Search PubMedSearch

Biomedical subjects

H L Atkins

Publications and source records attributed to H L Atkins.

At least 19 recordsLinked to original sources

Characterization of the structure of the erythropoietin receptor by ligand blotting.

Erythropoietin (Epo) regulates the growth and differentiation of erythroid cells by binding to a specific receptor. We characterized the native Epo receptor on erythroleukemia cell lines by ligand blotting. Solubilized cell membrane proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred onto nitrocellulose, and probed with 125I-Epo. Specificity was demonstrated by inhibition of 125I-Epo binding by unlabeled excess Epo but not other peptide growth factors and by the cellular distribution of the Epo binding protein. A single membrane protein of 61 Kd +/- 4 Kd was sufficient to bind 125I Epo in both human (OCIM2, K562) and murine (GM979, Rauscher, DA-1) cell lines. This finding is consistent with the predicted size of the Epo receptor from the murine cDNA clone. However, chemical crosslinking of 125I-Epo to its receptor has identified two Epo binding proteins of 105 Kd and 85 Kd. This difference may occur because the receptor is size fractionated before Epo binding in the ligand blot, but after Epo binding in crosslinking studies. Ligand blotting demonstrates that the native Epo receptor is composed of a single 61-Kd Epo binding protein, and suggests the presence of additional proteins of 20 to 25 Kd that associate with the receptor after Epo binding.

Animals

Stem cell factor is encoded at the Sl locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor.

We have cloned a partial cDNA encoding murine stem cell factor (SCF) and show that the gene is syntenic with the Sl locus on mouse chromosome 10. Using retroviral vectors to immortalize fetal liver stromal cell lines from mice harboring lethal mutations at the Sl locus (Sl/Sl), we have shown that SCF genomic sequences are deleted in these lines. Furthermore, two other mutations at Sl, Sld and Sl12H, are associated with deletions or alterations of SCF genomic sequences. In vivo administration of SCF can reverse the macrocytic anemia and locally repair the mast cell deficiency of Sl/Sld mice. We have also provided biological and physical evidence that SCF is a ligand for the c-kit receptor.

Amino Acid Sequence

The scintigraphic pattern of renal angiomyolipoma.

The patterns of renal and gallium scintigraphy in a patient with renal angiomyolipoma are presented. Renal study with Tc-99m DTPA demonstrated a photopenic area in the flow and delayed images. Ga-67 citrate imaging did not show any evidence of increased activity. Although this pattern is also seen in renal cysts, scintigraphy seems to be valuable in the evaluation of angiomyolipoma. It helps differentiate it from renal carcinoma or renal abscess (which may be gallium avid), especially when the tumor is characterized by a paucity of adipose tissue and complicated by hemorrhage, in which case CT and ultrasonographic patterns are not diagnostic.

Abscess

The role of factor analysis in the evaluation of new radiopharmaceuticals.

Factor analysis of dynamic scintigraphic studies has been proposed for a variety of clinical applications. This method also called FADS (Factor Analysis of Dynamic Structures) enables spatial separation of complex images into discrete factors according to their time/activity characteristics. FADS, which does not require a priori formulation of a compartmental model of tracer kinetics, is particularly suitable for the evaluation of new radiolabeled compounds as potential radiopharmaceuticals. In animals as well as in humans it is possible to obtain information on the spatial time-distribution of tracers by analyzing computer acquired scintigraphic studies. On the basis of data obtained and analyzed with this method using [123I]IMP in humans, dogs, rabbits and rats, with two 99mTc labeled monoclonal antibodies in dogs and with 99mTc DTPA in renal transplants, we recommend this method as an adjunct in radiopharmaceutical development and evaluation.

Amphetamines

Quantitative evaluation of renal excretion on the dynamic DTPA renal scan.

In order to evaluate the renal excretion quantitatively, the authors analyzed the Tc-99m DTPA renogram using mean transit time (MTT) with deconvolution analysis and compared it to the perfusion index. One hundred thirteen studies consisting of 25 normal, 11 obstruction, 35 transplant-norm, 12 transplant-obstruction, and 30 transplant-rejection were evaluated. In the non-transplant obstruction, MTT is significantly long (3.40 +/- 0.85 minutes vs 2.02 +/- 0.42 minutes) and has high sensitivity (100%) and specificity (93%, 23/25) for the diagnosis of obstruction. In the transplant-obstruction, if the field of view includes both transplant and liver or spleen as a blood pool image, MTT has high sensitivity for the diagnosis (10/11) and for the follow up of obstruction (12/12), with the same specificity, but low sensitivity for rejection (25%). Perfusion index is of value in the diagnosis of rejection (73% specificity, 77% sensitivity) but is useless for the detection of obstruction (25% specificity, 75% sensitivity). The authors conclude that MTT is a useful marker for diagnosis and serial quantitative evaluation of renal obstruction. Also, they suggest the use of multiple techniques based on different principles for the complete evaluation of the renal scan.

Humans

Asymmetric gallbladder contraction following cholecystokinin hepatobiliary imaging.

Three patients are presented with abnormal hepatobiliary images. A slow infusion of the terminal octapeptide of cholecystokinin caused asymmetric contraction in all three. Two of the patients displayed a bilobate appearance of the gallbladder. In one of the patients, there were typical changes associated with adenomyomatosis by other imaging modalities. The third patient showed good contraction of the fundus of the gallbladder but not of the proximal segment. In two of the patients, the global ejection fraction was considered to be normal. The asymmetrical contraction under the stimulus of cholecystokinin may be an important indicator of biliary dysfunction despite a normal ejection fraction.

Adolescent

Comparative dual-tracer studies of carbon-14 tryptophan and iodine-131 HIPDM in animal models of pancreatic diseases.

Our previous studies have shown that a significant amount of the diamine derivative 131I-N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3- propanediamine (HIPDM) is taken up and retained by the normal pancreas. Therefore, we studied the uptake of [131I]HIPDM in various pathophysiological models in mice (chronic alcoholism, diabetes with beta-cell atrophy and obesity with beta-cell hypertrophy) and compared to 14C-L-Tryptophan (TRY) distribution in order to determine the factors influencing their pancreatic uptake. In normal animals, the pancreas uptake of TRY was generally higher than HIPDM. In diabetes, the relative concentration of both compounds was higher over the controls; however, in obesity, TRY showed lower accumulation than in controls while HIPDM showed no significant difference. Chronic ethanol (20%) ingestion increased TRY uptake in the pancreas compared to controls (36.88 +/- 3.21 vs. 30.03 +/- 4.17% ID/g; p less than 0.01) after 5 wk study period, but it decreased by 10 wk (22.36 +/- 0.95% ID/g; p less than 0.005). There were no significant changes in [131I]HIPDM distribution in alcoholics as compared to the controls. Radioiodinated HIPDM has potential advantages over [11C]TRY for pancreatic imaging since conventional imaging techniques can be employed. Our data, however, suggest that 11C-L-TRY is a more sensitive indicator of various pancreatic disorders.

Animals

Regional left ventricular filling: does it reflect diastolic abnormalities in contiguous areas of myocardium?

To test the hypothesis that regional left ventricular filling reflects diastolic changes in contiguous areas of myocardium, we performed radionuclide ventriculograms on normal subjects, patients with left anterior descending coronary artery disease, and patients with anteroseptal myocardial infarctions. We reasoned that because diastolic properties of the anteroseptal myocardium should be different in the three groups of patients, regional filling in the anteroseptal area of the left ventricle should also be different, if regional filling does, indeed, reflect diastolic changes in the adjacent myocardium. While anteroseptal regional filling in the normal subjects was different than regional filling in the two patient groups, the degree of filling abnormality was similar in patients with and without myocardial infarctions. Our results suggest that regional left ventricular filling is not exclusively determined by diastolic changes in contiguous areas of myocardium.

Coronary Disease

Detection of cardiomyopathy in an animal model using quantitative autoradiography.

A fatty acid analog (15-p-iodophenyl)-3,3 dimethyl-pentadecanoic acid (DMIPP) was studied in cardiomyopathic (CM) and normal age-matched Syrian hamsters. Dual tracer quantitative wholebody autoradiography (QARG) with DMIPP and 2-[14C(U)]-2-deoxy-2-fluoro-D-glucose (FDG) or with FDG and 201Tl enabled comparison of the uptake of a fatty acid and a glucose analog with the blood flow. These comparisons were carried out at the onset and mid-stage of the disease before congestive failure developed. Groups of CM and normal animals were treated with verapamil from the age of 26 days, before the onset of the disease for 41 days. In CM hearts, areas of decreased DMIPP uptake were seen. These areas were much larger than the decrease in uptake of FDG or 201Tl. In early CM only minimal changes in FDG or 201Tl uptake were observed as compared to controls. Treatment of CM-prone animals with verapamil prevented any changes in DMIPP, FDG, or 201Tl uptake. DMIPP seems to be a more sensitive indicator of early cardiomyopathic changes as compared to 201Tl or FDG. The trial of DMIPP and SPECT in the diagnosis of human disease, as well as for monitoring the effects of drugs which may prevent it seems to be warranted.

Animals

Radionuclide venography vs Tc-99m-RBC equilibrium angiography: a comparative paired study.

Combined direct injection venography (DIV) and equilibrium angiography (EA) were performed in 13 patients, by injecting in vitro labeled 99mTc autologous RBC, via pedal veins, and imaging the first pass and the equilibrium phase. This paired comparative study of DIV with EA shows that DIV has advantages over EA because it provides selective information on the deep venous system from the calves to the inferior vena cava. DIV provides information on the flow dynamics and the high contrast first pass images provide better definition of non filling venous segments as well as visualization of collaterals. When using 99mTc-MAA, lung perfusion can also be imaged. DIV is recommended as the procedure of choice for the diagnosis of DVT and EA should be employed only when pedal vein injection is not possible.

Adult

Use of radiolabeled monoclonal anti-B1 antibody for B lymphocyte imaging in rhesus monkeys.

Imaging tissues rich in B lymphocytes in man using a radiolabeled monoclonal anti-B cell antibody would be extremely useful in the clinical staging of non-Hodgkins lymphomas. Studies were done in rhesus monkeys using radiolabeled monoclonal anti-B1 antibody to determine the feasibility of such an approach. Immunohistologic studies demonstrated that infused monoclonal anti-B1 binds in vivo with specificity to B cells in lymph nodes and spleen. The kinetics of clearance of 131I-labeled anti-B1 were determined. The B lymphocyte-rich spleen could be readily visualized by gamma camera scanning without significant background and without the need for image intensification or blood background subtraction techniques. These data support the feasibility of using anti-B1 for staging B cell lymphomas in man.

Animals