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Biomedical subjects

K A Morton

Publications and source records attributed to K A Morton.

36 records · Page 2Linked to original sources
PubMed1993

Enrichment for metallothionein does not confer resistance to cisplatin in transfected NIH/3T3 cells.

Evidence has been presented both that metallothionein does and does not produce resistance to cisplatin. The metallothionein-enriched cells described in most previous studies have been selected for resistance to heavy metals, such as cadmium, or have been maintained in a medium enriched for the metals. Exposure to toxic metals could alter the cells in many ways. This report addresses the effect of metallothionein content alone, independent of exposure to metals, on cellular resistance to cisplatin. The toxicity of cisplatin was compared in NIH/3T3 cells that vary in their content of metallothionein as a consequence of transfection with a plasmid that results in the constitutive expression of metallothionein. The plasmid contains the bovine papillomavirus genome and the mouse metallothionein-I gene; it is driven by a glucose-regulated protein of 78 kD. Control cells were transfected with a similar plasmid in which the coding sequences for metallothionein were inverted and separated from the promoter, thereby abolishing expression. Expression of metallothionein required neither selection nor maintenance of cells in the presence of heavy metals. Despite large differences between the two types of cells in their cellular content of metallothionein and in their resistance to the toxicity of cadmium, no differences in resistance to cisplatin were observed.

3T3 Cells↗
PubMed1993

Distribution of gallium-67 in normal and hypotransferrinemic tumor-bearing mice.

The mechanism by which 67Ga accumulates in tumors is controversial. The most popular theory is that 67Ga binds to transferrin and gains access to cells by the transferrin receptor. However, substantial evidence suggests that uptake of 67Ga may not be universally mediated by transferrin in tumors. To determine whether transferrin is required for uptake of 67Ga in vivo, we compared the uptake of 67Ga by two types of implanted tumors and by normal tissues in normal and severely hypotransferrinemic strains of Balb/C mice. One type of tumor was strongly gallium-avid in normal mice; the other was not. Uptake of 67Ga by normal soft tissues was markedly less in hypotransferrinemic than in normal mice. Uptake of 67Ga by bone was equivalent in the two types of mice. For the more gallium-avid tumor, uptake of 67Ga was similar and the ratio of tumor-to-background activity was substantially higher in the hypotransferrinemic than in the normal mice. For the less gallium-avid tumor, uptake was significantly less in hypotransferrinemic than in normal mice. These data suggest that uptake of 67Ga by bone and by some tumors may be a transferrin-independent process.

Animals↗
PubMed1993

Cerebrovascular accident associated with dipyridamole thallium-201 myocardial imaging: case report.

A patient with known aortoiliac occlusive disease and hypertension suffered a cerebrovascular accident 6.5 min after the administration of intravenous dipyridamole during a 201Tl myocardial study. Despite aminophylline administration, the patient developed a completed stroke. The mechanism most likely responsible for precipitating this patient's stroke is dipyridamole-induced vascular steal. Although dipyridamole-201Tl myocardial imaging is relatively free of major complications, the morbidity and mortality associated with a cerebrovascular accident is significant. The possibility of precipitating a cerebrovascular accident during dipyridamole-201Tl imaging should be considered in all patients with significant risk factors for stroke before performing a dipyridamole cardiac study.

Cerebrovascular Disorders↗
PubMed1993

Enthesopathy of the patellar tendon insertion associated with isotretinoin therapy.

A 99mTc-MDP bone scan performed on a 34-yr-old female for suspected osteomyelitis of the proximal tibia revealed focally increased activity in both tibial tuberosities due to enthesopathies secondary to chronic isotretinoin therapy. Physicians should be aware that isotretinoin therapy can cause abnormal bone scans and not mistake these abnormalities for other diseases such as osteomyelitis. Second, bone scans may be helpful in diagnosing and following isotretinoin bone toxicity.

Adult↗
PubMed1992

Uptake of cadmium is diminished in transfected mouse NIH/3T3 cells enriched for metallothionein.

To determine the relationship between cellular uptake of cadmium and content of metallothionein, we measured uptake of 109Cd in cells that differed in content of metallothionein (MT). MT cells were derived from NIH/3T3 cells by transfection with a plasmid containing the genome of bovine papilloma virus and the mouse metallothionein-I gene, driven by the promotor for the glucose-regulated protein of 78 kDa. Control cells were similarly transfected with bovine papilloma virus-based plasmids with the gene for metallothionein inverted and thus separated from the promoter (TM), or deleted, along with the promoter (BPA). The number of copies of bovine papilloma virus-based plasmids was similar in MT, TM, and BPA cells, approximately 100 per cell. MT cells were more than 10 times more resistant to the lethal effect of cadmium than were the control cells. Synthesis of metallothionein was 15-fold greater in the MT cells than in the TM or BPA cells. The uptake of 109Cd by the cells enriched in metallothionein was 4-fold less than by the control cells. These data suggest that an increased content of metallothionein may protect some cells from the toxic effects of cadmium, in part, by diminishing uptake of the metal.

3T3 Cells↗
PubMed1992

The use of computer-assisted diagnosis in cardiac-perfusion nuclear medicine studies: a review.

The use of computer-assisted diagnosis has become widespread in cardiac nuclear medicine. Quantitative programs are commercially available for ventriculography, phase analysis, and thallium 201 perfusion studies. The goal of these programs is to eliminate interobserver variability by objectively analyzing the studies without causing a loss of accuracy. In addition, by using quantitative data not apparent on visual inspection, some programs attempt to increase sensitivity for disease above that possible by the visual reading of images. Programs that analyze perfusion studies to detect coronary artery disease have received the most interest. Results have varied, but sensitivities as high as 95% have been reported. This review discusses the techniques of computer-assisted diagnosis for thallium 201 myocardial-perfusion studies. The circumferential and washout profile methods are discussed in detail.

Animals↗
PubMed1992

Embolization of hepatic arteriovenous malformations using radiolabeled and nonradiolabeled polyvinyl alcohol sponge in a patient with hereditary hemorrhagic telangiectasia: case report.

Polyvinyl alcohol sponge (PVA) radiolabeled with 99mTc-sulfur colloid was used to evaluate a large hepatic arteriovenous malformation (AVM) in a 71-yr-old white female prior to embolization. The patient had hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu) with severe left-to-right shunting through the hepatic AVM which resulted in high-output congestive heart failure. The patient also had severe pulmonary hypertension. Scintigraphic imaging of the embolized radiolabeled PVA particles allowed us to be certain that the particles did not flow through the liver and inadvertently embolize the lungs; with the patient's already poor pulmonary status, embolization could have been fatal.

Aged↗
PubMed1991

Physiological and pharmacological interventions in radionuclide imaging of the tubular gastrointestinal tract.

Radionuclide studies of the gastrointestinal tract (GI) are used to measure GI function and to detect anatomic lesions such as Meckel's diverticuli. A variety of physiological and pharmacological interventions have been applied to both types of studies to gain a better understanding of GI function and to improve detection of disease. This article will review interventions useful in imaging the tubular GI tract. Discussed are the measurement of GI motility and function by gastric emptying and imaging studies for GI bleeding including the Meckel's scan. Interventions involving the hepatobiliary system are covered elsewhere in this issue.

Cimetidine↗
PubMed1991

Radionuclide detection of occult infection: current strategies.

A number of new radionuclide techniques are available for diagnosing infection. These include the radiolabeling of neutrophils and lymphocytes with a variety of chelating agents and isotopes, and the use of antibodies directed against bacteria in the inflammatory exudate. Other new techniques include radiolabeled nanocolloids, chemotactic peptides, and liposomes. This article reviews the evolving role of these techniques in the detection of sites of occult infection.

Animals↗
PubMed1991

Naloxone reverses pattern of obstruction of the distal common bile duct induced by analgesic narcotics in hepatobiliary imaging.

It is widely known that narcotics, such as morphine, cause spasm of the sphincter of Oddi, increasing pressure in the common bile duct. This pharmacologic effect has been applied to hepatobiliary scintigraphy in patients with chronic cholecystitis or cholestasis to reducing the time required for a diagnostic study. However, this feature of narcotics could result in delayed or nonvisualization of the small bowel, simulating a distal common bile duct obstruction, in patients requiring parenteral narcotic analgesics who must undergo hepatobiliary scintigraphy. We report on three patients where administration of intravenous naloxone hydrochloride (Narcan), a narcotic antagonist, was helpful in distinguishing narcotic-induced spasm of the sphincter of Oddi from true obstruction of the common bile duct.

Adult↗
PubMed1991

Gastric emptying after gastric interposition for cancer of the esophagus or hypopharynx.

Transhiatal esophagectomy with primary anastomosis to the stomach (gastric pull-up) is an attractive surgical alternative to colic interposition in patients with cancer of the esophagus and hypopharynx. However, the lack of intrinsic gastric peristalsis and complaints by patients of postprandial regurgitation prompted us to measure the effect of body posture on the rates of gastric emptying in these patients. The rates of solid and liquid gastric emptying were measured in 14 patients who had undergone gastric interposition for esophageal and hypopharyngeal carcinoma. Rates of emptying were measured in both the supine and upright position using a dual-isotope radiolabeling technique. In these patients, the rate of gastric emptying of both solids and liquids was significantly slower in the supine position than in the upright position. Emptying in supine patients was also prolonged when compared with supine normal volunteers. Conversely, the upright rate of solid and liquid emptying in the patients was accelerated when compared with published values for upright normal volunteers. We conclude that gastric emptying after gastric interposition is dependent on upright posture after meals.

Adult↗
PubMed1990

Comparison of methods for calculating glomerular filtration rate: technetium-99m-DTPA scintigraphic analysis, protein-free and whole-plasma clearance of technetium-99m-DTPA and iodine-125-iothalamate clearance.

True glomerular filtration rate (GFR) was measured in normal volunteers and in patients with normal and impaired renal function by the iothalamate clearance (IC) method of Sigman. Within 24 hr, GFR was also determined by two other methods: technetium-99m- (99mTc) DTPA scintigraphic analysis (SA) utilizing a modification of the Gates computer program, and by measuring disappearance of 99mTc-DTPA from whole plasma (WPC) and from protein-free ultrafiltered plasma (PFPC). Determinations of GFR by IC and by PFPC methods were virtually identical (mean absolute error 5.36 ml/min, r = 0.99, p greater than 0.05). GFRs measured in protein-free, ultrafiltered plasma differed significantly from those obtained from whole plasma only in sicker patients and in those taking multiple medications (in whom alterations in protein-binding of DTPA may be seen). The SA method correlated less well with the iodine-125-(125I) IC method than did either the protein-free or whole-plasma clearance methods (mean absolute error 32.36 ml/min, r = 0.74, p less than 0.05). However, the SA method provided useful information with respect to differential (split) renal function.

Adult↗
PubMed1990

Diagnostic use of angiotensin converting enzyme (ACE)-inhibited renal scintigraphy in the identification of selective renal artery stenosis in the presence of multiple renal arteries: a case report.

In patients with renovascular hypertension, it is unknown whether the angiotensin converting enzyme-(ACE) inhibited renal scan will identify stenosis of a segmental branch of a single renal artery or of an accessory artery where multiple renal arteries are present. Since multiple renal arteries may be present in approximately 25% of all individuals, it will be important to establish whether the ACE-inhibited renal scan is useful in this population. We report a case of stenosis involving a renal artery in a patient with multiple renal arteries, successfully identified by ACE-inhibited renal scintigraphy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Uptake of cadmium-109, a metallothionein-binding radiometal, by tumors in mice as a function of the transformed phenotype.

Metallothionein (MT) is an intracellular protein that binds many metals with isotopes having imaging or radiotherapeutic potential. To determine whether uptake of radioisotopes that bind to MT is increased in tumors, we measured the uptake of cadmium-109 (Cd-109) in tumors and in normal tissues of mice. Tumors were grown in Balb/C mice from cultured Balb/3T3 cells transformed by the Moloney murine sarcoma virus (MMSV). Uptake of Cd-109 by MMSV tumors exceeded that by normal tissues examined, with the exception of liver and kidney (the organs known to be richest in metallothionein). The MMSV tumor:background ratios of activity were greater for Cd-109 than for gallium-67 for many of the normal tissues examined. The magnitude of uptake of Cd-109 by tumors from four related cell lines paralleled their degree of expression of two indices of the transformed, or malignant, phenotype. We conclude that metals that bind to MT may be useful for imaging or radiotherapy of cancer.

Animals↗
PubMed1987

SPECT thallium-201 scintigraphy for the detection of left-ventricular aneurysm.

We have noted that the presence of left ventricular anterior/apical aneurysm on contrast ventriculography or echocardiography correlates well with the finding of failure of convergence of the left ventricular walls toward the apex on single photon emission computed tomography (SPECT) thallium-201 images. To assess this observation, we analyzed the SPECT thallium scans of 74 sequential patients who had SPECT thallium scintigraphy and contrast ventriculography and/or echocardiography for evaluation of coronary artery disease. Immediate post-stress and 4-hr redistribution thallium-201 SPECT images, obtained following i.v. administration of 2 mCi of thallium-201, were reconstructed with no attenuation correction using three-dimensional linear and nonlinear filters and displayed in short, vertical-long, and horizontal-long axes. Of the 74 patients, contrast ventriculography and/or echocardiography showed anterior/apical aneurysms in 15 and a posterolateral aneurysm in one. SPECT thallium scans detected 14 of the 16 aneurysms, based on the criterion of failure of convergence of the ventricular walls toward the apex. There were two false-positives. Thus SPECT thallium-201 scintigraphy for the detection of left-ventricular aneurysm in this series had a sensitivity of 94%, a specificity of 97%, and an accuracy of 96%.

Adult↗
PubMed1983

Biosynthesis of 5-aminolevulinic acid and heme from 4,5-dioxovalerate in the rat.

We previously demonstrated an alternate pathway for the biosynthesis of 5-aminolevulinic acid (ALA) in bovine liver mitochondria and of tetrapyrroles in suspensions of rat hepatocytes (1980. J. Biol. Chem. 255: 3742; 1981. Proc. Natl. Acad. Sci. USA. 78: 5335). This pathway involves a transamination reaction that incorporates the intact 5-carbon skeleton of 4,5-dioxovaleric acid (DOVA) into ALA. We investigated this alternate pathway in vivo by the intraperitoneal injection of DOVA into rats. Incorporation of DOVA and [5-14C]DOVA into urinary ALA and hepatic and erythroid heme was quantified and compared with the incorporation of [4-14C]ALA and [2-14C]glycine into heme. Within 3 h of injection of 175 mumol of DOVA, urinary ALA excretion increased 2.4-fold over controls. After injection of [5-14C]DOVA, 0.11% of the radioactivity was recovered as urinary ALA, which quantitatively accounted for the 2.4-fold increase in ALA excretion. After the injection 175 mumol of [5-14C]DOVA, 0.14% of the radioactivity was recovered after 3 h as hepatic heme. The injection of 1.75 mmol of [2-14C]glycine or 175 mumol of [4-14C]ALA resulted in recovery of 0.2 and 3.4%, respectively, of the radioactivity as hepatic heme after 3 h. These doses of radiolabeled DOVA, glycine, and ALA were injected into rats with phenylhydrazine-induced anemia. Recovery of radioactivity after 3 h as splenic (erythroid) heme was 0.35% for DOVA, 0.072% for glycine, and 0.25% for ALA. These studies establish that the intact 5-carbon skeleton of DOVA can be incorporated into ALA and heme in vivo.

Aminolevulinic Acid↗
PubMed1981

Biosynthesis of porphyrins and heme from gamma, delta-dioxovalerate by intact hepatocytes.

The purpose of this study was to assess the ability of hepatocytes to synthesize porphyrins and heme from delta-aminolevulinic acid derived from gamma, delta-dioxovalerate and alanine. An alternate pathway for delta-aminolevulinic acid synthesis, in contrast to the condensation of succinate and glycine by delta-aminolevulinate synthase [succinyl-CoA:glycine C-succinyltransferase (decarboxylating), EC 2.3.1.37] has been suggested. This has been supported by the isolation of gamma, delta-dioxovalerate transaminase from liver mitochondria (Varticovski, L., Kushner, J. P. & Burnham, B. F. (1980) J. Biol. Chem. 255, 3742-3747). Gamma, delta-dioxovalerate transaminase catalyzes the formation of delta-aminolevulinic acid by a transamination reaction involving gamma, delta-dioxovalerate and alanine. To assess the significance of this alternate route, we prepared suspensions of respiring rat hepatocytes, which were incubated with optimal concentrations of various additives and then analyzed spectrophotometrically for synthesized porphyrins. No porphyrin synthesis was detected in cell suspensions incubated with succinate(1 mM) and glycine (20 mM). Cell suspensions incubated with gamma, delta-dioxovalerate (0.5-1.0 mM) and alanine (20 mM) synthesized 0.19 nmol of porphyrin per 10(7) cells per 2 hr (SD, 0.057). Cell suspensions incubated with delta-aminolevulinic acid (0.1 mM) synthesized 1.26 nmol of porphyrin per 10(7) cells per 2 hr (range, 1.18-1.32). Incubations with chemically synthesized gamma, delta-dioxo[5-14C]valerate were followed by extraction and purification of porphyrin esters and heme. Liquid scintillation counting revealed radiolabel incorporation into both porphyrins and heme. These studies demonstrate significant tetrapyrrole synthesis by the gamma, delta-dioxovalerate transaminase reaction. That gamma, delta-dioxovalerate is an important precursor of heme in vivo must be considered.

Alanine↗