PubMed Health⌕ Search

Biomedical subjects

J Irwin

Publications and source records attributed to J Irwin.

At least 19 recordsLinked to original sources
PubMed1995

Dietary control and tissue specific expression of branched-chain alpha-ketoacid dehydrogenase kinase.

The branched-chain alpha-ketoacid dehydrogenase complex, catalyst for the rate-limiting step of branched-chain amino acid catabolism, is controlled by a highly specific protein kinase (branched-chain alpha-ketoacid dehydrogenase kinase) that associates tightly with the complex. The activity state (proportion of the enzyme in its active, dephosphorylated state) of the complex varies dramatically in different rat tissues. The activity state of the complex in the liver is greater than that in any other tissue, and liver contains the lowest amount of kinase protein and kinase mRNA. However, protein malnutrition, a condition under which the complex is largely phosphorylated and inactive, resulted in a three- to fourfold increase in hepatic kinase activity with an accompanying increase in amounts of kinase protein and mRNA. Refeeding a 50% protein diet restored the normal activity state and the original levels of kinase protein and mRNA. The amount of kinase protein associated with the complex rather than changes in specific activity of the kinase appears responsible for observed differences in activity states of the complex in several rat tissues tested. Accordingly, the levels of kinase protein and mRNA measured are highest in tissues with greatest kinase activity (heart > kidney > liver), correlating reasonably well inversely with activity state of the branched-chain alpha-ketoacid dehydrogenase complex in the respective tissues. These observations suggest that the amount of kinase protein expressed in various tissues and in response to dietary protein deficiency is an important factor determining the activity state of the complex.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1995

The HIV information project for transfusion recipients a decade after transfusion.

OBJECTIVE: To gather information on which to base decisions about a general notification program for pediatric patients a decade after their receiving transfusions. DESIGN: The physicians of a cohort of 1793 patients who underwent cardiac surgery were sent letters asking them to contact and counsel patients identified from cardiovascular surgery and blood bank databases about their risk for human immunodeficiency virus (HIV) infection. Questionnaires were used to collect data about physicians' HIV practices; telephone interviews were conducted to collect information about patients' and parents' knowledge and attitudes about HIV and transfusions. Because of unexpected media interest, questionnaires and interviews were modified to include questions about the source of information. The HIV-testing status of patients reported by physicians was anonymously cross-referenced with specimens received by the Laboratory Services Branch, Ontario Ministry of Health, Toronto. SETTING: A large Canadian pediatric tertiary care hospital in Toronto. PARTICIPANTS: Seven hundred ninety-three patients undergoing cardiopulmonary bypass between 1980 and 1985. RESULTS: The HIV Information Project successfully reached most (approximately 75%) of this cohort and, with the help of the media, many other at-risk transfusion recipients. The information was new for many; almost all informed wanted to undergo testing. The seroprevalence of this group that received multiple transfusions was, at minimum, 8.5 patients in 1000. Six previously unsuspected HIV-seropositive cases were diagnosed. CONCLUSIONS: Although we had assumed that most patients receiving transfusions would be aware of their risk for HIV infection, our results indicate that, even a decade after the transfusion, many recipients were not aware of the risk and wanted to undergo testing. Testing identified asymptomatic infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed1995

The relationship between stool hardness and stool composition in breast- and formula-fed infants.

"Constipation" and "hard stools" are associated with formula feeding of both term and preterm infants and, in the latter, can lead to life-threatening complications. This study tested the hypothesis that stool hardness is related to excretion of fatty acid (FA) soaps in term infants, and in the extreme to milk bolus obstruction in premature infants. Stools (n = 44) were collected from 20 formula-fed and 10 breast-fed infants aged 6 weeks and were classified using visual charts for stool hardness on a 5-point scale (1, watery; 5, hard). Stools were analysed for nitrogen, minerals, and lipid, the latter divided between the soap and nonsoap fractions. We explored the relationship between stool hardness or solids content and stool constituents, relative to both wet and dry weight. Calcium and FA soaps were the dominant factors significantly related to stool solids and hardness score across the breast- and formula-fed groups. An 8% increase in stool dry weight FA soap content corresponded to a 1-point change in stool hardness score. Stools from formula-fed infants had a higher solids content and were classified as significantly harder than those from breast-fed infants (hardness scores, 4.0 +/- 0.5 versus 2.6 +/- 0.7, mean +/- SD) and on both a wet- and dry-weight basis contained severalfold higher levels of minerals and lipid and considerably less carbohydrate. Differences in lipids between formula- and breast-fed infants' stools were due almost entirely to FAs (mainly C16:0 and C18:0) excreted as soaps (27.7 +/- 7.5% compared to 3.1 +/- 4.1% of dry weight), suggesting the groups differed markedly in their handling of saturated FAs. An inspissated stool sample from a premature infant requiring surgical disempaction of an obstructed small intestine was found to be enriched in FA and calcium relative to the preterm formula. FA soaps, predominantly saturated, accounted for one third of the stool dry weight. These data support the hypothesis that calcium FA soaps are positively related to stool hardness; we speculate that this may, at least in part, explain the greater stool hardness in formula- versus breast-fed infants and milk bolus obstruction in preterm infants. This conclusion is consistent with the physical properties of calcium FA soaps.

Breast Feeding↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1984

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↗
PubMed1983

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↗