PubMed Health⌕ Search

Biomedical subjects

J K Moran

Publications and source records attributed to J K Moran.

12 recordsLinked to original sources
PubMed1999

Technetium-99m-EC and other potential new agents in renal nuclear medicine.

Search for the ideal radiopharmaceutical to measure effective renal plasma flow (ERPF) has been underway since the early 1960s. Although ortho-iodohippuran (OIH) has biological properties suited for measurement of ERPF, the imaging characteristics are less than desirable. With the advent of the molybdenum-99/technetium-99m generators, efforts have focused on the development of a technetium-99m agent to measure ERPF. Over the last 10 to 15 years several promising technetium-99m renal imaging agents have been developed. Early examples of technetium-99m renal agents such as 99mTc-CO2DADS and 99mTc-PAHIDA, although not ideal replacements for OIH, demonstrated that a technetium-99m complex could be actively transported by the renal tubules and provided the impetus for development of new technetium-99m renal agents. The next breakthrough in technetium-99m renal agents was the development of the triamide mercaptide class of chelating agents by Fritzberg et al. To date the most promising compound in this class is mercaptoacetyltriglycine (MAG3). 99mTc-MAG3 is currently the agent of choice, but it is by no means the perfect replacement for OIH. Problems with high plasma protein binding and clearances that are only 50% to 60% of the OIH clearance make measurement of ERPF difficult. The serendipitous discovery that metabolites of the brain agent 99mTc-ethylenedicysteine diethylester (99mTc-L,L-ECD) are rapidly excreted in the urine has led to the evaluation of 99mTc-L,L-ethylenedicysteine (99mTc-L,L-ECD) as a potential renal imaging agent. Studies that have evaluated 99mTc-L,L-EC in animals, normal human volunteers, and patients with various renal disorders reveal that the renal clearance of 99mTc-L,L-EC is higher than 99mTc-MAG3 and more closely approaches that of OIH. Other approaches that are being examined in the development of the ideal renal imaging agent include substitution of various amino acids for glycine residue in MAG3 and technetium-99m labeled organic cations.

Animals↗
PubMed1999

Optimization of urinary FDG excretion during PET imaging.

UNLABELLED: Accumulation of fluorodeoxyglucose (FDG) activity in the urine interferes with the visualization of pelvic and, sometimes, abdominal abnormalities. Although this is a major problem, there are few data on the physiological variables affecting FDG urinary excretion that are critical to minimizing urinary FDG interference during PET imaging. METHODS: The excretion of FDG in urine was determined during 90 min in four groups of rats (n = 24) under the following conditions: normal, hydrated, hydrochlorothiazide treated and phlorizin treated. FDG clearance rates were measured in both normal and phlorizin-treated animals and compared with the glomeruler filtration rate measured with 99mTc-diethylenetriamine pentaacetic acid. We measured FDG excretion in 10 patients who had no known renal disease and were undergoing PET scanning (divided into two groups: hydrated and dehydrated) to relate the animal data to humans. RESULTS: The hydrated and phlorizin-treated animals had the highest excretion of FDG (39.68+/-5.00 % injected dose (%ID) and 45.64+/-9.77 %ID, respectively). Animals given the hydrochlorothiazide had the highest urinary volume, but the percentage excreted was comparable with the normal rats. Measurement of the clearance of FDG in animals before and after the administration of phlorizin determined the amount of FDG reabsorbed in the proximal tubules to be 56%+/-9.15%. The hydrated patients had a higher excretion of FDG than dehydrated patients (16.98+/-1.99 %ID versus 14.27+/-1.00 %ID, P < 0.021), and the volume of urine voided was significantly higher (P < 0.020). CONCLUSION: Hydrochlorothiazide increases urine volume without enhancing FDG excretion. The hydration of patients before PET scanning may lead to more FDG reaching the bladder. Reduction of bladder activity by more frequent voiding facilitated by increased urine volume in hydrated patients may be offset by increased delivery of FDG to the bladder. A preferable means of increasing urinary volume without increasing delivery of FDG to the bladder may be the use of a diuretic.

Animals↗
PubMed1998

New anti-Cu-TETA and anti-Y-DOTA monoclonal antibodies for potential use in the pre-targeted delivery of radiopharmaceuticals to tumor.

Monoclonal antibodies were raised against yttrium(III)-1, 4, 7, 10-tetraazacyclododecane-N,N',N''N'''--tetraacetic acid (Y-DOTA) and copper(II)-1, 4, 8, 11-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid (Cu-TETA). Four hybridomas with high Y-DOTA binding activity and one hybridoma with Cu-TETA activity were selected. MAbs were purified from mouse ascites by Protein A affinity chromatography and characterized. Affinity constants were determined by equilibrium dialysis and the highest affinity Y-DOTA MAb (K(aff) = 1.9 x 10(8) M(-1)) was further characterized by competitive ELISA. Gd-DOTA competed as well as Y-DOTA, whereas In-DOTA required 740x higher concentrations for 50% inhibition of this Y-DOTA MAb binding to human serum albumin-Y-DOTA-coated microtiter plates. These anti-metal chelate MAbs have potential use as vehicles for the pretargeted delivery of radiometal chelates to tumors.

Animals↗
PubMed1982

Metabolic balance studies and dietary protein requirements in patients undergoing continuous ambulatory peritoneal dialysis.

Balance studies for nitrogen, potassium, magnesium, phosphorus, and calcium were carried out in eight men undergoing continuous ambulatory peritoneal dialysis (CAPD) to determine dietary protein requirements and mineral balances. Patients were fed high energy diets for 14 to 33 days which provided either 0.98 (seven studies) or 1.44 g (six studies) of primarily high biological value protein/kg body wt/day. Mean nitrogen balance was neutral with the lower protein diet (+0.35 +/- 0.83 SEM g/day) and strongly positive with the higher protein diet (+2.94 +/- 0.54 g/day). With the higher protein diet the balances for potassium, magnesium, and phosphorus were strikingly positive, there was an increase in body weight in all patients, and a rise in mid-arm muscle circumference in five of the six patients. The relation between protein intake and nitrogen balance suggests that the daily protein requirement for clinically stable CAPD patients should be at least 1.1 g/kg/day; to account for variability among subjects 1.2 to 1.3 g protein/kg/day is probably preferable. Potassium balance correlated directly with nitrogen balance (r = 0.81). High fecal potassium losses (19 +/- 1.2 mEq/day) in all patients probably helped maintain normal serum potassium concentrations. Mean serum magnesium was increased (3.1 +/- 0.1 mg/dl), and magnesium balances were positive suggesting that the dialysate magnesium of 1.85 mg/dl is excessive. The net gain of calcium from dialysate was 84 +/- 18 mg/day; this correlated inversely with serum calcium levels (r = -0.90).

Adult↗
PubMed1982

Plasma amino acid levels and amino acid losses during continuous ambulatory peritoneal dialysis.

Free amino acid losses into dialysate during a 24-h collection period and postabsorptive plasma amino acid concentrations were measured in 14 studies in nine clinically stable men undergoing continuous ambulatory peritoneal dialysis. Patients ingested diets containing 97 +/- 18 (SD) g/day of protein in a metabolic research unit. Total amino acid losses were 3.4 +/- 1.2 g/24 h and represented 3.9 +/- 1.9% ot total nitrogen output (in dialysate, urine and feces). The sum of plasma essential, nonessential, and total amino acid concentrations was normal, although plasma valine, leucine, and isoleucine were decreased and several amino acids were elevated. Neither plasma nor dialysate amino acids, varied with protein intake. Dialysate amino acid concentrations averaged 72 +/- 18% of plasma levels, and 29.0 +/- 3.6% of dialysate amino acids were essential. Dialysate concentrations and 24 h losses of individual amino acids each correlated with plasma levels (r = 0.83 and 0.78, respectively). Thus during continuous ambulatory peritoneal dialysis, postabsorptive plasma amino acids are, in general, well maintained. Daily losses of free amino acids during continuous ambulatory peritoneal dialysis are rather small and are easily replaced by food intake.

Adult↗
PubMed1981

Nitrogen and urea metabolism during continuous ambulatory peritoneal dialysis.

During continuous ambulatory peritoneal dialysis (CAPD), concentrations of serum urea nitrogen (SUN) have been reported that are lower than what would be predicted from estimated dietary protein intake and the calculated urea clearance by dialysis. Net urea generation (urea nitrogen appearance) and losses of various nitrogenous constituents were measured during 12 metabolic studies in patients undergoing CAPD. Patients ingested constant diets containing either 1.0 or 1.4 g or protein per kilogram of body wt per day; total daily urea "clearance" from peritoneal dialysis plus renal clearance averaged 10.8 +/- 0.3 liters/day. Urea nitrogen appearance was only 55 and 68% of total nitrogen output with the low and high protein diets, respectively, values that are substantially lower than those reported in normal subjects, patients with chronic renal failure, and those undergoing hemodialysis. The reduction fraction of nitrogen appearing as urea was largely accounted for by the loss of protein and free amino acids into the dialysate. These respective constituents accounted fro 11.5 and 4.4% of total nitrogen output. Urea nitrogen appearance correlated closely (r = 0.96) with total nitrogen output in the patients undergoing CAPD.

Adult↗
PubMed1981

Glucose absorption during continuous ambulatory peritoneal dialysis.

Patients undergoing continuous ambulatory peritoneal dialysis (CAPD) are exposed to a continuous infusion of glucose via their peritoneal cavity. We performed studies to quantitate the amount of energy derived from dialysate glucose. Net glucose absorption averaged 182 +/- (SD) 61 g/day in 19 studies with a dialysate dextrose concentration of 1.5 or 4.25 g/dl. The amount of glucose absorbed per liter of dialysate (y) varied with the concentration of glucose in dialysate (x), (y = 11.3x - 10.9, r = 0.96). The amount of glucose absorbed per day during a given dialysis regimen was constant. Energy intake from dialysate glucose was 8.4 +/- 2.8 kcal/kg of body wt per day, or 12 to 34% of total energy intake. This additional energy may contribute to the anabolic effect reported during CAPD. The ability to vary glucose absorption by altering the dialysate glucose concentration may prove a useful tool to modify energy intake.

Ambulatory Care↗
PubMed1979

Applications of the Redy sorbent system to hemodialysis and peritoneal dialysis.

The application of sorbent technology to the treatment of uremia has been limited by the inability to adsorb urea adequately. Conversion of urea to ammonium carbonate and adsorption by zirconium phosphate provides a practical means of removing urea. This combination, together with hydrated zirconium oxide and carbon, removes uremic waste products from dialysate. Over 1500 patients are undergoing maintenance hemodialysis with this system. The dialysate composition can be modified for the treatment of patients with acute renal failure. This sorbent system is now being used for the regeneration of peritoneal dialysate. Twenty patients have undergone a total of 90 dialyses, each of 4 to 24 hours duration. One home patient has been solely on this system for two months. The application of sorbent technology to peritoneal dialysis may be the most promising approach to a wearable dialysis system.

Adsorption↗
PubMedDate not supplied

Improved synthesis of 6-[p-(bromoacetamido)benzyl]-1,4,8,11-tetraazacyclotetradecane- N,N',N",N"-tetraacetic acid and development of a thin-layer assay for thiol-reactive bifunctional chelating agents.

Monoclonal antibodies labeled with radiometals such as copper-67 have applications in radioimmunodiagnosis and radioimmunotherapy. Moi et al. [(1985) Anal. Biochem. 148, 249-253] showed that 6-[p-(bromoacetamido)benzyl]-1,4,8,11-tetraazacyclotetradecane- N,N',N",N"-tetraacetic acid (BAT) is an effective reagent for linking copper to proteins, and antibodies labeled with copper radionuclides are currently undergoing clinical trials. Here we describe improvements in the original synthesis that increase the overall yield of BAT to 23%. We also describe a new assay useful to determine the activity of bifunctional chelating agents with thiol-reactive functional groups.

Chelating Agents↗
PubMedDate not supplied

Synthesis of the protein cutting reagent iron (S)-1-(p-bromoacetamidobenzyl)ethylenediaminetetraacetate and conjugation to cysteine side chains.

Convenient methodology for preparation and conjugation of the protein-cutting iron chelate iron (S)-1-(p-bromoacetamidobenzyl) ethylenediaminetetraacetate (Fe-BABE) is given. This formulation of the reagent can be handled in a manner analogous to many other protein-labeling reagents, such as fluorescent probes or cross-linkers. By taking advantage of the recently discovered peptide hydrolysis reaction, the chelate may be tethered to a single site (e.g., a cysteine side chain) and used to map its proximity to individual peptide bonds by automated Edman sequencing of the protein fragments produced. The method is illustrated by conjugation of Fe-BABE to the carboxy terminal domain (amino acid residues 234-329) of the Escherichia coli RNA polymerase alpha subunit. The molecular mass of the protein conjugate was confirmed by electrospray ionization mass spectrometry.

Chromatography, High Pressure Liquid↗