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1.
J Agric Saf Health ; 13(4): 375-93, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18075014

RESUMO

Children and adolescents who perform farm chores are exposed to cumulative trauma injury risks, particularly to the low back. For example, they may routinely handle heavy materials and need to adopt awkward postures during farm chores. Two potential interventions aimed at reducing low-back injury risk were examined in the laboratory: the use of a rugged cart and proper orienting of feed bags to ease feed transport; and the use of a modified feed bin, intended to allow easier access to product scooped from the bin at different levels. A lumbar motion monitor device was used to quantify trunk movement and determine injury risk level. Fourteen male and female youth who regularly perform these farm chores participated in the study. The cart significantly reduced low-back injury risk by nearly 10%, compared with manual feed bag lifting and carrying. The modified feed bin did not significantly reduce low-back injury risk, compared with traditional scooping. Regardless of the method used, however, scooping feed from the top of the bin reduced lower back disorder risk by 50% or more compared to the two lower levels. This study showed that relatively simple and low-cost solutions can be applied to farm environments to help protect the low backs of youth who perform farm chores.


Assuntos
Doenças dos Trabalhadores Agrícolas/prevenção & controle , Ração Animal , Dor Lombar/prevenção & controle , Adolescente , Animais , Criança , Serviços de Saúde da Criança , Feminino , Humanos , Masculino , Análise e Desempenho de Tarefas , Local de Trabalho
2.
Ergonomics ; 50(11): 1761-70, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17972201

RESUMO

A sequential manual lifting job is defined as a job where workers rotate between a series of manual lifting rotation slots or elements at specified time intervals during the course of a work shift. The original NIOSH lifting equation lacked a method for assessing the physical demands of these types of jobs. This paper presents the sequential lifting index (SLI), a new conceptual method for assessing the physical demands for sequential manual lifting jobs. The new method is similar to the composite lifting index (CLI) method that was provided by NIOSH for assessing multi-task jobs. The SLI method expands upon the methods originally provided by NIOSH by providing a simple method for estimating the relative magnitude of physical stress for sequential manual lifting jobs. It should also be useful in assisting safety and health specialists to prioritize or rank hazardous jobs within a plant.


Assuntos
Saúde Ocupacional , Levantamento de Peso , Suporte de Carga , Fenômenos Biomecânicos , Indicadores Básicos de Saúde , Humanos , Itália , Modelos Teóricos , National Institute for Occupational Safety and Health, U.S. , Medição de Risco , Análise e Desempenho de Tarefas , Estados Unidos
3.
J Agric Saf Health ; 10(4): 257-74, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15603225

RESUMO

Little information currently exists regarding the risk of low-back disorders among youth who perform physically demanding farm activities. Thus, afield study was conducted in which children and adolescents who engage in farm work were recruited, fitted with a lumbar motion monitoring system, and then observed performing their usual chores. The lumbar motion monitor was used to record the trunk movements required while youth were performing routine manual material handling tasks on a farm. Workplace factors and motions from both males and females were recorded on over 40 farm tasks, such as feeding animals, lifting bales of hay and straw, and other miscellaneous farm chores. Although the sample size and number of observations in this study were small, the results showed that the magnitude of several work-related factors, such as weight and horizontal moment arm, and trunk motions for many farm activities were equal to or greater than those associated with high injury risk jobs previously assessed in industrial workplaces. In this study, we quantified the physical demands of tasks performed by children and adolescents on farms. In addition, the specific farm chores more likely to load the spines of youth and thereby contribute to musculoskeletal injury were identified.


Assuntos
Doenças dos Trabalhadores Agrícolas/epidemiologia , Dor Lombar/epidemiologia , Adolescente , Serviços de Saúde do Adolescente , Doenças dos Trabalhadores Agrícolas/etiologia , Doenças dos Trabalhadores Agrícolas/prevenção & controle , Criança , Serviços de Saúde da Criança , Feminino , Humanos , Dor Lombar/etiologia , Dor Lombar/prevenção & controle , Masculino , Meio-Oeste dos Estados Unidos/epidemiologia , Fatores de Risco , Análise e Desempenho de Tarefas , Local de Trabalho
4.
Ergonomics ; 45(6): 399-414, 2002 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-12061965

RESUMO

The study documented three-dimensional spinal loading during lifting from an industrial bin. Two lifting styles and two bin design factors were examined in Phase I. The lifting style measures in Phase I were one hand versus two hand and standing on one foot versus two feet. The bin design variables were region of load in the bin and bin height. The Phase II study examined one-handed lifting styles with and without supporting body weight with the free hand on the bin as well as region and the number of feet. Twelve male and 12 female subjects lifted an 11.3 kg box from the bin. Spinal compression, lateral shear and anterior - posterior shear forces were estimated using a validated EMG-assisted biomechanical model. Phase I results indicated that the bin design factor of region had the greatest impact on spinal loading. The upper front region minimized spinal loading for all lifting styles. Furthermore, the lifting style of two hands and two feet minimized spinal loading. However, comparing Phase I two-handed lifting with Phase II one-handed supported lifting, the one-handed supported lifting techniques had lower compressive and anterior - posterior shear loads in the lower regions as well as the upper back region of the bin. A bin design that facilitates lifting from the upper front region of the bin reduces spinal loading more effectively than specific lifting styles. Furthermore, a bin design with a hand hold may facilitate workers using a supported lifting style that reduces spinal loading.


Assuntos
Remoção , Coluna Vertebral/fisiologia , Suporte de Carga/fisiologia , Adulto , Força Compressiva/fisiologia , Monitoramento Ambiental/métodos , Desenho de Equipamento , Feminino , Humanos , Masculino , Postura/fisiologia , Análise e Desempenho de Tarefas
5.
Assist Technol ; 13(2): 88-93, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-12530836

RESUMO

Work-related musculoskeletal disorders (MSDs) account for a major portion of the cost of work-related injury and illness in the United States. Many of these injuries and illnesses lead to temporary or permanent disability. It is generally accepted that the incidence of MSDs increases when the demands of the job exceed the capabilities of the worker. As the workforce ages and physical capabilities decline, it is anticipated that many more Americans will request disability-related leave resulting from musculoskeletal disorders because they are unable to meet the demands of the job. To prevent these disabilities and to accommodate a wider range of people in the workforce, physical job demands may have to be reduced so that a larger portion of the population will be capable of working. Providing engineering controls or alternative work arrangements allows for accommodation of workers with a wide range of capabilities and can assist in rehabilitation and early return to work following injury.


Assuntos
Transtornos Traumáticos Cumulativos/prevenção & controle , Ergonomia , Doenças Musculoesqueléticas/prevenção & controle , Doenças Profissionais/prevenção & controle , Humanos
7.
Mutat Res ; 462(2-3): 137-47, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10767625

RESUMO

About 23% of mutations in hereditary human diseases and 24% of mutations in p53 in human cancers are G to A transitions at sites of cytosine methylation suggesting that these sites are either foci for DNA damage, or foci for damage that is poorly repaired. Thymine produced at these sites by the hydrolytic deamination of 5-methylcytosine is removed by thymine-DNA glycosylase. Thymine-DNA glycosylase will also remove 3,N(4)-ethenocytosine and uracil from DNA. The action of this enzyme is limited by its very low k(cat) and by tight binding to the apurinic site produced when the thymine is removed. These properties of the enzyme suggest that the inefficiency of the base excision repair pathway that it initiates may be the underlying cause of the prevalence of these mutations.


Assuntos
Reparo do DNA , Endodesoxirribonucleases/metabolismo , Dano ao DNA , Desoxirribonuclease (Dímero de Pirimidina) , Endodesoxirribonucleases/química , Endodesoxirribonucleases/genética , Regulação Enzimológica da Expressão Gênica , Humanos , Mutação Puntual , Relação Estrutura-Atividade , Especificidade por Substrato , Timina/metabolismo , Proteína Supressora de Tumor p53/genética
8.
J Agric Saf Health ; 6(3): 191-201, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11202113

RESUMO

A series of eight focus groups were convened to: (1) identify tasks and activities performed by youth on farms with the potential for causing non-traumatic work-related Musculoskeletal Disorders (MSDs); (2) determine the participants perceptions about risks of MSDs for youths performing those tasks; and (3) determine other factors that might relate to MSDs for youth working on farms, such as possible interventions for prevention. Seventy-two farm family members, 40 adults and 32 farm youth aged 8-18, participated in focus groups. Ten questions were posed to each of the eight groups about what tasks youth perform on the farm, how the work is assigned, and what risk factors are associated with the work. There was general agreement among the adults that maturity rather than age is the dominant factor for determining what tasks are performed by youth workers on the farm. Youth, on the other hand, believed that task urgency dictated what jobs were assigned to youth workers. Most adults indicated that lifting objects, forking, or shoveling was responsible for most of the serious non-traumatic injuries. Bending over while working, sitting in an awkward position looking back at equipment from a tractor, sitting in a cramped position, looking down at a combine header, and long hours of work were also identified as potential problems. Youth described muscle aches and strains of the legs, arms, shoulder, back or neck as everyday occurrences. According to the youth, "If it's not broken, you're fine". Only basic training is provided and most respondents believed that youth learned best through observation. There was general agreement that physician recommended guidelines for assigning youth to tasks would be ignored unless they carried the force of the law.


Assuntos
Acidentes de Trabalho/prevenção & controle , Doenças dos Trabalhadores Agrícolas/prevenção & controle , Emprego , Doenças Musculoesqueléticas/prevenção & controle , Gestão da Segurança , Adolescente , Adulto , Criança , Ergonomia , Feminino , Grupos Focais , Humanos , Masculino , Pessoa de Meia-Idade , Ohio
9.
Spine (Phila Pa 1976) ; 24(4): 386-94; discussion 395, 1999 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-10065524

RESUMO

STUDY DESIGN: A cross-sectional study of the 1-year prevalence of low back pain was conducted in workers employed in manual lifting jobs. OBJECTIVES: To provide epidemiologic data to determine the correlation between the prevalence of low back pain and exposure to manual lifting stressors, measured with the lifting index component of the revised lifting equation from the National Institute for Occupational Safety and Health (NIOSH). SUMMARY OF BACKGROUND DATA: The NIOSH lifting equation has been proposed as a practical, yet valid tool for assessing the risks of low back pain caused by manual lifting. To date, however, there have been few studies in which the effectiveness of the equation to identify jobs with elevated rates of low back pain has been evaluated. METHODS: Fifty jobs from four industrial sites were evaluated with the NIOSH lifting equation. A symptom and occupational history questionnaire was administered to 204 people employed in lifting jobs and 80 people employed in nonlifting jobs. Regression analysis was used to determine whether there was a correlation between the lifting index and reported low back pain. RESULTS: As the lifting index increased from 1.0 to 3.0, the odds of low back pain increased, with a peak and statistically significant odds ratio occurring in the 2 < lifting index < or = 3 category (odds ratio = 2.45). For jobs with a lifting index higher than 3.0, however, the odds ratio was lower (odds ratio = 1.45). CONCLUSIONS: Although low back pain is a common disorder, the lifting index appears be a useful indicator for determining the risk of low back pain caused by manual lifting.


Assuntos
Remoção , Dor Lombar/epidemiologia , National Institute for Occupational Safety and Health, U.S./normas , Doenças Profissionais/epidemiologia , Exposição Ocupacional/efeitos adversos , Avaliação da Capacidade de Trabalho , Adulto , Estudos Transversais , Feminino , Seguimentos , Humanos , Remoção/efeitos adversos , Dor Lombar/diagnóstico , Dor Lombar/etiologia , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/diagnóstico , Doenças Profissionais/etiologia , Razão de Chances , Prevalência , Estresse Mecânico , Inquéritos e Questionários , Estados Unidos
10.
Ergonomics ; 42(1): 229-45, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9973881

RESUMO

Low-back disorders (LBD) continue to be the most costly and common musculoskeletal problem facing society today. Investigators have developed tools or measures that are intended to identify jobs that will probably be associated with an elevated risk of low-back disorders. However, an important and not widely discussed issue associated with these tools and procedures has been that of the validity or effectiveness of the tools. Therefore the objective of this study was to evaluate the validity and effectiveness of two commonly used types of LBD assessment methods in terms of their ability to correctly associate jobs with LBD risk. The 1981 NIOSH Work Practices Guide for Manual Lifting and the 1991 NIOSH revised lifting equation, along with psychophysical measures were assessed for their ability to correctly identify high-, medium-, and low-risk (of LBD) jobs. Risk was defined according to a database of 353 industrial jobs representing over 21 million person-hours of exposure. The results indicated that both NIOSH measures were predictive and resulted in odds ratios between 3.1 and 4.6. Higher odds ratios were found when the maximum horizontal distance was used to assess a job compared to the average horizontal distance. Further analyses indicated that the two NIOSH assessment methods classified risk in very different ways. The 1981 NIOSH Guide demonstrated good specificity (91%) in that it identified low-risk jobs well but it also displayed low sensitivity by only correctly identifying 10% of the high-risk jobs. The 1993 NIOSH revised lifting equation, on the other hand, had better sensitivity. It correctly identified 73% of the high-risk jobs but did not identify low- and medium-risk jobs well. Using psychophysical criteria it was observed that 60% of the high-risk jobs would be judged to be acceptable, whereas, 64% and 91% of the medium- and low-risk jobs, respectively, would be judged to be acceptable. This study indicates that the different measures have various strengths and weaknesses. When controlling for occupational LBD it should be recognized that a variety of measures exist and that the measure that most appropriately assesses risk depends upon the characteristics of the job.


Assuntos
Remoção , Dor Lombar/etiologia , Doenças Profissionais/etiologia , Avaliação da Capacidade de Trabalho , Bases de Dados Factuais , Humanos , Dor Lombar/prevenção & controle , National Institute for Occupational Safety and Health, U.S. , Doenças Profissionais/prevenção & controle , Psicofísica , Fatores de Risco , Gestão da Segurança , Estados Unidos
11.
J Biol Chem ; 274(1): 67-74, 1999 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-9867812

RESUMO

In vitro, following the removal of thymine from a G.T mismatch, thymine DNA glycosylase binds tightly to the apurinic site it has formed. It can also bind to an apurinic site opposite S6-methylthioguanine (SMeG) or opposite any of the remaining natural DNA bases. It will therefore bind to apurinic sites formed by spontaneous depurination, chemical attack, or other glycosylases. In the absence of magnesium, the rate of dissociation of the glycosylase from such complexes is so slow (koff 1.8 - 3.6 x 10(-5) s-1; i.e. half-life between 5 and 10 h) that each molecule of glycosylase removes essentially only one molecule of thymine. In the presence of magnesium, the dissociation rates of the complexes with C.AP and SMeG.AP are increased more than 20-fold, allowing each thymine DNA glycosylase to remove more than one uracil or thymine from C.U and SMeG.T mismatches in DNA. In contrast, magnesium does not increase the dissociation of thymine DNA glycosylase from G.AP sites sufficiently to allow it to remove more than one thymine from G.T mismatches. The bound thymine DNA glycosylase prevents human apurinic endonuclease 1 (HAP1) cutting the apurinic site, so unless the glycosylase was displaced, the repair of apurinic sites would be very slow. However, HAP1 significantly increases the rate of dissociation of thymine DNA glycosylase from apurinic sites, presumably through direct interaction with the bound glycosylase. This effect is concentration-dependent and at the probable normal concentration of HAP1 in cells the dissociation would be fast. This interaction couples the first step in base excision repair, the glycosylase, to the second step, the apurinic endonuclease. The other proteins involved in base excision repair, polymerase beta, XRCC1, and DNA ligase III, do not affect the dissociation of thymine DNA glycosylase from the apurinic site.


Assuntos
Carbono-Oxigênio Liases/metabolismo , DNA/metabolismo , Endodesoxirribonucleases/metabolismo , Pareamento Incorreto de Bases , Sequência de Bases , Ligação Competitiva , Catálise , Primers do DNA , Reparo do DNA , DNA Liase (Sítios Apurínicos ou Apirimidínicos) , Desoxirribonuclease (Dímero de Pirimidina) , Desoxirribonuclease IV (Fago T4-Induzido) , Humanos , Cinética , Ligação Proteica
12.
Am Ind Hyg Assoc J ; 59(12): 871-81, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9866167

RESUMO

Assessment of the physical demands of potentially hazardous manual material handling (MMH) activities is fundamental to the prevention of disabilities from occupationally related low back pain, a problem costing the nation billions of dollars annually. Although there is a variety of ergonomic assessment methods available for assessing MMH activities, there is a lack of practical information to assist users in choosing the most appropriate assessment methods of a particular job. This article reviews currently available assessment methods and presents case study results of a physically demanding repetitive manual lifting job in two grocery warehouses. The case study will provide a framework for a comparison of the methods and a discussion of relevant application issues designed to assist users in selecting appropriate methods for assessing MMH jobs. Based on the results of the study, it is concluded that all of the ergonomic methods were in agreement that the job of grocery selector has a high level of risk for low back pain. Differences between the methods were noted, however, that should be considered when choosing a specific method for a specific application.


Assuntos
Remoção , Análise e Desempenho de Tarefas , Antropometria , Fenômenos Biomecânicos , Humanos , Dor Lombar/etiologia , Dor Lombar/prevenção & controle , Masculino , National Institute for Occupational Safety and Health, U.S. , Doenças Profissionais/etiologia , Doenças Profissionais/prevenção & controle , Psicofísica , Fatores de Risco , Estados Unidos
13.
Appl Ergon ; 29(6): 433-8, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9796788

RESUMO

Twenty-seven non-ergonomists who participated in a one-day training session on the use of the NIOSH lifting equation (NLE) were subsequently tested on a simulated lifting task eight weeks later to determine their accuracy in measuring the variables. Analysis of the results indicate that (1) inter-observer variability was small, especially for the most important factor (i.e. horizontal distance); (2) individuals can be trained to make measurements with sufficient accuracy to provide consistent recommended weight limit and lifting index values; and (3) measurement of the coupling and asymmetric variables were the least accurate.


Assuntos
Capacitação em Serviço , Remoção , National Institute for Occupational Safety and Health, U.S./normas , Avaliação Educacional , Fidelidade a Diretrizes , Humanos , Variações Dependentes do Observador , Estados Unidos
14.
J Biol Chem ; 273(32): 20007-14, 1998 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-9685338

RESUMO

The time course of removal of thymine by thymine DNA glycosylase has been measured in vitro. Each molecule of thymine DNA glycosylase removes only one molecule of thymine from DNA containing a G.T mismatch because it binds tightly to the apurinic DNA site left after removal of thymine. The 5'-flanking base pair to G.T mismatches influences the rate of removal of thymine: kcat values with C.G, T.A, G.C, and A.T as the 5'-base pair were 0.91, 0.023, 0. 0046, and 0.0013 min-1, respectively. Thymine DNA glycosylase can also remove thymine from mismatches with S6-methylthioguanine, but, unlike G.T mismatches, a 5'-C.G does not have a striking effect on the rate: kcat values for removal of thymine from SMeG.T with C.G, T. A, G.C, and A.T as the 5'-base pair were 0.026, 0.018, 0.0017, and 0. 0010 min-1, respectively. Thymine removal is fastest when it is from a G.T mismatch with a 5'-flanking C.G pair, suggesting that the rapid reaction of this substrate involves contacts between the enzyme and oxygen 6 or the N-1 hydrogen of the mismatched guanine as well as the 5'-flanking C.G pair. Disrupting either of these sets of contacts (i.e. replacing the 5'-flanking C.G base pair with a T.A or replacing the G.T mismatch with SMeG.T) has essentially the same effect on rate as disrupting both sets (i.e. replacing CpG.T with TpSMeG.T), and so these contacts are probably cooperative. The glycosylase removes uracil from G.U, C.U, and T.U base pairs faster than it removes thymine from G.T. It can even remove uracil from A.U base pairs, although at a very much lower rate. Thus, thymine DNA glycosylase may play a backup role to the more efficient general uracil DNA glycosylase.


Assuntos
Endodesoxirribonucleases/metabolismo , Timina/farmacologia , Composição de Bases/genética , DNA/metabolismo , Proteínas de Ligação a DNA/metabolismo , Desoxirribonuclease (Dímero de Pirimidina) , Escherichia coli/enzimologia , Humanos , Cinética , Tioguanina/análogos & derivados , Uracila/metabolismo
15.
Ergonomics ; 41(8): 1155-68, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9715674

RESUMO

A study was performed to investigate how different types of handle coupling affect the loading on the spine. Ten male grocery item selectors performed a laboratory simulation of a warehouse palletizing task. Participants transferred the cases from a pallet in a storage bin to the destination pallet. The trunk motions and muscle activities were monitored by a Lumbar Motion Monitor (LMM) and electromyographic electrodes, respectively, and used as input to an EMG-assisted biomechanical model. The results of the study revealed that the presence of handles reduced the complex loads on the spine. This was particuarly true when lifting to the lowest positions of the pallet, where the highest forces occurred. It was determined that the maximum spinal compression forces were reduced by an average of 6.8% when handles were added to the cases. The presence of handles affected the moments imposed on the trunk in the lower regions on the pallet, indicating a difference in lifting style and/or more sagittal flexion. The results of this study suggest that the multiplier for handle coupling in the 1991 NIOSH Revised Lifting Equation was appropriate for higher lifts (at 133.8 cm), but needs to be more protective for 'poor' coupling conditions with lower vertical heights, which are the most common in industry. Based on these results, it is recommended that handles be designed into the cases that are commonly lifted from low levels in warehousing and other manual materials handling situations.


Assuntos
Ergonomia , Coluna Vertebral/fisiologia , Análise e Desempenho de Tarefas , Carga de Trabalho , Adulto , Eletromiografia , Desenho de Equipamento , Humanos , Remoção/efeitos adversos , Masculino , Pessoa de Meia-Idade , Suporte de Carga/fisiologia
16.
Biochemistry ; 36(9): 2501-6, 1997 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-9054555

RESUMO

It has been suggested that the cytotoxicity of 6-thioguanine depends upon (1) incorporation of 6-thioguanine into DNA, (2) methylation by S-adenosylmethionine (SAM) of the thio group to give S6-methylthioguanine, (3) miscoding during DNA replication to give [SMeG] x T base pairs, and (4) recognition of these base pairs by proteins of the postreplicative mismatch repair system. Here we have investigated systematically the ability of proteins present in human cell extracts to bind to DNA containing S6-methylthioguanine. We found that [SMeG] x T base mismatches were bound by the mismatch binding complex, hMutS alpha, and that the level of binding was dependent upon the base 5' to the S6-methylthioguanine in the order G > C = A > T. Extracts from cells that lack either hMSH2 (LoVo cells) or GTBP (HCT-15 cells), two components of the hMutS alpha complex, were unable to bind the [SMeG] x T base pair. We also found that hMutS alpha was able to bind to [SMeG] x C base pairs when the S6-methylthioguanine was in the sequence 5'-Cp[SMeG]. This suggests that miscoding by S6-methylthioguanine residues in DNA during DNA synthesis may not be an absolutely required step in the mechanism of cytotoxicity. Also, since CpG sequences are so important in gene regulation, this result may be of considerable significance.


Assuntos
Proteínas de Ligação a DNA/química , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Tioguanina/análogos & derivados , Tioguanina/toxicidade , Composição de Bases , Sequência de Bases/fisiologia , Extratos Celulares/química , Células HeLa , Humanos , Proteína 3 Homóloga a MutS , Relação Estrutura-Atividade , Tioguanina/química , Células Tumorais Cultivadas
17.
Science ; 273(5278): 1109-11, 1996 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-8688098

RESUMO

It is proposed here that the delayed cytotoxicity of thioguanine involves the postreplicative DNA mismatch repair system. After incorporation into DNA, the thioguanine is chemically methylated by S-adenosylmethionine to form S6-methylthioguanine. During DNA replication, the S6-methylthioguanine directs incorporation of either thymine or cytosine into the growing DNA strand, and the resultant S6-methylthioguanine-thymine pairs are recognized by the postreplicative mismatch repair system. Azathioprine, an immunosuppressant used in organ transplantation, is partly converted to thioguanine. Because the carcinogenicity of N-nitrosamines depends on formation of O6-alkylguanine in DNA, the formation of the analog S6-methylthioguanine during azathioprine treatment may partly explain the high incidence of cancer after transplantation.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Reparo do DNA , Replicação do DNA , DNA/metabolismo , Tioguanina/farmacologia , Animais , Antimetabólitos Antineoplásicos/metabolismo , Composição de Bases , Sequência de Bases , Células CHO , Sobrevivência Celular/efeitos dos fármacos , Cricetinae , Células HeLa , Humanos , Metilação , Dados de Sequência Molecular , S-Adenosilmetionina/metabolismo , Tioguanina/análogos & derivados , Tioguanina/metabolismo
18.
Biochemistry ; 35(26): 8723-33, 1996 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-8679635

RESUMO

The resonance Raman spectra of 4-thiothymidine [4ST] have been recorded (a) in the free deoxynucleoside form, (b) when incorporated into the single stranded oligodeoxynucleotide d(AG[4ST]-TC), and (c) within the double-stranded self-complementary dodecamer d(GACGA[4ST]ATCGTC). Vibrational mode assignments of almost all the major Raman bands observed in each spectra have been made, mainly by comparison with the published assignments of related nucleosides and nucleotides. Differences between the spectra were observed, particularly when [4ST] and d(AG[4ST]TC) were compared to d(GACGA[4ST]ATCGTC). This is explained in terms of the variations in structure between single-and double-stranded DNA. Good quality spectra were obtained at nucleotide/oligonucleotide concentrations of between 100 and 500 microM and this coupled with an apparatus that uses small volumes (100 microL) allowed measurement of the spectrum of d(GACGA[4ST]ATCGTC) bound to the EcoRV endonuclease. This well characterised nuclease, for which crystal structures are available, recognizes d(GATAT) sequences. When this is replaced with d(GA[4ST]ATC), a poor substrate results but turnover can be prevented during data accumulation by omission of the essential cation Mg2+. Large shifts in several of the Raman bands were observed, and these have been related to the environment of the [4ST] base in the protein-bound oligonucleotide as deduced from the crystal structure. The wavenumber for the C = S stretch vibration in free d(GACGA[4ST]ATCGTC) has been used to calculate the strength of the Watson-Crick hydrogen bond between the sulphur atom in [4ST] and the 6-NH2 group on its partner dA. On binding to the enzyme, the shift in the wavenumber of the C = S stretch indicates this Watson-Crick hydrogen bond is weakened, in good agreement with X-ray structures. The advantage of using [4ST] as a resonance Raman probe is that it absorbs at 340 nm, a wavelength where other nucleic acid and protein absorbance is minimal. Thus the spectra obtained are very simple and consist of signals that arise predominantly from the thiobase alone, and this facilitates data interpretation.


Assuntos
Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Oligodesoxirribonucleotídeos/química , Tionucleosídeos/química , Timidina/análogos & derivados , Sequência de Bases , Dados de Sequência Molecular , Ligação Proteica , Análise Espectral Raman , Termodinâmica , Tionucleosídeos/metabolismo , Timidina/química , Timidina/metabolismo
19.
Biochemistry ; 33(7): 1812-9, 1994 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-8110783

RESUMO

The interaction of the EcoRV restriction endonuclease with the dG and dC bases in its recognition sequence (GATATC) has been studied using base analogues. These modified dG and dC bases each have a single potential protein contact removed. The analogues have been incorporated into the self-complementary dodecamer d(pGACGATATCGTC) at the appropriate positions (underlined). Many of the analogues caused no change in the Tm of the duplex or else lowered the Tm by a small amount such that a duplex was still formed at temperatures suitable for enzyme assay. However, the dG analogue 2-aminopurine-1-beta-D-2'-deoxyriboside destabilized the duplex to such an extent that the 12'-mer could not be used for enzyme assays. To overcome this, a longer self-complementary 18'-mer was used with this modified base. The circular dichroism spectra of the modified base containing 12'-mers (and the 18'-mer in the case of 2-aminopurine) were very similar to the parent sequences lacking modified bases. This demonstrates the formation of B-DNA structures in all cases and similar overall conformations. The Km and kcat values for the various modified oligomers have been determined, and these data have been used to assess the roles that functional groups on the dG and dC bases play in the recognition and hydrolysis of GATATC sequences by the endonuclease. The results obtained here have been compared to the crystal structures of the EcoRV complexed with a GATATC sequence, and this has allowed a critical evaluation of the base analogue approach.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Desoxicitidina/metabolismo , Desoxiguanosina/metabolismo , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Oligodesoxirribonucleotídeos/metabolismo , Sequência de Bases , Sítios de Ligação , Cristalografia por Raios X , Ligação de Hidrogênio , Dados de Sequência Molecular , Estrutura Molecular , Oligodesoxirribonucleotídeos/química , Relação Estrutura-Atividade , Especificidade por Substrato , Termodinâmica
20.
Ergonomics ; 36(7): 749-76, 1993 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8339717

RESUMO

In 1985, the National Institute for Occupational Safety and Health (NIOSH) convened an ad hoc committee of experts who reviewed the current literature on lifting, recommend criteria for defining lifting capacity, and in 1991 developed a revised lifting equation. Subsequently, NIOSH developed the documentation for the equation and played a prominent role in recommending methods for interpreting the results of the equation. The 1991 equation reflects new findings and provides methods for evaluating asymmetrical lifting tasks, lifts of objects with less than optimal hand-container couplings, and also provides guidelines for a larger range of work durations and lifting frequencies than the 1981 equation. This paper provides the basis for selecting the three criteria (biomechanical, physiological, and psychophysical) that were used to define the 1991 equation, and describes the derivation of the individual components (Putz-Anderson and Waters 1991). The paper also describes the lifting index (LI), an index of relative physical stress, that can be used to identify hazardous lifting tasks. Although the 1991 equation has not been fully validated, the recommended weight limits derived from the revised equation are consistent with or lower than those generally reported in the literature. NIOSH believes that the revised 1991 lifting equation is more likely than the 1981 equation to protect most workers.


Assuntos
Dor Lombar/prevenção & controle , National Institute for Occupational Safety and Health, U.S. , Esforço Físico , Análise e Desempenho de Tarefas , Fenômenos Biomecânicos , Metabolismo Energético/fisiologia , Humanos , Vértebras Lombares/fisiopatologia , Estresse Fisiológico/fisiopatologia , Estados Unidos
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