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Biomedical subjects

A Goldstein

Publications and source records attributed to A Goldstein.

At least 181 records · Page 10Linked to original sources

Preparation of brain membranes containing a single type of opioid receptor highly selective for dynorphin.

Opioid receptors on guinea pig brain membranes were alkylated by the naltrexone analogue beta-chlornaltrexamine. Binding of the prototypical mu and kappa ligands, [3H]dihydromorphine and [3H]ethylketocyclazocine, was more readily affected by the reagent than was binding of the delta ligand, 3H-labeled [D-Ala2, D-Leu5]enkephalin. Treatment of membranes with beta-chlornaltrexamine in the presence of dynorphin resulted in significant protection of [3H]ethylketocyclazocine binding sites, without protection of [3H]dihydromorphine or 3H-labeled [D-Ala2, D-Leu5]enkephalin sites. Similarly, [D-Ala2, D-Leu5]enkephalin and sufentanil selectively protected binding sites for 3H-labeled [D-Ala2, D-Leu5]enkephalin and [3H]dihydromorphine, respectively. Scatchard analysis of [3H]ethylketocyclazocine binding to untreated membranes suggested two types of binding site with 40-fold difference in affinities. Membranes treated with beta-chlornaltrexamine in the presence of dynorphin retained about 40% of the high-affinity sites and lost the low-affinity sites. Selective protection of sites with high affinity for dynorphin and ethylketocyclazocine was confirmed in competition binding assays. These results strongly suggest that the three types of opioid receptor are not interconvertible and provide further evidence that the endogenous peptide dynorphin is a highly selective ligand of the kappa opioid receptor.

Animals↗

B-scan transducer peak frequency measurement by diffraction grating spectroscopy.

Making use of technology developed for optics, transmission diffraction grating spectroscopy is proposed as a method of measuring ultrasound transducer frequencies. Diffraction grating theory is presented and extended to the case of a new test object proposed to measure a B-scan transducer's peak frequency. A prototype test object was built and its feasibility tested. The experimental results indicate that the test object performed well and has high measurement precision. The question of measurement accuracy was not resolved by the feasibility test. This complex point is discussed in detail. Recent improvements of the test object and the author's ongoing studies of diffraction grating characteristics are presented.

Feasibility Studies↗

Dynorphin immunoreactivity in pituitary.

Tissue ir-dynorphin has been shown to be associated with three components separable by gel filtration. Similar components were found in both pituitary and brain, although there are differences in the relative amounts of each component in each tissue. Anterior lobe of rat pituitary contains predominantly the component with highest apparent molecular weight, while the component with smallest apparent molecular weight, which is the major form in neurointermediate lobe, was absent. Exposure of rats to NaCl resulted in a parallel depletion of ir-dynorphin and ir-[Arg]-vasopressin neurointermediate lobe stores. Thus a role for dynorphin, acting in concert with vasopressin, or in the regulation of vasopressin release, appears possible.

Animals↗

Mycosis fungoides. Small-bowel involvement complicated by perforation and peritonitis.

Mycosis fungoides (MF) is a malignant lymphoma that arises in the skin and subsequently may involve lymph nodes and viscera as part of the natural course of the disease. The disease has distinct histologic characteristics that may be recognized in extracutaneous tissues. A patient who had MF with ulcerating cutaneous nodules is presented herein. Death resulted from perforation of the small bowel involved by the disease and consequent peritonitis.

Female↗

Registration errors in compound B-scans.

The effect of B-scanner articulated arm angle measurement errors on B-mode registration is considered. For a single-angle articulated arm model, a mathematical equation predicting B-mode misregistration as a function of angular errors and compound scan angle is derived and discussed. This model accurately predicts registration errors for transducer connector/acoustic axis misalignment or third arm angle errors.

Diagnostic Errors↗

Range ambiguities in real-time ultrasound.

The frequent occurrence of low-level artifactual echoes in normally echo-free areas of real-time images is shown to be due to a range-ambiguity effect caused by the fast frame rate of real-time equipment. The experimental data demonstrates the range-ambiguous echoes to be present in linear array and mechanical sector scanner real-time images. Several suggestions are made to reduce the effect of the artifact in real-time images. A set of real-time acceptance tests that utilize this artifact are proposed.

Ultrasonics↗

Slice-thickness artifacts in gray-scale ultrasound.

We have become increasingly aware of the presence of a type of image artifact normally appearing in anechoic areas (eg, cyst, bladder, gallbladder) and giving the appearance of "sludge" or "debris." These artifactual echoes may be caused by the fact that the finite width of the transducer beam pattern produces a finite thickness of the patient scan plane. All echoes produced in this "thick" scan plane are misinterpreted as being due to structures in the normally assumed "thin" scan plane. We have tested and verified this hypothesis by simulating soft tissue interfaces with 400 grit silicon carbide sandpaper in a water tank. A set of clues are proposed to enable the rapid identification of these artifacts.

Diagnostic Errors↗

Characterization of the receptor mediating the nicotine discriminative stimulus.

The discriminative stimulus (cue) property of nicotine was studied in a T-maze paradigm, and the results were analyzed by a new statistical method. For rats trained on 0.4 mg/kg, the ED50 was 0.11 mg/kg. The enantinomer of natural nicotine (+)nicotine was much less potent, and both position isomers of nicotine were inactive. Anabasine, which is active at nicotinic cholinergic receptors, provided the nicotine cue. Cytisine, a potent nicotinic agonist in vitro, was ineffective after SC administration and this was shown to be due to its inability to enter the brain in adequate amounts. High doses of cytisine by the intracerebroventricular route partially provided the cue. The cue was blocked by low doses of mecamylamine and pempidine and by high doses of hexamethonium. The data indicate that the cue receptor is pharmacologically similar to the nicotinic cholinergic receptor in autonomic ganglia.

Alkaloids↗

Response of lymph node metastasis to sequential estrogen and radiation therapy in prostate carcinoma.

Increasingly sophisticated diagnostic studies have shown a high incidence of tumor spread to the regional lymph nodes. The status of the lymph nodes has been evaluated by noninvasive diagnostic procedures such as lymphangiography and computerized axial tomography. The applicability of these procedures has been enhanced by the use of stringent criteria. Gross lymph node metastasis can be diagnosed with considerable confidence. Serial observations of lymphangiograms and computerized axial tomograms before and two months after the administration of estrogens provide an added dimension to the interpretation of lymph node metastasis. The nature and range of the response of lymph node metastasis were observed. Survival of patients with gross lymph node metastasis treated by sequential estrogen and radiation therapy was evaluated. A total of 11/18 (61 per cent) of patients remained free of symptoms, 8/11 (74 per cent) with a favorable lymph node metastasis responsive to estrogen therapy, and 3/7 (42 per cent) with lymph node metastasis refractory to estrogen therapy. Follow-up computerized axial tomograms of the lymph nodes done at one and two years after irradiation showed a persistent favorable response. Five patients are alive with disease, and 2 patients died of the disease.

Aged↗

Endothelial cell presentation of antigen to human T cells.

Activation of human T cells requires presentation of antigen by Ia (HLA-DR in man) bearing cells of the mononuclear phagocytic series (macrophages, MO, and more recently Langerhans cells, dendritic cells, and vascular endothelial cells. Since T cells must cross endothelial barriers to enter extravascular tissues during immune reactions, we investigated the role of endothelial cells in antigen presentation. Endothelial cells were cultured from human umbilical veins and identified by classic morphology and specific markers (factor VIII related antigen, and so on). Antigen-pulsed endothelial cells were used to present antigen to MO-depleted human T cells; activation was assessed by 3H-thymidine uptake. The HLA-DR compatible endothelial cells were as effective as MO in reconstituting MO-depleted T-cell responses. The endothelial cell reconstituted responses were antigen specific, HLA-DR restricted, and blocked by monoclonal antibodies to HLA-DR framework structures. Moreover, the T-cell responses were clonal with respect to HLA-DR. A monoclonal antibody completely eliminated MO reconstitution of the MO-depleted response without diminution of endothelial cell reconstitution of the same response. Fibroblasts and smooth muscle cells cultured from the same umbilical veins could not reconstitute the MO-depleted T-cell response. These data indicate that endothelial cells play an important and distinctive role in lymphocyte triggering.

Antigens↗

Naltrexone treatment of heroin addiction: efficacy and safety in a double-blind dosage comparison.

The goals of this study were two-fold: (1) to test the hypothesis that retention of patients in naltrexone treatment could be improved by educating and preparing them for it while enrolled in a LAAM (l-alpha-acetylmethadol) detoxification program; and (2) to compare the safety and efficacy of 60 mg vs. 120 mg administered thrice weekly in a double-blind, sequential trial design. Patients were allowed a maximum of 365 days on naltrexone, and a maximum of four admissions; 119 patients received at least one dose of naltrexone. We found no clinically important differences between the two dosages, and retention in treatment was similar to that reported in earlier clinical trials. Slightly more than half the patients ever used heroin while receiving naltrexone, and only 9% of all urine tests were positive for opiates. Craving for heroin decreased dramatically by the end of the first week. We found no side-effect or toxicity due to naltrexone.

Adolescent↗

Specific receptor for the opioid peptide dynorphin: structure--activity relationships.

The structural features responsible for the high potency and opiate receptor specificity of the opioid peptide dynorphin in the guinea pig ileum myenteric plexus were examined. Successive removal of COOH-terminal amino acids from dynorphin-(1--13) demonstrated important contributions of lysine-13, lysine-11, and arginine-7 to the potency. Removal of the NH2-terminal tyrosine abolished the biologic activity. Several other structural modifications were shown to affect potency: substitution of D-alanine for glycine-2 reduced the potencies of dynorphin-(1--13) amide, -(1--11), and -(1--10); and methyl esterification of the COOH terminus enhanced the potencies of dynorphin-(1--12), -(1--10), -(1--9), -(1--8), and -(1--7). Within the dynorphin sequence, lysine-11 and arginine-7 were found to be important for selectivity of interaction with the dynorphin receptor, which is distinguishable from the mu receptor in this tissue.

Animals↗