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Biomedical subjects

R A Lewis

Publications and source records attributed to R A Lewis.

At least 343 records · Page 19Linked to original sources
PubMed1982

Inhibition of DNA polymerase by captan.

Captan inhibits DNA polymerases of both eukaryotic and prokaryotic sources. When polymerases were employed in assays with various nucleotides as template-primer, no specificity in the base sequence of polynucleotide was required for inhibition. Sucrose gradient centrifugation and preincubation studies showed the inhibition was caused by an irreversible alteration of the polymerase. Captan and DNA compete for the same site on the polymerase, thus DNA can serve a protective role in the elimination of captan's action. The pyrophosphate exchange activity associated with the polymerase is not inhibited by captan and the fidelity with which DNa polymerase I copies the DNA template also is not altered by captan treatment.

Animals↗
PubMed1982

Mechanism of inhibition of Escherichia coli RNA polymerase by captan.

Captan (N-trichloromethylthiocyclohex-4-ene-1,2-dicarboximide) was shown to inhibit RNA synthesis in vitro catalysed by Escherichia coli RNA polymerase. Incorporation of [gamma-32P]ATP and [gamma-32P]GTP was inhibited by captan to the same extent as overall RNA synthesis. The ratio of [3H]UTP incorporation to that of [gamma-32P]ATP or of [gamma-32P]GTP in control and captan-treated samples indicated that initiation was inhibited, but the length of RNA chains being synthesized was not altered by captan treatment. Limited-substrate assays in which re-initiation of RNA chains did not occur also showed that captan had no effect on the elongation reaction. Studies which measured the interaction of RNA polymerase with template DNA revealed that the binding of enzyme to DNA was inhibited by captan. Glycerol-gradient sedimentation of the captan-treated RNA polymerase indicated that the inhibition of the enzyme was irreversible and did not result in dissociation of its subunits. These data are consistent with a mechanism in which RNA polymerase activity was irreversibly altered by captan, resulting in an inability of the enzyme to bind to the template. This interaction was probably at the DNA-binding site on the polymerase and did not involve reaction of captan with the DNA template.

Binding Sites↗
PubMed1982

Corneal anesthesia after percutaneous radiofrequency trigeminal rhizotomy. A retrospective study.

Fifteen patients with intentional or unintentional V1 lesions one to five years after percutaneous radiofrequency trigeminal rhizotomy were examined. No corneal changes developed in the majority of patients. These findings raise the question as to the precipitating factor(s) for neuroparalytic keratitis. The suggested mechanism for preservation of corneal function appears to be intact axonal mechanism(s).

Aged↗
PubMed1982

The bacteriostatic action of captan: alterations of RNA metabolism in E. coli.

The growth of E. coli in broth cultures was inhibited in a concentration dependent manner by the addition of captan. Treated cells showed no evidence of lysis and maintained a viable character. Following a single exposure to 500 microM captan, cells exhibited a lag period of approximately six hr and then grew to maximum density. During the period of arrested growth, captan apparently inhibited the synthesis of RNA as measured by the incorporation of tritiated uridine into acid-insoluble material. This apparent inhibition was due in part to a captan mediated decrease in the uptake of uridine from the media into the soluble nucleotide pool. By means of RNA isolation, polyacrylamide gel electrophoresis, and RNA quantitation, it was demonstrated that captan caused a selective loss of large (16 and 23 S) ribosomal RNA's. However, cellular concentrations of transfer RNA and 5S ribosomal RNA were unaffected by captan treatment.

Captan↗
PubMed1982

A review of recent contributions on biologically active products of arachidonate conversion.

Leukotrienes (LTs) C4, D4 and E4, the recognized components of slow reacting substance of anaphylaxis (SRS-A), have previously been shown to have contractile activities for guinea pig pulmonary and ileal smooth muscles; LTB4 has been shown to possess chemotactic activity for neutrophils in vitro. Based on data obtained by the use of structural analogs of the SRS-A LTs and of LTB4, we have recently determined a number of the structural bases for the biological function of each moiety. With regard to the SRS-A leukotrienes, analogs differed from the native structures in the position of the peptide side chain and/or the hydroxyl group, the number and position of ethylenic bonds, the chirality at optically-active centers, or the structures of the four polar substituents in the C-1 to C-6 region. Analogs of LTB4, differing in the stereochemistry of their ethylenic bonds, were evaluated for chemotactic activity both in vitro, using human neutrophils, and in vivo intracutaneously in the rhesus monkey. We propose that true receptors exist on the pulmonary parenchyma of the guinea pig for the SRS-A LTs and on the primate neutrophil for LTB4. Further, LTC4, LTD4 and LTE4 have been shown to elicit a wheal and prolonged flare in human skin, whereas LTB4 evokes a time-dependent induration. The interaction of these secondary mediators may be critical to a fully developed host inflammatory response to both immunologic and non-immunologic injury.

Animals↗
PubMed1982

U-50,488, a selective kappa opioid agonist: comparison to other reputed kappa agonists.

1. U-50,488 is a structurally novel, non-mu opioid. In the present experiments it was compared to the reputed kappa opioid agonists, ketazocine, ethylketocyclazocine and bremazocine as regards analgesic cross tolerance to morphine and U-50,488, antagonism of analgesia by naloxone and MR-2266 (in vivo pA2 determination), and narcotic antagonist properties (antagonism of morphine analgesia and precipitation of abstinence in morphine-dependent mice). 2. The analgesic mechanism of bremazocine was similar to that of U-50,488 but the former compound had, in addition, considerable mu-antagonist activity. The analgesic mechanisms of the ketazocines were less selective; both shared both mu and kappa agonist properties. U-50, 488, however, had no such mu agonist or antagonist effects and thus is a more selective kappa agonist. 3. This compound and its congeners may prove useful in the elucidation of the functions of kappa receptors in the central nervous system.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1982

Oxidative inactivation of leukotriene C4 by stimulated human polymorphonuclear leukocytes.

Leukotriene C(4) (LTC(4)) was metabolized by human polymorphonuclear leukocytes (PMNs) stimulated with phorbol myristate acetate (PMA) into three sets of products. These products differed in mobility on reverse-phase high-performance liquid chromatography (RP HPLC) from LTC(4) and also from leukotriene D(4) (LTD(4)) and leukotriene E(4) (LTE(4)), the sequential products of peptide cleavage of LTC(4). Products I, II, and III were eluted as doublets with an average retention time for each doublet of 7.5 +/- 0.3, 10.5 +/- 0.6, and 16.3 +/- 1.1 min (mean +/- SD), respectively, as compared with 13.8 min for LTC(4). Doublet I material was biologically inactive and showed <5% of the immunoreactivity of LTC(4), doublet II material had 1% of the spasmogenic activity of LTC(4) on the guinea pig ileum and was equally immunoreactive, and doublet III material was neither biologically active nor immunoreactive. When [14,15-(3)H]LTC(4) and [(35)S]LTC(4) were metabolized, all three doublet products retained the (3)H label, whereas only the doublet I and doublet II products retained the (35)S label. The UV absorbance spectra of the three sets of metabolites were as follows: doublet I, maximum at 280 nm with shoulders at about 270 and 290 nm; doublet II, maximum at 284.5 nm with shoulders at about 275 and 295 nm; and doublet III, maximum at 269 nm with shoulders at about 259 and 279 nm. The metabolism of LTC(4) to the three classes of functionally inactive products by stimulated PMNs was completely blocked by catalase and azide, indicating a requirement for H(2)O(2) and myeloperoxidase. When hypochlorous acid (HOCl)-considered to be a natural product of the interaction of myeloperoxidase, H(2)O(2), and chloride ion-was formed chemically and allowed to react with LTC(4), the resulting products were indistinguishable by UV and HPLC analyses from the doublet II and doublet III metabolites of LTC(4). The doublet II products were identified as the two diastereoisomeric sulfoxides of LTC(4) by comparison with synthetic reference compounds. The doublet III products were shown to be identical with synthetic samples of (5S, 12S)- and (5S, 12R)-6-trans-LTB(4). The formation of two diastereoisomeric LTC(4) sulfoxides and 6-trans-LTB(4) can be explained in terms of an S-chlorosulfonium ion as the initial reactive intermediate, which subsequently undergoes conversion to product II by hydrolysis and product III by carbocation formation.

Catalase↗
PubMed1982

Generation of leukotriene C4 from a subclass of mast cells differentiated in vitro from mouse bone marrow.

Bone marrow-derived mast cells, differentiated in vitro, demonstrate surface IgE, receptors and contain histamine in metachromatic granules, which are composed of chondroitin sulfate E proteoglycan rather than heparin proteoglycan. Activation of this subclass of mast cells with calcium ionophore A23187 resulted in generation of immunoreactive C-6-sulfidopeptide leukotriene in a dose- and time-dependent fashion. Isolation of immunoreactive C-6-sulfldopeptide leukotriene by reverse-phase high-performance liquid chromatography (RP-HPLC) revealed a retention time and a specific biologic activity identical to those of synthetic leukotriene C4 (LTC4). Neither radiolabeled nor immunoreactive conversion products of [3H]LTC4/LTC4 were recognized during RP-HPLC resolution of the supernatants. The failure of fresh bone marrow cultures to generate C-6-sulfidopeptide leukotriene in response to ionophore indicates that leukotriene generation is dependent upon cellular differentiation into a mast cell population. The amount of LTC4 generated during optimal ionophore stimulation, 90.9 +/- 7.5 ng per 10(6) cells, contrasts with the relatively low amounts of C-6-sulfidopeptide leukotriene generated by the conventional heparin-containing rat mast cells or mouse mastocytoma cells.

Animals↗
PubMed1982

Radioimmunoassay for leukotriene B4.

A rabbit immunized with leukotriene B(4) [LTB(4); (5S,12R)-6, 14-cis-8, 10-trans-icosatetraenoic acid] coupled to bovine serum albumin via the 12-oxy function of the lipid produced antibodies having an average association constant (K(a)) for [14,15-(3)H]LTB(4) of 3.2 x 10(9) M(-1) at 37 degrees C and in a concentration of 0.37 mug/ml of the immune plasma. When 10 mul of anti-LTB(4) and 3.9 nCi of [14,15-(3)H]LTB(4) (28 Ci/mmol; 1 Ci = 3.7 x 10(10) becquerels) were incubated in a volume of 250 mul, 50% inhibition of radioligand binding was achieved with 0.31 ng of LTB(4) and with 1.95 ng of (5S,12S)-6-trans-8-cis-LTB(4). The sulfidopeptide leukotrienes, LTC(4) and LTD(4), displaced the radioligand from this antibody with less than 1/100th the activity of LTB(4), and the diastereoisomers of 6-trans-LTB(4), 5-L-hydroxy-6-trans-8,11,14-cis-icosatetraenoic acid (5-HETE), and three prostaglandins were minimally effective. The specificity of this radioimmunoassay was further shown by assessment of the immunoreactive products generated from calcium ionophore (A23187)-activated rat serosal mast cells and human neutrophils after reversed-phase HPLC. Resolution of the supernatants from each cell type yielded a single immunoreactive peak that coeluted with synthetic LTB(4) and quantitatively correlated with the physical measurement by integrated A(269) in that peak; UV-absorbing peaks eluting at other retention times were not immunoreactive. The immunoreactive LTB(4) generated averaged 4.6 ng per 10(6) rat mast cells and resolution of the supernatants by reversed-phase HPLC without a prior extraction step gave a recovery of 54%, validating the direct applicability of this sensitive and specific assay for LTB(4), a highly potent chemotactic factor, to unfractionated biologic fluids.

Animals↗
PubMed1982

Cockayne syndrome.

The diagnosis of Cockayne syndrome was established with the aid of cranial computed tomography (CT) in a child with growth deficiency, mental retardation, and neurologic findings which are typical for this rare childhood disorder. Calcification of basal ganglia and hydrocephalus ex vacuo are neuropathologic characteristics of Cockayne syndrome which may be present on CT as early as 3 years of age.

Child, Preschool↗
PubMed1982

An empirical typology of dyadic formation.

The background of and justification for empirical typologies are outlined. Various family typologies are discussed. Data from a random sample of 291 couples are subjected to a cluster analysis on the dyadic interaction, dyadic preference, dyadic stability, and identification as a pair by others of the couple. Seven types of dyadic formation were found: Uncommitted; Structurally Isolated, Wife-Supported; Self-Selected Committed; Structurally Committed; Vital; Unformed; and Wife-Removed. The types are shown to differ on value consensus and couple happiness, as well as on some background factors. The contribution of the work to theories of dyadic formation and family typologies is discussed.

Adolescent↗
PubMed1982

The electrodiagnostic distinctions between chronic familial and acquired demyelinative neuropathies.

We compared the electrodiagnostic studies of 40 patients with chronic acquired demyelinative neuropathy and 18 patients with familial demyelinative neuropathy. Patients with acquired neuropathy had differential slowing of conduction velocity when distal latencies were compared with more proximal conduction velocities in the same nerve, when equivalent segments of different nerves were compared, and when dispersion of compound motor action potentials was examined. Conduction block was noted in some patients. Patients with familial disease had uniform conduction slowly of all nerve segments, and conduction block was not seen. Chronic acquired demyelinative neuropathy is characterized by multifocal slowing of nerve conduction, whereas familial demyelinative neuropathy is characterized by uniform conduction slowing.

Demyelinating Diseases↗
PubMed1982

Multifocal demyelinating neuropathy with persistent conduction block.

We describe five patients with a chronic asymmetric sensorimotor neuropathy most pronounced in the upper extremities with focal involvement of individual nerves. Diagnosis was established by electrophysiologic evidence of persistent multifocal conduction block. Sural nerve biopsy in three patients showed primarily demyelinating-remyelinating changes with varying degrees of fiber loss. Two patients had acute optic neuritis, indicating that the disorder was not always restricted to the peripheral nervous system. Two patients treated with corticosteroids improved, whereas three untreated patients had static deficits or steady progression of symptoms. Chronic multifocal demyelinating neuropathy with persistent conduction block seems to be a variant of chronic acquired demyelinating polyneuropathy and may be immunologically mediated.

Adult↗
PubMed1982

Retinopathy in juvenile-onset type I diabetes of short duration.

We evaluated the prevalence and severity of diabetic retinopathy in 173 juvenile-onset, type I diabetic subjects and 78 nondiabetic controls of similar age, race, and sex distribution by stereoscopic fundus photography and fluorescein angiography, performed by a standardized protocol and evaluated by five expert, masked observers. The overall prevalence of retinopathy was 18% in the diabetic group and 0% in the controls. Retinopathy prevalence increased with duration of diabetes in the diabetic group, with a prevalence of 1% from 0--4 yr after diagnosis, 25% after 5--9 yr, and 67% 10--16 yr after onset of the systemic disease. There was an independent association with age, with little retinopathy before age 15 and a 48% prevalence in older persons. Retinopathy was also found to be independently associated with the following: diabetic "control," evaluated semiquantitatively but on a masked basis; lens opacities; and frequency of daily insulin injections. Among the 166 diabetic subjects who had both angiography and photography, a retinopathy prevalence of 17% was detected by angiography and 11% by photography. This difference was statistically significant (P = 0.01). This study provides baseline data for use in estimating sample size in controlled trials of therapeutic measures to prevent retinopathy in juvenile diabetic populations. The study also supports the hypothesis that long-term hyperglycemia as well as changes (possibly hormonal in nature) associated with puberty are causally related to diabetic retinopathy.

Adolescent↗
PubMed1982

Selective effects of myo-inositol administration on sciatic and tibial motor nerve conduction parameters in the streptozocin-diabetic rat.

Time-dependent effects of experimental diabetes and dietary myo-inositol supplementation on motor nerve conduction velocity (MNCV) were assessed in two populations of motor nerve fibers in the rat hind limb. These two populations of large myelinated motor fibers, which innervate the musculature of the calf and the foot, were differentially affected by growth, experimental diabetes, and dietary myo-inositol. Dietary myo-inositol supplementation ameliorated the diabetes-induced MNCV impairment in both nerve fiber populations but with different time courses. These observations suggest metabolic or physiologic heterogeneity among populations of large myelinated motor fibers which may partially explain published discrepancies regarding the efficacy of dietary myo-inositol supplementation in improving slowed MNCV in the streptozocin-diabetic rat.

Age Factors↗