Brian Reid - Profile on Academia.edu (original) (raw)
Papers by Brian Reid
Nature Biotechnology, 2002
HGS drug flop latest genomics setback
Nature Biotechnology, 2002
Measurement of Bioelectric Current with a Vibrating Probe
Journal of Visualized Experiments, 2011
Electric fields, generated by active transport of ions, are present in many biological systems an... more Electric fields, generated by active transport of ions, are present in many biological systems and often serve important functions in tissues and organs. For example, they play an important role in directing cell migration during wound healing. Here we describe the manufacture and use of ultrasensitive vibrating probes for measuring extracellular electric currents. The probe is an insulated, sharpened metal wire with a small platinum-black tip (30-35 μm), which can detect ionic currents in the μA/cm(2) range in physiological saline. The probe is vibrated at about 200 Hz by a piezoelectric bender. In the presence of an ionic current, the probe detects a voltage difference between the extremes of its movement. A lock-in amplifier filters out extraneous noise by locking on to the probe's frequency of vibration. Data are recorded onto computer. The probe is calibrated at the start and end of experiments in appropriate saline, using a chamber which applies a current of exactly 1.5 μA/cm(2). We describe how to make the probes, set up the system and calibrate. We also demonstrate the technique of cornea measurement, and show some representative results from different specimens (cornea, skin, brain).
Journal of applied physiology (Bethesda, Md. : 1985), 2011
Sun YH, Reid B, Fontaine JH, Miller LA, Hyde DM, Mogilner A, Zhao M. Airway epithelial wounds in ... more Sun YH, Reid B, Fontaine JH, Miller LA, Hyde DM, Mogilner A, Zhao M. Airway epithelial wounds in rhesus monkey generate ionic currents that guide cell migration to promote healing.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2005
Cataract is the most common cause of blindness but is at least curable by surgery. Unfortunately,... more Cataract is the most common cause of blindness but is at least curable by surgery. Unfortunately, many patients gradually develop the complication of posterior capsule opacification (PCO) or secondary cataract. This arises from stimulated cell growth within the lens capsule and can greatly impair vision. It is not fully understood why residual lens epithelial cell growth occurs after surgery. We propose and show that cataract surgery might remove an important inhibitory factor for lens cell growth, namely electric fields. The lens generates a unique pattern of electric currents constantly flowing out from the equator and entering the anterior and posterior poles. We show here that cutting and removing part of the anterior capsule as in cataract surgery significantly decreases the equatorial outward electric currents. Application of electric fields in culture inhibits proliferation of human lens epithelial cells. This inhibitory effect is likely to be mediated through a cell cycle control mechanism that decreases entry of cells into S phase from G1 phase by decreasing the G1-specific cell cycle protein cyclin E and increasing the cyclin-Cdk complex inhibitor p27 kip1 . Capsulorrhexis in vivo, which reduced endogenous lens electric fields, significantly increased LEC growth. This, together with our previous findings that electric fields have significant effects on the direction of lens cell migration, points to a controlling mechanism for the aberrant cell growth in posterior capsule opacification. A novel approach to control growth of lens epithelial cells using electric fields combined with other controlling mechanisms may be more effective in the prevention and treatment of this common complication of cataract surgery.
Investigative ophthalmology & visual science, 2011
PURPOSE. The PI3K/Akt pathway is required for cell polarization and migration, whereas the phosph... more PURPOSE. The PI3K/Akt pathway is required for cell polarization and migration, whereas the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) has inhibitory effects on the PI3K/Akt pathway. The authors therefore hypothesized that wounding would downregulate PTEN and that this downregulation would enhance wound healing. METHODS. In human corneal epithelial (HCE) cell monolayer and rat cornea scratch wound models, the authors investigated PTEN and Akt expression using Western blot and immunofluorescence analyses. The effects of PTEN and PI3K inhibitors dipotassium bisperoxo (picolinato) oxovanadate (bpv(pic)) and LY294002 on cell migration and wound closure were investigated using time-lapse imaging. Finally, the authors investigated the effect of PTEN inhibition on wound healing in whole rat eyes. RESULTS. In HCE cell monolayer and rat cornea, PTEN was downregulated at the wound edges within 30 minutes of wounding. The downregulation of PTEN was causal in a simultaneous increase in Akt activation, which was responsible for a significant increase in individual cell migration rate from 8.8 m/h to 17.3 m/h. An increased migration rate was maintained for 20 hours. PTEN inhibition significantly enhanced the wound healing rate in the HCE cell monolayer from 10 minutes onward after treatment and reduced the healing time in eye organ culture from 30 to 20 hours. CONCLUSIONS. Injury to the corneal epithelium downregulates the expression of PTEN at wound edges, allowing increased PI3K/Akt signaling, thereby contributing to a significant enhancement of cell migration and wound healing. These results suggest that PTEN inhibition may be an effective treatment for corneal injury. (Invest Ophthalmol Vis Sci.
Electric fields guide migration of epidermal stem cells and promote skin wound healing
Wound Repair and Regeneration, 2012
Migration of epidermal stem cells (EpSCs) into wounds may play an important role in wound healing... more Migration of epidermal stem cells (EpSCs) into wounds may play an important role in wound healing. Endogenous electric fields (EFs) arise naturally at wounds. Consistent with previous reports, we measured outward electric currents at rat skin wounds using vibrating probes. Topical use of prostaglandin E2 significantly promoted wound healing. However, it is not known whether EpSCs respond to EFs. We first isolated and characterized EpSCs from rat skin. We then demonstrated that EpSCs isolated from the epidermis migrated directionally toward the cathode in EFs of 50-400 mV/mm. The directedness values increased in a dose- and time-dependent fashion. The migration speed of EpSCs was significantly increased in EFs. EFs induced asymmetric polymerization of intracellular F-actin and activation of the extracellular signal-regulated kinase 1/2 and phosphatidylinositol-3-kinase (PI3K)/protein kinase B pathways. Inhibition of epidermal growth factor receptor, extracellular signal-regulated kinase 1/2, or PI3K significantly inhibited the cathodal distribution of F-actin and the electrotactic response of EpSCs. These data for the first time show that EpSCs possess obvious electrotaxis, in which the epidermal growth factor receptor-mitogen activated protein kinase-PI3K pathways are involved. These data thus suggest a novel aspect of electric signaling in wound healing-to stimulate and guide migration of EpSCs and to regulate wound healing.
NIH outlines goals to counter bioterror
Nature Biotechnology, 2002
New products highlight ambiguity of orphan drug law
Nature Biotechnology, 2003
Alteration of the coercivity spectrum and paleointensity determination
Geophysical Research Letters, 1987
Reply [to “Comment on ‘Alteration of the coercivity spectrum and Paleointensity determination by David J. Dunlop, Brian Reid, and Hironobu Hyodo’”]
Geophysical Research Letters, 1988
Endoscopic biopsy technique for acquiring larger mucosal samples
Gastrointestinal Endoscopy, 1991
Biopsies of the esophagus, stomach, and intestine are most often obtained using the traditional a... more Biopsies of the esophagus, stomach, and intestine are most often obtained using the traditional advance-and-close method with flexible endoscopes by extending an open forceps several millimeters beyond the endoscope tip to sample the mucosa, all under direct vision. We developed an alternative "turn-and-suction" endoscopic biopsy technique that permits the acquisition of larger mucosal samples. The biopsy forceps is advanced into the lumen, opened, and withdrawn backward until it is flush with the endoscope tip. Next, the endoscope tip is turned gently into the wall while air is suctioned from the lumen, and the biopsy forceps is very slightly advanced and then closed, usually without direct visualization. After straightening the endoscope tip, the biopsy is obtained by withdrawing the forceps and avulsing a superficial mucosal sample. By using this new method, we have safely taken over 10,000 biopsies without complications in endoscopic surveillance research protocols in patients at risk for gastrointestinal cancer. To compare the sizes of biopsies obtained with these two techniques, histologic sections of 341 mucosal samples from 12 patients with chronic ulcerative colitis were studied retrospectively. The mean greatest length of biopsy sections using the traditional technique was 4.72 mm, and using our new technique was 7.35 mm (56% longer). The turn-and-suction endoscopic biopsy method is best applied when flat mucosa is randomly sampled to seek microscopic pathologic changes that are not visible endoscopically, and may be advantageous for various non-histologic research analyses of gastrointestinal mucosa which are limited by tissue quantity.
Environment International, 2008
Due to their biological, chemical and physical actions, earthworms can be directly employed withi... more Due to their biological, chemical and physical actions, earthworms can be directly employed within bioremediation strategies to promote biodegradation of organic contaminants. Earthworms have been shown to aerate and bioturbate soils and improve their nutritional status and fertility, which are variables known to limit bioremediation. Earthworms have also been shown to retard the binding of organic contaminants to soils, release previously soil-bound contaminants for subsequent degradation, and promote and disperse organic contaminant degrading microorganisms. This review discusses these earthworm actions upon the soil environment and how they might influence the fate and behaviour of soil associated organic contaminants, subsequently improving bioremediation potential. The latter part of this review considers organic compounds in the following order: agrochemicals, petroleum and crude oil hydrocarbons, PAHs and PCBs.
Developmental Biology, 2009
Xenopus laevis tadpoles can regenerate tail, including spinal cord, after partial amputation, but... more Xenopus laevis tadpoles can regenerate tail, including spinal cord, after partial amputation, but lose this ability during a specific period around stage 45. They regain this ability after stage 45. What happens during this "refractory period" might hold the key to spinal cord regeneration. We hypothesize that electric currents at amputated stumps play significant roles in tail regeneration. We measured electric current at tail stumps following amputation at different developmental stages. Amputation induced large outward currents leaving the stump. In regenerating stumps of stage 40 tadpoles, a remarkable reversal of the current direction occurred around 12-24 h post-amputation, while non-regenerating stumps of stage 45 tadpole maintained outward currents. This reversal of electric current at tail stumps correlates with whether tails regenerate or not (regenerating stage 40-inward current; non-regenerating stage 45-outward current). Reduction of tail stump current using sodium-free solution decreased the rate of regeneration and percentage regeneration. Fin punch wounds healed normally at stages 45 and 48, and in sodium-free solution, suggesting that the absence of tail re-growth at stage 45 is regeneration-specific rather than a general inhibition of wound healing. These data suggest that electric signals might be one of the key players regulating regeneration.
Hereditary Gastrointestinal Polyposis Syndromes
American Journal of Surgical Pathology, 1986
Hereditary gastrointestinal polyposis syndromes can be divided into adenomatous and hamartomatous... more Hereditary gastrointestinal polyposis syndromes can be divided into adenomatous and hamartomatous types. Familial adenomatous polyposis coli (FAPC) is the prototype adenomatous polyposis syndrome and is defined by the autosomal dominant transmission of multiple (more than 100) colorectal adenomas. Virtually all affected patients develop colorectal carcinoma if untreated. Adenomas may develop also in the stomach and small bowel in FAPC patients, but the incidence of carcinoma in these sites is low. A variety of extracolonic manifestations has been reported in FAPC, with the name Gardner's syndrome applied to kindreds with osteomas of the skull and mandible, multiple epidermal cysts, and other skin and soft-tissue lesions. In Turcot's syndrome, brain tumors are present. The distinction between Gardner's and Turcot's syndromes and classical FAPC has become blurred because of marked overlap between them; some authorities consider them to be varying manifestations of a single genetic defect. The hamartomatous polyposes include Peutz-Jeghers syndrome, familial juvenile polyposis, Cowden's disease, intestinal ganglioneuromatosis, and the Ruvalcaba-Myrhe-Smith syndrome. The incidence of gastrointestinal cancer in patients with Peutz-Jeghers syndrome and familial juvenile polyposis exceeds that in the normal population, but is relatively low. In Cowden's disease, the gastrointestinal tract may be the site of multiple hamartomas, but there is no associated increase in the incidence of gastrointestinal cancers; instead, there is an increased incidence of carcinoma of the breast and thyroid. Intestinal ganglioneuromatosis occurs in von Recklinghausen's disease, in association with multiple endocrine neoplasia, type 2b, or as an isolated abnormality. Patients with ganglioneuromatosis do not appear to have an increased risk of developing gastrointestinal cancer. Ruvalcaba-Myrhe-Smith syndrome comprises macrocephaly, mental deficiency, an unusual craniofacial appearance, hamartomatous intestinal polyposis, and pigmented macules on the penis. No increased risk of developing cancer has been identified in the few reported cases.
Fems Microbiology Letters, 2001
This paper describes the validation and application of a simple flask-based 14 C-respirometer sys... more This paper describes the validation and application of a simple flask-based 14 C-respirometer system designed to assess mineralisation of 14 C-labelled substrates under defined conditions. Validation of this respirometer system indicated stoichiometric CO 2 trapping up to a maximum of 400 Wmol of CO 2 (in a single trap). Polycyclic aromatic hydrocarbon (PAH)-degrading bacteria were used to measure growthlinked biodegradation of [ 14 C]naphthalene to 14 CO 2 . A 14 C activity balance of 101.7 þ 8.9% (n = 6), after 74 h incubation time and 10 respirometer-opening events, indicated the suitability of the system for monitoring substrate mineralisation. This respirometric apparatus was then successfully applied to assess: (i) the PAH catabolism of microbes in a field contaminated soil, where naphthalene and phenanthrene were rapidly mineralised and (ii) soil-associated organic contaminant bioavailability, where increased soil^phenanthrene contact time resulted in a reduction in phenanthrene mineralisation in the soil. The described respirometer system differs from existing respirometer systems in that the CO 2 trap can be removed and replaced quickly and easily. The system is efficient, reproducible, adaptable to many situations, easy to construct and simple to use, it therefore affords advantages over existing systems. ß
Optimizing endoscopic biopsy detection of early cancers in Barrett's high-grade dysplasia
American Journal of Gastroenterology, 2000
The of high-grade dysplasia management (HGD) in Barrett's esophagus remains contr... more The of high-grade dysplasia management (HGD) in Barrett's esophagus remains controversial, in part, because of uncertainty about the ability of endoscopic biopsies to consistently detect early, curable cancers. Here we report cancers we have diagnosed in 45 patients with Barrett's HGD using a protocol involving serial endoscopies with four-quadrant biopsies taken at 1-cm intervals. We compare these results to a modeled endoscopic biopsy protocol in which four-quadrant biopsies are taken every 2 cm in the Barrett's segment. Thirteen cancers were detected at the baseline endoscopy and 32 in surveillance. In 82% of patients, cancer was detected at a single 1-cm level of the esophagus, and in 69% the cancer was detected in a single endoscopic biopsy specimen. A 2-cm protocol missed 50% of cancers that were detected by a 1-cm protocol in Barrett's segments 2 cm or more without visible lesions. The maximum depth of cancer invasion was intramucosal in 96% of patients. Only 39% of patients who had endoscopic biopsy cancer diagnoses had cancer detected in the esophagectomy specimen. Adverse outcomes included the development of regional metastatic disease during surveillance (1 of 32), operative mortality (3 of 36), including two patients who had their primary surgeries at other institutions, and death from metastatic disease after endoscopic ablation performed at another institution (1 of 3). A four-quadrant, 1-cm endoscopic biopsy protocol performed at closely timed intervals consistently detects early cancers arising in HGD in Barrett's esophagus and should be used in patients with HGD who do not undergo surgical resection.
Nature Biotechnology, 2002
HGS drug flop latest genomics setback
Nature Biotechnology, 2002
Measurement of Bioelectric Current with a Vibrating Probe
Journal of Visualized Experiments, 2011
Electric fields, generated by active transport of ions, are present in many biological systems an... more Electric fields, generated by active transport of ions, are present in many biological systems and often serve important functions in tissues and organs. For example, they play an important role in directing cell migration during wound healing. Here we describe the manufacture and use of ultrasensitive vibrating probes for measuring extracellular electric currents. The probe is an insulated, sharpened metal wire with a small platinum-black tip (30-35 μm), which can detect ionic currents in the μA/cm(2) range in physiological saline. The probe is vibrated at about 200 Hz by a piezoelectric bender. In the presence of an ionic current, the probe detects a voltage difference between the extremes of its movement. A lock-in amplifier filters out extraneous noise by locking on to the probe's frequency of vibration. Data are recorded onto computer. The probe is calibrated at the start and end of experiments in appropriate saline, using a chamber which applies a current of exactly 1.5 μA/cm(2). We describe how to make the probes, set up the system and calibrate. We also demonstrate the technique of cornea measurement, and show some representative results from different specimens (cornea, skin, brain).
Journal of applied physiology (Bethesda, Md. : 1985), 2011
Sun YH, Reid B, Fontaine JH, Miller LA, Hyde DM, Mogilner A, Zhao M. Airway epithelial wounds in ... more Sun YH, Reid B, Fontaine JH, Miller LA, Hyde DM, Mogilner A, Zhao M. Airway epithelial wounds in rhesus monkey generate ionic currents that guide cell migration to promote healing.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2005
Cataract is the most common cause of blindness but is at least curable by surgery. Unfortunately,... more Cataract is the most common cause of blindness but is at least curable by surgery. Unfortunately, many patients gradually develop the complication of posterior capsule opacification (PCO) or secondary cataract. This arises from stimulated cell growth within the lens capsule and can greatly impair vision. It is not fully understood why residual lens epithelial cell growth occurs after surgery. We propose and show that cataract surgery might remove an important inhibitory factor for lens cell growth, namely electric fields. The lens generates a unique pattern of electric currents constantly flowing out from the equator and entering the anterior and posterior poles. We show here that cutting and removing part of the anterior capsule as in cataract surgery significantly decreases the equatorial outward electric currents. Application of electric fields in culture inhibits proliferation of human lens epithelial cells. This inhibitory effect is likely to be mediated through a cell cycle control mechanism that decreases entry of cells into S phase from G1 phase by decreasing the G1-specific cell cycle protein cyclin E and increasing the cyclin-Cdk complex inhibitor p27 kip1 . Capsulorrhexis in vivo, which reduced endogenous lens electric fields, significantly increased LEC growth. This, together with our previous findings that electric fields have significant effects on the direction of lens cell migration, points to a controlling mechanism for the aberrant cell growth in posterior capsule opacification. A novel approach to control growth of lens epithelial cells using electric fields combined with other controlling mechanisms may be more effective in the prevention and treatment of this common complication of cataract surgery.
Investigative ophthalmology & visual science, 2011
PURPOSE. The PI3K/Akt pathway is required for cell polarization and migration, whereas the phosph... more PURPOSE. The PI3K/Akt pathway is required for cell polarization and migration, whereas the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) has inhibitory effects on the PI3K/Akt pathway. The authors therefore hypothesized that wounding would downregulate PTEN and that this downregulation would enhance wound healing. METHODS. In human corneal epithelial (HCE) cell monolayer and rat cornea scratch wound models, the authors investigated PTEN and Akt expression using Western blot and immunofluorescence analyses. The effects of PTEN and PI3K inhibitors dipotassium bisperoxo (picolinato) oxovanadate (bpv(pic)) and LY294002 on cell migration and wound closure were investigated using time-lapse imaging. Finally, the authors investigated the effect of PTEN inhibition on wound healing in whole rat eyes. RESULTS. In HCE cell monolayer and rat cornea, PTEN was downregulated at the wound edges within 30 minutes of wounding. The downregulation of PTEN was causal in a simultaneous increase in Akt activation, which was responsible for a significant increase in individual cell migration rate from 8.8 m/h to 17.3 m/h. An increased migration rate was maintained for 20 hours. PTEN inhibition significantly enhanced the wound healing rate in the HCE cell monolayer from 10 minutes onward after treatment and reduced the healing time in eye organ culture from 30 to 20 hours. CONCLUSIONS. Injury to the corneal epithelium downregulates the expression of PTEN at wound edges, allowing increased PI3K/Akt signaling, thereby contributing to a significant enhancement of cell migration and wound healing. These results suggest that PTEN inhibition may be an effective treatment for corneal injury. (Invest Ophthalmol Vis Sci.
Electric fields guide migration of epidermal stem cells and promote skin wound healing
Wound Repair and Regeneration, 2012
Migration of epidermal stem cells (EpSCs) into wounds may play an important role in wound healing... more Migration of epidermal stem cells (EpSCs) into wounds may play an important role in wound healing. Endogenous electric fields (EFs) arise naturally at wounds. Consistent with previous reports, we measured outward electric currents at rat skin wounds using vibrating probes. Topical use of prostaglandin E2 significantly promoted wound healing. However, it is not known whether EpSCs respond to EFs. We first isolated and characterized EpSCs from rat skin. We then demonstrated that EpSCs isolated from the epidermis migrated directionally toward the cathode in EFs of 50-400 mV/mm. The directedness values increased in a dose- and time-dependent fashion. The migration speed of EpSCs was significantly increased in EFs. EFs induced asymmetric polymerization of intracellular F-actin and activation of the extracellular signal-regulated kinase 1/2 and phosphatidylinositol-3-kinase (PI3K)/protein kinase B pathways. Inhibition of epidermal growth factor receptor, extracellular signal-regulated kinase 1/2, or PI3K significantly inhibited the cathodal distribution of F-actin and the electrotactic response of EpSCs. These data for the first time show that EpSCs possess obvious electrotaxis, in which the epidermal growth factor receptor-mitogen activated protein kinase-PI3K pathways are involved. These data thus suggest a novel aspect of electric signaling in wound healing-to stimulate and guide migration of EpSCs and to regulate wound healing.
NIH outlines goals to counter bioterror
Nature Biotechnology, 2002
New products highlight ambiguity of orphan drug law
Nature Biotechnology, 2003
Alteration of the coercivity spectrum and paleointensity determination
Geophysical Research Letters, 1987
Reply [to “Comment on ‘Alteration of the coercivity spectrum and Paleointensity determination by David J. Dunlop, Brian Reid, and Hironobu Hyodo’”]
Geophysical Research Letters, 1988
Endoscopic biopsy technique for acquiring larger mucosal samples
Gastrointestinal Endoscopy, 1991
Biopsies of the esophagus, stomach, and intestine are most often obtained using the traditional a... more Biopsies of the esophagus, stomach, and intestine are most often obtained using the traditional advance-and-close method with flexible endoscopes by extending an open forceps several millimeters beyond the endoscope tip to sample the mucosa, all under direct vision. We developed an alternative "turn-and-suction" endoscopic biopsy technique that permits the acquisition of larger mucosal samples. The biopsy forceps is advanced into the lumen, opened, and withdrawn backward until it is flush with the endoscope tip. Next, the endoscope tip is turned gently into the wall while air is suctioned from the lumen, and the biopsy forceps is very slightly advanced and then closed, usually without direct visualization. After straightening the endoscope tip, the biopsy is obtained by withdrawing the forceps and avulsing a superficial mucosal sample. By using this new method, we have safely taken over 10,000 biopsies without complications in endoscopic surveillance research protocols in patients at risk for gastrointestinal cancer. To compare the sizes of biopsies obtained with these two techniques, histologic sections of 341 mucosal samples from 12 patients with chronic ulcerative colitis were studied retrospectively. The mean greatest length of biopsy sections using the traditional technique was 4.72 mm, and using our new technique was 7.35 mm (56% longer). The turn-and-suction endoscopic biopsy method is best applied when flat mucosa is randomly sampled to seek microscopic pathologic changes that are not visible endoscopically, and may be advantageous for various non-histologic research analyses of gastrointestinal mucosa which are limited by tissue quantity.
Environment International, 2008
Due to their biological, chemical and physical actions, earthworms can be directly employed withi... more Due to their biological, chemical and physical actions, earthworms can be directly employed within bioremediation strategies to promote biodegradation of organic contaminants. Earthworms have been shown to aerate and bioturbate soils and improve their nutritional status and fertility, which are variables known to limit bioremediation. Earthworms have also been shown to retard the binding of organic contaminants to soils, release previously soil-bound contaminants for subsequent degradation, and promote and disperse organic contaminant degrading microorganisms. This review discusses these earthworm actions upon the soil environment and how they might influence the fate and behaviour of soil associated organic contaminants, subsequently improving bioremediation potential. The latter part of this review considers organic compounds in the following order: agrochemicals, petroleum and crude oil hydrocarbons, PAHs and PCBs.
Developmental Biology, 2009
Xenopus laevis tadpoles can regenerate tail, including spinal cord, after partial amputation, but... more Xenopus laevis tadpoles can regenerate tail, including spinal cord, after partial amputation, but lose this ability during a specific period around stage 45. They regain this ability after stage 45. What happens during this "refractory period" might hold the key to spinal cord regeneration. We hypothesize that electric currents at amputated stumps play significant roles in tail regeneration. We measured electric current at tail stumps following amputation at different developmental stages. Amputation induced large outward currents leaving the stump. In regenerating stumps of stage 40 tadpoles, a remarkable reversal of the current direction occurred around 12-24 h post-amputation, while non-regenerating stumps of stage 45 tadpole maintained outward currents. This reversal of electric current at tail stumps correlates with whether tails regenerate or not (regenerating stage 40-inward current; non-regenerating stage 45-outward current). Reduction of tail stump current using sodium-free solution decreased the rate of regeneration and percentage regeneration. Fin punch wounds healed normally at stages 45 and 48, and in sodium-free solution, suggesting that the absence of tail re-growth at stage 45 is regeneration-specific rather than a general inhibition of wound healing. These data suggest that electric signals might be one of the key players regulating regeneration.
Hereditary Gastrointestinal Polyposis Syndromes
American Journal of Surgical Pathology, 1986
Hereditary gastrointestinal polyposis syndromes can be divided into adenomatous and hamartomatous... more Hereditary gastrointestinal polyposis syndromes can be divided into adenomatous and hamartomatous types. Familial adenomatous polyposis coli (FAPC) is the prototype adenomatous polyposis syndrome and is defined by the autosomal dominant transmission of multiple (more than 100) colorectal adenomas. Virtually all affected patients develop colorectal carcinoma if untreated. Adenomas may develop also in the stomach and small bowel in FAPC patients, but the incidence of carcinoma in these sites is low. A variety of extracolonic manifestations has been reported in FAPC, with the name Gardner's syndrome applied to kindreds with osteomas of the skull and mandible, multiple epidermal cysts, and other skin and soft-tissue lesions. In Turcot's syndrome, brain tumors are present. The distinction between Gardner's and Turcot's syndromes and classical FAPC has become blurred because of marked overlap between them; some authorities consider them to be varying manifestations of a single genetic defect. The hamartomatous polyposes include Peutz-Jeghers syndrome, familial juvenile polyposis, Cowden's disease, intestinal ganglioneuromatosis, and the Ruvalcaba-Myrhe-Smith syndrome. The incidence of gastrointestinal cancer in patients with Peutz-Jeghers syndrome and familial juvenile polyposis exceeds that in the normal population, but is relatively low. In Cowden's disease, the gastrointestinal tract may be the site of multiple hamartomas, but there is no associated increase in the incidence of gastrointestinal cancers; instead, there is an increased incidence of carcinoma of the breast and thyroid. Intestinal ganglioneuromatosis occurs in von Recklinghausen's disease, in association with multiple endocrine neoplasia, type 2b, or as an isolated abnormality. Patients with ganglioneuromatosis do not appear to have an increased risk of developing gastrointestinal cancer. Ruvalcaba-Myrhe-Smith syndrome comprises macrocephaly, mental deficiency, an unusual craniofacial appearance, hamartomatous intestinal polyposis, and pigmented macules on the penis. No increased risk of developing cancer has been identified in the few reported cases.
Fems Microbiology Letters, 2001
This paper describes the validation and application of a simple flask-based 14 C-respirometer sys... more This paper describes the validation and application of a simple flask-based 14 C-respirometer system designed to assess mineralisation of 14 C-labelled substrates under defined conditions. Validation of this respirometer system indicated stoichiometric CO 2 trapping up to a maximum of 400 Wmol of CO 2 (in a single trap). Polycyclic aromatic hydrocarbon (PAH)-degrading bacteria were used to measure growthlinked biodegradation of [ 14 C]naphthalene to 14 CO 2 . A 14 C activity balance of 101.7 þ 8.9% (n = 6), after 74 h incubation time and 10 respirometer-opening events, indicated the suitability of the system for monitoring substrate mineralisation. This respirometric apparatus was then successfully applied to assess: (i) the PAH catabolism of microbes in a field contaminated soil, where naphthalene and phenanthrene were rapidly mineralised and (ii) soil-associated organic contaminant bioavailability, where increased soil^phenanthrene contact time resulted in a reduction in phenanthrene mineralisation in the soil. The described respirometer system differs from existing respirometer systems in that the CO 2 trap can be removed and replaced quickly and easily. The system is efficient, reproducible, adaptable to many situations, easy to construct and simple to use, it therefore affords advantages over existing systems. ß
Optimizing endoscopic biopsy detection of early cancers in Barrett's high-grade dysplasia
American Journal of Gastroenterology, 2000
The of high-grade dysplasia management (HGD) in Barrett's esophagus remains contr... more The of high-grade dysplasia management (HGD) in Barrett's esophagus remains controversial, in part, because of uncertainty about the ability of endoscopic biopsies to consistently detect early, curable cancers. Here we report cancers we have diagnosed in 45 patients with Barrett's HGD using a protocol involving serial endoscopies with four-quadrant biopsies taken at 1-cm intervals. We compare these results to a modeled endoscopic biopsy protocol in which four-quadrant biopsies are taken every 2 cm in the Barrett's segment. Thirteen cancers were detected at the baseline endoscopy and 32 in surveillance. In 82% of patients, cancer was detected at a single 1-cm level of the esophagus, and in 69% the cancer was detected in a single endoscopic biopsy specimen. A 2-cm protocol missed 50% of cancers that were detected by a 1-cm protocol in Barrett's segments 2 cm or more without visible lesions. The maximum depth of cancer invasion was intramucosal in 96% of patients. Only 39% of patients who had endoscopic biopsy cancer diagnoses had cancer detected in the esophagectomy specimen. Adverse outcomes included the development of regional metastatic disease during surveillance (1 of 32), operative mortality (3 of 36), including two patients who had their primary surgeries at other institutions, and death from metastatic disease after endoscopic ablation performed at another institution (1 of 3). A four-quadrant, 1-cm endoscopic biopsy protocol performed at closely timed intervals consistently detects early cancers arising in HGD in Barrett's esophagus and should be used in patients with HGD who do not undergo surgical resection.