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Biomedical subjects

N Johnson

Publications and source records attributed to N Johnson.

At least 289 records · Page 16Linked to original sources
PubMed1984

[3H]-beta-endorphin binding in rat brain.

The binding of [3H]-beta-endorphin to rat brain homogenates is complex. Although Scatchard analysis of saturation studies yields a straight line, detailed competition studies are multiphasic, suggesting that even at low concentrations of the compound, the 3H-ligand is binding to more than one class of site. A portion of [3H]-beta-endorphin binding is sensitive to low concentrations of morphine or D-Ala2-Leu5-enkephalin (less than 5 nM). The inhibition observed with each compound alone (5 nM) is the same as that seen with both together (each at 5 nM). Thus, the binding remaining in the presence of both morphine and the enkephalin does not correspond to either mu or delta sites. The portion of [3H]-beta-endorphin binding that is inhibited under these conditions appears to be equally sensitive to both morphine and the enkephalin and may correspond to mu1 sites. Treating membrane homogenates with naloxonazine, a mu1 selective antagonist, lowers [3H]-beta-endorphin binding to the same degree as morphine and D-Ala2-Leu5-enkephalin alone or together. This possible binding of [3H]-beta-endorphin to mu1 sites is consistent with the role of mu1 sites in beta-endorphin analgesia and catalepsy in vivo.

Animals↗
PubMed1984

Binding of [3H]naloxonazine to rat brain membranes.

[3H]Naloxonazine binds to opioid-binding sites in rat brain homogenates. Prior administration of either morphine or D-Ala2-D-Leu5-enkephalin to the homogenates inhibits in a concentration-dependent manner the specific binding of [3H]naloxonazine. Most important, all the binding competed by unlabeled naloxonazine at 1 microM is also competed by morphine and D-Ala2-D-Leu5-enkephalin. [3H]Naloxonazine binding is linear with tissue up to 10 mg/ml wet weight of tissue, is temperature dependent, and has a pH maximum of approximately 7.7. Maximal binding is reached within 90 min at 25 degrees. The affinity of [3H]naloxonazine for its binding sites is quite high with half-maximal binding obtained at a concentration of approximately 2 nM. Approximately 40% of the total specific binding of [3H]naloxonazine is resistant to multiple washes and to displacement by levallorphan (1 microM) added 60 min after the [3H]naloxonazine, suggesting that a portion of [3H]naloxonazine binding is not freely reversible. The percentage of total [3H] naloxonazine binding which is not freely reversible varies 3-fold between regions, with the hypothalamus (60%) being the highest and the brainstem (18%) the lowest.

Animals↗
PubMed1983

The binding to rat brain homogenates of Mr2034, a universal opiate.

Mr2034 has been proposed as a kappa opiate. While Mr2034 inhibited the binding of the kappa opiate 3H-ethylketocyclazocine better than unlabeled ethylketocyclazocine, it also displaced the binding of 3H-dihydromorphine and 3H-SKF 10047 more potently than morphine and SKF 10047, respectively. 3H-D-ala2-D-leu5-enkephalin was displaced equally well by Mr2034 and D-ala2-D-leu5-enkephalin. Saturation studies of 3H-Mr2034 binding demonstrated curvilinear Scatchard plots which could be dissected into two components by computer: KD1 0.06 nM, Bmax1 2.49 fmoles/mg tissue; and KD2 2.4 nM, Bmax2 6.57 fmoles/mg tissue. A portion of the higher affinity (KD 0.06 nM) component was inhibited by naloxonazine treatment in vitro (50 nM), suggesting that 3H-Mr2034 bound with very high affinity to mu1 sites. Displacement of 3H-Mr2034 binding by opioids was multiphasic, again implying that 3H-Mr2034 was binding to more than one class, of site. In view of its similar potency in inhibiting mu (3H-dihydromorphine), kappa (3H-ethylketocycla-zocine), sigma (3H-SKF 10047) and delta (3H-D-ala2-D-leu5-enkephalin) opioids Mr2034 might be considered a universal opiate.

Animals↗
PubMed1983

Biochemical and pharmacological evidence for opioid receptor multiplicity in the central nervous system.

Evidence from a variety of experimental models has suggested the existence of mu 1, mu 2 and delta binding sites for morphine and the enkephalins in the central nervous system. Additional biochemical experiments now support this concept of a common high affinity site for opiates and opioid peptides. Mu sites have now been implicated in a number of pharmacological actions, including supraspinal analgesia, prolactin release, and catalepsy, but not in others (spinal analgesia, respiratory depression, and the guinea pig ileum). The hypothesis of mu 1 sites was supported by the unique opioid meptazinol, which selectively bound to mu 1 sites. As expected from its mu 1 binding selectivity, its analgesic actions in the mouse, localized supraspinally, were antagonized by the selective mu 1 antagonist naloxonazine and it had no respiratory depressant actions. Other binding studies suggested the presence of discrete SKF10,047-selective (KD approximately 5 nM) binding sites in rat brain which differed from both kappa sites and the previously reported PCP-binding sigma sites. Additional binding and autoradiographical studies have also implied the presence of beta-endorphin, or epsilon, sites in the CNS.

Analgesia↗
PubMed1982

Assessment of plasma total cholesterol as a test to detect elevated low density (beta) lipoprotein cholesterol levels (type IIa hyperlipoproteinemia) in young subjects from a population-based sample.

The measurement of plasma total cholesterol as a screening test for an increased plasma level of low density lipoprotein cholesterol (greater than age- and sex-adjusted 95th percentile) with a normal plasma triglyceride level (type IIa hyperlipoproteinemia) was assessed in 1325 young subjects, aged 6 to 19 years, from seven North American populations during the years 1972-1976. When the age- and sex-specific 95th percentile for total cholesterol was used as the cutpoint for hypercholesterolemia, almost one third of young subjects with type IIa hyperlipoproteinemia were undetected (false negatives), and 40% of the test results were falsely positive. Ninety-eight per cent of all non-type IIa subjects were correctly identified. Lowering the percentile cutpoint decreased the false negative results but increased the false positive results; increasing the cutpoint had an opposite effect. Females had higher percentile cholesterol values than males; when extrinsic, arbitrary cholesterol cutpoints (175-210 mg/100 ml) for screening were used, there were fewer false negative but more false positive results in the females than in the males. When the prevalence of type IIa hyperlipoproteinemia was increased from 5 to 50%, the false positive tests decreased from 40 to 2%. A two-step screening for hypercholesterolemia did not improve efficiency. The use of plasma total cholesterol as a test for type IIa hyperlipoproteinemia in a general population results in a relatively large number of false positive and false negative tests.

Adolescent↗
PubMed1982

The complete V domain amino acid sequences of two myeloma inulin-binding proteins.

The myeloma proteins binding inulin afford a unique opportunity to study the V region patterns of variation because of the similarity in the VL as well as the VH regions. The diversity patterns in both the VL and VH regions suggest these proteins are encoded by multiple, very similar V gene segments or that somatic mutation may repeatedly generate identical variants. Because of the close similarity in the V domains of these proteins and the extensive idiotypic analyses that have been carried out previously, several interesting conclusions can be drawn about the nature of idiotypic determinants. First, a single amino acid residue may be involved in determining multiple idiotypic determinants. Second, hapten-inhibitable idiotypes may depend on residues within and outside the hypervariable regions. Third, idiotypic similarity does not always predict a corresponding sequence similarity.

Amino Acid Sequence↗
PubMed1981

Generation of visual representations.

The visual confusability of uppercase letters was manipulated in a successive same-different task to study the conditions under which visual generation from auditory inputs would occur and to investigate the figural specificity of the generated representations. Prior experiments have shown that visual confusions do occur when the initial stimulus is auditory and the second one is visual, which indicates that auditory stimuli can be encoded into visual forms. There has been some suggestion, however, that the generated visual code may have been too abstract to differentiate between the two cases in which letters can appear. In the present experiment, although the confusion effect was not eliminated when the subjects had no advance knowledge regarding the case in which the visual stimulus would appear, the marked confusion effect obtained when the visual stimulus was an uppercase letter was substantially attenuated when the letter appeared in lowercase. This was taken to indicate that the visual characteristics of a generated visual representation may be relatively specific. The results also suggested that subjects may wait until after the second stimulus is presented before they generate the visual representation of the initial auditory stimulus.

Discrimination Learning↗
PubMed1980

Femoropopliteal vein grafts for intermittent claudication.

Femoropopliteal vein grafts were performed for intermittent claudication in 160 patients (182 legs) over a 12-year period. The accumulative patency rate was 67 per cent at 5 years. However, patency rates improved significantly in the latter 6 years of the study, to 75 per cent at 5 years. Early postoperative occlusion and morbidity rates also markedly declined in this latter period. Patency rates were significantly better in males than in females, in patients who were able to stop smoking after operation and in legs with a three-vessel run-off compared with those with a two- or one-vessel run-off. The patients' age did not influence graft patency rates.

Adult↗
PubMed1980

Influence of broperamole, a new antiinflammatory agent, on gastrointestinal microbleeding in the dog.

59Ferrous sulfate was administered i.v. to 12 male beagles. Beginning 11 days later, gastrointestinal microbleeding was determined by comparison of the 59Fe specific activities of 24-h stool collections and of whole blood. During the following 48-day period the dogs received p.o. twice daily a placebo, two tablets containing 650 mg of acetylsalicylic acid (ASA), 22 mg/kg of phenylbutazone, or 24 mg/kg of N-2-[5'-(3"-bromophenyl-2'H-tetrazole]propionyl piperidine (broperamole) in four 7-day tratment periods (each of which was preceded by a 5-day period of no treatment) in complete crossover fashion. Average daily fecal blood volumes of 2.55 ml, 1.94 ml, 0.54 ml, and 0.48 ml were observed after treatment with ASA, phenylbutazone, broperamole, and placebo, respectively. The influence of ASA and phenylbutazone on gastrointestinal microbleeding was statistically greater than that of broperamole, which was equivalent to placebo.

Animals↗