Showing papers by "University of Kentucky published in 1998"
TL;DR: In this article, the authors describe version 90 (C90) of the code, paying particular attention to changes in the atomic database and numerical methods that have affected predictions since the last publicly available version, C84.
Abstract: CLOUDY is a large‐scale spectral synthesis code designed to simulate fully physical conditions within an astronomical plasma and then predict the emitted spectrum. Here we describe version 90 (C90) of the code, paying particular attention to changes in the atomic database and numerical methods that have affected predictions since the last publicly available version, C84. The computational methods and uncertainties are outlined together with the direction future development will take. The code is freely available and is widely used in the analysis and interpretation of emission‐line spectra. Web access to the Fortran source for CLOUDY, its documentation Hazy, and an independent electronic form of the atomic database is also described.
2,571 citations
TL;DR: Both ionic and covalent solution-phase chemistry with concomitant modulation of the SWNT band structure were demonstrated to study the effects of chemical modifications on the band gaps of theSWNTs.
Abstract: Naked metallic and semiconducting single-walled carbon nanotubes (SWNTs) were dissolved in organic solutions by derivatization with thionychloride and octadecylamine. Both ionic (charge transfer) and covalent solution-phase chemistry with concomitant modulation of the SWNT band structure were demonstrated. Solution-phase near-infrared spectroscopy was used to study the effects of chemical modifications on the band gaps of the SWNTs. Reaction of soluble SWNTs with dichlorocarbene led to functionalization of the nanotube walls.
2,506 citations
TL;DR: The costs and limits of phenotypic plasticity are thought to have important ecological and evolutionary consequences, yet they are not as well understood as the benefits of plasticity.
Abstract: The costs and limits of phenotypic plasticity are thought to have important ecological and evolutionary consequences, yet they are not as well understood as the benefits of plasticity. At least nine ideas exist regarding how plasticity may be costly or limited, but these have rarely been discussed together. The most commonly discussed cost is that of maintaining the sensory and regulatory machinery needed for plasticity, which may require energy and material expenses. A frequently considered limit to the benefit of plasticity is that the environmental cues guiding plastic development can be unreliable. Such costs and limits have recently been included in theoretical models and, perhaps more importantly, relevant empirical studies now have emerged. Despite the current interest in costs and limits of plasticity, several lines of reasoning suggest that they might be difficult to demonstrate.
2,109 citations
TL;DR: Concentrations of copper (Cu), iron (Fe) and zinc (Zn) were measured in the rims and cores of senile plaques (SP) and in the neuropil of the amygdala of nine Alzheimer's disease patients and in that of five neurologically normal control subjects using micro particle-induced X-ray emission (micro-PIXE).
1,963 citations
TL;DR: Patients with cancer and single metastases to the brain who receive treatment with surgical resection and postoperative radiotherapy have fewer recurrences of cancer in the brain and are less likely to die of neurologic causes than similar patients treated withurgical resection alone.
Abstract: Context.—For the treatment of a single metastasis to the brain, surgical resection
combined with postoperative radiotherapy is more effective than treatment
with radiotherapy alone. However, the efficacy of postoperative radiotherapy
after complete surgical resection has not been established.Objective.—To determine if postoperative radiotherapy resulted in improved neurologic
control of disease and increased survival.Design.—Multicenter, randomized, parallel group trial.Setting.—University-affiliated cancer treatment facilities.Patients.—Ninety-five patients who had single metastases to the brain that were
treated with complete surgical resections (as verified by postoperative magnetic
resonance imaging) between September 1989 and November 1997 were entered into
the study.Interventions.—Patients were randomly assigned to treatment with postoperative whole-brain
radiotherapy (radiotherapy group, 49 patients) or no further treatment (observation
group, 46 patients) for the brain metastasis, with median follow-up of 48
weeks and 43 weeks, respectively.Main Outcome Measures.—The primary end point was recurrence of tumor in the brain; secondary
end points were length of survival, cause of death, and preservation of ability
to function independently.Results.—Recurrence of tumor anywhere in the brain was less frequent in the radiotherapy
group than in the observation group (9 [18%] of 49 vs 32 [70%] of 46; P<.001). Postoperative radiotherapy prevented brain
recurrence at the site of the original metastasis (5 [10%] of 49 vs 21 [46%]
of 46; P<.001) and at other sites in the brain
(7 [14%] of 49 vs 17 [37%] of 46; P <.01). Patients
in the radiotherapy group were less likely to die of neurologic causes than
patients in the observation group (6 [14%] of 43 who died vs 17 [44%] of 39; P =.003). There was no significant difference between the
2 groups in overall length of survival or the length of time that patients
remained functionally independent.Conclusions.—Patients with cancer and single metastases to the brain who receive
treatment with surgical resection and postoperative radiotherapy have fewer
recurrences of cancer in the brain and are less likely to die of neurologic
causes than similar patients treated with surgical resection alone.
1,705 citations
TL;DR: A readily scalable purification process capable of handling single-wall carbon nanotube (SWNT) material in large batches, which should greatly facilitate investigation of material properties intrinsic to the nanotubes.
Abstract: We describe, in detail, a readily scalable purification process capable of handling single-wall carbon nanotube (SWNT) material in large batches. Characterization of the resulting material by SEM, TEM, XRD, Raman scattering, and TGA shows it to be highly pure. Resistivity measurements on freestanding mats of the purified tubes are also reported. We also report progress in scaling up SWNT production by the dual pulsed laser vaporization process. These successes enable the production of gram per day quantities of highly pure SWNT, which should greatly facilitate investigation of material properties intrinsic to the nanotubes.
1,400 citations
TL;DR: Results supported PSQI internal consistency reliability and construct validity, and individuals with sleep problems, poor sleep quality, and sleep restlessness had significantly higher PSQi scores in comparison to individuals without such problems.
1,302 citations
TL;DR: Two main types of emergent effect-risk reduction caused by predator-predator interactions and risk enhancement caused by conflicting prey responses to multiple predators are suggested.
Abstract: Although almost all prey live with many types of predator, most experimental studies of predation have examined the effects of only one predator at a time. Recent work has revealed new insights into the emergent impacts of multiple predators on prey and experimental studies have identified statistical methods for evaluating them. These studies suggest two main types of emergent effect-risk reduction caused by predator-predator interactions and risk enhancement caused by conflicting prey responses to multiple predators. Some theory and generalities are beginning to emerge concerning the conditions that tend to produce these two outcomes.
1,261 citations
TL;DR: Recommendations of the American Association of Physicists in Medicine for the radiochromic film dosimetry are presented and have been reviewed and approved by the AAPM Science Council.
Abstract: Recommendations of the American Association of Physicists in Medicine (AAPM) for the radiochromic film dosimetry are presented. These guidelines were prepared by a task group of the AAPM Radiation Therapy Committee and have been reviewed and approved by the AAPM Science Council.
963 citations
TL;DR: The data suggest that mitochondrial superoxide accumulation and consequent peroxynitrite production and mitochondrial dysfunction play pivotal roles in neuronal apoptosis induced by diverse insults in cell culture and in vivo.
Abstract: Oxidative stress is implicated in neuronal apoptosis that occurs in physiological settings and in neurodegenerative disorders. Superoxide anion radical, produced during mitochondrial respiration, is involved in the generation of several potentially damaging reactive oxygen species including peroxynitrite. To examine directly the role of superoxide and peroxynitrite in neuronal apoptosis, we generated neural cell lines and transgenic mice that overexpress human mitochondrial manganese superoxide dismutase (MnSOD). In cultured pheochromocytoma PC6 cells, overexpression of mitochondria-localized MnSOD prevented apoptosis induced by Fe 2+ , amyloid β-peptide (Aβ), and nitric oxide-generating agents. Accumulations of peroxynitrite, nitrated proteins, and the membrane lipid peroxidation product 4-hydroxynonenal (HNE) after exposure to the apoptotic insults were markedly attenuated in cells expressing MnSOD. Glutathione peroxidase activity levels were increased in cells overexpressing MnSOD, suggesting a compensatory response to increased H 2 O 2 levels. The peroxynitrite scavenger uric acid and the antioxidants propyl gallate and glutathione prevented apoptosis induced by each apoptotic insult, suggesting central roles for peroxynitrite and membrane lipid peroxidation in oxidative stress-induced apoptosis. Apoptotic insults decreased mitochondrial transmembrane potential and energy charge in control cells but not in cells overexpressing MnSOD, and cyclosporin A and caspase inhibitors protected cells against apoptosis, demonstrating roles for mitochondrial alterations and caspase activation in the apoptotic process. Membrane lipid peroxidation, protein nitration, and neuronal death after focal cerebral ischemia were significantly reduced in transgenic mice overexpressing human MnSOD. The data suggest that mitochondrial superoxide accumulation and consequent peroxynitrite production and mitochondrial dysfunction play pivotal roles in neuronal apoptosis induced by diverse insults in cell culture and in vivo .
872 citations
TL;DR: It is concluded that a principal protease capable of down-regulating the levels of secreted Aβ extracellularly is IDE, and activity was unexpectedly found be associated with a time-dependent oligomerization of synthetic Aβ at physiological levels in the conditioned media of cultured cells.
TL;DR: Comparisons of these scales with those developed by Nicholls and his colleagues provide evidence of convergent validity and confirmatory factor analysis attests to the discriminant validity of the scales.
TL;DR: The existence of IGEs alters the genotype-phenotype relationship, changing the evolutionary process in some dramatic and non-intuitive ways.
Abstract: Indirect genetic effects (IGEs) are environmental influences on the phenotype of one individual that are due to the expression of genes in a different, conspecific, individual. Historically, work has focused on the influence of parents on offspring but recent advances have extended this perspective to interactions among other relatives and even unrelated individuals. IGEs lead to complicated pathways of inheritance, where environmental sources of variation can be transmitted across generations and therefore contribute to evolutionary change. The existence of IGEs alters the genotype-phenotype relationship, changing the evolutionary process in some dramatic and non-intuitive ways.
TL;DR: In this article, the authors studied the effect of the catalyst on the tube yield and the evolution of the tube diameter distribution with increasing growth environment temperature, and found that the threshold temperature for significant SWNT production was found to be
Abstract: Pulsed laser vaporization of a heated, Fe/Ni or Co/Ni catalyzed, carbon target in argon gas has been used to synthesize single-wall carbon nanotubes (SWNTs). Electron microscopy, x-ray diffraction, and Raman spectroscopy were all used to study the effect of the catalyst on the tube yield, and the evolution of the tube diameter distribution with increasing growth environment temperature $T$. By controlling the temperature in the range $780lTl1050\ifmmode^\circ\else\textdegree\fi{}\mathrm{C}$, we have been able to tune the diameter of the tubules from $\ensuremath{\sim}0.81$ to $\ensuremath{\sim}1.51\mathrm{nm}$. The threshold temperature for significant SWNT production was found to be $\ensuremath{\sim}850\ifmmode^\circ\else\textdegree\fi{}\mathrm{C}$.
TL;DR: This study reports an increase in mean free HNE in multiple brain regions in AD compared with age-matched control subjects and suggests that HNE may be an important substance in the pathogenesis of neuron degeneration in AD.
TL;DR: In this paper, a study was conducted to empirically examine the extent to which businesses use relationship quality perceptions to differentiate their qualified vendors, and the findings support the notion that relationship quality is a higher-order construct that can be used as a basis for developing vendor stratification systems.
Abstract: Companies implement preferred supplier programs to reduce their vendor relationships to a reasonable few. Consequently, vendors who do not effectively manage their customer-based relationships are strong candidates for deletion from a customer’s list of long-term suppliers. The emergence of preferred supplier programs suggests that businesses are beginning to formally recognize and reward differences between their qualified vendors. Vendor stratification is proposed as a framework for understanding the evolution of preferred vendor programs. With the growing interest in relationship marketing, a study was conducted to empirically examine the extent to which businesses use relationship quality perceptions to differentiate their qualified vendors. The findings support the notion that relationship quality is a higher-order construct that can be used as a basis for developing vendor stratification systems. The article concludes with a discussion of the managerial and research implications of the study findings.
TL;DR: In this article, the absence of hMLH1 protein was associated with the methylation of the HMLH 1 gene promoter, which is intimately associated with this epigenetic silencing mechanism.
Abstract: Mutations of DNA mismatch repair genes, including the hMLH1 gene, have been linked to human colon and other cancers in which defective DNA repair is evidenced by the associated instability of DNA microsatellite sequences (MSI). Germ-line hMLH1 mutations are causally associated with inherited MSI colon cancer, and somatic mutations are causally associated with sporadic MSI colon cancer. Previ- ously however, we demonstrated that in many sporadic MSI colon cancers hMLH1 and all other DNA mismatch repair genes are wild type. To investigate this class of tumors further, we examined a group of MSI cancer cell lines, most of which were documented as established from antecedent MSI- positive malignant tumors. In five of six such cases we found that hMLH1 protein was absent, even though hMLH1-coding sequences were wild type. In each such case, absence of hMLH1 protein was associated with the methylation of the hMLH1 gene promoter. Furthermore, in each case, treatment with the demethylating agent 5-azacytidine induced expres- sion of the absent hMLH1 protein. Moreover, in single cell clones, hMLH1 expression could be turned on, off, and on again by 5-azacytidine exposure, washout, and reexposure. This epigenetic inactivation of hMLH1 additionally accounted for the silencing of both maternal and paternal tumor hMLH1 alleles, both of which could be reactivated by 5-azacytidine. In summary, substantial numbers of human MSI cancers appear to arise by hMLH1 silencing via an epigenetic mechanism that can inactivate both of the hMLH1 alleles. Promoter methyl- ation is intimately associated with this epigenetic silencing mechanism.
TL;DR: Current knowledge about lipid biosynthetic pathways in S. cerevisiae is summarized and characteristic features of the gene products involved are described, focusing on recent discoveries in these fields.
Abstract: The yeast Saccharomyces cerevisiae is a powerful experimental system to study biochemical, cell biological and molecular biological aspects of lipid synthesis. Most but not all genes encoding enzymes involved in fatty acid, phospholipid, sterol or sphingolipid biosynthesis of this unicellular eukaryote have been cloned, and many gene products have been functionally characterized. Less information is available about genes and gene products governing the transport of lipids between organelles and within membranes, turnover and degradation of complex lipids, regulation of lipid biosynthesis, and linkage of lipid metabolism to other cellular processes. Here we summarize current knowledge about lipid biosynthetic pathways in S. cerevisiae and describe the characteristic features of the gene products involved. We focus on recent discoveries in these fields and address questions on the regulation of lipid synthesis, subcellular localization of lipid biosynthetic steps, cross-talk between organelles during lipid synthesis and subcellular distribution of lipids. Finally, we discuss distinct functions of certain key lipids and their possible roles in cellular processes.
TL;DR: The results have identified PDK-1 as the kinase that phosphorylates and activates PKC zeta in the PI 3-kinase signaling pathway, and shows that a membrane-targeted PKCZeta is constitutively active in the absence of agonist stimulation.
TL;DR: Individual SAGs differed from the norms in different ways, suggesting that their gene products play a role in overlapping but not identical circumstances, and may indicate an indirect response via treatment-induced senescence.
Abstract: The expression of several Arabidopsis thaliana senescence-associated genes (SAGs) in attached and/or detached leaves was compared in response to age, dehydration, darkness, abscisic acid, cytokinin, and ethylene treatments Most of the SAGs responded to most of the treatments in a similar fashion Detachment in darkness and ethylene were the strongest inducers of both SAGs and visible yellowing Detachment in light was also a strong inducer of SAGs, but not of visible yellowing The other treatments varied more in their effects on individual SAGs Responses were examined in both older and younger leaves, and generally were much stronger in the older ones Individual SAGs differed from the norms in different ways, however, suggesting that their gene products play a role in overlapping but not identical circumstances Some SAGs responded quickly to treatments, which may indicate a direct response Others responded more slowly, which may indicate an indirect response via treatment-induced senescence Four new SAGs were isolated as part of this work, one of which shows strong similarity to late embryogenesis-abundant (Lea) genes
TL;DR: The data suggest that sphingosine kinase is a prototypical member of a new class of lipid kinases, and an important step in corroborating the intracellular role of SPP as a second messenger.
TL;DR: The FSI was established as a valid and reliable measure of fatigue in cancer patients and healthy individuals and Suggestions are made for the potential application of the measure in clinical research.
Abstract: Although fatigue is one of the most common and debilitating symptoms experienced by cancer patients, it has received little systematic attention. This situation is due in large part to the lack of adequate instruments to measure fatigue. The primary aim of this study was to validate a newly developed measure of fatigue for use with cancer patients: the Fatigue Symptom Inventory (FSI). This 13 item self-report measure was designed to measure the intensity and duration of fatigue and its impact on quality of life. The psychometric properties of the FSI were assessed in women undergoing treatment for breast cancer, women who had completed treatment for breast cancer and women with no history of cancer. A seven-item interference subscale was found to have good internal consistency, with α coefficients above 0.90 in all three groups. The complete FSI was found to have rather weak to moderate test-retest reliability among patients in active treatment and healthy comparison subjects assessed on three separate occasions. Convergent validity was demonstrated using comparisons with existing measures of fatigue. Construct validity was demonstrated using comparisons between and within groups as well as comparisons with measures of anxiety and depression. Overall, the FSI was established as a valid and reliable measure of fatigue in cancer patients and healthy individuals. Suggestions are made for the potential application of the measure in clinical research.
TL;DR: The finding that estradiol pretreatment reduces injury demonstrates that physiologic levels of Estradiol can protect against neurodegeneration.
Abstract: Clinical studies demonstrate that estrogen replacement therapy in postmenopausal women may enhance cognitive function and reduce neurodegeneration associated with Alzheimer's disease and stroke. This study assesses whether physiologic levels of estradiol prevent brain injury in an in vivo model of permanent focal ischemia. Sprague-Dawley rats were ovariectomized; they then were implanted, immediately or at the onset of ischemia, with capsules that produced physiologically low or physiologically high 17beta-estradiol levels in serum (10 or 60 pg/mL, respectively). One week after ovariectomy, ischemia was induced. Estradiol pretreatment significantly reduced overall infarct volume compared with oil-pretreated controls (mean+/-SD: oil = 241+/-88; low = 139+/-91; high = 132+/-88 mm3); this protective effect was regionally specific to the cortex, since no protection was observed in the striatum. Baseline and ischemic regional CBF did not differ between oil and estradiol pretreated rats, as measured by laser Doppler flowmetry. Acute estradiol treatment did not protect against ischemic injury. Our finding that estradiol pretreatment reduces injury demonstrates that physiologic levels of estradiol can protect against neurodegeneration.
TL;DR: The rostral-caudal distribution of neutrophils and macrophages/microglia at 4, 6, 24, and 48 h after contusion injury to the T10 spinal cord of rat was examined.
TL;DR: The results suggest that AD pathogenesis may involve the activation of oxidant-producing inflammatory enzyme systems, including nitric oxide synthase, as well as peroxynitrite scavenger systems.
Abstract: HPLC with electrochemical array detection (HPLC-ECD) was used to quantify 3,3'-dityrosine (diTyr) and 3-nitrotyrosine (3-NO2-Tyr) in four regions of the human brain that are differentially affected in Alzheimer's disease (AD). DiTyr and 3-NO2-Tyr levels were elevated consistently in the hippocampus and neocortical regions of the AD brain and in ventricular cerebrospinal fluid (VF), reaching quantities five- to eightfold greater than mean concentrations in brain and VF of cognitively normal subjects. Uric acid, a proposed peroxynitrite scavenger, was decreased globally in the AD brain and VF. The results suggest that AD pathogenesis may involve the activation of oxidant-producing inflammatory enzyme systems, including nitric oxide synthase.
TL;DR: The results add to the evidence that arsenic ingestion increases the risk of lung and kidney cancers by finding increasing trends for kidney and lung cancer mortality with arsenic exposure.
Abstract: Background Studies in Taiwan have found dose-response relations between arsenic ingestion from drinking water and cancers of the skin, bladder, lung, kidney and liver. To investigate these associations in another population, we conducted a study in Cordoba, Argentina, which has a well-documented history of arsenic exposure from drinking water. Methods Mortality from lung, kidney, liver and skin cancers during the period 1986‐1991 in Cordoba’s 26 counties was investigated, expanding the authors’ previous analysis of bladder cancer in the province. Counties were grouped a priori into low, medium and high arsenic exposure categories based on available data. Standardized mortality ratios (SMR) were calculated using all of Argentina as the reference population. Results We found increasing trends for kidney and lung cancer mortality with arsenic exposure, with the following SMR, for men and women respectively: kidney cancer, 0.87, 1.33, 1.57 and 1.00, 1.36, 1.81; lung cancer, 0.92, 1.54, 1.77 and 1.24, 1.34, 2.16 (in all cases, P , 0.001 in trend test), similar to the previously reported bladder cancer results (0.80, 1.28, 2.14 for men, 1.22, 1.39, 1.81 for women). There was a small positive trend for liver cancer but mortality was increased in all three exposure groups. Skin cancer mortality was elevated for women only in the high exposure group, while men showed a puzzling increase in mortality in the low exposure group. Conclusions The results add to the evidence that arsenic ingestion increases the risk of lung and kidney cancers. In this study, the association between arsenic and mortality from liver and skin cancers was not clear.
TL;DR: The cyclin-dependent protein kinase encoded by CDC28 is the master regulator of cell division in the budding yeast Saccharomyces cerevisiae and the processes controlling the abundance and activity of key Cdc28 regulators, especially transcriptional and proteolytic mechanisms are discussed in detail.
Abstract: The cyclin-dependent protein kinase (CDK) encoded by CDC28 is the master regulator of cell division in the budding yeast Saccharomyces cerevisiae. By mechanisms that, for the most part, remain to be delineated, Cdc28 activity controls the timing of mitotic commitment, bud initiation, DNA replication, spindle formation, and chromosome separation. Environmental stimuli and progress through the cell cycle are monitored through checkpoint mechanisms that influence Cdc28 activity at key cell cycle stages. A vast body of information concerning how Cdc28 activity is timed and coordinated with various mitotic events has accrued. This article reviews that literature. Following an introduction to the properties of CDKs common to many eukaryotic species, the key influences on Cdc28 activity—cyclin-CKI binding and phosphorylation-dephosphorylation events—are examined. The processes controlling the abundance and activity of key Cdc28 regulators, especially transcriptional and proteolytic mechanisms, are then discussed in detail. Finally, the mechanisms by which environmental stimuli influence Cdc28 activity are summarized.
TL;DR: PTSD can be precipitated by diagnosis and treatment of breast cancer, and the PCL-C can be a cost-effective screening tool for this disorder.
Abstract: The presence of a posttraumatic stress disorder (PTSD) diagnosis in women (n = 82) diagnosed with Stage 0-IIIA breast cancer was assessed 6 to 72 months after cancer therapy. The PTSD Checklist-Civilian Version (PCL-C) and the PTSD module for the Structured Clinical Interview for DSM-IV, Nonpatient Version, PTSD module (SCID-NP-PTSD) were administered in a telephone interview. SCID-NP-PTSD results indicated prevalence rates of 6% and 4% for current and lifetime PTSD, respectively. Use of the recommended cutoff score of 50 on the PCL-C to determine diagnosis of current cancer-related PTSD resulted in a sensitivity of .60 and a specificity of .99 with 2 false-negative diagnoses. In conclusion, PTSD can be precipitated by diagnosis and treatment of breast cancer, and the PCL-C can be a cost-effective screening tool for this disorder.
TL;DR: The decrease of PE and PI, which are rich in oxidizable arachidonic and docosahexaenoic acids, but not of PC, which contains lesser amounts of these fatty acids, suggests a role for oxidative stress in the increased degradation of brain phospholipids in AD.
Abstract: Regional levels of membrane phospholipids [phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylcholine (PC)] were measured in the brain of Alzheimer's disease (AD) and control subjects. The levels of PE-derived and PI-derived total fatty acids were significantly decreased in the hippocampus of AD subjects. Here significant decreases were found in PE-derived stearic, oleic and arachidonic and docosahexaenoic acids, and in PI-derived oleic and arachidonic acids. In the inferior parietal lobule of AD subjects, significant decreases were found only in PE and those decreases were contributed by stearic, oleic and arachidonic acids. In the superior and middle temporal gyri and cerebellum of AD subjects, no significant decreases were found in PC-, PE- and PI-derived fatty acids. The decrease of PE and PI, which are rich in oxidizable arachidonic and docosahexaenoic acids, but not of PC, which contains lesser amounts of these fatty acids, suggests a role for oxidative stress in the increased degradation of brain phospholipids in AD.
TL;DR: The results show that the elements of the contractile machinery are differentially responsive to changes in the oxidation‐reduction balance of the muscle fibres.
Abstract: 1. We used intact single fibres from a mouse foot muscle to study the role of oxidation-reduction in the modulation of contractile function. 2. The oxidant hydrogen peroxide (H2O2, 100-300 microM) for brief periods did not change myoplasmic Ca2+ concentrations ([Ca2+]i) during submaximal tetani. However, force increased by 27 % during the same contractions. 3. The effects of H2O2 were time dependent. Prolonged exposures resulted in increased resting and tetanic [Ca2+]i, while force was significantly diminished. The force decline was mainly due to reduced myofibrillar Ca2+ sensitivity. There was also evidence of altered sarcoplasmic reticulum (SR) function: passive Ca2+ leak was increased and Ca2+ uptake was decreased. 4. The reductant dithiothreitol (DTT, 0.5-1 mM) did not change tetanic [Ca2+]i, but decreased force by over 40 %. This was completely reversed by subsequent incubations with H2O2. The force decline induced by prolonged exposure to H2O2 was reversed by subsequent exposure to DTT. 5. These results show that the elements of the contractile machinery are differentially responsive to changes in the oxidation-reduction balance of the muscle fibres. Myofibrillar Ca2+ sensitivity appears to be especially susceptible, while the SR functions (Ca2+ leak and uptake) are less so.