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Biomedical subjects

A Wunderlich

Publications and source records attributed to A Wunderlich.

6 recordsLinked to original sources

Encystation and expression of cyst antigens by Giardia lamblia in vitro.

The cyst form of Giardia lamblia is responsible for transmission of giardiasis, a common waterborne intestinal disease. In these studies, encystation of Giardia lamblia in vitro was demonstrated by morphologic, immunologic, and biochemical criteria. In the suckling mouse model, the jejunum was shown to be a major site of encystation of the parasite. Small intestinal factors were therefore tested as stimuli of encystation. An antiserum that reacted with cysts, but not with cultured trophozoites was raised in rabbits and used as a sensitive probe for differentiation in vitro. Cultured trophozoites that were exposed to bile salts showed a more than 20-fold increase in the number of oval, refractile cells that reacted strongly with anticyst antibodies, and in the expression of major cyst antigens. Exposure to primary bile salts resulted in higher levels of encystation than exposure to secondary bile salts. These studies will aid in understanding the differentiation of an important protozoan pathogen.

Animals

Protection against gram-negative bacteremia and endotoxemia with human monoclonal IgM antibodies.

Hybridomas producing human monoclonal IgM antibodies (mAbs) against bacterial lipopolysaccharide (LPS) were generated by fusion of B lymphocytes from sensitized human spleen with heteromyeloma cells. The splenocytes were from patients undergoing splenectomy during staging for Hodgkin disease after vaccination with the J5 mutant of Escherichia coli, which is deficient in O antigenic side chains. This deficiency exposes the core oligosaccharide, common to LPS of all Gram-negative bacteria. The mAbs cross-reacted strongly with endotoxins from a wide range of unrelated species of Gram-negative bacteria. The mAbs also gave strong protection against LPS in the dermal Shwartzman reaction and against lethal Gram-negative bacteremia in mice. These findings indicate that monoclonal IgM against LPS endotoxin can neutralize its toxicity in vivo and might be valuable for treatment of patients with Gram-negative bacteremia. Analysis of one of the hybridoma clones, A6(H4C5), showed that the IgM mAb is directed against the covalently bound lipid A, which represents the most conservative and least variable structural element of LPS.

Animals

Immunity to pasteurellosis in compromised rabbits.

Pasteurellosis in the rabbit inoculated with a malignant variant of Shope fibroma virus (SFV-MV) is presented as a model for the study of immunosuppression and immunoprophylaxis in pasteurellosis. The rabbits, before the inoculation, were healthy carriers of Pasteurella multocida. They were intradermally inoculated with SFV-MV, and 3 to 6 days later, a primary tumor appeared at the site of inoculation. By postinoculation day (PID) 7 or 8, the rabbits had snuffles, conjunctivitis, and tumor metastases; death occurred on PID 10 to 14. Rabbits given the nonmalignant Patuxent strain of SFV developed local primary tumors, but not pasteurellosis nor metastases. In SFV-MV-inoculated rabbits, there was decreased responsiveness of spleen lymphocytes to B and T cell mitogens by day 6, and of spleen and peripheral blood lymphocytes by day 10. In addition, SFV-MV antigen was detected (by immunofluorescence) in mononuclear phagocytes in all major organs and in epithelial cells of the conjunctiva and nasal mucosa. Both nasal and conjunctival epithelia showed squamous metaplasia as well. These changes did not appear in SFV-infected rabbits. With SFV-MV-inoculated rabbits, we obtained partial protection against pasteurellosis by immunization with heat-killed P multocida or a cross-protective core lipopolysaccharide mutant of Escherichia coli (J5). Rabbits were immunized before the inoculation with SFV-MV which precipitated "spontaneous" pasteurellosis due to impaired defenses. Rabbits immunized with J5 or P multocida had less severe conjunctivitis and snuffles than nonimmunized controls, indicating that immunization with the J5 mutant may be useful as prophylaxis against pasteurellosis in compromised hosts.

Animals

Role of urinary solutes in natural immunity to gonorrhea.

Natural resistance of the male urethra to gonococci has not been explained by classical immune mechanisms but could result from antibacterial properties of urine. Accordingly, we measured survival in midmorning urine of 10(7) F-62 T2 gonococci per ml by serial dilutions and plate counts. Fifteen killer urines from eight people all killed greater than 3 logs (average, 5.3), and 13 of 15 were sterilized. Fourteen nonkiller (inhibitor) urines from seven subjects allowed no growth. Killer urines were more acidic (pH 5.4 versus 6.4) and more concentrated (861 versus 717 mosmol/kg) than nonkillers. Upon addition of hydrogen ion, urea, and sodium chloride to urines and broth, pH proved to be the major killing factor, but urea and NaCl were also bactericidal. Susceptibility to urine bactericidal power did not vary with colony type (T2 versus T4) or strain (F-62 versus two fresh isolates). Killing was rapid (0.5 to 3 h) and not bacteriolytic. Escherichia coli multiplied 10-fold in urines that inhibited growth of gonococci. Thus, the bacteriostatic effect of urine may explain why gonococci do not infect the bladder and kidney during gonorrhea. The bactericidal properties of urine may contribute to resistance against gonococcal urethritis.

Bacteriolysis