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Biomedical subjects

J R Scott

Publications and source records attributed to J R Scott.

At least 19 recordsLinked to original sources
PubMed2006

Immunotherapy for recurrent miscarriage.

BACKGROUND: Because immunological aberrations might be the cause of miscarriage in some women, several immunotherapies have been used to treat women with otherwise unexplained recurrent pregnancy loss. OBJECTIVES: The objective of this review was to assess the effects of any immunotherapy, including paternal leukocyte immunization and intravenous immune globulin on the live birth rate in women with previous unexplained recurrent miscarriages. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (December 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2004, Issue 3), MEDLINE (1966 to September 2004) and EMBASE (1980 to September 2004). SELECTION CRITERIA: Randomized trials of immunotherapies used to treat women with three or more prior miscarriages and no more than one live birth after, in whom all recognised non-immunologic causes of recurrent miscarriage had been ruled out and no simultaneous treatment was given. DATA COLLECTION AND ANALYSIS: The review author and the two co-authors independently extracted data and assessed study quality for all studies considered for this review. MAIN RESULTS: Twenty trials of high quality were included. The various forms of immunotherapy did not show significant differences between treatment and control groups in terms of subsequent live births: paternal cell immunization (12 trials, 641 women), Peto odds ratio (Peto OR) 1.23, 95% confidence interval (CI) 0.89 to 1.70; third party donor cell immunization (three trials, 156 women), Peto OR 1.39, 95% CI 0.68 to 2.82; trophoblast membrane infusion (one trial, 37 women), Peto OR 0.40, 95% CI 0.11 to 1.45; intravenous immune globulin, Peto OR 0.98, 95% CI 0.61 to 1.58. AUTHORS' CONCLUSIONS: Paternal cell immunization, third party donor leukocytes, trophoblast membranes, and intravenous immune globulin provide no significant beneficial effect over placebo in improving the live birth rate.

Abortion, Habitual↗
PubMed2003

Cotransfection of heme oxygenase-1 prevents the acute inflammation elicited by a second adenovirus.

The acute inflammatory response elicited by adenovirus vectors results in loss of gene expression and tissue injury in the target organ. This acute inflammation is now believed to be the major limiting factor for the use of adenovirus vectors in gene therapy. While exploring the level of acute inflammation caused by the adenovirus encoding the gene for the anti-inflammatory enzyme heme oxygenase-1, we discovered that this adenovirus not only did not elicit acute inflammation, but could prevent the inflammation caused by a second adenovirus. Here we describe a new approach to gene therapy, which uses the encoding of the potent anti-inflammatory enzyme heme oxygenase-1 to prevent early host inflammatory responses normally associated with adenovirus vectors.

Acute Disease↗
PubMed2002

Risks to the children born to mothers with autoimmune diseases.

This article reviews current information regarding the development and long-term effects on children born to women with connective tissue diseases. There are few data on specific effects attributed to the underlying maternal disease, but fetal growth restriction and preterm birth are relatively common. Antenatal use of prednisone as treatment for these disorders appears to be safe, and most children have developed normally. However, there is growing concern that prolonged fetal exposure to other glucocorticoids such as dexamethasone or betamethasone may lead to decreased growth and abnormal neuronal development. Low birth weight is reportedly associated with long-term medical complications such as adult-onset hypertension. Evidence also suggests that immunosuppressive agents taken during pregnancy might predispose the progeny to autoimmune disorders, malignancies and reproductive problems. Further research is warranted to determine that there are no unrecognized long-term risks to the offspring of these women.

Adrenal Cortex Hormones↗
PubMed2001

Secondary ion mass spectrometry of zeolite materials: observation of abundant aluminosilicate oligomers using an ion trap.

Oligomeric oxyanions were observed in the secondary ion mass spectra (SIMS) of zeolite materials. The oxyanions have the general composition AlmSinO2(m+n)H(m-1)(-)(m+n = 2 to 8) and are termed dehydrates. For a given mass, multiple elemental compositions are possible because (Al + H) is an isovalent and isobaric substitute for Si. Using 18 keV Ga+ as a projectile, oligomer abundances are low relative to the monomers. Oligomer abundance can be increased by using the polyatomic projectile ReO4- (approximately 5 keV). Oligomer abundance can be further increased using an ion trap (IT-) SIMS; in this instrument, long ion lifetimes (tens of ms) and relatively high He pressure result in significant collisional stabilization and increased high-mass abundance. The dehydrates rapidly react with adventitious H2O present in the IT-SIMS to form mono-, di-, and trihydrates. The rapidity of the reaction and comparison to aluminum oxyanion hydration suggest that H2O adds to the aluminosilicate oxyanions in a dissociative fashion, forming covalently bound product ions. In addition to these findings, it was noted that production of abundant oligomeric aluminosilicates could be significantly increased by substituting the countercation (NH4+) with the larger alkali ions Rb+ and Cs+. This constitutes a useful tactic for generating large aluminosilicate oligomers for surface characterization and ion-molecule reactivity studies.

Journal Article↗
PubMed2001

Radioiodinated N-[3-(4-morpholino)propyl]-N-methyl-2-hydroxy-5-iodo-3-methylbenzylamine (ERC9): a new potential melanoma imaging agent.

The role of nuclear medicine in the management of patients with malignant melanoma has expanded in recent years with the introduction of lymphoscintigraphy and sentinel lymph node biopsy, intense interest in positron emission tomography (PET) imaging using 2-[18F]fluoro-2-deoxyglucose (18F-FDG) as a tracer, and encouraging reports of several new single-photon-emitting radiopharmaceuticals. While PET imaging with FDG exhibits a high sensitivity for imaging patients with melanoma, specificity may not be as high and access to the technology remains limited. Single-photon emission tomography (SPET) imaging remains standard technology for most nuclear medicine departments. We report a novel radiopharmaceutical--radioiodinated N-[3-(4-morpholino)-propyl]-N-methyl-2-hydroxy-5-iodo-3-methylbenzylamine (ERC9)--which appears to show a sensitivity and specificity that are commensurate with expectations of a radiopharmaceutical for routine clinical imaging. In this phase II trial, 110 patients at risk for recurrence, with suspected recurrence or being restaged have been imaged with this novel tracer, demonstrating an overall sensitivity of 91% and specificity of 89%. The results of our study support a phase III trial to establish the clinical role of ERC9 in staging melanoma patients at presentation who are at high risk for metastasis, or restaging patients with known relapse to assess the extent of their disease, particularly if therapy or enrollment into a clinical trial is being considered.

Adult↗
PubMed2001

Evasion of human innate and acquired immunity by a bacterial homolog of CD11b that inhibits opsonophagocytosis.

Microbial pathogens must evade the human immune system to survive, disseminate and cause disease. By proteome analysis of the bacterium Group A Streptococcus (GAS), we identified a secreted protein with homology to the alpha-subunit of Mac-1, a leukocyte beta2 integrin required for innate immunity to invading microbes. The GAS Mac-1-like protein (Mac) was secreted by most pathogenic strains, produced in log-phase and controlled by the covR-covS two-component gene regulatory system, which also regulates transcription of other GAS virulence factors. Patients with GAS infection had titers of antibody specific to Mac that correlated with the course of disease, demonstrating that Mac was produced in vivo. Mac bound to CD16 (FcgammaRIIIB) on the surface of human polymorphonuclear leukocytes and inhibited opsonophagocytosis and production of reactive oxygen species, which resulted in significantly decreased pathogen killing. Thus, by mimicking a host-cell receptor required for an innate immune response, the GAS Mac protein inhibits professional phagocyte function by a novel strategy that enhances pathogen survival, establishment of infection and dissemination.

Acute Disease↗
PubMed2001

A secondary RNA polymerase sigma factor from Streptococcus pyogenes.

The important human pathogen Streptococcus pyogenes (the group A streptococcus or GAS) causes diseases ranging from mild, self-limiting pharyngitis to severe invasive infections. Regulation of the expression of GAS genes in response to specific environmental differences within the host is probably key in determining the course of the infectious process, however, little is known of global regulators of gene expression in GAS. Although secondary RNA polymerase sigma factors act as global regulators of gene expression in many other bacteria, none has yet been isolated from the GAS. The newly available GAS genome sequence indicates that the only candidate secondary sigma factor is encoded by two identical open reading frames (ORFS). These ORFS encode a protein that is 40% identical to the transcription factor ComX, believed to act as an RNA polymerase sigma factor in Streptococcus pneumoniae. To test whether the GAS ComX homologue functions as a sigma factor, we cloned and purified it from Escherichia coli. We found that in vitro, this GAS protein, which we call sigmaX, directed core RNA polymerase from Bacillus subtilis to transcribe from two GAS promoters that contain the cin-box region, required for transcription by S. pneumoniae ComX in vivo. On the other hand, GAS sigmaX did not promote transcription of a GAS promoter (hasA) expected to be dependent on sigmaA, the housekeeping or primary RNA polymerase sigma factor. Addition of monoclonal antibody that inhibited sigmaA-directed transcription had no effect on sigmaX-directed transcription, showing that the latter was not the result of contaminating sigmaA. Transcription of both cin-box-containing promoters initiated downstream of the cin-box and two different single basepair substitutions in the cin-box of the cinA promoter each caused a severe reduction of sigmaX-directed transcription in vitro. Thus, the cin-box is required for sigmaX-directed transcription.

Bacillus subtilis↗
PubMed2001

HLA-G genotypes and pregnancy outcome in couples with unexplained recurrent miscarriage.

HLA-G is a non-classical human leukocyte antigen expressed primarily in fetal tissues at the maternal-fetal interface. This expression pattern is unique among HLA genes and suggests that HLA-G may be involved in interactions that are critical in establishing and/or maintaining pregnancy. To evaluate the role of polymorphisms at this locus in maternal-fetal interactions, 113 couples with unexplained recurrent miscarriage were genotyped for seven polymorphisms that define 12 HLA-G alleles. Logistic regression analysis was used to assess whether HLA-G genotypes were associated with an increased risk for a subsequent miscarriage. The presence of an HLA-G*0104 or HLA-G*0105N allele in either partner was significantly associated with an increased risk for miscarriage, after adjustment for maternal age, number of previous miscarriages, history of a previous liveborn, and treatment with paternal mononuclear cells. The *0104 and *0105N alleles are defined by polymorphisms in the alpha-2 domain and encode protein variants that are present only in the full-length HLA-G1 protein. The significant genotype-specific risk in this population suggests that allelic variation in the alpha-2 domain of the HLA-G1 isoforms contributes to recurrent miscarriage.

Abortion, Habitual↗
PubMed2001

Novel group of virulence activators within the AraC family that are not restricted to upstream binding sites.

Several regulators within the AraC family control the expression of genes known or thought to be required for virulence of bacterial pathogens. One of these, Rns, activates transcription from an unprecedented variety of binding-site locations. Although nearly all prokaryotic activators bind within a small region upstream and adjacent to the promoter that they regulate, Rns does not bind within this region to activate its own promoter, Prns. Instead, to activate Prns, Rns requires one binding site 224.5 bp upstream and one downstream of the transcription start site. We show in this study that several other AraC family activators recognize the same binding sites as Rns and share with it the ability to utilize a downstream binding site. Like Rns, other members of this group of activators positively regulate the expression of virulence factors in pathogenic bacteria. These regulators are also able to activate transcription from promoter-proximal upstream binding sites since they are able to substitute for Rns at Pcoo, a promoter with only upstream binding sites. Thus, Rns is the prototype for a group of regulators, which include CfaR, VirF, AggR, and CsvR and which activate transcription from locations that are more diverse than those of any other known activator.

Amino Acid Sequence↗
PubMed2001

Generation and surface localization of intact M protein in Streptococcus pyogenes are dependent on sagA.

The M protein is an important surface-located virulence factor of Streptococcus pyogenes, the group A streptococcus (GAS). Expression of M protein is primarily controlled by Mga, a transcriptional activator protein. A recent report suggested that the sag locus, which includes nine genes necessary and sufficient for production of streptolysin S, another GAS virulence factor, is also needed for transcription of emm, encoding the M protein (Z. Li, D. D. Sledjeski, B. Kreikemeyer, A. Podbielski, and M. D. Boyle, J. Bacteriol. 181:6019-6027, 1999). To investigate this in more detail, we constructed an insertion-deletion mutation in sagA, the first gene in the sag locus, in the M6 strain JRS4. The resulting strain, JRS470, produced no detectable streptolysin S and showed a drastic reduction in cell surface-associated M protein, as measured by cell aggregation and Western blot analysis. However, transcription of the emm gene was unaffected by the sagA mutation. Detailed analysis with monoclonal antibodies and an antipeptide antibody showed that the M protein in the sagA mutant strain was truncated so that it lacks the C-repeat region and the C-terminal domain required for anchoring it to the cell surface. This truncated M protein was largely found, as expected, in the culture supernatant. Lack of surface-located M protein made the sagA mutant strain susceptible to phagocytosis. Thus, although sagA does not affect transcription of the M6 protein gene, it is needed for the surface localization of this important virulence factor.

Antigens, Bacterial↗
PubMed2001

Restoration of Mga function to a Streptococcus pyogenes strain (M Type 50) that is virulent in mice.

The Mga protein in B514Sm, a Streptococcus pyogenes strain isolated as a mouse pathogen, contains amino acid substitutions at conserved sites that render the protein defective. Replacement of mga50 with the functional homolog mga4.1 restored full expression of Mga-regulated proteins. Restoration of Mga function did not affect fibrinogen binding, nor did it affect virulence in several mouse models of group A streptococcus infection.

Animals↗
PubMed2001

A comparison of leg-to-leg bioelectrical impedance and skinfolds in assessing body fat in collegiate wrestlers.

A comparison of the leg-to-leg bioelectrical impedance (BIA) system and skinfold analysis in estimating % body fat in a large number of National Collegiate Athletic Association (NCAA) collegiate wrestlers was conducted. A series of 5 cross-sectional assessments, including the NCAA Division I and III Championships, were completed throughout the 1998-1999 wrestling season with samples ranging from (N = 90-274). Body density was determined from the 3 skinfold measures using the Lohman prediction equation. BIA measurements were determined using the Tanita body fat analyzer, model 305. Significant correlations between methods ranging from (r = 0.67-0.83, p < 0.001) and low standard error of estimates (SEE) for % body fat ranging from 2.1-3.5% were found throughout the 5 assessment periods. This preliminary study demonstrated that the leg-to-leg bioelectrical impedance system accurately estimated % body fat when compared to skinfolds in a diverse collegiate wrestling population.

Adolescent↗
PubMed2000

Human chorionic gonadotrophin for recurrent miscarriage.

BACKGROUND: There may be an association between recurrent miscarriage and abnormal hormone function in the follicular phase. Human chorionic gonadotrophin may play a role in preventing miscarriages. OBJECTIVES: The objective of this review was to assess the effects of human chorionic gonadotrophin administration during early pregnancy on the risk of miscarriage in women with a history of recurrent miscarriage. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register was searched. Date of last search: 9 January 1998. SELECTION CRITERIA: Randomised trials of human chorionic gonadotrophin compared with placebo or no treatment in women who have had two or more miscarriages. DATA COLLECTION AND ANALYSIS: Eligibility and trial quality were assessed by one reviewer. MAIN RESULTS: Four trials involving 180 women were included. The trials were of variable quality. Human chorionic gonadotrophin was associated with a reduced risk of miscarriage for women with a history of recurrent miscarriage (odds ratio 0.26, 95% confidence interval 0.14 to 0.52). This result should be interpreted cautiously because the apparent effect is greatly influenced by the two methodologically weaker studies. REVIEWER'S CONCLUSIONS: There is not enough evidence to evaluate the use of human chorionic gonadotrophin during pregnancy in order to prevent miscarriage in women with a history of unexplained recurrent spontaneous miscarriage.

Abortion, Habitual↗
PubMed2000

Immunotherapy for recurrent miscarriage.

BACKGROUND: Immunologic aberrations might be the cause of recurrent early pregnancy loss in some women. OBJECTIVES: The objective of this review was to assess the effects of leukocyte immunisation or other immunologic treatments such as intravenous immune globulin (IVIG) on the live birth rate in women with previous unexplained recurrent miscarriages. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register was searched. Individual patient data were obtained from the American Society for Reproductive Immunology and by MEDLINE search. Date of last search: December 1999. SELECTION CRITERIA: Randomised trials of immunotherapy in women with three or more prior miscarriages, no more than one live birth, all non-immunologic causes ruled out and no simultaneous treatment intervention. DATA COLLECTION AND ANALYSIS: Eligibility and trial quality were assessed by one reviewer. MAIN RESULTS: Eighteen trials of high quality were included. The various forms of immunotherapy did not show significant differences between treatment and control groups. For paternal cell immunisation, the odds ratios was 1.05, 95% confidence interval 0.75 to 1.47. For third party donor cell immunization, the odds ratio was 1.39, 95% confidence interval 0.68 to 2.82. For trophoblast membrane infusion the odds ratio was 0.40, 95% confidence interval 0.11 to 1.45. For intravenous immune globulin (IVIG), the odds ratio was 1.14, 95% confidence interval 0. 66 to 1.95. REVIEWER'S CONCLUSIONS: Paternal cell immunization, third party donor leukocytes, trophoblast membranes, and IVIG provide no significant beneficial effect over placebo in preventing further miscarriages.

Abortion, Habitual↗