A comparison of retinol binding in human hyperplastic and malignant prostate.
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Biomedical subjects
Publications and source records attributed to D Boyd.
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A retinoic acid binding protein has been detected in salt extracts of nuclei obtained from human prostate adenoma. The binding was characterized by competition experiments, temperature/time studies and saturation analysis. Substantial binding was only observed after sonication of nuclei and charcoal-pretreatment of a salt extract. The binding of radiolabelled all-trans-retinoic acid was displaced by all-trans-retinoic acid, retinol and to a lesser extent retinal and two synthetic retinoids, RO 10-1670 and RO 13-7410. Testosterone and dihydrotestosterone, at a 100-fold excess, had little effect on the binding. The association between retinoic acid and nuclear protein was both temperature and time dependent. At 37 degrees C, equilibrium was rapidly reached (30 min) whereas at 4 and 25 degrees C, ligand binding occurred at a slower rate. Saturation analysis performed under steady-state conditions yielded a dissociation constant of 15 +/- 2 nmol/l. Metabolism studies failed to show conversion of either radiolabelled all-trans-retinol or [3H]retinoic acid in vitro; these data suggest that both acid and alcohol forms of vitamin A are recognized by the extracted nuclear protein. The effect of three enzyme inhibitors on [3H]retinoic acid binding was studied. Binding was unaltered in the presence of aprotinin and phenylmethylsulphonyl fluoride but sodium molybdate (10 mmol/l) increased binding by 18%. The presence of a specific retinoid binding protein in prostate nuclei suggests that retinoids may play some role in the function of the gland.
Seven adult male mongrel dogs were monitored by electromagnetic flow probes and string occluders around the hepatic artery and portal vein. Then, time density curves of the liver, aorta and portal vein were recorded using dynamic CT scanning following the bolus injection of contrast material into a peripheral vein (n = 7) and a mesenteric vein branch (n = 5). Information on total hepatic blood flow could not be obtained from the mesenteric vein injection. The hepatic time density curve could, however, be broken into its two components, hepatic arterial and portal venous flow contribution, by selective ligation of the hepatic artery or portal vein. It could be demonstrated that the arterial component of liver enhancement reached its peak at the end of the aortic wash-out of contrast material. Thus, the hepatic time-density curve could be broken in its two components by superimposing the aortic time density curve onto the hepatic curve. An attempt was made to estimate relative portal venous blood flow by using the slopes or the peaks of both components of the hepatic curve. Using the slopes of the hepatic curve resulted in a consistent underestimation of portal venous blood flow, whereas the peaks gave an estimate of portal venous flow with an accuracy within +/- 8%.
Ferritin, the main iron-storage protein, is composed of two partially homologous subunits, heavy (H) and light (L), with MrS of 21,000 and 19,000, respectively. We have isolated a cDNA clone for human ferritin H chains by screening a human lymphocyte cDNA library with synthetic oligodeoxyribonucleotides. The oligonucleotide sequences were derived from two pentapeptides found in human spleen ferritin. The selected clone hybridized to both probes and selected H-chain mRNA, but not L-chain mRNA, when hybridized to HeLa cell mRNA. These results indicate that the cloned DNA codes for a H chain of human ferritin. Since the amino acid sequence derived from the cloned DNA was almost identical to the partial amino acid sequence of a minor component found in human spleen ferritin, we conclude that the minor sequence found in human spleen ferritin must be a H subunit. Genomic analysis gives a complex pattern that suggests that ferritin H chains are encoded by a multigene family or have an unusually large number of exons.
A retinol-binding protein has been detected in the cytosol of human prostates with benign hyperplasia. The binding was of high affinity and specific for retinol (Kd = 35 nM), with other retinoids such as trans-retinoic acid, retinal, and the synthetic analogues, all-trans-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nona tetraenoic acid and p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propenyl] benzoic acid, showing little or no competition. The retinol binding, which sedimented as a 2S component on sucrose density gradients, was also unaffected by the addition of excess unlabeled steroid hormones. Furthermore, pretreatment of the cytosol proteins with heat and/or trypsin totally abolished the retinol binding. Parallel experiments with trans-retinoic acid suggest that the hyperplastic prostate possesses a second retinoid-binding site which is specific for retinoic acid and distinct from the retinol-binding component. Experiments with serum from patients with benign prostate hyperplasia revealed no binding at the 2S sedimentation position; this suggests that the retinoid-binding proteins were exclusively associated with prostatic tissue and were not therefore derived from serum.
Opens surgical drainage of intraabdominal, intrahepatic, and mediastinal abscess is well established. Although this may be the procedure of choice when there are indications for treatment of concurrent intraabdominal and mediastinal surgical disease, with the advent of computerized axial tomography and ultrasonography we have identified a patient population best served by percutaneous catheter drainage. The procedure involves precise localization using ultrasound or CAT scanning, fine needle aspiration for confirmation of diagnosis, and injection of radiopaque contrast medium with fluoroscopic observation to localize the abscess. Catheter placement is usually achieved by a Seldinger technique, although a trochar-cannula method is occasionally required. Our experience with 4 patients, as well as review of the world literature provides a cumulative experience of 252 patients, has led us to believe that this approach is successful 83 percent of the time with a minimal incidence of complications. Percutaneous catheter drainage of intrahepatic, intraabdominal, and mediastinal abscess guided by computerized axial tomography is the treatment of choice in patients who do not have other indications for exploration.
Gentamicin is a very useful antimicrobial agent for the treatment of serious infections caused by gram-negative bacteria. However, it's low therapeutic index and potential ototoxic and nephrotoxic side effects necessitate frequent determinations of serum concentration to assist in maintaining therapeutic levels and avoiding toxic levels. Two bioassays and a latex agglutination inhibition card (LAIC) test were evaluated to determine gentamicin levels in nearly 100 patient sera. Results were compared with a radioimmunoassay (RIA). Two bioassays, the Bio-Monitor and the GentaSak, gave correlation coefficients of 0.987 and 0.982, respectively. The correlation coefficient for the LAIC test was 0.987. All three tests compared well with RIA in accurately detecting gentamicin levels in patients as well as simulated sera. The LAIC test, however, was more rapid, giving results within half an hour whereas bioassays required 6--8 hours for completion. The LAIC test was also found to be more economical. It provides a suitable alternative to RIA procedures in small laboratories and for performing 'stat' tests since batching is not necessary.
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A complex consisting of replicative origin DNA and several proteins was isolated from Escherichia coli. Cells of temperature-sensitive mutants were labeled at the origin and fractionated by sucrose gradient centrifugation. A complex highly purified in origin DNA sedimented as a unique band. This complex dissociated at high concentration, above 0.2 M KCl. Upon dialysis, the complex reformed, allowing further purification of its constituents. Three major protein bands were found, corresponding to proteins of the outer membrane. The complex did not sediment with membrane fractions, but adhered to the outer membrane in the presence of magnesium.
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Propranolol alone was used to prepare 20 thyrotoxic patients, 19 women and 1 man, for subtotal thyroidectomy. Serum thyroxine (T4) and triiodothyronine (T3) concentrations were measured immediately before, at several stages during and after the surgical procedure. As judged primarily by the cardiovascular response, an average of 80 mg (range 40 to 120 mg) of propranolol qid for 8 days (range 3 to 18 days) was required to prepare the patients. During the various stages of surgical removal there was no change from the initial mean (+/- SEM) T4 concentration of 25.0 +/- 2.5 microgram/dl (321.8 +/- 32.2 nmol/l) or T3 concentration of 4.2 +/- 0.6 microgram/l (6.45 +/- 0.92 nmol/l) (P greater than 0.2). At discharge on the fifth postoperative day values were significantly lower, 12.9 +/- 1.5 microgram/dl (166.0 +/- 19.3 nmol/l) and 1.9 +/- 0.2 microgram/l (2.9 +/- 0.31 nmol/l), respectively (P less than 0.001). There were no operative complications but four patients had transient hypoparathyroidism. After 1 year 2 of 18 patients had permanent hypoparathyroidism and 4 of the 18 followed up for 1 year had permanent hypothyroidism requiring thyroid hormone replacement. There was no instance of recurrent thyrotoxicosis. The authors conclude that during surgical manipulation of the gland no release of thyroid hormones into the circulation was detected and that, using propranolol as the sole agent, thyrotoxic patients can be rapidly and safely prepared for subtotal thyroidectomy.
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Previous work has suggested that patients with organic lesions causing pain may show as much emotional disturbance as patients with pain but without lesions. This study examined 141 chronic pain patients for their life experience, both currently and premorbidly, in terms of upbringing, neurotic traits and personality disturbance. Patients with an organic cause for pain reported significantly less family disturbance in childhood, less premorbid personality problems and less neurotic traits than patients who did not have any organic cause for their pain. The data provide support for the view that a significant proportion of the emotional disturbance associated with chronic pain is a secondary effect. Adjectives used to describe pain and factors causing exacerbation and relief of pain, although overlapping, also differed in the two groups.
Phantom studies comparing skull radiography and cranial computed tomography (CT) show that CT is 5 to 15 times more sensitive than skull radiography in the detection of intracranial calcifications. The difference in detectability varies with object size. The relative sensitivity of CT increases with increased object size within the constraints of the section thickness. The relationship of these findings to the detectability of pineal and choroid calcifications is discussed.
Angiocardiographic methods available for cardiac-chamber volume measurements are neither consistently accurate nor precise. To explore the capability of computed tomography for left ventricular volume measurement, Silastic casts of 24 normal human left ventricles were measured by a displacement method, a conventional angiocardiographic biplane volume method, and computed tomography. The displacement method used degassing to remove air trapped in the casts; displacement was measured by Archimedes' principle. Cast volumes measured by biplane methods displayed spread around the regression line, caused by the chamber's irregular shape and its variations in orientation. Computed tomographic measurements were independent of chamber orientation and significantly more accurate.
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