Binding characteristics of (+)-, (+/-)- and (-)-[125iodo] cyanopindolol to guinea-pig left ventricle membranes.
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Biomedical subjects
Publications and source records attributed to G Engel.
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Chest roentgenograms and medical records were reviewed on 91 consecutive patients having orchiectomy for advanced carcinoma of the prostate during a 4-year period. Our purpose was to investigate the potential of antiandrogen therapy for inducing regression of prostate pulmonary metastases and respiratory difficulty accompanying lymphangitic spread. Patients encountered during the study period who had lung metastases but refused orchiectomy and were treated with oral estrogens were also included. Antiandrogen therapy was found to be effective in inducing regression of prostatic pulmonary metastases and respiratory distress accompanying lymphangitic spread in those patients who had no prior hormonal manipulation.
The nephrogram is a sensitive indicator of renovascular compromise. An infrequently reported but characteristic nephrographic abnormality is the cortical rim nephrogram. This "rim sign" refers to a thin nephrographic rim outlining a kidney with an otherwise faint nephrogram. We report 2 patients with this nephrographic appearance due to acute renal artery insult. The rim nephrogram is a reliable sign of underperfusion of the kidney. It is dependent on collateral capsular vessels supplying the outer renal cortex. Underperfusion can be due to a primary renal artery problem or secondary to compromise of renal artery perfusion because of elevated interstitial or tubular pressure in the kidney. The sign has not been described with systemic circulatory problems.
Binding of (+/-)[125I]iodohydroxybenzylpindolol (IHYP) to beta-adrenoceptors on intact human peripheral blood lymphocytes was found to be associated with a high degree of non-specific intracellular uptake of the radioligand. Non-specific binding on cellular surfaces was identified by displacing IHYP from its specific binding sites with the cold competing antagonist (+/-)-propranolol. Another methodological approach, however, was necessary to eliminate the uptake problem: release of intracellularly accumulated IHYP was achieved by sedimentation of the IHYP-loaded cells and resuspension in hypotonic buffer (HME buffer) for 10 min at +4 degrees C. The true value of maximal IHYP binding measured after IHYP release was 970 binding sites/cell as compared with 2300 receptors/cell found under standard binding conditions. This difference in maximal IHYP binding obtained by the 2 methods is attributed to the strong interference of the uptake process with the measurement of specific IHYP binding. Further evidence for the efficiency of the procedure to reverse the uptake process was obtained with the very slowly dissociable beta-adrenoceptor antagonist FM 24. Pre-incubation of the cells with 5 x 10(-5) M FM 24 totally prevented specific IHYP binding. Any IHYP measured on cells in the presence of FM 24, therefore, must have been due to mere non-specific binding and cellular uptake of the radioligand. Even though the uptake of IHYP was enhanced in FM-24-treated cells, this influx could be completely reversed by exposing the IHYP-loaded cells to HME buffer for 10 min at +4 degrees C. Our findings indicate that our experimental conditions are suitable for beta-receptor binding studies on intact cells with IHYP, because the uptake of the labeled ligand is eliminated.
[125Iodo]2-[beta-(14-hydroxyphenyl)-ethyl-aminomethyl]-tetralone([125Iodo]BE 2254 or IBE 2254), a new iodinated radioligand of high specific radioactivity (2175 Ci/mmol), was synthesized and used to characterize alpha 1-adrenoceptors in rat lung and cerebral cortex membranes. The binding constants of IBE 2254, using rat lung and cortex membranes, were Kd = 53 +/- 10 pM, Bmax = 53 +/- 8 fmol/mg; and Kd = 78 +/- 14 pM, Bmas = 210 +/- 26 fmol/mg, respectively (Kd = dissociation constant of IBE 2254 determined in saturation experiments). In equilibrium binding experiments with IBE 2254, at concentrations of the free ligand up to 1.2 nM, only one class of binding sites could be detected. In kinetic experiments, the association and dissociation rate constants were 2.3 X 10(9) M-1 min-1 and 0.10 min-1, respectively. In rat cerebral cortex membranes, alpha-adrenoceptor antagonists competed for IBE 2254 binding in the following order: prazosin greater than BE 2254 greater than WB 4101 greater than phentolamine greater than corynanthine greater than yohimbine greater than rauwolscine, indicating strongly that IBE 2254 binds to alpha 1-adrenoceptors. The calculated affinities of different alpha-adrenoceptor blocking agents from inhibition of IBE 2254 binding were nearly identical in rat lung and cerebral cortex. The low dissociation constant of the ligand together with its high specific radioactivity allows binding studies to be carried out with tissue samples where only small densities of alpha 1-adrenoceptors are present.
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[125I]BE 2254 (IBE 2254), a new iodinated radioligand of high specific radioactivity (2175 Ci/mmol) was developed and used to characterize alpha 1-adrenoceptors in rat cerebral cortex membranes. IBE 2254 possessed a high affinity, KD 78 +/- 14 pM with a Bmax of 210 +/- 26 fmol/mg and 90% specific binding at KD value. alpha-Adrenergic antagonists competed for IBE 2254 binding in the following order: prazosin greater than or equal to WB 4101 greater than phentolamine greater than corynanthine greater than yohimbine greater than rauwolscine, a strong indication that IBE 2254 binds to alpha 1-adrenoceptors. IBE 2254 appears to be a very useful tool for studying alpha 1-adrenoceptors.
(+/-)[125Iodo] cyanopindolol (ICYP) is a radioligand which binds with an extraordinarily high affinity and specificity to beta-adrenoceptors. In contrast to (+/-) [125Ido]-hydroxybenzylpindolol (IHYP), the new ligand has neither affinity to alpha-nor to 5-HT-receptors. The dissociation constants of ICYP for beta- adrenoceptors in various tissues range from 27 to 40 pM, thereby exceeding the affinity of IHYP by a factor of approximately 3. ICYP does not discriminate between beta 1- and beta 2-adrenoceptors. Therefore, the densities of the two receptor subtypes can be determined from competition curves of ICYP by drugs previously found to show in vitro selectivity for beta 1-adrenoceptors. The guinea pig left ventricle contains only beta 1-adrenoceptors, whereas in a lung tissue, the ratio of beta 1-to beta 2-adrenoceptors is 1 to 4. The calculated affinities of five beta 1-selective antagonists for beta 1-adrenoceptors were nearly identical in the ventricle and the lung. Kinetic studies of ICYP binding to guinea pig lung membranes indicated that the dissociation reaction consists of two components, a fast process (t 1/2 = 9 min) and a slower process (t 1/2 = 8.8 h). A mathematical treatment revealed two possibilities of interpretation: 1. Two forms of the receptor exist which are interconvertible. 2. The (+)- and (-)- enantiomers of ICYP dissociate with different rate constants. The low dissociation constant of ICYP in combination with its high specific radioactivity (2175 Ci mmole -1) allows binding studies to be carried out with small protein and ligand concentrations, e.g. 3 microgram protein per assay in guinea pig lung membranes.
Cephalometric and visual craniofacial norms based on a native Japanese population of seventy-two subjects between the ages of 6 and 18 years were complied. These norms were obtained from measurements taken from lateral and frontal cephalograms. Norms for fifty cephalometric measurements were found for males and females at each age between 6 and 18 years. Normal composite tracings at there ages 8, 12, and 16 years are also shown. These tracings can be used to calculate the norms of any common cephalometric analysis.
Binding studies have been performed in guinea pig and human lung membranes with the radioligand ICYP and several 'cardioselective' beta-adrenoceptor antagonists. Analysis of data from displacement curves by means of a curve fitting procedure, based on a non-linear regression analysis, indicated that in both tissues beta 1- and beta 2-type adrenoceptors coexisted. The relative proportions of the two receptor subtypes in a single tissue remained constant, irrespective of the antagonist used. The percentage of distribution between beta 1- and beta 2-adrenoceptors was about 22:78 in the guinea pig lung and 30:70 in human lung. For the compounds investigated, the affinities of beta 1- and beta 2-adrenoceptors correlated highly significantly between both species, suggesting that the 'cardioselectivity ratio" of a compound is the same in the guinea pig and in man. Mathematical treatment of the displacement curves provided no evidence of a further class of beta-adrenoceptors in lungs of both species.
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We examined the roles of excretory urography and cystoscopy in the evaluation and management of 153 otherwise healthy women seen consecutively with recurrent urinary tract infections. The excretory urograms were entirely normal in 89 per cent of the patients; the abnormalities were incidental findings with no influence on subsequent management. These results, combined with the known expense and risks inherent in the use of iodinated radiologic contrast material, suggest that excretory urography be limited to those patients possessing other risk factors. These include a history of unexplained hematuria, obstructive symptoms, neurogenic bladder dysfunction, renal calculi, analgesic abuse, severe diabetes mellitus or bacteriologic evidence of rapid recurrence suggesting bacterial persistence within the urinary tract or an enterovesical fistula. On the other hand, cystoscopy under local anesthesia has essentially no risks and occasionally will yield information helpful in future management.
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