Biomedical subjects
Publications and source records attributed to D Steele.
Patients with treated Wilson's disease and no residual impairments should have successful pregnancies. We report a case of a neurologically impaired patient with Wilson's disease who had a successful pregnancy with no complications. This is the first case to document that compliance with penicillamine therapy as low as 500 mg/day avoids placental and fetal copper accumulation.
K+ channel gating currents are usually measured in the absence of permeating ions, when a common feature of channel closing is a rising phase of off-gating current and slow subsequent decay. Current models of gating invoke a concerted rearrangement of subunits just before the open state to explain this very slow charge return from opening potentials. We have measured gating currents from the voltage-gated K+ channel, Kv1.5, highly overexpressed in human embryonic kidney cells. In the presence of permeating K+ or Cs+, we show, by comparison with data obtained in the absence of permeant ions, that there is a rapid return of charge after depolarizations. Measurement of off-gating currents on repolarization before and after K+ dialysis from cells allowed a comparison of off-gating current amplitudes and time course in the same cells. Parallel experiments utilizing the low permeability of Cs+ through Kv1.5 revealed similar rapid charge return during measurements of off-gating currents at ECs. Such effects could not be reproduced in a nonconducting mutant (W472F) of Kv1.5, in which, by definition, ion permeation was macroscopically absent. This preservation of a fast kinetic structure of off-gating currents on return from potentials at which channels open suggests an allosteric modulation by permeant cations. This may arise from a direct action on a slow step late in the activation pathway, or via a retardation in the rate of C-type inactivation. The activation energy barrier for K+ channel closing is reduced, which may be important during repetitive action potential spiking where ion channels characteristically undergo continuous cyclical activation and deactivation.
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A recent advance in metallurgical technology has been the application of rapid solidification techniques to Al alloy production. FVS0812 is the designation given to a microcrystalline Al-based alloy consisting of 8 wt% Fe, 1 wt% V and 2 wt% Si. It is a two-phase alloy, consisting of ca. 27 vol percent of approximately spherical Fe-V-Si-rich dispersoids in an essentially pure Al matrix. The high strength, low density properties of this advanced material, and other related alloys, have not yet been realized, however, due, in part, to the inability of the alloy to form a thick, adherent, abrasion-resistant outer surface oxide film, a feature readily achieved at conventional Al alloys by normal anodizing methods. The present research has involved an electro-chemical study of oxide film growth at the 812 alloy, with the specific goals being to seek an understanding of the origin of the oxide film growth problem and ultimately to propose alternative approaches to the formation of a thick, stable oxide film at this material. The techniques used in this research have included electrochemical methodologies such as cyclic voltammetry and electrochemical impedance spectroscopy. Crucial information has been obtained through transmission electron microscopy (TEM) of ultramicrotomed specimens. Experiments were carried out initially in neutral borate solutions to characterize the compact barrier oxide film formed in this environment and expected to be present beneath the porous oxide film formed in the normal sulfuric acid anodizing medium.(ABSTRACT TRUNCATED AT 250 WORDS)
A 10-month-old female with developmental delay and failure to thrive was referred for genetic evaluation as part of an adoption assessment. Physical exam showed a mildly beaked nose and clinodactyly, but otherwise nothing remarkable. Chromosome analysis showed an inverted duplication of the p12.2-->p13 portion of chromosome 7[(46,XX, dup(7)(p13p12.2)]. The proposita's older brother, mother, and grandmother were cognitively delayed and had the same chromosome 7 duplication. A review of the literature showed no other cases involving this exact duplication.
This study explored the relationship between health and social support in wives who care for husbands with dementia. In order to understand how significant others begin mobilizing help for caregivers, the significant others' views of the carers' health and social support were analysed. Subjects comprised 75 significant others identified as being familiar with the caregiving situation of a like number of caregiving wives. Hypotheses, which were rejected, predicted that wife caregivers perceived as ill by the significant other would be seen as needing and receiving more social support as reported by the significant other. Findings indicated that healthy caregivers were perceived to have significantly more people in their social network.
BACKGROUND: Although both beta-adrenergic agonists and anticholinergic agents are widely used in the treatment of patients with COPD, they influence the pulmonary circulation and ventilation differently. We compared the effects of these two agents on gas exchange and distribution of ventilation in COPD. METHODS: Pirbuterol and ipratropium bromide were administered by inhalation via a metered-dose inhaler to 12 and 14 patients with COPD, respectively, in a randomized, double-blind fashion. Pulmonary function tests, arterial blood gas levels, heart rate, resting minute ventilation (VE), physiologic dead space volume to total ventilation ratio (VD/Vt) and oxygen consumption (VO2) were measured prior to and then 5, 15, 30, and 60 min after administration of the respective drugs. The changes in these measurements after administration of the two drugs were analyzed and compared with each other. RESULTS: The pulmonary function test measurements showed similar improvement after administration of both drugs. Heart rate fell in both groups. After administration of pirbuterol, the alveolar-arterial oxygen pressure difference (P[A-a]O2) and VE rose significantly and the rise in FEV1 showed a negative correlation with the fall in PaO2. In contrast, the use of ipratropium bromide did not produce these effects, but resulted in a fall in VO2 and a rise in VD/Vt. CONCLUSION: Pirbuterol and ipratropium are equally effective bronchodilators in COPD. Pirbuterol results in a significant rise in P(A-a)O2 and resting VE. Ipratropium does not affect these measurements and seems to reduce the oxygen cost of breathing. The results suggest significant differences between the effects of the two agents on gas exchange, ventilation, and VO2 which could be of clinical significance.
Blood samples were collected from 917 women attending the Obstetrics and Gynaecology Department at Ga-Rankuwa Hospital during a one year period. Each woman presented with an unfavourable outcome to pregnancy. Blood was also obtained from 99 newborn babies who were jaundiced, or who died within a few days of birth or who showed gross congenital abnormalities. IgM antibodies to cytomegalovirus (CMV), Herpes simplex virus type 2 (HSV-2) and rubella virus were determined by commercial ELISA. CMV was found to be the most prevalent infection in both groups of women (19.2 pc) and in the babies (24.2 pc) indicating the importance of this virus in intra-uterine infection in this community. Rubella and HSV-2 infection were identified in the population sample but seemed to play a much less significant role than CMV.
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Null cells (non-T and non-B lymphocytes) have previously been demonstrated to be obligatory participants for immunoglobulin synthesis and secretion by normal B cells in culture. Normal null cells have been demonstrated to secrete a factor, human immunoglobulin synthesis/secretion-facilitating factor (HISFF), which can replace the null cells in the culture. In this investigation, the B cells of an 8-month-old male infant and a 46-year-old male adult who presented with a humoral (antibody) immunodeficiency syndrome synthesized immunoglobulin but did not secrete immunoglobulin after culture with pokeweed mitogen and autologous T cells, monocytes, and null cells. In contrast, the patients' B cells synthesized and secreted immunoglobulin after the addition of allogeneic normal null cells or HISFF to the cultures. The same results were obtained with the cells of the infant and the adult patient tested at monthly intervals for 4 months. The results demonstrate that the patients' T cells, B cells, and monocytes functioned normally and that only the patients' null cells were defective. These findings provide an explanation for the absence of immunoglobulin in the circulation of "non(immunoglobulin)secretors," although they possess normal numbers of circulating immunoglobulin-synthesizing B cells. The defect is in the null cell and not in the B cell and consists of the inability of the null cell to secrete HISFF that facilitates the synthesis and secretion of immunoglobulin by the B cell.
Subjects' responses to nonarbitrary stimulus relations of sameness, oppositeness, or difference were brought under contextual control. In the presence of the SAME context, selecting the same comparison as the sample was reinforced. In the presence of the OPPOSITE context, selecting a comparison as far from the sample as possible on the physical dimension defined by the set of comparisons was reinforced. Given the DIFFERENT context, selecting any comparison other than the sample was reinforced. Subjects were then exposed to arbitrary matching-to-sample training in the presence of these same contextual cues. Some subjects received training using the SAME and OPPOSITE contexts, others received SAME and DIFFERENT, and others received SAME, OPPOSITE, and DIFFERENT. The stimulus networks established allowed testing for a wide variety of derived relations. In two experiments it was shown that derived performances were consistent with relational responding brought to bear by the contextual cues. In contexts relevant to the relation of sameness, stimulus equivalence emerged. Other kinds of relational networks emerged in the other contexts. Arbitrarily applicable relational responding may give rise to a very wide variety of derived stimulus relations. The kinds of performances seen in stimulus equivalence do not appear to be unique.
L-Glutamine is a requirement for many cells in tissue culture, an intermediate in many metabolic pathways, and an alternative substrate to glucose for energy metabolism. These properties suggest that glutamine concentration might be a determinant of cell viability in tumours, especially in regions that are deficient in other metabolites. We have therefore studied the effects of glutamine depletion on single cells in culture, on spheroids and on experimental tumours. Absence of glutamine suppressed the growth rate of two cell lines, but cells cultured for up to 6 h in the absence of glutamine had no decrease in plating efficiency. There was little effect on growth of MGH-U1 (human bladder cancer) spheroids of varying the glutamine concentration in the range of 0.1 to 2 mM and spheroids exposed to these concentrations did not develop central necrosis. Lower concentration of glutamine suppressed the rate of spheroid growth, and spheroids did not grow in the absence of glutamine. Pseudomonas 7A glutaminase reduced the survival of cells in glutamine-free culture and prevented growth of spheroids. Glutaminase was injected into mice bearing experimental tumours to reduce blood levels of glutamine; some animals also received 15 Gy radiation to their tumours to assess the effects of glutamine levels on surviving nutrient-deprived (i.e. hypoxic) cells. Glutaminase had no effect on cell survival in the Lewis lung tumour or in MGH-U1 xenografts, with or without radiation; glutaminase caused dose-dependent growth delay of the KHT tumour, which was additive to that caused by radiation. The present results suggest that (i) short-term changes of glutamine concentration have small effects on cell viability; and (ii) depletion of glutamine levels in blood through the in vivo use of glutaminase is unlikely to produce major therapeutic effects against nutrient-deprived cells in solid tumours.
Lymphocyte losses occur during repeat plateletpheresis and/or leukapheresis procedures and are potentially harmful to normal host immune function. This concern prompted us to study the effect of repeat lymphocytapheresis (lymphapheresis) on the immune system of healthy blood donors. Following a total of six lymphapheresis procedures over a 12-day period with removal of a mean of 41.6 X 10(9) lymphocytes, there were no significant changes in donor (n = 5) absolute lymphocyte counts, quantitative immunoglobulin levels or immune response capability as assessed by the following in vitro assays: percent of E, EA, and EAC rosette-forming cells, the percent of surface membrane immunoglobulin bearing cells, and the blastogenic responses to stimulation with phytohemagglutinin, pokeweed mitogen and concanavalin A. The procedures were well-tolerated without complications. During a follow-up period of 18 months, significant increases in total white cell counts (but not absolute lymphocyte counts), and in quantitative immunoglobulin levels (IgG, IgM, and IgA) were observed. The median increases in immunoglobulin levels ranged from 27.5% for IgG to 44% for IgA. We conclude that lymphapheresis as described is relatively safe and our results are reassuring in relation to lymphocyte losses that may occur during repeat cytapheresis procedures of normal blood donors.
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The effects of morphine (10mg/kg) on intracranial self-stimulation were studied in three separate test situations, each requiring rats to perform different types of responses. Self-stimulation was depressed in a test of rate of bar-pressing, to a lesser extent in a test of rate of wall-pressing in which a wider range of movements were reinforced, but not in a shuttle-box, with brain stimulation continuously available on one side of box. This resonse dependency suggests that the depressive effect of morphine on bar-pressing for lateral hypothalamic stimulation reflects a performance deficit rather than an effect on the reinforcing value of the stimulation.
In Experiment I, 26-week-old infants were repeatedly exposed to 1 object and then shown a second object that was different in color or that was different in shape and texture. During repeated exposures, infants looked at an manipulated the object less, but response latencies did not change. Looking and manipulation increased upon introduction of the novel object in the shape and texture change condition. The novel object in the color change condition elicited an increase in looking but not in manipulation. The purpose of Experiment II was to determine if the coordination of visual and manipulative exploration in the shape and texture change condition was primarily due to the new tactile information or because of the introduction of more than 1 physical change. In this experiment, the novel object differed either in shape or in texture, For both conditions, there was a decline in looking and manipulation times during familiarization and recovery of novel objects for both looking and manipulation. It was concluded that either shape or texture information is sufficient to coordinate visual and manipulative differential responding.