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Biomedical subjects

R J Anderson

Publications and source records attributed to R J Anderson.

At least 127 records · Page 7Linked to original sources

Adenine nucleotide and protein kinase C regulation of renal tubular epithelial cell wound healing.

The present studies were done to determine the effect of selected adenine nucleotides on healing of wounds made by mechanically denuding areas in confluent monolayers of renal tubular epithelial cells. We found that hydrolyzable and nonhydrolyzable forms of ATP but not UTP stimulated healing of LLC-PK1 cell wounds, while both ATP and UTP promoted healing of MDCK cell wounds, suggesting that different subtypes of purinoceptors regulated wound healing in these cells. Stimulation of wound healing by ATP was equivalent in control cells and in cells in which irradiation suppressed proliferation, suggesting a prominent role for cell migration in the healing process. Since ATP receptors are often linked to activation of protein kinase C, the effect of a protein kinase C activator (4 beta-phorbol 12-myristate 13-acetate, PMA) on wound healing was studied. Long-term (24 hr) exposure to PMA inhibited while short-term (30-120 min) exposure to PMA enhanced cell wound healing. Two chemically and mechanistically dissimilar protein kinase C inhibitors (calphostin C and chelerythrine) inhibited LLC-PK1 and MDCK cell wound healing, and calphostin C prevented ATP enhancement of LLC-PK1 healing. These observations suggest a role for protein kinase C in regulation of basal and adenine nucleotide-stimulated wound healing. Adenosine triphosphate did not affect cell-cell adhesion of either LLC-PK1 or MDCK cells. Adenine nucleotides and PMA enhanced and calphostin C inhibited short-term adhesion of LLC-PK1 and MDCK cells to plastic and to other substrates such as fibronectin, laminin and collagen type IV.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗

Human liver triiodothyronine sulfotransferase: copurification with phenol sulfotransferases.

To ascertain whether triiodothyronine (T3) sulfotransferase coeluted with the known phenol sulfotransferases (PSTs) during purification, human liver thermostable PST, thermolabile PST, and T3 sulfotransferase were assayed with p-nitrophenol, dopamine, and T3, respectively. Thermostable PST eluted from an ion-exchange column in two sequential peaks of activity (Peaks I and II), followed by a peak of thermolabile PST activity. There were three peaks of T3 sulfotransferase with thermostable PST: two within thermostable PST Peak I, and one peak of T3 sulfotransferase activity within thermostable PST Peak II. There was a minor peak of T3 sulfotransferase with thermolabile PST. Further purification of thermostable Peak I showed coelution of T3 sulfotransferase with thermostable PST during gel filtration and affinity chromatography. SDS-PAGE revealed a major protein band at 31 kDa. Dehydroepiandrosterone sulfotransferase comprised only 4% of the final activity. This report demonstrates coelution of T3 sulfotransferase with thermostable PST, shows a potential additional isozyme of T3 sulfotransferase, and points out the apparent minimal role of dehydroepiandrosterone sulfotransferase in T3 sulfation. The findings support the hypothesis that thermostable PST is the predominant human liver T3 sulfotransferase activity.

Adolescent↗

Financial analysis of alternative treatments for clinical mastitis associated with environmental pathogens.

For two large California dairy herds with twice daily milking, 171 infected quarters of lactating cows with mild clinical mastitis were randomly assigned to one of three treatment groups. Group A (50 cows) was treated with 62.5 mg of intramammary amoxicillin every 12 h for three milkings. Group C (50 cows) was treated with 200 mg of intramammary cephapirin every 12 h for two milkings. Group O (71 cows) was treated with 100 U of intramuscular oxytocin every 12 h for three milkings. Clinical cure rates did not differ among treatment groups. The cost per episode of clinical mastitis was higher ($54.47) for group C than for groups A ($38.53) or O ($34.88). Group O had a higher incidence of relapse (41%), and a greater percentage of group O cows (65%) experienced an additional mastitic event in the enrolled lactation than did cows in groups A and C. Treatment had no effect on the mean number of nonsalable milkings (24.7) associated with mastitis in the lactation interval subsequent to enrollment on the trial. Twenty-two percent of the cows accrued more than 30 nonsalable milkings and produced 55% of the total nonsalable milkings associated with mastitis. There was no treatment effect on total milk production, fat production, or time to removal of the enrolled cows from the herd.

Amoxicillin↗

Human skin and platelet minoxidil sulfotransferase activities: biochemical properties, correlations and contribution of thermolabile phenol sulfotransferase.

Human scalp skin high speed supernatants were used to test whether minoxidil sulfotransferase (MNX-ST) and phenol sulfotransferase (PST) activities were present. Platelet homogenates from the same skin donors were used to test whether levels of sulfotransferase activities in the blood platelet would reflect levels of the enzyme activities in skin. Dopamine, p-nitrophenol and minoxidil were used as substrates for skin and platelet thermolabile (TL PST), thermostable (TS PST) and MNX-ST activities, respectively. Biochemical properties of each skin enzyme were the same as the platelet enzymes with respect to apparent Km values for substrates, pH optima, thermal stabilities and responses to inhibition by 2,6-dichloro-4-nitrophenol (DCNP). An unexpected finding was that skin and platelet MNX-ST thermal stabilities and responses to DCNP were more similar to TL PST than to TS PST, the enzyme reported to be responsible for MNX-ST activity. There were significant positive correlations of platelet sulfotransferases with the relative levels of activities of the same skin sulfotransferases. Unexpected findings were significant positive correlations of MNX-ST and TL PST activities. Partially purified platelet TS PST assayed with minoxidil as the substrate showed a response to DCNP and thermal stability that were the same as TS PST. Platelet TL PST assayed with minoxidil showed thermal stability and a response to DCNP that were essentially the same as TL PST. The results indicated that not only TS PST, but also TL PST activities in human skin and platelet contributed to MNX-ST activity. It will be feasible to test whether measures of platelet PST activities will predict physiologic responses to minoxidil.

Arylsulfotransferase↗

Racial differences in the prevalence of atrophic-appearing macular lesions between black and white patients with retinitis pigmentosa.

We compared the prevalence of atrophic-appearing macular lesions between black and white patients with isolated or various genetic types of retinitis pigmentosa to determine if an appreciable difference existed between these two groups. The study included 720 patients of whom 138 (19.2%) were black patients from 115 families and 582 (80.8%) were white patients from 478 families. A logistic regression analysis combining isolated and all genetic types but randomly selecting one patient per family showed a statistically significant difference in the prevalence of atrophic-appearing macular lesions between black and white patients for the right eye (P = .0012) and left eye (P = .002). When considering either all patients or one patient per family, the estimated odds ratios were approximately 2.0 for blacks relative to whites. Our findings indicate that black patients with retinitis pigmentosa are approximately twice as likely as white patients to develop an atrophic-appearing macular lesion. This observation has implications for the prognosis of central visual function in such patients.

Adolescent↗

Pharmacokinetics services in Department of Veterans Affairs medical centers.

The provision of pharmacokinetics services in Veterans Affairs (VA) medical centers was studied. In October 1992 a questionnaire was mailed to the chief of pharmacy at each of the nation's 160 VA medical centers. The survey was designed to determine the percentage of centers providing pharmacokinetics services, the general characteristics of pharmacokinetics services provided, and whether the presence of these services was associated with specific characteristics of the medical centers. Of the 160 questionnaires mailed, 148 (93%) were returned and analyzed. Pharmacokinetics services were provided by 104 (70%) of the respondents. Of the 104 services, 58 (56%) had existed for less than five years. Of the 44 VA medical centers without a pharmacokinetics service, almost two thirds planned to start one in the future. Aminoglycosides, vancomycin, and theophylline were the drugs most frequently monitored. Fifty-four percent of the pharmacokinetics services evaluated 1-24 patients per month, and another 24% evaluated 25-49 patients monthly. VA medical centers with a pharmacy residency program were more likely to have a pharmacokinetics service than centers without such a program; an association with geographic region was also identified. Nearly three fourths of responding VA medical centers indicated that they provided pharmacokinetics services.

Drug Monitoring↗

Effect of methazolamide on chronic macular edema in patients with retinitis pigmentosa.

PURPOSE: To determine the effectiveness of methazolamide for improving visual acuity and macular edema in patients with retinitis pigmentosa. METHODS: Seventeen subjects with retinitis pigmentosa and chronic macular edema participated in a prospective, placebo-controlled, double-masked, crossover design study in which either methazolamide or a placebo was taken for 3 weeks. Visual acuity, fluorescein angiograms, and subjective impressions were obtained at baseline and after 3 weeks of treatment with each substance. A subgroup of subjects were enrolled in a more extended period of methazolamide treatment for an additional 3 months. RESULTS: Methazolamide resulted in the improvement of angiographic macular edema in 9 of 17 subjects. As a group, visual acuity statistically improved with methazolamide. However, improvement in at least one eye, of between two and four lines more than while taking placebo, occurred in only three (undilated pupils) or four (dilated pupils) subjects. Subjective improvement during treatment with methazolamide but not placebo occurred in only one subject. An extended period of methazolamide treatment for an additional 3 months in a subgroup of patients did not result in additional beneficial effects on visual acuity. In fact, a partial rebound in the extent of macular edema was found. CONCLUSIONS: Although angiographic improvement of macular edema can occur in patients with retinitis pigmentosa treated with methazolamide, notable (between 3 and 4 lines) or even moderate (between 2 and 3 lines) visual acuity improvement was seen in relatively few patients. When methazolamide was administered in a placebo-controlled fashion, subjective improvement in visual function also was not readily apparent. A more substantial subjective improvement in visual function had occurred with the use of acetazolamide in five of six subjects who also had participated in a previous treatment trial with the use of acetazolamide.

Adolescent↗

Escape from the antiproliferative effect of transforming growth factor-beta 1 in LLC-PK1 renal epithelial cells.

Transforming growth factor-beta 1 (TGF-beta 1) usually inhibits proliferation of epithelial cells. We find that LLC-PK1 renal tubular epithelial cells develop rapid in vitro resistance to the inhibitory effects of TGF-beta 1 and subsequently proliferate in response to TGF-beta 1. This unique response to TGF-beta 1 is not observed in another renal tubular epithelial cell line (MDCK cells). The proliferative response to TGF-beta 1 is additive to that produced by other growth factors. The proliferative response to TGF-beta 1 occurs despite an effect of TGF-beta 1 to suppress epidermal growth factor stimulated c-myc mRNA as determined by Northern analyses. These results suggest that LLC-PK1 cells develop rapid resistance to TGF-beta 1 inhibition of proliferation in vitro and that this resistance occurs despite continued suppression of c-myc mRNA.

Animals↗

Mechanisms of recovery from mechanical injury of renal tubular epithelial cells.

The mechanism(s) whereby a denuded renal tubular epithelial cell surface becomes reestablished remains unknown. We therefore measured the rate of renewal of mechanical wounds made in confluent monolayers of two established renal tubular epithelial cell lines. We found that wounds of MDCK cells heal at a faster rate than wounds of LLC-PK1 cells. The magnitude of wound healing did not differ when cells grown on plastic were compared with cells grown on fibronectin, laminin, or collagen. Irradiation (4,000 rads) of MDCK and LLC-PK1 cells significantly reduced indexes of proliferation (5-bromo-2'-deoxyuridine and thymidine uptake) without affecting wound healing. Serum and epidermal growth factor (EGF) enhance whereas transforming growth factor-beta 1 (TGF-beta 1) impairs wound healing. Hepatocyte growth factor (HGF) stimulates wound healing at low concentrations and inhibits healing at high concentrations in MDCK cells while not affecting healing of LLC-PK1 cell wounds at any concentration. Several interleukins (IL-1, IL-2, IL-3, and IL-6) did not affect wound healing in either cell type. Healing of LLC-PK1 but not MDCK cells was impaired by exposure to a peptide containing a RGD sequence. Conversely, healing of MDCK but not LLC-PK1 cells was impaired by the REDV tetrapeptide. Healing of both LLC-PK1 and MDCK was impaired by heparin but not by the LDVPS peptide. These results demonstrate that mechanical wounds of LLC-PK1 and MDCK cells heal, at least in part, by migration. Healing is regulated by serum and growth factors including EGF, HGF, and TGF-beta 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Molecular fingerprinting of Pasteurella multocida associated with progressive atrophic rhinitis in swine herds.

Ninety-six nasal isolates of Pasteurella multocida from swine herds with progressive atrophic rhinitis were characterized by restriction endonuclease analysis (REA) of whole-cell DNA, ribotyping, and plasmid analysis. For REA, bacterial DNA was digested with SmaI and electrophoresed in 0.7% agarose, and fragments were visualized with UV light. For ribotyping, EcoRI-digested and electrophoresed restriction fragments of whole-cell DNA were transferred to nitrocellulose membranes, hybridized with gamma-32P-labeled Escherichia coli ribosomal RNA, and visualized by autoradiography. Phenotypes of isolates were toxigenic capsular type D (n = 51), nontoxigenic type D (n = 28), nontoxigenic type A (n = 16), and toxigenic type A (n = 1). Plasmids of various sizes were evident in 92.2% and 17.9% of toxigenic and nontoxigenic D strains, respectively, but were absent from all type A strains. Among the 4 phenotypes, there were 17 REA profiles and 6 ribotypes. For 3 of 17 REA patterns, multiple ribotypes were evident, and several REA types were evident in 5 of 6 ribotypes. Thirty-seven isolates of toxigenic capsular type D from Australian herds were either SmaI type B or C and ribotype 2, whereas 14 toxigenic D isolates from the USA and other countries were more heterogeneous (7 REA types and 6 ribotypes). The fingerprinting results provided evidence in support of the hypothesis of a single source infection in Australia associated with the introduction of breeding pigs from overseas.

Animals↗

Lymphocyte profiles in patients with chronic low back pain enrolled in a clinical trial.

OBJECTIVE: Our earlier findings suggest that patients with musculoskeletal complaints have lower numbers and percentages of natural killer (NK) cells than asymptomatic subjects. This study examines patient lymphocyte profiles, as a secondary outcome measure, in a trial of manipulative therapies to treat chronic low back pain (LBP) of mechanical origin. DESIGN: The patients were compared in a randomized controlled trial. Baseline measures were collected at the initial visit; all patients were scheduled for 11 treatments in 14 days. Treatment consisted of either a high-force, high-velocity, low-amplitude manipulation procedure; a low-force, high-velocity, low-amplitude procedure or a series of educational lectures on lower back pain. Posttreatment measures were collected at the final treatment session; follow-up measures were obtained 2 wk later. SETTING: The study was conducted at a chiropractic teaching clinic in the suburban Chicago area. PARTICIPANTS: Individuals over 18 were eligible if they were new patients or repeat patients with a 6 month's hiatus, if the chief complaint was LBP of greater than 50 days' duration, if pain was elicited with palpation over one or more of the facet joints from the spinal levels between L1 and S1 and including the sacroiliac joints, and if there was absence of pain referral or if pain referral was only scleratogenous in nature. Criteria for excluding patients included hard neurologic signs, systemic disease potentially affecting the musculoskeletal system, contraindication to spinal manipulation such as osteoporosis, fracture or other bony pathology, or treatment with medication intended to relieve symptoms associated with their LBP. Eligibility was determined by a staff diagnostic team independent of the attending physician. Three hundred sixty-seven of 1,275 consecutive new patients met the eligibility criteria. Of these, 209 participated. These results are for 201 patients from whom flow cytometric data were obtained. OUTCOME MEASURES: Both absolute numbers and percentages of B-lymphocytes, T-lymphocytes, T-Helper (TH), T-Suppressor (TS) and NK lymphocytes were determined. Blood samples were collected at the same time that the primary outcome measures were obtained. Cells were stained with two-color monoclonal antibodies directed against specific cell surface antigens, and each lymphocyte subpopulation was quantified directly from lysed whole blood with a Coulter Epics Profile II flow cytometer. RESULTS: Thirty-five patients dropped out before the follow-up visit and technical problems resulted in the loss of data from 17 more and the exclusion of some subpopulation data. In all, 148 cases were analyzed for B cells, 146 for TH, TS and NK cells and 138 for cells that carried both the NK and TS marker. A one-way analysis of variance revealed no significant differences in the lymphocyte profiles at baseline among the three groups. All subpopulation baseline values were within reported reference ranges for normal adult populations. However, the percentage of NK cells (9.1%) was below the published minimum critical value. A repeated measures analysis of variance was used to determine whether treatment effects changed over time, that is, treatment-time interaction. The cell types for which the interaction tests were at or near statistical significance were: TH cells (p = .0208), total T cell percent (p = .0928) and absolute total T cells (p = .0908). Interaction tests for differences in either percent or absolute counts of B cells, TS cells, or NK cells were not statistically significant. CONCLUSIONS: This is the first report of lymphocyte profiles in patients with diagnosed chronic LBP. Our finding of a lower percentage of NK cells in these patients confirms our earlier finding that patients with musculoskeletal problems have a lower percentage of NK cells than do asymptomatic subjects. However, manipulative therapy was not shown to have a clinically significant effect on either the absolute n

Adult↗