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Biomedical subjects

D Henderson

Publications and source records attributed to D Henderson.

At least 19 recordsLinked to original sources

Voltage- and Ca(2+)-activated ionic currents in acutely dissociated cells of the chick pineal gland.

Previous research on cultured chick pineal cells suggests that melatonin production is modulated by Ca2+ influx through voltage-dependent Ca2+ channels. The possible existence of other ionic currents was investigated by means of whole-cell recordings from acutely isolated cells. Several different inward and outward currents were identified. Inward currents included L-type Ca2+ currents and voltage-activated tetrodotoxin (TTX)-sensitive Na+ currents. Sodium currents have not been reported previously in pineal cells of any species. These two inward currents were present in the majority of cells. Chick pineal cells also expressed several types of voltage-dependent and Ca(2+)-dependent K+ currents that differed in voltage dependence, kinetics, and pharmacology. These included two Ca(2+)-dependent outward currents which differed in sensitivity to tetraethylammonium chloride (TEA), and at least two distinct voltage-activated K+ currents. Considerable cell-to-cell variation in the amplitude and nature of the evoked outward currents was observed. These ionic currents may be important for the regulation of melatonin synthesis and the modulation of circadian rhythmicity.

Animals

Ingestive behavior and body temperature of pigeons during long-term cold exposure.

Pigeons well adapted to living in 21 degrees C ambient temperature (T(a)) were continuously exposed to cold T(a) for 6 days (Experiment 1) or 30 days (Experiment 2). The pigeons lived on a 12:12 L:D cycle where they could obtain short access to food and water at any time in the light phase by making 12 keypeck responses. Across the two experiments, the levels of cold exposure were 6 degrees C, 1 degrees C, and 0.6 degrees C. In cold, total daily food intake increased gradually across the first few days of the exposure, and the new level of food intake was inversely related to T(a). The daily ratio of total water drunk to total food eaten averaged approximately 1.3 in 21 degrees C, fell to approximately 1.0 on day 1 of cold exposure, and remained at that level for as long as 30 days. The day-night cycle in core body temperature was not changed by cold exposure. The bimodal temporal pattern of feeding in the light phase, which is characteristic of pigeons in moderate T(a), was preserved in the cold although the absolute level of feeding activity was enhanced. An analysis of the ways individual pigeons achieved total daily food intake by combining a number of feeding episodes with an average amount eaten per episode revealed considerable variation between birds, but a relatively constant feeding style within bird over time. In the colder temperatures used, however, the pigeons all increased the number of feeding episodes per day. The results provide the first detailed analysis of cold-induced changes in ingestive behavior in the pigeon and raise several questions about the behavioral expression of cold-sensitive regulatory processes.

Animals

The effect of 'conditioning' on hearing loss from a high frequency traumatic exposure.

The role of high frequency, low level 'conditioning' exposures as moderators of hearing loss from subsequent exposure to the same noise at a higher level was studied using monaural chinchillas. All the animals in the experimental groups were exposed to an octave band noise centered at 4 kHz at 85 dB SPL for 6 h a day for 10 days. One of the experimental groups was allowed to recover for 5 days and the other was allowed to recover for 18 h, prior to the higher level exposure at 100 dB for 48 h. A third group exposed only to the higher level constituted the control group. A comparison of threshold shifts and hair cell loss after 4 weeks of recovery across the three groups revealed: (a) the 5-day recovery group incurred greater threshold shifts than the other two groups; the hair cell loss in this group was greater than in the 18-h recovery group, but the same as in the control group and (b) the 18-h recovery group incurred considerably less threshold shift as well as hair cell loss than the other two groups. The results were also compared with the results from similar exposures using low frequency noise which indicated that the base vs. apex differences in the cochlea appear to extend to the effects of 'conditioning' exposures.

Animals

Factors influencing adjustment in the families of autistic children.

This study investigated factors influencing the adjustment of families of 49 autistic children (38 boys, 11 girls) to the stress of raising an autistic child. Analysis indicated that the severity of the child's disorder (stress), mother's social support (resources), and mother's perceived locus of control (perception) were significant factors in family adjustment. In addition, evidence suggested that agency affiliation also was an unexpected, yet important factor.

Adaptation, Psychological

A cyclic GMP-activated channel in dissociated cells of the chick pineal gland.

Phototransduction in the vertebrate retina is dependent in part on a cyclic GMP-activated ionic channel in the plasma membrane of rods and cones. But other vertebrate cells are also photosensitive. Cells of the chick pineal gland have a photosensitive circadian rhythm in melatonin secretion that persists in dissociated cell culture. Exposure to light causes inhibition of melatonin secretion, and entrainment of the intrinsic circadian oscillator. Chick pinealocytes express several 'retinal' proteins, including arrestin, transducin and a protein similar to the visual pigment rhodopsin. Pinealocytes of lower vertebrates display hyperpolarizing responses to brief pulses of light. Thus it is possible that some of the mechanisms of phototransduction are similar in retinal and pineal photoreceptors. We report here the first recordings of cyclic GMP-activated channels in an extraretinal photoreceptor. Application of GMP, but not cyclic AMP, to excised inside-out patches caused activation of a 15-25 pS cationic channel. These channels may be essential for phototransduction in the chick pineal gland.

Animals

Two types of antiprogestins identified by their differential action in transcriptionally active extracts from T47D cells.

Transcriptionally active nuclear extracts from human breast carcinoma cells (T47D) were used to compare the action of progestins and several antiprogestins of the 11 beta-aryl substituted steroid series on the DNA-binding properties and the trans-activating potential of progesterone receptor (PR) in vitro. Using the gel-shift assay we identified a novel type of antiprogestin (ZK98299, type I), which in contrast to type II antiprogestins, including RU486, does not induce binding of PR to progesterone response elements (PREs). In competition experiments excess of type I antiprogestin inhibits induction of DNA binding of PR by progestins and type II antiprogestins suggesting that its binding to PR interferes with the formation of stable receptor dimers. Moreover, we demonstrate that the antagonistic action of ZK98299 can be fully mimicked in vitro by using cell-free nuclear extracts from T47D cells and a 'simple' test promoter. In contrast, type II antiprogestins known to induce certain promoters in vivo exert strong agonistic effects on in vitro transcription of the test template used.

Base Sequence

Unusual aspects of allergic bronchopulmonary fungal disease: report of two cases due to Curvularia organisms associated with allergic fungal sinusitis.

We report two cases of allergic bronchopulmonary fungal disease (ABPFD) caused by Curvularia sp and associated with allergic fungal sinusitis (AFS). Curvularia lunata was cultured in one case and Curvularia senegalensis was cultured in the other. Based on these cases and a review of the literature, we discuss unusual clinical and pathologic features that can occur in ABPFD. Unusual clinical aspects of ABPFD include associated AFS, absence of asthma, progression to Churg-Strauss angiitis and granulomatosis, concomitant hypersensitivity pneumonitis, and underlying cystic fibrosis. Atypical pathologic features that may occur in ABPFD include follicular bronchiolitis, xanthomatous bronchiolitis, limited tissue invasion, fungus balls, and association with unusual fungi. Prominent follicular bronchiolitis and xanthomatous bronchiolitis were misleading histologic features in one of our cases and led to a delay in recognition of the diagnosis. Both patients presented primarily with AFS; ABPFD was detected subsequently. This suggests that a small subset of patients with AFS may be at risk for ABPFD. The goal of this review is to increase awareness of unusual clinical and pathologic manifestations of ABPFD. It is hoped that this will result in accurate diagnosis and proper therapy, especially for patients who present with atypical features. Unusual fungal species should be considered in patients who have clinical findings compatible with ABPFD but who do not demonstrate immunologic reactivity to Aspergillus sp, especially Aspergillus fumigatus. In addition, ABPFD should be considered in patients with AFS who develop new pulmonary lesions.

Adolescent

The effect of 'conditioning' exposures on hearing loss from traumatic exposure.

The role of 'conditioning' exposures as moderators of hearing loss produced by exposure to a higher level noise was explored using chinchillas. Monaural chinchillas were exposed to an octave band of noise centered at 0.5 kHz at 95 dB for six hours/day for ten days. The subjects were allowed to recover to pre-exposure sensitivity and at five days after the last exposure they were re-exposed to the same noise at 106 dB. Thresholds recorded at various time intervals following the second exposure were compared with those recorded in a control group exposed only to the higher level noise. The experimental animals were found to have less threshold shift at all stages of recovery. Results are discussed in the light of results of other related studies and possible mechanisms involved are hypothesized.

Acoustic Stimulation

Development of resistance to hearing loss from high frequency noise.

The effect of interrupted exposure on the development of progressive resistance to hearing loss from exposure to high frequency noise was studied using monaural chinchillas. The animals were exposed to an octave band noise centered at 4 kHz at 85 dB SPL for 6 h a day for ten consecutive days. Hearing thresholds were measured using evoked potential recording before and after each exposure. Results indicated a reduction in threshold shift with repeated exposures. This reduction in threshold shift or 'toughening' was more rapid for the high frequency exposures than the 'toughening' from similar low frequency exposures.

Acoustic Stimulation

The effect of exposure level on the development of progressive resistance to noise.

The effect of exposure level on the development of progressive resistance to temporary threshold shift caused by exposures to an octave band of noise centered at 0.5 kHz was explored using chinchillas. The animals were exposed to either 85, 95 or 100 dB SPL for six hours a day for ten days. Hearing thresholds were recorded electrophysiologically, prior to and after each daily exposure. A trend toward decreasing threshold shift with increase in the number of exposures was seen at all the levels. The amount of threshold shift appeared to depend upon the level as well as the test frequency. The findings are discussed in the light of results of previous studies and possible mechanisms involved in the process of 'toughening' are hypothesized.

Adaptation, Physiological

Co-operation of progestational steroids with epidermal growth factor in activation of gene expression in mammary tumor cells.

The progesterone receptor belongs to a class of ligand binding transcription factors that regulate transcription by interacting with specific DNA sequences on hormone regulated genes. In human mammary tumor T47D cells that contain both progesterone and epidermal growth factor (EGF) receptors, the progestin-induced transactivation at various hormone regulated promoters is enhanced by EGF. The effect of EGF is rapid and does not require new protein synthesis. EGF treatment does not alter the DNA binding activity of the progesterone receptor nor does it affect the total ligand-dependent phosphorylation of this receptor. These results suggest that EGF enhances the transactivation property of the progesterone receptor through mechanisms other than those involving a direct interaction of this receptor with its cognate binding sites.

Base Sequence

Giant cell arteritis associated with pericarditis and large vessel disease.

Giant cell arteritis is well recognised to affect branches of the external carotid artery and to cause systemic symptoms, but may also involve branches of the aorta producing a clinical syndrome that may be difficult to diagnose. A patient is described who presented with limb ischaemia, pericarditis and systemic symptoms. Treatment with corticosteroids improved the systemic manifestations but not the ischaemia. The patient died of bowel infarction four months after treatment was commenced.

Aged

Impact noise: the importance of level, duration, and repetition rate.

The applicability of the equal energy hypothesis (EEH) to impact noise exposures was studied using chinchillas. Hearing thresholds were estimated by recording the evoked potentials from a chronic electrode implanted in the inferior colliculus. The animals were exposed to broadband impacts of 200-ms duration. The study was carried out in two parts. In experiment I, six exposure levels (107, 113, 119, 125, 131, and 137 dB SPL) and three repetition rates (4/s, 1/s and 1/4s) were employed. In the second experiment, the total duration of the exposure as well as the total energy were kept constant by trading level and rate. Results indicate that hearing loss resulting from exposure to impact noise does not conform to the predictions of the EEH. The permanent threshold shift as well as the hair cell loss are more or less equal across the lower peak exposure levels. However, both the hearing loss and the hair cell damage increase for exposures with higher peak levels. Furthermore, hearing loss and cochlear damage are dependent upon the rate of exposure. Thus the amount of hearing loss and hair cell damage appears to depend on the interaction of several factors including peak level, rate, and the susceptibility of the animal.

Animals

The importance of "temporal pattern" in traumatic impulse noise exposures.

The equal energy hypothesis (EEH) was evaluated for impulse noise. Specifically, the experiments evaluated the importance of the temporal distribution of impulses; the trading relation between the number of impulses and peak level and the difference between continuous and impulse noise. Monaural chinchillas were exposed to one of seven conditions. Their hearing was evaluated before, immediately after, and 30 days after the exposure. Hair cell damage was reported in the form of a cochleogram. The experiments show that the EEH is more appropriate for low-level impulse (135-dB peak); for equal amounts of energy, 150-dB impulses produce more hearing loss and hair cell damage than 135-dB impulses; for equal amounts of energy, impulses presented in rapid bursts cause less damage than impulses presented at "1/s" and 50 microseconds. Pairs of impulses presented at "1/s" produce the largest amount of damage. The results are discussed in terms of implications for the EEH.

Animals