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J R Scott

Publications and source records attributed to J R Scott.

At least 181 records · Page 10Linked to original sources
PubMed1988

Spontaneous M6 protein size mutants of group A streptococci display variation in antigenic and opsonogenic epitopes.

Deletions of highly, but not entirely, homologous intragenic sequence repeats result in amino acid sequence and conformational changes in the M proteins of spontaneous M protein-size variants of group A streptococci. To determine if antigenic changes occurred as a result of these deletion mutations, monoclonal and polyclonal antibodies with defined epitopes were used in competition assays. Competing antigens were either purified pepsin-derived fragments (representing the amino-terminal half of the molecule) of parent and mutant M proteins or were intact bacterial cells. These assays showed that antigenic variation occurred at the site(s) of these deletions but not at adjacent or distant epitopes. Once cleaved from the bacterium by pepsin, the M molecules also underwent conformational changes, which were reflected in their ability to compete. A monoclonal antibody opsonic for M6 streptococci lost its ability to completely opsonize one of the size mutants in this study. Therefore, spontaneous intragenic events between repeats within emm-6, the structural gene for the M6 protein, do result in structural variations within the mutant M molecules. This variation alters the ability of certain antibodies, originally produced in response to sequences in the parental M molecule, to bind to the mutant M molecules or opsonize the mutant organisms. Group A streptococci have evolved a mechanism for generating antigenic diversity that differs from currently known mechanisms in other bacterial species.

Amino Acid Sequence↗
PubMed1988

Molecular cloning of the plasmid-located determinants for CS1 and CS2 fimbriae of enterotoxigenic Escherichia coli of serotype O6:K15:H16 of human origin.

The plasmid pCS001, isolated from an enterotoxigenic strain of Escherichia coli, mediates expression of the CS1 or CS2 and CS3 fimbrial adhesins in appropriate E. coli hosts. To characterize this further, HindIII-generated DNA fragments of this plasmid were cloned into the vector plasmid pBR322. A chimaera, called pCS200, which mediated expression of the CS1 or CS2 fimbrial antigen but not of CS3 fimbrial antigen in appropriate host strains, was obtained. The DNA inserted into the vector sequences of plasmid pCS200 comprised HindIII fragments of 4.7 kbp and 0.8 kbp. Plasmid pCS200-carrying wild-type E. coli hosts of serotype O6:K15:H16 that expressed the CS1 or CS2 antigen also caused mannose-resistant agglutination of bovine red blood cells, suggesting that functional fimbriae were present on the bacterial surface. As previously observed with strain K12 recipients of CS-fimbriae-associated plasmids mobilized from wild-type enterotoxigenic E. coli, K12 recipients of the chimaeric plasmid pCS200 did not express the CS1 or CS2 fimbrial antigen. An oligonucleotide probe, synthesized on the basis of the published N-terminal amino acid sequence of the CS2 fimbrial subunit, hybridized to plasmid pCS200, indicating that the gene for the structural subunit of this fimbria resided on the plasmid.

Adhesins, Escherichia coli↗
PubMed1988

Nucleotide sequence of the gene encoding the major subunit of CS3 fimbriae of enterotoxigenic Escherichia coli.

The complete nucleotide sequence of a 612-base-pair DNA fragment containing the gene for the major fimbrial subunit of CS3 of enterotoxigenic Escherichia coli is presented. A possible promoter region, a ribosome-binding site, and two potential signal peptidase cleavage sites are indicated. Unlike the best-studied fimbrial proteins, the predicted CS3 sequence has no Cys residues.

Amino Acid Sequence↗
PubMed1988

Occult placental abruption after maternal trauma.

Three cases of occult abruption after maternal trauma are presented. In each instance, there was no vaginal bleeding, and abdominal findings were subtle. By maintaining a high index of suspicion and monitoring the fetus continuously, the obstetrician may minimize the fetal complications of placental abruption in traumatized pregnant patients.

Abdominal Injuries↗
PubMed1987

Gallium-67 scintigraphy and non-small-cell bronchogenic carcinoma: a quantitative in-vivo predictive assay?

Gallium-67 scintigraphy has been of limited use in detecting lung cancers and micrometastases. To study its potential for determining the aggressiveness of a cancer, we reviewed the charts of 44 patients with non-small-cell bronchogenic carcinoma who had not been receiving treatment when 67Ga scintigraphy was performed. The mean length of survival for the 18 patients with low or little uptake of the tracer, corrected for tumour size, was 19.7 months, and for the 26 with high uptake 9.4 months (p less than 0.01). Such in-vivo predictive assays may be a rational goal for tumour scintigraphy.

Carcinoma, Bronchogenic↗
PubMed1987

Size variation in group A streptococcal M protein is generated by homologous recombination between intragenic repeats.

M protein, a major surface protein and virulence factor for the group A streptococcus, exhibits extraordinary size variation in strains of the same serotype (Fischetti et al. 1985). RNA sequence analysis of spontaneous M protein size variants shows that deletion mutations arise in a single strain by homologous recombination events between intragenic tandem repeats. Similar deletion and duplication events also occur in serial streptococcal isolates from a single patient and among related strains in a recent outbreak. We discuss how homologous recombination events can lead to the generation of antigenic variation.

Antigens, Bacterial↗
PubMed1987

No evidence for involvement of plasma proteins or blood-borne cells in amyloid plaque formation in scrapie-affected mice. An immunohistoperoxidase study.

The present study was designed to investigate blood-brain permeability and the possible involvement of plasma proteins and blood-borne cells in amyloid plaque formation in scrapie-affected mice. No abnormal extravasation of intravenously injected horseradish peroxidase (HRP) was found and with immunocytochemical techniques no plasma proteins were detected in neuropil from scrapie-affected mice. In contrast to an earlier report, these findings suggest that the blood-brain barrier is essentially intact in scrapie-affected mice. Using immunohistochemical and enzyme histochemical methods no cells belonging to the monocyte-macrophage lineage were detected in association with amyloid plaques. Thus, by these methods there was no evidence that plasma proteins or blood-borne cells are involved in amyloid plaque formation in scrapie-affected mice. However, astrocytes were consistently found to be associated with amyloid plaques at all stages of their development.

Amyloid↗
PubMed1987

The c4 gene of phage P1.

The c4 gene of phage P1 has been localized to 335 bp of the P1EcoRI-9 fragment, within 50 bp of the EcoRI-9/14 junction. DNA sequence analysis of this fragment reveals a single open reading frame of 66 amino acids. The location of two c4 mutations, both of which produce changes in the predicted amino acid sequence in this reading frame, suggests that the reading frame codes for the c4 repressor. A region with high homology to the E. coli promoter consensus sequence is located approximately 50 bp upstream from the reading frame. Deletion of this potential promoter region abolishes expression of c4, as indicated by the loss of complementation of c4 mutants for lysogeny. Complementation is restored by the introduction of a heterologous promoter (the T7 phi 10 promoter), indicating that c4 expression is absolutely dependent on transcription of the 66-amino acid reading frame.

Base Sequence↗
PubMed1987

Association of lupus anticoagulant with antibody against phosphatidylserine.

Lupus anticoagulant (LAC) is an antiphospholipid autoantibody identified by prolongation of in vitro phospholipid-dependent coagulation tests. Its presence is associated with thromboembolic disease and recurrent pregnancy loss in patients with or without clinical autoimmune disease. The purpose of this study was to identify the specific phospholipid(s) against which LAC is directed. The sera of 15 patients with LAC and of 41 LAC-negative controls were evaluated. Specific phospholipids were used to inhibit IgG binding in a partial thromboplastin ELISA, and serologic reactivity was measured with ELISAs which used specific phospholipids in the solid phase. Both phosphatidylserine and cardiolipin significantly inhibited IgG binding in the partial thromboplastin ELISA (76 and 75%, respectively); however, the serum of one patient who was strongly positive for LAC in coagulation assays was not inhibited by cardiolipin. In the specific phospholipid ELISAs, LAC-positive sera contained IgG (15 of 15 sera) and frequently IgM (9 of 15 sera; 60%) to phosphatidylserine. Most LAC-positive sera also contained IgG antibodies against other phospholipids: cardiolipin (10 of 11 sera; 91%), phosphatidylcholine (1 of 15 sera; 7%), phosphatidylethanolamine (12 of 15 sera; 80%), phosphatidylglycerol (12 of 15 sera; 80%), and phosphatidylinositol (10 of 15 sera; 67%). None of the LAC-negative controls had measurable IgG against any of these phospholipids. We conclude that LAC-positive sera contain antibody specificities against multiple phospholipids; however, anticoagulant activity is always associated with the presence of antibodies against phosphatidylserine.

Abortion, Habitual↗
PubMed1987

Platelet-binding immunoglobulins in pregnancy-induced hypertension. I. Platelet-associated IgM on fetal platelets: evidence of a fetal autoimmune reaction?

Pregnancy-induced hypertension (PIH) can be complicated by maternal or fetal thrombocytopenia, or both. In order to investigate possible immunologic causes of these thrombocytopenias, platelet-associated IgG (PAIgG) and IgM (PAIgM) were measured in mothers with PIH and in their infants and compared with those from patients with autoimmune thrombocytopenic purpura (ATP), a known immunodestructive platelet disorder. Many PIH patients (33.3%) and most ATP patients (68.1%) had elevated levels of maternal PAIgG. In both diseases, the amount of PAIgG was directly proportional with the degree of thrombocytopenia (r = 0.446 in PIH and r = 0.668 for ATP). But in neither disease did the degree of maternal thrombocytopenia correlate with the degree of neonatal thrombocytopenia (r = 0.153 for PIH and r = 0.175 for ATP). Umbilical cord samples from PIH patients contained PAIgG (53.3%) and PAIgM (53.8%), whereas the umbilical cord samples from ATP patients had elevated amounts of PAIgG but not PAIgM. PAIgM in the umbilical cord blood could not be accounted for by IgM rheumatoid factors, IgM-containing immune complexes, or non-specific adsorption because of elevated total IgM levels. The umbilical cord blood PAIgM was probably not of maternal origin because it was observed even when the maternal blood contained no PAIgM and maternal IgM is not normally transported transplacentally. Therefore, the PAIgM appears to be of fetal origin. These results suggest that both maternal and fetal immunologic mechanisms may be involved in PIH-induced thrombocytopenia; if so, this is one of the first reported examples of a possible fetal autoimmune response.

Autoantibodies↗
PubMed1987

Platelet-binding immunoglobulins in pregnancy-induced hypertension. II. Origin of circulating IgG and IgM antiplatelet antibodies in the umbilical cord serum.

IgG and IgM have been identified on the surface of maternal platelets in both autoimmune thrombocytopenia (ATP) and pregnancy-induced hypertension (PIH). IgG is also found on the umbilical cord platelets of patients with ATP and PIH, whereas IgM is only found on the umbilical cord platelets of patients with PIH. The possible maternal or fetal origins of these umbilical cord blood immunoglobulins were investigated by immunoblot analysis of antibodies in paired maternal and umbilical cord blood sera of ATP and PIH patients. Maternal sera contained IgG and IgM antibodies which reacted with several platelet proteins, however, a large amount of patient-to-patient variation was observed in the specific antigens that were identified. Analysis of paired maternal and umbilical cord sera from patients with ATP or PIH showed identical patterns of antigen specificity, which suggested that the IgG antibodies in the fetal circulation were of maternal origin. Circulating IgM antibodies were not observed in the umbilical cord sera of ATP patients. The umbilical cord sera of PIH patients, however, contained IgM antibodies that reacted against a variety of platelet antigens. In addition, most umbilical cord sera from PIH patients had identical patterns and relative intensities of reactivity, which differed from the patterns observed in the paired maternal sera. Antiplatelet IgM in the umbilical cord blood of PIH patients, therefore, appears to be a product of the fetal immune system.

Autoantibodies↗
PubMed1987

Identification of a gene that regulates expression of M protein, the major virulence determinant of group A streptococci.

By using Tn916 insertional mutagenesis, we have identified mry (M protein RNA yield), a gene required for high-level expression of the M protein, an essential virulence determinant of the group A streptococcus. The mry::Tn916 mutation causes a reduction by a factor of approximately equal to 50 in the amount of M protein produced, in the original strain and in a nonmutagenized host to which the mutation was transferred by transduction. The insertion is located approximately 1.8 kilobases upstream of the structural gene for M protein (emm) and its promoter. The genomic region including mry::Tn916 and emm was cloned on a cosmid vector and introduced into Escherichia coli. When the transposon excised precisely from the chimeric cosmid in E. coli, the resulting streptococcal DNA showed the same restriction pattern as the homologous chromosomal region in the parental nonmutagenized streptococcus. The sequence of the promoter for emm was not altered in the mry mutant. The reduction in protein correlates with a decrease in the amount of M protein-specific mRNA, indicating that mry regulates transcription of emm.

Antigens, Bacterial↗
PubMed1987

Peripheral blood leucocytes subpopulation dynamics during Trypanosoma congolense infection in Boran and N'Dama cattle: an analysis using monoclonal antibodies and flow cytometry.

A panel of monoclonal antibodies (MoAb) with specificities for bovine leucocyte subsets were used in conjunction with routine haematological procedures to analyse sequential changes in peripheral blood leucocyte populations during the course of tsetse fly-transmitted Trypanosoma congolense infection in trypanotolerant N'Dama and trypanosusceptible Boran cattle. Subsequent to the first parasitaemic wave, the N'Dama cattle maintained packed cell volumes (PCV) above 22 and lower levels of parasitaemia than Boran throughout the 160 days of the experiment. In contrast, the Borans developed severe anaemia and required curative drug therapy (i.e., PCV dropped to less than 15) by 55 days (range: 22-55 days) post infection. There were significant (P less than 0.05) decreases in total white blood cells and total lymphocytes from pre-infection levels to the first peak of parasitaemia (day 16 post-infection) in both groups. Flow cytometric analyses using MoABs revealed that this change was due to an absolute decrease in T cells expressing BoT2 and either BoT4 or BoT8, surface immunoglobulin M-positive (sIgM+) B cells, and null cells which did not express T cell, B cell or monocyte markers. During this period there was significant variation over time, but no overall increase or decrease, in the number of cells expressing class II major histocompatibility (MHC) molecules or monocyte markers, or in the number of circulating neutrophils or eosinophils. The BoT4/BoT8 ratios were significantly (P less than 0.01) increased in both groups of infected animals at the first peak of parasitaemia. After day 22 in the infected N'Damas and in the Borans which required drug therapy, there was a leucocytotic response characterized by an increase in the total number of B cells, T cells, and null cells. Prior to infection and throughout the course of the experiment N'Dama cattle had significantly (P less than 0.01) higher numbers of B cells and null cells than Boran.

Animals↗
PubMed1987

Non-IgE antibody mediated mechanisms in food allergy.

Food sensitivity or intolerance is not necessarily based on the Type I allergic reaction. Non-IgE antibody reactions, complement-dependent reactions, enzyme deficiencies such as lactase and non-immunologic histamine release (such as with some sea foods) have been described. Even the detection of specific antibodies on their own does not necessarily indicate that a given symptom is due to that antibody. Food allergy nevertheless exists. It is important that those observers fortunate enough to see many cases document their observations carefully and eventually publish them for the education of their less fortunate colleagues. Is food allergy more common in infants and young children? What happens as they grow older? How often is atopic eczema due to food allergy? Why are some foods more likely to be implicated than others? Does a negative RAST result eliminate the diagnosis or a positive one confirm it? Until the answers to these and other questions are known, the mainstay of diagnosis will be the history, and that of treatment will be the elimination diet.

Animals↗
PubMed1987

A new postpartum syndrome associated with antiphospholipid antibodies.

Three women with antiphospholipid antibodies and a postpartum syndrome of pleuropulmonary disease, fever, and cardiac manifestations are presented. Each patient had either lupus anticoagulant or anticardiolipin antibodies or both, but did not have antinuclear antibodies or fulfill the criteria for the diagnosis of systemic lupus erythematosus. No infection or embolus was detected that could explain the pulmonary findings. All three patients had electrocardiographic abnormalities, and one patient developed a cardiomyopathy with extensive immunoglobulin G (IgG), IgM, IgA, and C3 deposition in the myocardium. In addition to the reported association between antiphospholipid antibodies and fetal loss, fetal growth retardation, and preeclampsia, we suggest that patients with antiphospholipid antibodies are at risk for a previously unreported and serious autoimmune postpartum syndrome.

Adult↗
PubMed1987

Immunologic aspects of recurrent abortion and fetal death.

Although mechanisms that prevent rejection of the conceptus are incompletely understood, recent evidence suggests that maternal immunologic aberrations may cause repeated abortions. Autoimmune conditions associated with antiphospholipid antibodies sometimes produce vascular abnormalities in the decidua and placenta; successful pregnancies can be achieved in most of these women by treatment with corticosteroids and low-dose aspirin. Abnormal maternal immune responses to paternal or trophoblast alloantigens, with insufficient production of blocking antibodies or suppressor cells, have also been implicated. Immunization of these patients with paternal or third-party leukocytes has resulted in a number of live births. However, the mechanism of action, effectiveness, and safety of all treatment regimens remain controversial. Present recommendations for the evaluation of recurrent-abortion patients include diagnosis and appropriate treatment of traditional nonimmunologic and more recently recognized autoimmune factors. The remaining patients with no detectable cause for repetitive pregnancy loss are candidates for referral to research centers for further immunologic evaluation and experimental immunotherapy.

Abortion, Habitual↗