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Biomedical subjects

R L Taylor

Publications and source records attributed to R L Taylor.

At least 19 recordsLinked to original sources

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

Continuous administration of dopamine alters cellular immunity in chickens.

Dopamine administered continuously through osmotic pumps altered the PHA wattle response and in vitro leukocyte capillary tube migration in UNH 105 chickens. The PHA wattle response was suppressed significantly by 48 hr exposure to dopamine at a dose of 1 microgram/hr. Administration of 10 micrograms/hr dopamine for 48 hr enhanced significantly in vitro leukocyte migration.

Animals

Analysis of macrophage functions in Rous sarcoma-induced tumor regressor and progressor 6.B congenic chickens.

Macrophage functional competence was studied in two congenic chicken lines 6.6-2 (B2B2) and 6.15-5 (B5B5) which are regressors and progressors, respectively, of Rous sarcoma-induced tumors. Sephadex-elicited abdominal exudate cells (AEC) were harvested from 4-week-old chickens to determine their total number, glass adherence potential, percentage of adherent macrophages and phagocytosis of antibody coated (ops) and uncoated (unops) sheep red blood cells (SRBC). Tumoricidal abilities of culture medium conditioned with lipopolysaccharide treated macrophages and of macrophages cocultured with target cells were assessed against 51Cr-labelled tumor cell targets. The congenic lines did not differ in total AEC or percent macrophages. However, AEC from B5B5 birds exhibited significantly lower (P < 0.05) glass-adherence potential than AEC from B2B2 birds exhibited significantly lower (P < 0.05) glass-adherence potential than AEC from B2B2 birds. The percentage of phagocytic macrophages did not differ between lines for unop-SRBC, whereas a higher percentage of B5B5 compared with B2B2 birds (P < 0.05) macrophages phagocytized ops-SRBC. Macrophages from B5B5 birds had significantly (P < 0.05) lower activity in both tumoricidal tests. These results imply that the tumor progression in B5B5 birds is associated with reduced activation of macrophages towards a tumoricidal pathway.

Animals

Comparative development of Eimeria tenella in primary chick kidney cell cultures derived from coccidia-resistant and -susceptible chickens.

A sixfold difference in resistance to coccidia (Eimeria tenella) infection between a resistant and a susceptible line of Auburn White Leghorn chickens, derived by selective breeding, has been reported. The purpose of the following study was to determine whether the resistance or susceptibility phenomenon in the Auburn lines could be manifested in a homogeneous group of isolated host kidney cells that support E. tenella development in vitro but not normally in vivo. Propagation of the parasite in host cells in vitro eliminates humoral and cellular elements of immunity, and allows the study of host genetic influences at the cellular level. Differences in parasite development were examined between the two lines of cells in vitro after 48 and 96 h of incubation; time periods that reflect initial infection of the host cells by the parasite and the subsequent asexual development. Quantification of differences by liquid scintillation counting was based on parasite-specific incorporation of pyrimidines, specifically [3H]-uracil. The results supported previous findings that overall E. tenella development was significantly greater in the host cells from the susceptible line than in the cells from the resistant cultures at both time periods.

Animals

Biogenic amines regulate avian immunity.

Alzet mini-osmotic pumps were implanted subcutaneously to administer norepinephrine (NE) and epinephrine (E) to 6-wk-old line UNH 105 chickens. Dose-time studies showed the most effective NE and E dose and exposure time on two chicken cellular immune responses: the phytohemagglutinin (PHA) wattle response and leukocyte migration. Administration of 1 microgram/h NE for 72 h suppressed significantly the wattle stimulation index [2.48 +/- .3 (SE)] compared to that of saline controls (4.1 +/- .3) but enhanced mean leukocyte migration (7.7 +/- .3 versus 4.9 +/- .3). Epinephrine at 1 microgram/h for 72 h significantly suppressed the wattle index (1.8 +/- .2) compared to that of controls (2.8 +/- .3) but E at 1 microgram/h for 48 h enhanced leukocyte migration (9.5 +/- .2 versus 6.4 +/- .2). Continuous administration of NE and E at physiological levels alters cell-mediated immunity and appears to have an immune regulatory role in the chicken.

Animals

Major histocompatibility (B) complex control of the growth pattern of v-src DNA-induced primary tumors.

Observations that the major histocompatibility (B) complex is a determinant of the growth pattern of Rous sarcoma virus (RSV)-induced tumors raised the question as to whether control is exerted at the level of a v-src-determined, i.e., transformation-specific, function. To investigate this point, the tumor size scores and tumor profile indices of v-src-induced tumors were compared in two lines of chickens congenic for B complex genotypes. The finding that the growth patterns of tumors, induced by v-src DNA inoculation at 6 weeks posthatch, differ in these two lines establishes that the B complex exerts control over tumor growth at the level of a v-src-determined function. The potential importance of this control, in terms of the naturally occurring case of an avian sarcoma virus infection, is suggested by the observation that the patterns of tumor growth in a given congenic line are similar whether the tumors are induced by v-src DNA or by RSV.

Animals

Dietary arginine influences Rous sarcoma growth in a major histocompatibility B complex progressor genotype.

L-Arginine (L-Arg) can serve as a substrate for the production of reactive nitrogen intermediates. One of these metabolites, nitric oxide, has been shown to possess significant antitumor properties in vitro. To investigate the importance of this system in vivo, we have examined the dietary L-Arg host tumor interaction in the chicken. Since chickens are incapable of de novo L-Arg synthesis, concentration of this amino acid is readily controlled by diet. Line UNH 105 New Hampshire chickens having the major histocompatibility complex genotype, B24/B24, were used to study in vivo effects of dietary L-Arg on Rous sarcoma growth. After 5 weeks on a standard diet, 119 chicks were fed either a basal (0.92% L-Arg) diet or a high arginine (2.40% L-Arg) diet. One week later, chicks were wing-web inoculated with subgroup A Rous sarcoma virus. Tumor growth was monitored weekly for 12 weeks after inoculation. Plasma L-Arg levels and body weights from birds on each dietary treatment were analyzed. Neither body weight gains nor latent period for tumor development was affected by diet. However, plasma L-Arg levels were significantly different between dietary treatments (basal, 0.245 +/- 0.01 mumol/ml; high, 0.738 +/- 0.03 mumol/ml). In addition, mean tumor size scores were significantly (P less than 0.05) lower over time in chickens fed the high L-Arg diet. The results suggest that dietary L-Arg in excess of the amount required for growth reduces tumor load.

Animals

Differential resistance to Staphylococcus aureus challenge in major histocompatibility (B) complex congenic lines.

Ten inbred B-congenic Leghorn lines were challenged with two isolates of Staphylococcus aureus at 3 days and 6 wk of age. Significant differences in mortality were observed among such lines when challenged at 3 days with either S. aureus Isolate P4L (moderately pathogenic) or S. aureus Isolate 3727 (highly pathogenic). Line 331 (B2/B2 genotype) had lower mortality than either Line 004 (B17/B17, chi 2 = 4.13, P < .05) or Line 253 (B18/B18, chi 2 = 4.23, P < .05) challenged with Isolate P4L. The use of a susceptibility index allowed for the detection of additional differences among the various lines challenged by Isolate 3727. Line 336 (BQ/BQ) was more resistant than either Line 335 (B19/B19, P < .01) or Line 330 (B21/B21, P < .01). No significant differences were found among the lines challenged at 6 wk by either isolate. The results provide additional evidence for the importance of the B complex in genetically determined disease resistance, and further demonstrate the usefulness of congenic lines in such investigations.

Animals

Multisite immunochemiluminometric assay for simultaneously measuring whole-molecule and amino-terminal fragments of human parathyrin.

The immunochemiluminometric assay described uses immobilized anti-human parathyrin (parathyroid hormone, hPTH)(1-44) and anti-hPTH(44-68) antisera and acridinium ester-labeled anti-hPTH(1-34) to simultaneously measure both intact hPTH and its amino-terminal fragments. Results by the assay correlate well with those by a cAMP-based bioassay and the Nichols Allegro immunoradiometric assay. The minimal detection limit is 0.08 pmol/L. The normal range is 1.0-5.0 pmol/L, and values are higher in older women. About 90% of study patients with surgically proven parathyroid adenomas had above-normal preoperative PTH concentrations, whereas patients with hypercalcemia of malignancy had normal or suppressed values. This assay was designed to detect both intact PTH and amino-terminal PTH fragments; however, chromatographic fractionation of pools of primary and secondary hyperparathyroid plasma showed virtually no amino-terminal fragment activity. Nonetheless, the design is important because the absence of carboxyl-terminal binding sites prevents interference by carboxyl-terminal fragments and because bioactive amino-terminal fragments will react in the assay if they are present in the patients' sera or if they are produced by in vitro proteolysis of intact PTH.

Chromatography

Determination of plasma calcitonin gene-related peptide concentrations by a new immunochemiluminometric assay in normal persons and patients with medullary thyroid carcinoma and other neuroendocrine tumors.

There is doubt about concentrations of circulating calcitonin gene-related peptide (CGRP) and the value of plasma CGRP measurements in the detection and follow-up of medullary thyroid carcinoma (MTC). Thus, we developed an immunochemiluminometric sandwich assay for CGRP using antibodies purified from a polyclonal antiserum against human CGRP. The assay was sensitive (limit of detection, 0.4 pmol/L; multiply by 3.7892 to derive nanograms per L) and highly specific [no cross-reaction with human calcitonin (CT)]. Normal plasma CGRP values ranged from less than 0.4 to 4.5 pmol/L (median, 0.8; n = 31), with 61% having detectable levels. Values in samples from patients with MTC were elevated: unoperated patients (n = 10), 4.7-137 pmol/L (median, 7.1); and operated patients with gross persistent or recurrent tumor (n = 14), 4.7-171 pmol/L (median, 23.2). In contrast, CGRP values were normal in 78% of nine postoperative patients with elevated CT, but no detectable tumor (range, less than 0.4 to 6.3 pmol/L; median, 1.6). CGRP levels increased after pentagastrin injection in MTC patients, but less than did CT values. Cultured MTC cells in vitro secreted large amounts of CGRP, and rat nerve root ganglia, human osteoblasts, and microvessel endothelial cells secreted lesser amounts. We conclude that CGRP circulates in normal plasma, but at very low levels. Plasma CGRP concentrations are frequently high in patients with MTC, but primarily in those with gross tumor or metastases. Plasma CT assay is the preferable test for MTC, but CGRP assay deserves prospective study for a possible role in predicting gross metastasis.

Animals