PubMed HealthSearch

Biomedical subjects

E A Petersen

Publications and source records attributed to E A Petersen.

11 recordsLinked to original sources

Effective therapy of the LP-BM5 murine retrovirus-induced lymphoproliferative immunodeficiency disease with diethyldithiocarbamate.

The effects of therapy with the immunomodulator diethyldithiocarbamate (DTC) on the manifestation and natural history of LP-BM5 murine retrovirus infection in adult C57 Black 6 mice was investigated. DTC itself, had limited effects on the spleen weight, serum IgM, or mitogen responses of the non-virus-infected control mice when evaluated over a 9-week period. The virus inoculum administered was such that there was approximately a twofold increase in serum IgM and a halving of phytohemagglutinin (PHA) and lipopolysaccharide (LPS) responses in about two weeks and death of all animals by about 26 weeks postinfection. Doses of DTC of 20 and 200 mg/kg weekly or 5 days per week (intraperitoneally) in mice with LP-BM5 infection did not alter the manifestations or course of the disease. Doses of 400 or 600 mg/kg given 5 days per week, starting either 2 weeks before or the day of virus inoculation significantly reduced hypergammaglobulinemia, spleen weight, lymphadenopathy, and also prolonged survival. A dose of 400 mg/kg started 2 weeks after virus inoculation resulted in partial prevention of hypergammaglobulinemia, splenomegaly, and lymphadenopathy as well as 100% survival compared with 12.5% in non-drug-treated controls at 23 weeks after virus inoculation. The 9 surviving animals in the treated group were then allocated to continue treatment or stop treatment. In the animals without further treatment, lymphadenopathy and mortality occurred starting within 6 weeks after cessation of therapy while the animals with continued treatment remained in good condition for 40 weeks. There was only a very limited and transient effect of DTC therapy on the decline of the proliferative responses to phytohemagglutinin or lipopolysaccharide in any of the treated groups in the above described experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome

Transfer of delayed hypersensitivity in mice to microbial antigens with dialyzable transfer factor.

Dialyzable Lawrence-type transfer factor was prepared from the spleen cells of CF1 mice inoculated with Coccidioides immitis- and Candida albicans-killed vaccines and with live Mycobacterium tuberculosis vaccine (BCG). These preparations were shown to transfer antigen-specific cell-mediated immunity to naive mice, as measured by the delayed skin test and footpad-swelling methods. Reactivity could be demonstrated when the test antigens were given 24 h after the transfer factor, but not when they were given simultaneously. Coccidioides-specific transfer factor was shown to be sensitive to Pronase and resistant to trypsin and ribonuclease. A preparation of BCG transfer factor was sensitive to snake venom phosphodiesterase.

Animals

Delayed hypersensitivity to fungal antigens in mice. I. Use of the intradermal skin and footpad swelling tests as assays of active and passive sensitization.

Mice were sensitized to Coccidioides immitis and Candida albicans antigens and tested for sensitivity by the intradermal and footpad swelling methods. In mice actively sensitized with killed antigen, antigen-specific intradermal and footpad induration responses occurred 24 and 48 hr after sensitization. Antigen-specific intradermal and footpad responses were transferred to normal mice with spleen cells from immune animals. Such responses were also transferred with normal spleen cells that had been incubated in vitro with immune RNA preparations. Histologic studies of intradermal reactions showed a mixed response of neutrophilic and mononuclear leukocytes, with slight vascular involvement compatible with delayed hypersensitivity. No intradermal or footpad responses were observed 4, 24, or 48 hr after injection in recipients of serum from actively sensitized mice. Histologic examination of skin sites in these mice revealed only a polymorphonuclear response. It is concluded that these intradermal and footpad responses are the result of delayed hypersensitivity and can be used as assays for this type of immunity in mice.

Animals

Delayed hypersensitivity to fungal antigens in mice. II. Molecular classes in immunogenic RNA extracts that transfer delayed hypersensitivity.

The transfer of delayed hypersensitivity to Coccidioides immitis and Candida albicans antigens with immunogenic RNA extracts was studied in a mouse model. Sensitivity was measured by skin tests and footpad swelling responses. Immunogenic RNA converted normal spleen cells in vitro so that they produced antigen-specific delayed hypersensitivity in mice that were given injections of the cells. RNase reduced the rate of, but did not abolish, in vitro interaction of immunogenic RNA extracts with lymphocytes. Immunogenic RNA transferred sensitivity on direct intraperitoneal inoculation into mice. The transfer ability was resistant to RNase preparations active against both single- and double-stranded RNA. Sedimentation gradient fractions of the immunogenic RNA were assayed by intraperitoneal injection, and converting activity was found in two fractions, greater than 33S and 6S-13S. After treatment with RNase, all activity was shifted to the less than 6S fraction. Two fractions of the immunogenic RNA in its native state (greater than 33S and 6S-13S) were also able to convert spleen cells. The data indicate that the transfer of delayed hypersensitivity by immunogenic RNA preparations is associated with RNA but may not require the intact RNA molecule.

Animals

Delayed hypersensitivity to fungal antigens in mice. II. Characterization of the active component in immunogenic RNA extracts.

In a mouse model, cell-mediated immunity to Coccidioides immitis, as assayed by the delayed hypersensitivity skin test, was transferred with whole immunogenic RNA extract and its greater than 33S and 6S-13S sedimentation fractions. Both fractions were cleaved by RNase, but the products retained their transfer activity. The greater than 33S fraction of immunogenic RNA extract was inactivated by pronase, whereas the 6S-13S fraction was resistant to the proteolytic enzyme; however, after RNase treatment the latter fraction was sensitive to pronase. This finding suggests a protective role for RNA. Dialysis of immunogenic RNA extract yielded a dialysate with a ratio of absorbance at 260 nm to that at 280 nm (A260:A280) of 1.02. Similarly, the dialysis product of RNase-treated RNA is active and has an A260:A280 ratio of 1.34. The data indicate that at least part of the active moiety of immunogenic RNA extracts is an RNA-associated, pronase-labile peptide or nucleopeptide. Furthermore, it is possible that the dialyzable transfer factor may be the same peptide or nucleopeptide cleaved from immunogenic RNA during preparation of the transfer factor.

Animals

Bacterial endocarditis at Blegdamshospitalet in Copenhagen 1944-1973.

The clinical pattern of 34 cases ob subacute bacterial endocarditis (SBE) and 46 cases of acute bacterial endocarditis (ABE) is outlined. In the SBE group the mortality was 9% and the incidence of major complications during the treatment period was 15% for cerebrovascular accidents, 9% for other systemic or pulmonary emboli and 9% for congestive heart failure indicating valvular damage. In 31 bacteriologically proven cases growth was obtained in 68% of all blood cultures, and in 94% of the cases at least one positive culture was among the first 5 ones drawn. In the ABE group the overall mortality was 72% and mortality for cases occurring after 1960 was 58%. Major factors contributing to death were valvular incompetence, uncontrolled infection and embolisation. In order to reduce major complications and resulting disability in SBE it is suggested that treatment be started on clinical suspicion as soon as 5 blood cultures have been drawn over a period of 48 hours. Attempts to reduce mortality in ABE may include cardiac surgery in the acute phase.

Acute Disease

Coccidoidouria: clinical significance.

Twelve patients had urine cultures positive for Coccidioides immitis. Ten patients showed the usual criteria for dissemination, but 2 were believed, before urine culture, to have only chronic pulmonary involvement. In 8 patients, there was impairment of host defense mechanisms due either to associated disease or immunosuppressive drug therapy. Only 2 of 11 patients tested reacted to coccidioidin skin-test antigen. Colony counts of C. immitis in the first voided morning urine spacimens ranged from 0.03/ml to 17/ml. With prostatic involvement, colony counts in the expressed secretions ranged from 15/ml to 120/ml. The site of urinary tract coccidioidomycosis, which could be adduced in 9 patients, was the upper tract in 1, lower tract in 6, and in both upper and lower tracts in 2. In patients with lower tract infection, the prostate was involved in 4 and the epididymis in 2.

Adult

Varicella followed by glomerulonephritis. Treatment with corticosteroids and azathioprine resulting in recurrence of varicella.

The present report outlines the clinical features of a 2-year-old boy who following varicella developed purpura of the lower extremities, transient gastrointestinal bleeding and glomerulonephritis. The triad of symptoms suggests Schonlein-Henoch Syndrome, but coagulation studies and renal biopsy did not confirm this, and varicella is thought to be the cause of the complications. Therapy with corticosteroids and azathioprine had only a minor effect on the nephritis but caused depression of serum IgG and specific antibody resulting in reinfection or reactivation of varicella.

Azathioprine