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1.
Eur Arch Otorhinolaryngol ; 276(11): 3213-3219, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31388759

ABSTRACT

PURPOSE: Total laryngectomy and end tracheal stoma formation are often required to treat advanced laryngeal cancer. Resources on the internet are commonly accessed by patients as a source of healthcare information. YouTube™, the most popular video-hosting website, is one such resource. The aims of this study were to assess the thematic content of the most viewed YouTube™ videos concerning laryngectomy for laryngeal cancer and to evaluate user response to these videos. METHOD: A search of YouTube™ was performed and data were extracted from videos with > 100 views. Upload source, number of views, likes, dislikes and comments were collected and the content of comments was analysed. User response was compared between upload sources using Kruskal-Wallis testing. Inductive thematic analysis of video content was performed to identify overarching themes and subthemes. RESULTS: A total of 96 videos were identified, 16 uploaded by patients, 24 by individual healthcare professionals and 56 by professional healthcare institutions. There were 1214,503 views and no significant differences in the number of views, likes or dislikes between upload sources. Three overarching themes and 17 subthemes were identified. Comments were most frequently characterised as offering praise. CONCLUSION: YouTube™ has been shown to be a popular platform for sharing information about laryngectomy for laryngeal cancer. There is a lack of data concerning the quality of this information, however, and future work should focus on assessing this. Trusted institutions could make use of this medium to disseminate high-quality information to their patients, and to the wider public.


Subject(s)
Information Dissemination/methods , Internet , Laryngeal Neoplasms , Laryngectomy/methods , Social Media , Humans , Information Seeking Behavior , Laryngeal Neoplasms/psychology , Laryngeal Neoplasms/surgery , Video Recording
2.
Med Eng Phys ; 23(4): 239-47, 2001 May.
Article in English | MEDLINE | ID: mdl-11427361

ABSTRACT

Hybrid test dummies provide a safe alternative to human subjects when investigating mechanisms of wheelchair tips and falls. The data that researchers acquire from these test dummies are more useful if the test dummy represents the population being studied. The goal of this study was to measure the validity of a 50th percentile Hybrid II test dummy (HTD) as an accurate representation of a wheelchair user. A test pilot with T8 paraplegia due to traumatic spinal cord injury served as a basis for validation. Simple modifications were made to the HTD to approximate the trunk stability characteristics of a person with a spinal cord injury. An HTD, a modified HTD, and a human test pilot were seated in an electric-powered wheelchair and several braking tests performed. The standard HTD underestimated the kinematics when compared to the test pilot. The modified HTD had less trunk stability than the standard HTD during all braking methods. The modified HTD and wheelchair test pilot had similar trunk stability characteristics during kill switch and joystick full-reverse braking conditions. The modified HTD is a satisfactory representation of a wheelchair user with a spinal cord injury; however, the modified test dummy underestimates the trunk dynamics during the less extreme joystick release braking. Work should continue on the development of a low-speed, low-impact test dummy that emulates the wheelchair user population.


Subject(s)
Wheelchairs , Biomechanical Phenomena , Biomedical Engineering , Biophysical Phenomena , Biophysics , Human Experimentation , Humans , Models, Biological , Spinal Cord Injuries/physiopathology , Spinal Cord Injuries/rehabilitation , Wheelchairs/adverse effects
3.
Med Eng Phys ; 23(4): 267-73, 2001 May.
Article in English | MEDLINE | ID: mdl-11427364

ABSTRACT

GAME(Wheels) is an interface between a portable roller system and a computer that enables a wheelchair user to play commercially available computer video games. The subject controls the game play with the propulsion of their wheelchair's wheels on the rollers. The purpose of this study was to investigate whether using the GAME(Wheels) System during wheelchair propulsion exercise can help increase the individual's physiological response and aid in the motivation to exercise. Fifteen subjects participated in this study. The subjects propelled their wheelchairs on a portable roller that was equipped with the GAME(Wheels) System. There were two exercise trials consisting of 2 min of warm-up, 16 min of exercise and 2 min of cool-down. Physiological data (ventilation rate, oxygen consumption, heart rate) were collected. A significant difference (P<0.05) was found between exercise with GAME(Wheels) versus without GAME(Wheels) for average ventilation rate and average oxygen consumption. The differences were found during time periods of transition from warm-up to exercise, and before and after the midpoint of exercise. Written questionnaires showed that 87% of the individuals tested reported the system would help them work out on a regular basis. Playing the video game helped these individuals to reach their exercise training zone faster and maintain it for the entire exercise trial.


Subject(s)
Exercise , Motivation , Video Games , Wheelchairs , Adult , Computers , Ergonomics , Female , Heart Rate , Humans , Male , Metabolism , Oxygen Consumption , Respiration , Spinal Cord Injuries/physiopathology , Spinal Cord Injuries/psychology , Spinal Cord Injuries/rehabilitation
4.
Arch Phys Med Rehabil ; 82(5): 702-8, 2001 May.
Article in English | MEDLINE | ID: mdl-11346854

ABSTRACT

OBJECTIVE: To evaluate a novel pushrim-activated, power-assisted wheelchair (PAPAW) for compliance with wheelchair standards, metabolic energy cost during propulsion, and ergonomics during selected activities of daily living (ADLs). DESIGN: A 3-phase study, the second and third of which were repeated-measures designs. SETTING: A rehabilitation engineering center within a Veterans Affairs medical center. PATIENTS: Eleven full-time, community-dwelling, manual wheelchair users (4 women, 6 men) with spinal cord injuries or multiple sclerosis. INTERVENTIONS: Phase 1: Compliance testing, with a test dummy, in accordance with the wheelchair standards of the American National Standards Institute and the Rehabilitation Engineering and Assistive Technology Society of North America. Phase 2: Metabolic energy consumption testing-at 2 speeds and 3 resistance levels-in subjects' manual wheelchair and the PAPAW. Phase 3: Evaluation of ability to perform ADLs and ergonomics of the PAPAW compared with the subjects personal wheelchair. MAIN OUTCOME MEASURES: Phase 1: The PAPAW's static stability, static strength, impact strength, fatigue strength, environmental response, obstacle climbing ability, range, maximum speed, and braking distance. Phase 2: Subjects' oxygen consumption per minute, minute ventilation, and heart rate during different speeds and workloads with a PAPAW and their own wheelchairs. Phase 3: Subject ratings of perceived comfort and basic ergonomics while performing selected ADLs. Completion time, stroke frequency, and heart rate during each ADL. RESULTS: Phase 1: The PAPAW was found to be in compliance with wheelchair standards. Phase 2: With the PAPAW, the user had a significantly lower oxygen consumption (&Vdot;O(2)mL/min: p <.0001; &Vdot;O(2)mL/kg x min: p <.0001) and heart rate (p <.0001) when compared with a manual wheelchair at different speeds. Phase 3: The PAPAW had a significantly higher mean ergonomic evaluation (p <.01) than the subjects' personal wheelchairs. The results of comparing the ratings of the car transfer between the PAPAW and the subjects' personal wheelchair showed a significant difference in the task of taking the wheels off (p <.001) and putting the wheels back on (p =.001), with the PAPAW receiving lower ratings. CONCLUSION: This study indicated that the PAPAW is compliant with wheelchair standards, reduces the energy demand placed on the user during propulsion, and that subjects rated its ergonomics favorably when compared with their personal wheelchair. PAPAWs may provide manual wheelchairs with a less physiologically stressful means of mobility with few adaptations to the vehicle or home environment.


Subject(s)
Wheelchairs/standards , Adult , Durable Medical Equipment/standards , Energy Metabolism , Equipment Design , Equipment Safety/standards , Female , Humans , Male , Multiple Sclerosis/metabolism , Multiple Sclerosis/rehabilitation , Pilot Projects , Spinal Cord Injuries/metabolism , Spinal Cord Injuries/rehabilitation
5.
Neurorehabil Neural Repair ; 14(1): 21-31, 2000.
Article in English | MEDLINE | ID: mdl-11228946

ABSTRACT

The sedentary lifestyle of many people with spinal cord injury (SCI) has lead to cardiovascular diseases being a major health concern. A suitable exercise program may help improve the SCI individual's cardiovascular fitness level. GAMEWheels is an interface between a custom wheelchair roller system and a computer that enables an individual to control computer video games by driving his or her wheelchair. The purpose of Phase 1 was to evaluate the design of the GAMEWheels system and to determine the type of computer video game that is likely to motivate wheelchair users to exercise. Phase 2 included physiologic testing of wheelchair users and the GAMEWheels system to investigate whether the system elicits an exercise training response. Thirty-five subjects were recruited to evaluate the GAMEWheels by playing three commercial computer games (Phase 1) and to identify the computer game that they would prefer to use when exercising. The feedback from Phase 1 was used with test subjects to verify that the GAMEWheels system elicits an exercise training effect (Phase 2). Phase 2 included 10 subjects using the GAMEWheels system to play Need for Speed II. During game play, physiologic data were collected and the subjects' oxygen consumption and heart rate were analyzed. Analysis showed that the GAMEWheels system induced nine subjects to reach their training zone, defined as 50% and 60% of their maximum oxygen consumption and heart rate, respectively. This study demonstrates that the GAMEWheels system elicits an exercise training response.


Subject(s)
Exercise Therapy , Spinal Cord Injuries/rehabilitation , User-Computer Interface , Video Games , Wheelchairs , Adult , Equipment Design , Humans , Male , Middle Aged , Motivation
6.
Assist Technol ; 12(2): 106-15, 2000.
Article in English | MEDLINE | ID: mdl-11508400

ABSTRACT

There are about 1.4 million manual wheelchair users, 100,000 electric-powered wheelchair users, and 60,000 electric-powered scooter users. The current study was undertaken to determine if the fasteners of a clamp-type armrest receiver were prone to failure. The first test was used to examine the potential misalignment of the armrest receiver components that attach it to the frame. The second test was to evaluate the entire armrest using the American National Standards Institute/Rehabilitation Engineering and Assistive Technology Society of North America armrest static strength standard. Finally, we conducted three fatigue tests. The first fatigue test was performed by repeating the static stability tests multiple times. The last two tests were a modified version of the double-drum wheelchair fatigue test used to apply repeated loading and vibration simultaneously. A paired t-test showed that there is no statistically significant difference (p = 0.08), with a confidence of 95%, between critical alignment measurements. The armrest including the receiver passed the standard requirement of a force of 760 N being applied outward at 15 degrees. During fatigue testing, we found that armrests did not exhibit any visible or functional damage. Upon completion of the tests, the armrests and receivers functioned properly. At about 100,289 cycles on a double-drum test machine, three bolts failed on each armrest receiver when the screws were loosened to have only five threads engaged prior to commencing the test. The design of the armrest tested was in compliance with existing national and international standards. Currently, both International Standards Organization and American National Standards Institute/Rehabilitation Engineering and Assistive Technology Society committees are developing standards for seating systems that will include static, impact, and fatigue strength testing of devices like lateral torso supports, lateral hip support, etc. Methods similar to those explored in this study should be considered. This study may help manufacturers when designing products and purchasers or regulatory agencies when attempting to evaluate the safety and quality of armrest assemblies.


Subject(s)
Materials Testing , Wheelchairs , Equipment Design , Humans , Mechanics
7.
J Rehabil Res Dev ; 36(1): 48-54, 1999 Jan.
Article in English | MEDLINE | ID: mdl-10659894

ABSTRACT

Most of the 22 approved or developing ISO standards rely on a wheelchair test dummy, a specialized device described in ISO 7176-11. The purpose of this study was to develop a means for modifying the design of the ISO 7176-11 test dummy to be suitable for testing with higher masses. The changes are based upon published data for obese individuals. With these data, we derived equations for determining the distribution of the additional mass among the test dummy components, and the locations of the centers of mass. The results of this study provide guidelines for adding mass to the 100 kg wheelchair test dummy to accommodate testing of wheelchairs designed for obese individuals.


Subject(s)
Anthropometry , Body Weight , Ergonomics , Wheelchairs/standards , Equipment Design , Humans , Manikins , Materials Testing , Obesity/pathology , Obesity/rehabilitation
8.
Med Phys ; 25(10): 2020-6, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9800711

ABSTRACT

Film digitizers are common devices in radiology departments involved with picture archive and communication systems (PACS) and teleradiology. In this paper, we studied the performance of film digitizers based on charge-coupled device detectors (CCD digitizers), and compared this with the performance of a laser digitizer (the de facto standard). Our focus was on the assessment of signal, noise and useful optical density range performance. A function (L* delta D) derived from the Rose model was used to evaluate these parameters in absolute terms, based their predicted ability to detect objects of specific size and optical density difference with respect to background. We studied CCD digitizers from four different vendors and found that none was able to reliably operate up to the maximum density of 3.0 required to digitize plain radiographs, while the laser digitizer was capable of this task. Our analysis also indicated that two of the four CCD digitizers were adequate for digitizing laser-printed cross-sectional images in certain cases. Finally, our analysis indicated that digitization of SMPTE pattern films along with visual assessment of the 5% and 95% contrast patches was not sufficient for determining the utility of film digitizers for clinical tasks. Computation of the L* delta D function provides a useful means of assessing the performance of film digitizers (e.g., for acceptance testing and quality control), and this technique may be adaptable for evaluation of other digital imaging modalities.


Subject(s)
Radiographic Image Enhancement/instrumentation , Biophysical Phenomena , Biophysics , Evaluation Studies as Topic , Humans , Lasers , Signal Processing, Computer-Assisted
9.
Arch Phys Med Rehabil ; 79(10): 1244-9, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9779678

ABSTRACT

OBJECTIVE: To examine the influence of three electric-powered wheelchair braking conditions and four wheelchair seating conditions on electric-powered wheelchair motion and Hybrid II test dummy motion. This study provides quantitative information related to assessing the safety of electric-powered wheelchair driving. DESIGN: Rehabilitation engineering comparison and ANSI/ RESNA standards testing. Convenience sample of eight different electric-powered wheelchairs. Within-chair comparisons were conducted. INTERVENTION: Electric-powered wheelchairs were compared under three braking scenarios (joystick release, joystick reverse, power-off) and four seating conditions (seatbelt and legrests, seatbelt and no legrests, no seatbelt but legrests, no seatbelt and no legrests). SETTING: A rehabilitation engineering center. MAIN OUTCOME MEASURES: The braking distance, braking time, and braking accelerations for electric-powered wheelchairs during three braking scenarios; trunk motion, head motion, and trunk angular acceleration during three braking scenarios and four seating conditions; and number of falls from the wheelchairs for three braking scenarios and four seating conditions. RESULTS: Significant differences (p < .05) were found in braking distance, braking time, and braking acceleration when comparing the joystick release and joystick reverse scenarios with the power-off scenario. The mean braking distance was shortest with the power-off braking scenario (.89m), whereas it was longest when the joystick was released (1.66m). Significant differences (p < .05) in head displacement and trunk angular displacement were observed among braking conditions and between seating conditions. There were also significant differences (p = .0011) among braking conditions for maximum trunk angular acceleration. The Hybrid II test dummy fell from the wheelchairs with highest frequency when there were no legrests and no seatbelt used. CONCLUSION: The results of this study indicate that use of a seatbelt when driving an electric-powered wheelchair reduces the risk of falling from a wheelchair. Furthermore, the use of legrests can reduce the risk of injury to the wheelchair driver. This study shows that the most abrupt braking occurs when deactivating the power switch.


Subject(s)
Accidental Falls/prevention & control , Electricity , Motion , Seat Belts , Wheelchairs/standards , Analysis of Variance , Biomechanical Phenomena , Equipment Design , Ergonomics , Humans , Manikins , Wheelchairs/classification , Wheelchairs/supply & distribution
10.
J Pastoral Care ; 51(2): 195-206, 1997.
Article in English | MEDLINE | ID: mdl-10169315

ABSTRACT

Discusses issues in the evaluation of supervised pastoral education (SPE) programs. Explains four ways of applying triangulation in developing an accurate evaluation of SPE and presents a case study of an SPE program evaluated through triangulation Offers suggestions about the use of triangulation on SPE program evaluation.


Subject(s)
Education, Continuing/standards , Pastoral Care/education , Canada , Christianity , Program Evaluation
11.
Nature ; 380(6570): 149-52, 1996 Mar 14.
Article in English | MEDLINE | ID: mdl-8600386

ABSTRACT

The availability of dense genetic linkage maps of mammalian genomes makes feasible a wide range of studies, including positional cloning of monogenic traits, genetic dissection of polygenic traits, construction of genome-wide physical maps, rapid marker-assisted construction of congenic strains, and evolutionary comparisons. We have been engaged for the past five years in a concerted effort to produce a dense genetic map of the laboratory mouse. Here we present the final report of this project. The map contains 7,377 genetic markers, consisting of 6,580 highly informative simple sequence length polymorphisms integrated with 797 restriction fragment length polymorphisms in mouse genes. The average spacing between markers is about 0.2 centimorgans or 400 kilobases.


Subject(s)
Chromosome Mapping , Mice/genetics , Animals , Crosses, Genetic , Female , Genetic Markers , Genome , Human Genome Project , Male , Mice, Inbred Strains , Polymorphism, Genetic , Polymorphism, Restriction Fragment Length
12.
Biochem Cell Biol ; 74(4): 477-84, 1996.
Article in English | MEDLINE | ID: mdl-8960354

ABSTRACT

pp60c-src and the structurally related members of the Src family are non-receptor tyrosine kinases that reside within the cell associated with cell membranes and appear to transduce signals from transmembrane receptors to the cell interior. Many intracellular pathways can be stimulated upon Src activation, and a variety of cellular consequences can result, including morphological changes and cell proliferation. pp60c-src activity is normally suppressed by phosphorylation on its carboxy-terminal tail by an enzyme known as CSK. Various cellular stimuli or mutations within pp60c-src can activate its endogenous kinase activity. In this paper, we review aspects of pp60c-src activation and regulation and discuss results obtained in our laboratory in two experimental systems: (i) in melanoma cell lines and primary pigmented normal human melanocytes and (ii) using activated mutant forms of purified human pp60c-src protein.


Subject(s)
Melanocytes/enzymology , Melanoma/enzymology , Proto-Oncogene Proteins pp60(c-src)/metabolism , CSK Tyrosine-Protein Kinase , Cells, Cultured , Enzyme Activation , Humans , Mutation , Phosphorylation , Protein-Tyrosine Kinases/metabolism , Signal Transduction , Tumor Cells, Cultured , src-Family Kinases
13.
Science ; 270(5244): 1945-54, 1995 Dec 22.
Article in English | MEDLINE | ID: mdl-8533086

ABSTRACT

A physical map has been constructed of the human genome containing 15,086 sequence-tagged sites (STSs), with an average spacing of 199 kilobases. The project involved assembly of a radiation hybrid map of the human genome containing 6193 loci and incorporated a genetic linkage map of the human genome containing 5264 loci. This information was combined with the results of STS-content screening of 10,850 loci against a yeast artificial chromosome library to produce an integrated map, anchored by the radiation hybrid and genetic maps. The map provides radiation hybrid coverage of 99 percent and physical coverage of 94 percent of the human genome. The map also represents an early step in an international project to generate a transcript map of the human genome, with more than 3235 expressed sequences localized. The STSs in the map provide a scaffold for initiating large-scale sequencing of the human genome.


Subject(s)
Chromosome Mapping , Genome, Human , Human Genome Project , Sequence Analysis, DNA , Sequence Tagged Sites , Animals , Cell Line , Chromosomes, Artificial, Yeast , Databases, Factual , Gene Expression , Genetic Markers , Humans , Hybrid Cells , Polymerase Chain Reaction
14.
Arch Gen Psychiatry ; 52(11): 925-36, 1995 Nov.
Article in English | MEDLINE | ID: mdl-7487341

ABSTRACT

BACKGROUND: Recent genetic evidence suggests that the most important environmental influences on normal and pathologic development are those that are not shared by siblings in the same family. We sought to determine the relationship between differences in parenting styles and depressive symptoms and antisocial behavior in adolescence, and to compare the influence of these nonshared experiences with genetic influences. METHODS: We studied 708 families with at least two same-sexed adolescent siblings who were monozygotic twins (93 families), dizygotic twins (99 families), ordinary siblings (95 families), full siblings in step families (181 families), half siblings in step families (110 families), and genetically unrelated siblings in step families (130 families). Data on parenting style were collected by questionnaire and by video recording of interaction between parents and children. RESULTS: Almost 60% of variance in adolescent antisocial behavior and 37% of variance in depressive symptoms could be accounted for by conflictual and negative parental behavior directed specifically at the adolescent. In contrast, when a parent directed harsh, aggressive, explosive, and inconsistent parenting toward the sibling, we found less psychopathologic outcome in the adolescent. CONCLUSIONS: Parenting behavior directed specifically at each child in the family is a major correlate of symptoms in adolescents. Furthermore, harsh parental behavior directed at a sibling may have protective effects for adolescents, a phenomenon we call the "siblin barricade."


Subject(s)
Antisocial Personality Disorder/genetics , Depressive Disorder/genetics , Family Health , Social Environment , Adolescent , Adult , Antisocial Personality Disorder/epidemiology , Antisocial Personality Disorder/etiology , Child , Depressive Disorder/epidemiology , Depressive Disorder/etiology , Diseases in Twins/epidemiology , Diseases in Twins/genetics , Female , Humans , Male , Parent-Child Relations , Parenting/psychology , Regression Analysis
15.
Int J STD AIDS ; 6(4): 267-72, 1995.
Article in English | MEDLINE | ID: mdl-7548290

ABSTRACT

The effect of low pH, normally present in the female genital tract, on HIV viability was examined. HIV is more acid stable than previously reported with no substantial reduction in infectivity occurring until pH levels are reduced below 4.5. The virucidal activity of 3 topical spermicides and chlorhexidine was assessed in vitro using previously established and newly modified assay systems. None of the agents tested had a selectivity index (SI) greater than 5.2. Semen and cervical secretions were assessed for their ability to inhibit HIV-1. While no virucidal effect was found in the latter, seminal fluid was found to have significant activity against HIV-1 and a SI of approximately 50.


Subject(s)
Anti-Infective Agents, Local/pharmacology , Cervix Mucus/microbiology , HIV-1/drug effects , Semen/microbiology , Spermatocidal Agents/pharmacology , Administration, Intravaginal , Benzalkonium Compounds/pharmacology , Cell Adhesion , Cervix Mucus/drug effects , Chlorhexidine/pharmacology , Drug Evaluation, Preclinical , Female , HIV-1/pathogenicity , Humans , Hydrogen-Ion Concentration , Male , Nonoxynol/pharmacology , Octoxynol/pharmacology , Semen/drug effects , Time Factors
16.
Cell Growth Differ ; 6(2): 123-30, 1995 Feb.
Article in English | MEDLINE | ID: mdl-7538781

ABSTRACT

Normal human melanocytes, and some human melanoma cell lines, contain c-SRC which is constitutively activated by hypophosphorylation of tyrosine 530. We investigated the possibility that the activation of c-SRC in melanocytes might be attributable to elevated levels of tyrosine 530-directed protein tyrosine phosphatase activity in these cells. We found three times more of this phosphatase activity in cell extracts from melanocytes compared to fibroblasts. The majority of the tyrosine 530-dephosphorylating activity was present in the particulate fraction of cell homogenates, where c-SRC is also located. Treatment of melanocytes with the protein tyrosine phosphatase inhibitor, sodium orthovanadate, caused inactivation of c-SRC. From these results, we conclude that activation of c-SRC in human melanocytes may be attributed to an elevated level of protein tyrosine phosphatase activity directed against tyrosine 530.


Subject(s)
Melanocytes/metabolism , Protein Tyrosine Phosphatases/metabolism , Proto-Oncogene Proteins pp60(c-src)/metabolism , Tyrosine/metabolism , Amino Acid Sequence , Biological Assay , Cell Line , Fibroblasts/metabolism , Humans , Molecular Sequence Data , Particle Size , Peptides/metabolism , Protein Tyrosine Phosphatases/antagonists & inhibitors , Solubility , Vanadates/pharmacology
17.
Melanoma Res ; 5(1): 5-13, 1995 Feb.
Article in English | MEDLINE | ID: mdl-7537564

ABSTRACT

Elevated levels of c-SRC activity have been found in human melanocytes and some human melanoma cell lines. We examined c-SRC in B16 murine melanoma cells. B16-F0 non-metastatic melanoma cells contained threefold more c-SRC activity and protein than NIH 3T3 murine fibroblasts. Differentiation of B16-F1 metastatic melanoma cells with retinoic acid resulted in an elevation in c-SRC activity, protein and mRNA. The increase in c-SRC was detectable after about 48 h of retinoic acid treatment, as were changes in cellular morphology and growth rate. Thus, there is a correlation between differentiation and expression of c-SRC in B16 murine melanoma cells. These findings suggest a role for c-SRC in murine melanocyte differentiation or function.


Subject(s)
Melanoma, Experimental/metabolism , Melanoma, Experimental/pathology , Proto-Oncogene Proteins pp60(c-src)/metabolism , Skin Neoplasms/metabolism , Skin Neoplasms/pathology , 3T3 Cells , Animals , Cell Differentiation/drug effects , Fibroblasts , Melanocytes , Mice , RNA, Neoplasm/analysis , Tretinoin/pharmacology , Tumor Cells, Cultured
18.
FEBS Lett ; 322(3): 249-52, 1993 May 17.
Article in English | MEDLINE | ID: mdl-8387430

ABSTRACT

Nucleoside analogues previously found to be inactive against the human immunodeficiency virus (HIV) may be activated by simple chemical derivatisation. As part of our effort to deliver masked phosphates inside living cells we have discovered that certain phosphate triester derivatives of inactive nucleoside analogues become inhibitors of HIV replication. This discovery underlies the importance of the masked phosphate approach, and has significant implications for the future design of chemotherapeutic nucleoside analogues. If highly modified nucleoside analogues may be active without the intervention of nucleoside kinase enzymes, major advantage may accrue in terms of low toxicity and enhanced selectivity. Moreover, the increased structural freedom may have implications for dealing with the emergence of resistance. The concept herein described as 'kinase bypass' may thus stimulate the discovery of a new generation of antiviral agents.


Subject(s)
Antiviral Agents/pharmacology , HIV-1/drug effects , Nucleosides/pharmacology , Antiviral Agents/pharmacokinetics , Biotransformation , Cell Line , HIV-1/physiology , Humans , Molecular Structure , Nucleosides/pharmacokinetics , Phosphorylation , Phosphotransferases/metabolism , Virus Replication/drug effects , Zidovudine/pharmacology
19.
Cell Growth Differ ; 3(7): 435-42, 1992 Jul.
Article in English | MEDLINE | ID: mdl-1384653

ABSTRACT

Elevated levels of pp60c-src tyrosine kinase activity have been implicated in both tumorigenesis and cell differentiation. We have found a 2- to 4-fold elevation in pp60c-src specific activity in certain human melanoma cell lines compared to human foreskin fibroblasts. This activation of pp60c-src did not appear to be related to melanoma tumor progression, because when normal human epidermal melanocytes were examined, it was found that they contained pp60c-src having a 7-fold elevation in specific activity compared to pp60c-src from human fibroblasts. It was determined that pp60c-src from melanocytes was not the neuronal form, pp60c-src+. Melanocyte pp60c-src exhibited a reduced level of phosphorylation on its carboxyl-terminal regulatory site, tyrosine 530, which might be responsible for its elevated specific activity. These results suggest that, in melanocytes, regulation of tyrosine 530 phosphorylation-dephosphorylation favors activation of pp60c-src. This activation may be involved in the growth, differentiation, or function of human melanocytes.


Subject(s)
Fibroblasts/enzymology , Isoenzymes/metabolism , Melanocytes/enzymology , Melanoma/pathology , Neoplasm Proteins/metabolism , Proto-Oncogene Proteins pp60(c-src)/metabolism , Cells, Cultured , Eye Neoplasms/enzymology , Humans , Male , Melanoma/enzymology , Neurons/enzymology , Phosphorylation , Protein Processing, Post-Translational , Retinoblastoma/enzymology , Tumor Cells, Cultured/enzymology
20.
Antiviral Res ; 17(3): 197-212, 1992 Mar.
Article in English | MEDLINE | ID: mdl-1567187

ABSTRACT

Novel phosphate triester derivatives of 3'-acetylthymidine, and of the anti-HIV nucleoside analogue AZT have been prepared by phosphorochloridate chemistry. These materials are designed to act as membrane-soluble pro-drugs of the bio-active free nucleotides. In particular, novel glycolate and lactate phosphate derivatives have been prepared. In vitro evaluation revealed the AZT compounds to have a pronounced and selective antiviral effect, the magnitude of which varied considerably with the nature of the phosphate blocking group.


Subject(s)
Antiviral Agents/chemical synthesis , Antiviral Agents/pharmacology , HIV/drug effects , Organophosphorus Compounds/chemical synthesis , Organophosphorus Compounds/pharmacology , Zidovudine/analogs & derivatives , Zidovudine/chemical synthesis , Zidovudine/pharmacology
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