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Biomedical subjects

J B Robertson

Publications and source records attributed to J B Robertson.

At least 19 recordsLinked to original sources
PubMed1994

Epidermal growth factor receptors in human breast carcinoma cells: a potential selective target for transforming growth factor alpha-Pseudomonas exotoxin 40 fusion protein.

Epidermal growth factor (EGF) receptors are expressed in high levels by some poor prognosis breast tumors. We have examined the cytotoxic effect of the tumor growth factor alpha (TGF alpha)-delta Cys-Pseudomonas exotoxin (PE40) recombinant fusion protein on normal and tumorigenic human breast epithelial cells in vitro and in vivo. The MDA-468, MDA-231, BT-20, and MCF-7ADR estrogen receptor-negative, EGF receptor-rich breast cancer lines were exquisitely sensitive in vitro to TGF alpha-delta Cys-PE40 with a 50% inhibitory concentration of < or = 0.02 nM. The estrogen receptor-positive, low EGF receptor MCF-7, ZR75-1, and T47D cells were less sensitive to the fusion toxin with a 50% inhibitory concentration of > 0.2 nM. The nontumorigenic cell lines 184, 184A1, and 184B5 were relatively resistant to TGF alpha-delta Cys-PE40 despite exhibiting high levels of EGF receptors. Continuous i.p. administration of TGF alpha-delta Cys-PE40 via an osmotic minipump at a dose of 0.4 microgram/g/day over 7 days inhibited MDA-468, MA-231, and BT-20 but not MCF-7 tumor growth in female athymic mice. Host tissue toxicity was not observed with this dose of TGF alpha-delta Cys-PE40. Mixed MDA-468/MCF-7 tumors were established in nude mice after coinoculation of both cell types in estrogen-supplemented animals. EGF receptor immunohistochemistry and immunoblot procedures indicated that TGF alpha-PE40 eliminated the MDA-468 cells while sparing the adjacent MCF-7 cells. By immunoblot, EGF receptors were consistently more abundant in tumor tissue than in adjacent nontumor tissue from the same mastectomy specimen (n = 7). These data support the notion that EGF receptors can be selectively targeted in human breast cancer cells for the delivery of antitumor agents. Further clinical studies with TGF alpha-delta Cys-PE40 and other chimeric toxins using the same cellular target will address this possibility.

Animals↗
PubMed1994

Suboptimal treatment results with the Therasonics lithotriptor.

From July 1988 to August 1991, 174 stone treatments were attempted on 112 stones in 86 patients using a Therasonics lithotriptor. Mean stone diameter was 13 mm. (range 4 to 60). The success rate (defined as no debris or fragments less than 4 mm. in an asymptomatic patient) was 49% and the retreatment rate was 63%. Subjects reported moderate to severe pain during 70 treatment sessions (42%) despite sedation with parenteral narcotics (50 to 100 mg. meperidine and 50 mg. hydroxyzine intramuscularly). One patient had perirenal bleeding requiring a 7-unit blood transfusion. Of the treatments 24 (13%) were aborted, 10 due to pain and 13 because of inability of the operator to position the patient or localize the stone. These results appear to be inferior to those reported with alternative lithotriptors. Modifications that have been made in the Therasonics system may improve stone localization and treatment results.

Adult↗
PubMed1992

Oxidation of nitrotoluenes by toluene dioxygenase: evidence for a monooxygenase reaction.

Pseudomonas putida F1 and Pseudomonas sp. strain JS150 initiate toluene degradation by incorporating molecular oxygen into the aromatic nucleus to form cis-1,2-dihydroxy-3-methylcyclohexa-3,5-diene. When toluene-grown cells were incubated with 2- and 3-nitrotoluene, the major products identified were 2- and 3-nitrobenzyl alcohol, respectively. The same cells oxidized 4-nitrotoluene to 2-methyl-5-nitrophenol and 3-methyl-6-nitrocatechol. Escherichia coli JM109(pDTG601), which contains the toluene dioxygenase genes from P. putida F1 under the control of the tac promoter, oxidized the isomeric nitrotoluenes to the same metabolites as those formed by P. putida F1 and Pseudomonas sp. strain JS150. These results extend the range of substrates known to be oxidized by this versatile enzyme and demonstrate for the first time that toluene dioxygenase can oxidize an aromatic methyl substituent.

Biodegradation, Environmental↗
PubMed1991

Methods for dietary fiber, neutral detergent fiber, and nonstarch polysaccharides in relation to animal nutrition.

There is a need to standardize the NDF procedure. Procedures have varied because of the use of different amylases in attempts to remove starch interference. The original Bacillus subtilis enzyme Type IIIA (XIA) no longer is available and has been replaced by a less effective enzyme. For fiber work, a new enzyme has received AOAC approval and is rapidly displacing other amylases in analytical work. This enzyme is available from Sigma (Number A3306; Sigma Chemical Co., St. Louis, MO). The original publications for NDF and ADF (43, 53) and the Agricultural Handbook 379 (14) are obsolete and of historical interest only. Up to date procedures should be followed. Triethylene glycol has replaced 2-ethoxyethanol because of reported toxicity. Considerable development in regard to fiber methods has occurred over the past 5 yr because of a redefinition of dietary fiber for man and monogastric animals that includes lignin and all polysaccharides resistant to mammalian digestive enzymes. In addition to NDF, new improved methods for total dietary fiber and nonstarch polysaccharides including pectin and beta-glucans now are available. The latter are also of interest in rumen fermentation. Unlike starch, their fermentations are like that of cellulose but faster and yield no lactic acid. Physical and biological properties of carbohydrate fractions are more important than their intrinsic composition.

Animal Feed↗
PubMed1990

Analysis of foodstuffs for dietary fiber by the urea enzymatic dialysis method.

Total dietary fiber (TDF) values for cereal grains, fruits, vegetables, processed foods, and purified or semi-purified dietary fiber products were determined by a new method using 8M urea and enzymes (urea enzymatic dialysis, UED, method). The results are compared with the official AOAC procedure. Soluble and insoluble dietary fiber were determined for several of these foodstuffs and compared with the NDF values. Crude protein and ash contamination was usually lower with the UED method compared with the AOAC method, particularly for samples that formed gels during ethanol precipitation. Urea and the heat stable amylase were effective in removing starch even at relatively low temperatures of the assay (50 degrees C). The new assay is relatively economical in use of equipment, enzymes, and reagents. Studies are currently in progress to minimize the assay time for the UED method while further improving its flexibility and robustness. The results of the studies will be discussed.

Amylases↗
PubMed1989

AbrB, a regulator of gene expression in Bacillus, interacts with the transcription initiation regions of a sporulation gene and an antibiotic biosynthesis gene.

The abrB gene of Bacillus subtilis is believed to encode a repressor that controls the expression of genes involved in starvation-induced processes such as sporulation and the production of antibiotics and degradative enzymes. Two such genes, spoVG, a sporulation gene of B. subtilis, and tycA, which encodes tyrocidine synthetase I of the tyrocidine biosynthetic pathway in Bacillus brevis, are negatively regulated by abrB in B. subtilis. To examine the role of abrB in the repression of gene transcription, the AbrB protein was purified and then tested for its ability to bind to spoVG and tycA promoter DNA. In a gel mobility shift experiment, AbrB was found to bind to a DNA fragment containing the sequence from -95 to +61 of spoVG. AbrB protein exhibited reduced affinity for DNA of two mutant forms of the spoVG promoter that had been shown to be insensitive to abrB-dependent repression in vivo. These studies showed that an upstream A + T-rich sequence from -37 to -95 was required for optimal AbrB binding. AbrB protein was also observed to bind to the tycA gene within a region between the transcription start site and the tycA coding sequence as well as to a region containing the putative tycA promoter. These findings reinforce the hypothesis that AbrB represses gene expression through its direct interaction with the transcription initiation regions of genes under its control.

Amino Acid Sequence↗
PubMed1988

Development of a validation test for self-reported abstinence from smokeless tobacco products: preliminary results.

Using X-ray fluorescence spectrometry, 11 heavy elements at concentrations that are easily detectable have been identified in smokeless tobacco products. These concentrations were found to increase in cheek epithelium samples of the user after exposure to smokeless tobacco. This feasibility study suggests that the level of strontium in the cheek epithelium could be a valid measure of recent smokeless tobacco use. It also demonstrates that strontium levels become undetectable within several days of smokeless tobacco cessation. This absence of strontium could validate a self-report of abstinence from smokeless tobacco. Finally, the X-ray spectrum of heavy metal content of cheek epithelium from smokeless tobacco users could itself provide a visual stimulus to further motivate the user to terminate the use of smokeless tobacco products.

Cheek↗
PubMed1988

Comparison of the effects of psyllium and wheat bran on gastrointestinal transit time and stool characteristics.

Gastrointestinal transit time, frequency of defecation, stool weight, and stool consistency were studied in 12 subjects who were each given fiber supplements containing wheat bran, psyllium gum, a combination of wheat bran and psyllium gum, or a low-fiber control for 2 weeks. Gastrointestinal transit time was measured using four different markers: plastic pellets, chromium mordanted bran, cobalt-ethylenediamine-tetraacetic acid, and terbium oxide. The wet weight and dry weight of stools were measured, and a questionnaire accessed subjects' perceptions of the consistency of their stools. Fiber supplementation decreased transit time and increased the daily number of defecations and the wet weight and dry weight of stools. Bran had a greater effect on transit time than psyllium. Psyllium had a greater effect on the amount of water found in the stools and the total stool weight. On the days that stools were passed, 50% of the daily stool ratings were scored as "hard" when subjects received the control supplement. Less than 10% of the ratings were scored as "hard" when subjects received the high-fiber supplements. The type of marker used did not significantly affect the transit time measured.

Adult↗
PubMed1987

Effect of psyllium gum and wheat bran on spontaneous energy intake.

Energy intake, fecal energy output, and gastrointestinal symptoms were measured in 12 females who consumed either approximately 23 g/d supplementary fiber or a 4 g/d fiber control. Fiber supplements were crackers containing psyllium gum, wheat bran, or a combination of the two fiber sources. After 1 wk on the control cracker, subjects consumed the three high-fiber crackers and the control cracker for 2-wk periods in a balanced design. Gum and combination supplements gave increased bloating and flatulence. Increase in abdominal pain was reported with gum supplement. Mean daily fecal energy was 96 kcal/d with control crackers and was increased by 63 kcal with high-fiber crackers. Gum and combination supplements significantly decreased intake of digestible energy by 153 and 115 kcal/d, respectively. This suppression was not dependent upon fiber intolerance. Wheat bran supplement had no effect on energy intake.

Adult↗
PubMed1987

Mean transit time measurement by analysis of a single stool after ingestion of multicolored plastic pellets.

Mean transit time (MTT) was measured in 12 females and served as a standard to evaluate the validity of different methods of estimating transit by analysis of a single stool (SST). Each subject consumed three different fiber supplements and a low-fiber control for 14-d periods. On days 4-8 of each period, subjects were given 20 plastic pallets, which varied in color each day. SST was calculated using from two to five sets of colored pellets and different criteria for designation of the stool to be analyzed were compared. Results indicate that the following modifications in the SST method originally proposed by Cummings and Wiggins will result in improved prediction of MTT: 1) Increase the days of dosing from 3 to 6.2) Collect for study the first stool passed 3 h after the last dosing. 3) Include all pellets identified in the selected stool in the SST calculation.

Defecation↗
PubMed1987

The care of elderly patients by elderly physicians.

To examine the content of care that elderly patients receive from physicians greater than or equal to 65 years of age, data from the 1981 National Ambulatory Medical Care Survey were analyzed. Compared to physicians aged 35 to 54 years, elderly physicians devoted a larger proportion of their practices to the care of elderly patients. In caring for these patients, elderly physicians spent more time per visit than did younger physicians and were more likely to conduct general examinations and provide counseling. In contrast, elderly physicians were less likely to perform mental status or vision examinations. Elderly physicians were also less likely to provide telephone follow-up for those patients greater than or equal to 75 years of age and more likely to discharge patients greater than or equal to 65 years of age without any specific follow-up planned. These data suggest that the content of care for elderly patients may differ substantially depending upon the physician's age.

Aged↗
PubMed1984

The effect of X irradiation on the progression of mouse 10T1/2 cells released from density-inhibited cultures.

When mouse C3H 10T1/2 cells were allowed to reach the density-inhibited plateau phase of growth, 0-3% of the cells were in the S phase as determined by pulse-labeling indices and about 90% of cells were in the G1 phase as determined by flow microfluorometry (FMF). Density-inhibited cultures were exposed to moderate doses of X ray: immediately after X irradiation the cultures were trypsinized and the cells were subcultured at low density in fresh medium. FMF profiles and pulse and continuous-labeling indices were studied. It was determined by pulse-labeling indices that the cell population which was released from the plateau-phase cultures remained in the G1 phase longer than the duration of the normal G1 phase in exponentially growing cells. When plateau-phase cultures were irradiated with 400 rad before subculture, the cells moved into the S phase approximately 4 hr later than did nonirradiated cells. Despite the G1/S delay, both irradiated and nonirradiated cell populations showed a similar rate of progression through the S phase. As determined by cumulative labeling indices, the fraction of cells which remained in G1 up to 120 hr post-subculture (G1 block) increased linearly with X-ray doses. There was no measurable X-ray-induced G1 delay or G1 block in cells irradiated after subculture at the G1/S border during semi-synchronous growth.

Animals↗
PubMed1983

The influence of dietary fiber source on human intestinal transit and stool output.

Wheat bran ground to a coarse and fine particle size, purified cellulose and ethanol-extracted cabbage fiber, fed to 24 adult males during an 80-day metabolic trial, were examined for effects on intestinal transit time, laxation and stool composition. Brilliant blue, plastic pellets, polyethylene glycol (PEG)-4000 and Cr(III) mordanted onto isolated bran fiber were simultaneously administered for transit measurements. Intersubject variability in response to fiber source was highly significant for all transit and stool measurements. Only coarse bran or cellulose addition increased transit speed (decreased transit time) over basal rates. Grinding of bran significantly reduced fecal output because of reduced fecal water. Only subjects consuming cellulose or fine bran reported difficult or uncomfortable defecations. Though cabbage produced the smallest fecal output, stools had a high moisture content comparable to those obtained from coarse bran, which suggests a large microbial output in response to a fermentable substrate. Significant negative correlations were produced when changes in dry matter or cell wall intakes were regressed with Cr (III) transit. These findings suggest that the level of either food or fiber in the diet are variables that influence intestinal transit time and should be controlled in studies measuring it. Increases in fiber intake linearly increased fecal output of water and dry matter. Regression slopes were characteristic of each fiber source.

Adult↗
PubMed1983

Oncogenic transformation of mouse BALB/3T3 cells by plutonium-238 alpha particles.

The A31-11 mouse BALB/3T3 cell system was adapted for the study of malignant transformation induced by 5.3 MeV alpha particles from a specially constructed 238Pu source. The biologic effects were compared to those of 220 kVp X rays. The alpha-radiation survival curve showed a D0 of 70 rad and a relative biological effectiveness (RBE) of 3.5 at 50% survival. The transformation frequency increased exponentially with dose in the range examined (25-250 rad); the maximum RBE for the induction of transformation in growing cells was approximately 3. The RBE for alpha transformation in nonproliferating cells, however, appeared to be much higher; the yield of transformants among X-irradiated cells held in the stationary phase of growth for 6 to 220 hr after irradiation declined nearly 50-fold while no decrease occurred in alpha-irradiated cells. This finding supports the hypothesis that carcinogenic damage induced by high LET radiation in mammalian cells is inefficiently repaired compared with X-ray damage, and that the carcinogenic effect of exposures to high LET radiation may be simply cumulative in nature. It further suggests that the effective RBE for alpha radiation in nonproliferating cell populations in vivo may be much higher than one would predict based on measurements in dividing cells.

Alpha Particles↗
PubMed1982

Influence of dietary fibers on fermentation in the human large intestine.

Fiber sources were fed to 24 men to evaluate the effect of fiber on large intestinal microflora. The diets were low fiber basal or the basal diet supplemented with coarse bran, fine bran, cabbage, or cellulose (Solka floc). Twelve subjects (Group 1) were fed all fiber sources using a latin square design with 2-week experimental periods followed by a 3-week period on the basal diet. Group 2 made one diet change after the first experimental period, then remained on that diet throughout the experiment; during the last period their fiber intake was double (to approximately 26 g/day). A microbial culture system was utilized with fecal microflora to measure cell wall indigestibility and volatile fatty acid (VFA) production. Volatile fatty acids were also measured in fresh feces. The in vitro substrates were alfalfa, coarse bran, cabbage, or cellulose. In this system, dietary fiber had a significant (P less than .05) effect on resultant cell wall indigestibility and VFA level. Previous diet in group 1 subjects significantly (P less than .05) affected in vitro VFA. In groups 2 significant (P less than .05) period and subject effect were present for the in vitro VFA data. The VFA concentrations in feces of humans were significantly affected by the fiber consumed.

Brassica↗
PubMed1982

Utilization of bamboo by the giant panda.

Two giant pandas were used to assess the utilization of bamboo as a feedstuff. Three 1-week-long digestion trials were conducted during which feed intake and fecal output were recorded. Passage of digesta was measured from both fluid and particulate markers administered at feeding. Results indicate that the giant panda, although highly specialized for the consumption of bamboo, is a very inefficient digester of bamboo. The pandas consumed up to 6% of body weight in dry matter per day, with bamboo dry matter digestibility averaging less than 20%. Apparent digestion coefficients for the structural carbohydrates of bamboo (27% for hemicellulose and 8% for cellulose) indicate that, unlike most herbivores, pandas do not rely heavily on the microbial degradation of plant material to fulfill their nutritional requirements. Additionally, the passage of digesta through the gastrointestinal tract of the panda was extremely rapid, with complete clearance of markers in less than 12 hours. The giant panda seems to have specialized to a feed source high in plant fiber without extensive modification of the digestive tract by selectivity in feeding, effective mastication, ingestion of large quantities, digestion of cellular contents rather than cell walls and rapid fecal excretion of the undigested residue.

Animal Nutritional Physiological Phenomena↗