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Biomedical subjects

B M Gray

Publications and source records attributed to B M Gray.

At least 19 recordsLinked to original sources
PubMed1992

Case report: Rhodococcus equi pneumonia in a patient infected by the human immunodeficiency virus.

Rhodococcus equi, a facultative intracellular bacterium, is a common cause of pulmonary infection in farm animals, especially foals. Pulmonary and disseminated infection caused by this organism is occasionally seen in humans, especially in patients whose cell-mediated immunity has been altered by glucocorticoids or cytotoxic chemotherapy. Not surprisingly, the organism may cause serious disease in human immunodeficiency virus (HIV)-infected humans whose T cell-dependent immune system has been profoundly suppressed. This report describes an HIV infected patient with Rhodococcus equi pneumonia and reviews nine additional HIV-infected patients. Treatment in humans is not standardized. Studies in foals indicate that erythromycin and rifampin together are the treatment of choice. The patient in this report responded to this treatment briefly before relapsing and dying of the infection.

Actinomycetales Infections↗
PubMed1992

Strong association between capsular type and virulence for mice among human isolates of Streptococcus pneumoniae.

The relationship between capsular type and virulence for mice was examined with 69 fresh human isolates of Streptococcus pneumoniae. These isolates represented eight capsular types or groups. Serologic and molecular weight differences in PspA (pneumococcal surface protein A) indicated that the strains were clonally distinct. Mice were infected intravenously with washed bacteria of all 69 isolates in sterile salt solutions. Twenty-eight of the isolates were also injected intraperitoneally to permit comparisons between the intravenous and intraperitoneal routes. With a few exceptions, there was concordance between the ability of strains to cause fatal infections by the two routes. About 30% of the 69 isolates were virulent for mice. The abilities of the isolates to kill mice and the length of time between inoculation and death were strongly associated with capsular type. All type 4 isolates, 40% of type 3 isolates, and 60% of group 6 isolates were virulent for mice; type 1 isolates were marginally virulent; and all type or group 14, 19, and 23 isolates were avirulent. Times to death were generally longer for mice infected with group 6 or type 1 than for those infected with type 3 or 4 pneumococci. There was no relationship between clinical diagnosis or tissue source of the isolates and virulence for mice.

Animals↗
PubMed1992

Murine monoclonal antibodies to type Ib polysaccharide of group B streptococci bind to human milk oligosaccharides.

The chemical structures of the repeating units of the type Ib polysaccharide of group B streptococci and of the desialylated form of this antigen are almost identical to those of some oligosaccharides in human milk and certain fetal antigens. The structural similarities suggested that the molecules may be immunologically cross-reactive. Mouse monoclonal antibodies to the sialylated and nonsialylated forms of the type Ib polysaccharide were produced and tested for their ability to bind to immobilized human milk oligosaccharides. One antibody, SMB19, reacted specifically with the sialylated form of the type Ib polysaccharide and was also bound by an affinity column containing immobilized sialyllacto-N-tetraose a. The antibody was eluted from the affinity column with EDTA, since its binding to the antigen was calcium dependent. A second monoclonal antibody. SIbD2, bound specifically to the nonsialylated form of the type Ib polysaccharide and also to immobilized lacto-N-tetraose. The antibody was eluted from the affinity column at an acidic pH and retained immunologic activity. These results further extend our previous observations that certain antibodies raised against group B streptococci can also react with normal human glycoconjugates.

Antibodies, Monoclonal↗
PubMed1992

Streptococcus pyogenes pharyngitis: characterization of strains by multilocus enzyme genotype, M and T protein serotype, and pyrogenic exotoxin gene probing.

Multilocus enzyme electrophoresis, serological characterization of M and T proteins, and probing for pyrogenic exotoxin A and C genes were used to investigate the bacteriologic epidemiology of strains of Streptococcus pyogenes recovered primarily from patients with recurrent pharyngitis. A total of 164 strains recovered from individuals living in nine states of the United States was analyzed. Two-thirds of the patients in our sample were infected with the homologous strain following antibiotic therapy and presumably represented treatment failures, whereas the other one-third of the patients were infected with a heterologous strain after therapy and probably represented reinfections. Multilocus enzyme electrophoresis was as efficacious in strain discrimination as serologic typing techniques were and, in addition, successfully characterized all organisms that were serologically nontypeable. Two clones of S. pyogenes responsible for most of the episodes of toxic shock-like syndrome in the United States are geographically widespread, but they vary by locality in the frequency of their occurrence. Compared with a sample of strains cultured from patients whose pharyngeal infections were eliminated by antimicrobial therapy, these two clones were statistically overrepresented among organisms that cause recurrent pharyngitis.

Antigens, Bacterial↗
PubMed1992

Delayed thromboxane synthesis inhibition, but not cholinergic blockade, reverses group B streptococcus-induced pulmonary hypertension.

Anisodamine, an anticholinergic drug, is widely used in China for treatment of infants with septic shock and has been reported to inhibit thromboxane synthesis in cultured cells. Thromboxane A2 plays an important role in the early pulmonary hypertension in sepsis; however, the role of thromboxane A2 later in sepsis is unclear. We tested the hypothesis that thromboxane A2 synthesis inhibition with dazmegrel, and cholinergic blockade with anisodamine, would attenuate the later phase of pulmonary hypertension induced by 4 h of group B streptococcus (GBS) infusion. 1 mg/kg of dazmegrel reversed the pulmonary hypertension and slightly increased cardiac output; these hemodynamic improvements persisted for 30-60 min. Plasma thromboxane B2 levels returned toward pre-GBS baseline values after dazmegrel treatment. Thus, thromboxane A2 is still a major mediator of pulmonary hypertension in piglets after 4 h of continuous GBS infusion. 0.5 mg/kg of anisodamine had no significant hemodynamic effect. 2 and 4 mg/kg of anisodamine each caused transient, dose-related decreases in systemic artery pressure; cardiac output also fell after the highest anisodamine dose. Pulmonary hypertension was not alleviated by anisodamine. All hemodynamic changes induced by anisodamine were short-lived and returned to preanisodamine values within 10 min. Anisodamine did not ameliorate thromboxane-mediated pulmonary hypertension in this animal model, and therefore may not inhibit thromboxane synthesis in vivo. The results of this study do not support the use of anticholinergic therapy to improve hemodynamics in GBS sepsis, but do suggest that thromboxane synthesis inhibition may be a clinically useful therapy in advanced GBS sepsis.

Animals↗
PubMed1992

Role of capsule in pulmonary hypertension induced by group B streptococcus.

The type-specific polysaccharide capsule of group B streptococcus (GBS) is thought to be an important factor in the pathogenesis of disease. We used an acutely instrumented piglet model to assess the hemodynamic effects of rapid infusions of two heat-killed GBS type Ib strains isolated from the spinal fluid of an infant with late-onset meningitis and from the vaginal culture of his mother. These strains expressed different amounts of capsule, as determined by buoyant density centrifugation and electron micrographs, and they produced different hemodynamic effects in the piglets. The mother's strain, which had a smaller capsule, caused significantly higher increases in pulmonary artery pressure and vascular resistance than did the infant's strain, which had a larger capsule. Transposon mutants were then made from the infant's isolate to further study the role of capsule in pulmonary hypertension. Two mutants lacking detectable capsular type-specific polysaccharide were compared with the original isolate and with an isogenic mutant containing transposons but having a large capsule. The nonencapsulated mutants caused significantly higher changes in pulmonary artery pressure and resistance than did the encapsulated strains. Pulmonary hypertension may play a role in the pathophysiology of GBS sepsis, but the presence of a large capsule may partially cloak the hemodynamically active component(s) of the bacteria. The lower initial host response to heavily encapsulated GBS may play a role in pathogenesis by helping the organisms avoid host defense mechanisms.

Animals↗
PubMed1991

Epidemiologic studies of group 9 pneumococci in terms of protein type and 9N versus 9V capsular type.

The variability among Streptococcus pneumoniae isolates of capsular group 9 was analyzed with a panel of six monoclonal antibodies to pneumococcal proteins. These antibodies differentiated the 104 group 9 isolates into 18 protein types and a group (PO) not typable with the antibody panel was used. Capsular type was determined for 87 isolates: 70% were capsular type 9V, 28% 9N, and 2% 9A. In terms of protein type, the 9V isolates were four times as diverse as the 9N isolates. Significant associations were observed between the protein type, geographic origin, and year of isolation. Statistically significant associations were also observed between different manifestations of pneumococcal disease and protein type of the capsular type 9V isolates. Thus, even within capsular types, pneumococci can be highly diverse; pneumococcal protein types may be useful in epidemiologic studies to distinguish related strains in the environment.

Adolescent↗
PubMed1990

Variation in the molecular weight of PspA (pneumococcal surface protein A) among Streptococcus pneumoniae.

Pneumococcal surface protein A (PspA) has been shown to be a virulence factor of pneumococci and to elicit protective anti-pneumococcal antibodies in mice. PspAs from different pneumococcal isolates have been shown to exhibit antigenic variability. In previous studies with three strains, two different apparent molecular weights of PspA were observed. In this report we have studied the variation in molecular weight of PspA from 43 pneumococcal strains reactive with anti-PspA monoclonal antibodies, Xi64 and/or Xi126. The relative molecular mass (Mr) of the major PspA band ranged from 67 k to 99 k in the different strains. Variations in Mr of PspA were observed even within strains of the same capsular type. The molecular size of PspA from strain Rx1 was not affected by treatment with a variety of chemical, enzymatic, and physical procedures, suggesting that the differences in Mr of PspA among different strains, was not due to uncontrolled variations in PspA preparation. The Mr of PspA of a given strain was found to be stable both in vivo and in vitro. As a result variations in the Mr of PspA from clinical isolates, should allow discrimination between strains within a given capsular type in epidemiologic studies.

Antibodies, Monoclonal↗
PubMed1990

Risk factors for perinatal group B streptococcal disease after amniotic fluid colonization.

A group of 1031 parturient women at high risk for intraamniotic infection were studied. Women in whom group B streptococci grew from cultures of the amniotic fluid did not differ in clinical risk factors when compared with similar parturient women without group B streptococcal colonization of amniotic fluid. Patients who had perinatal group B streptococcal disease (maternal or neonatal bacteremia) did not differ from those without disease, by maternal or neonatal acute antibody levels or antibody response, inoculum size, or serotype of the colonizing strain.

Amniotic Fluid↗
PubMed1990

Double-blind comparison of topical lignocaine-prilocaine cream (EMLA) and lignocaine infiltration for arterial cannulation in adults.

In a double-blind, double-dummy study, the efficacy of topical 5% EMLA cream was compared with that of lignocaine infiltration in alleviating the pain of arterial cannulation. Forty unpremedicated adults were allocated randomly to four groups to receive EMLA cream alone, EMLA and 0.9% saline infiltration, EMLA and 1% lignocaine infiltration or placebo cream and 1% lignocaine infiltration. Following arterial cannulation, pain was assessed by the patient using a visual analogue score and by an independent observer using a four-category verbal rating score. Significantly lower pain scores were observed in all patients receiving EMLA compared with those receiving placebo cream and lignocaine infiltration by both patient (P less than 0.01) and observer (P less than 0.001) assessments. There were no significant differences between the three EMLA groups.

Administration, Topical↗
PubMed1990

Pneumococcal surface protein A (PspA) is serologically highly variable and is expressed by all clinically important capsular serotypes of Streptococcus pneumoniae.

Pneumococcal surface protein A (PspA) has been shown previously to elicit antibodies protective against pneumococcal infection and to be necessary for full pneumococcal virulence in mice. The protein was originally defined by the two mouse monoclonal antibodies Xi64 and Xi126, which together recognized PspA on 14% of pneumococcal isolates. Some PspA molecules reacted with both antibodies, but most reacted with only one or the other. In the present study we demonstrated that PspA is produced by all pneumococci, confirming our hypothesis that there are variants of PspA which are not detected by Xi64 and Xi126. We produced a rabbit antiserum and five additional monoclonal antibodies specific for PspA for these studies. The rabbit antiserum reacted with each of 95 pneumococcal isolated tested, comprising 16 capsular serotypes. One or more of the seven monoclonal anti-PspA antibodies reacted with 95% (53 of 57) of pneumococcal isolates tested. The specificity of the monoclonal and polyclonal antibodies to PspA was confirmed in two ways: (i) by detection of molecules on wild-type pneumococci that are identical in molecular weight to those detected in Western blots (immunoblots) with Xi64 and Xi126 and (ii) by the use of mutants of Streptococcus pneumoniae that fail to produce PspA or that produce a truncated form of PspA. By using the seven monoclonal antibodies, we observed 31 PspA types among the 57 isolates. When the 53 strains reactive with the monoclonal antibodies were analyzed by capsular type as well as by serologic type and molecular weight of PspA, we observed 50 different clonotypes of pneumococci.

Animals↗
PubMed1990

Opsonophagocidal activity in sera from infants and children immunized with Haemophilus influenzae type b conjugate vaccine (meningococcal protein conjugate).

Immunization with Haemophilus influenzae type b capsular polysaccharide (polyribosylribitol-phosphate [PRP]) has resulted in limited and variable antibody radioimmunoassay in infants younger than 2 years of age. Although an H influenzae type B vaccine has been in use for several years, it is not used now for the age group at greatest risk for disease. In an effort to enhance immunogenicity, PRP has been coupled to various carrier proteins and to an outer membrane protein complex (OMPC) from Neisseria meningitidis group B. The latter approach has yielded a vaccine that elicits a good antibody response after a single 15-micrograms dose of vaccine in infants as young as 2 months of age, as measured by radioimmunoassay and immune bacteriolysis. In this report we describe the results of a pilot study using this H influenzae type B conjugate vaccine, PedvaxHIB, in children from 2 months to 4 years of age. Three different vaccine lots were examined for consistency of response. Sera were measured for antibody levels by radioimmunoassay and for functional activity using an opsonophagocytic assay using human adult neutrophils. These assays correlated well and demonstrated the excellent immune response and biologic activity of sera from infants vaccinated with this unique H influenzae type B conjugate vaccine.

Antibodies, Bacterial↗
PubMed1988

Protein serotyping of Streptococcus pneumoniae based on reactivity to six monoclonal antibodies.

Six monoclonal antibodies to proteins of Streptococcus pneumoniae were tested in a dot blot assay for reactivity with 499 clinical isolates of pneumococci. Forty-four percent of the isolates reacted with at least one of the antibodies. Nineteen patterns of reactivity were identified and each designated as a provisional protein serotype. Protein serotyping identified pneumococcal strains independently of their capsular type and made it possible to differentiate strains within most capsular types. A protein serotyping system provides a new dimension to the phenotypic identification of S. pneumoniae and may eventually provide a basis for assessing the population structure of these organisms.

Animals↗
PubMed1988

Seroepidemiology of group B Streptococcus type II antibody specificity.

The specificity of human antibodies for the two major sidechain determinants of the type II group B streptococcal (GBS) polysaccharide was examined in 90 pairs of maternal and cord sera. Using an ELISA system, total antibody was measured against the complete (sialylated) type II antigen and the proportion of antibody against the galactose determinant was estimated by inhibition with free beta-methylgalactopyranoside. Mothers colonized by type II or by other GBS types had higher levels of total specific antibody (means, 3.3 and 4.7 micrograms/ml, respectively) than those not colonized (mean, 2.2 micrograms/ml). Cord sera averaged 1-2 micrograms/ml lower than maternal sera. Colonization with GBS was also associated with higher levels against the galactose determinant (mean, 1.5 micrograms/ml, compared to 0.7 micrograms/ml for those not colonized). The distribution of specificities favoured antibodies against the sialic acid determinant in maternal but not cord sera. Specificity as well as antibody level may play a role in the epidemiology of GBS type II.

Antibodies, Bacterial↗