evidence of HSV infection and to 25 patients with severe recurrent HSV infection. The immune response to the vaccine in these patients was compared to the immunological status of 20 non-vaccinated control patients with recurrent HSV infection. The vaccine elicited antibody and cell-mediated immunity (CMI) in the 15 subjects without past evidence of HSV infection and this response was similar to that observed after a natural infection. Among the 25 patients who were suffering from recurrent HSV infection the vaccine elicited complement dependent cytotoxic antibodies in 13 of these patients who did not possess these antibodies and increased significantly the titers of these antibodies in the 12 other patients. The vaccine gave a significant increase of the titers of the other specific antibodies as well as the level of cell-mediated immunity. The increase of the immunity level in these latter patient was not due to normal variations since in the non-vaccinated control group the antibody titers and CMI remained stable during the same period of time.

Adult↗

Immune responses to DNA free herpes simplex proteins in man.

The data presented confirm in human volunteers our previous observations in animal models. The DNA free HSV 2 subunit vaccine used elicited an antibody and a cell-mediated immune response in 15 subjects without past evidence of HSV 1 or HSV 2 infections and increased the immunity level in 28 subjects suffering from HSV 1 or HSV 2 infections. Although we did not follow a double-blind, placebo controlled protocol our results suggest that the vaccine may reduce the frequency and severity of HSV infections. The time between the recurrences, the pain and the time to complete healing decreased significantly after the vaccination.

Antibody Formation↗

Significance of persisting IgM anti-HBc antibodies in hepatitis B virus infection.

Igg and IgM antibodies to the core antigen of hepatitis B virus (HBV) were measured in 136 patients who developed acute HBV hepatitis and who were followed prospectively. After acute hepatitis all the patients developed transiently IgM anti-HBc lasting for two to five months. In contrast, IgM anti-HBc persisted 8 and 9 months in two patients who developed persistent hepatitis and were continuously detected for two years in nine patients who developed aggressive hepatitis. The results suggest that the determination of IgM anti-HBc might be useful to predict the outcome of chronic hepatitis B infection.

Acute Disease↗

Expression of retrovirus-related antigen in pregnancy. II. Cytotoxic and blocking specificities of immunoglobulins eluted from the placenta.

Immunoglobulins, mostly of the IgG class, were detected in eluates of the placenta of 75% of 50 healthy women in their first or second pregnancy, 92% of 30 women with more than two pregnancies, and 87% of 23 pre-eclamptic patients. The immunoglobulins were assayed for complement-dependent cytotoxicity on human and monkey cell-lines, as well as on the same cells chronically infected with either Mason-Pfizer Virus (M-P V) or Baboon Endogenous Virus (BeV). The frequency of cytotoxic reactions was very low, except with immunoglobulins from the pre-eclamptic placentae, where one third of the samples lysed virus-infected cells with occasional killing of virus-free cells. All placental immunoglobulins which were not cytotoxic were then assayed for blocking activity by testing whether they could compete with the action of anticellular sera of virus-free cells, or with the toxic effect of antiviral sera on virus producing cells. 64% of the immunoglobulins from normal placentae competed with antiviral antibodies while only 17% blocked the action of anticellular sera. The frequency of blocking immunoglobulins was no greater in eluates from pre-eclamptic placentae. The data indicate that the placenta possesses retrovirus antigen sites which bind blocking antibodies in normal pregnancy and complement-dependent cytotoxic antibodies in pre-eclampsia.

Animals↗

[Acute infections central nervous system. The significance of antiviral antibodies in the cerebrospinal fluid (author's transl)].

Examination of the CSF of 107 patients suffering from a viral infection of the central nervous system for the presence of antiviral antibodies indicated that 26 subjects (24 %) developed monospecific antibodies. The distribution of these antibodies differed according to whether the diagnosis was of meningitis or of encephalitis and myelitis since 3 patients out of 73 (4 %) with meningitis developed antibodies whilst the latter were detectable in 23 of the 34 subjects with encephalitis or myelitis (67 %). This difference was highly significant (p 0,001) and suggests that examination for antiviral antibodies in the CSF could be of use in the differential diagnosis between meningitis and encephalitis. Furthermore, the results presented suggest the existence of local production of antiviral antibodies in the CSF.

Acute Disease↗

Efficacy of a nucleic acid free herpetic subunit vaccine.

The efficacy of immunization with an herpes simplex subunit vaccine, free of nucleic acid, was evaluated in mice, rabbits and monkeys. One injection of 3 micrograms per kg of body weight elicited both humoral and cell-mediated immunity in all the animals studied. Furthermore, the immunization reduced significantly the mortality to a subsequent challenge with live herpes simplex virus in mice and rabbits (p less than 0.01).

Animals↗

Liver disease in patients undergoing hemodialysis and kidney transplantation.

Liver dysfunction was observed in 33% of patients treated by hemodialysis and kidney transplantation. Fifty-eight percent of these cases of hepatitis occurred in patients with past or present HBs antigenemia, and 77% of HBsAg-positive patients showed evidence of LD. However, during the course of a program conducted from 1969 to 1976 and involving 267 patients, the decrease in the prevalence of HBs antigenemia observed during the last two years did not lead to any reduction in LD incidence. In a small number of patients, potentially hepatotoxic drugs could be incriminated, but in our experience azathioprine never appeared to be involved. In a few patients, LD was due to granulomatous disease of the liver, such as tuberculosis and schistosomiasis. Twenty-one (7%) of the 267 patients at risk developed chronic hepatitis, which contributed to death in nine patients. In 12 cases (three deaths), this form of hepatitis occurred in HBsAg-positive patients, and in nine cases (six deaths), in HBsAg-negative patients. In three of these latter individuals, cytomegalovirus could be incriminated. Routine monthly screening for CMV in kidney recipients confirmed the high incidence of this viral infection in such patients. Studies on murine CMV infection have demonstrated that this infection can be enhanced by histoincompatible graft or by cyclophosphamide in a model that is very close to the kidney recipient. As in mice, CMV infection in kidney recipients apparently results from reactivation of a latent infection. It seems to play a major role in the LD observed and could apparently lead to chronic hepatitis and even to cirrhosis of the liver. Finally, the occurrence of LD in HBsAg-, anti-HBs- and antiCMV-negative patients would suggest the responsibility of other viruses for the pathogenesis of liver disease in patients treated by hemodialysis and kidney transplantation. Besides Epstein-Barr virus, other viruses, such as hepatitis C virus, should be thoroughly scrutinized.

Adult↗

Antibody and cell-mediated immunity to a DNA free herpes simplex subunit vaccine.

The immunogenicity of a DNA free herpes simplex subunit vaccine was evaluated in chimpanzees and rabbits. The results clearly demonstrate that 1 injection of 3 micrograms/kg elicited antibodies as well as cell-mediated immunity in all the animals studied. These antibodies persisted for at least 6 months. Furthermore the vaccine also protected 50% of the animals against an experimental infection and reduced the rate of latent infection in nervous sensory ganglia.

Animals↗

Diagnosis of hepatitis B by Dane particle associated DNA polymerase assay.

We have studied prospectively 478 subjects exposed to hepatitis B virus and 20 pregnant women who developed HBs antigen during the last trimester of pregnancy. The results suggest that the DNA polymerase assay might be useful for the diagnosis of hepatitis B infection and that in confirmed cases of hepatitis, the enzyme might be detected in the absence of HBs antigen. HBe antigen appeared in 19% of those subjects who developed HBs and a positive correlation between HBe antigen and DNA polymerase was found in 40% of the cases positive for this antigen. The data presented also suggest that HBe antigenemia in pregnant women is not consistently associated with HBs infection in the babies born to them. However the children born to HBe positive mothers are at higher risk than those born to HBe negative mothers.

Carrier State↗

Cytomegalovirus infection and graft survival in renal graft recipients.

We have studied 85 patients who received a renal transplant for CMV infection as well as for herpes simplex (HSV), herpes zoster (HZ), measles, mumps, rubella and hepatitis B. We found no evidence of primary or secondary infections for the non herpetic viruses except for hepatitis B infection that occurred in 17 per cent of the patients. CMV infection occurred in 87 per cent of the patients while antibody rises to HZ and HSV occurred in 30 and 13 per cent of the patients, respectively. The CMV infections occurred 2 to 4 months after the transplantation (mean time 11.1 weeks) and seemed to trigger the first episode of renal rejection that occurred earlier in the CMV infected group (mean time 12.1 weeks) than in the uninfected group (mean time 18.6 weeks). This difference in time is highly significant, p less than 0.001). However these CMV injections did not decrease the longterm survival of the grafted kidneys.

Adult↗