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Biomedical subjects

H K Smith

Publications and source records attributed to H K Smith.

At least 19 recordsLinked to original sources

Penalty shot importance, success and game context in international water polo.

To establish the incidence, timing and quantitative importance of penalty shots in water polo and to test whether or not penalty shot success would vary with the context (closeness, quarter, criticality) of the game, official records from six major international tournaments (n= 296 games) were analysed. Across all tournaments, penalties (n= 206) were awarded (1-3 per game) in 51% of games with no difference in frequency between game quarters. Penalty goals (n= 165) comprised only 3.7% of all goals scored, whereas the outcome of penalties (goal/no goal) within each game affected the final outcome (win/loss/tie) of 20% of games. The success rate of penalty shots (80.1%) was not significantly different between games classed as either close or non-close, by a mathematical expression of the running average goal difference up until the time of the penalty, and by the absolute difference of the score at the time of the penalty. Nor was this success rate significantly different between game quarters (72.7, 83.0, 81.5, and 81.8%), or between games classified by their criticality to final tournament placing (80.0, 79.5, and 80.6%, from highest to lowest). Thus, during international water polo, penalties contribute only modestly to game outcome, and penalty shot success is not significantly related to the closeness, quarter, or criticality of the game being played.

Adaptation, Psychological↗

Influence of female reproductive anatomy on the outcome of sperm competition in Drosophila melanogaster.

Females as well as males can influence the outcome of sperm competition, and may do so through the anatomy of their reproductive tracts. Female Drosophila melanogaster store sperm in two morphologically distinct organs: a single seminal receptacle and, normally, two spermathecae. These organs have different temporal roles in sperm storage. To examine the association between sperm storage organ morphology and sperm competition, we used a mutant type of female with three spermathecae. Although the common measure of sperm competition, P(2), did not differ between females with two and three spermathecae, the pattern of sperm use over time indicated that female morphology did affect male reproductive success. The rate of offspring production by females with three spermathecae rose and fell more rapidly than by females with two spermathecae. If females remate or die before using up second male sperm, then second male reproductive success will be higher when they mate with females with three spermathecae. The results indicate that temporal patterns of sperm use as well as P(2) should be taken into account when measuring the outcome of sperm competition.

Animals↗

Prolonged underfeeding of sheep increases myostatin and myogenic regulatory factor Myf-5 in skeletal muscle while IGF-I and myogenin are repressed.

The IGF axis is nutritionally sensitive in vivo and IGFs stimulate myoblast proliferation and differentiation in vitro, while myostatin inhibits these processes in vitro. We hypothesised that underfeeding would reversibly inhibit the myogenic activity of satellite cells in vivo together with decreased IGF-I and increased myostatin in muscle. Satellite cell activity was measured indirectly from the expression of proliferating cell nuclear antigen (PCNA) and the myogenic regulatory factors (MRFs), MyoD, Myf-5 and myogenin. Young sheep were underfed (30% of maintenance) and some killed after 1, 4, 12, 17, 21 and 22 weeks. Remaining underfed animals were then re-fed a control ration of pellets and killed after 2 days, and 1, 6 and 30 weeks. Expression of PCNA and MRFs decreased during the first week of underfeeding. This coincided with reduced IGF-I and myostatin mRNA, and processed myostatin. Subsequently, Myf-5, MyoD, myostatin mRNA and processed myostatin increased, suggesting that satellite cells may have become progressively quiescent. Long-term underfeeding caused muscle necrosis in some animals and IGF-I and MRF expression was increased in these, indicating the activation of satellite cells for muscle repair. Re-feeding initiated rapid muscle growth and increased expression of PCNA, IGF-I and the MRFs concurrently with decreased myostatin proteins. In conclusion, these data indicate that IGF-I and myostatin may work in a coordinated manner to regulate the proliferation, differentiation and quiescence of satellite cells in vivo.

Adaptation, Physiological↗

Foxn4--a new member of the forkhead gene family is expressed in the retina.

We report the cloning and expression of a novel murine forkhead/winged helix family member--Foxn4--that is expressed during neural development in the retina, the ventral hindbrain and spinal cord and dorsal midbrain. Retinal Foxn4 expression is associated with the zone of proliferating progenitor cells. In the mouse mutant ocular retardation (or(J)), Foxn4 expression in the retina is significantly reduced and terminates prematurely.

Amino Acid Sequence↗

Exercise-enhanced satellite cell proliferation and new myonuclear accretion in rat skeletal muscle.

The effects of increased functional loading on early cellular regenerative events after exercise-induced injury in adult skeletal muscle were examined with the use of in vivo labeling of replicating myofiber nuclei and immunocyto- and histochemical techniques. Satellite cell proliferation in the soleus (Sol) of nonexercised rats (0.4 +/- 0.2% of fibers) was unchanged after an initial bout of declined treadmill exercise but was elevated after two (1.0 +/- 0.2%, P < or = 0.01), but not four or seven, daily bouts of the same task. Myonuclei produced over the 7-day period comprised 0.9-1.9% of myonuclei in isolated fibers of Sol, tibialis anterior, and vastus intermedius of nonexercised rats. The accretion of new myonuclei was enhanced (P < or = 0.05) in Sol and vastus intermedius by the initial exercise followed by normal activity (to 3.1-3.4% of myonuclei) and more so by continued daily exercise (4.2-5.3%). Observed coincident with a lower incidence of histological fiber injury and unchanged fiber diameter and myonuclei per millimeter, the greater new myonuclear accretion induced by continued muscle loading may contribute to an enhanced fiber repair and regeneration after exercise-induced injury.

Animals↗

Expression of Drosophila omb-related T-box genes in the developing human and mouse neural retina.

PURPOSE: To examine the role of Drosophila optomotor blind (omb)-related T-box genes in development of human and mouse retina. METHODS: Mouse Tbx2, Tbx3, and Tbx5 and human TBX2 cDNAs were isolated from retinal cDNA libraries by hybridization to the Drosophila omb gene. Gene expression patterns in developing retina were analyzed by in situ hybridization. RESULTS: TBX2/Tbx2, TBX3/Tbx3, and TBX5/Tbx5 were expressed asymmetrically across the embryonic neural retina with highest levels of mRNA within dorsal and peripheral retina. The dorsoventral gradient of TBX2 expression disappeared before the ganglion cell layer (GCL) formed. Its expression then became restricted to the inner neuroblastic retina and later to the GCL and inner nuclear layer (INL). The dorsal expression domains of TBX5/Tbx5 and TBX3/Tbx3 were maintained during formation of the GCL. As the retina matured, TBX3/Tbx3 expression was restricted to the INL, and TBX5/Tbx5 was expressed within the GCL. CONCLUSIONS: The expression pattern of TBX2, TBX3, and TBX5 within the developing retina supports the idea that the encoded transcription factors play a role in providing positional information important for topographic mapping and in differentiation of distinct cell types across the laminar axis of the retina.

Animals↗

Oligodendrocyte lineage and the motor neuron connection.

One of the more surprising recent discoveries in glial biology has been that oligodendrocytes (OLs) originate from very restricted regions of the embryonic neural tube. This was surprising because myelinating OLs are widespread in the mature central nervous system, so there was no reason to suspect that their precursors should be restricted. What we now know about early OL development suggests that they might have as much (or more) in common with ventral neurons-specifically motor neurons (MNs)-as with other types of glia. This has implications for the way we think about glial development, function, and evolution. In this article we review the evidence for a shared MN-OL lineage and debate whether this is the only lineage that generates OLs. We decide in favour of a single embryonic lineage with regional variations along the anterior-posterior neuraxis.

Animals↗

Nuclear DNA fragmentation and morphological alterations in adult rabbit skeletal muscle after short-term immobilization.

Nuclear DNA fragmentation and ultrastructural changes, indicative of myonuclear apoptosis, were examined in adult skeletal muscle in response to short-term immobilization. Adult rabbits were allocated to 2 days (n=5) or 6 days (n=5) of unilateral casting of the ankle in full plantar flexion or were used as untreated controls (n=2). Atrophy of the soleus muscle was apparent by significant reductions in wet mass of 15% and 26% after 2 days and 6 days of casting (P< or =0.05), respectively. Mean fibre cross-sectional area and myonuclear number per section were also lower (17% and 9.1%, respectively) after 6 days of casting, in comparison with contralateral control muscles (P< or =0.05). Electron-microscopic examination showed condensed chromatin and irregularly shaped myonuclei in muscles immobilized for either 2 days or 6 days. Myofibrillar disruption and abnormalities of the subsarcolemmal mitochondria were also apparent in the absence of inflammation or plasma membrane alterations in cast muscles. Longitudinal and transverse sections showed abundant in situ end-labelling of DNA strand breaks (TUNEL) after 2 days, with less after 6 days, of immobilization. Positive labelling corresponded to myonuclear locations within fibres, yet the number of TUNEL-positive nuclei indicated DNA fragmentation in additional cell types such as capillary endothelial cells or fibroblasts. The data indicate that the immobilization of slow-twitch skeletal muscle in a shortened position rapidly induces morphological alterations consistent with mitochondrial injury and apoptotic myonuclear elimination.

Animals↗

Ergometer sprint performance and recovery with variations in training load in elite rowers.

The effects of 3 weeks of a 30% increase in training volume, followed by 1 week of reduced volume (approximately 75%) training, on ergometer sprint performance and physiological recovery responses, were determined from an initial group of ten male and eight female elite rowers. No significant (p > 0.05) differences in mean (+/- SD) 500 m time trial performances were found when comparing 500 m times prior to, and after 3 weeks of overload training (89.4 +/- 7.3 s vs. 88.1 +/- 7.3 s), or from the end of the overload training to after the regeneration week (88.6 +/- 6.8s), or over the full 4-week overload-regeneration cycle. Peak and recovery heart rate responses to the test did not differ with training. However, recovery blood lactate concentrations increased, and blood ammonia decreased, after the third and fourth weeks of training. The results indicate that 3 weeks of overload training did not compromise ergometer sprint performance, but altered the metabolic responses during passive recovery. A subsequent 1-week period of 25% reduced volume training was insufficient for positive regenerative adaptations and improved performance.

Adult↗

The stability of lactate concentration in preserved blood microsamples.

This study aimed to determine the stability of lactate concentration in blood samples preserved and stored using methods practical for field testing and experimental applications. Whole blood microsamples were obtained from venous samples drawn from 10 healthy subjects following bouts of moderate (approximately 5 mmol x l(-1), n = 12), or intense (approximately 10 mmol x l(-1), n = 12), treadmill exercise. Samples were analysed fresh (2 x 25 microl), or placed in preservative-containing tubes (12 x 75 microl) and analysed directly, or after storage at room temperature (RT) or 4 degrees C, for 1 h, 18 h, 2 d, 3 d or 7 d, or at -20 degrees C for 7 d. In comparison to preserved samples assayed directly after collection, lactate levels in all RT samples had declined significantly, whereas the 4 degrees C samples had not changed, by 2 d post-collection. After 7 d of refrigeration, the absolute value of the difference from lactate levels in samples measured after collection (mean +/- SD) was 0.38 +/- 0.34 mmol x l(-1), or 5.3 +/- 4.3%; with freezing, this difference was 0.27 +/- 0.27 mmol x l(-1), or 3.6 +/- 3.0%. These differences were less than the daily variation in the analyser readings of a 10 mmol x l(-1) standard, indicating that the blood preservation and storage methods identified herein are suitable for use during exercise testing.

Adult↗

A human YAC transgene rescues craniofacial and neural tube development in PDGFRalpha knockout mice and uncovers a role for PDGFRalpha in prenatal lung growth.

The platelet-derived growth factor alpha-receptor (PDGFRalpha) plays a vital role in the development of vertebrate embryos, since mice lacking PDGFRalpha die in mid-gestation. PDGFRalpha is expressed in several types of migratory progenitor cells in the embryo including cranial neural crest cells, lung smooth muscle progenitors and oligodendrocyte progenitors. To study PDGFRalpha gene regulation and function during development, we generated transgenic mice by pronuclear injection of a 380 kb yeast artificial chromosome (YAC) containing the human PDGFRalpha gene. The YAC transgene was expressed in neural crest cells, rescued the profound craniofacial abnormalities and spina bifida observed in PDGFRalpha knockout mice and prolonged survival until birth. The ultimate cause of death was respiratory failure due to a defect in lung growth, stemming from failure of the transgene to be expressed correctly in lung smooth muscle progenitors. However, the YAC transgene was expressed faithfully in oligodendrocyte progenitors, which was not previously observed with plasmid-based transgenes containing only upstream PDGFRalpha control sequences. Our data illustrate the complexity of PDGFRalpha genetic control, provide clues to the location of critical regulatory elements and reveal a requirement for PDGF signalling in prenatal lung growth, which is distinct from the known requirement in postnatal alveogenesis. In addition, we found that the YAC transgene did not prolong survival of Patch mutant mice, indicating that genetic defects outside the PDGFRalpha locus contribute to the early embryonic lethality of Patch mice.

Animals↗

Expression of developmental myosin and morphological characteristics in adult rat skeletal muscle following exercise-induced injury.

The extent and stability of the expression of developmental isoforms of myosin heavy chain (MHCd), and their association with cellular morphology, were determined in adult rat skeletal muscle fibres following injury induced by eccentrically-biased exercise. Adult female Wistar rats [274 (10) g] were either assigned as non-exercised controls or subjected to 30 min of treadmill exercise (grade, -16 degrees; speed, 15 m x min(-1)), and then sacrificed following 1, 2, 4, 7, or 12 days of recovery (n = 5-6 per group). Histologically and immunohistologically stained serial, transverse cryosections of the soleus (S), vastus intermedius (VI), and tibialis anterior (TA) muscles were examined using light microscopy and digital imaging. Fibres staining positively for MHCd (MHCd+) were seldom detected in the TA. In the VI and S, higher proportions of MHCd+ fibres (0.8% and 2.5%, respectively) were observed in rats at 4 and 7 days post-exercise, in comparison to all other groups combined (0.2%, 1.2%; P < or = 0.01). In S, MHCd+ fibres were observed less frequently by 12 days (0.7%) than at 7 days (2.6%) following exercise. The majority (85.1%) of the MHCd+ fibres had morphological characteristics indicative of either damage, degeneration, repair or regeneration. Most of the MHCd+ fibres also expressed adult slow, and/or fast myosin heavy chain. Quantitatively, the MHCd+ fibres were smaller (< 2500 microm2) and more angular than fibres not expressing MHCd. Thus, there was a transient increase in a small, but distinct population of MHCd+ fibres following unaccustomed, functional exercise in adult rat S and VI muscles. The observed close coupling of MHCd expression with morphological changes within muscle fibres suggests that these characteristics have a common, initial exercise-induced injury-related stimulus.

Animals↗

Interactions of mating, egg production and death rates in females of the Mediterranean fruit fly, Ceratitis capitata.

Costs of reproduction include costs of producing eggs and of mating itself. In the present study, we made an experimental investigation of costs of reproduction in the Mediterranean fruit fly (medfly, Ceratitis capitata). We demonstrated that virgins live longer than non-virgin females. However, in strong contrast to most findings within the Diptera, non-virginity had no detectable effect on egg production. Therefore the increased longevity of the virgin females cannot be attributed to an increase in egg production in non-virgin females, and instead indicates a cost of mating. A comparison of the life spans of normal females and those sterilized by low doses of X-irradiation, revealed an additional cost of egg production. There were no significant differences in remating levels between females that did and did not lay eggs, showing that the cost of producing eggs is independent of mating frequency. Medfly females therefore suffer a decrease in survival as a result of egg production and of mating, and these costs are independent of one another. To put our results into context, we reviewed the existing literature on the effects of mating on longevity, egg production and sexual receptivity for 64 species of Diptera, and examined the pattern of mating effects that emerged.

Animals↗

Pax6 influences the time and site of origin of glial precursors in the ventral neural tube.

Neuroepithelial precursors in the ventral ventricular zone (VZ) of the spinal cord generate motor neurons (MNs) and interneurons, and then a subset of precursors starts to produce oligodendrocyte progenitors (OLPs). We show that OLPs originate in the ventral-most part of the Pax6-positive VZ, which at earlier times generates somatic (Isl2/Lim3-positive) MNs. In Small eye (Pax6-deficient) mice, the origin of OLPs is shifted dorsally and both OLPs and Isl2/Lim3 MNs are delayed. We suggest that somatic MNs and OLPs are generated sequentially from a common set of MN-OL precursors whose position in the VZ is influenced by Pax6. Neuron-glia fate switching might be a preprogrammed property of these precursors or a response to feedback from newly generated neurons. OLs developed normally in explants of Isl1(-/-) spinal cords, which lack MNs, arguing against feedback control and suggesting that the neuron-glia switch is an intrinsic developmental program in a specific subset of neural precursors.

Animals↗

Applied physiology of water polo.

Water polo has been played for over a century. While the rules of the game have evolved considerably over this time, the sport has consistently remained, physiologically, a highly demanding activity. Much attention has been paid to the technical and strategic elements of the game; however, despite the potential for improvements in athletic performance and the maintenance of athletes' health, there are few published studies (particularly in English) on the physical and physiological demands and adaptations to water polo training and competition. Game analyses have demonstrated that water polo is an 'intermittent' sport comprised of intense bursts of activity of <15 seconds duration with intervening, lower intensity intervals averaging <20 seconds duration. Physiological measurements obtained during game play indicate a cumulative effect of the repeated sequences of activities and suggest there is a high metabolic demand on the athletes. The multiple individual skills and movements required for playing water polo also place considerable demands on the neuromuscular system. Observations of the frequency and duration of the different activities, and of the physiological responses to participating in a water polo match, are initial sources of information for designing training programmes specific to the game and to the different playing positions. The physical and physiological attributes of elite water polo players offer some insight into the minimum requirements for participation and the adaptations that result from training and competition. Further systematic documentation and experimentation are required to facilitate the design and specification of individual training programmes and to better understand the long term effects of water polo on athletes' health.

Exercise↗

Synthetic methods for polyamine linkers and their application to combinatorial chemistry.

Polyamines and polyamine conjugates display a diverse range of important biological functions, ranging from antibiotics to immunosuppressants and glutamate receptor antagonists. For these reasons, polyamines provide an excellent template/scaffold for combinatorial chemistry. In this paper we present methods for the solid-phase immobilisation of polyamines for use in synthetic and combinatorial chemistry and describe how they have been employed in the preparation of a number of important polyamine conjugates and polyamine libraries. Thus, we have designed, synthesised and utilised a number of polyamine linkers for both solution and resin screening combinatorial application.

Chemistry, Organic↗

Skeletal muscle damage in the rat hindlimb following single or repeated daily bouts of downhill exercise.

This study was conducted to quantify and compare the extent of fibre degenerative and regenerative processes in different muscles of the rat hindlimb following single or repeated daily bouts of treadmill exercise. Wistar rats were used as non-exercised controls, or subjected to one, five, or ten (n = 8 per group), 30-minute daily bouts (-16 degrees, 12-15m.min-1) of downhill exercise. Soleus (S), vastus lateralis (VL), medial gastrocnemius (MG), plantaris (P), and tibialis anterior (TA) muscles were analyzed from transverse cryosections stained with either H&E for morphological alterations indicative of fibre degeneration or regeneration, or mATPase activity for determination of fibre type. Results showed that in all groups, the percentage of morphologically altered fibres (%AF) was greater in S (4-8%) than in MG, VL, P, or TA (1-2%). The %AF across all muscles was greater following only one, versus multiple exercise bouts, or versus no exercise. The proportions of AF of different histochemical types followed the same distribution as the fibre type in the muscle area examined. These direct assessments indicate that the extent of fibre degenerative and regenerative processes varies among the different muscles involved, and is greater following a single bout, compared to repeated daily bouts of exercise.

Adenosine Triphosphatases↗

Outcome of aggressive removal of cavernous sinus meningiomas.

Despite recent advances in surgery of the cavernous sinus, meningiomas in that area offer a formidable challenge. The rationale for aggressive surgical removal of cavernous sinus meningiomas is based on the presumption that the extent of removal is inversely related to the rate of recurrence. Over the past 10 years, 41 patients with histologically benign meningiomas involving the cavernous sinus underwent aggressive surgery. Total removal, as confirmed by intraoperative inspection and postoperative radiological studies, was achieved in 31 patients (76%). Twelve patients have been followed for more than 5 years; 10 underwent total tumor removal and only one of these experienced recurrence (5 years after surgery). The other two patients underwent subtotal removal and had symptomatic and radiological evidence of regrowth 3 and 4 years after surgery. Pre-existing cranial nerve deficits improved in only 14% of the patients, remained unchanged in 80%, and worsened permanently in 6%. Seven patients experienced a total of 10 new cranial nerve deficits, four of which involved the nerves subserving ocular motor function. Extraocular muscle function did not worsen in the 25 patients with a seeing eye ipsilateral to the tumor, and no instance of visual worsening occurred. Two patients died 4 months after surgery, one from severe delayed vasospasm and hypothalamic infarction and the other because of a myocardial infarction. Another patient died from a pulmonary embolus on the 9th postoperative day. There were three instances of cerebral ischemia; one was transient, lasting less than 24 hours, while two were related to injury of the middle cerebral artery and resulted in residual hemiplegia. Other complications included three cases of nonfatal pulmonary emboli, two cerebrospinal fluid leaks, and one instance each of exposure keratitis, acute hypothyroidism, and cerebral edema.

Adult↗