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Biomedical subjects

L E Williams

Publications and source records attributed to L E Williams.

At least 91 records · Page 5Linked to original sources
PubMed1990

Further Characterization of the Red Beet Plasma Membrane Ca-ATPase Using GTP as an Alternative Substrate.

The GTP-driven component of Ca(2+) uptake in red beet (Beta vulgaris L.) plasma membrane vesicles was further characterized to confirm its association with the plasma membrane Ca(2+)-translocating ATPase and assess its utility as a probe for this transport system. Uptake of (45)Ca(2+) in the presence of GTP demonstrated similar properties to those previously observed for red beet plasma membrane vesicles utilizing ATP with respect to pH optimum, sensitivity to orthovanadate, dependence on Mg:substrate concentration and dependence on Ca(2+) concentration. Calcium uptake in the presence of GTP was also strongly inhibited by erythrosin B, a potent inhibitor of the plant plasma membrane Ca(2+)-ATPase. Furthermore, after treatment with EGTA to remove endogenous calmodulin, the stimulation of (45)Ca(2+)-uptake by exogenous calmodulin was nearly equivalent in the presence of either ATP or GTP. Taken together these results support the proposal that GTP-driven (45)Ca(2+) uptake represents the capacity of the plasma membrane Ca(2+)-translocating ATPase to utilize this nucleoside triphosphate as an alternative substrate. When plasma membrane vesicles were phosphorylated with [gamma-(32)P]-GTP, a rapidly turning over, 100 kilodalton phosphorylated peptide was observed which contained an acyl-phosphate linkage. While it is proposed that this peptide could represent the catalytic subunit of the plasma membrane Ca(2+)-ATPase, it is noted that this molecular weight is considerably lower than the 140 kilodalton size generally observed for plasma membrane Ca(2+)-ATPases present in animal cells.

Journal Article↗
PubMed1990

Hypoglycemia of squirrel monkey neonates: implications for infant survival.

Neonatal deaths are a serious problem in breeding colonies of squirrel monkeys. Seriously ill neonates in our colony are always hypoglycemic on presentation. To determine normal glucose values for squirrel monkey infants of various ages, serum glucose determinations were done at 1, 3, 7, 10, 14 days and 1 month of age using a standard laboratory test for serum glucose. Glucose concentration increased from a low of 49 +/- 3 mg/dl (Mean +/- SEM) at 1 day (n = 21) to 109 +/- 4 mg/dl at 1 month of age (n = 17). Glucose values for 1, 3 and 7 day-old infants were significantly lower than 1 month-old infants (P less than .05). To provide a time-averaged indication of blood glucose, glycosylated hemoglobin (GHb) measurements were made at 1 day, 1 week, 2 weeks, 1 month, 2 months, 1 year of age and in adults (greater than 3 years of age). GHb values ranged from 2.6% +/- 0.1 for 1 day old infants (n = 13) to 4.0 +/- 0.2 for adults (n = 10) with a steady increase during the first 2 months of life. Animals 1 year of age and younger had significantly lower glycosylated hemoglobin than adults. These studies indicate that blood glucose concentration is significantly lower in squirrel monkey neonates than in older infants, juveniles and adults. Maternal rejection, trauma, and associated problems occur commonly in socially reared squirrel monkeys. The marginal hypoglycemic state of these infants places them at high risk for clinical hypoglycemia as a sequel to such perturbations.

Age Factors↗
PubMed1989

Effect of specific antibody pretreatment on liver uptake of 111In-labeled anticarcinoembryonic antigen monoclonal antibody in nude mice bearing human colon cancer xenografts.

Administration of a large dose (0.2 mg) of unlabeled specific anticarcinoembryonic antigen (anti-CEA) monoclonal antibody (MAB) to nude mice bearing LS174T human colon cancer xenografts significantly decreased normal liver uptake of 111In-labeled anti-CEA MAB (Indacea). Mice bearing tumors of approximately 1 g showed liver accumulation of indium-111 at 48 h following injection of 2 micrograms/10 microCi Indacea of 33.8 +/- 1.5% injected dose per gram (%ID/g) (N = 25). Treatment with 0.2 mg unlabeled anti-CEA MAB reduced this to 8.9 +/- 0.5% ID/g (N = 22; P less than 0.001). The dose of pretreatment was found to be critical. Increasing the amount of unlabeled MAB to 2.0 mg did not significantly improve the liver level of indium-111, but did compromise the tumor uptake of Indacea (15.9 +/- 1.3 versus 12.4 +/- 0.4% ID/g; P less than 0.05). Lowering the dose of pretreatment 10-fold resulted in increased (P less than 0.001) liver uptake of the label (26.5 +/- 2.8% ID/g). The unlabeled anti-CEA MAB treatment given as a single dose or fractionated over several days gave the same results. The decrease in liver uptake was the same for i.v. administration of the unlabeled MAB given 1 week prior to Indacea injection or mixed together with Indacea. With i.p. administration, simultaneous injection of the unlabeled MAB with Indacea was not as effective as pretreatment (20 min to 7 days) in decreasing the liver uptake of 111In (P less than 0.05). Epitope specificity and affinity were shown to be important considerations in the choice of MAB combinations used for pretreatment and imaging. Pretreatment with nonspecific MAB was ineffective in decreasing liver uptake of Indacea.

Animals↗
PubMed1989

Impact of radiolabeled antibody imaging on management of colon cancer.

One hundred patients with known or suspected colorectal cancer were studied by radioimmunoconjugate scintigraphy prior to operation. Study subjects received murine monoclonal anticarcinoembryonic antigen labeled with indium 111 (Indacea). Sensitivity of imaging was 76 percent for primary tumors, 44 percent for hepatic metastases, 38 percent for extrahepatic abdominal metastases, and 78 percent for extraabdominal metastases. Seventeen of 46 patients (37 percent) with known or suspected hepatic metastases and no evidence of extrahepatic disease by conventional imaging methods had extrahepatic metastases at exploratory surgery. Nine of the 17 patients had disease accurately predicted by the Indacea scanning. The management of each of these nine patients was, or could have been, modified by the scan findings and unnecessary surgery eliminated. A number of patients without post-operative disease had an unexplained increase in plasma carcinoembryonic antigen level due to production of human antimouse antibody. The addition of excess mouse immunoglobulin to the plasma prior to assay blocked this artifactual increase.

Adenocarcinoma↗
PubMed1989

The effects of hyperthermia on tumor carcinoembryonic antigen expression.

The effects of hyperthermia on carcinoembryonic antigen (CEA) expression were investigated. The human colon adenocarcinoma cell line, LS174T, was heated in vitro for 42 degrees C/1 hr, 43 degrees C/1 hr, or 45 degrees C/30 min. Carcinoembryonic antigen membrane expression was assayed by live cell radioimmunoassay 0-6 days after heating. A heat exposure of 45 degrees C/30 min resulted in an initial decrease in carcinoembryonic antigen membrane expression 1 day post-heating followed by a 2-3 fold increase which peaked 3 days post-heating. Carcinoembryonic antigen expression began returning to normal by the sixth day. Heat exposures of 42 degrees C/1 hr and 43 degrees C/1 hr also resulted in increased carcinoembryonic antigen expression but this increase was of lesser magnitude and of shorter duration. Carcinoembryonic antigen shed into the medium, as measured by enzyme immunoassay, also increased after heating in a temperature-dependent fashion. Flow cytometry analysis demonstrated that cells in all phases of the cell cycle expressed this increase. We conclude that hyperthermia results in significant changes in carcinoembryonic antigen membrane expression and shedding. The implications that these findings have with regards to clinical hyperthermia and radioimmunotherapy are discussed.

Adenocarcinoma↗
PubMed1989

The effects of tumor mass, tumor age, and external beam radiation on tumor-specific antibody uptake.

The effects of external beam radiation on tumor uptake of radiolabeled monoclonal antibody were investigated. Nude mice bearing carcinoembryonic antigen (CEA)-producing subcutaneous human tumor xenografts (LS174T) were irradiated (60Co) with a single fraction of 0, 2 or 20 Gy, 6 or 11 days after tumor inoculation. An Indium-111 labeled anti-CEA monoclonal antibody (T84.66) was injected 1-2 hrs after irradiation. Biodistribution studies performed at 48 hrs showed a statistically significant (p less than 0.01) inverse correlation between tumor mass and tumor antibody uptake. Tumor age was also a significant factor with 11 day old tumors having significantly less uptake (p less than 0.0001) compared to 6 day old tumors for a given mass. Radiation increased tumor antibody uptake only in those tumors where growth inhibition also occurred. Multiple regression analysis showed that this inverse correlation between tumor mass and antibody uptake was the same for irradiated and nonirradiated tumors. We conclude that, in this model system, radiation does not act independently to enhance tumor antibody deposition. Radiation's primary effect is to reduce tumor mass, with mass reduction then resulting in an increase in antibody uptake. The clinical implications of this study are discussed.

Animals↗
PubMed1989

Net CO(2) Assimilation and Carbohydrate Partitioning of Grapevine Leaves in Response to Trunk Girdling and Gibberellic Acid Application.

Leaf net CO(2) assimilation rate (A), stomatal conductance (g(s)), carboxylation efficiency, and foliar nonstructural carbohydrates were measured on mature, field-grown Vitis vinifera L. (cv Thompson Seedless) vines that had been trunk girdled, sprayed with gibberellic acid, or both, shortly after anthesis. Girdling reduced A, g(s), and carboxylation efficiency when measured 2 weeks after imposition of the treatments. Diurnal measurements indicated that A of girdled vines was less than that of control vines between 1000 and 1800 hours. Gibberellic acid mitigated the depressing effect of girdling on g(s) during the same diurnal measurements. The concentrations of foliar carbohydrates were greatest for the girdled vines, followed by the combination treatment and were lowest for the control vines. Foliar carbohydrates were greater for girdled vines 4 weeks after the treatments were imposed, however, by this time there was no significant difference in A between the control and girdled vines. Two and 4 weeks after the experiment was initiated root carbohydrate concentrations were less for the girdled vines when compared to the control vines. The data indicate that the reduction in A of girdled grapevines is not associated with the accumulation of leaf nonstructural carbohydrates following the girdling treatment.

Journal Article↗
PubMed1989

Effects of Ambient and Acute Partial Pressures of Ozone on Leaf Net CO(2) Assimilation of Field-Grown Vitis vinifera L.

Mature, field-grown Vitis vinifera L. grapevines grown in open-top chambers were exposed to either charcoal-filtered air or ambient ozone partial pressures throughout the growing season. Individual leaves also were exposed to ozone partial pressures of 0.2, 0.4, or 0.6 micropascals per pascal for 5 hours. No visual ozone damage was found on leaves exposed to any of the treatments. Chronic exposure to ambient O(3) partial pressures reduced net CO(2) assimilation rate (A) between 5 and 13% at various times throughout the season when compared to the filtered treatment. Exposure of leaves to 0.2 micropascals per pascal O(3) for 5 hours had no significant effect on A; however, A was reduced 84% for leaves exposed to 0.6 micropascals per pascal O(3) when compared to the controls after 5 hours. Intercellular CO(2) partial pressure (c(i)) was lower for leaves exposed to 0.2 micropascals per pascal O(3) when compared to the controls, while c(i) of the leaves treated with 0.6 micropascals per pascal of 0(3) increased during the fumigation. The long-term effects of ambient O(3) and short-term exposure to acute levels of O(3) reduced grape leaf photosynthesis due to a reduction in both stomatal and mesophyll conductances.

Journal Article↗
PubMed1989

Trouble in the schoolhouse: new views on victimization, fear of crime, and teacher perceptions of the workplace.

The current study examines the self-reported victimizations of 90 public school teachers, over one-third of whom reported school-based theft of personal property or threats of violence. The study addressed two basic questions. First, what was the relationship between these school-based victimization experiences and the level of fear expressed by teachers? Second, what was the relationship between both the victimizations and fear and teacher satisfaction with their jobs and their employers? In order to provide a thorough examination of these relationships, several recognized correlates of teacher satisfaction, including respondent's sex, age, work assignments, and racial attitudes and orientations, were included in the analysis. It was found that teacher satisfaction was influenced not only by factors normally associated with teaching, but also by perceptions of and experiences with youthful misbehavior at school. For its part, fear of crime exhibited a strong direct link to both types of satisfaction, and it apparently mitigated the influences of racism on satisfaction with one's job and employer. These observations were consistent with an emerging perspective in victimization studies, which views the link between victimizations and fear of crime as part of the more general social climate, including perceptions of one's work environment, a perspective that frees the researcher from the confines of more traditional conceptualizations about crime.

Adult↗
PubMed1989

Measurement and estimation of organ Bremsstrahlung radiation dose.

Bremsstrahlung radiation doses were measured in an anthropomorphic phantom using thermoluminescent dosimeters. A single source of 90Y (beta-ray range less than or equal to 1.0 cm) was inserted in the bladder region and dosimeters were placed at distances greater than or equal to 3 cm to preclude detection of decay betas. Doses were corrected so as to represent the case of no biologic clearance. By comparing dosimeter location with the standard MIRD human geometry, sample organ doses could be determined. Representative results were 432 +/- 76 mrad/mCi at 3 cm (bladder), 260 +/- 60 mrad/mCi (uterus), 71 +/- 4 mrad/mCi (lower large intestine), and 1.4 +/- 0.7 mrad/mCi (liver). An estimation method, based on absorbed fraction tables, gave organ doses that were within the errors of measurement for all tissues with the exception of the bladder site. We conclude that organ bremsstrahlung radiation doses are not negligible and that they can be estimated using an integration over both the brake and beta-ray spectra.

Female↗
PubMed1988

Successful imaging of human cancer with indium-111-labeled phospholipid vesicles.

Twenty-four patients with proven primary and/or metastatic cancer received single intravenous injections of phospholipid vesicles containing 0.5 mCi of Indium-111. Gamma camera scintigraphy 1 to 72 hours later visualized tumors in 22 patients (92%), including carcinomas of breast, lung, colon, prostate, kidney, cervix, thyroid, and soft tissue sarcoma, lymphoma, and melanoma. Tumor sites that were identified included soft tissues, bone, lung, liver, lymph node, and spinal cord. There were only two false-positive images in metastatic sites and four false-negative images in metastatic sites. Overall sensitivity for tumors in 97 individual sites was 85%, whereas specificity was 96%. Unsuspected areas of malignancy were seen in the lumbar subdural space, pleura, liver, thyroid, and lung. Besides tumor accumulations, homogeneous uptake was observed in normal liver and spleen. Radiation doses to these two organs were 2.2 and 2.9 cGy/0.5 mCi In-111, respectively. Whole body radiation dose was 0.3 cGy/0.5 mCi. The use of Indium-111-labeled vesicles permits a wide variety of human tumors in primary and metastatic sites to be imaged without toxicity and with radiation doses comparable to other radionuclide scanning techniques.

Humans↗
PubMed1988

In-111-labeled liposomes: dosimetry and tumor depiction.

Neutral phospholipid vesicles (liposomes) were loaded with 0.5 mCi (18.5 MBq) indium-111 and administered to 24 patients with various types of cancer. The median diameter of the liposomes was 77 nm, and lipid dose was 0.78-6.25 mg/kg. Scans obtained 24 and 48 hours after injection of In-111 liposomes showed gradual blood clearance with homogeneous uptake in the normal liver and spleen. Dosimetric estimates for these organs were 2.3 +/- 1.1 and 2.3 +/- 1.4 rad (.02 +/- .01 Gy), respectively, with a whole-body estimate of 0.28 rad (.003 Gy). Radiation dose did not correlate with lipid dose. Total renal excretion of In-111 was less than 2% of the injected dose in all but two patients. Transient eosinophilia occurred in two patients. Tumor was seen in the scans of 22 of 24 patients (unbinded readings). In-111-labeled liposomes may enable the demonstration of suspected or unsuspected sites of tumor.

Breast Neoplasms↗
PubMed1988

Tumor uptake as a function of tumor mass: a mathematic model.

Inverse correlations of tumor uptake (u), measured in percent injected dose per gram, with tumor mass (m) are demonstrated for phospholipid vesicle, nonspecific and specific monoclonal antibody tracers. Correlation coefficients implied u = B mA in 11 different animal experiments. Experimental exponent (A) values lay in the range -0.28-0.64 with a mean of -0.43 while intercept (B) values varied from 3 to 18. Spherical and cylindrical tumor models implied exponents of -0.33 and -0.5, respectively. Comparison of three implantation sites of the human LS174T xenograft revealed a narrow range of exponents (-0.38- -0.46) indicating a consistent geometry for this tumor. Blood flow to the lesion site and inside its volume (as dictated by tumor size) are factors in tumor uptake. Our results indicate that biodistribution data should include the variation of tumor uptake with mass. For less than 10 g lesions, we predict that radiation absorbed dose will be highly dependent upon tumor size.

Animals↗
PubMed1988

Cage design and configuration for an arboreal species of primate.

The squirrel monkey (genus Saimiri) is an arboreal primate from equatorial South America. This species forms large social groups that consist of multiple females and males of varying ages, from infant to adult. As the use of squirrel monkeys in research continues to grow, an understanding of optimal cage design and environment is essential. The University of South Alabama Primate Research Laboratory houses a breeding colony of 350 squirrel monkeys. Each group cage, measuring 4.5 X 2.5 X 1.5 meters, can contain up to 20 animals. A breeding group consists of one adult male, eight to ten adult females, and varying numbers of infant and juvenile animals. In order to determine the most suitable cage environment for the squirrel monkey, a series of studies were carried out to compare various perch materials and cage configurations. Squirrel monkeys preferred a poly-vinyl-chloride pipe perch (rigid) over rope perches (non-rigid). When provided with multiple levels of perches, all levels were used. Males tended to distribute their activities randomly at different levels. In a two tiered perch arrangement, females concentrated 67% of their social activity on the top tier. In a triple tier configuration, females concentrated 66% of their travel on the top tier. These results indicate that by creating a cage environment with multiple tiers of horizontal perches the effective cage space can be doubled or tripled. This provides an effective means of reducing population density without enlarging the dimensions of the cage or reducing social group size.

Animals↗
PubMed1987

Imaging of colon carcinoma with 111-indium-labeled anti-CEA monoclonal antibodies (Indacea) prior to surgery.

Patients with primary and/or metastatic colorectal cancer who had been scheduled for operative intervention were injected intravenously with 200 micrograms of a high-affinity anti-carcinoembryonic antigen (CEA) monoclonal antibody labeled with 2 mCi of 111-indium (Indacea). Patients were imaged by gamma camera at 24 and 48 hours. Primary tumors were identified in 3/10 cases and were not visualized in 3/10 cases. Four scans were considered equivocal. Hepatic metastases were identified as image defects in 5/13 cases and were not visualized in 8/13 cases. All tumors contained CEA by immunoperoxidase staining. In all cases, the primary tumor uptake (5.44 +/- 1.07% ID/kg) was much higher than the uptake of the adjacent fat (0.18 +/- 0.04% ID/kg). There was a direct correlation between tumor CEA content, tumor radioactivity, and the imaging of primary tumor by Indacea. High liver uptake (30.3 +/- 3.0% ID/kg), seen when scanning all patients, was the main limitation of imaging and led to photopenic visualization of hepatic metastases. These results suggest that selection of patients with colorectal carcinoma on the basis of tumor CEA content will lead to improved rates of tumor imaging by Indacea in post-surgical scanning.

Antibodies, Monoclonal↗
PubMed1987

Net CO(2) Assimilation Rate of Grapevine Leaves in Response to Trunk Girdling and Gibberellic Acid Application.

Net CO(2) assimilation rate (A), stomatal conductance (g(s)), and weight per unit leaf area (W) were determined on Thompson Seedless grapevines grown in the field. Treatments included fruit set applications of gibberellic acid (40 milligrams gibberellic acid (GA(3)) per liter) to vines, shoots and clusters, alone and in combination with trunk girdling. Leaf A and g(s) were measured prior to and 3, 6, and 13 days after fruit set. Weight per unit leaf area was determined on leaves collected subsequent to gas exchange measurements. Leaf A of girdled vines was reduced approximately 30% when compared to the control 13 days after treatment. The reduction in A due to girdling was not as great when vines were sprayed with GA(3). GA(3) sprays alone had no significant effect on A. Stomatal conductance was reduced by girdling 13 days after treatment. Weight per unit leaf area was 17% greater for trunk girdled vines when compared to the controls. Results indicate GA(3) affected net CO(2) assimilation rate only on girdled vines, a treatment which increased weight per unit leaf area.

Journal Article↗
PubMed1986

The effect of tumor CEA content and tumor size on tissue uptake of indium 111-labeled anti-CEA monoclonal antibody.

This study was undertaken to determine the effect of tumor size and tumor carcinoembryonic antigen (CEA) content on the uptake of indium 111 (111In)-labeled anti-CEA monoclonal antibody in nude mice bearing xenografts. The tumor cell lines were WiDr, SW403, and LS174T, human colon cancer derivatives. The murine breast carcinoma cell line EMT-6 was used as a control. Tumor CEA levels (ng/g of tumor +/- standard error of the mean [SEM], measured by enzyme immunoassay (EIA) were: EMT-6, 0; WiDr, 105 +/- 5.7; LS174T, 2052 +/- 198; SW403, 17,575 +/- 1,785. The 111In-labeled monoclonal antibody was injected intravenously into mice bearing a single tumor. At 48 hours postinjection, scintiscan was performed, and the mice were killed so that biodistribution studies could be performed. The uptake of the monoclonal antibody was expressed as percent injected counts per minute per gram of tissue +/- SEM. The non-CEA-producing tumor, EMT-6, showed the lowest tumor uptake (1.4 +/- 0.3). WiDr, an intermediate CEA-producing tumor, showed some tumor uptake (16.4 +/- 1.5). The high CEA-producing tumors, SW403 and LS174T, had high tumor uptake (29.5 +/- 5.0 and 51.1 +/- 6.1, respectively). Biodistribution and scintiscan quality were closely related. Although LS174T had the best tumor uptake, SW403 had the highest CEA tumor content, indicating tumor CEA content cannot entirely predict scintiscan and biodistribution results. Tumor-to-blood (T/B), tumor-to-liver (T/L), and liver-to-blood (L/B) ratios were calculated for each animal and compared with tumor size. It was found that T/L had a negative correlation with tumor size (r = -0.72) and L/B had a positive correlation with tumor size (r = 0.94). These ratios may be useful clinically to follow response to therapy.

Animals↗