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Biomedical subjects

L C Knight

Publications and source records attributed to L C Knight.

At least 73 records · Page 4Linked to original sources
PubMed1988

Selenium-75-labeled sucralfate: comparison with other radiolabels and initial clinical studies.

Sucralfate was synthesized to include a 75Se label, then compared with 111In-sucralfate and 99mTc-Human serum albumin (HSA)-sucralfate in vitro and in an animal ulcer model. The 75Se label was the only one of the three that was stable in both human gastric juice and simulated intestinal fluid in vitro. In rats with gastric ulcers, ulcer:nonulcer ratios of bound radioactivity averaged 15.4, 6.3, and 5.6 for 75Se, 111In, and 99mTc-HSA labels, respectively. Biodistribution studies of 75Se-sucralfate indicated that little is absorbed from the gastrointestinal tract, and the distribution is similar to that of 14C-sucralfate. Selective binding of 75Se sucralfate was successfully imaged in patients with esophagitis (esophageal mean T1/2 binding = 65 +/- 32 min), gastritis (gastric mean T 1/2 binding = 118 +/- 34 min), and gastric ulcers (ulcer mean T 1/2 binding = 135 +/- 59 min). Duodenal ulcers were not successfully imaged. Normal subjects showed no abnormal localization of sucralfate, and esophageal and gastric clearances were rapid.

Adult↗
PubMed1987

Binding properties of 111In-diethylenetriaminepentaacetic acid (DTPA)-fragment E1,2, a fibrin-specific probe, are dependent on use of protecting complex during attachment of DTPA groups.

Fragments E1 and E2, plasmic degradation products of crosslinked fibrin, bind specifically to polymers of fibrin. A mixture of these fragments, denoted as fragment E1,2, was radiolabeled with 111In after covalently attaching metal chelating groups (diethylenetriaminepentaacetic acid, DTPA) to the fragment, using two approaches. In the first approach, DTPA groups were attached directly to purified fragment E1,2. In the second approach, attachment sites of DTPA groups were directed away from the active region of the molecule by having fragment E1,2 bound in complex, with its active sites protected during the derivatization. Direct attachment of DTPA groups to fragment E1,2 resulted in complete loss of binding to fibrin in vitro. When derivatized in complex, 111In-DTPA-fragment E1,2 retained a higher degree of binding to human fragment DD and human plasma clots in vitro than did radioiodinated fragment E1, even when up to eight DTPA groups were attached per molecule of fragment E1,2.

Fibrin Fibrinogen Degradation Products↗
PubMed1986

Infection in diabetic osteoarthropathy: use of indium-labeled leukocytes for diagnosis.

Indium-111 labeled leukocyte imaging was compared with three-phase skeletal scintigraphy as a means of determining whether osteomyelitis was complicating diabetic osteoarthropathy. Three-phase scintigraphy demonstrated increased activity in both infected and noninfected osteopathic bone, with a sensitivity of 75% and a specificity of 56% for osteomyelitis. Leukocyte imaging had the same sensitivity but was most helpful for excluding infection (specificity, 89%) when three-phase imaging could not. Abnormal leukocyte localization was seen at the primary site of infection in all cases within 4 hours after injection. Disadvantages of leukocyte imaging included long preparation time, low count rates resulting in poor spatial resolution, and absence of bone landmarks, which made it difficult to differentiate soft tissue from bone infection.

Adult↗
PubMed1986

Clearance of human platelet factor 4 by liver and kidney: its alteration by heparin.

Human 125I-labeled platelet factor 4 (PF4) injected into rabbits showed a biphasic exponential pattern of disappearance from the circulation [half-life of the fast components was 0.75 min, that of the slow components was 20 min] that was not affected by a 1,000-fold excess of unlabeled PF4. Heparin resulted in a single-compartment disappearance of 125I-labeled PF4 (half-life = 25-40 min). Five minutes after injection of 125I-labeled PF4 greater than 40% radioactivity had accumulated in the liver and 4% in the kidney. At that time, accumulation of 125I-labeled beta-thromboglobulin (beta-TG) in the organs was low, approximately 4% in the kidneys and less than 3.0% in the liver. Nuclear imaging studies revealed rapid clearance of 131I-labeled PF4 from blood and its predominant accumulation in the liver. The half-lives of 131I-labeled PF4 radioactivity in liver and kidney were 96 and 252 min, fitting a single-compartment model. 131I-labeled beta-TG accumulated predominantly in the kidney. The half-lives of 131I-labeled beta-TG radioactivity in the kidney and in the liver were 84 and 414 min. Simultaneous or subsequent injection of heparin did not affect the distribution of 131I-labeled beta-TG but caused partial loss of 131I-labeled PF4 radioactivity from the liver and accelerated its appearance in the urinary bladder. Injection of heparin resulted in a 100-fold increase of excretion in the urine of 125I-labeled Pf4 precipitable by 10% trichloroacetic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

High molecular weight kininogen binds to unstimulated platelets.

Studies were performed to determine if the unstimulated platelet membrane has a site for high molecular weight kininogen (HMWK) binding. 125I-HMWK bound to unstimulated platelets. Zn++ was required for 125I-HMWK binding to unstimulated platelets and binding was maximal at 50 microM Zn++. Neither Mg++ nor Ca++ substituted for Zn++ in supporting 125I-HMWK binding to unstimulated platelets, and neither ion potentiated binding in the presence of 50 microM zinc. 125I-HMWK competed with equal affinity with HMWK for binding, and excess HMWK inhibited 125I-HMWK-platelet binding. Only HMWK, not prekallikrein, Factor XII, Factor XI, Factor V, fibrinogen, or fibronectin inhibited 125I-HMWK-platelet binding. 125I-HMWK binding to unstimulated platelets was 89% reversible within 10 min with a 50-fold molar excess of HMWK. Unstimulated platelets contained a single set of saturable, high affinity binding sites for 125I-HMWK with an apparent dissociation constant of 0.99 nM +/- 0.35 and 3,313 molecules/platelet +/- 843. These studies indicate that the unstimulated external platelet membrane has a binding site for HMWK that could serve as a surface to modulate contact phase activation.

Binding, Competitive↗
PubMed1985

Fragment E1 labeled with I-123 in the detection of venous thrombosis.

Fragment E1, which has been shown to have specific binding affinity for thrombi in an animal model, was investigated in humans for its safety and ability to bind to venous thrombi. Human Fragment E1 was labeled with I-123 and administered intravenously to patients with proved or suspected deep vein thrombosis. The vascular distribution of radioactivity was documented by obtaining gamma camera images of the patients' legs for 30 minutes following administration of I-123-Fragment E1. All patients (n = 5) with documented venous thrombi had rapid localization of labeled Fragment E1 in the area of thrombus. Patients without evidence of thrombi (n = 5) showed no focal localization, although two of these patients showed diffuse uptake along the length of the veins, due to superficial phlebitis. Analysis of blood samples in four patients indicated that disappearance of Fragment E1 from the circulation was more rapid in individuals with thrombosis (t 1/2 = 20 min) than in individuals without thrombosis (t 1/2 = 90 min), and a radiolabeled species of high molecular weight was found in patients with thrombosis but was absent from patients without thrombosis. These early results suggest that radiolabeled Fragment E1 is a safe and potentially valuable agent for the rapid detection of venous thrombosis.

Adolescent↗
PubMed1984

Association of fibrin with the platelet cytoskeleton.

We have previously postulated that surface membrane proteins become specifically associated with the internal platelet cytoskeleton upon platelet activation (Tuszynski, G.P., Walsh, P.N., Piperno, J., and Koshy, A. (1982) J. Biol. Chem. 257, 4557-4563). Four lines of evidence are in support of this general hypothesis since we now show that platelet surface receptors for fibrin become specifically associated with the platelet Triton-insoluble cytoskeleton. 1) Fibrin was detected immunologically in the washed Triton-insoluble cytoskeletons of thrombin-activated platelets under conditions where fibrin polymerization and resultant precipitation was blocked with Gly-Pro-Arg-Pro, a synthetic peptide that inhibits polymerization of fibrin monomer. 2) Radiolabeled fibrin bound to thrombin-activated platelets and became associated with the cytoskeleton. 3) The amount of radiolabeled fibrin bound to thrombin-activated thrombasthenic platelets and their cytoskeletons amounted to about 20% of the fibrin bound to thrombin-activated control platelets and their cytoskeletons. 4) The association of fibrin with cytoskeletons and with the platelet surface was nearly quantitatively blocked by an antibody prepared against cytoskeletons (anti-C), an antibody against isolated membranes of Pronase-treated platelets (anti-M1), and a monoclonal antibody to the platelet surface glycoprotein complex, GPIIb-GPIII (anti-GPIII). These antibodies blocked ADP and thrombin-induced platelet aggregation as well as thrombin-induced clot retraction. Analysis of the immunoprecipitates obtained with anti-C, anti-M1, and anti-GPIII from detergent extracts of 125I-surface labeled platelets revealed that these antibodies recognized GPIIb-GPIII. These data suggest that thrombin activation of platelets results in the specific association of fibrin with the platelet cytoskeleton, that this association may be mediated by the GPIIb-GPIII complex, and that these mechanisms may play an important role in platelet aggregation and clot retraction induced by thrombin.

Blood Platelets↗
PubMed1984

Blood coagulation factor XIa binds specifically to a site on activated human platelets distinct from that for factor XI.

Binding of 125I-Factor XIa to platelets required the presence of high molecular weight kininogen, was enhanced when platelets were stimulated with thrombin, and reached a plateau after 4-6 min of incubation at 37 degrees C. Factor XIa binding was specific: 50- to 100-fold molar excesses of unlabeled Factor XIa prevented binding, whereas Factor XI, prekallikrein, Factor XIIa, and prothrombin did not. When washed erythrocytes, added at concentrations calculated to provide an equivalent surface area to platelets, were incubated with Factor XIa, only a low level of nonspecific, nonsaturable binding was detected. Factor XIa binding to platelets was partially reversible and was saturable at concentrations of added Factor XIa of 0.2-0.4 microgram/ml (1.25-2.5 microM). The number of Factor XIa binding sites on activated platelets was estimated to be 225 per platelet (range, 110-450). We conclude that specific, high affinity, saturable binding sites for Factor XIa are present on activated platelets, are distinct from those previously demonstrated for Factor XI, and require the presence of high molecular weight kininogen.

Binding, Competitive↗
PubMed1983

Labeling of platelet surface proteins with 125I by the iodogen method.

A procedure for the 125I-iodination of platelet suspensions is described. The procedure utilizes Iodogen, a solid-phase oxidizing agent similar to chloramine-T. Platelets were labeled under a variety of conditions, including in the presence of 0.1% albumin, and showed between 7 and 28% incorporation of 125I. Best labeling results were obtained at low platelet concentrations (3-5 x 10(8) platelets/ml), short reaction times (15 min), and with 2-ml glass vials coated with 100 micrograms of Iodogen. Analysis of the labeled platelet proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography revealed that the same major protein bands were labeled by this procedure as were labeled by the lactoperoxidase procedure. At low platelet concentrations, the Iodogen procedure gives twice the amount of iodine incorporation.

Blood Platelets↗
PubMed1983

Long-term effects of dietary fiber on glucose tolerance and gastric emptying in noninsulin-dependent diabetic patients.

Effects of long-term (2 months) supplementation of diet with 20 g of guar gum and 10 g of wheat bran on metabolic control was studied in 12 obese, poorly controlled noninsulin-dependent diabetic patients. Addition of fiber reduced urinary excretion of glucose from 30.5 +/- 6 to 8.3 +/- 2 g/24 h, (p less than 0.025), fasting plasma glucose concentration from 301 +/- 24 to 184 +/- 15 mg/dl (p less than 0.025), and plasma cholesterol concentration from 277 +/- 24 to 193 +/- 9 mg/dl (p less than 0.025). No significant changes were observed in the patients weight and serum concentrations of triglycerides, high-density lipoproteins, free fatty acids, and insulin. Addition of fiber also delayed gastric emptying of liquids and solids. This effect became statistically significant 60 and 90 min after intake of a test meal for liquids and solids, respectively. We conclude that addition of guar and bran to the diet resulted in long-term improvement of metabolic control in these patients and that delayed gastric emptying may be one of the mechanisms responsible for this beneficial effect.

Adolescent↗
PubMed1983

Specific uptake of radioiodinated fragment E1 by venous thrombi in pigs.

Fragment E1, a product of plasmic digestion of cross-linked fibrin, binds specifically in vitro to polymerized fibrin but not to fibrinogen. Purified human Fragment E1 was radiolabeled with 125I or 131I by the Iodogen technique. The uptake of radioiodinated Fragment E1 in vitro into forming or preformed clots was demonstrated. Animal biodistribution studies of radioiodinated Fragment E1 showed its rapid removal from the circulation; radioactive catabolites did not reside long in any organ and were excreted in the urine. The uptake in vivo was evaluated in pigs with preexisting venous thrombi of various ages from 1 h up to 5 d at the time of intravenous systemic injection of the tracer. Radioiodinated fibrinogen was also injected into the same animals to compare the uptake of the two tracers. Thrombus-to-blood ratios for Fragment E1 averaged 43:1 (range 10-108) and 29:1 (range 8-107) in thrombi 1-6 h and 1-5 d old, respectively. In contrast, mean thrombus-to-blood ratios for fibrinogen were, in the same time intervals, 26:1 (range 17-41) and 2:1 (range 0.5-3.9), respectively. It is concluded that radioiodinated Fragment E1 is a specific marker of thrombi in vivo: its uptake by fresh thrombi is better than that of labeled fibrinogen and, in contrast to radioiodinated fibrinogen, this fragment is incorporated into old thrombi as well.

Animals↗
PubMed1983

Radiation dose estimates for oral agents used in upper gastrointestinal disease.

Radiation dosimetry was calculated for a number of orally administered radiopharmaceuticals used for study of upper gastrointestinal function. These include: Tc-99m sulfur colloid in water, in a cooked egg, and in chicken liver labeled in vivo; In-111 DTPA; Tc-99m DTPA; In-113m DTPA; Tc-99m ovalbumin in cooked egg; and In-111 colloid in chicken liver labeled in vivo. Radiation burdens to the stomach, small intestine, upper and lower large intestine, ovaries, testes, and total body are calculated for each preparation.

Administration, Oral↗
PubMed1982

Scintigraphic evaluation of gastric emptying.

There has been recent, renewed interest in studies of gastric emptying due in part to the introduction of new therapies for peptic ulcer diseases and attempts to better understand gastric physiology. Of the methods available for studying gastric emptying patterns, nuclear medicine techniques are optimal due to their noninvasive character, reproducibility and quantitative ability. The modulation of gastric emptying is multifactorial, and includes motor control, electrical activity, hormonal influences, and the composition of the meal itself: liquid vs solid; protein, carbohydrate and fat content; fiber or particle size; osmolality; pH; and pharmacologic agents. Because of the ease of performing gastric emptying studies using radiolabeled physiologic meals, these tests are being employed with increasing frequency in the evaluation of patients with disorders such as diabetic gastroparesis, postgastrectomy gastroparesis or dumping syndrome, and in the study of normal gastric physiology in man. Present data suggests that combined liquid-solid, dual radionuclide studies afford the greatest information regarding simultaneous gastric emptying patterns of liquid and solid components of a meal, and that single radionuclide, solid tests of gastric emptying are the more sensitive technique for determining subtle abnormalities of gastric emptying, when only a single tracer is employed.

Gastric Emptying↗
PubMed1981

Radiolabeling of fibrinogen using the iodogen technique.

The properties of human fibrinogen labeled with 125-Iodine using Iodogen (1, 3, 4, 6-tetrachloro-3 alpha, 6 alpha-diphenylglycoluril) as an oxidizing agent were compared with those of an iodine monochloride labeled counterpart. It was found that thrombin clottability, binding to staphylococci, the relative specific radioactivity of the A alpha, B beta, and gamma chains and in vivo clearance from plasma in rabbits were the same in these two labeled fibrinogen preparations. Labeling efficiency was higher when iodogen was used. It is concluded that human fibrinogen labeled with radioiodine using the Iodogen technique is suitable for studies in vitro and in vivo.

Animals↗
PubMed1980

Abdominal staging of testicular tumors using ultrasonography and computed tomography.

There were 36 patients with testicular tumors who underwent abdominal staging by ultrasonography, computed tomography or both before removal and pathologic examination of the retroperitoneal lymph nodes. Results showed that ultrasonography and computed tomography are accurate in predicting retroperitoneal metastases in more than 80 per cent of the patients, although computed tomography is more accurate and specific. The 1 falsely negative result with both methods occurred in a patient with microscopic (pathologic stage IIA) retroperitoneal disease. The falsely positive results with either technique were found in patients with borderline enlargement of the nodes (1 to 1.5 cm). Either computed abdominal tomography or abdominal ultrasonography is recommended for pre-treatment staging of testicular tumors.

Abdominal Neoplasms↗
PubMed1980

Inhibition of leukocyte locomotion by tocainide, a primary amine analog of lidocaine: at study with 111indium-labeled leukocytes and scanning electron microscopy.

The ability of tocainide (a primary amine derivative of lidocaine, 2-amino 2, 6-propionoxylidide) to inhibit leukocyte adhesion to and invasion of canine jugular veins was investigated. Leukocyte adhesion and migration were quantitated by use of 111indium-labeled leukocytes, and the morphologic characteristics of leukocytes and vessel lumen were studied by scanning electron microscopy. The morphologic characteristics of adhering and migrating 111indium-labeled leukocytes were similar to leukocytes that had not been manipulated, thus establishing their suitability for use as a marker for flammation. Exposure of leukocytes to 200 micrograms. per ml. of tocainide in autologous plasma in vitro inhibited adhesion and migration by 68 per cent. When labeled leukocytes were returned to the donor and exposed to intravenously infused tocainide the extent of reduction in adhesion and migration depended on whether tocainide infusion was started before or after neck dissection. Inhibition was only 46 per cent when dissection and injection of 111indium-labeled leukocytes preceded the start of infusion of tocainide but was 87 per cent when tocainide infusion was started before dissection and injection of leukocytes. The plasma level ranged from 25 to 47 microM over the 3 hour, 20 minute-infusion period, being 35 to 40 microM for the last hour. Migration of leukocytes across interendothelial junctions and their accumulation between the endothelial sheet and the basement membrane caused extensive damage to the endothelial lining of these veins. This was reduced when leukocyte migration was reduced. These observations suggest that the leukocyte-induced damage occurring in some sterile inflammations might be reduced by the use of local anesthetic drugs.

Anilides↗
PubMed1979

Computer tomography, radionuclide imaging and ultrasonography in hepatic mass lesions.

The livers of 86 patients comprising this report were examined by both transmission computerized tomography (CT) and radionuclide scans (LS). Fifty-nine of them were also examined by gray-scale ultrasound (US). In a comparative study, the strengths and weaknesses of each modality were evaluated. CT demonstrated 85%. US 82%, and LS 73% of masses involving the liver. Because of better resolution and sectioning capabilities, together with stop-motion imaging, CT and US detected smaller and deeper mass lesions than did LS. However, LS was more informative in hepatocellular disorders than was US or CT. Our experience indicated that information obtained on the liver and surrounding structures by each imaging modality used here tends to be somewhat unique, and thus these procedures complement one another rather than being competitive.

Humans↗