Search PubMed⌕ Search

Biomedical subjects

C J Anderson

Publications and source records attributed to C J Anderson.

At least 109 records · Page 6Linked to original sources
PubMed1980

Permeability of lipid bilayers to methylmercuric chloride: quantification by fluorescence quenching of a carbazole-labeled phospholipid.

We investigated the permeabilities of lipid bilayers to the neurotoxin methylmercuric chloride (MMC). This mercurial is an efficient collisional quencher of the fluorescence of N-alkyl carbazole derivatives. Quenching of the fluorescence of beta-(3-(9-carbazole)-propionyl-L-alpha-phosphatidylcholine (CPA-PC) in vesicles of dimyristoyl phosphatidylcholine and of dioleoyl phosphatidylcholine reveal rapid diffusion of MMC in the alkyl side chain regions of these bilayers. By a combination of (1) the lipid concentration dependence of the apparent quenching constants, (2) the solubility of MMC in concentrated lipid dispersions and (3) the 270 MHz proton magnetic resonance of methylmercury in the presence of lipid bilayers we conclude that the lipid-water partition coefficient of this mercurial is less than or equal to two. Using the fluorescence quenching and the partitioning data we estimate the diffusion coefficient of MMC in these bilayers to range from 0.13 to 0.31 X 10(-5) cm2/sec, or 20--47% of its diffusion coefficient in ethanol. These data indicate that lipid bilayers do not pose a significant permeability barrier to the diffusional transport of MMC.

Diffusion↗
PubMed1980

Allergic bronchopulmonary aspergillosis and bilateral fungal balls terminating in disseminated aspergillosis.

A unique case of allergic bronchopulmonary aspergillosis associated with bilateral apical aspergillomas terminating in disseminated aspergillosis is presented. Postulated mechanisms of this combination are discussed with respect to the patient's clinical findings. The contribution of systemic and aerosolized corticosteroids are considered major contributing factors to dissemination of disease.

Adult↗
PubMed1980

Postural heart block.

A patient presented with orthostatic dizziness and syncope caused by postural heart block. When the patient was supine, atrioventricular conduction was normal and he was asymptomatic; when he was standing he developed second degree type II block and symptoms. The left bundle-branch block on his electrocardiogram and intracardiac electrophysiological study findings suggest that this heart block occurred distal to the His bundle. Orthostatic symptoms are usually presumed to be secondary to an inappropriate distribution of intravascular volume or to autonomic nervous system abnormalities. As shown in this patient, these symptoms may be the result of orthostatic heart block. Ambulatory monitoring may be useful in patients with orthostatic neurological symptoms, particularly when conduction abnormalities are present on the electrocardiogram.

Dizziness↗
PubMed1978

Toxicity of combined therapy with carbonic anhydrase inhibitors and aspirin.

A 67-year-old woman and a 75-year-old woman taking carbonic anhydrase inhibitors for therapy of glaucoma and high doses of aspirin for therapy of arthritis developed severe acid-base imbalance and salicylate intoxication. Neither patient exhibited ill effects when taking high aspirin doses without carbonic anhydrase inhibitor. Carbonic anhydrose inhibitor-induced acidemia increases the risk of developing salicylate intoxication in patients receiving high aspirin doses.

Acetazolamide↗
PubMed1971

Medullary carcinoma of the thyroid with parathyroid adenoma and hypercalcaemia.

A patient with hyperparathyroidism due to a parathyroid adenoma was found to have metastatic medullary carcinoma in lymph nodes close to the thyroid gland. The finding of normal calcitonin and parathormone concentrations after removal of the adenoma suggested that the parathyroid lesion was not the result of the hypocalcaemic action of calcitonin produced by the tumour in the thyroid. Seventeen other examples of the association between medullary carcinoma and parathyroid enlargement are briefly reviewed.The pathogenesis of the parathyroid lesions is discussed, and it is suggested that some may be caused by the hypocalcaemic action of calcitonin, while others may be part of a syndrome of multiple endocrine adenomatosis.

Adenoma↗
PubMedDate not supplied

Progestin radiopharmaceuticals labeled with technetium and rhenium: synthesis, binding affinity, and in vivo distribution of a new progestin N2S2-metal conjugate.

We have prepared and evaluated three metal conjugates of a progestin-monoamine-monoamide (MAMA') bisthiol chelate system. These conjugates of rhenium and technetium-99 and -99m, are structural analogs of the bisamino-bisthiol (BAT) conjugates we have described recently, but the MAMA' chelate, being more polar than the BAT system, gives a conjugate that is much less lipophilic, having an octanol-water partition coefficient that is nearly 80-fold lower. In competitive binding assays, the Re- and 99Tc-MAMA'-progestin conjugates bind to the progesterone receptor with affinities greater than that of progesterone itself, and in a direct binding assay, the equilibrium dissociation constant (Kd) of the 99mTc-MAMA' conjugate was 0.97 nM. As is typical for 11 beta-substituted progestins, these conjugates also have substantial binding affinity for glucocorticoid receptors. In tissue distribution studies in immature female rats, the progestin-99mTc-MAMA' conjugates show selective uptake for principal target tissue (such as uterus) over that of blood and nontarget tissue (such as muscle); these uptake ratios reach maximum levels of 5 and 4, respectively. Uptake by fat, liver, and kidney is quite high; however, only the uptake in uterus is displaceable upon coinjection of the selective progestin ORG2058. Metabolism studies show that the radioactivity in the uterus is essentially unmetabolized out to 4 h, while liver activity is completely due to metabolites. Other tissues show an intermediate fraction of unmetabolized conjugates that decreases with time. The in vivo behavior of the progestin-99mTc-MAMA' conjugate is similar to that of the labeled BAT conjugate: its uptake selectivity is somewhat greater than that of the BAT conjugate, but its target tissue uptake is lower. Factors that may be responsible for limiting the target tissue uptake properties of these conjugates are their moderate affinity for progesterone receptor, their substantial binding to glucorticoid receptors, and their large overall molecular size.

Animals↗
PubMedDate not supplied

Evaluation of radiolabeled type IV collagen fragments as potential tumor imaging agents.

The objective of this study was to examine radiopharmaceuticals that target the alpha3beta1 integrin to determine if these agents target tumors for diagnostic imaging and/or targeted radiotherapy of cancer. Prior studies had shown that residues 531-542 from the alpha1 chain of type IV collagen bind a variety of tumor cell alpha3beta1 integrins. A peptide mimic of this sequence containing all D-amino acids (designated D-Hep-III) was synthesized by solid-phase methods. The tetraazamacrocyclic chelator, TETA, was conjugated to the peptide while it was resin-bound. TETA-D-Hep-III and D-Hep-III were radiolabeled with 64Cu and 125I, respectively, in high specific activity and radiochemical purity. Heterologous competitive binding assays between D-Hep-III and either 125I-D-Hep-III or 64Cu-TETA-D-Hep-III indicated low micromolar affinity of D-Hep-III. The biodistribution of each radiolabeled analogue of D-Hep-III was carried out in rats and tumor-bearing mice. Both analogues were rapidly cleared from the blood in normal rats, with the kidneys receiving the highest accumulation of each. SKOV3 human ovarian tumor cells, known to strongly express alpha3beta1, were xenografted in SCID mice. Localization of 125I-D-Hep III and 64Cu-TETA-D-Hep III in the xenografts were low (<2% ID/g), and in the case of 125I-D-Hep III, not inhibited by a competitive dose of D-Hep III. The low tumor accumulation is likely not due to receptor down-regulation, but rather due to the weak affinity of the radioligands for the alpha3beta1 integrin.

Animals↗
PubMedDate not supplied

Comparison of four bifunctional chelates for radiolabeling monoclonal antibodies with copper radioisotopes: biodistribution and metabolism.

The bifunctional chelating agents (BFCs), 6-[p-(bromoacetamido)benzyl]-1,4,8,11-tetraazacyclotetradecane-1,4 ,8, 11-tetraacetic acid (BAT), 6-[p-(isothiocyanato)benzyl]-1,4,8, 11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid (SCN-TETA), 4-[(1,4,8,11-tetraazacyclotetradec-1-yl)methyl]benzoic acid (CPTA), and 1-[(1,4, 7,10,13-pentaazacyclopentadec-1-yl)methyl]benzoic acid (PCBA), were synthesized and conjugated to the anti-colorectal monoclonal antibody (mAB), 1A3, and antibody fragments, 1A3-F(ab')2, for radiolabeling with 64,67CU and comparison in animal models. In vivo metabolism studies were carried out in liver and kidneys in order to correlate the nature of the metabolites formed to the uptake and retention of the radiolabel in each organ. Animal biodistribution studies were performed in Golden Syrian hamsters bearing the GW39 human colon cancer tumors and in normal Sprague-Dawley rats. All conjugates showed good tumor uptake in hamsters. Biodistribution in rats showed that 64CU-BAT-2IT-1A3 had the lowest liver and kidney uptake of the intact 1A3 conjugates (p < 0.03), whereas in hamsters, there were no significant differences in liver and kidney uptake between the four intact BFC-1A3 conjugates. Tumor-bearing hamsters injected with 64CU-CPTA-1A3-F(ab')2 and 64CU-PCBA-1A3-F(ab')2 had from 3 to 7 times greater uptake in the kidneys than hamsters given 64CU-labeled BAT and SCN-TETA 1A3-F(ab')2 conjugates, while rats injected with 64Cu-CPTA-1A3-F(ab')2 and 64Cu-PCBA-1A3-F(ab')2 had nearly twice the uptake. The in vivo metabolism of the mAbs 1A3 and 1A3-F(ab')2 radiolabeled with 67Cu through the SCN-TETA, CPTA, and PCBA BFCs was investigated by excising the livers and kidneys of normal rats from 1-5 days post-injection of the radiolabeled conjugates. Liver and kidney homogenates were analyzed by size exclusion chromatography and thin layer chromatography (TLC). The size exclusion chromatography data showed that all of the 67Cu-labeled 1A3-F(ab')2 conjugates were > 85% degraded in the kidneys to small molecular weight metabolites by 1 day post-injection. In contrast, in the liver at 1 day post-injection, greater than 70% of the 67Cu-labeled 1A3 conjugates were unmetabolized. By day 5, a 35 kDa peak appeared in the liver of rats injected with the 67 Cu-labeled 1A3 conjugates, possibly due to transchelation of the 67Cu to proteins. Superoxide dismutase chromatographically elutes at the same retention time as this 67Cu-labeled metabolite. The TLC data indicate that the low molecular weight metabolite (< 5 kDa) of both 67Cu-CPTA-1A3 and 67Cu-CPTA-1A3-F(ab')2 conjugates co-chromatographed with a 67Cu-CPTA-epsilon-lysine standard. Our data suggest that chelate charge and lipophilicity play a large role in kidney retention of 64/67Cu-labeled BFC-1A3-F(ab')2 conjugates, while transchelation of the copper label appears to be the major factor for liver accumulation of 64/67Cu-labeled BFC-1A3 conjugates.

Animals↗
PubMedDate not supplied

Identification of the soluble in vivo metabolites of indium-111-diethylenetriaminepentaacetic acid-D-Phe1-octreotide.

Indium-111-diethylenetriaminepentaacetic Acid-D-phenylalanine-octreotide ([111]In-DTPA-octreotide) is a cyclic eight amino acid somatostatin analogue which is approved for gamma scintigraphy of neuroendocrine tumors. To address the factors that contribute to liver and kidney retention of this radiopharmaceutical, its metabolism was evaluated in normal and tumor-bearing rats. The soluble fractions from nontarget (liver and kidney) and target (tumor, pancreas, adrenals) organ homogenates were analyzed out to 21 h postinjection, and urine was analyzed out to 12 h postinjection. The blood was analyzed at shorter time intervals due to the rapid clearance of (111)In-DTPA-octreotide. Radio-TLC and HPLC were used to analyze organ homogenates, blood, and urine. By TLC, intact (111)In-DTPA-octreotide was resolved from the soluble metabolites, and a similar apparent rate of metabolism was observed in the liver, kidney, tumor, and pancreas with approximately 30% intact (111)In-DTPA-octreotide at 4 h postinjection. In the adrenals, metabolism occurred more slowly with approximately 60% intact (111)In-DTPAoctreotide at 4 h postinjection. At 4 h postinjection, the activity excreted in the urine consisted of 85% intact (111)In-DTPA-octreotide. HPLC provided resolution of the individual extractable metabolites. In an attempt to identify these metabolites, two DTPA-amino acid sequences were synthesized: DTPA-D-Phe-Cys and DTPA-D-Phe. Under the conditions used for metabolite analysis, (111)In-DTPA-D-Phe-Cys-OH eluted at 14.6 min and (111)In-DTPA-D-Phe-OH eluted at 7.0 min. Each of these standard sequences was combined with the soluble portion of the organ homogenate and was shown by HPLC to coelute with the metabolites. These data suggest that (111)In-DTPA-octreotide was initially degraded to (111)In-DTPA-D-Phe-Cys-OH and (111)In-DTPA-D-Phe-OH. The (111)In-DTPA-D-Phe-Cys-OH was further degraded to (111)In-DTPA-D-Phe-OH, which appeared to be the final metabolite that was extracted from the organs. From these results, it can be concluded that at longer time points (> 2 h postinjection) a significant amount of (111)In was retained in nontarget organs as (111)In-DTPA-D-Phe-OH and (111)In-DTPA-D-Phe-Cys-OH and not as intact (111)In-DTPA-octreotide.

Adrenal Glands↗
PubMedDate not supplied

In vivo transchelation of copper-64 from TETA-octreotide to superoxide dismutase in rat liver.

An understanding of the metabolic fate of radiometal-labeled peptides is important due to their application in the areas of diagnostic imaging and targeted radiotherapy. Radioisotopes of copper ((64)Cu, T(1/2) = 12.7 h; (67)Cu, T(1/2) = 62 h) have been labeled to monoclonal antibodies (mAbs) and peptides and have applications in the areas of PET imaging and targeted radiotherapy of cancer. Copper-64-TETA-D-Phe(1)-octreotide ([(64)Cu]TETA-OC) has been shown to bind to the somatostatin receptor, both in vitro and in vivo, and this agent inhibited the growth of somatostatin-receptor positive tumors in rats. Copper-64-TETA-OC, however, showed a retention of activity in the blood, liver, and bone marrow, suggesting possible dissociation of (64)Cu from TETA-OC in vivo. The purpose of this study was to determine if (64)Cu dissociates from [(64)Cu]TETA-OC and binds to the protein, superoxide dismutase (SOD) in rat liver. The liver metabolism of [(64)Cu]TETA-OC was examined in normal rats using a gel-electrophoresis assay specific for SOD and size-exclusion chromatography. The major metabolite in rat liver at 20 h postinjection had a molecular weight of 32 kDa as shown by size-exclusion chromatography. A gel electrophoresis assay specific for the detection of SOD [nitro-blue tetrazolium (NBT)] showed that a (64)Cu-labeled protein isolated from rat liver homogenates comigrated with SOD. Evaluating the metabolic fate of copper radiopharmaceuticals demonstrated that Cu(II) dissociates from macrocyclic chelators such as TETA and binds to proteins in high concentrations, namely SOD in rat liver.

Animals↗
PubMedDate not supplied

Cytology of angiosarcoma in effusions.

The cytologic and immunocytochemical findings in pleural effusions from three cases of angiosarcoma are presented. In two of the cases, the primary lesion was on the scalp; in the third case, an angiosarcoma of the small intestine developed after radiotherapy for Hodgkin's disease. Single malignant cells and small clusters of cells were seen in cytologic preparations from two cases while only single cells were seen in preparations from one case. The malignant cells had delicate, finely vacuolated cytoplasm with distinct borders. No specific morphologic features were noted. Immunoperoxidase studies revealed binding of Ulex europaeus and reactivity for vimentin in all three cases and expression of Factor VIII-related protein in two of the cases but no expression of epithelial markers. The clinical history and immunoperoxidase studies are necessary to distinguish angiosarcoma from metastatic adenocarcinoma and other malignancies in effusions.

Aged↗
PubMedDate not supplied

Disseminated histoplasmosis diagnosed by fine needle aspiration biopsy of the adrenal gland. A case report.

A case of disseminated histoplasmosis diagnosed by fine needle aspiration (FNA) biopsy of the adrenal gland is reported for a 60-year-old man who presented with a 40-pound weight loss and abdominal computed tomography showing bilateral adrenal enlargement. FNA biopsy of the adrenal gland revealed clusters of macrophages with abundant cytoplasm containing the yeast forms of Histoplasma capsulatum. This case emphasizes that FNA is effective in diagnosing infectious as well as neoplastic conditions of the adrenal glands.

Adrenal Glands↗