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Helene Hill

Rutgers NJ Medical School, Radiology, Faculty Member

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I am a photo- and radiobiologist interested in the role of melanin in the photobiology of skin cancer and the radiation resistance of melanoma. I am also a whistleblower who has spent the last 20 years trying to convince the scientific community that radiation research promulgated by members of the Division of Radiation Research in which I worked had been fabricated.

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Papers by Helene Hill

Transplantation, Growth, and Regression of Mouse Melanoma Xenografts in Neonatal Marsupials

Cancer Investigation, 1988

Marsupials are useful for cancer research since they are born in a fetal stage of development wit... more Marsupials are useful for cancer research since they are born in a fetal stage of development with little immunologic competence. In this study, mouse melanoma xenografts were grown in neonatal gray opossums (Monodelphis domestica) injected at 12-32 days of age. Tumors appeared between 1 and 3 weeks postinjection and at least 73% of tumor-bearing animals rejected their tumors. Initiation of tumor growth was rare in animals over 24 days of age and, in most cases, tumors size peaked at about 50 days of age after which tumors quickly regressed. These results are discussed with respect to the development of homeothermy (25 days of age) and gain of postpartum independence (50 days of age) in this marsupial species.

The gray opossum (Monodelphis domestica): A marsupial model for xenogeneic neoplasms

Cancer Letters, Jun 1, 1985

Marsupials are born in what is essentially a fetal stage of development and are largely unprotect... more Marsupials are born in what is essentially a fetal stage of development and are largely unprotected by endocrine or immune systems during early neonatal life. In this study, gray opossums (Monodelphis domestica) were injected during neonatal life, prepubertally and in adulthood with B16 melanoma from the syngeneic C57BL/6 mouse. Ten days following injection, tumors were found in animals injected on days 4, 6 and 13 of postnatal life but not in prepubertal or adult animals. Because xenogeneic tumors can be grown in it and it is easily maintained and bred in the laboratory, this marsupial species has the potential to become a practical model for cancer research.

Postreplication repair in three murine melanomas, a mammary carcinoma, and a normal mouse lung fibroblast line

PubMed, Jun 1, 1980

Repair of ultraviolet light-induced damage to DNA was studied in three melanoma lines, a mammary ... more Repair of ultraviolet light-induced damage to DNA was studied in three melanoma lines, a mammary carcinoma line, EMT6, and a normal lung fibroblast line, MLF, all from the mouse. The melanomas were B16CL4, a gamma-ray-resistant clonal line derived from B16; S91H-, an auxotrophic line derived from Cloudman S91; and HP, a freshly isolated line from s.c. grown Harding-Passey melanoma. The melanomas and MFL were found to perform minimal excision repair and photoreactivation. Postreplication repair, on the other hand, was an active process in all five of the lines. All three melanomas exhibited postreplication repair rates that were about twice that of MLF. The freshly isolated HP line evolved during subcultivation, and its postreplication repair rate dropped after 3 months to a rate comparable to EMT6, which was 1.5 times that of MLF. The results suggest that postreplication repair is an important process in melanomas and may be related to radiation response.

AB Coulter Counts

Ultraviolet B, melanin and mitochondrial DNA: Photo-damage in human epidermal keratinocytes and melanocytes modulated by alpha-melanocyte-stimulating hormone

F1000Research, May 12, 2016

Alpha-melanocyte-stimulating hormone (alpha-MSH) increases melanogenesis and protects from UV-ind... more Alpha-melanocyte-stimulating hormone (alpha-MSH) increases melanogenesis and protects from UV-induced DNA damage. However, its effect on mitochondrial DNA (mtDNA) damage is unknown. We have addressed this issue in a pilot study using human epidermal keratinocytes and melanocytes incubated with alpha-MSH and irradiated with UVB. Real-time touchdown PCR was used to quantify total and deleted mtDNA. The deletion detected encompassed the common deletion but was more sensitive to detection. There were 4.4 times more mtDNA copies in keratinocytes than in melanocytes. Irradiation alone did not affect copy numbers. Alpha-MSH slightly increased copy numbers in both cell types in the absence of UVB and caused a similar small decrease in copy number with dose in both cell types. Deleted copies were nearly twice as frequent in keratinocytes as in melanocytes. Alpha-MSH reduced the frequency of deleted copies by half in keratinocytes but not in melanocytes. UVB dose dependently led to an increase in the deleted copy number in alpha-MSH-treated melanocytes. UVB irradiation had little effect on deleted copy number in alpha-MSH-treated keratinocytes. In summary, alpha-MSH enhances mtDNA damage in melanocytes presumably by increased melanogenesis, while α-MSH is protective in keratinocytes, the more so in the absence of irradiation.

Transfection of nonmelanocytic cells with tyrosinase gene constructs for survival studies

Environmental and Molecular Mutagenesis, 2001

To better understand the role of melanin in the response of cells to radiation, the vector pcTYR ... more To better understand the role of melanin in the response of cells to radiation, the vector pcTYR containing the tyrosinase cDNA and a control vector pcTYW with no tyrosinase cDNA were transfected and expressed in nonpigmented CHOK1‐AL 1282B5 cells. A pigmented clone was selected from the pcTYR transfectants and an antibiotic‐resistant clone was selected from the controls. Melanin was assessed qualitatively by electron paramagnetic resonance (EPR) and quantitatively by a 14C‐based assay. The EPR signal detectable in pcTYR‐containing cells was at least twice that of pcTYW and parental CHOK1‐AL cells and the tyrosinase activity was found to be at least six times greater. Melanin was classified to be eumelanin. Survivals of the transfectants were compared to those of the parent cells after irradiation by UVC from a germicidal lamp, UVB from TL01 lamps, UVA from Alisun lamps, UVB/UVA from FS20 lamps, and by γ‐rays from a 137Cs source. Compared to the pcTYW‐containing cells, the pigmented cells were more sensitive to killing by UVC, and resistant to killing by UVA and γ‐rays. There were no significant differences in survival after the other irradiations. These results suggest that the pigment synthesized by the activity of tyrosinase alone, unmodified by the activities of TRP1 and TRP2, is protective against the types of reactive oxygen species produced by UVA and γ‐rays but not protective against lethal damage from photons in the UVB range and sensitizes to UVC photons. Environ. Mol. Mutagen. 38:216–222, 2001 © 2001 Wiley‐Liss, Inc.

Physiology of rat-liver polysomes. Protein synthesis by stable polysomes

Biochemical journal, May 1, 1967

Certain qualitative aspects of protein synthesis in the livers of starved, starvedre-fed and acti... more Certain qualitative aspects of protein synthesis in the livers of starved, starvedre-fed and actinomycin D-treated rats have been examined by polyacrylamide-gel electrophoresis. Animals were exposed to a mixture of 14C-labelled acids for 18-20min. and killed, and an ultrasonic extract of newly formed protein in microsomal vesicles was prepared and examined by gel electrophoresis. In normal and starved-re-fed animals, 27 % of the newly synthesized protein was albumin. During starvation, when RNA synthesis was decreased, the percentage of newly formed protein as albumin rose. After actinomycin D treatment of starved-re-fed rats, when only stable messenger RNA persisted in the cytoplasm, albumin synthesis increased to 63% of the total. This finding suggested that albumin was the primary protein synthesized on stable messenger RNA.

Statistical Analysis of Numerical Preclinical Radiobiological Data

ScienceOpen Research, Jan 22, 2016

Reviewing status: Please note that this article is under continuous review. For the current revie... more

Characterization of the glucose 6-phosphate dehydrogenase activity in rat liver mitochondria

Biochemical Journal, Dec 1, 1976

Glucose 6-phosphate dehydrogenase activity in rat liver mitochondria can be released by detergent... more Glucose 6-phosphate dehydrogenase activity in rat liver mitochondria can be released by detergent. The released activity is separated by chromatography into two peaks. One peak has the kinetic behaviour and mobility similar to the soluble sex-linked enzyme, whereas the other peak is similar to the microsomal hexose 6-phosphate dehydrogenase. There is no evidence for the existence ofa new glucose 6-phosphate dehydrogenase activity in rat liver mitochondria.-To whom requests 1or reprints should be addressed,

Differential regulation of full-length genome and a single-stranded 7S DNA along the cell cycle in human mitochondria

Nucleic Acids Research, Jun 8, 2010

Mammalian mitochondria contain full-length genome and a single-stranded 7S DNA. Although the copy... more Mammalian mitochondria contain full-length genome and a single-stranded 7S DNA. Although the copy number of mitochondrial DNA (mtDNA) varies depending on the cell type and also in response to diverse environmental stresses, our understanding of how mtDNA and 7S DNA are maintained and regulated is limited, partly due to lack of reliable in vitro assay systems that reflect the in vivo functionality of mitochondria. Here we report an in vitro assay system to measure synthesis of both mtDNA and 7S DNA under a controllable in vitro condition. With this assay system, we demonstrate that the replication capacity of mitochondria correlates with endogenous copy numbers of mtDNA and 7S DNA. Our study also shows that higher nucleotide concentrations increasingly promote 7S DNA synthesis but not mtDNA synthesis. Consistently, the mitochondrial capacity to synthesize 7S DNA but not mtDNA noticeably varied along the cell cycle, reaching its highest level in S phase. These findings suggest that syntheses of mtDNA and 7S DNA proceed independently and that the mitochondrial capacity to synthesize 7S DNA dynamically changes not only with cell-cycle progression but also in response to varying nucleotide concentrations. Recently, while establishing an in vitro assay system for human DNA replication, we observed de novo DNA

Mitochondrial DNA damage is associated with earlier ventilatory threshold in military veterans with unexplained fatigue

The FASEB Journal, Apr 1, 2016

Failure to Replicate: A Sign of Scientific Misconduct?

Publications, Sep 1, 2014

Repeated failures to replicate reported experimental results could indicate scientific misconduct... more Repeated failures to replicate reported experimental results could indicate scientific misconduct or simply result from unintended error. Experiments performed by one individual involving tritiated thymidine, published in two papers in Radiation Research, showed exponential killing of V79 Chinese hamster cells. Two other members of the same laboratory were unable to replicate the published results in 15 subsequent attempts to do so, finding, instead, at least 100-fold less killing and biphasic survival curves. These replication failures (which could have been anticipated based on earlier radiobiological literature) raise questions regarding the reliability of the two reports. Two unusual numerical patterns appear in the questioned individual's data, but do not appear in control data sets from the two other laboratory members, even though the two key protocols followed by all three were identical or nearly so. This report emphasizes the importance of: (1) access to raw data that form the background of reports and grant applications; (2) knowledge of the literature in the field; and (3) the application of statistical methods to detect anomalous numerical behaviors in raw data. Furthermore, journals and granting agencies should require that authors report failures to reproduce their published results.

Thioredoxin Reductase Induction Coincides with Melanin Biosynthesis in Brown and Black Guinea Pigs and in Murine Melanoma Cells

Journal of Investigative Dermatology, Dec 1, 1994

X-rays were used to induce melanin biosynthesis in brown and black guinea pigs in vivo. During th... more X-rays were used to induce melanin biosynthesis in brown and black guinea pigs in vivo. During the course of pigmentation, the expression of thioredoxin reductase was increased, whereas for the other antioxidant enzymes, superoxide dismutase (cytosol Cu/Zn-enzyme), catalase, and glutathione reductase, levels and activities decreased. Isobutylmethylxanthine induced eumelanin biosynthesis in murine melanoma cells T he role of the thioredoxin reductasejthioredoxin system in antioxidant defense gained widespread recognition after the discovery that adult T-cell leukemiaderived factor (ADF) has structural homology and identical activity to human thioredoxin [1]. Thioredoxinj ADF has the following activities: it protects against ultraviolet B (UVB)-induced skin injury,i: improves the survival of skin flaps or burned skin,i: regulates glutathione synthesis,i: protects against tumor necrosis factor-a [2], functions in antigen processing and presentation,i: induces interleukin-2 receptors [3], protects cells against peroxidative damage [4], and regulates human tyrosinase by an allosteric mechanism [5,6]. In each of these functions, thioredoxinj ADF serves as a redox catalyst with nicotinamide adenine dinucleotide phosphatejthioredoxin reductase as the electron-donating system [7,8]. Thioredoxin reductase is subject to allosteric regulation by calcium, and therefore this fast-exchange ion downregulates the activity of thioredoxin reductasejthioredoxin [9,10].

Raw data for 'Ultraviolet B, melanin and mitochondrial DNA: Photo-damage in human epidermal keratinocytes and melanocytes modulated by alpha-melanocyte-stimulating hormone', Bohm and Hill 2016

Progress in surface science. Vol. 1, part 4

Journal of Colloid and Interface Science, 1972

An analysis of 2‐day cardiopulmonary exercise testing to assess unexplained fatigue

Physiological Reports, 2020

Two consecutive maximal cardiopulmonary exercise tests (CPETs) performed 24 hr apart (2‐day CPET ... more Two consecutive maximal cardiopulmonary exercise tests (CPETs) performed 24 hr apart (2‐day CPET protocol) are increasingly used to evaluate post‐exertional malaise (PEM) and related disability among individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This protocol may extend to other fatiguing illnesses with similar characteristics to ME/CFS; however, 2‐day CPET protocol reliability and minimum change required to be considered clinically meaningful (i.e., exceeding the standard error of the measure) are not well characterized. To address this gap, we evaluated the 2‐day CPET protocol in Gulf War Illness (GWI) by quantifying repeatability of seven CPET parameters, establishing their thresholds of clinically significant change, and determining whether changes differed between veterans with GWI and controls. Excluding those not attaining peak effort criteria (n = 15), we calculated intraclass correlation coefficients (ICCs), the smallest real difference (SRD%), and repeated measures analysis of variance (RM‐ANOVA) at the ventilatory anaerobic threshold (VAT) and peak exercise in 15 veterans with GWI and eight controls. ICC values at peak ranged from moderate to excellent for veterans with GWI (mean [range]; 0.84 [0.65 – 0.92]) and were reduced at the VAT (0.68 [0.37 – 0.78]). Across CPET variables, the SRD% at peak exercise for veterans with GWI (18.8 [8.8 – 28.8]) was generally lower than at the VAT (28.1 [9.5 – 34.8]). RM‐ANOVAs did not detect any significant group‐by‐time interactions (all p > .05). The methods and findings reported here provide a framework for evaluating 2‐day CPET reliability, and reinforce the importance of carefully considering measurement error in the population of interest when interpreting findings.

A simple statistical analysis of Indian muntjac Giemsa band patterns

Cytogenetic and Genome Research, 1975

Indian Muntiacus muntjac G-banded chromosomes were used for computerized analysis for standardize... more Indian Muntiacus muntjac G-banded chromosomes were used for computerized analysis for standardized karyotype generation. Individual chromosomes on high-contrast photographic negatives were scanned densitometrically. Alignment of each chromosome for analysis was achieved by locating predominant peaks as well as the centromere. This provided better alignment than the use of the chromosome-end locations. The standardized set was obtained by determining the root-mean-square average density along 10–20 homologous chromosomes. The resulting standard karyotype differs from those published earlier. Prophase chromosomes exhibited greater detail than more condensed metaphase chromosomes. Although Indian muntjac chromosomes were used as a model, the method of analysis should be readily adaptable for examining chromosomes of any origin. The analytic technique should be within the capabilities of the smallest cytogenetic laboratories.

Cell Cycle Regulation

Bioscience, 1979

Transfer of Radioresistance to Radiosensitive Melanoma Cells by a Diffusible Factor from Radioresistant Cells

Radiation Research: A Twentieth-century Perspective, 1991

Veterans with Gulf War Illness exhibit distinct respiratory patterns during maximal cardiopulmonary exercise

PLOS ONE, 2019

All data were collected at the VA and the signed subject consent forms did not make provision for... more

Transplantation, Growth, and Regression of Mouse Melanoma Xenografts in Neonatal Marsupials

Cancer Investigation, 1988

Marsupials are useful for cancer research since they are born in a fetal stage of development wit... more Marsupials are useful for cancer research since they are born in a fetal stage of development with little immunologic competence. In this study, mouse melanoma xenografts were grown in neonatal gray opossums (Monodelphis domestica) injected at 12-32 days of age. Tumors appeared between 1 and 3 weeks postinjection and at least 73% of tumor-bearing animals rejected their tumors. Initiation of tumor growth was rare in animals over 24 days of age and, in most cases, tumors size peaked at about 50 days of age after which tumors quickly regressed. These results are discussed with respect to the development of homeothermy (25 days of age) and gain of postpartum independence (50 days of age) in this marsupial species.

The gray opossum (Monodelphis domestica): A marsupial model for xenogeneic neoplasms

Cancer Letters, Jun 1, 1985

Marsupials are born in what is essentially a fetal stage of development and are largely unprotect... more Marsupials are born in what is essentially a fetal stage of development and are largely unprotected by endocrine or immune systems during early neonatal life. In this study, gray opossums (Monodelphis domestica) were injected during neonatal life, prepubertally and in adulthood with B16 melanoma from the syngeneic C57BL/6 mouse. Ten days following injection, tumors were found in animals injected on days 4, 6 and 13 of postnatal life but not in prepubertal or adult animals. Because xenogeneic tumors can be grown in it and it is easily maintained and bred in the laboratory, this marsupial species has the potential to become a practical model for cancer research.

Postreplication repair in three murine melanomas, a mammary carcinoma, and a normal mouse lung fibroblast line

PubMed, Jun 1, 1980

Repair of ultraviolet light-induced damage to DNA was studied in three melanoma lines, a mammary ... more Repair of ultraviolet light-induced damage to DNA was studied in three melanoma lines, a mammary carcinoma line, EMT6, and a normal lung fibroblast line, MLF, all from the mouse. The melanomas were B16CL4, a gamma-ray-resistant clonal line derived from B16; S91H-, an auxotrophic line derived from Cloudman S91; and HP, a freshly isolated line from s.c. grown Harding-Passey melanoma. The melanomas and MFL were found to perform minimal excision repair and photoreactivation. Postreplication repair, on the other hand, was an active process in all five of the lines. All three melanomas exhibited postreplication repair rates that were about twice that of MLF. The freshly isolated HP line evolved during subcultivation, and its postreplication repair rate dropped after 3 months to a rate comparable to EMT6, which was 1.5 times that of MLF. The results suggest that postreplication repair is an important process in melanomas and may be related to radiation response.

AB Coulter Counts

Ultraviolet B, melanin and mitochondrial DNA: Photo-damage in human epidermal keratinocytes and melanocytes modulated by alpha-melanocyte-stimulating hormone

F1000Research, May 12, 2016

Alpha-melanocyte-stimulating hormone (alpha-MSH) increases melanogenesis and protects from UV-ind... more Alpha-melanocyte-stimulating hormone (alpha-MSH) increases melanogenesis and protects from UV-induced DNA damage. However, its effect on mitochondrial DNA (mtDNA) damage is unknown. We have addressed this issue in a pilot study using human epidermal keratinocytes and melanocytes incubated with alpha-MSH and irradiated with UVB. Real-time touchdown PCR was used to quantify total and deleted mtDNA. The deletion detected encompassed the common deletion but was more sensitive to detection. There were 4.4 times more mtDNA copies in keratinocytes than in melanocytes. Irradiation alone did not affect copy numbers. Alpha-MSH slightly increased copy numbers in both cell types in the absence of UVB and caused a similar small decrease in copy number with dose in both cell types. Deleted copies were nearly twice as frequent in keratinocytes as in melanocytes. Alpha-MSH reduced the frequency of deleted copies by half in keratinocytes but not in melanocytes. UVB dose dependently led to an increase in the deleted copy number in alpha-MSH-treated melanocytes. UVB irradiation had little effect on deleted copy number in alpha-MSH-treated keratinocytes. In summary, alpha-MSH enhances mtDNA damage in melanocytes presumably by increased melanogenesis, while α-MSH is protective in keratinocytes, the more so in the absence of irradiation.

Transfection of nonmelanocytic cells with tyrosinase gene constructs for survival studies

Environmental and Molecular Mutagenesis, 2001

To better understand the role of melanin in the response of cells to radiation, the vector pcTYR ... more To better understand the role of melanin in the response of cells to radiation, the vector pcTYR containing the tyrosinase cDNA and a control vector pcTYW with no tyrosinase cDNA were transfected and expressed in nonpigmented CHOK1‐AL 1282B5 cells. A pigmented clone was selected from the pcTYR transfectants and an antibiotic‐resistant clone was selected from the controls. Melanin was assessed qualitatively by electron paramagnetic resonance (EPR) and quantitatively by a 14C‐based assay. The EPR signal detectable in pcTYR‐containing cells was at least twice that of pcTYW and parental CHOK1‐AL cells and the tyrosinase activity was found to be at least six times greater. Melanin was classified to be eumelanin. Survivals of the transfectants were compared to those of the parent cells after irradiation by UVC from a germicidal lamp, UVB from TL01 lamps, UVA from Alisun lamps, UVB/UVA from FS20 lamps, and by γ‐rays from a 137Cs source. Compared to the pcTYW‐containing cells, the pigmented cells were more sensitive to killing by UVC, and resistant to killing by UVA and γ‐rays. There were no significant differences in survival after the other irradiations. These results suggest that the pigment synthesized by the activity of tyrosinase alone, unmodified by the activities of TRP1 and TRP2, is protective against the types of reactive oxygen species produced by UVA and γ‐rays but not protective against lethal damage from photons in the UVB range and sensitizes to UVC photons. Environ. Mol. Mutagen. 38:216–222, 2001 © 2001 Wiley‐Liss, Inc.

Physiology of rat-liver polysomes. Protein synthesis by stable polysomes

Biochemical journal, May 1, 1967

Certain qualitative aspects of protein synthesis in the livers of starved, starvedre-fed and acti... more Certain qualitative aspects of protein synthesis in the livers of starved, starvedre-fed and actinomycin D-treated rats have been examined by polyacrylamide-gel electrophoresis. Animals were exposed to a mixture of 14C-labelled acids for 18-20min. and killed, and an ultrasonic extract of newly formed protein in microsomal vesicles was prepared and examined by gel electrophoresis. In normal and starved-re-fed animals, 27 % of the newly synthesized protein was albumin. During starvation, when RNA synthesis was decreased, the percentage of newly formed protein as albumin rose. After actinomycin D treatment of starved-re-fed rats, when only stable messenger RNA persisted in the cytoplasm, albumin synthesis increased to 63% of the total. This finding suggested that albumin was the primary protein synthesized on stable messenger RNA.

Statistical Analysis of Numerical Preclinical Radiobiological Data

ScienceOpen Research, Jan 22, 2016

Reviewing status: Please note that this article is under continuous review. For the current revie... more

Characterization of the glucose 6-phosphate dehydrogenase activity in rat liver mitochondria

Biochemical Journal, Dec 1, 1976

Glucose 6-phosphate dehydrogenase activity in rat liver mitochondria can be released by detergent... more Glucose 6-phosphate dehydrogenase activity in rat liver mitochondria can be released by detergent. The released activity is separated by chromatography into two peaks. One peak has the kinetic behaviour and mobility similar to the soluble sex-linked enzyme, whereas the other peak is similar to the microsomal hexose 6-phosphate dehydrogenase. There is no evidence for the existence ofa new glucose 6-phosphate dehydrogenase activity in rat liver mitochondria.-To whom requests 1or reprints should be addressed,

Differential regulation of full-length genome and a single-stranded 7S DNA along the cell cycle in human mitochondria

Nucleic Acids Research, Jun 8, 2010

Mammalian mitochondria contain full-length genome and a single-stranded 7S DNA. Although the copy... more Mammalian mitochondria contain full-length genome and a single-stranded 7S DNA. Although the copy number of mitochondrial DNA (mtDNA) varies depending on the cell type and also in response to diverse environmental stresses, our understanding of how mtDNA and 7S DNA are maintained and regulated is limited, partly due to lack of reliable in vitro assay systems that reflect the in vivo functionality of mitochondria. Here we report an in vitro assay system to measure synthesis of both mtDNA and 7S DNA under a controllable in vitro condition. With this assay system, we demonstrate that the replication capacity of mitochondria correlates with endogenous copy numbers of mtDNA and 7S DNA. Our study also shows that higher nucleotide concentrations increasingly promote 7S DNA synthesis but not mtDNA synthesis. Consistently, the mitochondrial capacity to synthesize 7S DNA but not mtDNA noticeably varied along the cell cycle, reaching its highest level in S phase. These findings suggest that syntheses of mtDNA and 7S DNA proceed independently and that the mitochondrial capacity to synthesize 7S DNA dynamically changes not only with cell-cycle progression but also in response to varying nucleotide concentrations. Recently, while establishing an in vitro assay system for human DNA replication, we observed de novo DNA

Mitochondrial DNA damage is associated with earlier ventilatory threshold in military veterans with unexplained fatigue

The FASEB Journal, Apr 1, 2016

Failure to Replicate: A Sign of Scientific Misconduct?

Publications, Sep 1, 2014

Repeated failures to replicate reported experimental results could indicate scientific misconduct... more Repeated failures to replicate reported experimental results could indicate scientific misconduct or simply result from unintended error. Experiments performed by one individual involving tritiated thymidine, published in two papers in Radiation Research, showed exponential killing of V79 Chinese hamster cells. Two other members of the same laboratory were unable to replicate the published results in 15 subsequent attempts to do so, finding, instead, at least 100-fold less killing and biphasic survival curves. These replication failures (which could have been anticipated based on earlier radiobiological literature) raise questions regarding the reliability of the two reports. Two unusual numerical patterns appear in the questioned individual's data, but do not appear in control data sets from the two other laboratory members, even though the two key protocols followed by all three were identical or nearly so. This report emphasizes the importance of: (1) access to raw data that form the background of reports and grant applications; (2) knowledge of the literature in the field; and (3) the application of statistical methods to detect anomalous numerical behaviors in raw data. Furthermore, journals and granting agencies should require that authors report failures to reproduce their published results.

Thioredoxin Reductase Induction Coincides with Melanin Biosynthesis in Brown and Black Guinea Pigs and in Murine Melanoma Cells

Journal of Investigative Dermatology, Dec 1, 1994

X-rays were used to induce melanin biosynthesis in brown and black guinea pigs in vivo. During th... more X-rays were used to induce melanin biosynthesis in brown and black guinea pigs in vivo. During the course of pigmentation, the expression of thioredoxin reductase was increased, whereas for the other antioxidant enzymes, superoxide dismutase (cytosol Cu/Zn-enzyme), catalase, and glutathione reductase, levels and activities decreased. Isobutylmethylxanthine induced eumelanin biosynthesis in murine melanoma cells T he role of the thioredoxin reductasejthioredoxin system in antioxidant defense gained widespread recognition after the discovery that adult T-cell leukemiaderived factor (ADF) has structural homology and identical activity to human thioredoxin [1]. Thioredoxinj ADF has the following activities: it protects against ultraviolet B (UVB)-induced skin injury,i: improves the survival of skin flaps or burned skin,i: regulates glutathione synthesis,i: protects against tumor necrosis factor-a [2], functions in antigen processing and presentation,i: induces interleukin-2 receptors [3], protects cells against peroxidative damage [4], and regulates human tyrosinase by an allosteric mechanism [5,6]. In each of these functions, thioredoxinj ADF serves as a redox catalyst with nicotinamide adenine dinucleotide phosphatejthioredoxin reductase as the electron-donating system [7,8]. Thioredoxin reductase is subject to allosteric regulation by calcium, and therefore this fast-exchange ion downregulates the activity of thioredoxin reductasejthioredoxin [9,10].

Raw data for 'Ultraviolet B, melanin and mitochondrial DNA: Photo-damage in human epidermal keratinocytes and melanocytes modulated by alpha-melanocyte-stimulating hormone', Bohm and Hill 2016

Progress in surface science. Vol. 1, part 4

Journal of Colloid and Interface Science, 1972

An analysis of 2‐day cardiopulmonary exercise testing to assess unexplained fatigue

Physiological Reports, 2020

Two consecutive maximal cardiopulmonary exercise tests (CPETs) performed 24 hr apart (2‐day CPET ... more Two consecutive maximal cardiopulmonary exercise tests (CPETs) performed 24 hr apart (2‐day CPET protocol) are increasingly used to evaluate post‐exertional malaise (PEM) and related disability among individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This protocol may extend to other fatiguing illnesses with similar characteristics to ME/CFS; however, 2‐day CPET protocol reliability and minimum change required to be considered clinically meaningful (i.e., exceeding the standard error of the measure) are not well characterized. To address this gap, we evaluated the 2‐day CPET protocol in Gulf War Illness (GWI) by quantifying repeatability of seven CPET parameters, establishing their thresholds of clinically significant change, and determining whether changes differed between veterans with GWI and controls. Excluding those not attaining peak effort criteria (n = 15), we calculated intraclass correlation coefficients (ICCs), the smallest real difference (SRD%), and repeated measures analysis of variance (RM‐ANOVA) at the ventilatory anaerobic threshold (VAT) and peak exercise in 15 veterans with GWI and eight controls. ICC values at peak ranged from moderate to excellent for veterans with GWI (mean [range]; 0.84 [0.65 – 0.92]) and were reduced at the VAT (0.68 [0.37 – 0.78]). Across CPET variables, the SRD% at peak exercise for veterans with GWI (18.8 [8.8 – 28.8]) was generally lower than at the VAT (28.1 [9.5 – 34.8]). RM‐ANOVAs did not detect any significant group‐by‐time interactions (all p > .05). The methods and findings reported here provide a framework for evaluating 2‐day CPET reliability, and reinforce the importance of carefully considering measurement error in the population of interest when interpreting findings.

A simple statistical analysis of Indian muntjac Giemsa band patterns

Cytogenetic and Genome Research, 1975

Indian Muntiacus muntjac G-banded chromosomes were used for computerized analysis for standardize... more Indian Muntiacus muntjac G-banded chromosomes were used for computerized analysis for standardized karyotype generation. Individual chromosomes on high-contrast photographic negatives were scanned densitometrically. Alignment of each chromosome for analysis was achieved by locating predominant peaks as well as the centromere. This provided better alignment than the use of the chromosome-end locations. The standardized set was obtained by determining the root-mean-square average density along 10–20 homologous chromosomes. The resulting standard karyotype differs from those published earlier. Prophase chromosomes exhibited greater detail than more condensed metaphase chromosomes. Although Indian muntjac chromosomes were used as a model, the method of analysis should be readily adaptable for examining chromosomes of any origin. The analytic technique should be within the capabilities of the smallest cytogenetic laboratories.

Cell Cycle Regulation

Bioscience, 1979

Transfer of Radioresistance to Radiosensitive Melanoma Cells by a Diffusible Factor from Radioresistant Cells

Radiation Research: A Twentieth-century Perspective, 1991

Veterans with Gulf War Illness exhibit distinct respiratory patterns during maximal cardiopulmonary exercise

PLOS ONE, 2019

All data were collected at the VA and the signed subject consent forms did not make provision for... more