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Biomedical subjects

H L Johnson

Publications and source records attributed to H L Johnson.

At least 37 records · Page 2Linked to original sources

Folate requirement and metabolism in nonpregnant women.

Folate metabolism and requirements were studied in 10 adult nonpregnant women maintained for 92 d in a metabolic unit. After a folate depletion period of 28 d, the subjects received increasing supplements of folate from food items or as pteroylmonoglutamic acid (PGA). Plasma folate levels fell 60% during the depletion period and continued to fall until 200 micrograms/d of naturally occurring food folates were provided. Supplements of 300 micrograms/d of naturally occurring folates produced a small rise in plasma folate levels although erythrocyte folate levels continued to fall. Lymphocyte deoxyuridine suppression, neutrophil hypersegmentation, and other measurements related to folate metabolism were performed. When compared with PGA, dietary folates appeared to be no more than 50% available. A daily intake of 200-250 micrograms of dietary folates appears to meet the folate requirements of nonpregnant adult women whereas an intake of 300 micrograms/d provides an allowance for storage.

Adult↗

Black mental health client's preference for therapists: a new look at an old issue.

Thirty black clients from a community mental health center in the Los Angeles City were interviewed to determine whether black Clients prefer black therapists or therapists from other ethnic backgrounds, and the factors associated with their preferences. Both quantitative and qualitative analyses were employed. The results indicated that 60% of the respondents preferred black therapists. With the small sample size this difference between responders and non-responders was within the normal range expected. However, preference of blacks for blacks is an important finding. When a black client preferred a black therapist, the major reasons depended on the therapist's professional competence and attitudes, not just the cultural, race, and linguistic compatibility.

Black or African American↗

Methadone-maintained mothers: 3-year follow-up of parental functioning.

A group of 57 methadone-maintained mothers and 31 matched drug-free controls were compared on their ability to provide adequate child care, capacity for satisfying interpersonal relationships, and motivation for self-improvement. Results indicate that, as a group, methadone mothers require more assistance in parenting, are more socially isolated, and are less likely to pursue vocational and educational activities. The interpersonal and environmental impact of poor parenting further compounds the effects of in utero exposure to methadone, placing these infants at high risk.

Child Development↗

Synthesis and biological activity of an amino analogue of a tripeptide inhibitor of angiotensin-converting enzyme.

An amino analogue of N-benzoyl-phenylalanyl-glycyl-proline, a tripeptide inhibitor of angiotensin-converting enzyme, was synthesized. The analogue (III) has the phenylalanyl-glycine amide linkage of N-benzoyl-phenylalanyl-glycyl-proline reduced to a methylene amine. Compound III was tested as an inhibitor of porcine plasma angiotensin-converting enzyme and has an I50 of 620 microM compared with an I50 of 9.6 microM for its parent tripeptide. These results are explained in terms of a proposed model of the converting-enzyme active site.

Angiotensin-Converting Enzyme Inhibitors↗

Children of methadone-maintained mothers: follow-up to 18 months of age.

Limited information is available on the long-term effects of in utero methadone exposure. This report describes the somatic and neurobehavioral findings of children in the first 18 months of life born to methadone-maintained mothers and to a matched drug-free comparison group of mothers. Findings during the neonatal period were (1) a 75% incidence of moderate-to-severe narcotic abstinence syndrome, (2) a significant incidence of head circumferences below the third percentile, and (3) elevated systolic blood pressure. In follow-up, the methadone children had (1) a significantly higher incidence of otitis media; (2) a significant incidence of head circumferences below the third percentile; (3) neurologic findings of tone discrepancies, developmental delays, and poor fine motor coordination; (4) a high incidence of abnormal eye findings; and (5) significantly lower scores on the Bayley mental and motor developmental indices. These neurobehavioral findings in children of methadone-treated mothers at 18 months of age may be predictors of later learning and behavioral problems.

Abnormalities, Drug-Induced↗

Prenatal methadone exposure: effects on behavior in early infancy.

As part of an ongoing longitudinal study of the developmental effects of prenatal methadone exposure, 41 children born to methadone-maintained mothers and 23 children from matched backgrounds but with negative maternal history of drug abuse were evaluated at six months of age. Each child received physical and neurological examinations and a battery of behavioral assessments that included a visual habituation task, the Bayley Scales and the Object Permanence Scales. The groups did not differ significantly in frequency of suspect-abnormal neurological signs or in mean scores on the three behavioral measures. Despite the great within-group variances, performance on the behavioral measures was not related to maternal or neonatal characteristics. There were significantly more low PDI scores (predictors of developmental difficulties) among methadone subjects, particularly among methadone vs comparison males. These findings corroborate other studies that have shown 1) delayed motor development in methadone-exposed infants, 2) greater vulnerability of males to adverse environmental conditions, and 3) correlation between early methadone exposure and behavioral abnormalities in adult male rats. The significance of prenatal methadone exposure as a risk factor is discussed.

Adult↗

Comprehensive pharmaceutical services for a state correctional facility.

A contractual model for comprehensive pharmaceutical services involving a major medical center pharmacy, a university, and a state department of corrections is described. Project goals and methods for the provision of services are described. These include areas of formulary development, inventory management, drug distribution, on-site placement of pharmacy operations, and educational development. Impact of the program was assessed over a 30-month period. Development of policies and procedures for drug use in a correctional setting enabled implementation of a strict patient population-specific drug formulary. Procedural changes resulted in an 83% decrease in on-site drug inventories and a 62% decrease in quarterly drug expenditures. A one-time saving of more than $26,500 resulted from the decrease in on-site inventory, and an annual saving of $44,000 is projected for decreased drug expenditures. All but five controlled substances were removed from the formulary, and only 13 nonprescription items remained in the formulary. An educational course on health care in correctional settings provided exposure for pharmacy students to this new area of institutional practice. The contractual model proved both cost-effective and functional for the department of corrections.

Education, Pharmacy↗

Synthesis and biological activity of fluoroalkylamine derivatives of narcotic analgesics.

N-Ethyl-, N-(2-fluoroethyl)-, N-(2,2-difluoroethyl)-, and N-(2,2,2-trifluoroethyl)-substituted normeperidine (1b-e) and normetazocine (2b-e) derivatives were prepared. The analgesic activities of the compounds were determined in mice. Opiate receptor binding studies, in the presence and absence of sodium ion, were carried out. The antagonist activities of normetazocine derivatives were studied in monkeys. These were further examined in the isolated guinea pig ileum for relative agonist activity. The pKa values were measured; in vivo agonist acitivty was lost with weakly basic derivatives. For the normetazocine derivatives, opiate receptor binding data were consistent with guinea pig ileum agonist potency and mouse vas deferens antagonist potency but not with in vivo data. Opiate receptor binding was reduced for the less basic normetazocine derivatives. In the normeperidine series, there was no apparent direct relationship between pKa and opiate receptor binding. However, a relationship involving the hydrophobic character of the N-substituent is discussed. The N-(2-fluoroethyl) derivatives in both series were found to cause convulsions in rats at doses of 40-45 mg/kg ip. Elevated serum citrate levels were found in these rats, implicating in vivo oxidative deamination of the N-(fluoroalkyl) substituent to fluoroacetate.

Analgesics, Opioid↗

Synthesis and biological activity of a ketomethylene analogue of a tripeptide inhibitor of angiotensin converting enzyme.

An analogue of a tripeptide inhibitor of angiotensin converting enzyme, Bz-Phe-Gly-Pro, has been synthesized in which the amide bond connecting phenylalanine and glycine has been replaced by a ketomethylene group. This nonpeptide analogue, 20, shows more potent converting enzyme inhibiting activity, I50 = 0.07 microM, than Bz-Phe-Gly-Pro, I50 = 9.4 microM, or than the orally active D-3-mercapto-2-methylpropanoyl-L-proline (captopril, 1), I50 = 0.30 microM. Compound 20 has a Ki of 1.06 X 10(-7) and either competitive or noncompetitive enzyme kinetics depending on what substrate is used in the converting enzyme assay. In tests for inhibition of angiotensin I induced contractions in the guinea pig ileum, 20 has one-tenth the activity of 1.

Angiotensin I↗

Trace mineral intake of enlisted military personnel. Preliminary observations.

The results of this study indicate that copper intakes were generally significantly below the Food and Nutrition Board's recommended range. It is presently unknown whether the new, 1979 recommendation is too high or whether copper deficiency-related problems may eventually develop in these men. When compared with the new recommendations, zinc and manganese intakes appeared to be adequate. Individual intakes must either be monitored over several days or a large population surveyed to determine whether dietary intakes of minerals are adequate. This is due mainly to large day-to-day variations in individual dietary intakes.

Adult↗

Analgesics. 1. Synthesis and analgesic properties of N-sec-alkyl- and N-tert-alkylnormorphines.

A series of N-sec- and N-tert-alkylnormorphines was synthesized and evaluated for analgesic potency, antagonist activity, and opiate receptor binding. Computer-assisted conformational analysis profiles were utilized to assist in the selection of compounds for synthesis and correlation of receptor events with in vivo observations. N-tert-Alkylnormorphines 5a-c were devoid of agonist activity; however, some sec-alkyl analogues showed interesting mixed agonist-antagnoist actions. N-sec-Butyl- and N-(alpha-methylally)normorphine were separated into R and S isomers, which exhibited quantitative pharmacological differences. The N-sec-butyl S isomer 10a showed analgesia approximating morphine with nalorphine-like antagonist activity. Preliminary testing indicates only slight evidence for physical dependence with this compound.

Analgesics↗

Application of 13C-NMR spectroscopy to in vitro analysis of enzyme kinetics.

The conversion of D,L-alpha-13C-histidine to similarly labeled alpha-13C histamine by bacterial and mammalian histidine decarboxylase was studied by 13C-NMR spectroscopy and GLC-mass spectrometry. The results obtained with the partially purified bacterial enzyme were in essentially perfect agreement with results obtained simultaneously with a standard radioisotopic method using carboxyl-labeled-14C-L-histidine. For a crude tissue preparation of the mammalian enzyme, the radioisotopic method indicated an activity three times that based on 13C-NMR measurement of alpha-13C-histamine. The difference in results was accountable in terms of additional 13C-NMR signals attributable to products other than histamine due in part to enzymatic degradation of the latter.

Animals↗

Potential histidine decarboxylase inhibitors. 1. alpha- and beta-substituted histidine analogues.

Histidine analogues with alkyl substitution at Calpha and Cbeta were prepared as potential inhibitors of specific histidine decarboxylase. Activity was assessed in vitro using extracts of rat pyloric stomach and a radioisotopic assay of 14CO2 evolved from carboxyl-14C-labeled histidine. alpha-Substituted analogues (C2-C4) including 2-hydroxyethyl were less potent than alpha-methylhistidine; the alpha-n-butyl analogue was completely inactive at 10(-3) M. Similarly, beta,beta-dimethylhistidine and homohistidine failed to exhibit activity at 10(-3) M.

Animals↗