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Biomedical subjects

J B Robbins

Publications and source records attributed to J B Robbins.

At least 181 records · Page 10Linked to original sources

Reversal of aconitine-induced tachycardia by prostaglandins in the rabbit Langendorff preparation.

The ability of PGA2, E1, E2, and F2alpha to alter: (a) the refractory period (as judged by the maximal driving frequency); (b) the rate of automatically beating aconitine-treated papillary muscles; and (c) the rate of both untreated and aconitine-treated Langendorff preparations, was studied. The addition of PGA2 (3.0 mumol), PGE2 (2.84 mumol), and PGF2alpha (2.1 mumol) to the perfusate returned heart rate to pre-aconitine levels in the Langendorff preparation, but this action was frequently accompanied by atrioventricular dissociation. In contrast, PGE1 (2.82 mumol) was ineffective in antagonising aconitine-induced tachycardia. In the normally beating rabbit Langendorff, PGF2alpha (2.1 mumol) produced a slight but statistically significant negative chronotropic effect. Neither cardiac contractile force nor maximal driving frequency was altered by the addition of prostaglandins. These results suggest that PGA2, PGE2, and especially PGF2alpha may exert antiarrhythmic activity by direct action(s) upon in vitro rabbit myocardial preparations.

Aconitine↗

Cross-antigenicity and immunogenicity between capsular polysaccharides of group C Neisseria meningitidis and of Escherichia coli K92.

Antibodies to capsular polysaccharides of group C Neisseria meningitidis are often found in sera of young adults despite infrequent nasopharyngeal carriage and low rate of attack of N. meningitidis in the United States. Thus, experiments were designed for detection of bacteria cross-reactive with N. meningitidis. Among 3,264 cultures of stool, urine, blood, and cerebrospinal fluid, only 14 strains were found to be cross-reactive; all were Escherichia coli possessing the K92 capsular polysaccharide. The somatic O-antigens were 16, 13, 23, and 73; the flagellar antigens were H4 and 34. All K92 strains of E. coli showed the expected fermentations, were sensitive to common antibiotics, and lacked enteropathogenicity. Antigens of both E. coli K92 and group C N. meningitidis are capsular, acidic polysaccharides composed of sialic acid. The K92 polysaccharide is N- but not O-acetylated, sensitive to neuraminidase, and linked by alpha-2,8- alternating with alpha-2,9-ketosidic bonds. The K92 polysaccharides from all E. coli studied had similar biophysical and immunological properties. Intravenous injection of formalin-treated K92 organisms induced precipitating and bactericidal antibodies to polysaccharides of N. meningitidis. E. coli K92 strains may provide an alternative immunogen for prophylaxis against disease due to group C N. meningitidis in infants and young children.

Adult↗

The infant rat as a model of bacterial meningitis.

The pathogenesis of bacterial meningitis was studied in infant rats. Intranasal intoculation of greater than 10(3) Haemophilus influenzae type b resulted in an incidence of bacteremia that was directly related to the size of hte challenge inoculum. The temporal and quantitative relationship of bacteremia to meningitis indicated that bacteria spread to the meninges by the hematogenous route and that the magnitude of bacteremia was a primary determinant in the development of meningitis. In a sparate series of experiments, infant rats that were fed Escherichia coli strain C94 (O7:K1:H-) became colonized and developed bacteremia and meningitis, but invasive disease was rare when rats were fed E. Coli strain Easter (O75:K100:H5). A comparison of intranasal vs. oral challenge indicated that the nasopharynx was the most effective route for inducing H. influenzae bacteremia, whereas the gastrointestinal route was the more effective challenge route for the E. coli K1 serotype.

Animals↗

Interim report of a controlled field trial of immunization with capsular polysaccharides of Haemophilus influenzae type b and group C Neisseria meningitidis in Mecklenburg county, North Carolina (March 1974-March 1976).

Approximately 16,000 children, from two months to five years of age, were vaccinated with the capsular polysaccharide of either Haemophilus influenzae type b or group C Neisseria meningitidis. Immunizations were carried out in a double-masked, randomized manner; the doses of immunogens used were 10 microgram of H. influenzae type b polysaccharide and 25 micron g of the group CN. meningitidis polysaccharide. Immunogenicity of the two vaccines was measured in single, random specimens of blood taken from vaccinees of all ages at various intervals after immunization. A positive effect on formation of serum antibody was observed in children of all ages vaccinated with N. meningitidis polysaccharide, but increased levels of serum antibody to H. influenzae type b were observed only in recipients of that vaccine who were three years of age or older. No untoward reactions to either vaccine were noted, and both vaccines retained their original molecular size after storage for three years. Too few cases of disease have been studied for a definitive assessment of vaccine efficacy; however, a slightly protective effect against meningitis was observed for the H. influenzae type b vaccine in infants up to one year of age.

Age Factors↗

Sialic acid-containing polysaccharides of Neisseria meningitidis and Escherichia coli strain Bos-12: structure and immunology.

A polysaccharide antigenically related to that of group C Neisseria meningitidis was isolated from Escherichia coli strain Bos-12 (O48: K91:NM). Like the polysaccharides of groups B and CN. meningitidis, the Bos-12 antigen was shown to be a pure polymer of sialic acid. The 13C-nuclear magnetic resonance studies of the groups B and C polysaccharides indicated that the former consists of units of sialic acid joined in alpha-2 leads to 8 linkages, whereas the latter contains sialic acid residues linked by alpha-2 leads to 9 glycosidic bonds. Chemical and nuclear magnetic resonance studies of the polysaccharide of E. coli strain Bos-12 established that it is a heteropolymer containing both alpha-2 leads to 8 and alpha-2 leads to 9 linkages. Physical parameters including partial specific volume, reduced viscosity, diffusion and sedimentation coefficients, shape, weight-average molecular weight, and the Stokes radius of the polysaccharides of groups A, B, and C N. meningitidis have been determined. The results indicate that the polysaccharides are highly asymmetric and exist in solution as rigid rods; aggregates are formed by the association of these rods. The polysaccharides appear to have "restricted" length.

Antibodies, Bacterial↗

Neonatal meningitis due of Escherichia coli K1.

Human neonates are uniquely susceptible to serious infections due to Escherichia coli. Investigation of the serotypes of E. coli isolated from neonates with meningitis revealed that greater than 80% of the isolates possessed the capsular polysaccharide antigen designated K1. Cultures of stool from healthy infants, children, and adults have shown that K1 organisms are commonly found in individuals of all ages. Studies of mother-infant pairs have demonstrated transmission of K1 strains from mother to infant shortly after birth. In the rare infant who develops meningitis due to E. coli K1, serotype analysis frequently reveals that the same organism was isolated from the infant's cerebrospinal fluid and from the stools of both mother and infant. Preliminary investigations of humoral immunity demonstrated an age-related acquisition of antibodies to the capsular polysaccharide of E. coli K1 in healthy infants and children. An animal model was developed in which feeding of E. coli K1 to infant rats resulted in colonization, bacteremia, and meningitis in the animals.

Adult↗

Pathogenesis of neonatal Escherichia coli meningitis: induction of bacteremia and meningitis in infant rats fed E. coli K1.

Escherichia coli K1 strains, isolated from human newborns with meningitis, were fed to pathogen-free Sprague-Dawley infant rats by an oral gastric tube. Feeding of 10(3) to 10(11) organisms colonized the intestine of approximately 70% of the animals. At 5 days postfeeding of 3- to 5-day-old rats, bacteremia was detected in 60%, and meningitis occurred in 15% of bacteremic animals. Colonization and bacteremia were age-related. Rats 15 days old had only 19 colonization and 10% bacteremia, and those 30 days old were almost completely resistant to colonization and bacteremia. The intranasal route was less effective in inducing colonization and bacteremia. Intralitter transmission from E. coli K1-fed rats occurred, with 52% of water-fed controls becoming colonized and 15% become bacteremic. Colonization of mothers from their fed infants occurred, but none of five tested developed bacteremia. Other E. coli capsular polysaccharide types were studied. A K92 strain isolated from a newborn with meningitis induced a 77% colonization rate, and 8% of these developed bacteremia without detectable meningitis. An E. coli K100 strain showed a 32% colonization rate, and 2% developed bacteremia. The age relation, relatively high virulence of K1 compared with other capsular types, spontaneous appearance of colonization, bacteremia, and meningitis, and intralitter transmission of colonization and disease in newborn rats closely parellel E. coli epidemiology in human neonates.

Administration, Oral↗

Use of antiserum agar plates for serogrouping of meningococci.

A convenient and reliable method for serogrouping meningococci, based on immunospecific precipitation haloes in antiserum-agar plates, is described. It gave concordant results with conventional slide-agglutination in 900 strains of groups A, B or C tested. The antiserum-agar can also be used as a primary isolation medium for detecting nasopharyngeal carriers of a certain serogroup if antibiotics are added.

Agar↗

Problems posed by potential gonococcal vaccines viewed from the vantage point of a control agency.

Progress in the characterisation of Neisseria gonorrhoeae and other bacterial pathogens has suggested that immunoprophylaxis for gonorrhoea may be possible despite the well-known propensity for reinfection. Pili, outer membrane proteins, a capsular polysaccharide, and the lipopolysaccharide may be important gonococcal virulence factors, and immune components (probably antibodies) to more than one of these antigens may be required to confer immunity. A study of antigenic polymorphism of these structures should identify disease isolates more precisely and provide information about the relationship between variants of these gonococcal structures and gonococcal virulence.

Antigens, Bacterial↗

An outbreak of Hemophilus influenzae type b meningitis in an enclosed hospital population.

Five cases of HITB maningitis occurred within six months in an enclosed population of 28 to 32 chronically ill children. Studies of nasopharyngeal carriage and serum HITB anticapsular antibodies were started after the third case occurred. Two patients had low (less than 0.04 and 0.05mug/ml) antibodies and were not carriers when studied prior to onset of their disease. The carriage rate was approximately 20% among the children. Carriage was usually prolonged, and acquisition was not prevented by high antibody levels. Attempts to arrest this outbreak with type b polysaccharide immunization and ampicillin therapy are discussed in the context of HITB meningitis as a contagious disease.

Antibodies, Viral↗

Purification of heat-labile enterotoxin from Escherichia coli O78:H11 by affinity chromatography with antserum to Vibrio cholerae toxin.

Concentrated culture filtrate of Escherichia coli O78:H11, strain H10407, was applied to an affinity column prepared with IgG antibodies to the toxin of Vibrio cholerae. Elution of the retained material with 3 M KCNS yielded a nonenterotoxic protein that precipitated with antiserum to V. cholerae toxin and had three major protein components on sodium dodecyl sulfate gels. After treatment with 2-mercaptoethanol, two protein components were observed. Elution of the affinity column with 5 M guanidine yielded an enterotoxic protein that precipitated with antiserum to V. cholerae toxin. After treatment with 2-mercaptoethanol, only one protein component, with mobility identical to that of the slower component of the eluate (treated with 3 M KCNS and 2-mercaptoethanol), was observed.

Animals↗

Bacillus pumilus polysaccharide cross-reactive with meningococcal group A polysaccharide.

A polysaccharide, antigenically and structurally related to meningococcal group A polysaccharide, was isolated from Bacillus pumilus Sh-17. This enteric bacterium has been implicated as a source of natural meningococcal group A immunity (Myerowitz et al., 1973). The B. pumilus polysaccharide was composed of a homopolymer of (1-6)-N-acetyl-manosamine-1-phosphate, glycerol phosphate teichoic acid-containing N-acetylglucosamine and alkali-labile alanine esters, and a mucopeptide. The cross-reaction was due to the poly-(1-6)-N-acetyl-mannosamine-1-phosphate in the B. pumilus and the meningococcal group A polysaccharides, based on the following evidence. Both polysaccharides contained N-acetyl-mannosamine phosphate. Periodate oxidized the mannosamine phosphate residues of the polysaccharide and destroyed their precipitating activity with meningococcal group A antiserum. Mild acid treatment released phosphomonoesters and destroyed the meningococcal group A precipitating activity of both polysaccharides. N-acetyl-mannosamine-6-phosphate inhibited the precipitation reaction between strain Sh-17 and meningococcal group A antisera. Only mannosamine phosphate was detected in trichloroacetic acid extracts of Sh-17 polysaccharide and meningococcal group A antigen-antibody precipitates.

Amino Acids↗

A review: relation between invasiveness and the K1 capsular polysaccharide of Escherichia coli.

The conclusions from our studies to date may be summarized as follows. (1) Invasive E. coli strains causing neonatal meningitis are encapsulated. At least 80% of those strains inducing mengitis are K1 and approximately 40% of those strains isolated from infants with septicemia but without meningitis are also K1. Invasiveness is best related to the K1 antigen and not to E. coli O and H antigens. (2) The capsular content of CSF strains is not related to their invasiveness. In contrast to observations reporting higher K capsular polysaccharide content and molecular weight of E. coli invading the renal parenychma as compared with those E. coli confined to the bladder or in the stool, there were no differences among DSF K1 strains. Sepculation as to the mechanism of the invasive properties conferred by acidic capsular polysaccharides may be derived from the literature. Unencapsulated or "rough bacteria" are susceptible to the bactericidal action of agammaglobulinemice sera (15, 53). When injected into precolostral (agammaglobulinemic but complement containing), cesarian-delivered, and antigen-deprived piglets, unencapsulated bacteria are rapidly cleared from the circulation. In contrast, smooth bacteria injected into these same animals circulate without detectable splenic or hepatic clearance, multiply, and result in the death of these animals. The mechanism of the resistance of encapsulated bacteria has been postulated to be due to the inaccessibility of the deep somatic antigen structures capable of activating the alternate complement pathway system. Thus, opsoninization and other host complement-dependent activities may of necessity be antibody mediated for encapsulated bacteria. This complement resistance of encapsulated organisms may be quanititative and studies should be done to determine differences among various K1 E. coli strains. (3) K1 strains are widely prevalent among infants, children, and adults and are quickly transmitted to infants. In most cases the source of the infecting strain in diseased infants is the mother. However, transmission from attendants, demonstrable in our studies, is also a possible mechanism. (4) A protective role of serum anticapsular antibodies in animal models has been demonstrated. Our initial observations indicating low serum K1 antibodies in the general population and the finding that K1 antibodies are predominantly IgM in two animal species studied so far suggest that colostral K1 antibodies may be important in conferring immunity to this disease.

Animals↗

Intracranial carotid catastrophies encountered by the otolaryngologist.

Arteriographic studies are utilized to illustrate the presence and document the results of arterial ligation on three intracranial carotid aneurysms. All three aneurysms resulted from trauma, surgical and otherwise, and all presented as otolaryngologic dilemmas. All were successfully controlled by a combined Otolaryngological and Neurosurgical Team employing varying combinations of intra and extra cranial arterial ligations. None developed significant neurological impairments. The two major indications for common or internal carotid ligation are the resection of neoplasm and the control or prevention of hemorrhage. Sixty percent of patients undergoing elective carotid ligation survive these procedures without evidence of neurological sequelae. This uncompromised survival is based upon the presence or rapid development of collateral circulation to the cerebrovascular bed. Further arteriographic studies are employed to illustrate the development of intra and extra cranial collateralization to the internal carotid artery after surgical interruption of the ipsilateral common carotid. The major collateral circuits demonstrated via a case report are as follows: a. from the vertebral artery to the external carotid and hence to the internal carotid; b. from the posterior communicating artery to the internal carotid; and c. from the ophthalmic artery to the internal carotid.

Adult↗

Host factors and antibody response Haemophilus influenza type b meningitis and epiglottitis.

Levels of antibody in serum after infection with Haemophilus influenza type b or challenge with polysaccharide vaccine are highly variable. Convalescent-phase serum antibody to the capsular polysaccharide of H. influenzae type b was measured in two groups of patients with pathophysiologically distinct diseases, meningitis and acute epiglottitis. Antibody response after H. influenzae meningitis was subnormal. Mean levels of antibody, the distribution of antibody levels by age, and erythrocyte and genetic marker lymphocyte antigens were studied; all results suggested that these two groups of patients were genetically and immunologically different from each other. Evidence suggested that the magnitude of the important host immunologic response was under host genetic control.

Adolescent↗

Induction of serum Haemophilus influenzae type B capsular antibodies in adult volunteers fed cross-reacting Escherichia coli 075:K100:H5.

Serum Haemophilus influenzae Type b (HITB) anticapsular antibodies were induced in adult volunteers by feeding of either of two strains of a cross-reacting Escherichia coli 075:K100:H5. In all the fed volunteers colonization for a finite period lasting up to eight weeks occurred, without adventitious reactions. Nine of 14 normal volunteers and one of two volunteers previously immunized with the Type 6 H.influenzae polysaccharide responded with a greater than twofold increase in serum Type 6H. influenzae antibodies. These antibodies induced by Esch. coli were specific for the capsular polysaccharide and had bactericidal activity. The safety of this procedure, the comparable results in laboratory animals and the identification of other cross-reacting strains of Esch. coli with meningococcal and pneumococcal capsular polysaccharides suggest that colonization with these nonpathogenic organisms at birth may provide a general method of preventive immunization to diseases caused by encapsulated bacteria.

Adult↗

Epidemiology of Escherichia coli K1 in healthy and diseased newborns.

Although at least 100 different Escherichia coli capsular antigens have been recognised, strains possessing the K1 antigen are responsible for 77% of neonatal E. coli meningitis cases. K1 strains were found in 20-40% of rectal swab cultures from healthy infants, children, and adult women. Vertical transmission from mother to infant was the most common means of aquiring K1 organisms in term infants. Premature babies in a nursery with little maternal contact aquired K1 strains later then did term infants, and this aquisition may have been related to carriage by nursery staff. Capsular content and fermentation reactions of cerebrospinal-fluid K1 organisms were comparable to those found in rectal strains from healthy individuals. E. coli K1 with identical O and H antigens were found in maternal and infantile cultures of babies with E. coli meningitis. It seems very likely that host immune mechanisms play a significant role in the pathogenesis of neonatal E. coli K1 meningitis.

Adolescent↗

Cross-reactive antigens and immunity to diseases caused by encapsulated bacteria.

Antigenic structures may be shared among naturally occurring polymers, including proteins and polysaccharides. Proteins are polymers of amino acids. Cross-reactions between proteins are due to similarities in their overall shape rather than their individual amino acid components. Cross-reactions have been demonstrated among proteins with similar evolutionary development and structure, such as serum albumins or immunoglobulins. Polysaccharides are polymers of monosaccharides. In contrast to proteins, antigenic specificities may be conferred by mono-, di-, and trisaccharides. Since there are about 150 known naturally occurring monosaccharides, it is not unexpected that cross-reactions are demonstrable between polysaccharides from widely divergent sources.

Adult↗