Biomedical subjects

Larry F Hughes

Publications and source records attributed to Larry F Hughes.

27 records · Page 2Linked to original sources

PubMed2003

Age-related synaptic changes in the anteroventral cochlear nucleus of Fischer-344 rats.

Previous studies have demonstrated age-related decreases in the transmitters glycine and glutamate in the cochlear nucleus (CN) of the Fischer-344 (F344) rat, along with declining levels of binding for glycine receptors. The purpose of this study was to evaluate structural correlates to the transmitter and receptor losses that accompany aging in the anteroventral CN (AVCN). Thin sections were obtained from the middle-frequency area of the right AVCNs from five 3-month-, four 19-month-, and five 28-month-old F344 rats. Montages were constructed from electron micrographs taken of several sites in each AVCN section. The presynaptic terminals were classified by vesicle type and postsynaptic target, and their perimeters and synaptic lengths were traced using morphometry software. The calibers of all dendritic profiles were also measured, and cell counts were performed on semi-thin sections. The data were compared among the three age groups using analysis of variance followed by Tukey's Honestly Significant Difference for pairwise comparisons. There were significant age-related decreases in the size of terminals contacting small-caliber (<2 microm) dendrites. Dendrites of this size comprised the largest percentage of dendrites in the AVCN. On these targets, round and pleomorphic-vesicle terminals were reduced in volume by nearly 44% and 24%, respectively, in 28-month olds when compared to the 3-month olds. On the other hand, the densities and numbers of synaptic terminals and dendritic profiles did not differ among age groups, and no neuronal losses were evident in the older animals. Also, there were no detectable changes in synaptic area among groups. The decrease in terminal size may be related to age-associated reductions in neurotransmitter levels previously described in the F344 CN. The observations presented here contrast with those previously described in the inferior colliculus (IC), in which there were significant age-related losses of synaptic terminals and dendrites, but no change in the size of synaptic terminals. The lack of synaptic and dendritic losses suggests that the structural connectivity of the rat AVCN remains relatively intact during aging, which is interesting in light of the synaptic and dendritic changes evident in the IC, a major target of its projections.

Age Factors↗

PubMed2003

Using a Rasch scale to characterize the clinical features of patients with a clinical diagnosis of uncertain, probable, or possible Alzheimer disease at intake.

OBJECTIVE: This study examined the clinical features of patients with clinical diagnoses of probable Alzheimer disease (AD), possible AD, and uncertain. DESIGN: Case study comparing three groups of AD patients diagnosed at their initial visit to an Alzheimer outpatient clinic. SETTING: Southern Illinois University School of Medicine's Center for Alzheimer Disease and Related Disorders (CADRD) assessment sites (20) in rural Illinois. PARTICIPANTS: 300 patients assessed at CADRD between January 1, 1994 and July 1, 2000. MEASUREMENTS: Patients were given an extensive clinical battery consisting of physical and neurologic examination, mental status testing including the Mini-Mental State Exam (MMSE), Short Blessed Dementia (SBD) and Blessed Dementia Scale (ADL), medical history evaluation, and laboratory tests. Other data included age at visit, gender, and medical history variables. RESULTS: Mean MMSE, SBD, and ADL scores differed significantly between groups (p's < 0.01). In all three cognitive tests, the uncertain group was the least impaired while the probable AD group was the most impaired. A Rasch model indicated that only the cognitive measures were useful in discriminating between the three diagnostic groups. CONCLUSION: In general, probable AD patients were distinguished from possible AD patients by the severity of their dementia as measured by the MMSE, ADL and SBD as well as Hachinski-Ischemic Score (HIS) scores. A Rasch model did well at predicting group membership based upon dementia measures only. The uncertain group differed from the AD groups in age and dementia severity as measured by the MMSE, ADL and SBD. Noting differences between this and previous studies, we speculate disparity may be related to differences in population ethnicity.

Activities of Daily Living↗

PubMed2003

Glutathione ester but not glutathione protects against cisplatin-induced ototoxicity in a rat model.

Glutathione (GSH) provides an important antioxidant and detoxification pathway. We tested to determine if direct administration of GSH or GSH ester could reduce cisplatin- (CDDP) induced ototoxicity. We tested eight groups of five rats each: a control group, a group receiving 16 mg/kg ip CDDP infused over 30 minutes, and six groups receiving either GSH or GSH ester at 500, 1000, or 1500 mg/kg intraperitoneally 30 minutes prior to 16 mg/kg CDDP. Auditory brainstem response thresholds were measured for click and tone-burst stimuli at baseline and 3 days later. Outer hair cell (OHC) loss was measured for the apical, middle and basal turns. The 500 mg/kg GSH ester reduced hearing loss and OHC loss, but protection decreased as dosage increased, suggesting possible toxicity. GSH was not significantly protective. The best GSH ester protection was less than we have previously reported with D-methionine.

Acoustic Stimulation↗

PubMed2003

Antioxidant enzyme levels inversely covary with hearing loss after amikacin treatment.

This study's purpose was to determine if a correlation exists between cochlear antioxidant activity changes and auditory function after induction of amino-glycoside (AG) ototoxicity. Two groups of five 250-350 g albino guinea pigs served as subjects. For 28 days, albino guinea pigs were administered either 200 mg/kg/day amikacin, or saline subcutaneously. Auditory brainstem response testing was performed prior to the first injection and again before sacrifice, 28 days later. Cochleae were harvested and superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase activities and malondialdehyde levels were measured. All antioxidant enzymes had significantly lower activity in the amikacin group (p < or = 0.05) than in the control group. The difference in cochlear antioxidant enzyme activity between groups inversely correlated significantly with the change in ABR thresholds. The greatest correlation was for the high frequencies, which are most affected by aminoglycosides. This study demonstrates that antioxidant enzyme activity and amikacin-induced hearing loss significantly covary.

Amikacin↗

PubMed2003

The effect of D-methionine on cochlear oxidative state with and without cisplatin administration: mechanisms of otoprotection.

D-methionine (D-met) protects against cisplatin (CDDP) ototoxicity, but the mechanisms are not well understood. This study investigated D-met protection of cochlear oxidative state as measured by superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), and malondiadehyde (MDA) levels. The design comprised four groups of five rats each: (1) a saline control group, (2) a CDDP-only-treated group, (3) a CDDP group pretreated with D-met, and (4) a group receiving only D-met. Auditory brainstem response testing (ABR) was performed before and 3 days after injection. CDDP alone caused marked hearing loss; significantly reduced SOD, CAT, and GR levels; and increased MDA levels, but D-met pretreatment protected against these changes. These studies suggest that D-met protects cochlear antioxidant enzyme levels from CDDP-induced decrements. The excellent correlation of enzyme levels with hearing loss and weight loss suggests that antioxidant enzyme level protection may underlie, at least in part, D-met's otoprotective action.

Animals↗

PubMed2002

The Mini-Mental State exam may help in the differentiation of dementia with Lewy bodies and Alzheimer's disease.

OBJECTIVE: Since patients with dementia with Lewy bodies (DLB) tend to have greater impairment of attention and construction and better memory ability on neuropsychological tests than patients with Alzheimer's disease (AD), we determined if the items that measure attention, memory, and construction in the Mini-Mental State Examination (MMSE) help to distinguish DLB from AD early in the course of the dementia. DESIGN: We retrospectively studied the first available MMSE exam for each of our patients with DLB or AD and compared their MMSE subscores for attention, memory, and construction. SETTING: A university dementia brain bank in central Illinois, USA. PATIENTS: All patients with neuropathologically-proven DLB or AD with MMSE scores > or =13. RESULTS: We identified 17 DLB and 27 AD patients for whom we had MMSE exams. The attention and construction subtest scores of the DLB group were worse (p=0.0071 and p=0.0038, respectively) than those of the AD group. The memory subscores of the DLB group were better, although the difference did not reach statistical significance (p=0.22). When a mathematical equation was used to combine the three subscores with equal weighting (Attention-5/3Memory+5.Construction), the scores of the DLB group were worse (p=0.00007). Using this equation, a score less than 5 points was associated with DLB with a sensitivity of 0.82 (95% Confidence Interval (CI)=0.57-0.96) and a specificity of 0.81 (95% CI=0.62-0.94). CONCLUSIONS: Our findings support the work of others regarding the relative neuropsychological impairments of DLB and AD and indicate that the MMSE may be helpful in the differentiation of DLB and AD.

Aged↗

PubMed2002

GABAergic inputs shape responses to amplitude modulated stimuli in the inferior colliculus.

The inferior colliculus (IC) is an important auditory processing center receiving inputs from lower brainstem nuclei, higher auditory and nonauditory structures, and contralateral IC. The IC, along with other auditory structures, is involved in coding information about the envelope of complex signals. Biologically relevant acoustic signals, including animal vocalizations and speech, are spectrally and temporally complex and display amplitude and frequency variations over time. Certain IC neurons respond selectively over a narrow range of modulation frequencies to sinusoidally amplitude modulated (SAM) stimuli. Responses to SAM stimuli can be measured in terms of discharge rate, with rate plotted against the modulation frequency to generate rate modulation transfer functions (rMTF). A role for the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), in shaping selective responses to SAM stimuli has been suggested. The present study examined the role of GABA in shaping responses to SAM stimuli in the IC of anesthetized chinchilla. Responses from 94 IC neurons were obtained before, during and after iontophoretic application of the GABA(A) receptor antagonist bicuculline methiodide. Complete responses to SAM stimuli were obtained from 55 extensively tested neurons, displaying band-pass (38) and low-pass rMTFs (17). For neurons showing band-pass rMTFs, GABA(A) receptor blockade selectively increased discharge rate at low modulation frequencies for 14 units, increased discharge near the best modulation frequency for 12 units. For neurons showing low-pass rMTFs, GABA(A) receptor blockade selectively increased discharge rate at low modulation frequencies for nine units. GABA(A) receptor blockade consistently reduced peak modulation gain, producing low-pass gain functions in a subset of IC neurons. In support of previous findings suggesting that selective temporal responses to SAM stimuli are coded in lower brainstem nuclei, temporal responses to SAM stimuli were relatively unaffected by GABA(A) receptor blockade. These findings support a role for GABA in shaping selective rate responses to SAM stimuli for a subset of chinchilla IC neurons.

Acoustic Stimulation↗

PubMed2002

Hsp70 in the inferior colliculus of Fischer-344 rats: effects of age and acoustic stress.

Heat shock proteins 72 and 73 (hsp72 and hsp73) were studied in the inferior colliculus (IC) of Fischer-344 rats to determine if their levels are altered during normal aging and following exposure to intense acoustic noise. Three age groups of rats (3, 18, and 25 months) were exposed to ambient sound (control) or broad-band noise at 108 dB sound pressure level (0.0004 dyn/cm2) for 30 min. Western blotting procedures were used to measure hsp72 and hsp73 in ICs and cerebella (positive control). Immunohistochemistry was performed using 3-month olds to study the localization patterns of hsp72 and hsp73 in both structures. The IC and cerebellum exhibited immunolabeling over neuronal somata and proximal dendrites. Ambient levels of hsp72 in supernatants from aged rats were reduced 56.5%+/-7.8% in the IC relative to 3-month olds. This decrease may render the IC more susceptible to stress-related damage. An increase in constitutive hsp73 (350.7%+/-70.4%) was observed in IC pellet fractions from animals exposed to the 108-dB noise when compared to the ambient-noise controls, suggestive of a lipoprotective role for hsp73. This elevation was consistent across age groups. No noise-induced changes in hsp72 were detectable in the IC, indicating that loud sounds may not be an appropriate stimulus for hsp72 induction in this structure.

Aging↗

PubMed2002

Assessing olfactory abilities with the University of Pennsylvania smell identification test: a Rasch scaling approach.

The strategy of delaying or retarding the progression of Alzheimer's disease requires early diagnosis and treatment. Previous research indicates that measurement of changes in olfaction and cognition will play an important role in the early detection of AD and in the monitoring of therapy effectiveness. Using the data of 177 subjects, our objective was to study the measurement properties of the University of Pennsylvania Smell Identification Test (UPSIT) using a Rasch scaling framework. The results indicate that the UPSIT can yield a linear, unbiased, and unidimensional Rasch measure of human smell recognition abilities. As expected, olfactory recognition ability decreased with age, and at the rate of about 0.05 Logits per year. Also, Alzheimer's patients showed a decrease in smell recognition equivalent to that experienced by healthy subjects over the course of 30 years. Hormone replacement therapy was not found to affect healthy women's olfactory recognition ability. Additional diagnostic information can be extracted from the analysis of incorrect responses patterns that is relevant to group membership.

Aged↗