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Biomedical subjects

R Lake

Publications and source records attributed to R Lake.

At least 19 recordsLinked to original sources
PubMed2006

Remediation of bromate-contaminated groundwater in an ex situ fixed-film bioreactor.

Use of a pilot-scale fixed-film bioreactor was investigated for remediation of bromate contamination within groundwater. Bromate reduction with stoichiometric production of bromide was observed, providing supporting evidence for complete reduction of bromate with no production of stable intermediates. Reduction of 87-90% bromate from an influent concentration of 1.1 mg L(-1) was observed with retention times of 40-80 h. Lower retention times led to decreases in bromate reduction capability, with 11.5% removal at a 10 h retention time. Nitrate reduction of 76-99% from a 30.7 mg L(-1) as NO(3)(-) influent was observed at retention times of 10-80 h, although an increase in nitrite production to 2.7 mg L(-1) occurred with a 10 h retention time. Backwashing was not required, with the large plastic packing media able to accommodate biomass accumulation without decreases in operational efficiency. This study has provided proof of concept and demonstrated the potential of biological bromate reduction by fixed-film processes for remediation of a bromate contaminated groundwater source.

Biomass↗
PubMed2005

Reduction of bromate in groundwater with an ex situ suspended growth bioreactor.

A potential remediation technique for groundwater contaminated by bromate has been investigated, utilising biological bromate reduction to bromide by augmentation of indigenous microbial populations. This technique, involving addition of a carbon source to contaminated groundwater, is being developed as an ex-situ methodology analogous to commercial denitrification systems, but may also have in-situ applications. Trials have focussed on a laboratory-scale anaerobic suspended growth chemostat system, investigating glucose addition to real groundwater supplies. Steady states for a range of glucose and bromate concentrations demonstrated bromate reduction up to 700 microgl(-1) (50% of 1400 microgl(-1) influent) with glucose excess (above 52 mgl(-1)), but specific reduction rates (up to 2.83 micromol Br.g dry wt(-1) hr(-1) for 1400 microgl(-1) bromate influent) were low compared to denitrification (up to 305 micromol N g dry wt(-1) hr(-1)). More recent enrichment trials have demonstrated reduction of 32 mgl(-1) bromate within a 40 hour residence time with specific reduction rates of up to 160.48 micromol Br.g dry wt(-1) hr(-1), suggesting the presence of high rate bromate reducing bacterial strains.

Bacteria, Anaerobic↗
PubMed2001

Postcibal gastric emptying of pancreatin pellets: effects of dose and meal oil.

To treat pancreatic exocrine insufficiency, physicians often prescribe enterically coated pellets of pancreatin to be taken with meals. The pellets are only partially effective in correcting the digestion and absorption of fat. We sought to determine in normal subjects whether emptying of pellets from the postcibal stomach was dose-related and whether the gastric emptying of lipophilic Creon-20 or Pancrease was altered by the presence or the absence of oil in a meal. Gastric emptying of pellets surface-labeled with 113mIn or 99mTc was followed with a gamma camera for 300 min after isocaloric meals. From our observations, we concluded that gastric emptying of 0.28-1.12 g of 1-mm or 2-mm pellets was dose-related (P < 0.01) and emptying of neither Creon-20 nor Pancrease was much affected by oil in the meal.

Adult↗
PubMed2000

MAML1, a human homologue of Drosophila mastermind, is a transcriptional co-activator for NOTCH receptors.

Notch receptors are involved in cell-fate determination in organisms as diverse as flies, frogs and humans. In Drosophila melanogaster , loss-of-function mutations of Notch produce a 'neurogenic' phenotype in which cells destined to become epidermis switch fate and differentiate to neural cells. Upon ligand activation, the intracellular domain of Notch (ICN) translocates to the nucleus, and interacts directly with the DNA-binding protein Suppressor of hairless (Su(H)) in flies, or recombination signal binding protein Jkappa (RBP-Jkappa) in mammals, to activate gene transcription. But the precise mechanisms of Notch-induced gene expression are not completely understood. The gene mastermind has been identified in multiple genetic screens for modifiers of Notch mutations in Drosophila. Here we clone MAML1, a human homologue of the Drosophila gene Mastermind, and show that it encodes a protein of 130 kD localizing to nuclear bodies. MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. These studies provide a molecular mechanism to explain the genetic links between mastermind and Notch in Drosophila and indicate that MAML1 functions as a transcriptional co-activator for NOTCH signalling.

3T3 Cells↗
PubMed2000

Increased regional cerebral perfusion by 99mTc hexamethyl propylene amine oxime single photon emission computed tomography in post-traumatic stress disorder.

OBJECTIVE: Because of the treatment resistance and chronic affective lability of many post-traumatic stress disorder (PTSD) patients and the hypothesized association of these behaviors with temporal and limbic structures, a study was conducted to determine whether these patients would exhibit alterations in regional cerebral perfusion in the temporal and limbic regions compared with age-matched normal volunteers at rest. METHOD: We studied 17 patients using 99mTc hexamethyl propylene amine oxime single photon emission computed tomography. Seven of the patients were on a selective serotonin reuptake inhibitor, five were on a tricyclic antidepressant, and five were on no medication at the time of the study. Patients were compared with eight age-matched normal controls. RESULTS: All PTSD patients showed a relative increase in regional cerebral perfusion in the anterior and posterior cingulate regions bilaterally, the right temporal and parietal regions, the right caudate/putamen region, and the left orbital and hippocampal regions compared with the control group. When the group of PTSD patients who were free of medication were compared with the control group, increased regional cerebral perfusion was found in the right and left caudate/putamen regions and the right orbital and anterior cingulate cortex bilaterally. CONCLUSIONS: PTSD is associated with increased regional blood flow in limbic areas and the right temporal and parietal cortex compared with age-matched normal volunteers.

Adult↗
PubMed1999

Gastric emptying of indigestible versus digestible oils and solid fats in normal humans.

Recent scintigraphic studies indicate that lipolytic products in the small intestine do not inhibit gastric emptying of fat as potently as previously suggested by studies that compared a liquid indigestible oil with a solid digestible fat. The older studies left open the confounding possibility that solid fats emptied differently than liquid oil. We studied eight normal subjects who ingested four meals in which fat was (1) liquid, digestible Crisco oil, (2) liquid, indigestible sucrose polyester oil, (3) digestible, solid Crisco, and (4) indigestible, solid olestra. Fats were labeled with iodine-123, and their gastric emptying was followed with a gamma camera. Indigestible fats (whether liquid or solid) emptied consistently faster than digestible fats (P < 0.005), although differences were small. Solid fats emptied about as rapidly as oils in the first hour; but more slowly thereafter (P < 0.01). A comparison of present scintigraphic with older studies suggested that solid fats were not well tracked by duodenal, marker-perfusion techniques, which misled previous investigators.

Adult↗
PubMed1998

Cytokine gene therapy or infusion as treatment for solid human cancer.

In the induction of tissue-directed immune responses, cytokines tend to be released within the affected tissues. We used two strategies to expose tumor tissues to continuous high levels of cytokines: First, a vaccinia interleukin (IL)2 recombinant was injected directly intratumorally 3-weekly at 10(7) pfus/dose in six patients with the solid tumor malignant mesothelioma (MM). No virus excretion was detectable. At each cycle vaccinia-IL-2 mRNA (SQ [semi-quantitative] reverse transcription polymerase chain reaction) was maximal 24-72 h following injection reduced at 8 days and faded by 21 days. No tumor regression occurred. Second, based on the success of granulocyte macrophage colony-stimulating factor (GM-CSF) in gene transfer experiments, we conducted a study using continuous intratumoral GM-CSF infusion in eight patients with MM using a portable pump at doses of 10 micro/cg/24 h over 8 weeks. Systemic neutrophil agglutination and local catheter-related difficulties occurred. Two patients demonstrated tumor necrosis, one of whom had a marked progressive mononuclear cell infiltration of the tumor associated with a partial response (>50% reduction in tumor area). Murine studies using our MM model in CBA and BALB/C mice have demonstrated that B7-1 and allo-class I transfections induce strong tumor-specific cytotoxic T lymphocyte responses: GM-CSF, IL-12, and IL-2 induced mixed nonspecific plus specific responses, whereas B7-2 and class II transfections were not effective. We conclude that increased intratumoral cytokine concentrations can be generated using both gene transfer and cytokine infusion approaches; however, both have their limitations and, at this stage, have not produced dramatic antitumor effects in humans.

Cytokines↗
PubMed1997

Mismatch of duodenal deliveries of dietary fat and pancreatin from enterically coated microspheres.

Gastric emptying of dietary fat is affected by both chemical and physical factors; but when ingested as a free oil or an aqueous emulsion, fat may empty most rapidly immediately after the meal. In contrast, gastric transit of 1- to 3-mm spheres (like those of enterically coated pancreatins) is known to vary inversely with sphere diameter; and spheres leave the stomach initially slowly, if their diameter is > or = 1.6 mm. Our objective was to determine whether 2-mm microspheres of Pancrease would empty much more slowly than free or emulsified oil and whether 1.2-mm microspheres of Creon would empty as fast as free oil. We used a gamma camera to track the concurrent gastric emptying of 123I-labeled oil and 113mIn-labeled spheres of Pancrease or Creon in pancreatic-insufficient subjects with cystic fibrosis who ingested 20 g of free oil in spaghetti meals or 20 g of oil emulsified in a milk meal. We found that either type of oil emptied rapidly initially but slowed later, whereas either dosage form emptied slowly initially but rapidly later. Unexpectedly, the smaller spheres of Creon emptied about the same as Pancrease did after the spaghetti meal. For example, 50% of oil but < 25% of either dosage form had left the stomach by 90 min after the meals. Both dosage forms were lipophilic, forming aggregates in vitro. We concluded that the gastric emptying of either dosage form frequently lagged behind the emptying of oil from ordinary meals. We speculated that the similar transits of the 1.2-mm Creon and the 2-mm Pancrease resulted from aggregation of these microspheres in the presence of free oil.

Adult↗
PubMed1996

Gastric emptying of oil from solid and liquid meals. Effect of human pancreatic insufficiency.

Digestion of fat in pancreatic insufficiency (PI) is strongly affected by how rapidly fat enters the duodenum. We postulated that: (1) oil empties faster in PI than in normals and (2) in both, it empties in a load-dependent fashion. We used a gamma camera to test these ideas by comparing gastric emptying of iodine-123 iodinated oil in normal and pancreatic-insufficient subjects after 15 g of free oil were ingested in a small spaghetti meal and 60 g of oil were ingested in a large spaghetti meal and in a milk emulsion. Indium-113m marked gastric emptying of water in the milk. In both groups after all meals, oil emptied fastest initially, slowing later; and oil emptied three to four times faster when 60 g vs 15 g were ingested. There were no significant differences between the groups of subjects with respect to gastric emptying of the spaghetti meals, but the pancreatic-insufficient subjects emptied both oil and water faster from the milk emulsion than did the normal subjects. The slower emptying of oil in the normal subjects was associated with significantly more layering of oil to the top of the intragastric milk emulsion.

Adult↗
PubMed1994

Control of canine gastric emptying of fat by lipolytic products.

Dietary fat is ingested in three forms: 1) in solid food, 2) as aqueous emulsions, and 3) as unemulsified, liquid oil. On the basis of a scant previous literature, we postulated that liquid fat (emulsions or oils) would empty from the stomach at speeds that varied with the amounts ingested but that this dynamic would be modulated by feedback inhibition from lipolytic products. To test these ideas, we used a gamma camera to track gastric emptying of 123I-labeled fat in dogs with chronic pancreatic fistulas by which lipase was excluded from or replenished in the duodenum in varied amounts after dogs were fed 15-, 30-, and 60-g loads of liquid fat given with solid foods or as emulsions. We also tracked concurrent gastric emptying of 113mIn, which marked the solid food phase or the water phase of emulsions. In some studies, we used a potent and specific inhibitor (orlistat) of pancreatic and gastric lipases to assess how lipolytic products modulated emptying of liquid fat. In the absence of pancreatic enzymes, both oils and emulsions emptied initially at high speeds that varied with fat loads, but emptying slowed 20 min after ingestion of emulsions and 60 min after ingestion of unemulsified oil. Studies with orlistat indicated that these changes in rates resulted from liberation of gastric lipolytic products. Emptying of oil emulsions was not altered by duodenal replenishment with pancreatic enzymes, but emptying of unemulsified oil was inhibited in a dose-related fashion, such that maximal inhibition was achieved when pancreatic enzymes were replenished at > or = 40% of normal amounts. Studies with orlistat confirmed that this dose-dependent slowing was due specifically to lipase. Emptying of solid food was much more sensitive to replenishment with enzymes, so that a 10% replenishment maximally inhibited solid emptying.

Animals↗
PubMed1994

Immunological events underlying the induction of T cell non-responsiveness.

T lymphocytes recognise antigen in the form of short peptides complexed with the class I and II products of the Major Histocompatibility Complex (MHC). Cellular activation follows T cell recognition of peptide-MHC complexes at immunogenic cell surface concentrations together with the participation of the appropriate costimulatory signals. Interaction of TCRs and peptide-MHC complexes under inappropriate conditions may result in antigen-specific non-responsiveness, commonly referred to as anergy. Here we review some recent model systems which have been employed to study the phenomenon of anergy and the use of peptides to induce antigen-specific non-responsiveness both in vitro and in vivo.

Allergens↗
PubMed1994

Effects of beta-hydroxy-beta-methyl butyrate on performance and carcass quality of feedlot steers.

Beta-hydroxy-beta-methyl butyrate (HMB), a compound formed during catabolism of leucine, was fed to 256 crossbred steers as 0 or .03% of diet dry matter. Effects on performance, carcass characteristics, and tissue composition were measured. Groups of 32 steers per diet were slaughtered after 105, 119, 133, and 147 d on feed. The HMB was fed to each group only during the final 82 d they were fed. Averaged across slaughter date, animal performance was not altered by HMB; however, an interaction between HMB and time on feed was detected. Feeding HMB increased (P < .01) daily gain of steers slaughtered at 105 d but decreased (P < .01) daily gain of steers slaughtered at 147 d. Steers fed HMB had numerically higher marbling scores that resulted in a trend toward higher carcass quality grades. Steers receiving HMB tended to have less (P < .08) s.c. fat and fewer steers with yield grades of 4 or greater (1.6 vs 4.7%). Supplementation of HMB to feedlot steers tended to increase (P < .07) the ratio of intramuscular fat to subcutaneous fat. Steers fed HMB had higher (P < .001) blood plasma concentrations of HMB (3.06 vs 1.70 mg/L) and lower (P < .03) blood plasma concentrations of cholesterol (108.4 vs 118.7 mg/dL). Feeding HMB tended to increase (P < .10) lipid content of the longissimus muscles of those steers slaughtered at 105 d.

Adipose Tissue↗
PubMed1992

Arctic contaminants: sources, occurrence and pathways.

Potentially toxic organic compounds, acids, metals and radionuclides in the northern polar region are a matter of concern as it becomes evident that long-range transport of pollution on hemispheric to global scales is damaging this part of the world. In this review and assessment of sources, occurrence, history and pathways of these substances in the north, the state of knowledge of the transport media--the ocean and atmospheric circulation--is also examined. A five-compartment model of the northern region is developed with the intent of assessing the pathways of northern contaminants. It shows that we know most about pathways of acids, metals and radionuclides and least about those of complex synthetic organic compounds. Of the total annual inputs of anthropogenic acidic sulphur and the metals lead and cadmium to the Arctic via the atmosphere, an estimated 10-14% are deposited. A water mass budget for the surface layer of the Arctic Ocean, the most biologically active part of that sea, is constructed to examine the mass budget for one of the major persistent organochlorine compound groups found in remote regions, hexachlorocyclohexanes (HCH), one isomer of which is lindane. It is concluded that both the atmosphere and the ocean are important transport media. Even for the HCH substances which are relatively easily measured and simple in composition compared to other synthetic organics, we know little about the occurrence and environmental physical/chemical characteristics that determine pathways into the food chain. More environmental measurements, chemical characterization studies and environmental chemical transport modelling are needed, as is better knowledge of the circulation of the Arctic Ocean and the marine food web.

Acids↗