Biomedical subjects

C R Mitchell

Publications and source records attributed to C R Mitchell.

At least 19 recordsLinked to original sources

PubMed2002

Effect of subsequent acute-dose irradiation on cell survival in vitro following low dose-rate exposures.

PURPOSE: Following acute irradiation, excess radiosensitivity is generally seen at doses <1 Gy, a phenomenon termed "low-dose hyper-radiosensitivity" (HRS). A very strong, HRS-like inverse dose-rate effect has also been described following continuous low dose-rate (LDR) irradiation at <30 cGy h(-1). We report on the sequential irradiation of a cell line by such LDR exposures followed by low acute doses, where either treatment individually would elicit a hypersensitive response. The aim was to determine if a prior LDR exposure would remove the HRS normally seen in response to very small acute radiation doses. MATERIALS AND METHODS: T98G human glioma cells were given single continuous LDR exposures of 5-60 cGy h(-1) using a (60)Co gamma-source. At intervals of 0 or 4 h following LDR irradiation, cells were further irradiated with a range of acute doses using 240-kVp X-rays. The response to the combined treatment was assessed using high-precision clonogenic cell survival assays, and the amount of HRS at acute doses <1 Gy was determined. RESULTS: LDR at > or = 60 cGy h(-1) to total doses up to 5 Gy in asynchronously growing cells did not remove HRS in the subsequent acute-dose survival curve. In confluent cultures, subsequent acute-dose HRS was not present after an LDR dose of 5 Gy at either 60 or 30 cGy h(-1), but returned if a 4-h interval was left between LDR and acute-dose irradiation. In confluent cultures, acute-dose HRS remained for LDR treatments at 5 or 10 cGy h(-1) or if the total dose was 2 Gy. Taking all cultures and dose-rates together, the "degree" of acute-dose HRS, as measured by alpha(s), was significantly greater in cells irradiated at LDR to a total dose of 2 than of 5Gy. CONCLUSIONS: Initial LDR exposure can affect a subsequent HRS response. HRS is reduced after LDR exposures at greater dose intensity, but can recover again within 4 h of completion of LDR exposure. This suggests that processes determining increased resistance to small acute doses (removal of HRS) might be governed by the level of repairable DNA lesions.

Cell Survival↗

PubMed2002

Evidence for the involvement of DNA-dependent protein kinase in the phenomena of low dose hyper-radiosensitivity and increased radioresistance.

PURPOSE: To investigate the role of DNA-dependent protein kinase (DNA-PK) in the phenomena of low dose hyper-radiosensitivity (HRS) and increased radioresistance (IRR) using the genetically related M059 cell lines of disparate PRKDC status. MATERIALS AND METHODS: Clonogenic survival was measured for the three cell lines following low doses of X-irradiation using a flowactivated cell sorting (FACS) plating technique. The presence of PRKDC, G22p1 and Xrcc5 proteins was determined by Western blotting and a kinase assay used to measure DNA-PK complex activity. RESULTS: The survival responses for the three cell lines over the 0-0.3Gy dose range were comparable, but differences in radiosensitivity were evident at doses >0.4Gy. M059K and M059J/Fus1 cells (both PRKDC competent) exhibited marked HRS/IRR responses, albeit to different extents. M059J cells (PRKDC incompetent) were extremely radiosensitive exhibiting a linear survival curve with no evidence of IRR. The presence of IRR was coincident with the presence of PRKDC protein and functional DNA-PK activity. CONCLUSIONS: HRS is a response that is independent of DNA-PK activity. In contrast, IRR showed a dependence on the presence of PRKDC protein and functional DNA-PK activity. These data support a role for DNA-PK activity in the IRR response.

Blotting, Western↗

PubMed2000

Twenty-stimulus train for rapid acquisition of auditory brainstem responses in humans.

This study addressed the clinical need to obtain frequency-specific auditory brainstem responses (ABRs) more rapidly than is currently possible. ABRs were obtained from 20 subjects using two different methods: a conventional method with tone bursts presented singly and a multiple-stimulus method using a train of 20 tone bursts. For both methods, tone bursts were presented at frequencies 1, 2, 4, and 8 kHz, shaped with a Blackman-Harris window and having intensity levels up to 105 dB peak equivalent sound pressure level (peSPL). The single tone bursts were presented at a 17.2/sec repetition rate. The 20 tone-burst train used the four frequencies at five intensities each and a repetition rate of 3.7/sec (separations between tone bursts of 9-12 msec, with 77 msec off-time between trains). Mean latencies and mean amplitudes for wave V were compared using t-tests for each of 12 conditions (four frequencies, each at the three highest output levels). For latency, only one comparison was significantly different (2 kHz, 77 dB peSPL). Similarly, only one comparison was significant for amplitude (2 kHz, 97 dB peSPL). There was, however, a trend for the tone bursts presented in trains to have longer latencies and reduced amplitudes compared to the respective responses for the single tone-burst condition. These results indicate the presence of some response adaptation when tone bursts are presented in a train. The use of a properly designed stimulus train can result in a significant time savings for obtaining frequency-specific ABRs as compared with single tone-burst presentations.

Adult↗

PubMed1998

Failure of elevated heat shock protein 70 antibodies to alter cochlear function in mice.

Heat shock protein 70 (HSP70) has been suggested as the putative cochlear antigen underlying a proposed autoimmune etiology in certain cases of Meniere's disease and idiopathic hearing loss. To determine if antibodies to this cellular protein are capable of altering cochlear function, BALB/c (N= 3) and CBA/J (N= 9) mice were inoculated with bovine HSP70 by intraperitoneal injections (10 microg in saline) every 10 days for 7 or 10 months, respectively. An equal number of control mice were injected with PBS according to the same schedule. ABR thresholds at 4, 8, 16, and 32 kHz in the HSP70-inoculated mice did not change over the 10 month period and were similar to saline controls. Furthermore, serum immune complexes and antinuclear antibodies did not increase over the inoculation period. ELISA analysis demonstrated the mice created antibodies to the foreign HSP70, but these apparently caused no abnormalities in the auditory or immune systems. It was concluded that foreign HSP70 is antigenic and inoculation with it will raise antibodies, but these antibodies were neither immunopathogenic nor cochleopathic. Therefore, these findings do not support current theories that elevated anti-HSP70 antibodies are the underlying cause of hearing loss in patients with such antibodies present.

Animals↗

PubMed1997

Otitis media incidence and impact on the auditory brain stem response in lipopolysaccharide-nonresponsive C3H/HeJ mice.

Although mice of the C3H strain normally respond to bacterial lipopolysaccharide with appropriate immune system activation, mice of the C3H/HeJ substrain do not because of a gene defect. This suggests they may be more susceptible to opportunistic bacterial infections and more likely to have otitis media than a normally responding substrain, such as the C3H/HeSnJ. Therefore these two substrains were evaluated for incidence of spontaneous middle ear disease at 2, 4, 6, 10, 12, 15, and 18 months of age. Auditory brain stem response audiometry to pure tones of 4, 8, 16, 24, and 32 kHz was performed to establish the impact of middle ear disease on auditory function. None of the lipopolysaccharide-responsive C3H/HeSnJ mice demonstrated middle ear disease. However, middle ear disease was present in 33% of the C3H/HeJ mice. The conductive loss caused by the otitis media resulted in auditory brain stem response threshold shifts of 15 to 40 dB SPL, lowered peak amplitudes, and increased latencies. Reduced lipopolysaccharide responsiveness by C3H/HeJ mice makes them less capable of reacting immunologically to bacterial infection and presumably underlies the failure to clear middle ear disease. The C3H/HeJ mouse may provide a valuable model in which to study lipopolysaccharide biologic activity and related middle ear inflammatory or immune mechanisms.

Age Factors↗

PubMed1995

Psychophysical tuning curves in subjects with tinnitus suggest outer hair cell lesions.

A study by Penner (J Speech Hear Res 1980;23:779-86) found evidence for impaired lateral suppression in subjects with tinnitus and sensorineural hearing loss. If lateral suppression is related to tuning curve sharpness and lateral suppression is impaired, the shape of the tuning curve should be affected. The purpose of this study was to determine whether subjects with tinnitus have psychophysical tuning curves that are different from those of subjects without tinnitus. Psychophysical tuning curves and hearing thresholds were obtained from 18 subjects, 7 with tinnitus and 11 without tinnitus. Only subjects with normal audiograms (through 8 kHz) were selected for this study. In subjects with tinnitus psychophysical tuning curves were obtained in the region pitch-matched to their tinnitus. In nontinnitus subjects psychophysical tuning curves were determined at the same frequencies as for the tinnitus subjects in a yoked-control design. The slopes of the tails and tips and the Q10 and other measures were calculated for each tuning curve. The psychophysical tuning curves in subjects with tinnitus were significantly different (0.01 level) from those of control subjects and often had hypersensitive tails and some elevated tips. These shapes of tuning curves are consistent with cochlear lesions involving the loss of outer hair cells without damage to the inner hair cells or nerve fibers.

Adolescent↗

PubMed1994

Paired tone-burst study of auditory brainstem response adaptation in guinea pigs: implications for development of multiple-stimulus methods.

In clinical testing using auditory evoked potentials, the practical length of a test session is limited. Thus, the amount of information that can be obtained during a routine test session is limited in electrocochleography and auditory brainstem testing. Attempts to obtain more information within a test session by increasing the stimulus repetition rate yields adapted responses. Multiple-stimulus method that present sequences of stimuli at different frequencies and intensities can increase the efficiency of data collection while avoiding adaptation. This study was designed to investigate rapid adaptation of these early responses to enable more efficient data acquisition using multiple stimuli. Five experiments in guinea pigs using single and paired tone-burst stimuli are described. The intrapair time, frequency, and intensity were varied to determine when adaptation, measured by a latency delay, occurred. The effects of adaptation on waves I through IV are described. The differences in stimulus parameters that avoid adaptation can be determined from these experiments.

Acoustic Stimulation↗

PubMed1994

Multiple-stimulus method for rapid collection of auditory brainstem responses using high-frequency (> or = 8 kHz) tone bursts.

Auditory brainstem responses (ABR) to high-frequency (> or = 8 kHz) tone-burst stimuli have shown potential for objective early detection of ototoxicity. In the case of ill, unresponsive, or otherwise difficult-to-test individuals, the patient group for whom this test is targeted, a threshold-seeking process can be too lengthy. A new method is described for obtaining responses to several high-frequency tone bursts in the same amount of time as that used in obtaining a single responses. Using 10 normal-hearing subjects, four high-frequency tone-burst stimuli (14, 12, 10, and 8 kHz) were presented singly, then in a multiple-stimulus sequence with onsets separated by 10 msec. Wave V response latencies from the multiple-stimulus sequences are compared to those presented singly, with small but statistically significant longer latencies observed for all stimuli following the initial stimulus (14 kHz) in the multiple sequence. Test-retest reliability was comparable between multiple and single conditions. These findings support the development of this technique for clinical auditory monitoring.

Acoustic Stimulation↗

PubMed1993

Measuring tinnitus parameters: loudness, pitch, and maskability.

Improved procedures have been developed for obtaining hearing thresholds, loudness matches, pitch matches, and masking curves of tinnitus. Computer programs enable all of these measures to be obtained in a single session. These measures have been obtained in tinnitus and nontinnitus subjects, with an external stimulus used to simulate tinnitus in nontinnitus subjects. These measures, obtained in repeated sessions, were used to determine the test-retest variability of each measure. The test-retest standard error of measurement, across-subjects, is reported, which enables changes in tinnitus to be determined. In nontinnitus subjects, the accuracy, as well as the reliability, is described.

Acoustic Stimulation↗

PubMed1992

Effects of selected process parameters on emission rates of volatile organic chemicals from carpet.

There has been increased interest over the last several years in issues related to indoor air quality. Although the factors affecting indoor air quality are recognized to be very broad, ranging from building design, operation, and ventilation to biological contamination, recent emphasis has been placed on chemical contaminants, particularly volatile organic chemicals (VOCs). New floor covering systems, including new carpets, have been identified as a potential, short-term source of VOCs in the indoor air of new or renovated buildings. This report describes an exploratory study designed to examine several manufacturing variables and their effects on VOC emission rates from new carpets. It was based on a statistical experimental design and was conducted at a single carpet mill on a full-scale production line. The outcome variable, VOC emission rate, was examined relative to selected independent variables: latex type, latex amount, makeup air into the drying oven, residence time in the drying oven, and their interactions. Significant variables were identified for a number of emission rate models. The study results suggest that there are no simple answers for easily reducing VOC emission rates, but several conclusions could be inferred from the study as to future directions to pursue.

Air Pollution, Indoor↗

PubMed1991

Rise time and center-frequency effects on auditory brainstem responses to high-frequency tone bursts.

The effects of rise time and center frequency on the auditory brainstem response (ABR) elicited by high-frequency tone bursts were examined in six normal-hearing adults. Tone bursts with rise times of 0.1, 0.25, 0.5, and 1.0 msec, duration of 2 msec, and center frequencies of 8, 10, and 12 kHz were used in this study. The absolute latencies of waves I, III, and V were obtained in all subjects, and interpeak intervals of I-III, III-V, and I-V were calculated. As would be expected, rise time significantly affected the absolute latencies of waves I, III, and V, i.e., faster rise times shortened the absolute latencies, but did not affect the interpeak latencies. The tone-burst frequency significantly affected the latency of wave I but not the later waves. No significant differences were found in reliability of the response at different rise times or frequencies, within or across sessions. An estimate of the effective bandwidth of the stimulus suggests that frequency specificity of the response is maintained with fast rise time tone-burst stimuli.

Acoustic Stimulation↗

PubMed1991

Reliability of evoked responses to high-frequency (8-14 kHz) tone bursts.

Instrumentation to evaluate the auditory brainstem response to high-frequency (8-14 kHz) tone bursts has been developed in the Auditory Research Laboratory, Portland, Oregon VA Medical Center. This system is intended to monitor the audition of patients receiving ototoxic drugs who are unresponsive to behavioral test procedures. The reliability of responses obtained with the high-frequency tone-burst system was studied in 30 normal ears. Intrasubject variability of intersession data from response waves I, III, and V to tone bursts of frequencies 8, 10, 12, and 14 kHz was not significantly different from click response variability. The results of this study demonstrate the reliability of the ABR to these high-frequency tone-burst stimuli. This technique may provide early identification of hearing loss in unresponsive subjects receiving treatment with potentially ototoxic agents, thus allowing alternative treatments to minimize or prevent communicative handicap.

Acoustic Stimulation↗

PubMed1987

Effects of improved contrast on lung-nodule detection. A clinical ROC study.

We evaluated the effects of unsharp masking and highly efficient scatter rejection on film-screen chest radiographs of cancer patients. Unsharp masking significantly improved the detectability of lung nodules and visibility of anatomic structures in poorly penetrated areas of the chest. Highly efficient scatter rejection by an improved antiscatter grid provided only modest additional benefits. The study supports the conclusion that nodule detection in poorly penetrated areas on conventional chest radiographs is limited primarily by display contrast, whereas in the well-penetrated lung fields it is limited primarily by confusing background structures, rather than inadequate contrast. A method for analyzing clinical nodule detection data by transforming the FROC data to ROC coordinates also is demonstrated.

Humans↗

PubMed1987

Evaluation of optical unsharp masking and contrast enhancement of low-scatter chest radiographs.

Conventional chest radiography poses a challenging technical problem because of its requirement for simultaneous high-contrast display and wide-latitude recording across the entire image. We developed and evaluated a method of producing chest radiographs by using a tantalum air-interspace grid for highly efficient scatter rejection, wide-latitude X-ray film for recording the low-scatter image, and a LogEtronics printer for optical unsharp masking and contrast enhancement of the recorded image (TWL technique). TWL images can be readily obtained and have excellent contrast and detail across the entire image. In comparison with a conventional technique, the TWL technique provides about a 15% improvement in image contrast in well-penetrated areas and a threefold to tenfold improvement in poorly penetrated areas. A detection study using simulated lung nodules and a chest phantom showed about 10% overall improvement in nodule detection with the TWL technique (51% vs 42%), most of which was due to improvement in detection rates in poorly penetrated areas of the chest (62% vs 26%). In well-penetrated areas, there was a decrease in detection rates (52% vs 44%) using TWL images despite measured improvements in image contrast in these areas. Possibly this was due to the observers' unfamiliarity with the reversed-contrast TWL images. Our results show the TWL technique to be valuable for improving image quality and diagnostic accuracy in chest radiography.

Data Display↗

PubMed1980