David Mitchell | Monash University (original) (raw)

Papers by David Mitchell

Research paper thumbnail of Susceptibility of mutant, recombinant plasminogen activators to proteolytic breakdown: Removal of the F domain by plasmin

Fibrinolysis, 1993

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Research paper thumbnail of Time course for early adaptive responses to ultraviolet B light in the epidermis of SKH-1 mice

Cancer research, Jan 15, 1999

Hairless SKH-1 mice were exposed once to UVB light (180 mJ/cm2), and mechanistically important ea... more Hairless SKH-1 mice were exposed once to UVB light (180 mJ/cm2), and mechanistically important early adaptive responses in the epidermis were evaluated by immunohistochemical and morphological methods. Interrelationships in the time course for these UVB-induced responses were examined. The number of epidermal cells with DNA strand breaks (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells) or with thymine dimers increased to maximal levels within 30 min after UVB. The number of cells with DNA strand breaks located specifically in the basal layer of the epidermis was increased substantially by 3-30 min after UVB and gradually increased further over the next 5.5 hours. DNA strand breaks specifically in the basal layer of the epidermis were increased maximally at 6 h after UVB. The number of epidermal cells with DNA strand breaks or thymine dimers decreased markedly between 12 and 36 h. Pyrimidine (6-4) pyrimidone photodimers (6-4 photoproducts) in iso...

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Research paper thumbnail of Novel Chinese hamster ultraviolet-sensitive mutants for excision repair form complementation groups 9 and 10

Cancer research, 1991

In this paper we demonstrate that the mutants CHO7PV and CHO4PV isolated by us from the CHO-K1 pr... more In this paper we demonstrate that the mutants CHO7PV and CHO4PV isolated by us from the CHO-K1 prol- cell line represent two new complementation groups of UV-sensitive excision repair-defective rodent mutants. We have classified the mutant CHO7PV as representative of Group 9 and CHO4PV as representative of Group 10. Cellular and biochemical characterization of these mutants indicates that they are moderately sensitive to a broad spectrum of mutagens (UV and mono- and bifunctional alkylating agents), partially unable to perform UV-induced DNA repair synthesis, and partially defective in the incision step of the DNA excision repair pathway and in the removal of the two main lesions caused by UV [cyclobutane pyrimidine dimers and (6-4) photo-products]. In terms of UV survival and incision, CHO4PV is apparently more defective than CHO7PV (40% and 50% of wild-type survival, respectively, and 55% and 75% of wild-type incision), whereas when repair DNA synthesis and lesion removal are comp...

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Research paper thumbnail of Resolution of UV-induced DNA damage in Xiphophorus fishes

Marine biotechnology (New York, N.Y.), 2001

The genus Xiphophorus is an important model for investigating the etiology and genetics of sunlig... more The genus Xiphophorus is an important model for investigating the etiology and genetics of sunlight-induced melanoma as well as other cancers. We investigated the role DNA damage plays in tumorigenesis in Xiphophorus using a variety of immunological techniques to examine the induction, distribution, and repair of the major photoproducts in DNA after exposure to solar (ultraviolet-B) radiation. We found that cyclobutane pyrimidine dimers (CPDs) were induced at 5- to 10-fold greater frequency than the (6-4) photoproduct ((6-4)PD) in Xiphophorus signum, and the efficiency of photoproduct formation was tissue-dependent, with the scales providing considerable photoprotection against both types of damage. Both of these lesions are efficiently repaired in the presence of visible light by photoenzymatic repair with CPDs repaired at about twice the rate of (6-4)PDs. Photoenzymatic repair of cyclobutane dimers is inducible by prior exposure to low levels of visible light and can be extremely ...

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Research paper thumbnail of Effects of chronic low-dose ultraviolet B radiation on DNA damage and repair in mouse skin

Cancer research, Jan 15, 1999

Chronic exposure to sunlight causes skin cancer in humans, yet little is known about how habitual... more Chronic exposure to sunlight causes skin cancer in humans, yet little is known about how habitual exposure to low doses of ultraviolet B radiation (UVB) affects DNA damage in the skin. We treated Skh-1 hairless mice with daily doses of suberythemal UVB for 40 days and analyzed the amount and distribution of DNA photodamage using RIAs and immunofluorescence micrography. We found that DNA damage accumulated in mouse skin as a result of chronic irradiation and that this damage persisted in the dermis and epidermis for several weeks after the chronic treatment was terminated. Although the persistent damage was evenly distributed throughout the dermis, it remained in the epidermis as a small number of heavily damaged cells at the dermal-epidermal boundary. Rates of DNA damage induction and repair were determined at different times over the course of chronic treatment in response to a higher challenge dose of UVB light. The amount of damage induced by the challenge dose increased in respo...

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Research paper thumbnail of Dye-mediated photolysis is capable of eliminating drug-resistant (MDR+) tumor cells

Blood, 1993

We evaluated the potential role of photoradiation therapy with a benzoporphyrin derivative, monoa... more We evaluated the potential role of photoradiation therapy with a benzoporphyrin derivative, monoacid ring A (BPD-MA), and dihematoporphyrin ether (DHE), for the ex vivo purging of residual tumor cells from autologous bone marrow (BM) grafts. BPD-MA and DHE photosensitizing activity was tested against two human large-cell lymphoma cell lines and colony-forming unit-leukemia (CFU-L) derived from patients with acute myelogenous leukemia (AML). In mixing experiments, 4-log elimination of tumor cell lines was observed after 1 hour of incubation with 75 ng/mL of BPD-MA or 30 minutes of treatment with 12.5 micrograms/mL of DHE followed by white light exposure. By comparison, using the same concentration of BPD-MA, the mean recovery of normal BM progenitors was 4% +/- 0.8% (mean +/- SD) for granulocyte-macrophage colony-forming unit (CFU-GM) and 5% +/- 0.8% for burst-forming unit-erythroid (BFU-E). Similarly, DHE treatment resulted in the recovery of 5.2% +/- 2% and 9.8% +/- 3% of CFU-GM an...

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Research paper thumbnail of Principles of renal access surgery and transplantation

Surgery (Oxford), 2010

ABSTRACT The treatment of end stage renal failure is renal replacement therapy. This may be by di... more ABSTRACT The treatment of end stage renal failure is renal replacement therapy. This may be by dialysis (blood or peritoneal) or by kidney transplantation. The outlook for those who have a successful renal transplant has improved significantly over the past 20 years: graft survival from non-heart-beating donation is now a mean of 14 years, and 18 years for live donor transplants.Unfortunately the number of renal transplants fails to meet the demand from patients on the transplant waiting list. The shortfall has to be managed by dialysis. Life expectancy of a patient on haemodialysis is one-fifth to one-quarter of that of the age-matched healthy population, but doubles following successful transplantation.The predominant type of dialysis is blood dialysis. To provide this, patients require a portal of access to the circulation. This patient group requires timely and well-planned renal access surgery. Circulatory access is their lifeline. Failure of access, coupled with the need for emergency admission, is a major cause of morbidity and mortality.

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Research paper thumbnail of Environmental Ultraviolet Photobiology: Introduction

Photochemistry and Photobiology, 1996

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Research paper thumbnail of Development of a marrow transplant regimen for acute leukemia using targeted hematopoietic irradiation delivered by 131I-labeled anti-CD45 antibody, combined with cyclophosphamide and total body irradiation

Blood, Jan 15, 1995

In an attempt to decrease the relapse rate after bone marrow transplantation (BMT) for advanced a... more In an attempt to decrease the relapse rate after bone marrow transplantation (BMT) for advanced acute leukemia, we initiated studies using 131I-labeled anti-CD45 antibody (BC8) to deliver radiation specifically to hematopoietic tissues, followed by a standard transplant preparative regimen. Biodistribution studies were performed in 23 patients using 0.5 mg/kg trace 131I-labeled BC8 antibody. The BC8 antibody was cleared rapidly from plasma with an initial disappearance half-time of 1.5 +/- 0.2 hours, presumably reflecting rapid antigen-specific binding. The mean radiation absorbed doses (cGy/mCi131I administered) were as follows: marrow, 7.1 +/- 0.8; spleen, 10.8 +/- 1.4; liver, 2.7 +/- 0.2; lungs, 2.1 +/- 0.1; kidneys, 0.7 +/- 0.1; and total body, 0.4 +/- 0.03. Patients with acute myelogenous leukemia (AML) in relapse had a higher marrow dose (11.4 cGy/mCi) than those in remission (5.2 cGy/mCi; P = .001) because of higher uptake and longer retention of radionuclide in marrow. Twent...

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Research paper thumbnail of Comparison of the responses of human melanocytes with different melanin contents to ultraviolet B irradiation

Cancer research, Jan 15, 1995

Melanin is thought to serve in photoprotection. To investigate this, we have compared the respons... more Melanin is thought to serve in photoprotection. To investigate this, we have compared the responses of cultured human melanocytes derived from different pigmentary phenotypes (skin types I-VI) to a single irradiation with different doses of UVB light, ranging between 11.7 and 70.1 mJ/cm2. After UVB irradiation, heavily pigmented melanocytes had the same percent survival but a greater capacity to resume proliferation than their lightly pigmented counterparts. A significant increase in melanin content was observed in heavily pigmented but not in lightly pigmented melanocytes. Irradiation with UVB light blocked melanocytes, regardless of their melanin content, in G1, and induced the expression of the tumor suppressor p53 protein within 4 h. This induction steadily increased up to 48 h in lightly pigmented melanocytes; however, in heavily pigmented melanocytes, p53 level peaked at 24 h after UVB treatment and declined thereafter. Additionally, DNA from lightly pigmented melanocytes cont...

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Research paper thumbnail of Pyrimidine dimer removal enhanced by DNA repair liposomes reduces the incidence of UV skin cancer in mice

Cancer research, 1992

UV exposure has been linked to skin cancer in humans by epidemiology and the rare genetic disease... more UV exposure has been linked to skin cancer in humans by epidemiology and the rare genetic disease xeroderma pigmentosum. However, UV produces multiple photoproducts in DNA, and their relative contribution is uncertain. An enzyme which specifically repairs cyclobutane pyrimidine dimers in DNA, T4 endonuclease V, was encapsulated in liposomes for topical delivery into mouse and human skin. In both species, liposomes applied after UV exposure localized in the epidermis and stimulated the removal of cyclobutane pyrimidine dimers. UV-irradiated mice treated with these liposomes had a dose-dependent decrease in the incidence of squamous cell carcinoma compared to controls. The results demonstrate that unrepaired cyclobutane pyrimidine dimers in DNA are a direct cause of cancer in mammalian skin.

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Research paper thumbnail of (6-4) photoproducts and not cyclobutane pyrimidine dimers are the main UV-induced mutagenic lesions in Chinese hamster cells

Mutation research, 1992

A partial revertant (RH1-26) of the UV-sensitive Chinese hamster V79 cell mutant V-H1 (complement... more A partial revertant (RH1-26) of the UV-sensitive Chinese hamster V79 cell mutant V-H1 (complementation group 2) was isolated and characterized. It was used to analyze the mutagenic potency of the 2 major UV-induced lesions, cyclobutane pyrimidine dimers and (6-4) photoproducts. Both V-H1 and RH1-26 did not repair pyrimidine dimers measured in the genome overall as well as in the active hprt gene. Repair of (6-4) photoproducts from the genome overall was slower in V-H1 than in wild-type V79 cells, but was restored to normal in RH1-26. Although V-H1 cells have a 7-fold enhanced mutagenicity, RH1-26 cells, despite the absence of pyrimidine dimer repair, have a slightly lower level of UV-induced mutagenesis than observed in wild-type V79 cells. The molecular nature of hprt mutations and the DNA-strand specificity were similar in V79 and RH1-26 cells but different from that of V-H1 cells. Since in RH1-26 as well as in V79 cells most hprt mutations were induced by lesions in the non-trans...

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Research paper thumbnail of A model for growth of a single fungal hypha based on well-mixed tanks in series: simulation of nutrient and vesicle transport in aerial reproductive hyphae

PloS one, 2015

Current models that describe the extension of fungal hyphae and development of a mycelium either ... more Current models that describe the extension of fungal hyphae and development of a mycelium either do not describe the role of vesicles in hyphal extension or do not correctly describe the experimentally observed profile for distribution of vesicles along the hypha. The present work uses the n-tanks-in-series approach to develop a model for hyphal extension that describes the intracellular transport of nutrient to a sub-apical zone where vesicles are formed and then transported to the tip, where tip extension occurs. The model was calibrated using experimental data from the literature for the extension of reproductive aerial hyphae of three different fungi, and was able to describe different profiles involving acceleration and deceleration of the extension rate. A sensitivity analysis showed that the supply of nutrient to the sub-apical vesicle-producing zone is a key factor influencing the rate of extension of the hypha. Although this model was used to describe the extension of a sin...

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Research paper thumbnail of Dryandra Woodland

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Research paper thumbnail of Histological Comparison of Fibrous Root Infection of Disease-Tolerant and Susceptible Citrus Hosts by Phytophthora nicotianae and P. palmivora

Phytopathology, 1998

Phytophthora nicotianae and P. palmivora infect and cause rot of fibrous roots of susceptible and... more Phytophthora nicotianae and P. palmivora infect and cause rot of fibrous roots of susceptible and tolerant citrus rootstocks in Florida orchards. The infection and colonization by the two Phytophthora spp. of a susceptible citrus host, sour orange (Citrus aurantium), and a tolerant host, trifoliate orange (Poncirus trifoliata), were compared using light and electron microscopy. Penetration by both Phytophthora spp. occurred within 1 h after inoculation, regardless of the host species. No differences were observed in mode of penetration of the hypodermis or the hosts' response to infection. After 24 h, P. palmivora had a significantly higher colonization of cortical cells in susceptible sour orange than in tolerant trifoliate orange. Intracellular hyphae of both Phytophthora spp. were observed in the cortex of sour orange, and cortical cells adjacent to intercellular hyphae of P. palmivora were disrupted. In contrast, the cortical cells of sour orange and trifoliate orange adjace...

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Research paper thumbnail of Immobilization and Characterization of a New Regioselective and Enantioselective Lipase Obtained from a Metagenomic Library

PLOS ONE, 2015

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Research paper thumbnail of Modelling fungal growth on surfaces

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Research paper thumbnail of ChemInform Abstract: Recent Developments in the Design, Operation and Modeling of Bioreactors for Solid-State Fermentation

ChemInform, 1999

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Research paper thumbnail of Australian wetlands: the monitoring challenge

Wetlands Ecology and Management, 1999

Management of Australian wetlands is confounded by an absence of adequate environmental monitorin... more Management of Australian wetlands is confounded by an absence of adequate environmental monitoring data. To a large extent we are still not sure of the exact location and extent of many wetlands. Inventory and monitoring information are intricately linked and at the heart of successful wetland management. Monitoring addresses the extent of change in the environment, yet, for wetlands, it

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Research paper thumbnail of THROMBOLITE COMMUNITY OF COASTAL FRESHWATER LAKES (LAKE RICHMOND), INTERIM RECOVERY PLAN (Coastal freshwater lakes thrombolitic aragonite community formed by biologically influenced precipitation of a mineral phase) 2003-2008

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Research paper thumbnail of Susceptibility of mutant, recombinant plasminogen activators to proteolytic breakdown: Removal of the F domain by plasmin

Fibrinolysis, 1993

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Research paper thumbnail of Time course for early adaptive responses to ultraviolet B light in the epidermis of SKH-1 mice

Cancer research, Jan 15, 1999

Hairless SKH-1 mice were exposed once to UVB light (180 mJ/cm2), and mechanistically important ea... more Hairless SKH-1 mice were exposed once to UVB light (180 mJ/cm2), and mechanistically important early adaptive responses in the epidermis were evaluated by immunohistochemical and morphological methods. Interrelationships in the time course for these UVB-induced responses were examined. The number of epidermal cells with DNA strand breaks (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells) or with thymine dimers increased to maximal levels within 30 min after UVB. The number of cells with DNA strand breaks located specifically in the basal layer of the epidermis was increased substantially by 3-30 min after UVB and gradually increased further over the next 5.5 hours. DNA strand breaks specifically in the basal layer of the epidermis were increased maximally at 6 h after UVB. The number of epidermal cells with DNA strand breaks or thymine dimers decreased markedly between 12 and 36 h. Pyrimidine (6-4) pyrimidone photodimers (6-4 photoproducts) in iso...

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Research paper thumbnail of Novel Chinese hamster ultraviolet-sensitive mutants for excision repair form complementation groups 9 and 10

Cancer research, 1991

In this paper we demonstrate that the mutants CHO7PV and CHO4PV isolated by us from the CHO-K1 pr... more In this paper we demonstrate that the mutants CHO7PV and CHO4PV isolated by us from the CHO-K1 prol- cell line represent two new complementation groups of UV-sensitive excision repair-defective rodent mutants. We have classified the mutant CHO7PV as representative of Group 9 and CHO4PV as representative of Group 10. Cellular and biochemical characterization of these mutants indicates that they are moderately sensitive to a broad spectrum of mutagens (UV and mono- and bifunctional alkylating agents), partially unable to perform UV-induced DNA repair synthesis, and partially defective in the incision step of the DNA excision repair pathway and in the removal of the two main lesions caused by UV [cyclobutane pyrimidine dimers and (6-4) photo-products]. In terms of UV survival and incision, CHO4PV is apparently more defective than CHO7PV (40% and 50% of wild-type survival, respectively, and 55% and 75% of wild-type incision), whereas when repair DNA synthesis and lesion removal are comp...

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Research paper thumbnail of Resolution of UV-induced DNA damage in Xiphophorus fishes

Marine biotechnology (New York, N.Y.), 2001

The genus Xiphophorus is an important model for investigating the etiology and genetics of sunlig... more The genus Xiphophorus is an important model for investigating the etiology and genetics of sunlight-induced melanoma as well as other cancers. We investigated the role DNA damage plays in tumorigenesis in Xiphophorus using a variety of immunological techniques to examine the induction, distribution, and repair of the major photoproducts in DNA after exposure to solar (ultraviolet-B) radiation. We found that cyclobutane pyrimidine dimers (CPDs) were induced at 5- to 10-fold greater frequency than the (6-4) photoproduct ((6-4)PD) in Xiphophorus signum, and the efficiency of photoproduct formation was tissue-dependent, with the scales providing considerable photoprotection against both types of damage. Both of these lesions are efficiently repaired in the presence of visible light by photoenzymatic repair with CPDs repaired at about twice the rate of (6-4)PDs. Photoenzymatic repair of cyclobutane dimers is inducible by prior exposure to low levels of visible light and can be extremely ...

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Research paper thumbnail of Effects of chronic low-dose ultraviolet B radiation on DNA damage and repair in mouse skin

Cancer research, Jan 15, 1999

Chronic exposure to sunlight causes skin cancer in humans, yet little is known about how habitual... more Chronic exposure to sunlight causes skin cancer in humans, yet little is known about how habitual exposure to low doses of ultraviolet B radiation (UVB) affects DNA damage in the skin. We treated Skh-1 hairless mice with daily doses of suberythemal UVB for 40 days and analyzed the amount and distribution of DNA photodamage using RIAs and immunofluorescence micrography. We found that DNA damage accumulated in mouse skin as a result of chronic irradiation and that this damage persisted in the dermis and epidermis for several weeks after the chronic treatment was terminated. Although the persistent damage was evenly distributed throughout the dermis, it remained in the epidermis as a small number of heavily damaged cells at the dermal-epidermal boundary. Rates of DNA damage induction and repair were determined at different times over the course of chronic treatment in response to a higher challenge dose of UVB light. The amount of damage induced by the challenge dose increased in respo...

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Research paper thumbnail of Dye-mediated photolysis is capable of eliminating drug-resistant (MDR+) tumor cells

Blood, 1993

We evaluated the potential role of photoradiation therapy with a benzoporphyrin derivative, monoa... more We evaluated the potential role of photoradiation therapy with a benzoporphyrin derivative, monoacid ring A (BPD-MA), and dihematoporphyrin ether (DHE), for the ex vivo purging of residual tumor cells from autologous bone marrow (BM) grafts. BPD-MA and DHE photosensitizing activity was tested against two human large-cell lymphoma cell lines and colony-forming unit-leukemia (CFU-L) derived from patients with acute myelogenous leukemia (AML). In mixing experiments, 4-log elimination of tumor cell lines was observed after 1 hour of incubation with 75 ng/mL of BPD-MA or 30 minutes of treatment with 12.5 micrograms/mL of DHE followed by white light exposure. By comparison, using the same concentration of BPD-MA, the mean recovery of normal BM progenitors was 4% +/- 0.8% (mean +/- SD) for granulocyte-macrophage colony-forming unit (CFU-GM) and 5% +/- 0.8% for burst-forming unit-erythroid (BFU-E). Similarly, DHE treatment resulted in the recovery of 5.2% +/- 2% and 9.8% +/- 3% of CFU-GM an...

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Research paper thumbnail of Principles of renal access surgery and transplantation

Surgery (Oxford), 2010

ABSTRACT The treatment of end stage renal failure is renal replacement therapy. This may be by di... more ABSTRACT The treatment of end stage renal failure is renal replacement therapy. This may be by dialysis (blood or peritoneal) or by kidney transplantation. The outlook for those who have a successful renal transplant has improved significantly over the past 20 years: graft survival from non-heart-beating donation is now a mean of 14 years, and 18 years for live donor transplants.Unfortunately the number of renal transplants fails to meet the demand from patients on the transplant waiting list. The shortfall has to be managed by dialysis. Life expectancy of a patient on haemodialysis is one-fifth to one-quarter of that of the age-matched healthy population, but doubles following successful transplantation.The predominant type of dialysis is blood dialysis. To provide this, patients require a portal of access to the circulation. This patient group requires timely and well-planned renal access surgery. Circulatory access is their lifeline. Failure of access, coupled with the need for emergency admission, is a major cause of morbidity and mortality.

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Research paper thumbnail of Environmental Ultraviolet Photobiology: Introduction

Photochemistry and Photobiology, 1996

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Research paper thumbnail of Development of a marrow transplant regimen for acute leukemia using targeted hematopoietic irradiation delivered by 131I-labeled anti-CD45 antibody, combined with cyclophosphamide and total body irradiation

Blood, Jan 15, 1995

In an attempt to decrease the relapse rate after bone marrow transplantation (BMT) for advanced a... more In an attempt to decrease the relapse rate after bone marrow transplantation (BMT) for advanced acute leukemia, we initiated studies using 131I-labeled anti-CD45 antibody (BC8) to deliver radiation specifically to hematopoietic tissues, followed by a standard transplant preparative regimen. Biodistribution studies were performed in 23 patients using 0.5 mg/kg trace 131I-labeled BC8 antibody. The BC8 antibody was cleared rapidly from plasma with an initial disappearance half-time of 1.5 +/- 0.2 hours, presumably reflecting rapid antigen-specific binding. The mean radiation absorbed doses (cGy/mCi131I administered) were as follows: marrow, 7.1 +/- 0.8; spleen, 10.8 +/- 1.4; liver, 2.7 +/- 0.2; lungs, 2.1 +/- 0.1; kidneys, 0.7 +/- 0.1; and total body, 0.4 +/- 0.03. Patients with acute myelogenous leukemia (AML) in relapse had a higher marrow dose (11.4 cGy/mCi) than those in remission (5.2 cGy/mCi; P = .001) because of higher uptake and longer retention of radionuclide in marrow. Twent...

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Research paper thumbnail of Comparison of the responses of human melanocytes with different melanin contents to ultraviolet B irradiation

Cancer research, Jan 15, 1995

Melanin is thought to serve in photoprotection. To investigate this, we have compared the respons... more Melanin is thought to serve in photoprotection. To investigate this, we have compared the responses of cultured human melanocytes derived from different pigmentary phenotypes (skin types I-VI) to a single irradiation with different doses of UVB light, ranging between 11.7 and 70.1 mJ/cm2. After UVB irradiation, heavily pigmented melanocytes had the same percent survival but a greater capacity to resume proliferation than their lightly pigmented counterparts. A significant increase in melanin content was observed in heavily pigmented but not in lightly pigmented melanocytes. Irradiation with UVB light blocked melanocytes, regardless of their melanin content, in G1, and induced the expression of the tumor suppressor p53 protein within 4 h. This induction steadily increased up to 48 h in lightly pigmented melanocytes; however, in heavily pigmented melanocytes, p53 level peaked at 24 h after UVB treatment and declined thereafter. Additionally, DNA from lightly pigmented melanocytes cont...

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Research paper thumbnail of Pyrimidine dimer removal enhanced by DNA repair liposomes reduces the incidence of UV skin cancer in mice

Cancer research, 1992

UV exposure has been linked to skin cancer in humans by epidemiology and the rare genetic disease... more UV exposure has been linked to skin cancer in humans by epidemiology and the rare genetic disease xeroderma pigmentosum. However, UV produces multiple photoproducts in DNA, and their relative contribution is uncertain. An enzyme which specifically repairs cyclobutane pyrimidine dimers in DNA, T4 endonuclease V, was encapsulated in liposomes for topical delivery into mouse and human skin. In both species, liposomes applied after UV exposure localized in the epidermis and stimulated the removal of cyclobutane pyrimidine dimers. UV-irradiated mice treated with these liposomes had a dose-dependent decrease in the incidence of squamous cell carcinoma compared to controls. The results demonstrate that unrepaired cyclobutane pyrimidine dimers in DNA are a direct cause of cancer in mammalian skin.

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Research paper thumbnail of (6-4) photoproducts and not cyclobutane pyrimidine dimers are the main UV-induced mutagenic lesions in Chinese hamster cells

Mutation research, 1992

A partial revertant (RH1-26) of the UV-sensitive Chinese hamster V79 cell mutant V-H1 (complement... more A partial revertant (RH1-26) of the UV-sensitive Chinese hamster V79 cell mutant V-H1 (complementation group 2) was isolated and characterized. It was used to analyze the mutagenic potency of the 2 major UV-induced lesions, cyclobutane pyrimidine dimers and (6-4) photoproducts. Both V-H1 and RH1-26 did not repair pyrimidine dimers measured in the genome overall as well as in the active hprt gene. Repair of (6-4) photoproducts from the genome overall was slower in V-H1 than in wild-type V79 cells, but was restored to normal in RH1-26. Although V-H1 cells have a 7-fold enhanced mutagenicity, RH1-26 cells, despite the absence of pyrimidine dimer repair, have a slightly lower level of UV-induced mutagenesis than observed in wild-type V79 cells. The molecular nature of hprt mutations and the DNA-strand specificity were similar in V79 and RH1-26 cells but different from that of V-H1 cells. Since in RH1-26 as well as in V79 cells most hprt mutations were induced by lesions in the non-trans...

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Research paper thumbnail of A model for growth of a single fungal hypha based on well-mixed tanks in series: simulation of nutrient and vesicle transport in aerial reproductive hyphae

PloS one, 2015

Current models that describe the extension of fungal hyphae and development of a mycelium either ... more Current models that describe the extension of fungal hyphae and development of a mycelium either do not describe the role of vesicles in hyphal extension or do not correctly describe the experimentally observed profile for distribution of vesicles along the hypha. The present work uses the n-tanks-in-series approach to develop a model for hyphal extension that describes the intracellular transport of nutrient to a sub-apical zone where vesicles are formed and then transported to the tip, where tip extension occurs. The model was calibrated using experimental data from the literature for the extension of reproductive aerial hyphae of three different fungi, and was able to describe different profiles involving acceleration and deceleration of the extension rate. A sensitivity analysis showed that the supply of nutrient to the sub-apical vesicle-producing zone is a key factor influencing the rate of extension of the hypha. Although this model was used to describe the extension of a sin...

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Research paper thumbnail of Dryandra Woodland

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Research paper thumbnail of Histological Comparison of Fibrous Root Infection of Disease-Tolerant and Susceptible Citrus Hosts by Phytophthora nicotianae and P. palmivora

Phytopathology, 1998

Phytophthora nicotianae and P. palmivora infect and cause rot of fibrous roots of susceptible and... more Phytophthora nicotianae and P. palmivora infect and cause rot of fibrous roots of susceptible and tolerant citrus rootstocks in Florida orchards. The infection and colonization by the two Phytophthora spp. of a susceptible citrus host, sour orange (Citrus aurantium), and a tolerant host, trifoliate orange (Poncirus trifoliata), were compared using light and electron microscopy. Penetration by both Phytophthora spp. occurred within 1 h after inoculation, regardless of the host species. No differences were observed in mode of penetration of the hypodermis or the hosts' response to infection. After 24 h, P. palmivora had a significantly higher colonization of cortical cells in susceptible sour orange than in tolerant trifoliate orange. Intracellular hyphae of both Phytophthora spp. were observed in the cortex of sour orange, and cortical cells adjacent to intercellular hyphae of P. palmivora were disrupted. In contrast, the cortical cells of sour orange and trifoliate orange adjace...

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Research paper thumbnail of Immobilization and Characterization of a New Regioselective and Enantioselective Lipase Obtained from a Metagenomic Library

PLOS ONE, 2015

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Research paper thumbnail of Modelling fungal growth on surfaces

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Research paper thumbnail of ChemInform Abstract: Recent Developments in the Design, Operation and Modeling of Bioreactors for Solid-State Fermentation

ChemInform, 1999

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Research paper thumbnail of Australian wetlands: the monitoring challenge

Wetlands Ecology and Management, 1999

Management of Australian wetlands is confounded by an absence of adequate environmental monitorin... more Management of Australian wetlands is confounded by an absence of adequate environmental monitoring data. To a large extent we are still not sure of the exact location and extent of many wetlands. Inventory and monitoring information are intricately linked and at the heart of successful wetland management. Monitoring addresses the extent of change in the environment, yet, for wetlands, it

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Research paper thumbnail of THROMBOLITE COMMUNITY OF COASTAL FRESHWATER LAKES (LAKE RICHMOND), INTERIM RECOVERY PLAN (Coastal freshwater lakes thrombolitic aragonite community formed by biologically influenced precipitation of a mineral phase) 2003-2008

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