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Biomedical subjects

R L Hayes

Publications and source records attributed to R L Hayes.

At least 199 records · Page 11Linked to original sources

[1-11C] DL-valine, a potential pancreas-imaging agent.

There is a great need for a better pancreas-imaging agent. Studies with [1-14C] DL-valine have shown this amino acid to have a high pancreatic specificity in the four animal species examined. The tissue distribution was almost optimal by 30 min after injection, and no carrier effect was observed through a dose of 5 mg/kg. [1-11C] DL-Valine was synthesized in amounts up to 363 mCi using a rapid (T1/2 = 20.4 min for C-11), high-temperature, high-pressure modification of the Bücherer-Strecker amino acid synthesis. Purification was by anion-exchange followed by cation-exchange chromatography. [1-11C] DL-Valine was obtained in a 70% chemical yield with a total synthesis and purification time of 45 min. Studies in animals have demonstrated that it is a potentially useful new agent for clinical pancreatic imaging.

Animals↗

Isolation and partial characterization of a 67Ga-binding glycoprotein from Morris 5123C rat hepatoma.

A Glycoprotein, particularly high in tumors, has been extracted from Morris 5123C rat hepatomas and purified. The compound constitutes a major binding component for 67Ga in this hepatoma. It has a molecular weight of approximately 45,000. Its molecular weight was determined by sodium dodecyl sulfate:polyacrylamide gel electrophoresis and by Sephadex G-200 superfine gel filtration. The steps involved in its extraction and purification include ultrafiltration, gel filtration through Sephadex G-200 superfine, ion-exchange chromatography on diethylaminoethyl Sephadex A-50, and hydroxylapatite chromatography. The homogeneity of the compound was established by gel electrophoresis. The NH2-terminal residue, the percentage of nitrogen, the nonamino carbohydrate content, and the amino acid composition are reported.

Amino Acids↗

Neural representation of cutaneous aftersensations by spinothalamic tract neurons.

Temporal summation of second pain and long-lasting tactile-evoked aftersensations are examples of sensory phenomenons that cannot be explained on the basis of responses of primary afferents. Two distinct classes of monkey spinothalamic tract neurons have responses to controlled natural stimuli that parallel and thus could account for the above phenomenons. One class, termed wide-dynamic-range, receives excitatory effects from sensitive mechanoreceptive afferents and from various nociceptive afferents including Adelta and C mechanothermal nociceptive afferents. Another class, termed nociceptive-specific, receives excitatory effects exclusively from primary nociceptive afferents. Both classes respond with an early and late response to a single noxious heat pulse (peak temperature = 51 C). The late response, unlike C nociceptive afferents but like second pain, summates in magnitude with each successive heat pulse. Gentle moving tactile stimuli evoke long-lasting (20-56 sec) after-discharges only in wide dynamic range neurons, and are similar in duration to the tactile after-sensation evoked by similar stimuli. Both the after-discharges and after-sensations can be abruptly terminated by rubbing the affected region. Temporal summation of second pain and cutaneous after-sensations are at least partly subserved by spinal cord mechanisms within the dorsal horn and are manifested in the output of spinothalamic tract neurons.

Animals↗

The use of rare-earth radionuclides and other bone-seekers in the evaluation of bone lesions in patients with multiple myeloma or solitary plasmacytoma.

Twenty-four patients with multiple myeloma and 4 with solitary plasmacytoma had total-body scans after intravenous injection of 67Ga-citrate alone (17 patients) or combined with other agents (11 patients). The latter included 99mTc-diphosphonate (99mTc-DP), 99mTc-polyphosphate (99mTc-PP), or 99mTc-sulfur colloid (99mTc-SC) given alone or combined with 171Er, 157Dy, or 167Tm as citrate. In some patients more than one agent was compared to 67Ga and radiographic bone surveys. In general, localization of the rare-earth "bone-seekers" was poor except for 157Dy, which compared well with 99mTc-PP and 99mTc-DP; 157Dy was also helpful in studies of the abdomen and pelvis because of its failure to concentrate in the gastrointestinal tract. No toxic or nonspecific effects were noted.

Dysprosium↗

Intracellular crystal-bearing vesicles in the epidermis of scleractinian corals, Astrangia danae (Agassiz) and Porites porites (Pallas).

Orthorhombic aragonitic crystals, embedded with a granular lipo-protein matrix and surrounded by a trilaminar membrane, are localized in the apical cytoplasm of epidermal cells of Scleractinian corals. Adult specimens of Astrangia danae (Agassiz) and settled planulae of Porites porites (Pallas) contain crystals averaging 0.7 mu by 0.1 mu by 0.3 mu within Golgi-derived vesicles. Short-term labelling with 45Ca reveals distribution of radioactivity amont a basic tissue fraction (92%) an acid tissue fraction (5%) and a skeletal fraction (3%). Identification of the primordial crystal population within membrane-bound visicles provides overwhelming evidence for the intracellular mode of calcification in Scleractinia. Moreover, it permits development of a novel concept of cellular regulation over these dynamic events. The membrane-bound vesicel is a miniature crystal fabrication station and a vehicle responsible for transportation of seed crystals and an organic matrix material to sites of discharge from the cell. The vesicle membrane becomes a probable locus of active transport and enzymatic activity as well as a physical barrier to be penetrated for release of vesicle contents into the extracellular milieu. Contact between the vesicle membrane and the plasmalemma would result in exocytosis and the onset of skeletogenesis. Principles governing crystal growth would prevail from then on. The released crystal becomes a nucleation catalyst and the organic matrix, a supply of ionic calcium for self-limiting crystallization. Crystals are produced by the organism spontaneously and continuously from shortly after larval attachment throughout the life of the polyp. Therefore, these membrane-bound vesicles signal the dynamic process by which initiation, differentiation, growth and limitation of the coral skeleton is regulated.

Animals↗

Hypotonic exchange-loading of erythrocytes. II. introduction of hemoglobins S and C into normal red cells.

A rapid, simple technique whereby erythrocytes transiently exposed to hypotonic hemoglobin preparations undergo exchange of endogenous for exogenous hemoglobin has now been applied to normal, hemoglobin A-containing erythrocytes into which hemoglobin S or hemoglobin C have been introduced. Erythrocytes containing an average of 12 to 61 percent of hemoglobin S undergo sickling when incubated in isotonic dithionite solution and are morphologically indistinguishable from natural sickle cells. Ultrastructural studies of thin sections of these artificial sickle cells show microfialments and fascicles which appear typical of microtubular tactoids of hemoglobin S seen in natural sickle cells. Erthrocytes containing 43 percent introduced hemoglobin C developed all of the morphologic alterations associated with intra-erythrocytic hemoglobin C, including hemoglobin aggregation, targetting, and intracellular crystallization, after inclbation for 24 hours in isotonic saline: dithionite. The results support the concept that the sickling process, and morphologic erythrocyte alterations occurring in hemoglobin C disorders are primary to the respective hemoglobins rather than the membrane. They also suggest that any role played by the inner surface of the erythrocyte membrane in the development of these alterations is probably secondary and not specific to the inner membrane surface of the natural sickle cell or hemoglobin C-containing cell.

Cell Membrane↗

Tumor location with 1-aminocyclopentane [11C] carboxylic acid: preliminary clinical trials with single-photon detection.

High specific activity [11C] Carboxyl-labeled 1-aminocyclopentane-carboxylic acid ([11C] ACPC) was tested as a tumor-scanning agent in thirty-eight patients. This artificial amino acid clears the blood to a level of less than 12% within 45 min; thus, imaging is possible within the useful life of C-11. [11C] ACPC can be produced in amounts adequate for clinical scanning. Doses between 12 and 45 mCi were given by i.v. injection, and scans obtained only in the single-photon mode gave clinical information on the sites of tumors. There was no evidence of any toxic effects from [11C] ACPC, and the radiation doses as extrapolated from animal data are approximately 0.01 rad per mCi for the whole body and less than 0.06 rad per mCi for the pancreas. In all but five of the 38 patients [11C] ACPC scans were compared with those obtained with Ga-67 citrate. There were 19 positive [11C] ACPC scans and 24 positive Ga-67 scans. The results indicate that [11C] ACPC is likely to be of diagnostic value for cancer patients if used in conjunction with positron tomography instrumentation.

Amino Acids↗

A quantitative study of the subcellular localization of 67Ga.

This paper describes a quantitative procedure for the isolation of 67 Ga-binding granules (GBG) from normal rat liver and Morris 5123C hepatoma homogenates by a combination of rate and isopyknic density gradient zonal centrifugation. Another class of GBG has been found that is much smaller than the lysosomal GBG we have previously described. These smaller particles, or microvesicles, bind the largest portion of the 67Ga found in the hepatoma whereas, in the liver, the GBG lysosomes are the major binding component. Previously, we had shown that considerably more 67Ga is taken up in hepatoma than in liver (as percentage of administered dose per g of tissue). The preferential association of 67Ga with these microvesicles in the 5123C hepatoma may be indicative of a basic difference between normal and malignant tissue.

Animals↗

Carboxyl-labeled 11C-1-aminocyclopentanecarboxylic acid, a potential agent for cancer detection.

Carboxyl-labeled 11C-1-aminocyclopentanecarboxylic acid (11C-ACPC) has been prepared in multimillicurie amounts. The conversion of H11CN to 11C-ACPC (t1/2 = 20.4 min) was accomplished by a rapid (20-min) two-step high-temperature modification of the Bücherer-Strecker amino acid synthesis technique, which should be applicable at other accelerator installations. Purification was by ion exchange techniques. Animal studies have indicated that 11C-ACPC is a potential tumor-localizing agent for detecting cancer in humans by nuclear medicine scanning techniques.

Animals↗

Stimulation-produced analgesia: development of tolerance and cross-tolerance to morphine.

Analgesia resulting from focal electrical stimulation of the brain of the rat shows tolerance with repeated exposures; this tolerance dissipates after a period of nonstimulation. Addiction to morphine reduces greatly the analgesia produced by electrical stimulation of the brain, which demonstrates cross-tolerance between morphine analgesia and stimulation-produced analgesia. Recovery of the stimulation-produced analgesia is seen after discontinuing administration of morphine. These results suggest that morphine and electrical stimulation produce analgesia by common mechanisms. The fact that tolerance occurs to the analgesic effect of electrical stimulation indicates that tolerance may be an alteration of an endogenous neuronal process.

Analgesia↗