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Biomedical subjects

J R Scott

Publications and source records attributed to J R Scott.

At least 199 records · Page 11Linked to original sources
PubMed1987

Pregnancy after tubo-ovarian transplantation.

A rat model was developed for microsurgical en bloc vascularized adnexal isografts and allografts. Transplantation of the fallopian tube and ovary from donors to syngeneic, bilaterally tubo-oophorectomized recipients was technically successful in six of eight animals, and four litters of healthy offspring were delivered at 44, 45, 85, and 105 days after transplantation. Twelve tubo-ovarian allografts using cyclosporine for immunosuppression resulted in seven viable grafts and three pregnancies. Cyclosporine at 15 mg/kg/day was found to be teratogenic, but normal progeny were delivered when the dose was lowered to 5 mg/kg/day during pregnancy. These results suggest that microsurgical tubal transplantation with an appropriate immunosuppressive regimen warrants further investigation as potential treatment for certain infertility problems in the human.

Animals↗
PubMed1986

Conversion of an M- group A streptococcus to M+ by transfer of a plasmid containing an M6 gene.

An M28-derived group A streptococcal strain deleted for the gene encoding M protein was converted to M+ by introduction of a plasmid carrying emm6, the structural gene for type 6 M protein from strain D471. The reconstituted M+ strain, JRS2, resists phagocytosis in human blood and is opsonized by anti-M6 hyperimmune serum, but not by anti-M28 serum. Immunofluorescent microscopy and ELISA demonstrate the presence of M protein on its surface. In addition, JRS2 removes opsonic antibodies from hyperimmune rabbit sera generated by immunization with purified ColiM6 protein and with a synthetic amino-terminal peptide derived from M6. Immunization of rabbits with JRS2 generates opsonic anti-M6 antibodies. These results indicate that the cloned emm6 gene contains the information necessary to convert a phagocytosis-sensitive streptococcus to phagocytosis resistance. Furthermore, it also contains the determinants for M type specificity and those required to elicit opsonic antibodies. It thus appears to determine all the traits associated with M protein.

Antibodies, Bacterial↗
PubMed1986

Immunochemical localization and amino acid sequences of crossreactive epitopes within the group A streptococcal M6 protein.

mAbs 10A11, 10B6, and 10F5, raised against the native group A streptococcal M6 protein, were examined for their crossreactivity with non-laboratory passaged clinical isolates, representing 58 M serotypes, by bacterial dot blot immunoassay. mAb 10A11 crossreacted with 9, mAb 10B6 with 30, and mAb 10F5 with 30 different non-M6 serotypes. To identify the epitopes for these antibodies, the native M6 protein was cleaved with pepsin or staphylococcal V8 protease. Resultant peptides were purified by HPLC, examined for binding to crossreactive mAbs in ELISA, and reactive peptides were subjected to amino acid sequence analysis. Peptides were aligned with the amino acid sequence of the entire M6 protein predicted by the DNA sequence of the M6 gene. Competitive inhibition studies using peptides synthesized on the basis of peptide and DNA sequences, in concert with selective blocking of amino acid residues, allowed for the further identification and placement of these crossreactive epitopes within the M6 molecule. The 10A11 epitope was located within the six amino acid residues at position 134-139, which repeat at positions 159-164 and 184-189 within the variable amino terminal half of the native molecule. The conserved 10B6 and 10F5 epitopes were positioned within a 15-amino-acid span at position 275-289, with the possibility that either epitope could have been repeated at residues 239-247. Chemical modification of amino acids within this sequence aided in the differentiation of these two epitopes. Such studies should aid in the recognition of a sequence(s) common to a greater number of M serotypes, which may be useful for future vaccine development or group A streptococcal identification.

Amino Acid Sequence↗
PubMed1986

Streptococcal M protein size mutants occur at high frequency within a single strain.

Streptococcal M protein, the antiphagocytic molecule on the surface of the organism, was previously found to exhibit extensive size heterogeneity between as well as within M serotypes. In this study, methods were devised to isolate M protein size mutants within a laboratory-grown culture. We were able to isolate three independent M protein deletion mutants and one additional mutant, which was derived from the first deletion mutant. We found that these deletion mutants occur at a frequency of approximately 1 in 2 X 10(3) CFUs in culture. Functional studies revealed that the deletion mutants were able to survive as well as the parental strain in human blood. They also had the determinants necessary to absorb opsonic antibodies as well as the parent. Pepsin digestion experiments localized the deletions within the N-terminal half of the M molecule, which is distal to the cell wall surface. This is the region of the molecule in which extensive sequence repeats are found. This is consistent with the suggestion that the size changes may be the result of homologous recombination between the repeat regions in the gene. These results support the idea that strains showing M protein size variation within successive clinical isolates from single patients may be derived from the initial infecting organisms, and are not the result of separate unrelated acquisitions of the same serotype. This size change may be important in the survival of the streptococcus in vivo.

Antigens, Bacterial↗
PubMed1986

Complete nucleotide sequence of type 6 M protein of the group A Streptococcus. Repetitive structure and membrane anchor.

The DNA sequence of the gene for type 6 M protein of Streptococcus pyogenes contains two extended tandem repeat regions and one nontandem repeat region. We suggest that the duplication and deletion of these repeats generates the observed diversity in size and sequence among the family of M proteins in the group A streptococci. In addition, the DNA sequence reveals the presence of a 42-amino-acid signal peptide, a region rich in proline that is thought to be located in the cell wall, and a membrane anchor sequence at the carboxyl-terminal end of the protein. Signals similar to the consensus sequences recognized for the initiation of transcription and translation in Gram-positive bacteria have been identified in the DNA sequence. Codon usage is similar to that of other Gram-positive bacteria and significantly different from that of Escherichia coli.

Amino Acid Sequence↗
PubMed1986

The demonstration of lupus anticoagulant by an enzyme-linked immunoadsorbent assay.

Lupus anticoagulant, an autoantibody associated with thromboembolic disease and pregnancy loss, is currently identified by its capability to prolong phospholipid-dependent coagulation tests, such as the activated partial thromboplastin time (APTT). The use of a coagulation assay for the detection of an antibody has several inherent disadvantages: fresh plasma is required for accurate testing, prolongation of coagulation test(s) is not specific for lupus anticoagulant, and coagulation assays are not easily manipulated for the characterization of antigen-antibody interactions. Using partial thromboplastin an the antigen, we have developed an enzyme-linked immunoadsorbent assay (ELISA) for the detection of lupus anticoagulant. Fifteen women with lupus anticoagulant (being evaluated for recurrent pregnancy loss or autoimmune disease) and 40 lupus anticoagulant-negative controls (including 20 with recurrent pregnancy loss, 12 parous women, and 8 with known autoimmune disease) were evaluated using the APTT and ELISA assays for lupus anticoagulant. All patients with lupus anticoagulant, as defined by the APTT, had significantly elevated IgG (sensitivity and specificity, 100%) or IgG + IgM (sensitivity 93%, specificity 95%) levels compared to controls.

Autoantibodies↗
PubMed1986

Abdominoplasty combined with gynecologic surgical procedures.

Cosmetic surgery of the abdomen is requested frequently by patients and is being performed increasingly at the time of elective gynecologic surgery. However, little information is available regarding the safety of combining these procedures. In this study intraoperative and postoperative morbidity was compared in the following groups of patients: 1) abdominoplasty plus one of five common gynecologic procedures (N = 76); 2) one of the five gynecologic procedures alone, matched for age, weight, and time of operation (N = 76); and 3) abdominoplasty alone (N = 70). Patients in group 1 experienced significantly longer operative time, longer hospital stays, and greater blood loss, which required more transfusions than group 2 or 3. These problems were accentuated in patients who weighed more than 70 kg or were older than age 35. In addition, five patients (6.6%) in group 1 had a documented pulmonary embolus within 18 days of surgery, whereas no pulmonary emboli occurred in group 2 or 3. Because of the increased morbidity, careful patient selection is necessary when abdominoplasty and gynecologic procedures are performed at the same time.

Abdomen↗
PubMed1986

IS1-dependent generation of high-copy-number replicons from bacteriophage P1 Ap Cm as a mechanism of gene amplification.

Mutant P1 Ap Cm lysogens were isolated in which the drug resistance genes resident on the plasmid prophage P1 Ap Cm are amplified by a novel mechanism. The first step required for amplification is IS1-mediated rearrangement of the P1 Ap Cm prophage. The drug resistance genes are amplified from the rearranged P1 Ap Cm prophage by the formation of a plasmid (P1dR) which contains the two resistance genes. The P1dR plasmid is an independent replicon about one-half the size of P1 Ap Cm that can be maintained at a copy number eightfold higher than that at which P1 Ap Cm can be maintained. It contains no previously identified replication origin and is dependent on the Rec+ function of the host.

Bacterial Proteins↗
PubMed1985

Obstetric complications associated with the lupus anticoagulant.

We identified eight patients with the lupus anticoagulant (an autoantibody acquired by some patients with systemic lupus erythematosus), by observation of an increased activated partial thromboplastin time and abnormal results on a tissue thromboplastin-inhibition test. The patients had experienced a total of 30 spontaneous abortions and fetal deaths in 31 previous pregnancies (96.8 per cent). During their next pregnancy, the patients were treated with 40 to 50 mg of prednisone per day and 81 mg of aspirin per day. The therapy shortened their activated partial thromboplastin times, produced normal values for tissue thromboplastin inhibition, and reduced the rate of pregnancy loss to 37.5 per cent. However, preeclampsia developed in the five patients who gave birth to live infants, and fetal growth retardation occurred in three cases. The corticosteroid and low-dose aspirin regimen appears to improve perinatal outcome in cases in which the mother has the lupus anticoagulant, but such practices as careful fetal surveillance and preterm delivery when appropriate are also important to successful obstetric management of such cases.

Abortion, Spontaneous↗
PubMed1985

Unsuccessful treatment of fetal immunologic thrombocytopenia with dexamethasone.

Corticosteroid therapy near term for mothers with immunologic thrombocytopenia has recently been suggested as a clinically useful method to prevent neonatal thrombocytopenia. The unreliability of this approach is illustrated by the case of an infant with a low platelet count delivered after the maternal administration of dexamethasone.

Adult↗
PubMed1985

Size variation of the M protein in group A streptococci.

In addition to the type-specific antigenic variation that is a well-known characteristic for the group A streptococcal M protein, we have now found that the M molecules vary with respect to their molecular size, both between M types and within an M type. By the use of an M6 monoclonal antibody, which crossreacts with 20 different M protein types, and antibodies to the N-acetyl glucosamine determinant of the cell wall, we have been able to identify the M protein molecules released from the streptococcal cell wall with muralytic enzymes, particularly group C phage-associated lysin. Immunoblot analysis of the cell extract identified M protein molecules bound to various cell wall fragments, suggesting a peptidoglycan linkage for the M molecule. M protein extracted from 20 different streptococcal serotypes revealed size variations from 41,000 to 80,000 in molecular weight. This extreme variation is unusual for related proteins. Similar size variations in the M molecule were also found in random clinical isolates of type 6 streptococci. No size change was seen in M6 protein isolated from: (a) strains within a limited epidemic, (b) a strain passaged in mice 192 times, and (c) a strain passaged in the laboratory for 156 generations, suggesting that the observed variation is not a rapid process. The results indicate that, within the broad limits observed in this study, the size of the M protein may not be critical to the antiphagocytic activity of the molecule.

Antigens, Bacterial↗
PubMed1985

Location of variable and conserved epitopes among the multiple serotypes of streptococcal M protein.

In studies primarily confined to the amino-terminal region of the fibrillar group A streptococcal M protein, only limited immunological crossreactions have been observed among M serotypes. In this investigation, two monoclonal antibodies generated against nearly the entire M6 molecule (LysM6) were used to determine the extent of crossreactions among M serotyping strains and to localize their epitopes on the M molecule. Colony blot and immunoblot analyses revealed that an epitope responsible for crossreactions among 5 of the 56 strains of different M serotypes tested is located in the amino-terminal half of the molecule, distal to the cell surface. In contrast, a more common crossreactive epitope, reacting with 20 of the 56 strains, is located near the middle of the M molecule. These studies also reveal that the more conserved determinant, located more proximally to the cell surface, is accessible to the immune system, even on the whole organism, and, thus, may be useful in devising means to protect against infections by multiple group A streptococcal M serotypes.

Antibodies, Bacterial↗
PubMed1985

Assessment of coping strategies associated with syncope in blood donors.

Characteristics associated with vasovagal syncope in blood donors were investigated in two studies. An initial goal was to examine the potential role of physical and health variables. The primary goal was to assess coping strategies that might be related to the second phase (i.e., bradycardia; hypotension) of the vasovagal reaction pattern. Findings in both studies revealed that physical characteristics and health variables were unrelated to syncope. Donors who experienced reactions were characterized, however, by fewer prior blood donations and a greater likelihood of previous syncope. Multivariate analysis also indicated that in the context of the variables just noted, reacting donors reported less awareness of anxiety-related physiological cues. Other findings suggested that Suppression, a coping strategy that has been previously associated with heart rate decrease in blood donors, may be linked to syncope. Prospective assessment of coping is suggested for future studies of psychological factors involved in syncope.

Adaptation, Psychological↗