The genetics of type I (insulin dependent) diabetes mellitus.
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Asian People↗
Biomedical subjects
A Barnett
Publications and source records attributed to A Barnett.
Scotch eggs in a residential school.
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Adolescent↗
Pharmacology of non-sedating H1 antihistamines.
A review of the preclinical pharmacology of non-sedating H1 antihistamines includes comparative data on potency, duration of action, side effect liability, especially CNS depressant and anticholinergic activity and new approaches that may further enhance the efficacy of these newer compounds. Data discussed mainly involve studies in which multiple comparative agents were used and usually include astemizole, cetirizine, loratadine and terfenadine. New research approaches include the combination of PAF inhibition with antihistamine activity and the inhibitory effects these compounds may have on cellular influx in allergic diseases.
Animals↗
11C-SCH 39166, a selective ligand for visualization of dopamine-D1 receptor binding in the monkey brain using PET.
The new selective D1-dopamine receptor antagonist SCH 39166 was labelled with the positron emitting isotope 11C and used as ligand for visualization of dopamine-D1 receptor binding in Cynomolgus monkeys by PET. After intravenous administration of the ligand a marked uptake of radioactivity was recorded in the D1-dopamine receptor-rich striatum and neocortex but not in the dopamine receptor-poor cerebellum. The uptake of radioactivity in striatum and neocortex was markedly displaced after the intravenous injection of a high dose of the D1-dopamine receptor antagonist SCH 23390 but not after the 5-HT2 receptor antagonist ketanserine. 11C-SCH 39166 should be a useful tool to explore D1-dopamine receptor characteristics in the living human brain by PET.
Animals↗
Anaphylactic reactions to a psyllium-containing cereal.
Historical data were obtained by questionnaire and telephone survey on 20 of 24 women with reported allergic reactions to a psyllium-containing cereal, Heartwise. Protein fractions from this new cereal, as well as from psyllium mucilloid and a psyllium-containing laxative, Metamucil, were extracted, quantitated, and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Patients' sera were collected, and specific IgE and IgG antibodies to these psyllium antigens were detected by immunoblotting techniques. Of the 20 women evaluated, all but six were nurses. Eighteen (90%) of the women had historical and/or laboratory evidence of atopy. Exposures included ingestion or dispensing of psyllium-containing products. Only three women denied prior exposure to psyllium. Symptoms developed shortly after small amounts of the cereal were ingested and most commonly included moderate to severe wheezing, throat and chest tightness, and urticaria. All the women required medical therapy, 11 (55%) in an emergency room. Specific IgE and IgG antibodies to various psyllium protein fractions were documented in all the subjects. It was concluded that individuals sensitized by occupational exposure to psyllium dust are at high risk for allergic reactions to ingested psyllium-containing products.
Adult↗
Synthesis of carbon-11 labelled SCH 39166, a new selective dopamine D-1 receptor ligand, and preliminary PET investigations.
SCH 39166 [(-)-trans-6,7,7a,8,9, 13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo(d)naphtho-(2,1- b)azepine] is a new more selective dopamine D-1 receptor antagonist than the widely used SCH 23390. [11C]SCH 39166 was prepared by N-methylation of the desmethyl compound SCH 40853 [(-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-5H- benzo(d)naphtho-(2,1-b)azepine] with [11C]methyl iodide. Reaction in acetone with subsequent straight-phase semi-preparative HPLC resulted in 20-30% radiochemical yield (from EOB and decay-corrected) with a total synthesis time of 35-40 min and a radiochemical purity greater than 99%. The specific activity obtained at EOS was about 1500 Ci/mmol (55 GBq/mumols). [11C]SCH 39166 was injected into a Cynomolgus monkey. PET-analysis demonstrated accumulation in the striatum, a region known to have a high density of dopamine D-1 receptors. In a displacement experiment, radioactivity in the striatum was markedly reduced after injection of 6 mg unlabelled SCH 23390, thus demonstrating the specificity and reversibility of [11C]SCH 39166 binding to dopamine D-1 receptors.
Animals↗
[3H]SCH 39166, a new D1-selective radioligand: in vitro and in vivo binding analyses.
SCH 39166 [(-)-trans-6,7,7a,8,9, 13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo-[d]naphtho[2, 1b]azepine] has recently been described as a selective D1 antagonist and has entered clinical trials for the treatment of schizophrenia. The tritiated analogue of this compound, [3H]SCH 39166, has now been synthesized and characterized for its in vitro and in vivo binding profiles. [3H]SCH 39166 binds to D1 receptors in a saturable, high-affinity fashion, with a KD of 0.79 nM. In competition studies, D1-selective antagonists like SCH 23390 displaced the binding of [3H]SCH 39166 with nanomolar affinities, whereas antagonists of other receptors exhibited poor affinity. In vivo, [3H]SCH 39166 bound to receptors in rat striatum in a fashion suggestive of D1 selectivity. Further, when the time course for the binding of [3H]SCH 39166 was compared with the behavioral time course of the unlabeled compound, the two durations of action were virtually indistinguishable. Similar studies were performed for SCH 23390 and its tritiated analogue, but the in vivo binding of this radioligand exhibited a duration of action far greater than the behavioral activity of the unlabeled drug. In concert, these data demonstrate that [3H]SCH 39166 selectively labels D1 receptors in vitro and in vivo, and that this drug is superior for in vivo imaging of the D1 receptor.
Animals↗
In vivo binding of SCH 39166: a D-1 selective antagonist.
SCH 39166 [(-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl- 5H-benzo[d]naphtho-[2,1b]-azepine] has been identified previously as a potent and selective D-1 antagonist. These studies demonstrated that SCH 39166 binds to the D-1 receptor in vitro and inhibits the rat conditioned avoidance response, a test predictive of antipsychotic activity. The current study demonstrates that SCH 39166 inhibits the in vivo binding of [125I]SCH 38840 to D-1 receptors in rat striatal tissue with an ED50 of 11.67 nmol/animal or 0.016 mg/kg s.c. SCH 39166 did not inhibit the in vivo binding of [125I]SCH 38840 to rat frontal cortex, suggesting that, unlike other D-1 antagonists, SCH 39166 was not binding to 5-hydroxytryptamine (5-HT)2 receptors in vivo. The in vivo binding of SCH 39166 to D-2 receptors was studied using [3H]raclopride and demonstrated that SCH 39166 did not bind to D-2 receptors up to doses of 100 mumol/animal or approximately 150 mg/kg s.c. Further studies to determine the in vivo selectivity of SCH 39166 utilized N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) to inactivate selected neurotransmitter receptors. Preadministration of SCH 39166, at doses as low as 0.01 mg/kg s.c., produced a statistically significant protection of D-1 receptors from EEDQ inactivation. SCH 39166 produced a similar protection of 5-HT2 receptors only at the highest dose tested, 10 mg/kg s.c., whereas there was no protection of D-2 sites even at this high dose.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
High-resolution linkage mapping for susceptibility genes in human polygenic disease: insulin-dependent diabetes mellitus and chromosome 11q.
Insulin-dependent diabetes mellitus (IDDM) has a complex pattern of genetic inheritance. In addition to genes mapping to the major histocompatibility complex (MHC), several lines of evidence point to the existence of other genetic susceptibility factors. Recent studies of the nonobese diabetic mouse (NOD) model of IDDM have suggested the presence, on mouse chromosome 9, of a susceptibility gene linked to the locus encoding the T-cell antigen, Thy-1. A region on human chromosome 11q is syntenic to this region on mouse chromosome 9. We have used a set of polymorphic DNA markers from chromosome 11q to investigate this region for linkage to a susceptibility gene in 81 multiplex diabetic pedigrees. The data were investigated by maximization of lod scores over genetic models and by multiple-locus affected-sib-pair analysis. We were able to exclude the presence of a susceptibility gene (location scores less than -2) throughout greater than 90% of the chromosome 11q homology region, under the assumption that the susceptibility factor would cause greater than 50% of affected sib pairs to share two alleles identical by descent. Theoretical estimates of the power to map susceptibility genes with a high-resolution map of linked markers in a candidate region were made, using HLA as a model locus. This result illustrates the feasibility that IDDM linkage studies using mapped sets of polymorphic DNA markers have, both for other areas of the genome in IDDM and for other polygenic diseases. The analytic approaches introduced here will be useful for affected-sib-pair studies of other complex phenotypes.
Chromosome Mapping↗
The current-voltage relation of an aqueous pore in a lipid bilayer membrane.
In a recent paper, Glaser et al. [1988) Biochim. Biophys. Acta 940, 275-287) use an inappropriate formula for the current-voltage relation of a pore to analyze the data from an electroporation experiment. They proceed to use their data analysis to support their contention that the voltage dependence of the membrane conductivity is caused entirely by the nonlinearity of the current-voltage relation of the pores, changes in pore size and number being unimportant. This contention is no longer justified. The formula that Glaser et al. use is valid for a one-dimensional problem, but they apply it to a pore that has a three-dimensional structure. Although the corresponding one-dimensional problem can be reduced to quadratures, only upper and lower bounds on the conductivity can be found for the three-dimensional problem without solving a partial differential equation.
Electrodes↗
Transaxillary subpectoral augmentation in the ptotic breast: augmentation by disruption of the extended pectoral fascia and parenchymal sweep.
A new approach to transaxillary subpectoral breast augmentation based on an understanding of the anatomy of the extended pectoral fascia and the inframammary fold allows for the widespread application of this technique. Previous authors have stated that transaxillary augmentation is only applicable to a small subset of the general population and is contraindicated in mild degrees of ptosis or in large augmentations. The new approach, augmentation by disruption of the extended pectoral fascia technique and the parenchymal sweep maneuver, prevents high-riding implants and double folds. By disrupting the fascia, the lower portion of the implant is able to sit in a partially subglandular rather than subfascial plane. The anatomy and clinical implications of the extended pectoral fascia are discussed, as is the augmentation by disruption of the extended pectoral fascia technique. The parenchymal sweep maneuver is also described. Clinical cases are presented.
Breast↗
The radiographic changes of scleroderma in the hands.
Hand radiographs from 160 patients with scleroderma were reviewed. The presence of calcinosis distal to the metacarpophalangeal joints was significantly associated with the female sex, disease duration over 10 years, digital ulceration, telangiectasia, tuft erosion and the presence of anticentromere antibodies. The presence of calcinosis proximal to the metacarpophalangeal joints was significantly associated with tuft erosions and erosions involving all joints. The lack of distal calcinosis was significantly associated with anti Scl 70 and antinucleolar antibodies. The prevalence of other radiological manifestations of scleroderma such as osteoarthritis, erosions and dorsal tuft modelling was documented. Specific radiological findings correlate with certain clinical and serological characteristics in scleroderma.
Calcinosis↗
Nipple-areola location in breast reconstruction: a simplified approach.
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Breast↗
SCH 39370, a neutral metalloendopeptidase inhibitor, potentiates biological responses to atrial natriuretic factor and lowers blood pressure in desoxycorticosterone acetate-sodium hypertensive rats.
SCH 39370 (N-[N-[1-(S)-carboxyl-3-phenylpropyl]-(S)-phenyl-alanyl]-(S)-isoserin e) is a potent and specific inhibitor of neutral metalloendopeptidase (NEP) from rabbit kidney (IC50 = 11.2 +/- 1.9 nM) and is devoid of angiotensin-converting enzyme inhibitory activity at 1 microM. We evaluated the effect of NEP inhibition with SCH 39370 on the inactivation of atrial natriuretic factor (ANF) and on cardiovascular function in rats. SCH 39370 effectively prevented in vitro degradation of ANF (99-126) by a purified rabbit kidney NEP. SCH 39370 (30 mg/kg s.c) significantly delayed the disappearance of immunoreactive (ir) ANF from plasma in rats after an i.v. infusion of ANF (1 microgram/kg/min for 30 min): the plasma ir ANF level at 15 min postinfusion was 1.5 +/- 0.3 ng/ml vs. 0.3 +/- 0.04 ng/ml in the control. SCH 39370 also delayed the disappearance of ir ANF after infusion of the peptide (0.1 microgram/kg/min for 30 min) which increased plasma levels to those observed during volume expansion. This effect was accentuated markedly in rats with bilateral nephrectomy. The hypotensive response to injection of ANF (30 micrograms/kg i.v.) in spontaneously hypertensive rats (-38 +/- 6 mm Hg vs. -13 +/- 2 mm Hg in the control) and the diuretic and natriuretic responses to ANF in normal rats were potentiated by SCH 39370 (30 mg/kg s.c.), respectively. The results suggest that NEP can play a role in ANF disposition in vivo and that potentiation of the biological activities of high doses of ANF by SCH 39370 may be consequent to its inhibitory effect on ANF degradation.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Autoantibody to gp50, a glycoprotein shared in common between fibroblasts and lymphocytes, in progressive systemic sclerosis.
Five out of 51 sera (10%) from patients with progressive systemic sclerosis reacted by immunoblotting with tissue concanavalin A binding glycoproteins of 50 kD and 45 kD Mr, whereas only one out of 133 control sera gave the same reaction (P less than 0.001). The antigens were localized to the microsomal fractions of tissues and were eluted from concanavalin A affinity columns by the competing sugar alpha-D-methymannoside but not by lactose, fucose or N-acetylglucosamine. Serum reactivity with these antigens was seen with a variety of human and porcine tissues and with human, porcine, bovine and canine spleens. Immunoblotting with cultured human fibroblasts and with human lymphocytes showed reactivity with the 50-kD component (gp50) only. No reactivity was seen with bovine or human endothelial cells or with HeLa, Hep-2 or mouse 3T3 cells. The gp50 antigen in human fibroblasts and lymphocytes and in human spleen had identical isoelectric points by two-dimensional immunoblotting, suggesting that they are the same molecule. These observations suggest that circulating autoantibodies to a 50-kD glycoprotein of fibroblasts and lymphocytes are present in some patients with progressive systemic sclerosis. The microsomal localization of the molecule suggests that it may have a role in the pathogenesis of progressive systemic sclerosis.
Adult↗
Use of the selective benzodiazepine-1 (BZ-1) ligand [3H]2-oxo-quazepam (SCH 15-725) to localize BZ-1 receptors in the rat brain.
Receptor autoradiographic techniques have been used to localize benzodiazepine-1 (BZ-1) receptor sites by employing a tritiated form of 2-oxo-quazepam (SCH 15-725), a metabolite of the benzodiazepine quazepam (SCH 16-134). Labeling of the receptors was quantitatively determined to be most abundant in areas of the rat brain known through previous autoradiographic studies to bind preferentially with BZ-1 selective ligands. These areas include lamina IV of the parietal cortex, substantia innominata, anterior amygdaloid nucleus, substantia nigra, zona incerta, and molecular layer of the cerebellum. Autoradiographic localization of binding sites for [3H]2-oxo-quazepam provides additional support for the hypothesis that this compound identifies the BZ-1 receptor subtype and demonstrates the utility of this ligand for quantitation of the distribution and density of these sites.
Animals↗
Pharmacological and behavioral effects of D1 dopamine antagonists.
This work includes the effects of SCH 23390 and related benzazepines on behavior and attempts to relate these effects to their D1 dopamine antagonist action. Effects on conditioned avoidance responding (CAR) in rats were studied under the same conditions in which in vivo binding of the radioiodinated D1 specific benzazepine 125I-SCH 38840 was measured. It was found that there is very close agreement between the time-course for antagonism of CAR and for in vivo displacement of 125I-SCH 38840 from rat striatum. The effect of SCH 23390 in CAR in monkeys was compared with standard anti-psychotics and although its oral potency was reasonable, its duration was very short (1-2 hours at 5 times its minimal effective dose for statistically significant reduction of avoidance). It is concluded from this and prior work that SCH 23390 and other D1 specific benzazepines inhibit CAR at the same doses that bind to D1 receptors in the CNS and that D1 specific antagonists are behaviorally effective at doses that do not produce D2 receptor effects (e.g. increased plasma prolactin levels, catalepsy).
Animals↗