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Biomedical subjects

G M Nelson

Publications and source records attributed to G M Nelson.

16 recordsLinked to original sources
PubMed2004

Changes in cecal microbial metabolism of rats induced by individual and a mixture of drinking water disinfection by-products.

Disinfection of drinking water has been one of the greatest public health successes. Numerous halogenated disinfection by-products (DBPs) occur and chronic ingestion has been associated with an increased risk for colorectal cancer in human populations. Because the intestinal microbiota can bioactivate xenobiotics, studies have been performed to examine the effects of individual DBPs on intestinal microbial metabolism. No studies have been conducted on a defined mixture of DBPs to determine if there is an enhancement of response to a mixture. Ten-week-old male Long-Evans rats were treated in their drinking water for 17 weeks with 0.4 g/l potassium bromate, 1.8 g/l chloroform, 0.7 g/l bromodichloromethane (BDCM), 0.07 g/l 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), or a mixture of the four chemicals or distilled water. Cecal nitroreductase (NR), azoreductase (AR), dechlorinase (DC), beta-glucuronidase (GLR), beta-galactosidase (GAL), and beta-glucosidase (GLU) were assayed. No change in GLU or GLR activity was detected after treatment. BDCM treatment reduced DC and GAL activities and elevated NR and AR activity. GAL, AR, and NR activities were significantly different after treatment with bromate, chloroform, BDCM, and MX, but not the mixture. DC activity after chloroform-, MX-, or BDCM-treatment was significantly below control levels. The present study shows that changes in intestinal microbial metabolism do occur after treatment with individual and a mixture of DBPs but the changes were not additive in the mixture group.

Animals↗
PubMed2001

Oral treatment of Fischer 344 rats with weathered crude oil and a dispersant influences intestinal metabolism and microbiota.

When oil is spilled into aquatic systems, chemical dispersants frequently are applied to enhance emulsification and biological availability. In this study, a mammalian model system was used to determine the effect of Bonnie Light Nigerian crude oil, weathered for 2 d with continuous spraying and recirculation, and a widely used dispersant, Corexit (Cx) 9527, on intestinal microbial metabolism and associated populations. To determine the subchronic dose, concentrated or diluted (1:2, 1:5, 1:10, 1:20) Cx9527 or oil was administered by gavage to Fischer 344 rats and the effect on body weight was determined. Next, rats were treated for 5 wk with oil, dispersant, or dispersant + oil. Body and tissue weights, urine mutagenicity, and the impact on the intestinal microflora and three microbial intestinal enzymes linked to bioactivation were determined in the small and large intestines and cecum. Two tested dispersants, Cx9527 and Cx9500, were toxic in vitro (1:1,000 dilution), and oil was not mutagenic in strains TA98 and TA100(+/-S9). None of the treated rats produced urine mutagens detected by TA98 or TA100. Undiluted dispersant was lethal to rats, and weight changes were observed depending on the dilution, whereas oil generally was not toxic. In the 5-wk study, body and tissue weights were unaffected at the doses administered. Small-intestinal levels of azoreductase (AR), beta-glucuronidase (BG), and nitroreductase (NR) were considerably lower than cecal and large-intestinal activities at the same time point. A temporal increase in AR activity was observed in control animals in the 3 tissues examined, and large-intestinal BG activity was elevated in 3-wk controls. No significant changes in cecal BG activity were observed. Oil- or dispersant-treated rats had mixed results with reduced activity at 3 wk and elevated activity at 5 wk compared to controls. However, when the dispersant was combined with oil at 3 wk, a reduction in activity was observed that was similar to that of dispersant alone. One-week nitroreductase activity in the small intestine and cecum was unaffected in the three treatment groups, but elevated activity was observed in the large intestines of animals treated with oil or dispersant. The effect of the combination dose was not significantly different from the control value. Due to experimental error, no 3- or 5-wk NR data were available. By 5 wk of treatment, enterobacteria and enterococci were eliminated from ceca of oil-treated rats. When oil was administered in combination with dispersant, an apparent protective effect was observed on the enterococci and lactose-fermenting and nonfermenting enterobacteria. A more detailed analysis at the species level revealed qualitative differences dependent on the treatment. This study suggests that prolonged exposure of mammals to oil, dispersant, or in combination impacts intestinal metabolism, which ultimately could lead to altered detoxification of oil constituents and coexposed toxicants.

Animals↗
PubMed2001

Expanded Möbius syndrome.

A woman presented at 33 weeks gestation with reduced fetal movements and a nonreactive nonstress test. Fetal ultrasound examination revealed a peculiar unilateral arm tremor. At emergency cesarean section, performed for fetal indications, a 1,672-gm male infant was delivered requiring intubation for feeble respiratory effort. After delivery the neonate was transiently hypertonic and later hypotonic. Continuing ventilatory support at minimal settings was necessary. The work-up for aneuploidy, metabolic disorders, and infection was negative. The infant died after being removed from ventilatory support on day 22. Postmortem examination revealed extensive bilateral brain gliosis and mineralization without evidence of inflammation, partial absence of cranial nerve nuclei III-XI, and a total absence of cranial nerve roots VI-XI. Together these finding are compatible with a diagnosis of expanded Möbius syndrome.

Adult↗
PubMed2001

Metabolism, microflora effects, and genotoxicity in haloacetic acid-treated cultures of rat cecal microbiota.

Haloacetic acids are by-products of drinking water disinfection. Several compounds in this class are genotoxic and have been identified as rodent hepatocarcinogens. Enzymes produced by the normal intestinal bacteria can transform some promutagens and procarcinogens to their biologically active forms. The present study was designed to investigate the influence of the cecal microbiota on the mutagenicity of haloacetic acids, and to look at changes in the microbiota populations and enzyme activities associated with exposure to haloacetic acids. PYG medium containing 1 mg/ml of monochloroacetic (MCA), monobromoacetic (MBA), dichloroacetic (DCA), dibromoacetic (DBA), trichloroacetic (TCA), tribromoacetic (TBA), or bromochloroacetic (BCA) acid was inoculated with rat cecal homogenate and incubated anaerobically at 37 degrees C. Growth curves were performed with enumeration of the microflora populations on selective media. Mutagenicity in a Salmonella microsuspension bioassay was determined after incubation for various lengths of time, with or without the cecal microbiota. At 15 h of incubation, enzyme assays determined the activities for beta-glucuronidase, beta-galactosidase, beta-glucosidase, azoreductase, nitroreductase, dechlorinase, and dehydrochlorinase. The haloacetic acids, with the exception of BCA, were toxic to the cecal microbiota, and especially to the enterococci. DBA, TBA, and BCA were mutagenic in the microsuspension assay, but the presence of the intestinal flora did not significantly alter the mutagenicity. BCA increased the activities of several enzymes, and therefore has the potential to affect the biotransformation of co-exposed compounds.

Acetates↗
PubMed2000

The disinfection by-products dichloro-, dibromo-, and bromochloroacetic acid impact intestinal microflora and metabolism in Fischer 344 rats upon exposure in drinking water.

Human consumption of chlorinated drinking water has been linked epidemiologically to bladder, kidney, and rectal cancers. The disinfection by-product (DBP) dichloroacetic acid is a hepatocarcinogen in Fischer 344 rats and B6C3F1 mice. The objective of this study is to determine the effect of the DBPs dichloro-, bromochloro-, and dibromoacetic acids (DCA, BCA, DBA) on intestinal microbial populations and their metabolism, with emphasis on enzymes involved in the bioactivation of procarcinogens and promutagens. One-month-old male Fischer 344 rats were provided water ad libitum containing 1 g/l DCA, BCA, or DBA for up to 5 weeks. At 1, 3, and 5 weeks of treatment, beta-glucuronidase (GLR), beta-galactosidase (GAL), beta-glucosidase (GLU), nitroreductase (NR), azoreductase (AR), and dechlorinase (DC) activities were determined in cecal and small and large intestinal homogenates. After 5 weeks of treatment, intestinal populations were enumerated on selective media. Cecal GAL (DCA, BCA, DBA) and GLR (DCA, DBA) activities were reduced after 1 and 3 weeks of treatment and GAL activity was elevated at 5 weeks (BCA). Large intestinal GAL (DCA, BCA) and GLU (DCA, BCA, DBA) activities were elevated after 5 weeks of treatment. Week 5 cecal AR (DCA, BCA, DBA), NR (DCA), and DC (DCA, DBA) activities were reduced. Even though some significant changes in intestinal populations were observed, use of selective media was not sensitive enough to explain fluctuations in enzyme activity. Haloacetic acids in the drinking water alter intestinal metabolism, which could influence bioactivation of promutagens and procarcinogens in the drinking water.

Acetates↗
PubMed1999

Colonization and clearance of environmental microbial agents upon intranasal exposure of strain C3H/HeJ mice.

Environmental dissemination of biotechnology agents is becoming a common practice. Most applications use historically innocuous species; however, potential health effects of individual products are not scrutinized unless they contain genetically engineered microorganisms. In order to investigate possible health concerns, four surrogate microbial agents were studied in vivo. Male C3H/HeJ (endotoxin-resistant) mice were administered intranasally (i.n.) with approximately 10(7) Pseudomonas aureofaciens, Burkholderia cepacia, P. fluorescens, or P. putida. To determine clearance of the dosed bacterial strains, lungs, small intestine, large intestine, cecum, mesenteric lymph nodes (MLN), spleen, and liver were homogenized individually, plated, and dilutions inoculated onto selective media. Pseudomonas fluorescens and P. putida were eliminated from the lungs by 2 d posttreatment, and P. aureofaciens was not detected in the lungs by 5 d posttreatment. Burkholderia cepacia was reisolated from the lungs and cecum for the experimental duration (14 d). Translocation to extraintestinal sites (MLN, spleen, and liver) also occurred. Burkholderia cepacia was recovered from the MLN for 10 d after treatment of mice. Pulmonary exposure to several bacterial strains resulted in unexpected mortality. Pseudomonas aureofaciens was lethal at the lowest dose (8.26 x 10(6) CFU/ mouse), while P. fluorescens and B. cepacia were fatal at higher doses (6.15 x 10(8) CFU/mouse and 1.34 x 10(8) CFU/mouse, respectively). By using the model described in this study, human safety issues can be more easily addressed and evaluated.

Administration, Intranasal↗
PubMed1998

Biology of taste buds and the clinical problem of taste loss.

Taste buds are the anatomical structures that mediate the sense of taste. They comprise taste cells and nerve fibers within specialized epithelial structures. Taste cells are traditionally described by histologic methods as basal, dark, intermediate, and light cells, with the nerve fibers surrounding and infiltrating the taste buds. By means of immunohistochemical methods, taste cells and gustatory nerve fibers can be classified in functional groups based on the expression of various cell adhesion molecules and other proteins. When taste buds become damaged, the loss of the ability to taste results. This loss is not uncommon and can impact health and quality of life. Patients who receive radiation therapy for head and neck cancer often experience taste loss, which leads to compromised nutritional intake and a worse outcome than patients who do not experience taste loss. The mode of radiation damage to taste cells and nerve fibers has been investigated using cell adhesion molecules, synaptic vesicle proteins, and other cell markers. The light and intermediate cells are preferentially affected by ionizing radiation, whereas the nerve fibers remain structurally intact. Experimental studies of radiation-induced taste loss are performed via a unique animal/human model.

Ageusia↗
PubMed1998

Rabbit Streptococcus pneumoniae keratitis model and topical therapy.

PURPOSE: To develop a model for experimental Streptococcus pneumoniae keratitis and to evaluate the chemotherapeutic efficacy of 12 common topical antibiotics in vivo. METHODS: Five-hundred (CFUs of log-phase S. pneumoniae were injected into the central corneal stroma of 36 eyes of 18 rabbits. After 0, 4, 8, 16, 24, and 48 hours, the in vivo growth was assayed as the CFU per cornea. Epithelial removal (to promote antibiotic entry and mimic human keratitis) was evaluated. Disc or tube dilution verification of the sensitivity or resistance of three S. pneumoniae strains was performed: a penicillin sensitive ("S"), an intermediate sensitive ("I"), and a resistant ("R") strain. Keratitis was established with S. pneumoniae "S" in 65 eyes, S. pneumoniae "I" in 107 eyes, and S. pneumoniae "R" in 78 eyes. Sixteen hours later, control corneas were harvested and the epithelium removed from treatment corneas. Every half hour saline, penicillin, gentamicin, bacitracin, ciprofloxacin, ofloxacin, erythromycin, vancomycin, ceftriaxone, cefotaxime, or chloramphenicol was applied for 5 hours. One hour later CFUs/cornea were assayed. RESULTS: After 24 hours, S. pneumoniae "S" and "I" had proliferated to 9.18+/-6.65 x 10(6) CFUs and 9.26+/-6.90 x 10(6) CFUs. Epithelial removal at 16 hours was not significant. The in vitro antibiotic sensitivity was as expected. However, in vivo, penicillin, gentamicin, or cefazolin sterilized S. pneumoniae "S." S. pneumoniae "R" responded best to fortified gentamicin with or without vancomycin; all others antibiotics were significantly less effective (P < 0.001). CONCLUSIONS: A small intracorneal S. pneumoniae inoculum in rabbit corneas grew and was maintained for 24 hours (with epithelial removal) to provide a model for testing antibiotic sensitivity in vivo. Topical penicillin is best for treating keratitis from penicillin-sensitive S. pneumoniae, whereas topical gentamicin or a combination of gentamicin and vancomycin was most effective against penicillin-resistant S. pneumoniae.

Administration, Topical↗
PubMed1996

Attributions and behavior in functional and dysfunctional marriages.

The study examined whether spouses' attributions for partner behavior are related to their own behavior by assessing their attributions and observing the problem-solving discussions of couples in which (a) neither spouse was depressed or maritally distressed, (b) the wife was depressed and both spouses were maritally distressed, and (c) the wife was not depressed and both spouses were maritally distressed. To the extent they made maladaptive attributions, wives displayed less positive behavior and more negative behavior. Husbands' attributions and behavior were unrelated, and associations between attributions and behavior were not moderated by marital distress and depression. These results highlight the need to clarify how partner behavior contributes to the attributions spouses make and to reexamine interventions designed to modify attributions in marital therapy.

Adult↗
PubMed1993

Immunolocalization of different forms of neural cell adhesion molecule (NCAM) in rat taste buds.

Taste buds consist of approximately 100 taste cells, including three morphological types of short receptor cells which synapse on the peripheral gustatory nerves. Some of the receptor cells produce neural cell adhesion molecule (NCAM), which may play a role in formation of specific connections in this system. Antibodies directed against different forms of NCAM were utilized in an attempt to define not only the distribution, but also the type of NCAM within taste buds. Within each taste bud approximately 10% of the taste cells exhibit abundant immunoreactivity for 180 kD (ld) or 140 kD (sd) forms of NCAM (i.e., those with an intracellular domain) along virtually the entire surface of the cell. Ultrastructural analysis reveals that these abundantly immunoreactive taste cells are of the intermediate morphological type, although not all of the intermediate taste cells within any bud are immunoreactive. In addition, the ultrastructural studies show that punctate (ld/sd) NCAM-immunoreactivity occurs on the membranes of taste cells and nerve fibers throughout each taste bud. The embryonic form of NCAM (E-NCAM), rich in polysialic acid residues, is present only in association with nerve fibers and other unidentified elongate, thin profiles of a few taste buds. The nerve plexus beneath the gustatory epithelium is also rich in NCAM-immunoreactivity. These fibers occasionally reveal immunoreactivity indicative of only the 120 kD (ssd) form of NCAM, typical of glial cells.

Animals↗
PubMed1993

The continuum of care revisited: a rural perspective.

This study examines resource data for a variety of services in North Carolina's continuum of care for older adults. It qualifies the widespread contention that older adults in urban areas receive a greater number and more varied services than their rural counterparts. It also demonstrates that one of the most important differences between these communities is the greater variability of services among rural compared to urban counties. The comparative findings on urban and rural variations in the continuum of care for older adults have implications for further research and future policy development.

Aged↗
PubMed1989

Cloning and expression of an adhesin antigen of Streptococcus sanguis G9B in Escherichia coli.

A genomic library of Streptococcus sanguis, strain G9B, was constructed and expressed in Escherichia coli using a lambda gt11 expression vector. The amplified library was probed with polyclonal anti-G9B IgG and 13 antigen-positive clones were isolated. A lysate of one clone, designated PP39, absorbed the adhesion-inhibitory activity of anti-G9B IgG. This clone contained an insert of approximately 2000 bp and expressed unique 200 and 53 kDa proteins that reacted with monospecific anti-adhesin antibody. The 200 kDa protein also reacted with anti-beta-galactosidase IgG, indicating that it is a fusion protein of which 84 kDa represents the streptococcal adhesin. The 84 and 53 kDa proteins are similar in size to the major polypeptides in a streptococcal antigen complex which is associated with the adhesion of G9B to saliva-coated hydroxyapatite. The 53 kDa fragment may result from post-translational cleavage of the recombinant polypeptide.

Antigens, Bacterial↗
PubMed1988

Characterization of an adhesion antigen of Streptococcus sanguis G9B.

An antigen possessing the attributes of an adhesion has been identified in Streptococcus sanguis G9B. Cell surface components were extracted from G9B and a spontaneously occurring nonadherent mutant of G9B, strain Adh-, with a 2 mM barbital buffer, pH 8.6. The extract of G9B but not of Adh- absorbed more than 80% of the adhesion-inhibitory activity of anti-G9B immunoglobulin G (IgG). Immunoblots revealed 80- and 52-kilodalton (kDa) antigens present in the G9B extract but not in the Adh- extract. Absorption of anti-G9B IgG with Adh- and G9B barbital extracts showed a correlation between the loss of the 80- and 52-kDa antibodies and the loss of adhesion-inhibitory activity. An antibody prepared against the 80-kDa antigen excised from sodium dodecyl sulfate-polyacrylamide gels recognized the 80- and 52-kDa antigens and another antigen of 62 kDa but did not inhibit adhesion. However, an antibody from an electroblot containing the native protein from which the 80-kDa and related antigens were derived (the 80-kDa antigen complex) inhibited adhesion to the same extent as anti-G9B IgG. Periodate oxidation of the G9B barbital extract modified the 80-kDa antigen complex and resulted in the loss of 40% of its absorbing activity. The barbital extract also contained an endogenous enzyme responsible for producing the 62- and 52-kDa antigens from the 80-kDa protein and which, under optimal conditions, degraded the antigen completely, resulting in the loss of antibody-absorbing activity. The 80-kDa antigen complex has a molecular mass of more than 200 kDa in native polyacrylamide gels and a pI of 4.1 to 4.8. These observations suggest that the adhesion antigen in S. sanguis G9B is a large glycoprotein from which an 80-kDa antigen complex is derived.

Absorption↗
PubMed1980

An integrated approach to developing administrators and organizations.

Can administrators increase their administrative capabilities in isolation from the rest of the institution? The authors of this article contend that administrative competency can be defined only in terms of contributions to organizational performance and that the motivation to achieve a high level of competency must be supported and reinforced at the institutional level. They establish a basis for the interdependency of administrators and institutions and outline an approach to their simultaneous development.

Administrative Personnel↗