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Biomedical subjects

C R Young

Publications and source records attributed to C R Young.

At least 91 records · Page 5Linked to original sources
PubMed1980

Nutritive value of globin-amino acid and complementary globin-cereal mixtures.

Protein efficiency ratios (PER) were determined using male weanling rats fed diets containing bovine globin alone and with wheat and corn gluten. Simultaneous equations and graphical methods were devised for selecting combinations of globin and cereal proteins to provide optimal and suboptimal profiles of limiting amino acids. Supplementation of the globin with amino acids established isoleucine and methionine as limiting amino acids. Addition of globin, whose amino acid pattern is complementary to that of the cereal proteins, markedly improved the PER values of the proteins. However, growth rates of rats fed various combinations of proteins were not identical, even though PER values differed only slightly. The PER of combined proteins were not predictable from amino acid composition or from correlations between PER and chemical score based on National Research Council (NRC) requirements for essential amino acids. The inability of the optimal mixtures to meet expected nutritional performance clearly indicated that other factors affecting availability of amino acids are implicated. Nevertheless, mutual improvement of two incomplete proteins such as globin and wheat or corn gluten was demonstrated. Addition of globin to widely used diets consisting mainly of corn or wheat can be nutritionally beneficial.

Amino Acids↗
PubMed1980

Lack of person-to-person transmission of enterotoxigenic Escherichia coli despite close contact.

The scanty epidemiologic evidence available suggests that enterotoxigenic Escherichia coli (ETEC) are usually spread by contaminated food and water vehicles; little is known of the risk of secondary spread by contact transmission. Studies carried out in a 22-bed isolation Ward at the U. of Maryland Hospital gave the opportunity to determine whether individuals excreting ETEC, with and without diarrhea, would transmit the pathogen to controls living in close contact. In one combined study, seven volunteers who had ingested 10(8) virulent ETEC (strain H10407), were housed day and night for two weeks with eight other volunterrs participating in an intranasal attenuated influenza vaccine study. In a second study, four persons ingesting 10(8) ETEC (strain 214-4) lived with 13 who were inoculated with intranasal influenza vaccine. The individuals in the E. coli and influenza groups were randomly mixed in bedrooms and shared bathrooms, dining and recreation areas of the ward. Seven persons who ingested ETEC developed diarrhea; all 11 excreted the pathogen (10(7)-10(9) organisms/gm or ml of stool), and 10 had significant rises in anti-O or antitoxin antibody. In contrast, no influenza vaccinees, despite close sharing of facilities, developed diarrhea, excreted ETEC or had rises in antibody to E. coli antigens. These data suggest that ETEC are not readily transmitted to healthy adults by direct person-to-person contact. Precautions to prevent contamination of shared food sources would appear to be the most rational intervention to avoid secondary cases of ETEC diarrhea.

Adolescent↗
PubMed1980

Microtiter enzyme-linked immunosorbent assay for immunoglobulin G cholera antitoxin in humans: method and correlation with rabbit skin vascular permeability factor technique.

A microtiter enzyme-linked immunosorbent assay (ELISA) to measure immunoglobulin G cholera antitoxin in human serum has been developed. The ELISA employs commercially available reagents, including cholera enterotoxin and goat anti-human immunoglobulin G. It is specific, sensitive, and reproducible and requires as little as 5 microliter of serum. ELISA, moreover, permits quantitative determination of cholera antitoxin at a single serum dilution of 1:200. A total of 162 pre- and post-challenge sera from 49 volunteers who ingested Vibrio cholerae classical biotype, and 165 sera from 43 volunteers who ingested V. cholerae El Tor biotype, were tested for cholera antitoxin by ELISA and by the rabbit skin vascular permeability factor assay. The correlation between the two assays was statistically significant (P less than 0.001). ELISA for immunoglobulin G cholera antitoxin thus provides a valuable in vitro correlate of in vivo toxin-neutralizing capacity. Microtiter ELISA permits duplicate evaluation of at least 14 sera per 96-well plate including blanks and controls, is readily adapted to use in field studies, and therefore is particularly well suited to seroepidemiological surveys.

Animals↗
PubMed1980

Microtiter enzyme-linked immunosorbent assay for immunoglobulin g cholera antitoxin in humans: sensitivity and specificity.

Serum samples were obtained from 92 informed, community volunteers before and 10, 21, and 28 days after they ingested 10(3) to 10(6)Vibrio cholerae of Inaba or Ogawa serotype and classical or El Tor biotype as part of a cholera vaccine development program. Pre- and postchallenge sera were examined for neutralizing antibody to cholera toxin by the rabbit skin permeability factor and adrenal cell techniques. Immunoglobulin G-binding antibodies to cholera toxin were quantitated by enzyme-linked immunosorbent assay (ELISA) in serum diluted 1:200. The results obtained in these cholera volunteers were compared with a negative control population comprising 30 people who ingested enteropathogenic Escherichia coli or E. coli which produced heat-stable but not heat-labile enterotoxin. Although all three antitoxin assays correlated closely with each other in both groups of volunteers, ELISA was more sensitive than either neutralization assay in detecting both subclinical and overt cholera infections. Seroconversion was demonstrated by ELISA in 58 of 66 (88%) volunteers who excreted V. cholerae, including 50 of 54 (93%) with clinical cholera, compared with 47 of 66 (71%) and 52 of 66 (79%) by the rabbit skin permeability factor and adrenal cell techniques, respectively. Although ELISA does not measure the toxin-neutralizing activity of antibodies directly, it provides a practical alternative to the rabbit skin permeability factor and adrenal cell assays.

Journal Article↗
PubMed1980

Osteocartilaginous exostosis.

An osteocartilaginous exostosis (osteochondroma) is a developmental defect in which there is a disturbance in the location and direction of cartilaginous growth. It is found in children and adolescents, and several theories are found in the literature regarding its growth and etiology. When the lesion causes discomfort because of pressure on peripheral nerves and vessels, surgical excision is indicated. The authors discuss a case of osteocartilaginous exostosis in a 12-year-old black male whose postoperative course was uneventful. To date there has been no regrowth of the lesion.

Bone Neoplasms↗
PubMed1979

Genetic control of the immune response to mammalian chymotrypsins in mice. I. The immune response to high doses of bovine alpha-chymotrypsin.

The primary and secondary immune response to the antigen bovine pancreatic alpha-chymotrypsin was investigated in inbred mice. It was found that strain differences in the immune response only became apparent after secondary immunization. The genetic control of the immune response was investigated in twelve different strains of mice, F1, F2 and F1 backcross hybrids, following secondary immunization. A continuous distribution for the mean antibody responsiveness was obtained. High responsiveness was associated with both the H-2 haplotype and three non-H-2 loci. Furthermore the F1 hybrids produced a greater quantitative antibody response to chymotrypsin than either of the corresponding parental strains.

Animals↗
PubMed1979

Genetic control of the immune response to mammalian chymotrypsins in mice. II. The immune response to low doses of bovine alpha-chymotrypsin.

The immune response to the antigen bovine pancreatic alpha-chymotrypsin was investigated in ten recombinant strains of mice. Using a fixed antigen-percentage bound isotope technique, it was found that the quantity of antibody produced was related to the H-2 haplotype of the responding animal. A continuous distribution for the mean antibody responses was obtained for the ten strains of mice. High responsiveness was associated with the H-2 haplotype gamma2. The genetic control of the immune response to this immunogen was found to be both quantitative and qualitative.

Animals↗
PubMed1979

Immunity to enterotoxigenic Escherichia coli.

Enterotoxigenic Escherichia coli strains represent the most frequent etiological agent of travelers diarrhea. Challenge studies with several of these strains were undertaken in volunteers to evaluate the mechanisms of disease-induced immunity. Seventeen students and other community volunteers were given 10(6) or 10(8) organisms of E. coli B7A (O148:H28), which produces heat-labile and heat-stable enterotoxins. Ten individuals developed diarrheal illness closely resembling natural travelers diarrhea; of these ten, rises in titer of serum antitoxin and anti-O antibody occurred in eight (80%). Eight of the volunteers who developed diarrhea in the first test agreed to undergo rechallenge 9 weeks later with 10(8) B7A organisms. Only one of these eight "veterans" developed diarrhea versus seven of twelve controls given the same challenge (P = 0.05). Despite clinical protection, all "veterans" excreted B7A after rechallenge. Four controls who developed diarrhea during the homologous B7A rechallenge test were rechallenged 9 weeks later with 10(9) organisms of E. coli strain E2528-C1 (O25:H-), which produces only heat-labile enterotoxin and possesses a different O, H, and pili antigen composition than B7A. Three of four "veterans" and two of six controls developed comparable diarrhea. These studies demonstrate that prior disease due to enterotoxigenic E. coli confers homologous immunity against subsequent challenge, and the operative mechanism apparently is not bactericidal and is not mediated by serum anti-O antibodies. Heterologous protection was not conferred where the only common antigen was heat-labile enterotoxin, indicating that serum infection-derived antitoxin to heat-labile enterotoxin also is not protective.

Antibodies, Bacterial↗
PubMed1978

Escherichia coli strains that cause diarrhoea but do not produce heat-labile or heat-stable enterotoxins and are non-invasive.

Three enteropathogenic Escherichia coli (E.P.E.C.) strains (O127:K63:H6, O128:K67:H2, and O142:K86:H6) isolated from outbreaks of infantile diarrhoea and one strain from the "normal" colonic flora (E. coli HS) of a healthy adult were fed in doses of 10(6), 10(8), and 10(10) organisms in NaHCO3 to adult volunteers. The strains, which had been stored for 7--9 years, gave negative results in sensitive tests for heat-labile (L.T.) enterotoxin (Y-1 adrenal-cell test), heat-stable (S.T.) enterotoxin (infant mouse assay), invasiveness (guineapig eye test), and gross fluid accumulation (infant rabbit assay). Two strains (O142 and O127) caused diarrhoea. L.T. or S.T. enterotoxins were not found in E. coli stool isolates from individuals with diarrhoea and no one had a rise in L.T. antitoxin titre; the findings suggest that L.T. and S.T. enterotoxins were not involved in pathogenesis of the diarrhoea. Non-invasive E.P.E.C. strains probably induce diarrhoea by a mechanism (presumably an enterotoxin) distinct from L.T. or S.T. enterotoxins.

Adult↗
PubMed1978

Antigenicity of purified glutaraldehyde-treated cholera toxoid administered orally.

The antigenicity of orally administered glutaraldehyde-treated cholera toxoid was investigated in healthy volunteers. Fourteen volunteers ingested two or three 2-mg doses of toxoid with saline, with the doses spaced at 28-day intervals. Thirteen other volunteers received comparable toxoid doses with NaHCO3 and milk to neutralize gastric acid. Increments in circulating antitoxin levels were used to assay the antigenicity of oral toxoid. Antitoxin was measured by adrenal cell, rabbit skin permeability factor, and passive hemagglutination assays in sera collected on days 0, 28, 35, 56, 63, and 84 after primary immunization. Adrenal cell and rabbit skin assays exhibited identical sensitivity in detecting antitoxin rises in the 27 vaccinees (19/27) and were significantly more sensitive than passive hemagglutination (11/27) (P less than 0.03). Volunteers who ingested toxoid with NaHCO3 and milk had a higher rate of seroconversion (77%) than those who received toxoid with saline (64%); they also had earlier rises in antitoxin titer and consistently higher geometric mean titers on all days tested. These studies demonstrate that purified cholera toxoid is antigenic in humans after oral administration. The possible role of oral toxoid in enhancing the protective effect of killed whole-cell vaccines can now be investigated.

Adult↗
PubMed1978

Increased Escherichia coli enterotoxin detection after concentrating culture supernatants: possible new enterotoxin detectable in dogs but not in infant mice.

The heat-stable enterotoxin (ST) of Escherichia coli can be detected by infant mouse or dog intestinal loop tests. These tests differ in that the dog assay uses concentrated culture supernatants and is based on measurements of net intestinal absorption, whereas the mouse test uses unconcentrated supernatants and depends on gross fluid accumulation. To compare the relative sensitivities of these assays, culture supernatants of randomly selected E. coli isolates from 34 Bangalee diarrhea patients were tested for ST in dog loops and infant mice. Supernatants were also tested for heat-labile enterotoxin (LT) in dog loops, Y-1 adrenal cells, and Chinese hamster ovary cells. E. coli supernatants that produced positive responses for both ST and LT in the dog loop assay (ST+/LT+) also produced positive responses when tested for ST in infant mice and for LT in cell lines. Supernatants of strains negative for ST and LT in dog loop (ST-/LT) were also negative in other assays. Of 10 strains positive for just ST in the dog loop test (ST+/LT-), only 5 were ST positive in the standard infant mouse test. Supernatants of the other five strains (dog loop positive, mouse test negative) were then concentrated 100-fold and retested in mice. Three of these five gave consistently positive results after concentration, and two were only intermittently positive. Concentrated supernatants of negative control strains (ST-/LT-) were all negative in mice. The dog assay detects more strains producing ST than the infant mouse test. The infant mouse test, which detects only gross fluid accumulation, failed to detect approximately half of the 10 strains which produced ST alone (ST+/LT-; P = 0.025). Concentrating supernatants for the mouse assay increases sensitivity for detection of ST, but certain E. coli strains produce a variety of ST to which infant mice do not respond.

Animals↗
PubMed1978

Immune response inversion after hyperimmunisation. Possible mechanism in the pathogenesis of HLA-linked diseases.

The crosstolerance hypothesis suggests that animals sharing antigens with some microorganisms will produce low antibody levels in the early part and high levels in the latter part of an infection. Antibody responses have been measured in high responder B10.M and B10.D2 mice and low responder C3H and A.Thy-1.1, as well as F1 hybrids (B10.M X A.Thy-1.1) and (B10.M X C3H/He), after repeated immunisation with the antigen ferritin, involving altogether 483 mice. An inversion in the immune response was found to occur and similar delayed high antibody responses have been described in rheumatic fever. It is suggested a mechanism of immune inversion may operate in the pathogenesis of HLA and blood group-linked diseases.

Animals↗
PubMed1978

Cross-reactivity with mouse antigens in the ferritin immunogenetic (IR-gene) system.

Structural similarity between antigens and self molecules could be responsible for low antibody responses in different immunogenetic (IR-gene) systems. B10.M and B10.D2 strains are high responders, whilst A. Thy-1-1 mice are low responders, following primary immunization with ferritin in saline. Cross-reactivity between mouse-self antigens and ferritin was tested by antigen excess and radioimmunoassay techniques, using cells obtained from normal, unimmunized high- and low-responder mice, to compete for specific antibody. Low-responder A.Thy-1-1 mouse cells consistently displaced more anti-ferritin antibodies than did high-responder B10.M and B10.D2 mouse cells at varying antibody and cell concentrations and these differences were statistically significant (P less than 0.001). It is suggested that the responder status of different strains of mice, following primary immunization with ferritin in saline, could be explained by the degree of cross-activity between self determinants and antigen, such that low responders cross-react to a greater degree with the test antigen than do high-responder mice. A similar mechanism of cross-reactivity could operate in the pathogenesis of HLA-linked diseases.

Animals↗
PubMed1978

Antigen dose and strain variation as factors in the genetic control of the immune response to sperm whale myoglobin.

The primary and secondary immune response to the antigen sperm whale myoglobin was investigated in DBA/2, 129 and B10.BR mice over a dose range of immunization from 10 to 2000 microgram. Using an antigen excess technique, the quantity of antibody produced after secondary immunization followed a sigmoidal dose-response curve and the maximal plateau level was found to be different for each strain of mice. Furthermore, the genetic control of the immune response was investigated in twelve different inbred strains of mice following secondary immunization with 500 microgram of myoglobin. A continuous distribution for the mean antibody responses was obtained for the twelve different strains of mice. High responsiveness was associated with H-2 haplotypes d, f and k located on chromosome 17, the non-agouti gene 'a' located on chromosome 2 and the chinchilla gene 'c(ch)' located on chromosome 7. It is concluded that either a large number of IR-genes to myoglobin are present in many loci located on different chromosomes or the antibody differences could be explained by a cross-tolerance mechanism requiring no IR-genes at all.

Animals↗
PubMed1977

Genetic control of the immune response to ferritin in F1 hybrid mice.

The immune response to the antigen horse spleen ferritin, has been investigated in ten inbred parental strains and seven different F1 hybrid strains of mice, using an antigen excess technique. The degree of dominance in an F1 hybrid system can be estimated by using the Fisher dominance index. The responses in F1 hybrid animals, obtained from crosses of high and low responder parents, varied from dominant to recessive but the overall mean dominance index for the ferritin immunogenetic system was found to be -0.0467 +/- 0.0083 (mean +/- s.e.), a value close to zero, which suggests a codominant mode of inheritance of IR-genes to ferritin and this is consistent with most published data in other F1 IR-gene systems.

Animals↗