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J D Coonrod

Publications and source records attributed to J D Coonrod.

13 recordsLinked to original sources

Interaction of pneumococcal antigens with complement in rats.

Complement activation with pneumococcal antigens was studied both in vitro and after injection of the antigens into rats. Whole pneumococci of various serotypes activated C3-C9 in rat serum treated with ethyleneglycol-bis (beta-aminoethyl ether)-N,N'-tetraacetic acid, although serotypes differed greatly in the extent of activation. Some purified pneumococcal capsular polysaccharides also activated C3-C9 in rat serum, but only when the antigens were present in concentrations of 500 to 1,000 mug/ml. Much of the activation with capsular polysaccharides was eliminated by the use of ethyleneglycol-bis (beta-aminoethyl ether)-N,N'-tetraacetic acid. Activation of C3-C9 by capsular polysaccharides did not correlate with the level of reactivity observed with whole organisms of the same serotypes. After injection of 5 x 10(9) pneumococci (type 3 or type 4) intravenously into rats, there was a transient decline in serum C3-C9 activity, but there was no decline in C3-C9 levels after intravenous injection of 1,000 mug of type 3 or type 4 capsular polysaccharides. As determined by immunofluorescence, circulating capsular polysaccharide was deposited in several tissues, including the vascular endothelium and glomerular mesangium of the kidney. C3 was not detectable in these deposits, and there was no histological evidence of an inflammatory response. Capsular polysaccharides appear to be only weak activators of complement. Other pneumococcal antigens may be more important in the pathogenesis of hypocomplementemia in pneumococcal infection.

Animals

Complement levels in pneumococcal pneumonia.

Levels of complement proteins and functional activity of the alternate complement pathway were assessed in 39 patients with pneumococcal pneumonia. Mean levels of C3 and properdin and the functional activity of the alternate pathway in acute sera were significantly (P less than 0.05) below normal, whereas levels of components of the early classical pathway were normal. Although levels of factor B were in the normal range, they correlated significantly with C3 levels; there was no significant relation between C3 levels and C4 or C1q levels. The 19 patients iwth pneumococcal pneumonia and bacteremia had significantly lower mean values of properdin and factor B than the 20 patients without bacteremia, suggesting a more severe depression of the alternate complement pathway with bacteremia. During convalescence, complement levels were normal or elevated in most of the patients, but mean levels of properdin remained significantly below normal in bacteremic patients. Functional activity of the alternate pathway also remained below normal. These results indicate that there is a selective depression of the alternate pathway in patients with pneumococcal pneumonia, and they are consistent with the concept that the alternate pathway has an important role in host defenses in pneumococcal infection.

Adult

Complement-fixing antibody response in pneumococcal pneumonia.

Previous studies of complement-fixing antibodies to pneumococcal capsular polysaccharides in humans have yielded conflicting results. We studied 65 sera from 25 patients with pneumococcal pneumonia, using both fresh sera and heat-inactivated sera with added human complement. Only 4 of the 25 patients developed detectable levels of complement-fixing anticapsular antibody. Of the 25 patients, 22 developed detectable levels of hemagglutinating anticapsular antibody, indicating that they were able to develop an immunological response during the infection. Most of the antibody detected by hemagglutination was sensitive to 2-mercaptoethanol, but some 2-mercaptoethanol-resistant antibody was also detected. In studies with rabbit antiserum, the complement fixation test was found to be as sensitive as the hemagglutination test for detection of anticapsular antibody. It is not clear why detectable levels of complement-fixing antibody do not develop more often in patients with pneumococcal pneumonia. Studies of purified anticapsular antibody would be of interest to determine whether or not these antibodies are restricted to immunoglobulin subclasses having a limited capacity to fix complement.

Adult

Detection of penumococcal antigens in the sputum in pneumococcal pneumonia.

Forty-seven patients with bacterial pneumonia were grouped by use of clinical criteria according to the relative certainty of a diagnosis of pneumococcal pneumonia. Sputums were tested for pneumococcal antigens by counterimmunoelectrophoresis with polyvalent pneumococcal antiserum. Antigens were detected in the sputum of 29 of 39 patients with evidence of pneumococcal pneumonia, and there was good correlation between the detection of antigens and the degree of certainty of the clinical diagnosis. Antigens persisted briefly in the sputum during therapy with antimicrobial drugs and could be detected during the first 48 hours of therapy in most cases of pneumococcal pneumonia. Pneumococci were isolated from the sputum in only 18 of 39 cases of pneumococcal pneumonia, and sputum cultures did not correlate as well as counterimmunoelectrophoresis with clinical diagnoses. In studies of 27 patients with chronic bronchitis without pneumonia, pneumococci were isolated from sputum in 10 cases, whereas counterimmunoelectrophoresis was positive in 5 cases. Counterimmunoelectrophoresis provides a simple and rapid method for detecting pneumococcal antigens in sputum, and it appears to be more reliable than sputum cultures in establishing a presumptive diagnosis in pneumococcal pneumonia.

Adult

Antigenicity of type-specific pneumococcal polysaccharides in rats.

Hemagglutinating antibody responses of Lewis-Wistar and Sprague-Dawley rats to graded doses of type-specific pneumococcal polysaccharide were measured. Rats given a small dose (0.2 to 50 mug)of type 1 or 8 polysaccharide intraperitoneally developed type-specific hemagglutinating antibody. Rats given larger doses of polysaccharide (greater than or equal to200 mug) did not develop detectable hemagglutinating antibody, and they were unresponsive to a subsequence injection of a small (and normally antigenic) dose of polysaccharide. There was prolonged antigenemia in rats injected with a large dose of polysaccharide. There was prolonged antigenemia in rats injected with a large dose of polysaccharide, and the kinetics of antigen clearance in these animals resembled that reported for mice with polysaccharide immunological paralysis. These results indicate that a phenomenon resembling immunological paralysis with type-specific pneumococcal polysaccharides can be produced in rats.

Animals

Latex agglutination in the diagnosis of pneumococcal infection.

A latex agglutination (LA) method for detection of pneumococcal antigens was evaluated and compared with counterimmunoelectrophoresis (CIE). LA was 2 to 10 times more sensitive than CIE for the detection of purified capsular polysaccharides in defined media, but only when a 1+ or 2+ agglutination reaction was interpreted as positive. LA was much less sensitive than CIE with clinical samples. In 50 cases of pneumococcal pneumonia, antigen was detected in the serum almost twice as often with CIE (40%) as with LA (22%). LA was positive in six cases of pneumonia where CIE was negative; however, in three of these cases, antigen was detected only in undiluted sera, which raised some question about the specificity of the result. With 18 samples of cerebrospinal fluid (CSF) from 11 patients with pneumococcal meningitis, the CIE test was positive more frequenlty (14 samples) than was LA (11 samples). Moreover, antigen was detected in CSF by LA in only one additional patient than was positive by CIE alone. There was one false-positive LA reaction among 45 samples of CSF from patients without pneumococcal infection. Although LA is a less complicated method than CIE, it is not a sensitive test for pneumococcal antigens and would be of little value as a routine diagnostic method.

Antigens, Bacterial

Etiologic diagnosis of intrapleural empyema by counterimmunoelectrophoresis.

Cultural methods failed to identify the infecting organism in 4 patients with intrapleural empyema. Antimicrobial drugs had been administered to 3 of the patients before their admssion to the hospital. In each case, soluble polysaccharides believed to be those of pneumococcus or hemophilus were detected in the empyema fluid by counterimmunoelectrophoresis. These findings provided a rational basis for management of antimicrobial therapy for 3 of the patients and useful information on the origins of the empyema in the fourth patient. Counterimmunoelectrophoresis is a useful additional method for presumptively identifying the infecting organism in patients with intrapleural empyema.

Adult

Pneumococcal pneumonia: capsular polysaccharide antigenemia and antibody responses.

Capsular polysaccharide was detected in the serum in 19 of 46 patients with pneumococcal pneumonia. Antigenemia was strongly associated with bacteremia and with infection by low-numbered serotypes. During antibiotic therapy, the concentration of polysaccharide in the circulation declined progressively, but circulating antigen remained detectable in two thirds of cases for 2 weeks or longer. The development of measurable type-specific antibody was delayed in patients with antigenemia. It is not known whether this delay was due to diminished antibody production or to neutralization of antibody by circulating antigen. Despite effective antibiotic therapy many patients with antigenemia had a severe and protracted illness; this may have been related to diminished availability of antibody early in the infection.

Adult

Antigenemia in fulminant pneumococcemia.

Two asplenic patients with fulminant pneumococcemia developed purpura and coagulopathy. Levels of C3 and C4 in the serum were low. Both patients had high levels of circulating capsular polysaccharide, and one patient had visible diplococci on a smear of the peripheral blood. Pneumococcal group C polysaccharide (C-substance) was detected in the serum of one of the patients. Possible pathogenetic relation of circulating pneumococcal antigens to the development of coagulopathy in pneumococcemia is discussed.

Adolescent