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Effect of phenylalanine on chloramphenicol antibiotic action
Volume 67
Number 5
Abstracts
part 2
Mary A. South,* Frank A. Wollheim,* Warren J. Warwick, Max D. Cooper,* and Robert A. Good, Pediatric Research Laboratories, Variety Club Heart Hospital, and Department of Medicine, University of Minnesota, Minneapolis, Minn. Tomasi and others have shown that the major immune globulin constituent of various body secretions, including saliva, bronchial, and nasal secretions, is IgA. Studies in our laboratory have indicated that there is a selective transport mechanism for IgA, which involves the addition of an antigenically distinct protein, the "transport piece," to the IgA molecule. Patients with absence of IgA, the agammaglobulinemics treated with IgG, and ataxia-telangiectasia patients, are susceptible to infections of the respiratory tract. Although they have no IgA they do have the transport piece free in the saliva. Children, who have not yet developed normal adult levels of IgA in serum or saliva, also have free transport piece in saliva. Three teen-aged patients (two of whom are siblings) with unexplained chronic otitis media, sinusitis, bronchitis, and bronchiectasis, were studied. They had low salivary IgA relative to the adult normal of 1 to 3 mg. per cent. Age-specific normal values have not been established. These findings indicate that there is a local antibody defense system which involves the IgA class of antibodies. Defects are possible at 3 points in the transport mechanism: (1) production of IgA in plasma cells either locally or in distant parts of the body, (2) production of the transport piece, (3) their coupling together and subsequent secretion into the salivary collecting ductules. A defect at any of these points would result in a local immune deficiency state.
55. Repeated injections with respiratory syncytial virus: Their occurrence, and the significance of antigenic variations o[ virus in such rein[ections Marc O. Beem, University of Chicago School of Medicine, Department of Pediatrics, Chicago, Ill.
941
Exper. Biol. & Med. 115: 240, 1964) have shown antigenetic heterogeneity of naturally occurring RS virus strains, but the significance of this variation in the epidemiology of this virus is uncertain. This report concerns 10 children observed to have two separate, symptomatic RS virus shedding infections in successive seasons of virus prevalence. Both virus strains were available from 8 patients, and there were suitable serum specimens on 6. Using animal immune serums (ferret, postinfection) and determining the rate at which they neutralized the plaque forming capacity of the various strains of virus, antigenic differences could be demonstrated between certain of the virus pairs. However, when virus strains were compared using the patient's serum obtained early in the course of the second infection, these differences were not evident. These studies document the occurrence of symptomatic virus shedding reinfection with RS virus, extend observations of others on the existence of antigenic variants of this virus, but suggest that susceptibility is not to be explained on the basis of such antigenic variation.
56. Effect o[ phenylalanine on chloramphenicol antibiotic action F. Coekburn,* J. O. Klein,* D. Ingall,* J. D. Sherman,* and R. Klein, Boston University School of Medicine, Boston, Mass. Since phenylalanine protects against some of the toxic effects of chloramphenicol, the present study was undertaken to ascertain whether phenylalanine interfered with antibiotic action chloramphenicol. There was no suggestion of this from clinical observations. Mice were injected intraperitoneally with a standard dose of 10-2 Klebsiella pneumonia organisms. Phenylalanine was administered subcutaneously in an acidic solution. The dose was either 50 to 150 rag. per kilogram which was chosen to correspond to the amount of phenylalanine given by mouth to infants or 400 mg. per kilogram. Control animals were injected with the phenylalanine carrier solution without phenylalanine. Those animals given chloramphenicol succinate received one injection of the antibiotic in water in a dose of 40 mg. per kilogram.
Table I Respiratory syncytial virus is probably the most important single virus causing acute respiratory infections in children. Evidence, primarily of a serologic nature, indicates reinfection with this virus may occur (significant neutral antibody titers in patients shedding virus, increasing neutral antibody titers with age). Coates and Chanock (Proc. Soc. Exper. Biol. & Med. 112: 958, 1963) and Wulff and W e n n e r (Proe. Soe.
Phenylalanine
Base
No. of mice Deaths % Mortality from control
209 102 49
50 to 150 400 (mg./kg.) (mg./kg.) 240 102 43 0.2 > p >0.1
168 104 62 p ~ 0.05
94 2
Society for Pediatric Research
November 1965
In addition to those groups in the table, other animals were given the infection and phenylalanine without chloramphenicol. Phenylalanine had no effect in these animals. It is concluded from this that a dose of 100 rag. per kilogram or less of phenylalanine does not inhibit the antibacterial effect of chloramphenicol in mice infected with Klebsiella pneumonia. It is further concluded that a similar trial in infants with infection would not be unreasonable or unduly hazardous.
57. Antimicrobial activity of cerebrospinal fluid (CSF) and serum in patients under treatment for purulent meningitis M. Grossman and W. Ticknor,* University of California-San Francisco Medical Center and San Francisco General p i t a l , S a n F r a n c i s c o , Calif.
Hos-
The study was conducted to determine the antimicrobial activity against the infecting organism of CSF and blood serum in patients with purulent meningitis who were placed on commonly accepted regimens of antibiotic therapy (25 with pneumococcal meningitis, 8 with meningococcal, 8 with H. influenzae and 13 with various organisms). Blood serum and CSF were collected simultaneously, usually on the third day of therapy. In patients with pneumococcal meningitis the range of CSF antimicrobial activity (maximal bactericidal dilution of CSF or serum set up in vitro against causative organism of meningitis) was from 1:4 to 1:2,048. In most patients CSF activity was 1-2 tube dilution less than serum activity but sometimes the disparity was much greater (serum 1:4,096; CSF 1:128). In 3 instances, CSF was obtained within 3 hours of the start of therapy. The CSF bactericidal activity in these patients ranged from 1:256 to 1:1,024. The CSF activity against the infecting organism was found to be of lesser magnitude in patients with N. meningitides meningitis (range ~ 1:4 to 1:128) and even less in patients with H. influenzae meningitis (range < 1 : 4 to 1:16). The least antimicrobial activity was found in patients whose meningitis was caused by gram-negative enteric organisms.
58. Characterization of a myxovirus recovered from serum and urine o/ patients with infectious hepatitis Harvey Lelebhaber,~ Philip H. Prose,* S a u l K r u g m a n , a n d J o a n P. Giles,* N e w Y o r k U n i v e r s i t y S c h o o l of M e d i c i n e , N e w Y o r k , N. Y.
Cytopathic agents have been isolated from four serum specimens and two urine specimens obtained from children with infectious hepatitis. The original isolations were made in cultures of human embryonic diploid lung fibroblasts (WI-38). The agents have also been isolated and serially propagated in a continuous line of green monkey kidney cells ( W G M - 1 ) , and have also been grown in HeLa and h u m a n embryonic kidney cells. The six isolates are antigenically related and possess the properties of parainfluenza viruses. However, they are quite resistant to inactivation at pH 3.0. In protein free solutions, the agents are ether sensitive and inactivated at temperatures of 57 ° C. for 30 minutes. They are considerably less sensitive to ether and heat when suspended in 50 per cent protein solutions. On the basis of neutralization and hemagglutination inhibition tests they are antigenically distinct from parainfluenza viruses types 1, 2, 3, and 4, SV-5, mumps, and SA-1 viruses. Serologic evidence relating these agents to the disease has not been consistent; a significant rise in neutralizing antibody to the agent was observed in only 5 of 10 patients with infectious hepatitis. Commercial lots of gamma globulin contain high titers of neutralizing antibody for these agents. Electron microscopic studies have revealed that the morphology of the agent and its relationship to the cell are similar to previously described myxoviruses.
59. Identification of passively protecting antibody as A~,Gimmunoglobulin Joseph A. Bellanti* and Edward L. Buescher,* Walter Reed Army Institute of Research and Georgetown University School of Medicine, Washington, D. C. Introduced by Philip L. Calcagno Although passive immunization for the prevention or modification of several viral diseases has been available for several decades, nothing is known of the physicochemical properties of the protective antibodies. It has been shown previously that following experimental arbovirus infection of guinea pigs, the earliest detectable hemagglutination-inhibiting (HI) and neutralizing (N) antibodies at 7 to 10 days are associated with a 19S 7M-immunoglobulin; the earliest complementfixing antibody with a 7S yG-immunoglobulin. Antibodies of all 3 types obtained after 14 days are of the 7S variety. The present studies were undertaken to compare the neutralizing antibody of isolated yM- and YG-immunoglobulin fractions of sera of guinea pigs experimentally infected with Russian spring-summer encephalitis (RSSE) virus to its passive protective capacity. Concentrated pools of yM-immunoglobulins, shown to contain significant neutralizing antibody by a standard in vitro neutralization test, did not afford susceptible mice significant protection to subsequent
Number 5
Abstracts
part 2
Mary A. South,* Frank A. Wollheim,* Warren J. Warwick, Max D. Cooper,* and Robert A. Good, Pediatric Research Laboratories, Variety Club Heart Hospital, and Department of Medicine, University of Minnesota, Minneapolis, Minn. Tomasi and others have shown that the major immune globulin constituent of various body secretions, including saliva, bronchial, and nasal secretions, is IgA. Studies in our laboratory have indicated that there is a selective transport mechanism for IgA, which involves the addition of an antigenically distinct protein, the "transport piece," to the IgA molecule. Patients with absence of IgA, the agammaglobulinemics treated with IgG, and ataxia-telangiectasia patients, are susceptible to infections of the respiratory tract. Although they have no IgA they do have the transport piece free in the saliva. Children, who have not yet developed normal adult levels of IgA in serum or saliva, also have free transport piece in saliva. Three teen-aged patients (two of whom are siblings) with unexplained chronic otitis media, sinusitis, bronchitis, and bronchiectasis, were studied. They had low salivary IgA relative to the adult normal of 1 to 3 mg. per cent. Age-specific normal values have not been established. These findings indicate that there is a local antibody defense system which involves the IgA class of antibodies. Defects are possible at 3 points in the transport mechanism: (1) production of IgA in plasma cells either locally or in distant parts of the body, (2) production of the transport piece, (3) their coupling together and subsequent secretion into the salivary collecting ductules. A defect at any of these points would result in a local immune deficiency state.
55. Repeated injections with respiratory syncytial virus: Their occurrence, and the significance of antigenic variations o[ virus in such rein[ections Marc O. Beem, University of Chicago School of Medicine, Department of Pediatrics, Chicago, Ill.
941
Exper. Biol. & Med. 115: 240, 1964) have shown antigenetic heterogeneity of naturally occurring RS virus strains, but the significance of this variation in the epidemiology of this virus is uncertain. This report concerns 10 children observed to have two separate, symptomatic RS virus shedding infections in successive seasons of virus prevalence. Both virus strains were available from 8 patients, and there were suitable serum specimens on 6. Using animal immune serums (ferret, postinfection) and determining the rate at which they neutralized the plaque forming capacity of the various strains of virus, antigenic differences could be demonstrated between certain of the virus pairs. However, when virus strains were compared using the patient's serum obtained early in the course of the second infection, these differences were not evident. These studies document the occurrence of symptomatic virus shedding reinfection with RS virus, extend observations of others on the existence of antigenic variants of this virus, but suggest that susceptibility is not to be explained on the basis of such antigenic variation.
56. Effect o[ phenylalanine on chloramphenicol antibiotic action F. Coekburn,* J. O. Klein,* D. Ingall,* J. D. Sherman,* and R. Klein, Boston University School of Medicine, Boston, Mass. Since phenylalanine protects against some of the toxic effects of chloramphenicol, the present study was undertaken to ascertain whether phenylalanine interfered with antibiotic action chloramphenicol. There was no suggestion of this from clinical observations. Mice were injected intraperitoneally with a standard dose of 10-2 Klebsiella pneumonia organisms. Phenylalanine was administered subcutaneously in an acidic solution. The dose was either 50 to 150 rag. per kilogram which was chosen to correspond to the amount of phenylalanine given by mouth to infants or 400 mg. per kilogram. Control animals were injected with the phenylalanine carrier solution without phenylalanine. Those animals given chloramphenicol succinate received one injection of the antibiotic in water in a dose of 40 mg. per kilogram.
Table I Respiratory syncytial virus is probably the most important single virus causing acute respiratory infections in children. Evidence, primarily of a serologic nature, indicates reinfection with this virus may occur (significant neutral antibody titers in patients shedding virus, increasing neutral antibody titers with age). Coates and Chanock (Proc. Soc. Exper. Biol. & Med. 112: 958, 1963) and Wulff and W e n n e r (Proe. Soe.
Phenylalanine
Base
No. of mice Deaths % Mortality from control
209 102 49
50 to 150 400 (mg./kg.) (mg./kg.) 240 102 43 0.2 > p >0.1
168 104 62 p ~ 0.05
94 2
Society for Pediatric Research
November 1965
In addition to those groups in the table, other animals were given the infection and phenylalanine without chloramphenicol. Phenylalanine had no effect in these animals. It is concluded from this that a dose of 100 rag. per kilogram or less of phenylalanine does not inhibit the antibacterial effect of chloramphenicol in mice infected with Klebsiella pneumonia. It is further concluded that a similar trial in infants with infection would not be unreasonable or unduly hazardous.
57. Antimicrobial activity of cerebrospinal fluid (CSF) and serum in patients under treatment for purulent meningitis M. Grossman and W. Ticknor,* University of California-San Francisco Medical Center and San Francisco General p i t a l , S a n F r a n c i s c o , Calif.
Hos-
The study was conducted to determine the antimicrobial activity against the infecting organism of CSF and blood serum in patients with purulent meningitis who were placed on commonly accepted regimens of antibiotic therapy (25 with pneumococcal meningitis, 8 with meningococcal, 8 with H. influenzae and 13 with various organisms). Blood serum and CSF were collected simultaneously, usually on the third day of therapy. In patients with pneumococcal meningitis the range of CSF antimicrobial activity (maximal bactericidal dilution of CSF or serum set up in vitro against causative organism of meningitis) was from 1:4 to 1:2,048. In most patients CSF activity was 1-2 tube dilution less than serum activity but sometimes the disparity was much greater (serum 1:4,096; CSF 1:128). In 3 instances, CSF was obtained within 3 hours of the start of therapy. The CSF bactericidal activity in these patients ranged from 1:256 to 1:1,024. The CSF activity against the infecting organism was found to be of lesser magnitude in patients with N. meningitides meningitis (range ~ 1:4 to 1:128) and even less in patients with H. influenzae meningitis (range < 1 : 4 to 1:16). The least antimicrobial activity was found in patients whose meningitis was caused by gram-negative enteric organisms.
58. Characterization of a myxovirus recovered from serum and urine o/ patients with infectious hepatitis Harvey Lelebhaber,~ Philip H. Prose,* S a u l K r u g m a n , a n d J o a n P. Giles,* N e w Y o r k U n i v e r s i t y S c h o o l of M e d i c i n e , N e w Y o r k , N. Y.
Cytopathic agents have been isolated from four serum specimens and two urine specimens obtained from children with infectious hepatitis. The original isolations were made in cultures of human embryonic diploid lung fibroblasts (WI-38). The agents have also been isolated and serially propagated in a continuous line of green monkey kidney cells ( W G M - 1 ) , and have also been grown in HeLa and h u m a n embryonic kidney cells. The six isolates are antigenically related and possess the properties of parainfluenza viruses. However, they are quite resistant to inactivation at pH 3.0. In protein free solutions, the agents are ether sensitive and inactivated at temperatures of 57 ° C. for 30 minutes. They are considerably less sensitive to ether and heat when suspended in 50 per cent protein solutions. On the basis of neutralization and hemagglutination inhibition tests they are antigenically distinct from parainfluenza viruses types 1, 2, 3, and 4, SV-5, mumps, and SA-1 viruses. Serologic evidence relating these agents to the disease has not been consistent; a significant rise in neutralizing antibody to the agent was observed in only 5 of 10 patients with infectious hepatitis. Commercial lots of gamma globulin contain high titers of neutralizing antibody for these agents. Electron microscopic studies have revealed that the morphology of the agent and its relationship to the cell are similar to previously described myxoviruses.
59. Identification of passively protecting antibody as A~,Gimmunoglobulin Joseph A. Bellanti* and Edward L. Buescher,* Walter Reed Army Institute of Research and Georgetown University School of Medicine, Washington, D. C. Introduced by Philip L. Calcagno Although passive immunization for the prevention or modification of several viral diseases has been available for several decades, nothing is known of the physicochemical properties of the protective antibodies. It has been shown previously that following experimental arbovirus infection of guinea pigs, the earliest detectable hemagglutination-inhibiting (HI) and neutralizing (N) antibodies at 7 to 10 days are associated with a 19S 7M-immunoglobulin; the earliest complementfixing antibody with a 7S yG-immunoglobulin. Antibodies of all 3 types obtained after 14 days are of the 7S variety. The present studies were undertaken to compare the neutralizing antibody of isolated yM- and YG-immunoglobulin fractions of sera of guinea pigs experimentally infected with Russian spring-summer encephalitis (RSSE) virus to its passive protective capacity. Concentrated pools of yM-immunoglobulins, shown to contain significant neutralizing antibody by a standard in vitro neutralization test, did not afford susceptible mice significant protection to subsequent