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Biomedical subjects

R L Taylor

Publications and source records attributed to R L Taylor.

At least 37 records · Page 2Linked to original sources

Ropinirole for the treatment of early Parkinson's disease. The Ropinirole Study Group.

A prospective, randomized, placebo-controlled, double-blind, parallel-group, 6-month study assessed the efficacy and safety of ropinirole, a nonergoline D2-dopamine agonist, in patients with early Parkinson's disease (n = 241; Hoehn & Yahr stages I to III) with limited or no prior dopaminergic therapy. Patients (mean age, 62.8 years), stratified by concomitant use of selegiline, were randomized to ropinirole (n = 116) or placebo (n = 125). The starting dose of ropinirole was 0.25 mg tid with titration to at least 1.5 mg tid (maximum dose, 8 mg tid). Primary efficacy endpoint was the percentage improvement in Unified Parkinson's Disease Rating Scale (UPDRS) motor score. Ropinirole-treated patients had a significantly greater percentage improvement in UPDRS motor score than patients who received placebo (+24% vs -3%; p < 0.001). Ropinirole was well tolerated and patient withdrawals were infrequent. Most adverse experiences were related to peripheral dopaminergic activity. Ropinirole monotherapy is an effective and well-tolerated therapeutic option for treatment of early Parkinson's disease.

Aged↗

Increased parathyroid hormone-related peptide in patients with hypercalcemia associated with islet cell carcinoma.

OBJECTIVE: To report the high prevalence of increased parathyroid hormone-related peptide (PTHrP) in patients with islet cell carcinoma and associated hypercalcemia. DESIGN: We conducted a retrospective study of PTHrP levels in patients with hypercalcemia and eucalcemia associated with islet cell carcinoma and compared these findings with those in healthy subjects. MATERIAL AND METHODS: Using a sensitive PTHrP immunochemiluminometric assay, we measured PTHrP levels in 17 patients with islet cell carcinoma and 110 healthy subjects. The differences between PTHrP levels in patients with normal and those with high serum calcium concentrations were analyzed statistically. RESULTS: PTHrP levels were significantly higher (P < 0.01) in 10 patients with hypercalcemia and islet cell carcinoma (median, 14.0 pmol/L; range, undetectable to 40.1) than in 7 patients with eucalcemia and islet cell carcinoma (median, undetectable; range, undetectable to 1.3 pmol/L) or in the 110 healthy subjects (median, undetectable; range, undetectable to 4.2 pmol/L). The range of increased PTHrP levels in hypercalcemic islet cell carcinoma was 2 to 20 times the upper normal limit (2.0 pmol/L). Decreased PTHrP and serum calcium and increased parathyroid hormone levels were demonstrated in two patients after effective therapy. For all seven eucalcemic patients with islet cell carcinoma, PTHrP levels did not differ significantly from those in healthy subjects. CONCLUSION: PTHrP levels are increased in a substantial proportion of patients with hypercalcemia and islet cell carcinoma and seem to decrease after treatment of the underlying tumor. Measurement of PTHrP levels may be useful for confirming the diagnosis of hypercalcemia associated with malignant disease and for monitoring of therapy.

Adult↗

Governance of integrated delivery systems/networks: a stakeholder approach.

The health care environment is complex and turbulent, and traditional governance forms face many challenges. As integrated delivery systems/networks are formed, governance structures must be responsive to both internal and external stakeholders. Both internal efficiencies and socially responsible actions are required of these relatively new organizational forms. To meet these needs, a two-tier governance structure is presented that consists of overarching and facilitating boards.

Decision Making, Organizational↗

Sequence variation in the src gene product affects metastasis formation: the central, but not exclusive, role of the tumor immune response.

Sequence variation in the src gene product could, in principle, influence metastasis formation through either of 2 effects: an alteration in tumor antigenicity or a non-immune-mediated change in one or more src-associated functions. Our present results establish that both mechanisms underlie the difference in relative levels of metastasis formation induced by the v-src vs. the c-src(527) oncogene. A point that emerges from this analysis is the segregation, within a chicken line genotypically uniform at the major histocompatibility (B) complex (MHC), of a phenotype defined by strong resistance to secondary v-src-induced tumor challenge. The pattern of segregation is consonant with the possibility that a gene unlinked to the MHC governs immune response levels to v-src-encoded tumor antigen.

Animals↗

Assignment of Rfp-Y to the chicken major histocompatibility complex/NOR microchromosome and evidence for high-frequency recombination associated with the nucleolar organizer region.

Rfp-Y is a second region in the genome of the chicken containing major histocompatibility complex (MHC) class I and II genes. Haplotypes of Rfp-Y assort independently from haplotypes of the B system, a region known to function as a MHC and to be located on chromosome 16 (a microchromosome) with the single nucleolar organizer region (NOR) in the chicken genome. Linkage mapping with reference populations failed to reveal the location of Rfp-Y, leaving Rfp-Y unlinked in a map containing >400 markers. A possible location of Rfp-Y became apparent in studies of chickens trisomic for chromosome 16 when it was noted that the intensity of restriction fragments associated with Rfp-Y increased with increasing copy number of chromosome 16. Further evidence that Rfp-Y might be located on chromosome 16 was obtained when individuals trisomic for chromosome 16 were found to transmit three Rfp-Y haplotypes. Finally, mapping of cosmid cluster III of the molecular map of chicken MHC genes (containing a MHC class II gene and two rRNA genes) to Rfp-Y validated the assignment of Rfp-Y to the MHC/NOR microchromosome. A genetic map can now be drawn for a portion of chicken chromosome 16 with Rfp-Y, encompassing two MHC class I and three MHC class II genes, separated from the B system by a region containing the NOR and exhibiting highly frequent recombination.

Animals↗

Endogenous c-src as a determinant of the tumorigenicity of src oncogenes.

We have compared the tumorigenicity of two src oncogenes, v-src and c-src(527), whose respective protein products pp60v-src and pp60c-src(527) show a different spectrum of amino acid substitutions vis-à-vis the c-src protooncogene-encoded product pp60c-src. Whereas the extent of primary tumor growth induced by c-src(527) was quite similar in the two chicken lines tested, the extent of v-src-induced tumor growth showed a marked line dependence. As examined with a line of chickens that shows immune-mediated regression of v-src-induced tumors, a weaker tumor immunity, as correlated with a greater level of primary tumor growth, resulted from inoculation of c-src(527) DNA than of v-src DNA. These observations indicated that the v-src-specific amino acid substitutions define a major tumor antigenicity. That a separate src-associated antigenicity is also targetable by the tumor immune response followed from the finding that the level of protective immunity against the growth of c-src(527) DNA-induced tumors was augmented under conditions of the prior regression of v-src DNA-induced tumors. As this latter antigenicity may include one or more c-src(527)-encoded peptides that are equivalent to c-src-encoded self peptides, these observations suggest that a host tolerance to pp60c-src can be broken so as to permit a tumor immune response based on recognition of self peptides of pp60c-src(527).

Animals↗

Eliminating inappropriate classroom behavior using a DRO schedule: a preliminary study.

The purpose of this study was to eliminate out-of-seat behavior of a 14-yr.-old boy with learning disabilities using a single-subject design. Based on functional analysis, a Differential Reinforcement of Other Behavior interval schedule was used to eliminate an inappropriate behavior. During baseline, an average of 15 out-of-seat behavior problems were recorded. After 4 wk. of intervention, the inappropriate out-of-seat behavior was eliminated and on-task behavior improved.

Adolescent↗

Differential antibody responses in 6.B major histocompatibility (B) complex congenic chickens.

Lines 6.6-2 (B2B2) and 6.15-5 (B2B2), congenic for the major histocompatibility (B) complex with > 99.9% background gene uniformity, were used to examine primary antibody responses to two antigens. In each of two trials, 1 mL of 5% SRBC, a T cell-dependent antigen, or 0.1 mL of Brucella abortus (BA), a T cell-independent antigen, was injected into separate groups of each B genotype aged 3 and 6 wk. Blood samples were taken from the chickens 7 d after immunization. Serum titers (log2) for both total antibody and mercaptoethanol (ME)-sensitive antibody to detect IgG were assayed by microtiter procedures. Least squares analysis of variance and Fisher's protected Least Significant Difference at P < 0.05 were used to evaluate the data. The total anti-SRBC antibody titer was significantly higher in B5B5 chicks than in B2B2 chicks at 4 and 7 wk of age. There was no significant difference in ME sensitive antibody to SRBC. Chicks of the B5B5 genotype also had significantly higher total and IgG antibody titers to BA at both ages than B2B2 chicks. The results indicate that 4- and 7-wk-old B5B5 chicks had a significantly stronger antibody response to SRBC or BA than B2B2 chicks.

Aging↗

Antibody response to sheep red blood cells in major histocompatibility (B) complex aneuploid line of chickens.

An integral part of the immune response is the production of antibodies specific for different antigenic challenges. Genes of the MHC encode products that regulate immunity. This study utilized the FCT-15 line of chickens, which is aneuploid for the chromosome containing the ribosomal RNA genes (rDNA) and the MHC or B complex to determine whether an antibody response to SRBC would vary as a function of B complex gene dose. Mating of trisomic parents (B15B15B15) animals produced progeny having either a disomic (B15B15), trisomic (B15B15B15), or tetrasomic (B15B15B15B15) B complex dosage. The number of B/rDNA chromosomes, and thus the B complex dosage was determined by feather pulp nucleolar typing of chicks at hatch. A 5% SRBC antigenic challenge, which induces a T cell-dependent antibody response, was injected at 6 wk of age. Samples taken prior to SRBC injection as well as 5, 8, and 12 d postinjection were assayed for total and mercaptoethanol-resistant antibody. Peak antibody titers (log2), day of peak titer and rate of titer decline were calculated using a quadratic equation for each bird. Differences among the three B complex dosages were evaluated by analysis of variance. Antibody titers rose from 5 to 8 d postinjection and declined thereafter without significant differences among the three B complex doses. Calculations from the quadratic equations showed that B complex dose affected neither peak antibody titer nor day of peak titer. However, trisomic and tetrasomic animals had significantly more rapid rates of decline from the maximum titer. In aneuploid chickens, changes in antigen processing, antigen presentation, or persistence of processed antigen may maintain levels of antibody production found in disomic chickens and explain the more rapid decline of titer.

Aneuploidy↗

Avian hematopoiesis in response to avian cytokines.

The objective of this study was to examine the hematopoietic cell proliferation and differentiation potential of growth factors produced by chicken macrophages. Bone marrow (BM) cells (25 x 10(3)) from newly hatched B15B15 K-strain Leghorn chicks were seeded in .5 mL serum-free semi-solid culture supplemented with 10% (vol/vol) of a conditioned medium (CM) from a chicken macrophage cell line, MQ-NCSU. The conditioned medium was obtained by culturing MQ-NCSU cells either in LM-HAHN (CMI) or RPMI-1640 (CMII) growth medium. The control cultures contained only LM-HAHN or RPMI medium. Bone marrow cells in the presence of CMI differentiated predominately into granulocyte colonies (Experiment 1 = 84 +/- 9.2; Experiment 2 = 105 +/- 5). No colonies were observed in the control cultures. Stimulation of MQ-NCSU cells with lipopolysaccharide (LPS) produced a CM that differentiated BM cells predominantly into macrophage colonies (122 +/- 16.3 in CMI and 92 +/- 5.6 in CMII). These data suggest that MQ-NCSU cells spontaneously secrete a factor with the potential to promote granulocyte differentiation. However, upon stimulation with LPS, the factor secreted had macrophage colony stimulation potential (M-CSF), which was similar in activity when compared with the activity of recombinant chicken myelomonocytic growth factor (r-cMGF). Another CM from chicken fibroblasts (FCM) was tested on BM cells from K-strain Leghorns and Arbor Acres x Arbor Acres broiler chicks. Data from three experiments showed that 25 x 10(3) BM cells from K-strain chicken yielded more macrophage and granulocytes colonies (82 +/- 14) than those from broilers (56 +/- 12). This study suggests that avian cytokines exhibit progenitor cell differentiation potential and that this activity is dependent upon the source of cytokines and their targets.

Animals↗

Major histocompatibility (B) complex control of the formation of v-src-induced metastases.

Previous observations have shown that the major histocompatibility (B) complex is a determinant of the growth of v-src-induced primary tumors. In the present study, we have observed with two chicken lines congenic for B complex alleles that the control of v-src-mediated oncogenesis by the B complex extends to metastasis formation. In addition, our results show that the differences in metastasis frequencies between these two lines are correlated with the relative strengths of their respective tumor immune responses.

Animals↗

Intraoperative monitoring of parathyroid procedures by a 15-minute parathyroid hormone immunochemiluminometric assay.

OBJECTIVE: To report the recent development and validation of a sensitive 15-minute immunochemiluminometric assay (ICMA) of parathyroid hormone (PTH). DESIGN: The characteristics and applications of a new "rapid" PTH ICMA are described, and the advantages in comparison with other assays are discussed. MATERIAL AND METHODS: The 15-minute PTH ICMA was achieved by using a higher incubation temperature (45 degrees C rather than room temperature) and a concentration of tracer antibodies that was 5 times that in the regular 18-hour assay. The sensitivity, recovery, and linearity of dilution of the rapid ICMA were assessed, as was its ability to reflect intraoperative changes in PTH concentration after parathyroidectomy in patients with hyperparathyroidism. RESULTS: The sensitivity of the ICMA was 0.3 pmol/L in comparison with 0.08 pmol/L for the regular 18-hour assay (normal range, 1.0 to 5.0). The recovery of added PTH was 84% by using ethylene-diaminetetraacetic acid-plasma as the specimen. Moreover, the linearity of specimens after dilution was good. The assay demonstrated a rapid response to parathyroid gland removal. In most patients, PTH levels declined precipitously (to less than 30% of basal values) within 5 minutes after parathyroid resection. PTH levels remained low to undetectable at 10 and 20 minutes after excision. CONCLUSION: This rapid PTH ICMA may be of assistance to endocrine surgeons in the monitoring of PTH function after both parathyroid and thyroid surgical procedures.

Humans↗

Correlates of interventions with self-injurious behaviour.

A review was conducted of published intervention research on the self-injurious behaviour (SIB) of individuals with severe or profound mental retardation. The review comprised articles published between 1980 and 1990. Thirty-eight biodemographic and environmental variables were investigated, with type of SIB and intervention type considered primary variable classes. Efficacy was also investigated as an additional variable. Cross-tabulations were performed on selected variables with 24 significant and five marginally significant results obtained. These results indicated that there were possible biases in treatment approaches, problems in compliance with standards of practice, and differential efficacy levels related to certain variable types. Findings were discussed in relation to establishing a prototype for successful SIB interventions.

Behavior Therapy↗

Proinsulin by immunochemiluminometric assay for the diagnosis of insulinoma.

We used a newly developed immunochemiluminometric assay of proinsulin to determine its relative utility vis-à-vis C-peptide and insulin for the diagnosis of insulinoma. The evaluation was conducted in 20 consecutive patients with histologically confirmed insulinoma and 22 normal subjects who underwent a prolonged fast according to a standard protocol. Patients with insulinoma fasted to the point of demonstrating Whipple's triad; normal subjects fasted to 72 h. At the end of the prolonged fast, when the glucose value was 2.8 mmol/L or less (50 mg/dL), all three hormones had equal sensitivity (100%) in detecting insulinoma with no overlap with the values of normal subjects. When glucose levels were between 2.8 mmol/L (50 mg/dL) and 3.3 mmol/L (60 mg/dL) at the end of the prolonged fast, proinsulin was better than C-peptide and insulin in the diagnosis of insulinoma. The sensitivity was 90% for proinsulin and 85% for both C-peptide and insulin. Therefore, proinsulin not only is useful for the diagnosis of insulinoma, but it may have greater diagnostic accuracy than C-peptide and insulin.

Animals↗

Resistance to Marek's disease in chickens with recombinant haplotypes to the major histocompatibility (B) complex.

Genetic resistance to Marek's disease (MD) is associated with the B-F region of the MHC. The resistance of chickens possessing either of two MHC haplotypes to challenge with different strains of MDV was examined. Chickens with serologically similar MHC recombinants BR2 and BR4 (both BF2-G23) were backcrossed for four generations to the highly inbred UCD-003 line (B17B17). Heterozygotes (B17BF2-G23) were mated to produce BR2BR2 and BR4BR4 homozygotes with 93% background gene uniformity. Both genotypes were highly resistant to GA-5 MDV, having an incidence of 0 and 8% MD for BR2BR2 and BR4BR4, respectively, whereas the incidence of MD in the UCD-003 birds was above 80%. Challenge with the very virulent RB-1B strain caused 10% and 31% MD in the BR2BR2 and BR4BR4 chickens, respectively, compared with 100% and 52% in the B17B17 (UCD-003) and B23B23 (New Hampshire 105) lines, respectively. Viremia levels at 5 and 6 d postinfection were significantly lower in BR2BR2 and B23B23 than in B17B17 genotypes.

Animals↗

Response of six major histocompatibility (B) complex recombinant haplotypes to Rous sarcomas.

Six B complex recombinants, BR1 (F24-G23), BR2 (F2-G23), BR3 (F2-G23), BR4 (F2-G23), BR5 (F21-G19), and BR6 (F21-G23), from the fourth backcross generation to highly inbred line UCD 003 (B17B17) were studied for their response to Rous sarcomas. Eight hatches were produced from heterozygous (BRnB17) parents. Chicks were wingweb inoculated with 50 pock-forming units of Rous sarcoma virus (RSV) at 6 wk of age. A tumor profile index (TPI), based on degree of tumor regression, was evaluated by analysis of variance. BR2, BR3, and BR4 are serologically similar F2-G23 recombinants. Haplotype B2, the origin of BF2, is a known tumor regressor, yet BR2BR2 chickens had a significantly lower TPI than BR3BR3 and BR4BR4 chickens. The TPI of BR2BR2 (F2-G23) chickens was also significantly lower than the TPI of chickens homozygous for BR1 (F24-G23) and BR5 (F21-G19). The BR6BR6 (F21-G23) chickens had significantly lower TPI than all homozygotes except BR2BR2 (F2-G23). Among heterozygous genotypes, BR2B17, BR5B17, and BR6B17 differed significantly from BR1B17, BR3B17, and BR4B17. These results suggest that serologically similar recombinants that contain (F2-G23) possess different genes affecting tumor regression. In addition, degrees of tumor regression in BR5 (F21-G19) and BR6 (F21-G23), both of which contain BF21, may be due to genetic differences within the B-F/B-L or B-G regions.

Animals↗

Catecholamines modulate chicken immunoglobulin M and immunoglobulin G plaque-forming cells.

Norepinephrine (NE) and epinephrine (E) function as chemical messengers in the central nervous and the endocrine systems of the chicken. The effects of in vivo and in vitro exposure of NE and E on IgM and IgG splenic plaque-forming cell (pfc) formation were determined to the antigen SRBC. Six-week-old Line UNH 105 New Hampshire chickens were injected i.v. with NE (500 micrograms/kg BW) or E (100 micrograms/kg BW) followed by 1 mL of 5% SRBC 30 min later. Five days after antigen injection, IgM and IgG pfc were assayed. Compared with controls, in vivo NE suppressed (P < .05) IgM and IgG pfc formation. In vitro NE treatment of splenic lymphocytes reduced (P < .05) IgM pfc but did not affect IgG pfc numbers. In vivo treatment with E increased (P < .05) IgM pfc whereas in vitro E exposure increased (P < .05) IgM pfc. Immunoglobulin G pfc were suppressed (P < .05) by both in vivo and in vitro E exposure. The presence of surface receptors for NE and E on splenic lymphocytes was determined using in vitro incubation with antagonists to alpha and beta receptors. These data suggest that there are alpha and beta receptor sites on lymphocytes for NE and E, and that these catecholamines have a regulatory role in plaque cell proliferation.

Animals↗