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Biomedical subjects

J Cole

Publications and source records attributed to J Cole.

At least 19 recordsLinked to original sources

Evidence for stronger visuo-motor than visuo-proprioceptive conflict during mirror drawing performed by a deafferented subject and control subjects.

It has been proposed that mirror drawing is difficult because of the conflict between visual and proprioceptive signals from the arm. However, even without proprioception, there should be difficulties in planning movements to visual targets observed in a mirror, as the mirror-reversed spatial information must be translated into appropriate hand actions. Mirror drawing tasks suggest these planning conflicts are likely to be most obvious at corners, when encountering sharp changes in direction. We have therefore tested the speed of mirror drawing in a chronically deafferented man and in a control group of normal subjects, and hypothesized that increases in template complexity (number of corners) would result in reduced drawing speeds in all subjects. Indeed, all subjects, including the deafferented man, showed movement durations that increased linearly as the complexity of the drawings increased. However, the deafferented man was significantly faster than the control subjects at tracing curved templates. We suggest that the major difficulty in mirror tracking is in the visuo-motor planning of actions based on mirror-reversed visual information, and is not a conflict between visual and proprioceptive signals about arm motion.

Adult↗

Granular materials: packing grains by thermal cycling.

A long-standing problem in managing the behaviour of a collection of solid grains concerns the nature of the grain packing, a property that is typically controlled by how the grains are poured or shaken. Here we show that a systematic and controllable increase in granular packing can be induced by simply raising and then lowering the temperature, without the input of mechanical energy. This thermal processing may have important practical implications for the handling and storage of granular materials.

Journal Article↗

Social defeat increases alcohol preference of C57BL/10 strain mice; effect prevented by a CCKB antagonist.

RATIONALE: In humans, social stress over long and short term can increase alcohol consumption, but the mechanisms involved are not understood. OBJECTIVES: This study was conducted to examine the effects of social defeat, using the resident/intruder paradigm, on the alcohol preference of "low alcohol drinking" individuals in a colony of C57BL/10 strain mice and the effects of two anxiolytic drugs. METHODS: Alcohol preference, in a two-bottle choice (8% v/v alcohol or water), was measured, in separate experiments, after either a single experience of social defeat by a resident male mouse, five consecutive daily defeat experiences or one experience per week for 4 weeks. Comparison was made with effects of repeated social defeat on the preference for dilute sucrose. In addition, the actions of the CCKB receptor antagonist, CAM1028, and of diazepam were examined on the effects of repeated defeat experiences. RESULTS: Five consecutive daily defeat experiences had a slow onset effect in increasing alcohol preference and consumption, compared with five daily exposures to a novel environment. A single defeat, or one defeat per week, did not significantly alter alcohol preference or intake. There were no effects of five daily defeat experiences on sucrose preference or consumption. The effect of repeated defeats on alcohol preference was significantly decreased by administration of the CCKB receptor antagonist, CAM1028, prior to each experience, but not by corresponding administration of diazepam. CONCLUSION: The results show that social stress increases alcohol intake in low alcohol preference C57BL/10 mice and suggest that CCK transmission may be involved in this effect.

Alcohol Drinking↗

Effects of postnatal exposure to mixtures of non-ortho-PCBs, PCDDs, and PCDFs in prepubertal female rats.

There are concerns that postnatal exposure to organochlorines present in breast milk could lead to adverse health effects. We reconstituted four mixtures of aryl-hydrocarbon receptor (AhR) agonists (3 non-ortho polychlorinated biphenyls [PCBs], 6 polychlorinated dibenzodioxins [PCDDs], 7 polychlorinated dibenzofurans [PCDFs], or all 16 chemicals together [referred to as AhRM]) based on their concentrations in breast milk, and examined their effects following exposure by gavage from day 1 until day 20 of age. Female neonates received dosages of AhRM equivalent to 1, 10, 100, or 1000 times the amount consumed by an infant over the first 24 days of life. Other groups received the PCBs, the PCDDs, or the PCDFs at the 1000x level. All rats were sacrificed at 21 days of age. Changes in ethoxyresorufin-o-deethylase hepatic activity, thymus and body weights, and serum thyroxin were linked to the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxic equivalents (TEQ) of the four mixtures (1000x-AhRM > PCDDs > PCBs > PCDFs). To test for AhRM antiestrogenicity, two additional groups received 1.5 microg/kg of 17alpha-ethynyl estradiol (EE) with or without the 1000x-AhRM. The AhRM had no effect on uterine weight or EE-stimulated uterine growth. The actions of the combined EE and AhRM treatments suggest additive effects in decreasing pentoxyresorufin-o-deethylase activity and spleen weight, but nonadditive/antagonistic effects on adrenal weight and serum thyroxin. In conclusion, (1) 10x-AhRM had no detectable effects, (2) TEQ values relate to observed toxicities, even when testing complex mixtures of AhR agonists, and (3) indications of tissue-specific additive and nonadditive/antagonistic effects, but no synergism, were observed when doses of AhRM were increased, or combined with EE.

Animals↗

Effect of postural supports on neuromotor function in very preterm infants to term equivalent age.

OBJECTIVE: To determine the effect of a postural support nappy and/or a postural support roll on neuromotor function in very preterm infants when nursed prone to term equivalent age. METHODS: A randomized observer blind controlled trial of 123 very preterm infants was conducted in the neonatal intensive care unit of the sole tertiary referral centre in Western Australia. Infants were stratified by gestational age (< 29 weeks or 29-30 weeks), then randomized into one of three intervention groups: postural support nappy, postural support nappy and postural support roll, or disposable nappy and postural support roll. Interventions started when infants were stable and ceased when routine side-lying commenced. Measurements of shoulder and hip posture were performed pre-intervention, 5 weeks post-intervention and term postmenstrual age. RESULTS: Infants nursed with a postural support roll and a postural support nappy demonstrated improved hip posture to term equivalent age compared with infants nursed with either a postural support roll only, or a postural support nappy only. Infants nursed with a postural support roll either with or without a postural support nappy demonstrated improved shoulder posture to term equivalent age. CONCLUSIONS: Combined use of a postural support roll and a postural support nappy while very preterm infants are nursed prone improves hip posture up to term postmenstrual age. Use of a postural support roll improves shoulder posture up to term equivalent age.

Child Development↗

Self-induced versus reactive triggering of synchronous movements in a deafferented patient and control subjects.

The present study investigates the contribution of tactile-kinesthetic information to the timing of movements. The relative timing of simultaneous tapping movements of finger and foot (hand-foot asynchrony) was examined in a simple reaction time task and in discrete self-initiated taps (Experiment 1), and in externally triggered synchronization tapping (Experiment 2). We compared the performance of a deafferented participant (IW) to the performance of two control groups of different ages. The pattern of results in control groups replicates previous findings: Whereas positive hand-foot asynchronies (hand precedes foot) are observed in a simultaneous reaction to an auditory stimulus, hand-foot asynchronies are negative with discrete self-initiated as well as auditorily paced sequences of synchronized finger and foot taps. In the first case, results are explained by a simultaneous triggering of motor commands. In contrast, self-initiated and auditorily paced movements are assumed to be controlled in terms of their afferent consequences, as provided by tactile-kinesthetic information. The performance of the deafferented participant differed from that of healthy participants in some aspects. As expected on the basis of unaffected motor functions, the participant was able to generate finger and foot movements in reaction to an external signal. In spite of the lack of movement-contingent sensory feedback, the deafferented participant showed comparable timing errors in self-initiated and regularly paced tapping as observed in control participants. However, in discrete self-initiated taps IW's hand-foot asynchronies were considerably larger than in control participants, while performance did not differ from that of controls in continuous movement generation. These findings are discussed in terms of an internal generation of the movement's sensory consequences (forward-modeling).

Adult↗

Cervical neuropathy following mantle radiotherapy.

The majority of newly diagnosed patients with Hodgkin's lymphoma are expected to survive because of effective therapies established during the last 40 years. Long-term observations from large populations of treated patients have disclosed a variety of late effects of the disease and its therapy that have contributed morbidity and excess mortality to Hodgkin's lymphoma survivors. As such complications have been recognized treatment approaches have been modified. Here we report a case of cervical neuropathy secondary to mantle radiotherapy, a complication not previously reported in the literature.

Adult↗

Laboratory investigations following an unexpectedly positive crossmatch result in a patient awaiting renal transplantation.

In the preparation of patients for renal transplantation tests of human leucocyte antigen (HLA) sensitisation are performed to detect "unacceptable" HLA antigens that, if present on donor cells, would be expected to result in a positive crossmatch. Individuals bearing such specificities may then be excluded from consideration as donors. Unexpected positive crossmatch results are sometimes obtained when a serum specificity has not been detected on screening. Failure to identify a donor relevant HLA antibody in a recipient at the time of crossmatch may result in hyperacute rejection of the graft. This report describes laboratory investigations performed after a positive crossmatch result in a live donor situation. The pattern of crossmatch results indicated that reactivity resulted from HLA class I antibody. Previously performed serum screening using a standard complement dependent cytotoxicity technique had failed to identify donor relevant antibody specificities in the recipient. Retrospective flow cytometric screening of the same serum samples identified an HLA-A24 specificity of donor relevance. The lower sensitivity of methods used for routine serum screening compared with those used for crossmatching accounts for the findings in this case. The laboratory has amended its serum screening protocol to include flow cytometric analysis.

Adult↗

The Escherichia coli CcmG protein fulfils a specific role in cytochrome c assembly.

In Escherichia coli K-12, c-type cytochromes are synthesized only during anaerobic growth with trimethylamine-N-oxide, nitrite or low concentrations of nitrate as the terminal electron acceptor. A thioredoxin-like protein, CcmG, is one of 12 proteins required for their assembly in the periplasm. Its postulated function is to reduce disulphide bonds formed between correctly paired cysteine residues in the cytochrome c apoproteins prior to haem attachment by CcmF and CcmH. We report that loss of CcmG synthesis by mutation was not compensated by a second mutation in disulphide-bond-forming proteins, DsbA or DsbB, or by the chemical reductant, 2-mercaptoethanesulphonic acid. An anti-CcmG polyclonal antibody was used in Western-blot analysis to probe the redox state of CcmG in mutants defective in the synthesis of other proteins essential for cytochrome c assembly. The oxidized form of CcmG accumulated not only in trxA or dipZ mutants defective in the transfer of electrons from the cytoplasm for disulphide isomerization and reduction reactions in the periplasm, but also in ccmF and ccmH mutants. The requirement of both CcmF and CcmH for the reduction of the disulphide bond in CcmG indicates that CcmG functions later than CcmF and CcmH in cytochrome c assembly, rather than in electron transfer from the membrane-associated DipZ (also known as DsbD) to CcmH. The data support a model proposed by others in which CcmG catalyses one of the last reactions specific to cytochrome c assembly.

Antibodies↗

Effect of a developmental program on motor performance in infants born preterm.

A randomised controlled trial was conducted to evaluate the effect of a motor developmental program in improving motor performance in Thai infants born preterm. Eighty-four preterm born infants were randomly assigned to either a control or intervention group. Additionally, 27 low-risk preterm infants were included forming a comparative group for this study. From term equivalent age to four months adjusted age, all infants had their motor performance assessed monthly with the Test of Infant Motor Performance by one of the physiotherapist research assistants blind to group assignment and infants' adjusted age. In addition, the intervention infants received a developmental program at each monthly visit. Motor performance for each group plotted against age revealed linear trends of progression. The intervention group showed the greatest improvement. Two-way repeated measures ANOVA revealed significant differences across age and among groups. Scheffé comparisons indicated that the mean differences between each pair of the three groups were significant and supported the finding of greater improvement of the intervention infants over the control group. Thus the results suggest that the intervention program is likely to have beneficial effects when offered to a similar population of preterm born infants.

Child Development↗

Nitrate reduction in the periplasm of gram-negative bacteria.

In contrast to the bacterial assimilatory and membrane-associated, respiratory nitrate reductases that have been studied for many years, it is only recently that periplasmic nitrate reductases have attracted growing interest. Recent research has shown that these soluble proteins are widely distributed, but vary greatly between species. All of those so far studied include four essential components: the periplasmic molybdoprotein, NapA, which is associated with a small, di-haem cytochrome, NapB; a putative quinol oxidase, NapC; and a possible pathway-specific chaperone, NapD. At least five other components have been found in different species. Other variations between species include the location of the nap genes on chromosomal or extrachromosomal DNA, and the environmental factors that regulate their expression. Despite the relatively small number of bacteria so far screened, striking correlations are beginning to emerge between the organization of the nap genes, the physiology of the host, the conditions under which the nap genes are expressed, and even the fate of nitrite, the product of Nap activity. Evidence is emerging that Nap fulfills a novel role in nitrate scavenging by some pathogenic bacteria.

Amino Acid Sequence↗

A phase I-II trial of topotecan and gemcitabine in patients with previously treated, advanced non-small cell lung cancer (LOA-3).

The purposes of this study were to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), toxicity profile, and antitumor activity of topotecan (TOP) and gemcitabine (GEM) combination therapy when administered to patients with previously treated, advanced, non-small cell lung cancer. Both compounds were administered intravenously over 30 min, with TOP on days 1-5 and GEM on days 1 and 5 only. Nineteen patients were treated with 75 courses at three dose levels. The MTD was 0.75 and 400 mg/m2 for TOP and GEM, respectively, with thrombocytopenia and neutropenia as the DLTs. Partial responses were achieved in 3 of 17 patients (18%) with measurable disease. Six patients (32%) had disease stabilization for at least four courses of treatment. The median survival was 10 months from the initiation of TOP and GEM. This combination was relatively well tolerated and exhibited promising antitumor activity in patients with advanced, previously treated, non-small cell lung cancer.

Adult↗

Genetic manipulation of the renin-angiotensin system.

The renin-angiotensin system is widely known for its importance in control of blood pressure, electrolyte homeostasis and volume regulation. Recently, renin-angiotensin system function was studied using homologous recombination in embryonic stem cells to manipulate the mouse genome. Angiotensinogen, angiotensin-converting enzyme and angiotensin II receptors were each eliminated in separate lines of mice. These null animals share similar phenotypes, such as a lowering of blood pressure, abnormal renal development, malfunction of the kidney and, unexpectedly, a decrease in hematocrit. In addition, angiotensin-converting enzyme null male mice sire far smaller litters than male wild-type mice. This suggests an unexplored role for angiotensin-converting enzyme in conception. Future studies with these and other genetically engineered mice lines will reveal novel physiological effects of angiotensin II.

Anemia↗