Biomedical subjects
Publications and source records attributed to G Cukor.
Analysis by radioimmunoassay of pediatric sera from three populations showed that antibody to Norwalk virus is acquired at a significantly earlier age in a less developed and tropical area (Philippines) than in two more developed and nontropical countries (United States and Taiwan).
A prospective study of diarrhea was conducted among 98 U.S. Army soldiers during their first six weeks in South Korea. Diarrhea developed in 54 (55%) of 98 soldiers and had a mean duration of five days. Infections with Salmonella, Shigella, Vibrio, enterotoxigenic Escherichia coli, enteroviruses, and intestinal parasites were uncommon. Four (8%) of 50 soldiers with documented diarrhea, two (6%) or 32 with a history of diarrhea, and one (3%) of 29 who denied gastrointestinal symptoms had serologic evidence of a recent rotavirus infection. The etiology of diarrhea among U.S. soldiers who had recently arrived in South Korea differed from the etiology among travelers in warmer climates, where enterotoxigenic strains of E. coli were responsible for the majority of cases. Further efforts are needed to define other enteric pathogens in the etiology of diarrhea among new arrivals in different parts of the world.
A solid-phase microtiter radioimmunoassay was established for the detection of Norwalk virus and its antibody, with clinical materials from human volunteers previously studied in Massachusetts as reagents. A study of 308 Massachusetts residents showed that serum antibody to Norwalk agent was rarely present during childhood but was detectable in approximately 50% of adults. All volunteers inoculated with Norwalk virus who developed illness seroconverted (10/10), whereas only one-third (5/15) of nonill volunteers seroconverted (P = 0.0009). The 10 nonill, nonseroconverting subjects had undetectable to low preexisting antibody levels. Paradoxically, 10/13 subjects with preexisting antibody became ill, whereas 17/25 lacking antibody did not (P = 0.009). All 3 subjects with preexisting anti-Norwalk radioimmunoassay blocking activity in duodenal intraluminal fluids became ill, whereas only 5/11 lacking such activity developed illness (P = 0.15). These data further support the unique concept that some individuals are susceptible to repeated infections with this agent, whereas others are incapable of developing infection.
Human milk obtained from 21 American nursing mothers was studied for the presence of secretory immunoglobulin A antibody to rotavirus, the most common etiological agent of infantile gastroenteritis. Antibody was quantitated by adaptation of a recently described solid-phase radioimmunoassay technique that employs simian rotavirus as a convenient substitute antigen for human rotavirus. Of the mothers tested, 80% (12 of 15) possessed milk antibody within a week of parturition, whereas 56% of those tested (5 of 9) secreted milk antibody as late as 6 or 9 months postpartum. Specificity of the radioimmunoassay was demonstrated by absorption of antibody with purified rotavirus. Our detection by radioimmunoassay of antibody to rotavirus in milk samples collected past the colostrum stage is in contrast to other studies that have failed to detect antibody in human milk by immunofluorescence or neutralization tests. The present study also suggested that the appearance of secretory immunoglobulin A antibody in the milk of mothers previously lacking milk antibody may be correlated with subclinical infection of the mother with rotavirus.
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Of 82 children hospitalized with diarrhea in the Philippines during January-June 1976, 14 (17%) had infections due to a reovirus-like agent as determined by detection of viral particles in stools by electron microscopy (12 [15%] of 82) and/or by a rise in titer of antibody to the serologically related Nebraska calf diarrhea virus (eight [20%] of 39). Escherichia coli producing heat-labile enterotoxin were found in six (7%) of 82 ill children and two (4%) of 49 healthy control children, while E. coli producing heat-stable enterotoxin were isolated from three children with diarrhea and two without gastroenteritis. Thirty-eight percent of enterotoxigenic E. coli isolated from children with diarrhea, but only 6% of isolates from healthy control, were of serotypes similar to those of enterotoxigenic E. coli isolated in previous studies of these pathogens by other investigators in geographically diverse areas (serotypes O6:H16, O8:H9, and O78:H12) (P less than 0.05). Eight (10%) of the children had infections with multiple enteric pathogens.
A simplified radioimmunoassay (RIA) technique was developed to facilitate the diagnosis of human rotavirus in stools of infants with diarrhea. This microtiter solid-phase RIA utilizes as a critical reagent hyperimmune serum against a tissue culture-grown simian rotavirus that is immunologically closely related to the human agent. One hundred thirteen pediatric stool samples were tested. Thiry-five specimens known to be positive for rotavirus by electron microscopy were also positive by RIA. All RIA-positive reactions (36) were shown to be specific for rotavirus by means of an antibody-blocking test. Nonspecific RIA-positive reactions were not encountered. This accurate, sensitive RIA technique is practical for use in diagnostic laboratories because critical serum reagents are prepared against culture-grown virus and not against rotavirus derived from carefully selected stools of humans or experimentally infected gnotobiotic animals.
A battalion of United States Marines traveling to South Korea in the spring of 1976 was studied to determine the incidence and etiology of gastroenteritis. During the three weeks they visited South Korea, 21% of 694 marines developed diarrhea. Stool and serum specimens collected before, during, and after their stay were examined for evidence of infection with Salmonella, Shigella, and Vibrio species, enterotoxigenic and invasive Escherichia coli, reovirus-like agent (RVLA), and intestinal ova and parasites. Infections with these agents were uncommon; 91% of 44 closely studied cases of gastorenteritis were unexplained. Five per cent of 169 marines had serologic evidence of recent infection with RVLA, and 3% of 273 marines had serologic evidence of infection with heat-labile enterotoxin producing E. coli over an eight-week period. However, infections with these agents were not associated with most cases of diarrhea in South Korea. It is concluded that infectious agents previously thought responsible for travelers' diarrhea were not responsible for gastroenteritis among United States Marines arriving in a temperate climate.
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Infection of herpes simplex virus type-2-transformed hamster tumor cells with adeno-associated virus type 1 before inoculation into hamsters specifically delayed the appearance of palpable tumors and increased the survival time of the animals. The data indicated that a defective virus of humans can influence cancer expression by a virus-transformed cell.
Normal and transformed rabbit kidney cells are killed by heat-dissociated diphtheria toxin fragments, whereas human (heLa), mouse (L929), and hamster (BHK and 333-8-9) cells are not affected.
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Diphtheria toxin splits into two fragments when heated at 100 C for 10 min in a phosphate buffer. The separated fragments have molecular weights of 24,000 and 39,000, respectively. These molecular weights are similar to those of the A and B fragments found in diphtheria toxin preparations after thiol reduction. Since the separation of toxin into fragments is not complete, it is likely that only nicked toxin molecules having a cleaved peptide bond are split by heating. When toxin is suspended in phosphate buffer at pH 6.4, the B-like fragment precipitates, but at pH 7.8 it does not. Heated toxin is unable to intoxicate sensitive cells or cause a necrodermal response in animals. Fragment A produced by heating is active in inhibiting cell-free protein synthesis. It is able to intoxicate both HeLa and L cells when the uptake of the fragment is facilitated by addition of polyornithine to the cultures. Fragment B produced by heating is involved with binding to the cell surface. It is able to delay the action of toxin on KB cell cultures preincubated with fragment B.