Helping to find the "hidden cancer".
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Alberta↗
Biomedical subjects
J Irwin
Publications and source records attributed to J Irwin.
One aid or two?--more visits please!
A prospective trial of hearing aid provision was undertaken to define factors which might be used to allow hearing aids to be fitted optimally. Patients referred for the provision of a hearing aid were studied prospectively at each of five visits when they were questioned by means of a proforma. Fifty-six patients completed the trial and gave adequate responses for analysis. No audiometric or symptomatic criteria were found to be of use in predicting the final choice of hearing aid combination. It may be that initial sequential monaural aiding leads to a higher uptake of binaural aids in the long term. Patients valued multiple visits to the clinic and sequential trials of monaural aiding, the majority felt that binaural aids should be tried.
Adult↗
Stressor-induced alterations of natural killer cell activity and central catecholamines in mice.
Natural killer (NK) cell cytotoxicity was determined at various intervals (0.5, 24 or 48 h) following exposure to uncontrollable footshock in 3 strains of mice. Stressor application provoked reductions of NK activity, but the time course of the NK changes varied across strains. Whereas NK cytotoxicity was markedly reduced in C57BL/6J mice 0.5-48 h following stressor exposure, this effect was delayed in C3H/HeJ mice, being evident 24-48 h following stressor application. In BALB/cByJ mice, NK activity was significantly reduced 24 h after footshock, but in contrast to the other strains returned to control levels within 48 h of stressor exposure. Central NE and DA concentrations and activity were influenced by the stressor treatment in a strain-dependent fashion. However, the relationship between the central amine variations and the alterations of NK cytotoxicity associated with the stressor was limited.
3,4-Dihydroxyphenylacetic Acid↗
Behavioral characterization of intracranial self-stimulation from mesolimbic, mesocortical, nigrostriatal, hypothalamic and extra-hypothalamic sites in the non-inbred CD-1 mouse strain.
A behavioral analysis of intracranial self-stimulation (ICSS) was provided for mesolimbic/mesocortical, nigrostriatal, hypothalamic and extrahypothalamic sites in the CD-1 mouse. Robust responding and rapid acquisition of mesocortical ICSS appeared dorsally along notably fluorescent sites in rostral and caudal planes. ICSS was diminished demonstrably in medial and ventral positions in posterior planes. Mesolimbic ICSS from the medial and ventral nucleus accumbens (Nas), was accompanied by significant elevations in locomotor activity, corresponding to regions of dopamine (DA) and cholecystokinin co-localization. Stimulation-induced seizures appeared from both the Nas as well as the mesocortex. ICSS from the ventral tegmental field (VTA) was evident along its medial, lateral and dorsal borders with longer pulse durations more likely to elicit responding. Seizure activity was absent from the VTA. Striatal ICSS was conspicuously poor in dorsal and medial locations; regions presumably devoid of tegmental innervation. ICSS emerged from both the ventrocaudal and anteromedial striatum; regions linked to innervation by the dorsolateral and ventromedial VTA. The red nucleus, a previously neglected self-stimulation site supported marked responding for ICSS. Regions supporting rubral ICSS were correlated with thalamic innervation sites; notably the ventrolateral thalamic nucleus and the parafascicular nucleus, regions found to support ICSS. The substantia nigra supported high rates of responding for ICSS when electrode placement was restricted to the dorsomedial portion of the pars compacta. Electrode deviations lateral and dorsal to the substantia nigra pars medialis induced a progressive decline in responding. Hypothalamic sites were found to support significant responding for ICSS, although such performance was frequently associated with seizure induction. Taken together these data (1) provide the first behavioral analysis of ICSS in mice responding from previously unexamined DA sites in the mesolimbic (e.g. VTA, Nas) and nigrostriatal systems (e.g. caudate, red nucleus) (2) suggest an anatomical reconsideration of the assumptions underlying the elicitation of ICSS from the frontal cortex (3) suggest that the neural circuitry underlying thalamic, caudate, rubral and frontal cortical ICSS are interrelated and (4) suggest that the Nas and the frontal cortex, like the hypothalamus, in the mouse appear to be particularly sensitive to stimulation-induced seizures.
Animals↗
The effect of antidepressants on immune function in mice.
Depression or its treatment with antidepressant agents may have an impact on the normal function of the immune system. To address this issue in an animal model, we studied the effect of maprotiline and desipramine treatment of mice on several immunological activities associated with host resistance to cancer and infections. Our results indicate that chronic maprotiline treatment depressed natural killer (NK) cell function, measured in vivo as clearance of tumor cells from the lung or in vitro as cytolytic activity. Cell-mediated immunity, measured as delayed hypersensitivity in vivo and T and B lymphocyte proliferative responses in vitro, was largely unaffected. Although antidepressant toxicity at high concentrations inhibited T, B, and NK cell activity, it is unlikely that this is the basis for the in vivo effects.
Animals↗
Sudden death due to diabetic ketoacidosis.
Two obese women not known to be diabetic died suddenly of diabetic ketoacidosis (DKA). To our knowledge, sudden unexpected death due to DKA has not been reported as the only manifestation of diabetes mellitus. The investigation of sudden death in patients with risk factors for diabetes, especially in the absence of significant disease of the internal organs, should include determination of vitreous glucose and ketones.
Adult↗
Variations of norepinephrine concentrations following chronic stressor application.
Exposure to acute uncontrollable footshock increased utilization of central norepinephrine (NE), and in some brain regions, most notably the hypothalamus, a decline in amine concentrations was induced. Utilization of NE was likewise increased in mice exposed to footshock on 14 consecutive days, but the NE reduction was not evident, suggesting that the chronic stressor provoked a compensatory increase of amine synthesis. In mice that were decapitated 24 hr after the chronic shock regimen, NE concentrations exceeded those of nonshocked animals or mice decapitated immediately after the last shock session, possibly reflecting a sustained increase of amine synthesis. The altered NE utilization and concentrations associated with chronic footshock were evident irrespective of whether the stressor was applied on a predictable schedule or on an intermittent basis, although the former treatment was somewhat more effective in increasing concentrations and utilization.
Animals↗
Behavioral influences on the immune system: stress and conditioning.
Several investigators have demonstrated that immune responses may be subject to classical conditioning processes. Conditioning effects in both cell-mediated and humoral immune responses have been reported. Strong evidence for behavioral effects on immune responses has been provided by studies of stress-induced immunosuppression. Stressors may increase morbidity due to infectious agents, depress antibody responses, inhibit lymphocyte reactions, and attenuate several other cell-mediated immune functions. In our studies, acute inescapable footshock inhibited natural killer cell (NK) activity in CD-1 and C57BL/6J mice, but not in DBA/2J mice. Genetic factors play a role in the immunological responses to stress. In contrast to the effects of acute stress, NK activity of mice exposed to chronic inescapable footshock was not reduced from control levels. Adaptive processes may be invoked during repeated stress exposure, thereby limiting the potentially damaging effects of the stressor.
Animals↗
Sensitization of norepinephrine activity following acute and chronic footshock.
Acute inescapable shock provokes an increase of norepinephrine (NE) utilization, leading to transient reductions of amine concentrations. In contrast, increased amine levels are evident after chronic shock, apparently because of a compensatory increase in synthesis. In acutely shocked animals subsequent re-exposure to even a limited amount of shock reinduced the NE reduction, whereas in chronically shocked mice a comparable re-exposure stressor increased amine levels and utilization. It is suggested that the mechanisms responsible for the amine release in acutely stressed animals, as well as those mechanisms subserving the increased amine levels evident after chronic stressor application, may be subject to conditioning or sensitization processes.
Animals↗
Central norepinephrine and plasma corticosterone following acute and chronic stressors: influence of social isolation and handling.
Exposure to acute inescapable shock resulted in a decline of hypothalamic norepinephrine (NE), and an increase of plasma corticosterone concentrations. With repeated application of the stressor over 15 successive days the reduction of NE was eliminated and concentrations of the amine actually exceeded those of control animals. In contrast to the NE variations, plasma corticosterone concentrations were elevated irrespective of whether mice received a single or repeated sessions of inescapable footshock. Moreover, unlike NE concentrations, handling mice on successive days in the absence of the shock treatment was sufficient to provoke a modest, but reliable increase of corticosterone concentrations. It is suggested that the hypothalamic NE and plasma corticosterone changes may be reflective of different attributes of the stressor or are subserved by different mechanisms. It is suggested that variations in both these systems represent adaptive changes to meet environmental demands.
Animals↗
A mammalian cell variant in which 3-aminobenzamide does not potentiate the cytotoxicity of dimethyl sulphate.
Variants of mouse leukaemia L1210 cells have been isolated in which cytotoxicity to dimethyl sulphate is not fully potentiated by ADP-ribosyl transferase inhibitor 3-aminobenzamide, as occurs in normal L1210 cells. These variants were selected after mutagenesis by growing the cells in dimethyl sulphate and 3-aminobenzamide. The characterisation of one of these variants is described. Variant 3 cells repair low doses of DNA damage in the presence of ADP-ribosyl transferase inhibitors. The Vmax of the ADP-ribosyl transferase enzyme in these cells is only increased 35% compared to normal wild-type L1210 cells. The basal DNA ligase I activity is increased 66% above wild-type whereas DNA ligase II activity appears to be unchanged. The most striking observation, however, is that the DNA ligase II activity is not increased after dimethyl sulphate treatment as occurs in wild-type L1210 cells. It seems that by increasing DNA ligase I levels these cells can survive DNA damage in the presence of 3-aminobenzamide. This variant (mutant) provides genetic evidence for our previously published hypothesis that (ADP-ribose)n biosynthesis is required for efficient DNA repair after DNA damage by monofunctional alkylating agents, because ADP-ribosyl transferase activity regulates DNA ligase activity. This variant is the first mammalian cell reported in which DNA ligase activity is altered, as far as we are aware. In yeast, a DNA ligase mutant has a cell division cycle (cdc) phenotype. Presumably, DNA ligase is essential for DNA synthesis, repair and recombination. The present variant provides further evidence that in mammalian cells, DNA ligase II activity is related to ADP-ribosyl transferase activity.
Animals↗
Hearing-loss and calciferol deficiency.
Vitamin D (calciferol) deficiency has recently been claimed to cause cochlear hearing-loss (Brookes and Morrison, 1981; Brookes, 1983, 1984). In view of the therapeutic and pathophysiological implications of this finding, a confirmatory study was undertaken in the Department of Neuro-otology at The Royal National Throat, Nose and Ear Hospital. Screening of 112 consecutive new referrals revealed 32 patients with biochemical abnormalities compatible with vitamin D deficiency. Of these, 26 agreed to serum vitamin D assay and normal values were obtained in all of these cases. This study does not support the claim that vitamin D deficiency is a cause of hearing-loss.
Adult↗
Brain stem signs in acute cervical cord trauma.
Four cases are reported which illustrate mechanisms by which patients with cervical cord trauma may develop signs of acute brain stem damage. Two patients suffered vertebro-basilar ischaemia as a result of trauma to the vertebral arteries. The remaining two patients developed cavitating lesions within the cervical cord which later dissected rostrally into the brain stem.
Brain Stem↗
Audiological rehabilitation of patients with brainstem disorders.
A brief account is given of the course of rehabilitation of three patients with severe brainstem injuries. Particular use has been made of synthetic speech pattern assessment procedures which have been integrated into the management model of Goldstein and Stephens (1981). The use of speech stimuli of controllable simplicity has two main clinical benefits: the early course of re-acquisition can be examined analytically, second, aspects of speech receptive and productive rehabilitation can be facilitated. Re-acquisition of perceptive ability in some of these patients may follow a progression from simple to complex acoustic pattern contrasts and this may provide an effective basis for future techniques of rehabilitation.
Adult↗
Upper genital tract abnormalities and pregnancy outcome in diethylstilbestrol-exposed progeny.
Previous studies have suggested that there is an association between genital tract abnormalities and pregnancy outcome in women exposed to diethylstilbestrol (DES) in utero. In a collaborative study, 676 DES-exposed women had hysterosalpingographic examinations, and the findings were related to the outcome of pregnancy in 327 of these women. The findings revealed that (1) there is a considerable variation of frequency of different types of upper genital tract anomalies in women from different sources and with different motivations for enrollment in the study, (2) the presence of structural cervical changes and vaginal epithelial changes are markers for the likelihood of abnormalities in the uterine fundus, (3) women with upper genital tract abnormalities have increased odds for poor pregnancy outcome as compared to women with normal hysterosalpingographic findings, and (4) although some abnormalities were most often or consistently associated with poor pregnancy outcome, no specific changes could be related to specific types of pregnancy outcomes.
Abortion, Spontaneous↗
Alteration of exploration and the response to food associated cues after treatment with pimozide.
A series of experiments assessed the effects of pimozide on spontaneous alternation in a Y- and 8-arm radial maze, and on approach to food or cues that had previously been associated with food. Mice treated with pimozide (0.2, 0.4 and 0.8 mg/kg) displayed a dose dependent reduction of alternation performance, without engendering a perseverative tendency and apparently without affecting the course of habituation. When food deprived mice entered an arm of the maze that was baited with a food pellet they consumed the food and remained in the vicinity of the food cup. Moreover, upon retesting in the non-drug state mice still exhibited a preference for cues that had been associated with food. It seems that although pimozide at the doses tested produced a haphazard pattern of exploration, the drug did not alter the rewarding value of secondary reinforcers. Contrary to an anhedonic hypothesis, it is suggested that higher doses of pimozide may actually increase, rather than decrease, the saliency of biologically significant stimuli.
Animals↗
Cross-stressor immunization against the behavioral deficits introduced by uncontrollable shock.
Exposure to inescapable shock disrupted performance in both shock- and water-escape tasks. These deficits were prevented in mice that were previously trained in the same task. However, an asymmetrical immunization effect was seen in a cross-stressor paradigm. Whereas deficits of water-escape performance engendered by inescapable shock were prevented by prior shock-escape training, the deficits of shock-escape performance were not eliminated by prior water-escape training. Evidently, the immunization effect occurs when initial training and subsequent testing are conducted in the same task, or when the initial training and uncontrollable stress session involve the same aversive stimulus. Norepinephrine determinations revealed that reductions of the amine introduced by inescapable shock were unaffected by prior shock-escape training and were enhanced by prior exposure to the stress of water immersion. Thus, although the performance deficit introduced by inescapable shock may be related to variations of norepinephrine, the immunization effect probably was unrelated to alterations of this transmitter. Rather, the data provisionally suggested that the immunization stems from two independent factors: Namely, initially training animals in an active escape task may (a) disrupt subsequent learning that the inescapable stress actually is uncontrollable and (b) limit the influence of the motor deficits introduced by uncontrollable shock on subsequent escape performance.
Animals↗