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Biomedical subjects

L E Williams

Publications and source records attributed to L E Williams.

At least 109 records · Page 6Linked to original sources
PubMed1986

Imaging of human colorectal adenocarcinoma with indium-labeled anticarcinoembryonic antigen monoclonal antibody.

Twenty patients with 21 primary colorectal adenocarcinomas were studied with 2 mCl (7.6 X 10(7) becquerels) of indium-labeled monoclonal antibody (200 micrograms) specific for carcinoembryonic antigen (CEA). Fifteen lesions (71%) were visualized by gamma camera scintigraphy at 48 hours postinjection. Tumors that were identified by immunoscintigraphy were large (38.10 +/- 17.76 cm3 vs 6.00 +/- 1.65 cm3), had a grossly fungating component, had a high content of CEA by enzyme immunoassay (12.9 +/- 3.6 micrograms/g vs 3.3 +/- 1.7 micrograms/g), and had an apical and/or intraluminal staining pattern on immunohistologic section. Patients whose tumors were visualized had a low serum CEA level (1.9 +/- 0.4 ng/mL vs 14.6 +/- 8.0 ng/mL). Prospective selection of patients for follow-up imaging or therapy with radiolabeled monoclonal antibodies may be feasible using these measurements.

Antibodies, Monoclonal↗
PubMed1986

Carbohydrate partitioning and the capacity of apparent nitrogen fixation of soybean plants grown outdoors.

Patterns of leaf carbohydrate partitioning and nodule activity in soybean plants grown under natural conditions and the irradiance level required to produce sufficient carbohydrate to obtain maximum rates of apparent N(2)-fixation (acetylene reduction) were measured. Soybean plants, grown outdoors, maintained constant levels of leaf soluble sugars while leaf starch pools varied diurnally. When root temperature was kept at 25 degrees C and shoot temperature was allowed to vary with ambient temperature, the plants maintained constant rates of apparent N(2)-fixation and root+nodule respiration. Results from a second experiment, in which the entire plant was kept at 25 degrees C, were similar to those of the first experiment. Shoot carbon exchange rate of plants from the second experiment was light saturated at photosynthetic photon flux densities between 400 and 600 micromoles per square meter per second. When plants were subjected to an extended 40-hour dark period to deplete carbohydrate reserves, apparent N(2)-fixation was unaffected during the first 10 hours of darkness, decreased rapidly between 10 and 16 hours, and plateaued at one-third the initial level thereafter. After the extended dark period, plants were exposed to photosynthetic photon flux density from 200 to 1000 micromoles per square meter per second for 10 hours. Photosynthetic photon flux densities of 200 micromoles per square meter per second and greater resulted in maximum leaf soluble sugar content and nodule activity. Leaf starch content increased with irradiance levels up to 600 micromoles per square meter per second with no further increase at higher irradiance levels. Results presented here indicate that maximum nodule activity occurs at irradiance levels that do not saturate the plant's photosynthetic apparatus. This response would allow for maximum N(2)-fixation to occur in a nodulated legume during periods of inclement weather.

Journal Article↗
PubMed1986

Preoperative imaging of colorectal carcinoma with 111In-labeled anticarcinoembryonic antigen monoclonal antibody.

Patients with primary, recurrent, or metastatic colorectal adenocarcinoma were given injections of 200 micrograms of anticarcinoembryonic antigen (CEA) monoclonal antibody labeled with 2 mCi of 111In (Indacea). Patients were imaged at 24 and 48 h. Celiotomy was performed on 40 patients between 3 and 17 days post-Indacea injection. Of 16 primary tumors, 11 (69%) were imaged. Of six extrahepatic recurrences, none was imaged. Intrahepatic metastases were visualized as negative images in 10 of 24 (42%) patients. On the basis of the activity in tissue expressed as a percentage of the total radioactive dose per kg injected into the patient (% ID/kg), extrahepatic tumors that were imaged using Indacea had a significant uptake of radiolabel in the tumor [5.99 +/- 0.91% ID/kg (SE)] and in the associated normal mesenteric lymph nodes (12.0 +/- 2.4% ID/kg). The CEA content of these tumors was high (13.3 +/- 4.7 micrograms/g), and, histologically, the CEA was located primarily apically or intraluminally. Intrahepatic tumor imaging correlated only with tumor size. The greatest Indacea uptake was seen in normal liver (22.1 +/- 3.2% ID/kg). Low Indacea uptake was seen in fat (0.21 +/- 0.05% ID/kg) and bowel wall (1.11 +/- 0.17% ID/kg). In conclusion, Indacea imaging of colorectal carcinoma is specific for high concentrations of accessible CEA in CEA-bearing tumors or in lymph nodes draining these tumors. The successful clinical use of monoclonal antibodies for tumor imaging and therapy will require careful selection of patients for a number of antigen-related parameters including antigen content and distribution in tumors. This information will only come from careful correlation between image results and tissue analysis. High uptake by normal liver tissue is the major unresolved problem with labeled antibody imaging.

Antibodies, Monoclonal↗
PubMed1986

Testis imaging with 111In-labeled anticarcinoembryonic antigen monoclonal antibody: identification of carcinoembryonic antigen in normal germ cells.

A monoclonal antibody to carcinoembryonic antigen (CEA) labeled with 111In (Indacea) was used to image tumors in patients with colorectal cancer. The anti-CEA antibody has a high affinity (2.6 X 10(10) M-1) for CEA and does not cross-react with normal cross-reacting antigen, biliary glycoprotein-1, or tumor-extracted, CEA-related antigen. During the course of these studies, it was noted that a significant number of male patients (20 of 27, 74%) showed uptake of Indacea in the testes. In order to determine if the Indacea uptake was specific, 20 testicular specimens were analyzed by immunohistological methods using five different anti-CEA CEA monoclonal antibodies recognizing five different epitopes on CEA. In 18 cases (90%) germ cells were uniformly stained by all five antibodies. Fresh frozen testis tissue was homogenized in water and precipitated with 1.0 M perchloric acid. The supernatant contained a CEA-like material as measured by an enzyme immunoassay specific for CEA. The same supernatant was radiolabeled with 125I and immunoprecipitated with anti-CEA monoclonal antibodies. Sodium dodecyl sulfate:polyacrylamide gel electrophoresis of the immunoprecipitates revealed a single species (Mr 180,000) which was indistinguishable from CEA. This study documents the first description of CEA in the germ cells of normal testis. The CEA in the testis was accessible to circulating monoclonal antibodies in the majority of male patients tested.

Adult↗
PubMed1985

Biodistribution of phospholipid vesicles in mice bearing Lewis lung carcinoma and granuloma.

Murine biodistributions of vesicle-encapsulated [111In]NTA were obtained under a number of conditions. These included normal animals, those bearing s.c.- or i.v.-implanted Lewis Lung Carcinoma (LLC) and those having both s.c.-LLC and sterile granuloma. Variations in the distributions were observed with a preinjection of unlabeled aminomannose (AM) vesicles or an increase in the labeled vesicle size. It was found that s.c. LLC exhibited uptake of between 10 and 25% injected dose/g (% ID/g) depending upon tumor mass with larger lesions having lower accumulation. Significant uptake enhancement (p less than 0.05) occurred after AM blockade. Similar results hold for the i.v.-injected LLC cells implying targeting to both primary and metastatic sites. By increasing vesicle size by a factor of 4, uptake by s.c. LLC declined to essentially blood levels; e.g., 2% ID/g. Granuloma accumulations were also at circulating values and, unlike s.c. LLC, could not be imaged.

Animals↗
PubMed1985

Is stability a key parameter in the accumulation of phospholipid vesicles in tumors?

Phospholipid vesicle (liposome) stability in human plasma was determined using perturbed angular correlation (PAC) with 111In as the aqueous phase marker. Using compositions given in earlier tumor imaging studies, liposomes were made with either egg lecithin (EL) or distearoyl phosphatidylcholine (DSPC) as the dominant phospholipid. With fresh human plasma at 37 degrees C. EL vesicles lysed much more rapidly with survival half times being 7 hr at 6.7 mg lipid/ml plasma. DSPC liposomes had a half-time of 130 hr independent of lipid concentration. No lysis occurred with plasma previously stored for 1 wk at 5 degrees C. The addition of 143 USP units of heparin per 4.5 ml sample decreased both half-times by two orders of magnitude. We conclude that EL vesicles exhibit plasma survival times much shorter than those found with DSPC liposomes; this may preclude the former agents from having significant tumor accumulation in vivo.

Half-Life↗
PubMed1985

High-specific-activity 111In-labeled anticarcinoembryonic antigen monoclonal antibody: improved method for the synthesis of diethylenetriaminepentaacetic acid conjugates.

A new method has been developed for conjugating diethylenetriaminepentaacetic acid (DTPA) to proteins using the N-hydroxysuccinimide active ester of DTPA. The DTPA-active ester was prepared using diisopropylcarbodiimide in a simple single step synthesis. DTPA-conjugated proteins were prepared by adding the DTPA-active ester reaction mixture to protein solutions (5 mg/ml) buffered at pH 7.0 and purified by Sephadex G-50 chromatography. A monoclonal antibody directed against carcinoembryonic antigen was reacted with four different amounts of the DTPA-active ester. Solid-phase enzyme immunoassay showed that the immunological activity of the antibody conjugate was not altered when the active ester: antibody molar ratio was 36:1 or 72:1; however, it decreased when the ratio was 180:1 or 360:1. The antibody heavy and light chains had slightly decreased electrophoretic mobilities when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, a result consistent with the covalent attachment of DTPA to the protein. Sephadex G-200 chromatography showed that the native and conjugated antibodies were the same size. When the DTPA-conjugated antibody was incubated with 10, 50, and 100 microCi of 111In/micrograms of protein, specific activities of 9.8, 43.1, and 56.3 microCi/micrograms were obtained. Enzyme immunoassay and radioimmunoassay of the 111In-labeled antibody showed that it retained its full immunological activity. The high specific activity of the 111In-labeled antibody makes it suitable for imaging carcinoembryonic antigen-bearing tumors using low doses of antibody.

Animals↗
PubMed1985

High-specific-activity 111In-labeled anticarcinoembryonic antigen monoclonal antibody: biodistribution and imaging in nude mice bearing human colon cancer xenografts.

Tumor imaging and biodistribution of an indium-labeled monoclonal antibody (MAB) to carcinoembryonic antigen (CEA) [anti-CEA MAB-diethylenetriaminepentaacetic acid (DTPA)-111In] have been investigated using LS174T human colon cancer xenografts in nude mice. Antibody specificity, dose, and specific activity were examined with respect to tumor uptake and quality of scintiscans at different times following injection. The CEA-bearing LS174T tumors were imaged specifically with anti-CEA MAB-DTPA-111In. Using 62.5 ng of indium-labeled MAB (50 microCi/micrograms) the ratio of activity in tissue expressed as a percentage of the total radioactive dose injected into the animal per gram tissue for tumor:blood increased from 0.66 +/- 0.02 (SE) at 1 h to 14.8 +/- 1.1 at 72 h. Scintiscan quality improved with the rise in tumor:blood ratio until 48 h. At longer intervals insufficient counts remained for imaging. The tumor:blood ratio and the scintiscan quality were not improved by increasing the MAB dose to 625 or 6250 ng but good images were obtained at longer times postinjection. By decreasing the 111In from 50 to 10 microCi/micrograms of MAB, the unbound 111In was decreased from 7 microCi/micrograms (14%) to 0.2 microCi/micrograms (2%). Even with the lower specific activity (9.8 microCi/micrograms) of the 10-microCi/micrograms preparation, scintiscan quality at the 62.5-ng dose was maintained. This anti-CEA MAB-DTPA-111In preparation was stable, retained immunological activity, did not require column chromatography to remove unbound 111In, was specific for a CEA-bearing tumor, and was effective for tumor imaging over a wide range of antibody doses (3 to 300 micrograms MAB/kg body weight). This anti-CEA MAB-DTPA-111In preparation is feasible and practical for imaging CEA-bearing tumors in humans.

Animals↗
PubMed1985

Serum hormone patterns during abortion in the Bolivian squirrel monkey.

Serum measurements of chorionic gonadotropin (CG), estradiol (E-2) and progesterone (P) were used to describe patterns of hormonal change in Bolivian squirrel monkeys undergoing spontaneous abortion. During early pregnancy, serum CG levels gradually increased, reaching maximum levels at the end of the first 50 days of pregnancy (range: 200-1964 ug protein/ml). E-2 concentrations also increased to high levels (10-30 ng/ml) toward the end of pregnancy, while serum P remained fairly constant at levels above 100 ng/ml. A gradual decline in serum hormone concentrations was observed in aborting animals. CG levels declined to less than 100 ug protein/ml while E-2 and P decreased to concentrations characteristic of nonpregnant cycling animals, less than 500 pg/ml and 20 ng/ml respectively. The data suggest that two weekly measurements of CG and E-2 could be used to identify monkeys undergoing abortion and those which have already aborted.

Abortion, Veterinary↗
PubMed1983

Liposomal blockade of the reticuloendothelial system: improved tumor imaging with small unilamellar vesicles.

The reticuloendothelial system of mice bearing EMT6 tumors was effectively blocked by intravenous injections of small unilamellar vesicles that incorporated a 6-aminomannose derivative of cholesterol in the lipid bilayer. Neutral liposomes loaded with indium-111-nitrilotriacetic acid were then injected. Fifty percent more radioactivity was deposited in tumors of the animals with blocked reticuloendothelial systems than in controls. Twenty-four hours after the injection of radioactive vesicles, well-defined tumor images were observed in whole-body gamma camera scintigraphs. Biodistribution studies showed that tumors from animals with blocked reticuloendothelial systems had more than twice the radioactivity per gram than any other tissue analyzed.

Animals↗
PubMed1983

Introduction and dominance manipulations involving old rhesus males.

Many investigators may feel that studies involving group manipulations involving older animals are untenable, fearing that such manipulations may harm or over-stress aged subjects. The present study demonstrates the safety of a technique which not only introduced aged rhesus monkeys into two groups, but resulted in their attaining planned dominance rank positions in each of the groups: one set of 4 as the highest ranking and the other set of 4 as the lowest ranking. The manipulation also effected the social behavior of the old animals isolating the high ranking males from social activity in their group.

Age Factors↗
PubMed1983

Tumor-imaging potential of liposomes loaded with In-111-NTA: biodistribution in mice.

EMT6 tumors in BALB/c mice have been successfully imaged with small (less than 0.1 mu), unilamellar lipid vesicles (SUVs) loaded with In-111 nitrilotriacetic acid (In-111 NTA). Neutral SUVs prepared from distearoyl phosphatidylcholine (DSPC) and cholesterol (CH) (ratio 2:1) delivered sufficient radioactivity to allow tumor visualization 24 hr after i.v. injection; so did positively and negatively charged SUVs with the ratio 4:1:1 for DSPC:CH:X, were X was stearylamine or dicetyl phosphate. Other SUVs containing a 6-aminomannose or 6-aminomannitol derivative of cholesterol did not cause significant tumor accumulation of In-111 NTA, and tumor images were not readily discernible. The maximum tumor-associated radioactivity, 18.5% of injected dose per gram of tissue, was achieved with neutral SUVs. This level of tumor-associated In-111 was over 4 times that observed when unencapsulated In-111 NTA was injected. Neutral SUVs also gave the lowest specific activities in the liver and spleen (14.6% and 18.8% of dose respectively).

Acetates↗
PubMed1982

Effect of changes in shoot carbon-exchange rate on soybean root nodule activity.

The effect of short- and long-term changes in shoot carbon-exchange rate (CER) on soybean (Glycine max [L.] Merr.) root nodule activity was assessed to determine whether increases in photosynthate production produce a direct enhancement of symbiotic N(2) fixation. Shoot CER, root + nodule respiration, and apparent N(2) fixation (acetylene reduction) were measured on intact soybean plants grown at 700 microeinsteins per meter per second, with constant root temperature and a 14/10-hour light/dark cycle. There was no diurnal variation of root + nodule respiration or apparent N(2) fixation in plants assayed weekly from 14 to 43 days after planting. However, if plants remained in darkness following their normal dark period, a significant decline in apparent N(2) fixation was measured within 4 hours, and decreasing CO(2) concentration from 320 to 90 microliters CO(2) per liter produced diurnal changes in root nodule activity. Increasing shoot CER by 87, 84, and 76% in 2-, 3-, and 4-week-old plants, respectively, by raising the CO(2) concentration around the shoot from 320 to 1,000 microliters CO(2) per liter, had no effect on root + nodule respiration or acetylene-reduction rates during the first 10 hours of the increased CER treatment. When the CO(2)-enrichment treatment was extended in 3-week-old plants, the only measured parameter that differed significantly after 3 days was shoot CER. After 5 days of continuous CO(2) enrichment, root + nodule respiration and acetylene reduction increased, but such changes reflected an increase in root nodule mass rather than greater specific root nodule activity. The results show that on a 24-hour basis the process of symbiotic N(2) fixation in soybean plants grown under controlled environmental conditions functioned at maximum capacity and was not limited by shoot CER. Whether N(2)-fixation capacity was limited by photosynthate movement to root nodules or by saturation of metabolic processes in root nodules is not known.

Journal Article↗
PubMed1981

Carbon and nitrogen limitations on soybean seedling development.

Carbon and nitrogen limitations on symbiotically grown soybean seedlings (Glycine max [L.] Merr.) were assessed by providing 0.0, 1.0, or 8.0 millimolar NH(4)NO(3) and 320 or 1,000 microliters CO(2)/liter for 22 days after planting. Maximum development of the Rhizobium-soybean symbiosis, as determined by acetylene reduction, was measured in the presence of 1.0 millimolar NH(4)NO(3) under both levels of CO(2). Raising NH(4)NO(3) from 0.0 to 8.0 millimolar under 320 microliters CO(2)/liter increased plant dry weight by 251% and Kjeldahl N content by 287% at 22 days after planting. Increasing NH(4)NO(3) from 1.0 to 8.0 millimolar under 320 microliters CO(2)/liter increased total dry weight and Kjeldahl N by 100 and 168%, respectively, on day 22. Raising CO(2) from 320 to 1,000 microliters CO(2)/liter during the same period had no significant effect on Kjeldahl N content of plants grown with 0.0 or 1.0 millimolar NH(4)NO(3). The maximum CO(2) treatment effects were observed in plants supplied with 8.0 millimolar NH(4)NO(3), where dry weight and Kjeldahl N content were increased 64% and 20%, respectively. An increase in shoot CO(2)-exchange rate associated with the CO(2)-enrichment treatment was reflected in a significant increase in leaf dry weight and starch content for plants grown with 1,000 microliters CO(2)/liter under all combined N treatments. These data show directly that seedling growth in symbiotically grown soybeans was limited primarily by N availability. The failure of the CO(2)-enrichment treatment to increase total plant N significantly in Rhizobium-dependent plants indicates that root nodule development and functioning in such plants was not limited by photosynthate production.

Journal Article↗