SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
A patient with botulism (type E) has been subject to complex therapy, which involved specific serotherapy, infusion therapy, and controlled lung ventilation with the following assisted lung ventilation.
Using a model system in which mature lymphocytes were adoptively transferred into immunodeficient C.B17-scid/scid recipients, the requirement for CD4+ T cells in rejection of previously healed-in multiple minor-H-antigen-disparate skin grafts was investigated. Depletion of functional CD4+ cells was accomplished by anti-CD4 antibody + complement treatment prior to adoptive transfer followed by chronic anti-CD4 serotherapy in vivo. Homozygous scid mice harboring nondepleted naive donor cells effectively rejected minor-H-antigen-disparate grafts, whereas scid/scid mice harboring CD4+ T-cell-depleted naive cells did not. Homozygous scid mice harboring minor-H-antigen-primed cells rejected the minor-H-antigen-disparate allografts regardless of whether or not the animals had received anti-CD4 treatment, although rejection by the mice receiving anti-CD4 treatment was retarded compared to mice not receiving anti-CD4 treatment. All the mice that received viable donor cells rejected minor + H-2 disparate allografts, demonstrating effective immunity in this case was not dependent upon the activity of CD4+ T cells. These data suggest that in responses against multiple minor-H-antigen-disparate tissue, primary allograft rejection is absolutely dependent upon CD4+ cells, and secondary allograft rejection is not. The implications of these findings in understanding interactions of T cell subsets in vivo and of the utility of using homozygous scid mice as recipients for exploring the function of transferred lymphoid cell populations are discussed.
Lymphokine-activated killer (LAK) cells were successfully generated in all cases from blood mononuclear cells obtained from six patients with lymphoma. The LAK cells from three of these patients and from five normal adult donors were tested for their effector abilities in antibody-dependent cellular cytotoxicity (ADCC) against guinea pig leukemic lymphocytes coated with various antiidiotype antibodies. Cells from all the donors behaved similarly. Mouse monoclonal antibodies of IgG1, IgG2a, and IgG2b isotypes invoked no ADCC. However, substantial ADCC was invoked by the chimeric antibody FabFc, in which Fab'gamma from mouse antiidiotype is thioether-bonded to human normal Fc gamma. Similar results were obtained on testing LAK cells from a normal donor against uncultured human lymphoma targets coated with native or chimeric antiidiotype. The ADCC invoked by the mouse-human chimeric antibodies appears to depend on the human Fc gamma they display and not on the univalency of the derivatives used. The findings imply that LAK technology could usefully augment serotherapy that uses antibody derivatives displaying human Fc gamma.
Tetanus immunity has been studied in a population of mechanics working at the car-factory "Renault". For the study, 283 individuals were divided into 3 groups. The first group consisted of non-vaccined individuals, the second of vaccinated individuals and the third of individuals who had been boostered. The influence of different parameters on tetanus immunity status was considered, i. e. the age of the subjects, the time at which boostering was given, the serotherapy (when it was administered) and the contact with machine lubricating and cooling fluids. Clostridium tetani bacilli and spores were frequently found in aqueous machine fluids. Their presence is a potential hazard for non-vaccinated mechanics coming to contact with the fluids. Tetanus antibody levels in the sera of the tested population were determined in vivo by the toxin neutralization test. The influence on tetanus immunity of the different parameters considered in this paper was subjected to statistical analysis. From the whole population, 27% of the individuals were found to have no protection against tetanus. When age was taken into account, 53% of the individuals over 45 years old and 10% of those under 45 years old were shown to be devoid of tetanus immunity. It could be shown that younger individuals were better protected than older ones, because the formers had been immunized with adsorbed tetanus toxoid and most of the latters with fluid toxoid. Of the individuals in the third group who had received a booster injection within 15 years after primo-vaccination, 98% showed protective tetanus antibody levels in their sera in contrast to 25% when boostering had occurred more than 15 years after primo-vaccination. Contact with machine fluids was found to influence the degree of immunity of only those individuals whose boostering dated back to more than 25 years. Unexpectedly, 3 mechanics seemed to develop immunity after coming into contact with machine fluids. From the results reported here, it is concluded that tetanus immunity in vaccinated individuals should be renewed by a compulsory booster injection given every 5, 10 or, at the minimum, 15 years. Moreover, high-risk populations such as that represented by the mechanics should be immunized or boostered on commencing employment.
Acute digitalis intoxication is infrequent and severe. The mortality rate is between 15 and 20 per cent. Its treatment has been greatly improved with the appearance, in 1976, of a specific serotherapy: Fab fragments of antidigoxin antibodies. The clinical experiment reported in the literature relates to approximately one hundred cases and establishes that this therapy has a practically constant and non dangerous efficacy. The lack of availability of these fragments Fab represents presently the only obstacle to the development of this treatment, but the use of monoclonal antibodies, already available experimentally, should, in the future, circumvent this last hurdle.
Contemporary bacterial serology relevant to medicine involves poly- and monoclonal antibodies to study pathogenic bacteria and nonpathogenic organisms useful in controlling infectious diseases. Monoclonal antibody applications include immunodiagnostics, prophylaxis and serotherapy, and microbial biotechnology and molecular immunochemistry. If used in parallel with antisera, the analytic potential of monoclonal antibodies is better realized. However, the entire range of advantages from the use of monoclonal antibodies can only be attained if the antibodies are well characterized.
The surface immunoglobulin of B-lymphocytic tumours is well characterized at the molecular level and in its idiotypic determinants offers antigenic targets which are effectively tumour-specific. Anti-idiotype antibodies raised individually for each tumour have been used for passive serotherapy in animals and man. The advent of monoclonal technology has added further precision, and can readily provide the large quantities of antibody which might sometimes be necessary. However, the therapeutic use of unmodified anti-idiotype has yielded a significant remission in only a minority of cases. Some factors thwarting the antibody can be readily identified; prominent among these are extracellular idiotypic immunoglobulin and antigenic modulation. Another major factor is our ignorance of appropriate effector mechanisms to be recruited, with one candidate mechanism being the activation of immunological suppressor circuits. Without such knowledge there is a large arbitrary element in the selection of antibody isotype, doses and schedules. Some groups suspect that antibody derivatives will eventually prove more effective than the native molecules. Univalent, chimeric univalent and toxin-bearing antibodies are among those being investigated. Monoclonal and molecular genetic technologies may play an increasing role in the engineering of such derivatives. The fast-growing animal lymphomas presently available as models cannot mimic more than a tiny fraction of human lymphomas. So the arena in which antibody therapy of B lymphoma will be decided is the clinic. Here the relatively innocuous nature of antibody treatment is a tremendous boon. However, with the mechanisms involved being multiple, complex and only partially understood we are unlikely to be favoured with rapid answers.
The ability of rat monoclonal antibodies to promote antibody-dependent cell-mediated cytotoxicity with human effector cells was tested by using a variety of antibodies against different human and mouse leukocyte antigens. It was found that only IgG2b antibodies were effective. This isotype has already been shown to be efficient in fixing human complement, which suggests that among rat monoclonal antibodies, the IgG2b subclass might be a good choice for attempts at serotherapy. Further studies with other antibody-mediated effector mechanisms as well as suitable clinical trials are merited.
Immunity in meningococcal diseases has been inadequately studied and, until now, most attempts at serotherapy and immunization against meningococcal meningitis have been unsuccessful. To ascertain the status of immunity among children at greatest risk of contracting the disease, 267 serum specimens from healthy children aged from 1 month to 5 years were examined with Farr's radioimmunological technique, as simplified by Gotschlich. The results showed that the children must have received maternal antibodies through the transplacental route. Antibodies persisted up to the third month of life, after which they were virtually undetectable until, at about 8 months of age, antibodies reappeared. Subsequently there was a gradual rise, especially from 2 to 5 years, 97% of children in the highest age group having serum antibody levels of 0.479 mug/ml or more. These children may have had meningococcal infections that were wrongly diagnosed as respiratory disease of unknown etiology.
Considerable variations were found in the content of virus neutralizing antibodies (VNA) to smallpox in 35 children with postvaccinal encephalitis (PVE) which developed after vaccination against smallpox: the titre of VNA was high in 7 children, negligible in 14, and in 6 children VNA were not present 3-4 weeks after vaccination. Dependence of the production of VNA on the peculiarities of individual development and premorbid state of the patients as well as on serotherapy was analysed; the role of the inhibitory effect of immunoglobulin on the process of antibody formation was excluded. No correlation was found between the isolation of vaccinia virus from the blood, liquor and throat of the children suffering from PVE (virus was isolated from 17 children) and the level of VNA. The content of immunoglobulins A, M and G in PVE patients did not essentially differ from the corresponding age norm, though the increase in IgM and IgG in response to vaccination was absent or considerably delayed in most children. Importance of the obtained results for understanding the pathogenesis of PVE is discussed.
In experimental tick-borne encephalitis (TBE) in mice with suppressed immunity, the effectiveness of serotherapy increases markedly. Antibodies prevented the development of persistent infection in the immunosuppressed animals. Antiviral antibodies were shown in vivo to be capable of inhibiting the development of the damaging effect of T-killers immune to the virus. The experimental evidence permits one to formulate the principle of pathogenetic immunotherapy of acute forms of experimental TBE stipulating the use of specific antibodies in the presence of temporary inhibition of the T-cell function.
The regular finding of Pseudomonas aeruginosa in Burns Units has always been a source of worries. Following a brief review of the natural history of this micro-organism, the authors examine all possible therapeutic measures. They underline the importance of measures aimed at controlling environmental and epidemiological factors and at improving surveillance. These measures, together with baths, topical applications of antibacterial agents and prophylactic vaccination and serotherapy tend to circumscribe the infection. When therapeutic measures are not as effective as expected and natural defences collapse, sepsis develops with clinical features that male diagnosis uneasy. The conditions in which antibiotics are given are peculiar in burned patients, and the therapeutic approach to Pseudomonas infections is particularly difficult in such cases.
Graft-versus-host disease is one of the major problems in clinical bone marrow transplantation. Many experiments in animals have shown that it could be greatly reduced if mature T lymphocytes were removed from the donor marrow. Here we describe a new rat monoclonal antibody, CAMPATH 1, which is suitable for depleting lymphocytes from human marrow grafts. CAMPATH 1 is an IgM that fixes human complement. It binds to both T and B lymphocytes and some monocytes but not to other hemopoietic cells. When peripheral blood mononuclear cells were treated with CAMPATH 1 and complement, more than 99% of lymphocytes were killed and viable T cells could no longer be detected. Under these conditions, in vitro multipotential erythroid and myeloid colony-forming cells were unaffected. As well as being used for in vitro treatment of bone marrow to remove T cells, CAMPATH 1 could potentially be applied to other experimental and clinical situations where depletion of lymphoid cells is required, including serotherapy to achieve immunosuppression for organ transplants or to treat lymphocytic leukemias.
The authors conducted a comparative study of the therapeutical effectivity of ribonuclease, hetero- and homologic specific gamma-globulin used in 189 children with tick-borne encephalitis in the acute period of the disease. It was established that there was a significant advantage of ribonuclease before serotherapy. During ribonuclease treatment the febrile period of the disease was much less, while the meningeal symptoms disappeared more rapidly with normalization of the CSF.
We describe two cases of botulism caused by home-prepared under olive oil mushrooms. We stress the importance of an accurate anamnestic study and of the recovery of the toxic material for the diagnosis and therapy. The serological test on patient's blood, the isolation and the identification of botulinic toxin give the possibility to confer a specific character to the serotherapy The prevention of these toxic infections require a wide education on the preparation and storage of foods.
The authors report a case of tetanus in a 19 months infant who has only received BCG. After a four days period during which two laryngeal spasms occurred, the infant presents a generalized tetanus. The outcome was favorable with specific serotherapy myorelaxants and assisted ventilation of four weeks duration.
We infused the murine monoclonal antibody T101 into two patients with advanced refractory chronic lymphocytic leukemia (CLL) after confirming its reactivity with their CLL cells. One patient received doses of 1, 3, and 12 mg; the second patient received 10 mg. Antibody was delivered over 10--15 min. The major observations were: (1) T101 murine monoclonal antibody did bind to cells with T65 surface antigen and saturated these cells in vivo; (2) cells that bound T101 disappeared from the circulation by 2 hr after treatment, as evidenced by a marked drop in lymphocyte counts; (3) T101 serotherapy resulted in some intravascular cell injury associated with sequestration and probably destruction in the liver and lung; (4) free serum T101 was demonstrable, but disappeared by 2--4 hr after infusion; (5) rapid infusion of T101 did not induce significant modulation of T65; (6) rapid infusion of greater than 10 mg of T101 was associated with significant systemic reactions. Monoclonal antibodies may someday have an application in leukemia therapy, but additional experimental trials are clearly indicated.
We have conducted a clinical trial utilizing anti-thymocyte globulin (ATG) for the treatment of patients with non-Hodgkin's lymphomas. Six patients were treated; 50% reductions in tumor mass of short duration were observed in one patient with a T-cell lymphoma and two patients with B-cell lymphomas. In vitro assays have been performed in an attempt to study the reactivity and potential mechanism of antitumor action of the ATG. The ATG bound to essentially all normal blood mononuclear leukocytes as well as tumor cells from patients with T-, B-, or null cell lymphomas demonstrating its lack of specificity. Furthermore, complement-mediated lysis of normal mononuclear leukocytes, normal T- or B-cells, and tumor cells from two unresponsive patients were all comparable; moreover, since this lysis occurred only at concentrations of ATG that are not attainable in vivo, it is unlikely that complement-mediated cytotoxicity accounts for the responses observed. Peripheral blood lymphocyte counts and total erythrocyte rosettes did decrease during ATG treatment. Thus, objective tumor responses in both B- and T-cell non-Hodgkin's lymphomas can be achieved with a very nonspecific antiserum although significant toxicity resulted. Whether the magnitude or duration of response can be increased with monoclonal antibodies remains to be determined. Future success with serotherapy might require use of either a battery of different monoclonal antibodies or a single monoclonal antibody that can deliver radioisotopes, chemotherapy, or toxins to the tumor cells.