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Biomedical subjects

M Johnson

Publications and source records attributed to M Johnson.

At least 685 records · Page 38Linked to original sources
PubMed1986

Pharmacokinetics of single dose intravenous ciprofloxacin in patients undergoing gastrointestinal surgery.

The pharmacokinetics of single dose intravenous ciprofloxacin in patients undergoing gastrointestinal surgery (100 mg, n = 8; 200 mg n = 18) have been studied. Following 100 mg therapeutic serum levels were maintained for approximately 40 min only and tissue concentrations were frequently less than 0.15 mg/kg. 200 mg maintained therapeutic serum levels for at least 150 min and produced mean concentrations in fat, muscle, peritoneum and gut wall of 1.04, 1.94, 1.59, and 3.39 mg/kg respectively. 200 mg iv ciprofloxacin would appear to provide adequate serum and tissue concentrations for at least 150 min.

Abdominal Muscles↗
PubMed1986

Neocortical cholinergic enzyme and receptor activities in the human fetal brain.

In the human fetus, obtained postmortem at estimated gestational ages of 8-22 weeks, biochemical activities of cortical choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) were comparable to those of adult brain tissue. In contrast cholinergic receptor binding, including muscarinic M1 and M2 subtypes (measured by displacement of [3H]N-methylscopolamine with, respectively, pirenzepine and carbachol) and [3H]nicotine (putative nicotinic) binding were undetectable before 13-14 weeks and even at 22 weeks were substantially (three- to fourfold) below the respective adult values. Cortical ChAT activity decreased significantly with gestational age whereas binding to the three receptors, including the proportion M1/M2, increased significantly. AChE was present at all ages investigated as the two molecular monomeric (G1) and tetrameric (G4) forms. The proportion of G4, which was much more soluble in fetal compared with adult cortex, increased approximately threefold. Histochemically AChE, although intense in the nucleus of Meynert, was generally confined to subcortical white matter at early fetal developmental periods, appearing later in the cortex localized to nerve fibres and occasional cell bodies. These observations suggest that during the second trimester of human fetal development, cortical cholinergic function may be preceded by relatively high ChAT activity and paralleled not only by increasing receptor binding but also by a proportional increase in the tetrameric form and histochemical reactivity of AChE.

Acetylcholinesterase↗
PubMed1986

Lithium ion transport by erythrocytes of randomly selected blood donors and manic-depressive patients: lack of association with affective illness.

The authors measured the in vitro lithium ion ratio and maximal rate of sodium-lithium countertransport in erythrocytes of 739 randomly selected blood donors and 42 manic-depressive patients to determine the frequency distributions of these two variables in a general population and their relationship to one another and to affective illness. A large interindividual variation was found for the ratio and countertransport, and there was evidence of bimodality in the frequency distributions for these two traits. There was a moderate negative correlation (r = -.61) between the ratio and countertransport for 126 individuals. Neither the ratio nor countertransport was found to be a useful marker for affective illness.

Adult↗
PubMed1986

How to construct a subjective index.

We present a method of constructing quantitative indices, which is based on the subjective opinions of a panel of experts, and discuss how a Bayesian probability model and panel opinions can be used together to produce an index. Among the advantages of the method are its face validity and ease of construction. Research shows that when expert opinions are solicited according to certain guidelines, subjective methods may be as accurate as the more objective ones. Guidelines along with a brief report of a recent application are also discussed.

Abstracting and Indexing↗
PubMed1986

Changes in the granule population of gonadotrophs of hypogonadal (hpg) and normal female mice associated with the priming effect of LH-releasing hormone in vitro.

Changes in the size and position of secretory granules in pituitary gonadotrophs have been studied in relationship to LH release and self-priming induced by LH-releasing hormone (LHRH) in pituitary glands from normal and hypogonadal (hpg) female mice. Hemipituitary glands were preincubated and then incubated for either 1 or 2 h in the absence or presence of LHRH (8.5 nmol/l). The glands were either processed for ultrastructural morphometry or homogenized for the determination of pituitary LH content. Morphometry was carried out on gonadotrophs identified by immunocytochemistry for LH beta using the thin/semi-thin section method. Pituitary LH content and the amount of LH released were determined by radioimmunoassay. The amount of LH released in response to the first and second hours of incubation with LHRH were similar in hpg and normal mice with a clear priming effect (three- to fourfold increase in pituitary responsiveness to LHRH) occurring in both strains. Despite a substantially reduced total number of granules (and amount of LH) in unstimulated hpg gonadotrophs, the number of granules in the outer 500 nm marginal zone of the cells was similar to that in normal mice. This could explain the similar amount of LH released from normal and hpg glands by the first LHRH challenge. The initial exposure to LHRH was also associated with a marked translocation of secretory granules from the central to the outer marginal region of cytoplasm subjacent to the gonadotroph plasmalemma, such that in 'primed' glands 60% of granules were found in this marginal zone compared with 40% (hpg) or 33% (normal) in unstimulated glands. The mean diameter of granules in the marginal zone was significantly less than that of granules in the central zone of the gonadotrophs of unstimulated glands from both normal and hpg animals. Exposure to LHRH for 1 h was associated with an increase in the number of small granules in the marginal zone and a significant decrease in the mean diameter of the gonadotroph granule population as a whole. After the primed release of LH, increased proportions of granules were still located in the marginal zone of gonadotrophs, indicating that granule migration continued during the second hour of exposure to LHRH in which primed release occurred. The primed release was associated with a detectable reduction in both the LH and granule content of gonadotrophs in normal, but not hpg glands.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Release of eicosanoids from white blood cells, platelets, smooth muscle cells, and endothelial cells in response to endotoxin and A23187.

Endotoxin produces numerous pathophysiologic changes in animals, including vascular endothelial cell damage and hematologic changes. Direct effects of endotoxin on arachidonic acid metabolism and the release of eicosanoids from endothelial cells and neutrophils have been reported. A rapid release of these autocoids occurs when cells are incubated with endotoxin, and this appears to be one of the earliest endotoxin-induced changes. Some of these eicosanoids may result in beneficial effects, and others may result in detrimental effects. This study was to determine the release of eicosanoids from white blood cells, platelets, smooth muscle cells, and endothelial cells in response to varying amounts of endotoxin and the calcium ionophore A23187. The results indicate that endotoxin has a major direct effect on vascular endothelial cells and smooth muscle cells as indicated by its ability to increase the synthesis of predominately i6-keto-PGF1 alpha by these cells. These effects were seen within a dose range of endotoxin that is lethal in horses. Very high concentrations of endotoxin (100 micrograms/ml) were required to stimulate a small increase in the production of i6-keto-PGF1 alpha and iLTC4 by freshly isolated neutrophils. Stimulation of cells with A23187 revealed that, of the eicosanoids measured, the one produced predominately by endothelial cells and smooth muscle cells was 6-keto-PGF1 alpha, by platelets was TxB2, and by neutrophils was LTC4 (LTB4 was not measured). A mixture of all white blood cells including platelets when incubated with A23187 produced large amounts of TxB2, LTB4, and LTC4 with smaller amounts of 6-keto-PGF1 alpha. The results indicate that endotoxin directly affects cells and stimulates them to produce thromboxane and prostacyclin, but very high concentrations of endotoxin were required to stimulate neutrophils to produce rather small increases in iLTC4.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

The flow of aqueous humor through micro-porous filters.

Flow resistance was measured as bovine and primate aqueous humor was passed through Nuclepore polycarbonate filters having flow dimensions similar to those found within the juxtacanalicular meshwork of the aqueous outflow network. The results indicate that aqueous humor has a greater flow resistance than isotonic saline; this greater resistance is attributable to proteins or glycoproteins in aqueous humor that obstruct the filters. If the same phenomenon is operative in the aqueous outflow network, it would help to explain discrepancies between calculated and measured aqueous outflow resistance.

Animals↗
PubMed1985

Evidence for the early prenatal development of cortical cholinergic afferents from the nucleus of Meynert in the human foetus.

A combined histochemical and biochemical approach has shown that the cholinergic system in the nucleus of Meynert region of the substantia innominata is well defined both histochemically and neurochemically within the first 3 months of gestation in the human foetus. Thus, at between 12 and 22 weeks of development the most intense acetylcholinesterase (AChE) histochemical reactivity was observed in the neuropil, cell bodies and processes in the nucleus of Meynert. AChE-stained fibres were observed which coursed from the nucleus of Meynert towards the cortical mantle and within the mantle AChE-stained fibres were also present. Micropunch samples from within the nucleus of Meynert contained higher levels of choline acetyltransferase (ChAT) activity than any other area examined including the striatum, while in the cortical mantle the level of ChAT activity was comparable to that found in the adult cerebral cortex. These observations suggest that the cholinergic innervation from the nucleus of Meynert--considered to be the major source of cholinergic afferents in the adult cerebral cortex--may play a key role in the early development of the human neocortex.

Acetylcholinesterase↗
PubMed1985

Naloxone inhibits superoxide release from human neutrophils.

Using the superoxide dismutase inhibitable reduction of cytochrome c assay, we studied, the effect of (-) naloxone on N-formyl-methionyl-leucyl-phenylalanine (FMLP) stimulated superoxide (O2-) release from human neutrophils. Neutrophils were pre-incubated with the range of concentrations of (-) naloxone that is administered in models of experimental sepsis (10(-6) - 10(-4.5) M). (-) Naloxone inhibited O2- release in a dose dependent manner. 02- produced by a cell-free xanthine-xanthine oxidase system was not inhibited by (-) naloxone, indicating that (-) naloxone was not scavanging O2-. There was no difference between the effect of (-) and (+) naloxone suggesting that the inhibition of O2- was not specific for an opiate receptor. Another opiate antagonist, nalorphine, as well as the opiate agonist, morphine, also inhibited O2- release in the same concentration range. There was no difference between the effect of naloxone and morphine.

Dose-Response Relationship, Drug↗
PubMed1985

Difference in monoamine oxidase activity measured by either liquid ion exchange or ion exchange resin chromatography in rat and cat brain.

Cat and rat brain monoamine oxidase (MAO) activity was measured with a radioisotopic procedure and two extraction methods. Results indicated an underestimation of MAO activity when liquid ion exchange chromatography (LIEC) was used instead of an ion exchange chromatographic method (IEC) to separate the different products of the deaminated tyramine, phenylethylamine, or serotonin. MAO produced aldehydic products which may be found in the incubation medium and may be extracted with the substrate in the chloroform phase by the LIEC method. In cat brain, the resulting underestimation of the MAO activity was prevented by the addition of nicotinamide adenine dinucleotide (10(-3) M) in the incubation medium or by allowing a 2-h period between the end of incubation and the LIEC extraction procedure. In the rat brain, the same result was obtained by the addition of an equimolar mixture of nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate in reduced form (NAD-NADPH, 10(-3) M). Using the IEC method, the NAD decreased only the deamination of tyramine and serotonin in rat brain. This study suggests that the use of an IEC method to evaluate MAO activity is more accurate for the estimation of the enzymatic activity.

Animals↗
PubMed1985

Synergistic combination of menogarol and melphalan and other two drug combinations.

Menogarol is a new anthracycline undergoing phase I clinical trial. We report here the lethality after 2 hr exposure to 2 drug combinations of menogarol and several antitumor agents. A new statistical procedure was used to identify synergistic combinations. Most of these combinations were additive, except for menogarol plus melphalan, which was synergistic. Adriamycin plus melphalan was also synergistic. The menogarol-melphalan combination wa studied in detail with regard to the effect of dose and drug-schedule, lethality for exponential and plateau phase cells and effect on cell cycle progression. Although the combination was synergistic for exponential cells it was additive for plateau phase cells. The combination exerted a synergistic effect in inhibiting progression of cells through the cell cycle. After 2 hr menogarol exposure cells were blocked in G2 for about 12 hr following which the block was reversed. This reversal was inhibited when menogarol was combined with melphalan. The uptake of menogarol or melphalan was not changed in the presence of the other drug.

Animals↗
PubMed1985

Induction of experimental autoimmune thyroiditis in mice with in vitro activated splenic T cells.

Spleen cells from CBA/J or SJL mice sensitized with mouse thyroglobulin (MTg) and lipopolysaccharide (LPS) could be activated in vitro with MTg to transfer experimental autoimmune thyroiditis (EAT) to normal syngeneic recipients. EAT induced by these transferred cells was similar in incidence and severity to EAT induced by active immunization of mice with MTg and adjuvant and cells from EAT-resistant Balb/c mice could not be activated to induce EAT. The specific antigen MTg was required both for initial sensitization of the mice and for activation of spleen cells in vitro. The cells that were active in transferring EAT to mice were shown to be T cells. Removal of B cells from the cultured spleen cells had no effect on the ability of the cells to induce EAT.

Animals↗