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R K Johnson

Publications and source records attributed to R K Johnson.

At least 181 records · Page 10Linked to original sources
PubMed1986

Modulation of the antitumor and biochemical properties of bis(diphenylphosphine)ethane with metals.

Bis(diphenylphosphine)ethane (DPPE) and its bis[chlorogold(I)] [DPPE(Au2Cl2)], and bis[trichlorogold(III)] [DPPE(Au2Cl6)], complexes have in vivo antitumor activity. To determine if interaction with metals in situ can play a role in the antitumor activity of DPPE, we have studied the effects of DPPE, DPPE(Au2Cl2), DPPE(Au2Cl6) and mixtures of DPPE with metal salts on in vitro and in vivo biological systems. The in vitro cytotoxic potencies of the two DPPE-gold complexes were approximately 10-fold greater than that of DPPE. In addition, the cytotoxic potency of DPPE was increased when incubated with cells in the presence of Au(III) and Cu(II) salts, whereas Mg(II), Zn(II), Mn(II), Fe(II), Co(II), and Cd(II) had no effect. The effects of DPPE, DPPE(Au2Cl2) and mixtures of DPPE and metal salts on the activity of a model enzyme system, DNA polymerase alpha were measured. While DPPE did not inhibit the activity of DNA polymerase alpha, the DPPE(Au2Cl2) complex and mixtures of DPPE and Cu(II) salts inhibited the activity of the enzyme. Consistent with the effects observed in vitro, coadministration of Cu(II) or Au(III) increased the in vivo potency of DPPE in mice bearing i.p. P388 leukemia. Fifteen other DPPE analogues were evaluated for in vivo antitumor activity and for the effect of Cu(II) on their in vitro cytotoxic potency; there was a relationship between the ability of Cu(II) to potentiate the cytotoxic activities of DPPE analogues and their having in vivo antitumor activity.

Animals↗
PubMed1986

In vivo antitumor activity and in vitro cytotoxic properties of bis[1,2-bis(diphenylphosphino)ethane]gold(I) chloride.

We have previously reported the cytotoxicity and antitumor activity of bis(diphenylphosphino)ethane (DPPE) and a variety of its transition metal complexes. During studies of the chemistry of a gold complex of this group [(AuCl)2(DPPE)], it was observed that this complex readily underwent ring closure on reaction with DPPE to form the tetrahedral complex [Au(DPPE)2]+. Various counterion forms (e.g., Cl-) of this cation were isolated and were found to exhibit a remarkably high stability in solution. Evaluation of [Au(DPPE)2]Cl in mice bearing i.p. P388 leukemia demonstrated that the compound produced an average of 87% increase in life span at its maximally tolerated dose (2-3 mumol/kg/day for 5 days). Activity was also seen in i.p. M5076 reticulum cell sarcoma (60% increase in life span) and s.c. mammary adenocarcinoma 16/c. Modest activity was evident in i.p. B16 melanoma and L1210 leukemia. A subline of P388 leukemia resistant to cisplatin was not cross-resistant to [Au(DPPE)2]Cl. In addition, combination therapy of [Au(DPPE)2]Cl and cisplatin against i.p. P388 demonstrated an advantage over single-agent therapy. In vitro studies of [Au(DPPE)2]Cl showed that the compound: is cytotoxic to tumor cell lines; is only minimally inhibited in its cytotoxic activity by the presence of serum; produces DNA protein cross-links and DNA strand breaks in cells; and inhibits macromolecular synthesis with a preferential inhibitory effect on protein synthesis relative to DNA and RNA synthesis. 31P nuclear magnetic resonance spectroscopy indicated that the compound is stable in the presence of serum proteins, thiols, or disulfides and that it reacts with Cu(II) resulting in the formation of a Cu(I)DPPE complex. The results of these in vivo and in vitro experiments suggest that the contrasting pharmacological profile of [Au(DPPE)2]Cl with respect to other gold(I) phosphine complexes may be related to both the kinetic stability of the complex and its stability in the presence of thiols.

Animals↗
PubMed1986

Soft-tissue injuries of the forearm and hand.

In general, musculotendinous injuries of the forearm are not uncommon and are generally self-limited. The fact that there are so many different modalities of treatment speaks well for the human body to repair itself under some very adverse circumstances. Rest and splinting of the part, elevation, and judicious use of analgesics is still the treatment of choice. The injudicious use of heat and cold and electrical appliances of various types usually indicate a therapist in search of a treatment.

Athletic Injuries↗
PubMed1986

Psychological evaluation of patients with industrial hand injuries.

Psychological evaluations with hand injury patients provide diagnostic information and treatment recommendations that can be included with the findings from physical and neurologic examinations. Assessment of psychosocial factors that can either complicate recovery from injury or aid in rehabilitation is discussed. Four clinical cases are presented.

Adult↗
PubMed1986

Role of murine tumor models in cancer treatment research.

Two major factors have contributed to a widely held disenchantment with murine tumor models for drug screening in cancer research: (a) the higher costs of these models in comparison to studies performed with tumor cells in vitro; and (b) the perception that these models have failed to demonstrate satisfactory correlation of chemosensitivity with analogous human tumor types; i.e., murine tumors generally have proved to be sensitive to many more agents than are found to be active in the clinic. The perceived failure of the murine models is discussed with particular reference to the difference in criteria used for evaluating drug sensitivity in murine tumor models versus clinical trials, and we conclude that the perception about murine models is not tenable in light of present information. The very important role of murine tumor models in optimizing dosage and administration schedules and, most importantly, in the development of a new drug to its most useful potential in combination chemotherapy is discussed. The value of this in vivo methodology is stressed.

Animals↗
PubMed1985

Selection practices and genetic and phenotypic trends estimated from Nebraska SPF swine field records.

Records collected during 1971 through 1979 from 101,606 pigs raised in 18 herds that were members of the Nebraska SPF Swine Accrediting Association were evaluated for phenotypic trends and predicted and observed genetic trends. Traits considered were backfat at 100 kg (BF) and weight at 140 d of age (WT). Phenotypic change on average was beneficial for BF (-.05 mm/yr) but undesirable for WT (-.2 kg/yr). However, the average observed genetic trend was nil for BF and .6 kg/yr for WT. An average, predicted response based on observed selection differentials and estimates of within herd-sex genetic parameters was in good agreement with observed response for BF, but was three times higher for WT.

Adipose Tissue↗
PubMed1985

Mechanism of resistance of a variant of P388 leukemia to L-(alpha S,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (acivicin).

Acivicin [L-(alpha S,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid; NSC 163501] is a fermentation-derived amino acid antibiotic antagonistic to L-glutamine which exhibits potent oncolytic properties. We have developed a variant of P388 leukemia resistant to acivicin (P388/ACIA) and compared its properties with those of the parent line (P388/S). An examination of the enzymes utilizing L-glutamine revealed that the basal specific activities of L-asparagine synthetase and L-glutaminase were 1-to 3-fold higher in the parent line. The activities of carbamoyl phosphate synthetase II, L-asparagine synthetase, formylglycinamide ribonucleotide amidotransferase, and guanosine monophosphate synthetase were about equally inhibited in the two cell lines, while there was a partial inhibition of 5-phosphoribosyl-1-pyrophosphate amidotransferase, fructose-6-phosphate amidotransferase, and L-glutaminase activities, found only in the sensitive line. Cytidine triphosphate synthetase activity was not inhibited in either line. There was no difference in the dose response or restitution of L-glutamine utilizing enzyme activities between the two lines. Acivicin treatment produced a 2- to 3-fold augmentation of the L-glutamine pools only in the sensitive line. Drug injection induced increased 5-phosphoribosyl-1-pyrophosphate levels in both lines. Acivicin perturbed guanosine nucleotide pools only in the sensitive line, indicating that the primary mechanism of action of acivicin in P388 leukemia may be directed at guanosine monophosphate synthetase. Transport studies demonstrated a restricted uptake of acivicin by the resistant cells. These studies suggest that the transport of acivicin and L-glutamine plays an important role in determining the sensitivity or resistance to acivicin in these tumors.

Animals↗
PubMed1985

Influencing prolificacy of sows by selection for physiological factors.

The potential to improve prolificacy, with major emphasis on selection for components of litter size, ovulation rate and prenatal survival, and selection for physiological factors are reviewed. Response to selection for physiological factors is superior to direct selection if physiological factors have moderate heritabilities and moderate to high genetic correlations with the trait to be improved. There are very few estimates of the genetic parameters needed to calculate the relative efficiency of direct and indirect selection. Testis size is highly heritable and positively correlated genetically with ovulation rate in both mice and pigs and may be potentially useful in an index with litter size to improve ovulation rate and prenatal survival. Selection for growth, ovulation rate or litter size has increased ovulation rate in mice, but the physiological explanations are different. Selection for litter size in a line of pigs previously selected for ovulation rate was effective; the realized heritability was 0.18 +/- 0.06. Potential improvements in litter size from index selection for ovulation rate and prenatal survival are discussed and compared to direct selection for litter size.

Animals↗
PubMed1985

Evaluation of the in vivo antitumor activity and in vitro cytotoxic properties of auranofin, a coordinated gold compound, in murine tumor models.

The coordinated gold compound, 2,3,4,6-tetra-O-acetyl-1-thio-beta-D-glucopyranosato-S-triethyl phosphine gold (auranofin; Ridaura), was evaluated for antitumor activity in a variety of mouse tumor models. Of the 15 tumor models evaluated, auranofin was found to be active only against i.p. P388 leukemia. A number of dose schedules was used to measure activity against P388 with optimal activity observed at 12 mg/kg given daily, i.p., on Days 1 to 5. Auranofin was active against i.p. P388 leukemia only when administered i.p.; the drug was completely inactive when administered i.v., s.c., or p.o. on Days 1 to 5. Evaluation of the effects of auranofin in vitro demonstrated that survival curves for B16 melanoma cells as measured by the clongenic and dye exclusion assays were exponential and monophasic; cell cycle distribution was not altered, and auranofin displayed no preferential cytotoxicity to logarithmic or plateau growth phase cell populations; auranofin inhibited DNA, RNA, and protein synthesis at cytotoxic concentrations but showed no selective effect; the cytotoxic activity and cellular association of gold from auranofin were dose, time, and temperature dependent; and binding of auranofin gold to serum proteins markedly decreased cellular uptake of gold and cytotoxicity of auranofin in vitro.

Animals↗
PubMed1984

Relationship between serum luteinizing hormone and estradiol in prepubertal boars.

Effects of estradiol on serum luteinizing hormone (LH) were studied in prepubertal boars. In Exp. 1, 15-wk-old boars were given (iv) 50 mug estradiol, 1 mg testosterone or 1.5 ml ethanol. Estradiol (P<0.05) decreased LH over a 2.5-hr period, but testosterone did not. In Exp. 2, an estradiol implant reduced LH sample variance (P<0.01) while LH (547 +/- 96 vs 655 +/- 43 pg/ml) and estradiol (14.2 +/- 3.3 vs 18.4 +/- 1.0 pg/ml; control vs implant) were unchanged in 12-wk-old boars. Pulsatile LH releases (4.3 +/- 1.1 vs 3.0 +/- 0.4 pulses/pig/8 hr; control vs treated) and pulse amplitude (272 +/- 34 vs 305 +/- 40 pg/ml) were not affected. The implant tended to decrease serum testosterone (4.86 +/- 0.75 vs 7.66 +/- 1.51 ng/ml; P<0.10). In Exp. 3, LH was higher after zero implants than after four implants (279 +/- 7 vs 227 +/- 9 pg/ml; P<0.01), and LH after two implants was also higher than after four implants (263 +/- 7 pg/ml; P<0.01) in 14-wk-old boars in a Latin square design. Peak LH after 40 mug gonadotropin releasing hormone (GnRH) was less after two and four implants (1,100 +/- 126 and 960 +/- 167 pg/ml, respectively; P<0.01) than after zero implants (1,742 +/- 126 pg/ml). Slope of the first 20 min of LH response to GnRH was greater after zero implants (45.3 pg/min; P<0.05) than after either two or four implants (20.6 and 16.9 pg/min, respectively). Implant treatment decreased serum testosterone (P<0.025) but increased estradiol (P<0.10). Small changes in serum estradiol resulted in changes in LH. These changes in sample variance and mean LH were recognized by boars as different from normal because serum testosterone decreased. Changes in LH may result from estradiol's negative effect on pituitary responsiveness to endogenous GnRH because response to exogenous GnRH was depressed by estradiol.

Journal Article↗
PubMed1984

Improved genetically modified Escherichia coli strain for prescreening antineoplastic agents.

Clinical experience suggests that drugs that interact with and damage DNA are useful in cancer chemotherapy (H. Umezawa , p. 43-72, in V. T. DeVita , Jr., and H. Busch [ed.], Methods in Cancer Research; Cancer Drug Development, vol. XVI, 1979). Prescreening systems for antitumor agents in natural products require assays that are exquisitely sensitive, since the active components are often produced in quantities of micrograms per milliliter or less. One assay used to identify agents that interact with DNA is the biochemical induction assay, utilizing Escherichia coli BR 513 (R. K. Elespuru and R. J. White, Cancer Res. 43:2819-2830, 1983). In this paper we describe a genetic modification of strain BR 513 that displays an expanded spectrum of activity. This strain may provide an improved prescreen for detecting natural products that interact with DNA.

Ampicillin↗
PubMed1984

Testicular development and endocrine characteristics of boars selected for either high or low testis size.

Thirty-six Landrace x Large White cross boars were selected from litters with either high or low estimated breeding values for 150-d paired testis weight. Blood samples were taken via jugular venipuncture at eight ages (42, 56, 70, 84, 98, 112, 126 and 140 d). At each sampling age, nine blood samples were taken at 30-min intervals. Luteinizing hormone (LH) was determined on the individual serum samples. Serum samples from each boar at each age were pooled and concentrations of follicle-stimulating hormone (FSH), estradiol-17 beta (E2) and testosterone (T) were determined. Paired testis width, testis length and body weight were measured at 98, 112, 126 and 140 d of age. Backfat probe, weights of excised testes and histological data on testes were obtained at 140 d of age. Boars with high testis weight (HTW) were heavier (P less than .05), had higher adjusted backfat probes (P less than .01) and had consistently larger in situ testis measurements (P less than .01) than did low testis weight (LTW) boars. Boars with HTW had heavier (P less than .01) testes and epididymides at 140 d of age. They also had a higher percentage of seminiferous tubules in which spermatogenesis was present (P less than .05), a larger percentage of tubules with a lumen (P less than .05) and tubules had a larger mean diameter (P less than .01) than did those of boar with LTW. Adjustment of in situ testis measurements and excised testis weights for body weight reduced line differences by less than 20%. A rise in LH concentrations occurred at approximately 100 d of age. Boars with HTW had higher (P less than .05) and more variable (P less than .01) LH concentrations than did boars with LTW. Boars with HTW also had higher maximum concentrations of LH during the pubertal rise (P less than .01) and these concentrations tended to reach maximum levels at younger ages. Concentrations of T increased in a fashion that was nearly linear with age (P less than .01) and tended to be higher for the boars with HTW (P less than .10). Concentrations of E2 changed little from 42 to 84 d of age but increased steadily thereafter. Boars with HTW had a more rapid increase in E2 concentrations than did boars with LTW (P less than .05).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Relationships among measures of testicular development and endocrine function in boars.

Nine blood samples were taken at 30-min intervals from 36 Landrace X Large White boars at each of eight ages (42, 56, 70, 84, 98, 112, 126 and 140 d). Serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T) and estradiol-17 beta (E2) were quantified by radioimmunoassay procedures. The maximum concentration of LH and the age at maximum concentration were predicted for each boar. Variability of LH samples was described for each boar by the pooled within age variance among LH samples and by the number of LH peaks. Measurements of testicular development taken at 140 d of age included: in situ testis width and length, excised testis weights and histological traits of excised testes (seminiferous tubule diameter, percentage of tubules with a lumen and percentage of tubules with active spermatogenesis). Pooled within line correlations were calculated with data from boars selected for either high or low testis weight. Correlations among the testicular traits ranged from .45 to .88. Luteinizing hormone concentration (mean over all ages) was related to measures of testicular development (r = .24 to .49). Concentrations of LH from 42 to 84 d of age were more highly correlated with testicular traits than were the concentrations from 98 to 140 d.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1984

Effect of castration on plasma luteinizing hormone concentrations in prepubertal boars.

Mean concentrations and the occurrence of pulsatile release of luteinizing hormone (LH) were determined in 14-wk-old crossbred boars (50.5 +/- 1.5 kg) after bilateral or unilateral castration at 10 wk of age. Blood was collected at 10-min intervals for 5 h. Then gonadotropin releasing hormone (GnRH; 40 micrograms) was given and sampling was continued at 5-min intervals for 1 h. Compared with intact boars, bilateral castration increased (P less than .001) mean LH (982 +/- 56 vs 389 +/- 56 pg/ml), pulsatile releases of LH (7.0 +/- .6 vs 2.0 +/- .6 pulses/5 h) and LH pulse amplitude (617 +/- 29 vs 360 +/- 58 pg/ml). Unilaterally castrated boars did not differ from intact boars in any of the above measures of LH secretion. Testis weight increased more between 10 and 14 wk of age in the unilateral castrates than in the intact boars (432 +/- 42 vs 245 +/- 34%; P less than .05). Thus, compensatory hypertrophy occurred within 4 wk of castration. Plasma testosterone was lower for bilateral castrates than for intact animals (.1 +/- .8 vs 3.6 +/- .9 ng/ml; P less than .05) while unilateral castrates (3.8 +/- 1.0 ng/ml) and intact boars did not differ. Plasma estradiol concentrations in bilateral and unilateral castrates were not different from levels found in intact boars (1.8 +/- 1.8, 8.8 +/- 2.1 and 6.0 +/- 1.8 pg/ml, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Sow productivity comparisons for four breeds of swine: purebred and crossbred litters.

Data were collected from 366 litters produced in a four-breed (Duroc, Yorkshire, Spotted and Landrace) diallel mating system. Purebred and crossbred litters were farrowed during five consecutive (fall and spring) farrowing seasons (fall 1976 through fall 1978). Litters were produced by randomly mating boars of each breed to at least one female of each breed. Litter size and weight at birth, litter size and weight at 42 d and pig survival to 42 d were analyzed. There were significant parity effects for all traits except survival rate, and significant year and season effects for litter size at birth and 42 d and litter weight at 42 d. Large breed of dam differences were detected for most sow productivity traits. Litters from Spotted females were smaller and lighter in weight. Landrace females were most productive in terms of litter weight at weaning and proportion of their pigs raised from birth to weaning. Breed of sire differences were not significant for any trait. Significant heterosis estimates were obtained for litter size and weight at weaning and for survival rate. Crossbred litters had .79 more pigs, were 11.72 kg heavier at weaning and had a 5.56% greater survival rate than the average of all purebreds.

Animals↗
PubMed1984

Reproductive performance for four breeds of swine: crossbred females and purebred and crossbred boars.

Matings and litters were studied involving all three-breed crosses (sired by purebred boars) and four-breed crosses (sired by cross-bred boars) from the Duroc, Yorkshire, Landrace and Spotted breeds. There were 764 female mating records and 161 boars used over five sequential breeding seasons. A sample of pregnant gilts was slaughtered each season and the remainder were allowed to carry their litters to term so that 493 litters resulted. Crossbred and purebred boars and crossbred females were evaluated for their contributions to conception rate (first service and over an 8-wk breeding season), number of services/conception, litter size and weight at birth, 21 and 42 d and survival rate to 21 and 42 d. Crossbred boars had a 17.9% higher first service conception rate, a 5.3% higher breeding season conception rate and performed .11 fewer services/conception compared with purebred boars. There were no significant differences among the boar breeding groups for litter size, weight or survival rate. The six crossbred female groups (reciprocal crosses were combined) did not differ significantly in conception rate or number of services/conception. There were significant differences in litter weight born and differences that approached significance (P less than .10) for litter size at 42 d and litter weight at 21 d. Yorkshire-Landrace females had the largest litters at birth, 21 and 42 d and the heaviest litters at 21 and 42 d. The smallest litters at 21 and 42 d were from Yorkshire-Spotted females, and they also had the lightest weight litters at all three stages.

Animals↗