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Biomedical subjects

R L Johnson

Publications and source records attributed to R L Johnson.

At least 271 records · Page 15Linked to original sources

Synthesis of Pro-Leu-Gly-NH2 analogues modified at the prolyl residue and evaluation of their effects on the receptor binding activity of the central dopamine receptor agonist, ADTN.

Several analogues of L-prolyl-L-leucylglycinamide (PLG) were synthesized wherein the prolyl residue was replaced with other heterocyclic amino acid residues. Among the analogues synthesized were D-Pro-Leu-Gly-NH2 (2), less than Glu-Leu-Gly-NH2 (3), Thz-Leu-Gly-NH2 (4), Pip-Leu-Gly-NH2 (5), Aze-Leu-Gly-NH2 (6), L-delta 3,4-Pro-Leu-Gly-NH2 (7), and D-delta 3,4-Pro-Leu-Gly-NH2 (8). These analogues were tested for their ability to enhance the binding of the agonist 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene to central dopamine receptors. Analogues 2, 3, and 5-7 showed activity comparable to that of PLG, while the tripeptides 4 and 8 were found to be inactive. The results show that the N-terminal prolyl residue of PLG is not an essential requirement for this tripeptide's ability to modulate dopamine receptors.

Animals↗

Volatility and opportunity: industry forecast.

Although hospitals have grown and prospered by "doing good," that purpose no longer is the only consideration in health care decisions. Business and the federal government now play key roles in controlling costs, and the once orderly prepayment industry is now a tangle of competitive interests. For the next few years, economic considerations will force quality-of-care issues to the background. In fact, until the current malpractice crisis, which causes physicians to practice defensive medicine, is resolved, it is unlikely that "doing good" will be the dominant concern. The future does not, however, hold greater and stiffer economic competition as far as one can see. Payers will be able to wring concessions from hospitals for only so long. When patient care is jeopardized, payers then will loosen the purse strings, and hospitals will return to a balance between "doing good" and "at what price".

Economic Competition↗

L-prolyl-L-leucyl-glycinamide analogues--a new class of peptide antihypertensives.

Accumulating evidence suggests that there is an increase in the density (maximum binding sites) of striatal dopamine receptors in the central nervous system of spontaneously hypertensive rats (SHR). A tripeptide of hypothalamic origin, PLG (L-Prolyl-L-Leucyl-Glycinamide) has been found to have modulatory effect on the dopamine receptors in the central nervous system of rats. Two analogues of PLG with cyclic amino-acid residues, L-Prolyl-L-Leucyl-(-)-thiazolidine-2-carboxamide and L-Prolyl-L-Leucyl-(+)-thiazolidine-2-carboxamide, have shown antihypertensive effect at the established phase of hypertension in 16-week old SHRs at a dose of 35 mg/kg per day per 7 days i.p. It was also observed from studies of radioligand [3H]-spiroperidol binding that the laevo-isomer of the PLG analogue has down-regulated the up-regulated dopamine receptors. Our findings confirm the role of central dopaminergic pathways in the pathogenesis of hypertension in SHR.

Animals↗

The evaluation and treatment of adolescent overdoses in an adolescent medical service.

Aspects of the mental health care provided in an adolescent medical setting are examined. Over a six-month period, 38 patients were admitted to an inpatient adolescent medical unit because of drug ingestion. Following evaluation by the adolescent medical team, psychiatric consultations were requested in 47 percent of the cases. Most patients were referred for follow-up "counseling" in an adolescent clinic. In comparing the "consult" and "non-consult" groups, data are given on the demographics, diagnoses, reasons for the consultation request, lengths of hospital admission, follow-up dispositions, and compliances. Illustrations are given of the counseling process in the adolescent clinic. Patients in both groups had substantial psychosocial problems. Many patients received conduct-disorder diagnoses with varying degrees of subjective distress. It was generally the degree of depression, as assessed by the pediatrician, that determined whether a psychiatric consultation was requested. The acceptance of follow-up recommendations was approximately 50 to 60 percent in both groups.

Accidents↗

Structure-function relationships for kynurenic acid analogues at excitatory pathways in the rat hippocampal slice.

Eight kynurenic acid analogues were bath-applied to rat hippocampal slices while recording extracellular synaptic field potentials and the potencies of these analogues for inhibition of these responses were compared to that of kynurenic acid. Quinaldic acid, 4-hydroxyquinoline, 4-hydroxypicolinic acid, L-kynurenine and picolinic acid inhibited evoked field potentials, but were at least 15-fold less potent than kynurenic acid in all pathways tested. Xanthurenic acid was inactive in the pathways tested. Quinolinic acid and dipicolinic acid showed signs of agonist activity with IC50's of approx. 400 microM and 2500 microM, respectively. These studies show that the 2-carboxy group and the 4-hydroxy moiety are essential for the antagonist activity exhibited by kynurenate. They also show that the unsubstituted second aromatic ring greatly enhances the affinity of kynurenate for these receptors and that substitution in at least one position on this aromatic ring abolishes activity.

Animals↗

Displacement of DL-[3H]-2-amino-4-phosphonobutanoic acid ( [3H]APB) binding with methyl-substituted APB analogues and glutamate agonists.

The binding of the excitatory amino acid antagonist DL-2-amino-4-phosphonobutanoic acid (DL-APB) to rat brain synaptic plasma membranes was characterized. As determined by Scatchard analysis, the binding was saturable and homogeneous with a Kd = 6.0 microM and Bmax = 380 pmol/mg of protein. The binding was dependent on the presence of Ca2+ and Cl- ions and was diminished upon freezing. The association rate constant was 6.8 X 10(-3) microM-1 min-1, and the dissociation rate constant was 2.0 X 10(-2) min-1. The L isomers of APB, glutamate, and aspartate were more potent as displacers of APB binding than the D isomers. Previously determined inhibition data obtained for APB-sensitive inputs to hippocampal granule cells are compared to the present displacement data in an attempt to identify this binding protein as the recognition site of the receptor mediating the APB-induced inhibition of synaptic transmission. With the exception of kynurenic acid, all compounds examined in both systems were more potent as displacers of APB binding than as inhibitors of synaptic transmission. This difference in potency was most pronounced for agonists at dentate granule cells. L-Glutamate, D-glutamate, and L-glutamate tetrazole were between 140- and 7500-fold more potent as displacers of DL-APB binding than as inhibitors of synaptic transmission. D-2-Amino-5-phosphonopentanoic acid and alpha-methyl-APB were between 10- and 20-fold more potent as displacers of binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Antagonist activity of methyl-substituted analogues of 2-amino-4-phosphonobutanoic acid in the hippocampal slice.

Four monomethyl-substituted analogues of 2-amino-4-phosphonobutanoic acid (APB), an antagonist of excitatory pathways in the central nervous system, were prepared in order to investigate the steric requirements of the APB receptor. Methyl groups were incorporated at the amino, alpha-, beta-, and gamma-positions. The beta- and gamma-methyl-substituted analogues of APB were found to be moderately potent antagonists in excitatory synapses of the hippocampal perforant path, as judged by extracellular recording techniques, while the N- and alpha-methyl-substituted analogues had much lower potencies. All of these APB analogues had very low potencies in the Schaffer collateral pathway. The APB receptors in the perforant path displayed more tolerance of methyl-substitution at the beta- and gamma-positions of APB than at the amino or alpha-positions in this system.

Aminobutyrates↗

Cardiac output distribution and uteroplacental blood flow in the pregnant rabbit: a comparative study.

This study presents data on cardiac output distribution and uterine and placental blood flows in pregnant rabbits under chronic steady-state conditions. Ten liters and 67 fetuses were studied at 29 days of gestation, by means of radioactive microspheres. Five nonpregnant female animals were also studied for comparison. Mean cardiac outputs were 747.16 +/- 55.7 and 613.80 +/- 63.76 ml/min in the pregnant and nonpregnant states, respectively. In the pregnant animals, uterine and mammary blood flows were 6.7% +/- 0.7% and 5.1% +/- 0.5% of cardiac output, respectively. Within litters, the highest placental blood flows occurred at the ovarian and vaginal ends of the uterine horn. Placental blood flow per gram of fetus was 0.106 +/- 0.008 ml X min-1 X gm-1. A comparison with analogous data in the guinea pig and sheep demonstrates that toward the end of pregnancy placental blood flow per gram of fetus is approximately 2.5-times higher in sheep than in rabbits and guinea pigs. Expressed as a percentage of cardiac output, near-term uterine blood flow is significantly less in rabbits than in guinea pigs and sheep, whereas mammary blood flow is significantly higher. These interspecies differences are related to differences in placental structure, fetal/maternal mass ratio, and maturity at birth.

Animals↗

Sexual victimization of boys. Experience at an adolescent medicine clinic.

Most information pertaining to male child sexual abuse victims is derived from cases presenting to the criminal-justice system, the mental-health system, hospital emergency rooms, and retrospective studies of college populations, all of which may be biased samples. This paper reports a six-year experience in an adolescent medicine clinic in which all medical interviews of adolescent males included questions about sexual molestation. Forty adolescent males reported sexual victimization during their preadolescent years. This study group of 40 was compared with a randomly selected age-matched group whose responses were negative to the same questions. None of the study group had previously been identified by medical or legal systems as having been molested. Twenty-five percent of the victimized males reported sexual dysfunction compared to 5% of the nonvictimized males, and 60% stated that the sexual abuse had a significant impact on their lives. Consequently, we conclude that questions about sexual molestation should be included as part of routine histories in adolescent clinics.

Adolescent↗

Treatment of trichiasis with a lid cryoprobe.

A series of 112 eyelids with symptomatic aberrant eyelashes were treated by cryotherapy using a specially designed large-surfaced high-flow nitrous oxide probe. Either thermocouple control to -20 degrees C or timing of the application to 20 seconds (lower lid) or 25 seconds (upper lid) was used to monitor the freeze. Both techniques obtained a high cure rate and a low incidence of complications.

Cryosurgery↗

Functional capacities of lungs and thorax in beagles after prolonged residence at 3,100 m.

Functional capacities of the lungs and thorax in beagles taken to high altitude as adults for 33 mo or in beagles raised from puppies at high altitude were compared with functional capacities in corresponding sets of beagles kept simultaneously at sea level. Comparisons were made after reacclimatization to sea level. Lung volumes, airway pressures, esophageal pressures, CO diffusing capacities (DLCO), pulmonary blood flow, and lung tissue volume (Vt) were measured by a rebreathing technique at inspired volumes ranging from 15 to 90 ml/kg. In beagles raised from puppies we measured anatomical distribution of intrathoracic air and tissue using X-ray computed tomography at transpulmonary pressures of 20 cm H2O. Lung and thoracic distensibility, DLCO, and Vt were not different between beagles that had been kept at high altitude for 33 mo as adults and control subjects kept simultaneously at sea level. Lung distensibility, DLCO, and Vt were significantly greater in beagles raised at high altitude than control subjects raised simultaneously at sea level. Thoracic distensibility was not increased in beagles raised at high altitude; the larger lung volume was accommodated by a lower diaphragm, not a larger rib cage.

Altitude↗

Metabolic quotients of the gravid uterus of the chronically catheterized guinea pig.

The uptake of substrates by the pregnant uterus defines the "diet" of the uterus and conceptus. In order to determine the uterine substrate uptake, catheters were placed in the femoral artery and uterine veins of guinea pigs at 40-49 days gestation. After at least 2 days recovery from perioperative stress, systemic arterial and uterine venous concentrations of oxygen, glucose, lactate, acetoacetate, beta-hydroxybutyrate, acetate, and free fatty acids were measured and metabolic quotients were calculated. The glucose/O2 quotient was 1.22 +/- 0.07 (mean +/- SEM), the lactate/O2 quotient was -0.40 +/- 0.09, the acetoacetate/O2 quotient was 0.03 +/- 0.02, the beta-hydroxybutyrate/O2 quotient was 0.01 +/- 0.006, the acetate/O2 quotient was 0.03 +/- 0.01, and the free fatty acid/O2 quotient was 0.24 +/- 0.21. Among the substrates measured, glucose appears to be the major metabolic fuel of the pregnant guinea pig uterus, but does not account for all of the oxygen consumed by the uterus if adjusted for lactate production, since lactate is produced within the gravid uterus in large quantities. Acetoacetate and beta-hydroxybutyrate are utilized in negligible amounts.

Animals↗

Old memories and new dreams: economics for nonprofit hospitals.

Economics has been introduced as an aspect of competition among hospitals. Pricing systems are growing in importance. In general, wise economics is being stressed. This study considers the characteristics of networks, investor-owned hospitals, and nonprofit hospitals. The author suggests ways for nonprofit organizations to recover and remain strong.

Economics, Hospital↗