Characteristic findings of toxoplasmosis in utero: a case report.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
M E Martin
Publications and source records attributed to M E Martin.
Free fatty acid-induced alterations in the steroid-binding properties of rat androgen-binding protein.
The free fatty acid (FFA) concentration in the epididymal cytosol of the adult rat was found to be 20-fold higher than in the serum. The binding of [3H] dihydrotestosterone to epididymal rat androgen binding protein (rABP) was modified by physiological concentrations of saturated and unsaturated fatty acids. Polyunsaturated fatty acids inhibited the binding more efficiently than monounsaturated or saturated fatty acids. Scatchard analysis and Dixon plots indicated that the number of binding sites decreased in presence of unsaturated fatty acids with an inhibition constant (Ki) of 4 microM for arachidonic acid (C20:4) and 20 microM for oleic acid (C18:1). These results indicate that unsaturated fatty acids induce alterations in rABP steroid-binding properties that could modulate the endocrine function of rABP.
Androgen-Binding Protein↗
A new serum-responsive, cardiac tissue-specific transcription factor that recognizes the MEF-2 site in the myosin light chain-2 promoter.
We have identified a serum-responsive, cardiac tissue-specific transcription factor, BBF-1, that recognizes an AT-rich sequence (element B), identical to the myocyte enhancer factor (MEF-2) target site, in the cardiac myosin light chain-2 (MLC-2) promoter. Deletion of the element B sequence alone from the cardiac MLC-2 promoter causes, as does that of the MEF-2 site from other promoters and the enhancer of skeletal muscle genes, a marked reduction of transcription. BBF-1 is distinguishable from cardiac MEF-2 on the basis of immunoprecipitation with an antibody which recognizes MEF-2 but not BBF-1. Unlike MEF-2, BBF-1 is present exclusively in nuclear extracts from cardiac muscle cells cultured in a medium containing a high concentration of serum. Removal of serum from culture medium abolishes BBF-1 activity selectively with a concomitant loss of the positive regulatory effect of element B on MLC-2 gene transcription, indicating that there is a correlation between the BBF-1 binding activity and the tissue-specific role of the element B (MEF-2 site) sequence. The loss of element B-mediated activation of transcription is reversed following the refeeding of cells with serum-containing medium. These data demonstrate that cardiac muscle cells contain two distinct protein factors, MEF-2 and BBF-1, which bind to the same target site but that, unlike MEF-2, BBF-1 is serum inducible and cardiac tissue specific. BBF-1 thus appears to be a crucial member of the MEF-2 family of proteins which will serve as an important tool in understanding the regulatory mechanism(s) underlying cardiogenic differentiation.
Animals↗
Stimulation of the binding properties of adult rat corticosteroid-binding globulin by a lipolysis-induced rise in plasma free fatty acids.
In vitro studies have shown that FFA induce conformational changes in human corticosteroid-binding globulin (CBG). We increased the plasma FFA concentrations of adult male rats by injecting heparin to determine whether such changes in CBG binding and immunological properties also occur in vivo. The in vivo transient activation of lipase by heparin produced a large increase in plasma FFA at 10 and 20 min (P < 0.01), which was maximal at 60 min (P < 0.005) and remained elevated at 120 min (P < 0.01) postinjection. This rise in FFA was associated with a 2- to 3-fold increase in the binding indices (C values; liters per g) of corticosterone (B) and progesterone to CBG 60-120 min postinjection (P < 0.001). There was a good positive correlation (r = 0.85) between the increase in B binding and the rise in plasma FFA in heparin-treated rats. The enhanced B binding to CBG resulted from a 2-fold increase in the apparent number of binding sites, without any significant change in the affinity constant (Ka). FFA extracted from postheparin plasma and a standard FFA mixture induced similar changes in B binding to purified mature rat CBG. The immunological behavior of CBG was not significantly changed after heparin-induced lipolysis, but the immunoreactivity of CBG from heparin-treated rats was more reduced by incubation with exogenous FFA than that from controls. FFA extracted from the plasma of heparin-treated rats and a standard FFA mixture both produced a dose-dependent drop in the immunodetection of pure CBG. These binding and immunological studies indicate that FFA mediate conformational changes in rat CBG in vivo. Thus, FFA, in addition to their roles as metabolic energy sources and components of complex lipids, can be rapid potent endogenous modulators of steroid-protein interactions.
Animals↗
Alcohol and drug education at the University of Oklahoma College of Dentistry.
Explore the source record for details and available documents.
Alcoholism↗
In vivo transient rise in plasma free fatty acids alters the functional properties of alpha-fetoprotein.
Previous in vitro studies have shown that unsaturated fatty acids (UFA) induce conformational changes in rodent and human alpha-fetoprotein (AFP). To determine whether such changes in the binding and immunological properties of rat AFP also occur in vivo, plasma free fatty acid (FFA) concentrations were increased in young male rats (15, 21 and 28 days old) by acute i.v. injection of heparin (200 IU/kg). Plasma estrogens (estrone and estradiol) did not change after injection of heparin. There was a large increase in plasma FFA 10-20 min post-heparin injection, with a return to normal 60 min later. This transient rise in FFA plasma was associated with a 50% drop (P less than 0.001) in the binding of estradiol to rat AFP of 15-, 21- and 28-day-old rats by reducing the number of binding sites (P less than 0.001), leaving the affinity constant (Ka) unchanged. FFA extracts from post-heparin plasma induced similar changes in estradiol binding to purified rat AFP. The rise in plasma FFA induced a loss of AFP immunoreactivity, in 21- (P less than 0.001) and 28-day-old rats (P less than 0.001), but not in 15-day-old rats. This age-dependent response correlated with the FFA/AFP molar ratio (38 in 15-day-old rats, 388 in 21-day-old rats, and 5600 in 28-day-old rats). These results indicate that an in vivo rise in FFA induces rapid and reversible conformational changes in AFP which may modulate the endocrine and immune function of this oncofetal protein.
Animals↗
Alterations in the concentrations and binding properties of sex steroid binding protein and corticosteroid-binding globulin in HIV+patients.
The abnormal concentrations of steroid hormones and free fatty acids in the plasma of HIV-infected subjects are associated with qualitative and quantitative alterations in two of the major steroid hormones carrier proteins, sex steroid-binding protein (SBP) and corticosteroid-binding globulin (CBG). The properties of SBP and CBG in the sera of two age-matched groups of 67 men healthy blood donors (controls) and 64 HIV+subjects: 11 CDC group II and III (ASY), 6 CDC group IVA and 47 groups IV C1+D (AIDS) were analyzed. The HIV+patients had SBP concentrations 39-51% above those of controls. The sera of AIDS patients had higher SBP association constants (Ka) for testosterone than did those of the II, III and IVA groups and controls. In contrast, the CBG concentrations in all the HIV+subjects were similar to those of the controls. However, the binding properties of HIV+CBG were abnormal: the Ka's for cortisol and 17 alpha hydroxyprogesterone binding were 50% below normal, while the number of binding sites was significantly higher. Such changes in these carrier proteins could result from conformational transitions; they may cause abnormal transfer of hormonal information and/or steroid hormones metabolism, thus modifying the impact of steroids on the immune response in HIV+subjects.
17-alpha-Hydroxyprogesterone↗
Imported fire ant immunotherapy: effectiveness of whole body extracts.
The purpose of this study was to determine if whole body extract (WBE) immunotherapy for imported fire ant (IFA) hypersensitivity is effective. This evaluation was carried out by retrospectively interviewing 76 patients with a history of generalized allergic reactions to IFA stings and positive skin tests to IFA-WBE. The study groups consisted of 65 patients on immunotherapy and 11 similar patients who were not treated for various reasons. In addition, an IFA sting challenge was performed in 30 volunteers of the 65 patients on immunotherapy. The retrospective review showed that of the 65 patients on immunotherapy there had been 112 subsequent field-sting episodes in 47 patients. Only one sting episode in this group (2.1%) produced an anaphylactic reaction. Six of the 11 patients not on immunotherapy have had subsequent field re-sting episodes, and each has had a systemic reaction. Repeat skin testing on 31 of the 65 patients in the immunotherapy group showed persistent positive responses in five (16%), but each was at a lower dilution than initially. Responses of the other 26 of the 31 patients who had skin testing had become negative. The four untreated patients who were available for skin testing continued to have positive responses at comparable dilutions on skin testing. Sting challenges carried out on 30 volunteers from the 65 patients (all from the 31 who had repeat skin tests) on immunotherapy resulted in only local reactions.(ABSTRACT TRUNCATED AT 250 WORDS)
Anaphylaxis↗
Expression of a 91-kilodalton PEA3-binding protein is down-regulated during differentiation of F9 embryonal carcinoma cells.
Proteins binding to the PEA3 enhancer motif (AGGAAG) activate the polyomavirus early promoter and help comprise the viral late mRNA initiator element (W. Yoo, M. E. Martin, and W. R. Folk, J. Virol. 65:5391-5400, 1991). Because many developmentally regulated cellular genes have PEA3 motifs near their promoter sequences, and because Ets family gene products activate the PEA3 motif, we have studied the expression of PEA3-binding proteins and Ets-related proteins during differentiation of F9 embryonal carcinoma cells. An approximately 91-kDa protein (PEA3-91) was identified in F9 cell nuclear extracts by UV cross-linking to a radiolabeled PEA3 oligonucleotide probe, and expression of PEA3-91 was down-regulated after differentiation of F9 cells to parietal endoderm. The c-ets-1 gene product binds to a sequence in the murine sarcoma virus long terminal repeat that is similar to the PEA3 motif (cGGAAG), but PEA3-91 was not cross-linked to this Ets-1-binding motif, nor did antiserum which recognizes murine c-ets-1 and c-ets-2 proteins have any effect on PEA3-binding activity in mobility shift assays. Furthermore, c-ets-1 mRNA was not detected in undifferentiated or differentiated F9 cells, and c-ets-2 mRNA levels remained high after differentiation. Antiserum against the Drosophila Ets-related E74A protein, however, recognized an approximately 92-kDa protein in F9 cells whose expression during differentiation varied in a manner identical to that of PEA3-91. These data suggest that PEA3-91 is not the product of the ets-1 or ets-2 genes but is likely to be the product of a murine homolog of the Drosophila E74 gene.
Animals↗
fos-mediated repression of cardiac myosin light chain-2 gene transcription.
The transcription of the chicken cardiac myosin light chain-2 (MLC-2) promoter containing a 1.3 Kb 5'-flanking DNA segment is repressed upon co-transfection with an expression vector (pMMV) containing the proto-oncogene fos in embryonic chicken cardiac muscle cells in culture. Similar concentrations of co-transfectants containing other genes e.g. luciferase were ineffective. To identify the DNA element(s) in MLC-2 gene that responds to fos-mediated inhibition, 5'-sequential deletion mutants of MLC-2 promoter were tested in a transient transfection assay. A mutant, in which the 5' distal sequence was deleted upto -1200 bp upstream of the mRNA start site was sensitive to fos inhibition, but the mutant containing -1130 bp was not, suggesting that a fos responsive element (FRE) is located between -1130 to -1200 bp upstream of the transcription initiation site. The same FRE sequence was also responsive to fos-inhibition in chicken skeletal muscle cells as well. Since over-expression of fos is implicated in repression of myogenic process, the selective inhibition of MLC-2 promoter activity by fos and identification of FRE sequence potentially important in understanding the relationship between myogenesis and the oncoprotein-mediated signal pathway(s).
Animals↗
Measurement of an adhesion molecule as an indicator of inflammatory disease activity. Up-regulation of the receptor for hyaluronate (CD44) in rheumatoid arthritis.
The hyaluronate receptor (CD44) molecule is a multifunctional cell surface protein involved in T cell activation, monocyte cytokine release, fibroblast locomotion, and lymphocyte binding to high endothelial venules. To study the roles CD44 molecules play in inflammatory synovitis, we measured expression of CD44 in inflamed and noninflamed synovial fluid and tissue, using indirect immunofluorescence assays on tissue sections and quantitative Western blot analysis. The ability of purified CD44 protein to modulate T cell responses was tested in T cell activation assays in which CD44-containing liposomes were added in vitro. CD44 was widely expressed on many synovial cell types, and synovial tissue from rheumatoid arthritis (RA) patients contained 3.5 times more CD44 than tissue from osteoarthritis patients and 10.7 times more than tissue from patients with joint trauma. The level of soluble CD44 in RA synovial fluid was elevated only in fluids with low cell counts (less than or equal to 7,000/mm3), and not in RA synovial fluid with higher cell counts. Soluble purified CD44 protein in liposomes partially suppressed T cell activation in vitro. These data demonstrate that CD44 is up-regulated on many synovial cell types in patients with RA, and that the level of CD44 present in synovial tissue is related to the degree of synovial inflammation. Determination of ways to inhibit the proinflammatory functions of immune cell membrane CD44 molecules may provide new therapeutic modalities for RA.
Adult↗
The genome of human herpesvirus 6: maps of unit-length and concatemeric genomes for nine restriction endonucleases.
More than 50 fragments resulting from complete digestion of the DNA of human herpesvirus 6 (HHV-6, strain U1102) with BamHI, EcoRI, HindIII, KpnI, NruI, SalI or SmaI have been isolated as clones in M13, plasmid, cosmid and lambda vectors. Using these clones, maps have been constructed for the fragments produced by nine restriction enzymes from unit-length virus genomes and from their concatemeric precursors. The unit-length genome is a linear, double-stranded molecule of 161.5 kbp composed of a central segment of a largely unique sequence of 141 kbp (U) with a sequence of 10 kbp duplicated in the same orientation at both 'left' and 'right' genomic termini (i.e. 'left' and 'right' copies of the direct repeat; DRL and DRR). Adopting as standard an orientation in which the major capsid protein gene is 'left' of the gene for alkaline exonuclease, then the 'right' genome termini and DRL. U junctions occur close to or within repetitive (GGGTTA)n sequences. Repetitions of short sequence motifs are present in at least two other regions of the genome. One of these regions consists of a simple repeat (TC/G) of approximately 1.5 kbp in length and is unstable as clones in bacterial vectors. The second region is stably maintained in such vectors and consists of a tandem array of at least 25 copies of a 110 bp sequence containing a single KpnI site. Comparisons of fragments arising from unit-length DNA with those from virus DNA from the nuclei of infected cells have shown that the concatemeric junctions in intracellular DNA contain head-to-tail dimers of the terminal duplications (i.e. ...U1.DRR1.DRL2.U2...). The gross structure established here for the genome from the U1102 isolate of HHV-6 resembles closely that suggested by Pellett and his colleagues for the Z29 isolate and differs from that of the five previously characterized human herpesviruses. This structure of HHV-6 DNA bears a superficial resemblance to that proposed for DNA from channel catfish virus and equine cytomegalovirus.
Base Sequence↗
Identification of a transactivating function mapping to the putative immediate-early locus of human herpesvirus 6.
Sequencing studies have indicated that the unique component of the human herpesvirus 6 (HHV-6) genome and the unique long segment of the human cytomegalovirus genome are genetically colinear. Of particular interest is the identification of a region of local CpG dinucleotide suppression in the genome of HHV-6, a feature conserved in the genomes of human cytomegalovirus, murine cytomegalovirus, and simian cytomegalovirus, and a characteristic of the major immediate-early loci of these viruses. Adjacent to this region in HHV-6 are approximately 30 copies of a 103- to 108-bp sequence element, which contains consensus binding sites for the transcription factors AP2 and NF kappa B, in addition to a single KpnI recognition site. Together, these KpnI repeat units may compose an immediate-early enhancer, analogous to those found in the cytomegaloviruses. We present the sequence of this region of HHV-6 and demonstrate that a transactivating function is encoded by this region. We have used polymerase chain reaction to synthesize fragments containing open reading frames and 5' sequences with or without the upstream KpnI repeat units. Effector plasmids containing these HHV-6 coding and 5' sequences were able to effect activation of heterologous promoter-chloramphenicol acetyltransferase (CAT) constructs, including adenovirus E3-CAT and E4-CAT, human T-cell lymphotropic virus type I long terminal repeat (LTR)-CAT, and human immunodeficiency virus LTR-CAT, in cotransfection experiments in Vero cells and peripheral blood lymphocytes. Furthermore, we have identified the major open reading frame (RF4; 2.3 kb) as being essential for activation, and we have shown that the NF kappa B, SP1, and TATA box motifs in the human immunodeficiency virus LTR are all required for full induction of the promoter by the HHV-6-encoded transactivator.
Amino Acid Sequence↗
PEA1 and PEA3 enhancer elements are primary components of the polyomavirus late transcription initiator element.
The circular polyomavirus genome is transcribed from divergent promoter regions. Early mRNAs are initiated from a transcription complex formed at a TATA motif, the site of binding of transcription factor TFIID. Early transcription is promoted at a distance by the viral enhancer, which includes DNA motifs bound by cellular proteins of the PEA1 and PEA3 families of transcription activators. In contrast, the predominant viral late mRNAs are initiated within the viral enhancer, which lacks a TATA motif, near the PEA1 and PEA3 DNA motifs. Here, we demonstrate that these PEA1 and PEA3 binding sites are primary components of an autonomous transcription initiator element (Inr). They cause transcription of most polyomavirus late mRNAs and can direct the transcription of heterologous reporter genes. Alternative roles of these DNA motifs as activators of early mRNA transcription and as an initiator element for late mRNA transcription help explain how polyomavirus gene expression is regulated during lytic growth and provides a model for cellular transcription during development.
Animals↗
Objective antihistamine side effects are mitigated by evening dosing of hydroxyzine.
First-generation antihistamines have potency, pharmacokinetic, and cost advantages compared with nonsedating second-generation antihistamines. Bedtime dosing of hydroxyzine was investigated as a dosing strategy to minimize reaction time degradation and adverse subjective symptoms previously documented for hydroxyzine in divided doses. Hydroxyzine, 50 mg qhs, was compared with terfenadine, 60 mg bid, in this double-blind, placebo-controlled crossover study of 15 healthy, asymptomatic adults. Computer-based eye-hand reaction time tests of simple reaction time (SRT) and choice reaction time (CRT) were not statistically different among the three drugs. Drowsiness, dry mouth, and irritability were significant for hydroxyzine (P = .0001, .001 and .02, respectively) compared with terfenadine or placebo, but less than seen in a previous study of hydroxyzine, 25 mg bid. Symptom scores with terfenadine were comparable to placebo. Histamine skin test wheal and flare were both significantly and comparably suppressed by hydroxyzine and terfenadine (P = .0001). While wheal suppression by hydroxyzine was universal, four of the 15 subjects showed little or no suppression with terfenadine (P = .03). Although bedtime dosing of hydroxyzine did not eliminate subjective symptoms, it maintained skin H1-receptor antagonism the following morning and alleviated the prolongation of reaction times previously reported with hydroxyzine in divided doses. The significant adverse subjective symptoms and psychomotor performance degradations caused by first-generation antihistamines can be mitigated by creative dosing schedules.
Administration, Oral↗
Synthetic peptides containing T and B cell epitopes from human immunodeficiency virus envelope gp120 induce anti-HIV proliferative responses and high titers of neutralizing antibodies in rhesus monkeys.
We have previously described a synthetic peptide (T1-SP10) derived from two noncontiguous regions of HTLVIIIB envelope gp120 (T1, amino acids 428-443; SP10, amino acids 303-321) that induced type-specific anti-HIV neutralizing antibodies and T cell proliferative responses against native HIV gp120 when used as a carrier-free immunogen in goats. In this study, HTLVIIIB T1-SP10 synthetic peptides were used to immunize rhesus monkeys to determine if the peptides were capable of eliciting HIV-specific neutralizing antibody and proliferative responses in primates. Four compounds (alum, polyA:polyU, threonyl-muramyldipeptide (MDP) and IFA) were also compared for efficacy as adjuvants in this system. Rhesus monkeys immunized with T1-SP10 peptides generated high titers of antibodies against the immunogens and also against HTLVIIIB gp120. Sera from all four animals given T1-SP10 in IFA or threonyl-MDP neutralized infection by HTLVIIIB and blocked virus-dependent cell fusion events. A peak neutralization titer of 1:940 was seen in one animal given IFA (19600) and a titer of 1:900 was seen in one of the monkeys (17371) given threonyl-MDP. Proliferative responses of immune rhesus PBMC to T1-SP10 appeared after the first injection. After eight immunizations, two of eight monkeys (one injected with peptides in threonyl-MDP and one given peptides in IFA) had PBMC proliferative responses to native HTLVIIIB gp120. These data demonstrate that the carrier-free T1-SP10 synthetic peptide construct can induce high titers of neutralizing anti-HIV antibody responses and PBMC proliferative responses to HIV in primates.
Adjuvants, Immunologic↗
Allergic Bipolaris sinusitis: clinical and immunopathologic characteristics.
Allergic Aspergillus sinusitis was first reported in 1983. We present the first three cases of allergic fungal sinusitis caused by the black fungus Bipolaris spicifera. The patients were young, atopic, and immunocompetent. All three patients demonstrated pansinusitis with nasal polyps and underwent multiple surgical procedures. Pathologic features included a characteristic mucoid exudate containing eosinophils, Charcot-Leyden crystals, and fungal hyphae. In two cases there was bony erosion revealed by computed tomography scan but no histologic evidence of direct fungal invasion into the mucosa or bony trabeculae. Immunologic features, including total eosinophil count, total serum IgE, immediate and late-phase skin response to B. spicifera, serum precipitins, and specific IgE and IgG to B. spicifera, are described. B. spicifera is a previously unrecognized cause of allergic fungal sinusitis that may be an underdiagnosed disorder. This diagnosis should be considered in atopic patients with nasal polyps and pansinusitis unresponsive to conventional medical therapy. Diagnostic criteria include characteristic histologic allergic mucin, culture identification of fungus, positive immediate cutaneous reactivity to fungal extract, positive serum precipitins, and elevated specific IgE and IgG antibodies.
Adolescent↗
Corticosteroid modifications in HIV infection: a role for nonesterified fatty acids.
Explore the source record for details and available documents.
Adrenal Cortex Hormones↗