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Biomedical subjects

D Bryant

Publications and source records attributed to D Bryant.

At least 19 recordsLinked to original sources
PubMed1999

Magnetic resonance imaging and invasive evaluation of development of heart failure in transgenic mice with myocardial expression of tumor necrosis factor-alpha.

BACKGROUND: Transgenic mice expressing tumor necrosis factor-alpha (TNF-alpha) in cardiac myocytes develop dilated cardiomyopathy, but the temporal progression to cardiac dysfunction is not well characterized. We asked (1) Does magnetic resonance imaging (MRI) provide a reproducible assessment of cardiac output in mice that correlates with invasive measurements obtained with thermodilution? (2) What is the time course of left ventricular (LV) remodeling in transgenic mice with myocardial expression of TNF-alpha? METHODS AND RESULTS: Transgenic mice from 2 different lineages with differing amounts of myocardial TNF-alpha expression [lineage 1 (L1) and lineage 2 (L2)] and littermate controls (LC) were studied. In protocol 1, cardiac output (CO) and stroke volume (SV) were measured by MRI and thermodilution (TD) in 15 mice (3 L1, 4 L2, 8 LC). In protocol 2, 23 mice (7 L1, 8 L2, 8 LC) were scanned at 1 month of life and every 4 weeks thereafter. In both protocols, cine-MRI was performed with the use of a 1.5-T clinical system (1.5-mm slices, 195x195 microm in-plane resolution). MRI CO and SV correlated well with TD [COTD (mL/min)=0.94*COMRI+0.72, r=0.84; SVTD( microL)=1. 01*SVMRI-1.07, r=0.94]. Serial MRI studies showed significant increase in LV mass and volumes over time and a significant decrease in ejection fraction in transgenic mice when compared with littermate controls. Compared with lineage 2, lineage 1 showed significantly larger LV mass and volumes and significantly lower ejection fraction. CONCLUSIONS: MRI assessment of cardiac function in mice correlates well with invasive measurements. Serial MRI studies in the TNF-alpha mouse model demonstrate that the rate of progression and severity of LV dysfunction are dependent on the degree of TNF-alpha overexpression.

Animals↗
PubMed1999

Sequential molecular abnormalities are involved in the multistage development of squamous cell lung carcinoma.

To understand the molecular pathways involved in the pathogenesis of squamous cell lung carcinoma, we obtained DNA from 94 microdissected foci from 12 archival surgically resected tumors including histologically normal epithelium (n=13), preneoplastic lesions (n=54), carcinoma is situ (CIS) (n=15) and invasive tumors (n=12). We determined loss of heterozygosity (LOH) at 10 chromosomal regions (3p12, 3p14.2, 3p14.1-21.3, 3p21, 3p22-24, 3p25, 5q22, 9p21, 13q14 RB, and 17p13 TP53) frequently deleted in lung cancer, using 31 polymorphic microsatellite markers, including 24 that spanned the entire 3p arm. Our major findings are as follows: (1) Thirty one percent of histologically normal epithelium and 42% of mildly abnormal (hyperplasia/metaplasia) specimens had clones of cells with allelic loss at one or more regions; (2) There was a progressive increase of the overall LOH frequency within clones with increasing severity of histopathological changes; (3) The earliest and most frequent regions of allelic loss occurred at 3p21, 3p22-24, 3p25 and 9p21; (4) The size of the 3p deletions increased with progressive histologic changes; (5) TP53 allelic loss was present in many histologically advanced lesions (dysplasia and CIS); (6) Analyses of 58 normal and non-invasive foci having any molecular abnormality, indicated that 30 probably arose as independent clonal events, while 28 were potentially of the same clonal origin as the corresponding tumor; (7) Nevertheless, when the allelic losses in the 30 clonally independent lesions and their clonally unrelated tumors were compared the same parental allele was lost in 113 of 125 (90%) of comparisons. The mechanism by which this phenomenon (known as allele specific mutations) occurs is unknown; (8) Four patterns of allelic loss in clones were found. Histologically normal or mildly abnormal foci had a negative pattern (no allelic loss) or early pattern of loss while all foci of CIS and invasive tumor had an advanced pattern. However dysplasias demonstrated the entire spectrum of allelic loss patterns, and were the only histologic category having the intermediate pattern. Our findings indicate that multiple, sequentially occurring allele specific molecular changes commence in widely dispersed, apparently clonally independent foci, early in the multistage pathogenesis of squamous cell carcinomas of the lung.

Aged↗
PubMed1998

Cardiac failure in transgenic mice with myocardial expression of tumor necrosis factor-alpha.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional cytokine that has been detected in several human cardiac-related conditions, including congestive heart failure and septic cardiomyopathy. In these conditions, the origin of TNF-alpha secretion is, at least in part, cardiac myocytes. METHODS AND RESULTS: To determine the consequences of TNF-alpha production by cardiac myocytes in vivo, we developed transgenic mice in which expression of a murine TNF-alpha coding sequence was driven by the murine alpha-myosin heavy chain promoter. Four transgenic founders developed an identical illness consisting of tachypnea, decreased activity, and hunched posture. In vivo, ECG-gated MRI of symptomatic transgenic mice documented a severe impairment of cardiac function evidenced by biventricular dilatation and depressed ejection fractions. All transgenic mice died prematurely. Pathological examination of affected animals revealed a globular dilated heart, bilateral pleural effusions, myocyte apoptosis, and transmural myocarditis in both the right and left ventricular free walls, septum, and atrial chambers. In all terminally ill animals, there was significant biventricular fibrosis and atrial thrombosis. CONCLUSIONS: This is the first report detailing the effects of tissue-specific production of TNF-alpha by cardiac myocytes in vivo. These findings indicate that production of TNF-alpha by cardiac myocytes is sufficient to cause severe cardiac disease and support a causal role for this cytokine in the pathogenesis of human cardiac disease.

Animals↗
PubMed1998

Otitis media, the caregiving environment, and language and cognitive outcomes at 2 years.

OBJECTIVE: To examine the relationship between otitis media with effusion (OME) and associated hearing loss between 6 and 24 months of age and children's language and cognitive development at 2 years of age. STUDY DESIGN: A prospective cohort design in which 86 African-American infants who attended group child-care centers were recruited between 6 and 12 months of age. Between 6 and 24 months, assessments included serial ear examinations using otoscopy and tympanometry, serial hearing tests, two ratings of the childrearing environment at home and in child care, and language and cognitive outcomes at 2 years. RESULTS: Children experienced either unilateral or bilateral OME an average of 63% and reduced hearing sensitivity an average of 44% of the time between 6 and 24 months of age. Although proportion of time with OME or with hearing loss was modestly correlated with measures of language and cognitive skills, these relationships were no longer significant when the ratings of the home and child-care environments were also considered. Children with more OME or hearing loss tended to live in less responsive caregiving environments, and these environments were linked to lower performance in expressive language and vocabulary acquisition at 2 years. CONCLUSIONS: Both OME and hearing loss were more strongly related to the quality of home and child-care environments than to children's language and cognitive development. Study results might be explained either by suggesting that children in less responsive caregiving environments experience conditions that make them more likely to experience OME and/or by suggesting that it may be more difficult for caregivers to be responsive and stimulating with children with more OME.

Black People↗
PubMed1998

Effects of processing at 45 C on staining.

Tissue processed at a constant temperature of 45 C including the use of paraffin wax with a melting point of 45 C displays staining characteristics that are sometimes reversed from those associated with the more usual processing schedules and wax with a melting point of 58-60 C. Staining with acid dyes, particularly in trichrome methods, are most susceptible to these changes. We suggest that this is directly related to dye molecular size and to differences in the tissue structure resulting from the heat to which the tissues were exposed.

Animals↗
PubMed1997

Immunological response in the primate oviduct to a defined recombinant sperm immunogen.

Assessment of immune responses in the oviduct is of importance in understanding reproductive tract responses to infections, vaccination against reproductive tract pathogens, or contraceptive immunogens. This review discusses a technique that permits repeated sampling of oviductal fluid from the same monkey at intervals spanning up to several years, and the analysis of antigen-specific immunoglobulins in the fluid. This technique is important to immunocontraceptive development because previous studies in primates have lacked information on oviductal immune responses and contraceptive efficacy may not correlate well with serum antibody titers. Thus, a reliable method of sampling oviductal fluid before and after immunization with a defined antigen is required to determine the quantity and type of local immune responses necessary to achieve contraceptive effects. Implantation of access ports proved useful for repeatedly aspirating oviductal fluid in vivo from cynomolgus monkeys that was free from artifactual contaminants and with no observable changes in the behavior or health of the animals. Subsequent assays of relative and absolute concentrations of antibodies in oviductal fluid and serum demonstrated the presence of IgA and IgG specific for the recombinant sperm immunogen SP-10 in fluid collected from the periovulatory oviduct of primates after intramuscular inoculations. The antibodies evoked by the recombinant sperm vaccinogen recognized the endogenous antigen target on both human and macaque sperm, lending support for the possibility of developing a contraceptive immunogen that prevents fertilization.

Acrosome↗
PubMed1997

Studies on the mutagenicity of mild gasification products of coal and their subfractions by the Salmonella/microsomal assay.

Mild gasification of coal is a technology being developed in the United States in order to upgrade lower rank coals and facilitate their use in coal-burning electric generation plants. Thirteen coal-derived mild gasification products from different coal sources and processing conditions have been examined for their potential biohazards. The mutagenicity of these samples was tested with the Ames Salmonella/microsomal assay. Two solvents, dimethyl sulfoxide (DMSO) and polyoxyethylene-sorbitan monooleate (Tween 80), were used to dissolve samples in a manner to facilitate their interaction with the test organisms. The results showed that 9 of the 13 samples displayed mutagenic activity in test strains TA98 and/or TA100 with or without metabolic activation, whether dissolved in Tween 80 or DMSO. Five mutagenic and two nonmutagenic samples were class-fractionated into basic, acidic, nonpolar, and polar neutral subfractions to examine their class-related mutagenic activities. Results of the testing of subfractions of the five mutagenic and one nonmutagenic samples showed mutagenic activity in at least the nonpolar neutral fraction. The subfractions of the another nonmutagenic sample did not display any mutagenic activity. Chemical characterization of the subfractions revealed the existence of aromatic hydrocarbons in certain subfractions, which may be responsible for the mutagenic activity of the coal-derived mild gasification products.

Animals↗
PubMed1997

Oviductal antibody response to a defined recombinant sperm antigen in macques.

Macaque oviductal fluids were assayed for specific antibodies to the intra-acrosomal sperm protein SP-10 after immunizations with recombinant macaque SP-10 (re-mqSP-10), a candidate contraceptive vaccinogen. Access ports, consisting of a subcutaneous collecting reservoir and a catheter to cannulate the oviduct, were implanted into monkeys for repeated aspiration of oviductal fluid. Monkeys were inoculated i.m. once a month with an emulsion consisting of 2 mg re-mqSP-10 in a vehicle of squalene and mannin monooleate. Oviductal fluids and serum were collected during the periovulatory period for six menstrual cycles, and IgG and IgA antigen-specific antibodies in preimmune and immune fluids were compared by ELISA. Both relative and absolute concentrations of SP-10-specific immunoglobulins (Ig) were determined. Oviductal fluids from immunized animals showed significant increases in anti-SP-10 IgG at cycle 2 and at all subsequent intervals. Anti-SP-10 IgA significantly increased in oviductal fluid at cycles 4, 5, and 6. Serum anti-SP-10 IgG increased at cycle 2 and remained significantly elevated through cycle 6, while serum anti-SP-10 IgA was higher than in preimmune samples at cycle 4. Serum antibodies generated to the recombinant SP-10 recognized SP-10 extracted from macaque sperm on Western blots. Immunocytochemical staining of macaque and human sperm showed acrosomal immunofluorescence with both immune oviductal fluids and serum using both anti-IgG and anti-IgA secondary antibodies. This study demonstrates for the first time 1) IgG and IgA antibodies to a defined recombinant sperm-specific antigen in primate oviductal fluids after systemic immunization and 2) the recognition by primate oviductal fluid IgG and IgA of the endogenous contraceptive target on both human and macaque sperm.

Acrosome↗
PubMed1997

Presence of UDP-N-acetylmuramyl-hexapeptides and -heptapeptides in enterococci and staphylococci after treatment with ramoplanin, tunicamycin, or vancomycin.

Analyses of the peptidoglycan nucleotide precursor contents of enterococci and staphylococci treated with ramoplanin, tunicamycin, or vancomycin were carried out by high-pressure liquid chromatography coupled with mass spectrometry (MS). In all cases, a sharp increase in the UDP-N-actetylmuramoyl-pentapeptide or -pentadepsipeptide pool was observed. Concomitantly, new peptidoglycan nucleotide peptides of higher molecular masses with hexa- or heptapeptide moieties were identified: UDP-MurNAc-pentapeptide-Asp or pentadepsipeptide-Asp in enterococci and UDP-MurNAc-pentapeptide-Gly or -Ala and UDP-MurNAc-pentapeptide-Gly-Gly or -Ala-Gly in staphylococci. These new compounds are derivatives of normal UDP-MurNAc-pentapeptide or -pentadepsipeptide precursors with the extra amino acid(s) linked to the lysine epsilon-amino group as established by various analytical procedures (MS, MS-MS fragmentation, chemical analysis, and digestion with R39 D,D carboxypeptidase). Except for tunicamycin-treated cells, it was not possible to ascertain whether these unusual nucleotides were formed by direct addition of the amino acids to UDP-MurNAc-pentapeptide (or -pentadepsipeptide) or whether they arose by reverse reactions from lipid I intermediates to which the amino acids had been added.

Anti-Bacterial Agents↗
PubMed1997

Evaluating replacement mattresses.

A multidisciplinary team evaluated four replacement mattresses. The mattress that was found to be most effective in preventing pressure ulcers was then compared to the static air mattress. The study's results and outcomes are presented.

Bedding and Linens↗
PubMed1996

Peptidoglycan structure of Enterococcus faecium expressing vancomycin resistance of the VanB type.

Resistance to glycopeptide antibiotics in enterococci is due to the synthesis of UDP-MurNAc-tetrapeptide-D-lactate (where Mur is muramic acid) replacing the normal UDP-MurNAc-pentapeptide precursor. The peptidoglycan structures of an inducible VanB-type glycopeptide-resistant Enterococcus faecium, D366, and its constitutively resistant derivative, MT9, were determined. Using HPLC, 17 muropeptides were identified and were present regardless of whether resistance was expressed or not. The structures of 15 muropeptides were determined using MS and amino acid analysis. The cross-bridge between D-alanine and L-lysine consisted of one asparagine. No monomer pentapeptide or tetrapeptide-D-lactate could be identified. These results obtained with D366 (non-induced) and MT9 indicate that, in the absence of vancomycin, the cell wall synthetic machinery of E. faecium can process the lactate-containing precursor as efficiently as the normal pentapeptide. In contrast, the presence of subinhibitory inducing concentrations of vancomycin interfered with the synthesis of oligomers.

Amino Acid Sequence↗
PubMed1996

Peristomal hidradenitis suppurativa.

Hidradenitis suppurativa is a chronic, suppurative, and cicatricial cutaneous disease with clinical manifestations including inflammatory lesions and nodules, abscesses, and sinus tracts. We describe an unusual case of peristomal lesions that may represent hidradenitis suppurativa. Peristomal hidradenitis suppurativa has not been previously reported. This unusual complication demonstrates the need for a thorough patient history to identify any systemic disease that may contribute to peristomal skin problems.

Crohn Disease↗
PubMed1996

Hunting for trees in binary character sets: efficient algorithms for extraction, enumeration, and optimization.

We describe a useful and efficient tree building technique that is closely related to the maximum compatible subset method. Given a set of binary characters C and a degree bound d, the algorithm we describe counts the number of trees T that satisfy (1) the edges of T correspond to characters contained in C, and (2) the vertices of T have degree bounded by d. If the characters are weighted then we can efficiently determine which of these trees have maximum summed edge weight, where the weight of an edge equals the weight of the corresponding binary character in C. The complexity of the algorithms equals O(nk + ndK(d-1), where n is the number of taxa, k is the number of characters, and K is the number of distinct characters. A number of new tree consensus methods based on the algorithm are introduced, including one that uses edge weighted trees. As well, we illustrate the applicability of the algorithm for large sequence data sets by analyzing sequences from the "Out of Africa" mtDNA data set.

Algorithms↗
PubMed1996

Peptidoglycan synthesis and structure in Staphylococcus haemolyticus expressing increasing levels of resistance to glycopeptide antibiotics.

The structures of cytoplasmic peptidoglycan precursor and mature peptidoglycan of an isogenic series of Staphylococcus haemolyticus strains expressing increasing levels of resistance to the glycopeptide antibiotics teicoplanin and vancomycin (MICs, 8 to 32 and 4 to 16 microg/ml, respectively) were determined. High-performance liquid chromatography, mass spectrometry, amino acid analysis, digestion by R39 D,D-carboxypeptidase, and N-terminal amino acid sequencing were utilized. UDP-muramyl-tetrapeptide-D-lactate constituted 1.7% of total cytoplasmic peptidoglycan precursors in the most resistant strain. It is not clear if this amount of depsipeptide precursor can account for the levels of resistance achieved by this strain. Detailed structural analysis of mature peptidoglycan, examined for the first time for this species, revealed that the peptidoglycan of these strains, like that of other staphylococci, is highly cross-linked and is composed of a lysine muropeptide acceptor containing a substitution at its epsilon-amino position of a glycine-containing cross bridge to the D-Ala 4 of the donor, with disaccharide-pentapeptide frequently serving as an acceptor for transpeptidation. The predominant cross bridges were found to be COOH-Gly-Gly-Ser-Gly-Gly-NH2 and COOH-Ala-Gly-Ser-Gly-Gly-NH2. Liquid chromatography-mass spectrometry analysis of the peptidoglycan of resistant strains revealed polymeric muropeptides bearing cross bridges containing an additional serine in place of glycine (probable structures, COOH-Gly-Ser-Ser-Gly-Gly-NH2 and COOH-Ala-Gly-Ser-Ser-Gly-NH2). Muropeptides bearing an additional serine in their cross bridges are estimated to account for 13.6% of peptidoglycan analyzed from resistant strains of S. haemolyticus. A soluble glycopeptide target (L-Ala-gamma-D-iso-glutamyl-L-Lys-D-Ala-D-Ala) was able to more effectively compete for vancomycin when assayed in the presence of resistant cells than when assayed in the presence of susceptible cells, suggesting that some of the resistance was directed towards the cooperativity of glycopeptide binding to its target. These results are consistent with a hypothesis that alterations at the level of the cross bridge might interfere with the binding of glycopeptide dimers and therefore with the cooperative binding of the antibiotic to its target in situ. Glycopeptide resistance in S. haemolyticus may be multifactorial.

Amino Acid Sequence↗
PubMed1996

Effects of transforming growth factor-beta 1 on nitric oxide synthesis by C2C12 skeletal myocytes.

The production of nitric oxide (NO) via the inducible form of NO synthase (iNOS) is regulated by a complex network of cytokines and endogenous hormones. Among these, transforming growth factor-beta (TGF-beta 1) is known to suppress iNOS expression and NO production by many cell types. To determine the effect of TGF-beta 1 on NO production by skeletal muscle cells, we stimulated C2C12 myocytes with interferon-gamma (IFN) and interleukin-1 (IL-1) in the presence or absence of TGF-beta 1. In contrast to findings in macrophages, TGF-beta 1 markedly enhanced NO production by skeletal muscle cells. Increases in NO production reflected significant increases in iNOS immunoreactive protein and iNOS mRNA. Elevated iNOS mRNA levels associated with TGF-beta 1 treatment were not due to an alteration in mRNA stability, but rather reflected a significantly increased transcriptional rate of the iNOS gene. These findings indicate that TGF-beta 1 enhances iNOS expression in skeletal muscle cells and suggest that the regulation of NO production by TGF-beta 1 may depend on the cell type studied.

Animals↗
PubMed1996

Expression of the inducible nitric oxide synthase gene in diaphragm and skeletal muscle.

Nitric oxide (NO) is a pluripotent molecule that can be secreted by skeletal muscle through the activity of the neuronal constitutive isoform of NO synthase. To determine whether skeletal muscle and diaphragm might also express the macrophage-inducible form of NO synthase (iNOS) during provocative states, we examined tissue from mice at serial times after intravenous administration of Escherichia coli endotoxin. In these studies, iNOS mRNA was strongly expressed in the diaphragm and skeletal muscle of mice 4 h after intravenous endotoxin and was significantly diminished by 8 h after challenge. Induction of iNOS mRNA was followed by expression of iNOS immunoreactive protein on Western immunoblots. Increased iNOS activity was demonstrated by conversion of arginine to citrulline. Immunochemical analysis of diaphragmatic explants exposed to endotoxin in vitro revealed specific iNOS staining in myocytes, in addition to macrophages and endothelium. These results may be important in understanding the pathogenesis of respiratory pump failure during septic shock, as well as skeletal muscle injury during inflammation or metabolic stress.

Animals↗
PubMed1996

Reliability of a single fecal egg per gram determination as a measure of individual and herd values for trichostrongyle nematodes of cattle.

OBJECTIVES: To determine precision of a single fecal egg count, to evaluate the necessity of repeated testing to ascertain the number of parasite eggs found per gram of fecal material (EPG) of a given animal, and to infer the number of cattle that must be sampled to estimate the mean EPG value of a given herd. DESIGN: Calves born in 4 successive years were tested for 3 consecutive days in May, July, and September to determine their fecal EPG value. Results were analyzed to determine important sources of variance in the EPG values. ANIMALS: 427 Black Angus calves. PROCEDURES: Nematode EPG values were determined by zinc sulfate flotation of fecal samples taken from the rectum. Variance components were estimated by restricted maximal likelihood procedures. RESULTS: The largest source of variation in fecal egg counts arose from differences among calves. Variation associated with sampling within calf was larger than that associated with year of sampling or day when samples were taken. Repeatability of EPG determinations was between 0.4 and 0.7. CONCLUSIONS: Collection of 3 replicate samples reduced variance associated with a single calf mean by 25 to 30%. Additional replication would further reduce the variance, but at a diminishing rate. To accurately estimate mean EPG for a herd, a randomly drawn sample should be similar in composition to the herd and include at least 1 animal from the high EPG group, which often constitutes 15 to 20% of the calves. To ensure that, on average, 95% of the samples drawn contain 1 or more animals with high EPG, the sample must include 15 to 20 animals within the grazing group under study.

Analysis of Variance↗