The distribution of binding sites for [125I]Bolton-Hunter substance P (BHSP) was investigated in vasa deferentia from normal, capsaicin-pretreated and vehicle-pretreated guinea-pigs, using qualitative and quantitative autoradiography. Dense binding of BHSP was seen over the outer longitudinal muscle with less over the inner longitudinal muscle. Very low specific binding occurred to the circular muscle and was absent in the mucosa. Characterization in slide-mounted sections showed that binding was saturable and of high affinity, with equilibrium dissociation constant (KD) 91 +/- 15 pM. BHSP was displaced by substance P greater than neurokinin A greater than neurokinin B, suggesting binding to NK-1 receptors. Capsaicin pretreatment had no effect on the lengthwise distribution of binding sites but significantly altered their relative distribution between the different smooth muscle layers. There was a very marked increase in BHSP binding over the inner longitudinal muscle and the inner part of the circular muscle layer, whereas binding was virtually abolished over the outer longitudinal muscle, compared with vehicle control. Capsaicin-sensitive binding sites over the outer longitudinal muscle may be located presynaptically on capsaicin-susceptible primary afferent sensory neurons. In contrast, the increase in number of binding sites associated with the inner longitudinal muscle may be due to receptor upregulation resulting from loss of sensory innervation, and suggests that these binding sites are postsynaptic.

Animals↗

PubMed1989

Dopamine transporter: solubilization from dog caudate nucleus.

3H-GBR 12935 was used to label the digitonin-solubilized dopamine transporter from dog caudate nucleus. Specific binding to soluble fractions was observed in dog caudate but was absent in rat cerebellum. Binding to the solubilized transporter sites was saturable and of high affinity (Bmax = 2.57 +/- 0.60 pmol/mg protein, KD = 23.42 +/- 2.24 nM, n = 4). Heating or addition of trypsin abolished specific binding in the soluble fractions. In competition studies, soluble 3H-GBR 12935 binding was inhibited by mazindol, GBR 12909, nomifensine, dimethocaine, dopamine, (-) cocaine, and (+) cocaine in a manner typical of binding to the dopamine transporter. As expected, tomoxetine and citalopram, inhibitors of norepinephrine and serotonin uptake, respectively, were weak competitors of 3H-GBR 12935 binding.

Animals↗

PubMed1989

Serum thyrotropin concentrations are more highly correlated with serum triiodothyronine concentrations than with serum thyroxine concentrations in thyroid hormone-infused thyroidectomized rats.

To assess the relative role of circulating T4 and T3 in the regulation of serum TSH, we have measured serum T4, T3, and TSH concentrations in normal and thyroidectomized rats, some of which were chronically infused with T3 or T4. Serum T3, T4, and TSH concentrations were measured 7 and 14 days after surgery. Some groups of infused rats were mildly hypothyroid, as judged by elevated serum TSH concentrations. At both 7 and 14 days, there was a significant inverse correlation between serum T3 and serum TSH concentrations (day 7, r = 0.65, P less than 0.01; day 14, r = 0.71, P less than 0.01). The coefficients for the inverse correlations between serum T4 and TSH concentrations were 0.37 on day 7 (P less than 0.05) and 0.37 (P less than 0.05) on day 14. Linear regression analysis was performed using TSH as the dependent variable for outcome and serum T3 and T4 concentrations as the independent predictor variables. This analysis revealed that after controlling for T3, TSH and T4 were no longer significantly correlated (P = 0.14). The correlation between T3 and TSH remained highly significant. These results suggest that in the euthyroid and mildly hypothyroid rat, serum T3 has a greater inhibitory effect on TSH secretion than does serum T4.

Animals↗

PubMed1989

Dopamine transport sites selectively labeled by a novel photoaffinity probe: 125I-DEEP.

The dopamine transporter was labeled using a photosensitive compound related to GBR-12909, 125I-1-[2-(diphenylmethoxy)ethyl]-4-[2- (4-azido-3-iodophenyl)ethyl]piperazine (125I-DEEP). 125I-DEEP bound reversibly and with high affinity to the dopamine transport protein in the absence of light and could be covalently attached to the protein following exposure to UV light. In rat striatal homogenates, 125I-DEEP was found to incorporate covalently into a protein with apparent molecular weight of 58,000 Da. The properties of this binding protein were characteristic of the dopamine transporter since covalent attachment could be inhibited by dopamine-uptake blockers with the proper pharmacological rank order of potencies. Covalent binding was also inhibited in a stereospecific manner by (+) and (-) cocaine, as well as other cocaine analogs. The protein was not found in the cerebellum. The dopamine transporter appears to exist in a glycosylated form since photoaffinity-labeled transport sites could adsorb to wheat germ-agglutinin and could be specifically eluted from the column by beta-N-acetylglucosamine.

Affinity Labels↗

PubMed1989

Reduction of sternal infection by application of topical vancomycin.

Sternal or mediastinal infection after heart operations occurs infrequently but carries a high cost in money, morbidity, and mortality. At our hospital, Staphylococcus nonaureus causes most of these infections and is uniformly sensitive to vancomycin. In a prospective study of 416 patients having cardiac operations, randomized by hospital record number, topical vancomycin was applied to the cut sternal edges in 223 patients (group V) and was omitted in the control group (C) of 193 patients. The vancomycin was applied in a hemostatic paste of topical thrombin and powdered absorbable gelatin; in the control group only the hemostatic paste was applied. All patients received prophylactic systemic antibiotics for 2 days. Sternal infection occurred in one patient in group V (0.45%) and in seven patients in group C (3.6%) (p = 0.02). Infection also correlated with longer operative times (p = 0.027). By multivariate testing, vancomycin (p = 0.013) and shorter operative times (p = 0.014) independently predicted reduced infection rates. In the one patient with an infection in group V, Staphylococcus aureus was cultured; this organism was also cultured in two patients in group C, with Staphylococcus nonaureus being the culprit in the other five patients with sternal infections in group C. Topical vancomycin applied to the cut sternal edges reduces the risk of postoperative sternal infection.

Administration, Topical↗

PubMed1988

Should prophylactic anticonvulsants be administered to patients with newly-diagnosed cerebral metastases? A retrospective analysis.

We analyzed a retrospective series of 195 patients with documented intracerebral metastases (ICM) to assess the frequency of late seizure development and the impact of prophylactic anticonvulsants. Eighteen percent of the patients presented with seizures. Of the remaining patients, 40% received prophylactic anticonvulsants (diphenylhydantoin [DPH] in greater than 90%). Ten percent developed late seizures at an interval from the diagnosis of ICM ranging from 1 to 59 weeks. No patient with a posterior fossa lesion developed seizure; conversely, patients with evidence on initial examination of cerebral hemispheric dysfunction had a higher incidence of late seizure development. The incidence of seizure was virtually identical in patients who received DPH compared with those in whom it was withheld, although two thirds of patients who developed seizure while on DPH had a serum anticonvulsant level that was subtherapeutic. Based on the above findings and until prospective data become available, we recommend that anticonvulsants be withheld in newly-diagnosed patients with ICM until the first seizure.

Adult↗

PubMed1988

The role of epsilon-aminocaproic acid in reducing bleeding after cardiac operation: a double-blind randomized study.

Sixty patients scheduled for elective coronary artery bypass graft operations were randomly assigned to receive epsilon-aminocaproic acid or placebo to test whether antifibrinolytic therapy would decrease postoperative bleeding. A small but significant decrease in bleeding was observed in the treated group without complications resulting from treatment with epsilon-aminocaproic acid.

Aminocaproates↗

PubMed1987

The distribution of beta-adrenoceptors in dog kidney: an autoradiographic analysis.

The distribution of beta-adrenoceptors in slide-mounted dog kidney sections was determined using the radioligand (-)-[125I]cyanopindolol ((-)-[125I]CYP) and autoradiography. Using conditions designed to prevent (-)-[125I]CYP binding to non-beta-adrenoceptor sites, biochemical studies revealed that (-)-[125I]CYP binding equilibrated within 150 min (K1 = 3.2 X 10(8) M-1 min-1), was saturable (KD = 30.72 +/- 2.96 pM; Bmax = 0.57 +/- 0.03 fmol/section, n = 4) and stereoselective with respect to the stereoisomers of propranolol and pindolol. Delineation of beta-adrenoceptor subtypes with the selective beta 1-adrenoceptor antagonist betaxolol and beta 2-adrenoceptor antagonist ICI 118,551 demonstrated that the proportions of beta 1-: beta 2-adrenoceptors was between 1:6 and 1:11. Autoradiographic studies showed that beta 1-adrenoceptors were localized on the juxtaglomerular apparatus and glomeruli, while beta 2-adrenoceptors were localized on medullary rays. The distribution of beta-adrenoceptors with respect to renal function in the dog kidney is discussed.

Adrenergic beta-Antagonists↗

PubMed1987

Characterization and localization of (-)[125I]-cyanopindolol binding to non-beta-adrenoceptor sites in dog kidney.

1. (-)[125I]-Cyanopindolol (CYP) binding to non-beta-adrenoceptor sites in dog kidney was characterized in homogenate preparations and their distribution in sections determined using autoradiography. 2. In homogenate studies, (-)[125I]-CYP bound to a single population of non-interacting sites (Bmax = 5.45, s.e.m. = 1.00 fmol/mg wet weight; nH = 0.99, s.e.m. = 0.01) with high affinity (KD = 3.84, s.e.m. = 0.76 nmol/l, n = 40. 3. In competition studies, compounds selective for alpha- and beta-adrenoceptors, muscarinic cholinoceptors and receptors for 5-HT, histamine and benzodiazepines, calcium channel antagonists, catecholamine uptake inhibitors, MAO inhibitors and adrenergic neurone blockers were ineffective at concentrations of 10 mumol/l. 4. Compounds selective for dopamine D1-receptors (fluphenazine, SCH 23390 and SK & F 82526) and D2-receptors (pimozide, domperidone, spiperone, haloperidol, sulpiride, cis- and trans-flupenthixol) competed with similar affinities (5-25 mumol/l) for (-)[125I]-CYP binding. 5. In autoradiographic studies, (-)[125I]-CYP binding to non-beta-adrenoceptor sites was localized over glomeruli, juxtaglomerular apparatus, distal tubules, blood vessels and medullary rays and tubules. 6. It is concluded that in dog kidney, (-)[125I]-CYP binds to a site closely associated with dopamine receptors.

Adrenergic beta-Antagonists↗

PubMed1987

Malignant melanoma in the elderly.

Explore the source record for details and available documents.

Age Factors↗

PubMed1986

Autoradiographic analysis of (-)-[125I]-CYP binding in mouse kidney.

The distribution and binding characteristics of the radioligand (-)-[125I]-cyanopindolol (CYP) have been examined in slide mounted mouse kidney sections, using the technique of in vitro labelling and autoradiography. (-)-[125I]-CYP binding to sections was of high affinity (KD = 55.8 pmol/l, s.e.m. = 8.1, n = 4) to a single population of non-interacting sites (nH = 0.95, s.e.m. = 0.01, Bmax = 0.74 fmol/section, s.e.m. = 0.12, n = 4) and stereoselective with respect to the (-)- and (+)-isomers of both propranolol and pindolol. Autoradiographic studies showed that (-)-[125I]-CYP binding was localized to areas in the renal cortex and medulla. Both cortical and medullary binding were abolished by the inclusion of (-)-propranolol (1 mumol/l) in the incubation medium, whereas (-)-isoprenaline (200 mumol/l) selectively abolished cortical binding. Medullary binding could be prevented by the inclusion of the lipophilic compounds cinanserin (10 mumol/l), haloperidol (10 mumol/l) or phentolamine (10 mumol/l), either alone or together or by washing at 37 degrees C. These results suggest that medullary binding sites are lipid rather than receptor-related. In conclusion, in mouse kidney sections, (-)-[125I]-CYP binds to discrete areas in the cortex and medulla. Cortical binding sites have the molecular characteristics of beta-adrenoceptors while medullary binding sites are lipid-related. Caution should therefore be exercised when defining non-specific binding of lipophilic radioligands. The autoradiographic technique is useful for discriminating between receptor and non-receptor binding sites.

Animals↗

PubMed1986

Multipoint linkage analysis.

A formula is given for the advantage of n-point sampling, which approaches infinity with n. However, 2-point and 3-point analyses extract nearly all the information in such samples and at the same time communicate this information as lods and chi 2, which can be combined with other data by simple addition without reevaluation of the likelihood. When null interference is assumed, map distances and multiple recombination frequencies are inflated, and there is substantial loss of efficiency and of support for the correct order.

Animals↗

PubMed1985

Efficiency of lod scores for representing multiple locus linkage data.

The problem of compact, fully efficient representation of multilocus data has not yet been solved. Lod scores can be used to map multilocus data, but because of certain statistical problems, this method loses some information. However, simulation studies show that for distances less than 10 or 20 cMo, where there is little danger of huge overestimates of distance, the lod score method yields estimators just as good as maximum likelihood (ML). Since short distances are the most important, the lod method is quite efficient. Its main drawback is misrepresentation of the likelihood under wrong gene orders. This problem can be ameliorated with a single multipoint calculation under each order. Thus, representation of multipoint data with lod scores can be very practical.

Biometry↗

PubMed1985

Construction of conditional lod tables from multiple-locus linkage data.

Although multipoint linkage data are becoming quite common, economical and efficient methods for presenting these data are not yet in use. Tables giving the full likelihood function would be very voluminous, whereas reduction to standard lods destroys part of the information. We suggest a special lod table representation which preserves nearly all the information about both gene order and genetic map distance at a great reduction in data presented. Conditional lods, coined "c-lods" to distinguish them clearly from ordinary lods, are calculated for distances between each adjacent pair of loci, with all distances among other loci in the system conditionally optimized. Thus, in an n-locus system, conditional lods are presented for the n - 1 adjacent pairs of loci only. The principal reason for reporting lod scores is the potential for combining data from separate studies to reach conclusive evidence for linkage and gene order. Because estimates of recombination are different in each set of data, the crux of the problem is to present scores that provide a close approximation to the true likelihood away from maximum likelihood (ML). The sum of conditional lods closely approximates the likelihood throughout the domain. Therefore, conditional lods contribute appropriately when mapping from several sources of data, so contradictory estimates can be reconciled efficiently.

Biometry↗