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Biomedical subjects

R Condon

Publications and source records attributed to R Condon.

At least 19 recordsLinked to original sources

Role of biotin-containing membranes and nuclear distribution in differentiating human endometrial cells.

Human Ishikawa endometrial cells form domes when confluent monolayers are stimulated with fresh fetal bovine serum. Extensive structural and biochemical changes have been detected during the approximately 30 h differentiation period. The earliest detectable change involves the formation of multinucleated structures and the appearance of "granules" that stain for biotin within those structures. Nuclei become associated with each other and are ultimately enclosed within a biotin-containing membrane. Aggregated membrane-sheathed nuclei and the cells containing them begin to elevate from the dish as biotin staining becomes apparent in apical membranes. The elevated structures are called predomes and consist of one or more very large cells containing the sheathed nuclei. Apical membranes of these unusual cells extend far out into the medium in structures that resemble endometrial pinopods. A lumen under the elevated cells fills with transcytosed fluid. As differentiation proceeds, highly concentrated chromatin material that was flattened against apical and lateral membranes of the predome cells begins to disperse. Small mononuclear cells evolve from larger predome cells. Apical membranes of predome and dome cells continue to stain for biotin. Gel electrophoresis of SDS-solubilized biotin-containing membranes, followed by Western blot analysis using avidin-linked peroxidase, resulted in three stained bands with molecular weights similar to those of the mitochondrial carboxylases: propionyl carboxylase, methylmalonyl carboxylase, and pyruvate carboxylase.

Biotin

Measuring the impact of conjugate vaccines on invasive Haemophilus influenzae type b infection in Western Australia.

Haemophilus influenzae type b (Hib) causes serious infections in 26-59 per 100,000 non-Aboriginal Australian children under five years of age. Aboriginal children suffer much higher rates of infection (> or = 150 per 100,000), and at an earlier age, and have a greater risk of death and disability due to Hib infection. In 1992 and 1993, four conjugate Hib vaccines were introduced in Australia, and a nationally funded program of infant vaccination was begun in July 1993. This study aimed at evaluating the effectiveness of Hib vaccination in Aboriginal and non-Aboriginal children in Western Australia using a population-based active surveillance system for non-Aboriginal children and a case control study for Aboriginal children. The incidence of invasive Hib disease in non-Aboriginal children fell from 30.9 per 100,000 before vaccination was available to 6.3 per 100,000 in the second year after its introduction. The vaccine efficacy was estimated to be 80 per cent for Aboriginal children (odds ratio 0.20, 95 per cent CI 0.01-2.76) and, after adjustment for confounders, 75 per cent (odds ratio 0.25, CI 0.02-3.66). Based on the adjusted value (75 per cent), and using a Bayesian approach, we estimate that the posterior probability was 0.55 that the true vaccine efficacy is greater than 70 per cent, and 0.69 that the efficacy is greater than 50 per cent. We conclude that Hib vaccination is effective in preventing invasive Hib disease in Aboriginal and non-Aboriginal children in Australia.

Bacteremia

Induction of heat labile alkaline phosphatase by butyrate in differentiating endometrial cells.

The addition of 2 mM sodium butyrate to monolayers enhances differentiation of Ishikawa endometrial cells. Cells from this cell line have been shown to enlarge and lift off the dish into dome structures over a period of 24-48 h in response to a factor in fetal bovine serum (FBS) [Fleming, 1995 J Cell Biochem in press]. When butyrate is added to monolayers, together with FBS, three- to fourfold higher numbers of differentiated structures, domes and predomes, can be counted. It had previously been shown [Holinka et al., 1986b] that estradiol induces heat stable placental alkaline phosphatase in Ishikawa cells. The addition of butyrate, on the other hand, results in a significant increase in levels of a heat labile alkaline phosphatase isozyme. The heat labile isozyme is also increased to some extent in cells stimulated to differentiate in response to FBS in the absence of butyrate. Differential inhibition by homoarginine and phenylalanine indicates that butyrate is inducing the liver-bone kidney isozyme that is found in endometrial glands in vivo.

Alkaline Phosphatase

Reward shifts and motor responses following microinjections of opiate-specific agonists into either the core or shell of the nucleus accumbens.

Differences in pharmacology, anatomical connections, and receptor densities between the "core" and "shell" of the nucleus accumbens suggest that behavioral activity normally modulated by the accumbens, such as reward and motor functions, may be differentially regulated across the mediolateral axis. This study investigated the effects of opiate receptor-specific agonists on reward and motor functions in either the accumbens core or shell, using the intracranial self-stimulation (ICSS) rate-frequency curve-shift method. Microinjections of the mu opiate receptor-specific agonist, DAMGO (vehicle, 0.03 nmol, and 0.3 nmol), or the delta opiate receptor-specific agonist DPDPE (vehicle, 0.3 nmol, 3.0 nmol), were administered bilaterally in a random dose order with a minimum of 3 days between injections. Rats were tested over three consecutive 20-min rate-frequency curves immediately following a microinjection to investigate the time course of drug effects. Both opiate agonists decreased the ICSS frequency necessary to maintain half-maximal response rates when injected into the medial and ventral shell region of the accumbens. However, DAMGO microinjections into the lateral accumbens core or the control site of the caudate increased the frequency necessary to elicit half-maximal response rates, while DPDPE microinjections into these regions had no effect. Evaluation of motor effects show that administration of DAMGO resulted in a suppression of activity in all locations. In contrast, DPDPE microinjections resulted in little or no effect on lever pressing activity at any location.

Analgesics

Sequelae of Haemophilus influenzae type b meningitis in aboriginal and non-aboriginal children under 5 years of age.

Between 1984 and 1990, 257 cases of Haemophilus influenzae type b (Hib) meningitis occurred in children under five years of age in Western Australia. We obtained information on possible sequelae in 131 cases (all non-Aboriginal) by medical record review and parental interview, and in a further 116 cases (60 non-Aboriginal, 56 Aboriginal) by medical record review only; no follow-up information was available for ten children (nine non-Aboriginal, 1 Aboriginal). The incidence of Hib meningitis in children under five years of age was 26.3 per 100,000 for non-Aboriginal and 152.2 per 100,000 for Aboriginal children. The case fatality rate was 3.5% for non-Aboriginal children and 14.0% for Aboriginal children. Sequelae were recorded for 17.1% of non-Aboriginal and 22.4% of Aboriginal children who survived Hib meningitis. Surviving Aboriginal children experienced severe sequelae following Hib meningitis almost three times more frequently than surviving non-Aboriginal children (10.5% vs 3.6%), although mild and moderate sequelae were not more common in Aboriginal children. The information on incidence and severity of sequelae in this study was obtained by chart review and parental interview, and hence may be subject to error or bias, particularly for mild and moderate disabilities. Outcomes like death and severe sequelae, such as cerebral palsy and profound intellectual and physical disability, are less subject to bias. Of Aboriginal children who contracted Hib meningitis in Western Australia over the study period, 22.8% either died or had severe sequelae, while only 7.0% of non-Aboriginal children experienced these severe outcomes.

Cerebral Palsy

Cytoplasmic and periplasmic expression of a highly basic protein, human interleukin 4, in Escherichia coli.

Human IL-4 (hIL-4) has been cloned from a human T cell line based on its homology to the murine IL-4 cDNA sequence. We have compared cytoplasmic and extra-cytoplasmic expression of this basic protein in Escherichia coli using various combinations of promoters, replicons and host strains. Strains producing a cytoplasmic product were most successful at heterologous protein expression, producing up to 500 mg/l of an inactive aggregated form of the protein. The biological activity of the protein could be restored by refolding the protein with guanidine hydrochloride and glutathione giving a specific activity identical to that of IL-4 derived from CHO cell lines stably transformed with an hIL-4 expression plasmid. Strains designed to secrete human IL-4 into the periplasmic space produced far less protein (approximately 5 mg/l). However, a significant fraction of this protein was detected in the culture medium. This fraction appeared to be soluble after ultracentrifugation, and demonstrated high specific activity without refolding. Leakage of heterologous protein into the culture medium may be a viable way to recover biologically active products without relying on the denaturation and refolding in vitro that can, at times, yield incorrectly folded gene product.

Amino Acid Sequence

Work at sea: a study of sleep, and of circadian rhythms in physiological and psychological functions, in watchkeepers on merchant vessels. III. Rhythms in physiological functions.

Oral and rectal temperature, urinary excretion of adrenaline and noradrenaline, and heart rate were measured in 28 watchkeepers working a "4-on/8-off" routine, and in 25 dayworkers, on board ships. Readings of oral temperature were taken over 4-hourly periods of up to two weeks; the rectal temperature, urine, and heart rate data were collected on selected days within these periods. Analysis of watchkeepers' temperatures and unconjugated catecholamine excretions showed slight signs of an interactive adaptation to time of day and hours of work, but it was clear that full phase adjustment of the circadian rhythms to shifted hours of work did not occur. The "split" pattern of sleep imposed by the watch system may be a major factor in preventing complete adaptation of physiological rhythms to shift work in the shipboard situation; this problem could be overcome by devising a system that allows sleep to be taken in a single uninterrupted block each day.

Body Temperature

Work at sea: a study of sleep, and of circadian rhythms in physiological and psychological functions, in watchkeepers on merchant vessels. IV. Rhythms in performance and alertness.

Performance scores on both a simple detection task and a complex visual judgment task, together with subjective alertness ratings, were collected 4-hourly from 19 watchkeepers working a "4-on/8-off" routine, and from 20 dayworkers, over consecutive days of voyages on merchant ships. Adaptation of the circadian rhythms in the measures to the shifted hours of work of the three sections of the watchkeeping crews was at best only partial. These rhythms resulted in a depression of the levels of most measures during the night hours, which was exacerbated by the effects of recent awakening from sleep. It is suggested that these unwanted variations in operational effectiveness could be largely removed by replacing the 4-on/8-off watchkeeping system, with its associated "split" sleep pattern, by one which allows a single full length sleep each day. Such a system would encourage better adaptation of the rhythms; effects of recent awakening could be avoided by the provision of an adequate "waking up" period before duty begins.

Arousal

Work at sea: a study of sleep, and of circadian rhythms in physiological and psychological functions, in watchkeepers on merchant vessels. V. Effects of time zone crossings.

Daily diary records of sleep and activity, and 4-h measurements of body temperature, performance and subjective alertness were collected on board ship from 15 watchkeepers on the 4-on/8-off system, and from 28 dayworkers, on both westward and eastward transatlantic voyages. The data from a balanced sample of the subjects were analysed over selected 8-d periods of the voyages where four or five time zones were crossed. During these periods the average amount of daily sleep obtained by dayworkers on the eastward voyage was more than 1 h less than that on the westward voyage, and its quality was rated lower. Watchkeepers' main sleep was also shorter when travelling eastward, but this reduction was partially compensated for by a slightly longer secondary sleep. With the exception of subjective alertness on the eastward voyage, the basic phase of the circadian rhythms in the measured variables adjusted appropriately to the clock changes associated with the time zone crossings. The normal shape of the average daily curves was, however, altered differentially in the two directions of travel; as a result, morning levels of all variables were lower on the eastward voyage than on the westward, but evening levels were higher. These distortions of rhythm waveforms, which probably arose from a combination of endogenous and exogenous factors, add another dimension to the basic problem caused by the effects of circadian rhythms on operational efficiency in the shipboard situation. This problem can only be solved by the development of alternative watchkeeping systems which take full account of these rhythms.

Attention

Work at sea: a study of sleep, and of circadian rhythms in physiological and psychological functions, in watchkeepers on merchant vessels. I. Watchkeeping on board ships: a methodological approach.

The safety of a ship depends substantially on its bridge watchkeepers, whose alertness and efficiency must be maintained at all hours of the day and night. Fatigue, circadian rhythms, and sleep disruption occasioned by the unusual working hours of these personnel may all affect their performance. A methodology for assessing the magnitude of this problem is proposed. The application of this methodology in a large-scale shipboard study of merchant mariners on extended voyages is then described, and details given of the techniques used to measure sleep and activity, and temporal variations in a range of physiological und psychological parameters. A summary of the data collected in the study is provided as a reference point for the reports on the different aspects of the results that follow in subsequent articles.

Body Temperature

Work at sea: a study of sleep, and of circadian rhythms in physiological and psychological functions, in watchkeepers on merchant vessels. II. Sleep duration, and subjective ratings of sleep quality.

Sleep length and sleep quality scores were collected on board ships over periods of up to two weeks from 38 watchkeepers working a '4-on/8-off routine' and 29 dayworkers. All watchkeepers exhibited fragmented sleeping patterns, which indicated a lack of adaptation of the sleep/wakefulness cycle to the hours of work. There were only slight differences in total sleep length between watchkeepers and dayworkers, however, both groups did not obtain an adequate amount of sleep. Within the watchkeeping crews the 3rd Officers had by far the shortest sleep length. Concerning sleep quality, daytime sleep was generally given the lowest ratings, whereas sleep starting before midnight was on average evaluated as the best, both by watchkeepers and dayworkers. Watchkeeping personnel do not normally have any "days off" during a voyage so that missed sleep might even amount to a sleep deficit. A solution for this problem could perhaps be a new, stabilized system that allows a single uninterrupted sleep, which is required for full recuperation, to be taken each day.

Circadian Rhythm

Night shift paralysis.

12% of night nurses surveyed claimed to have suffered from a totally incapacitating paralysis that may be related to sleep paralysis, and contribute to impaired levels of safety on the night shift. The incidence of this paralysis is shown to be age-related, largely confined to the early hours of the morning, and to increase over consecutive night shifts.

Adult