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Black widow spider (Latrodectus mactans) envenomation is found throughout both the temperate and tropical latitudes, and is one of the leading causes of death from arthropod envenomations worldwide. The venom is highly neurotoxic, affecting the presynaptic motor endplate to allow massive noradrenaline (norepinephrine) and acetylcholine release into synapses causing excessive stimulation and fatigue of the motor end plate and muscle. Clinically, patients develop a bite site lesion and pain, abdominal pain and tenderness, and lower extremity pain and weakness within minutes to hours of envenomation. Symptoms progress over several hours, then subside over 2 to 3 days. The recommended treatment of 'common' envenomation is calcium gluconate 10% intravenously, titrated to relief of symptoms; antivenin, although effective, may cause hypersensitivity and serum sickness reactions, and should be restricted to life-threatening envenomations only. Brown recluse spider (Loxosceles reclusa) envenomations are seen in the Americas and in Europe, and are endemic to the south and central United States. The venom contains at least 8 enzymes, consisting of various lysins (facilitating venom spread) and sphingomyelinase D, which causes cell membrane injury and lysis, thrombosis, local ischaemia, and chemotaxis. Local envenomations begin as pain and itching that progresses to vesiculation with violaceous necrosis and surrounding erythema, and ultimately ulcer formation. Systemic envenomations may be life threatening, and present with fever, constitutional symptoms, petechial eruptions, thrombocytopenia, and haemolysis with haemoglobinuric renal failure. Treatment of local envenomations is conservative (local wound care, cryotherapy, elevation, tetanus prophylaxis, and close follow-up); systemic envenomation requires supportive care and treatment of arising complications, corticosteroids to stabilise red blood cell membranes, and support of renal function. Dapsone 100mg daily has emerged as a promising therapeutic agent in both animal studies and clinical trials. Over 650 species of scorpions are known to cause envenomation (mostly in children under 10 years); they are endemic mostly in arid and tropical areas. Different venoms and clinical presentations are seen across the different species. Most commonly, an inflammatory local reaction occurs with envenomation, which is treated with wound debridement and cleaning, tetanus prophylaxis, and antihistamines. Occasionally the venom is allergenic, and the resultant allergic reaction is treated in a standard fashion.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Acute arthropod envenomation. Incidence, clinical features and management. 266 28

Six characteristics of life events and difficulties, namely loss (L), threat (T), anti-social act (A), hopeless situation (H), uncertain outcome (U) and choice of action (C), were used to score life situations experienced by 1060 adults over three months. Certain patterns of these, together with the respondents' sex, close and more superficial support discriminated significantly between subjects who had: depression the predominant symptom, anxiety predominant, tiredness predominant, backache predominant, none of these reaching pathological level. A hierarchy emerged from depression down through anxiety to tiredness and backache such that more severe life situations were associated with symptoms higher up the hierarchy. Situations with both choice of action (C) and loss (L) tended to be associated with depression. Anxiety related situations were mainly those containing threat (T) and at least two other characteristics. Tiredness went with situations characterised purely as CUH or CH or UH, and backache with minor situations containing only one characteristic. Lack of close confidant was most associated with depression; being a woman was associated with tiredness and anxiety equally and lack of superficial support with anxiety and depression equally. A parallel was drawn with Finlay-Jones and Brown.
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PMID:Dimensions of experience and symptomatology. 293 14

The winter athlete has several potential tactics for sustaining body temperature in the face of severe cold. An increase in the intensity of physical activity may be counter-productive because of increased respiratory heat loss, increased air or water movement over the body surface, and a pumping of air or water beneath the clothing. Shivering can generate heat at a rate of 10 to 15 kJ/min, but it impairs skilled performance, while the resultant glycogen usage hastens the onset of fatigue and mental confusion. Non-shivering thermogenesis could arise in either brown adipose tissue or white fat. Brown adipose tissue generates heat by the action of free fatty acids in uncoupling mitochondrial electron transport, and by noradrenaline-induced membrane depolarisation and sodium pumping. The existence of brown adipose tissue in human adults is controversial, and although there are theoretical mechanisms of heat production in white fat, their contribution to the maintenance of body temperature is small. Acclimatisation to cold develops over the course of about 10 days, and in humans the primary change is an insulative, hypothermic type of response; this reflects the intermittent nature of most occupational and athletic exposures to cold. Nevertheless, with more sustained exposure to cold air or water, humans can apparently develop the humoral type of acclimatisation described in small mammals, with an increased output of noradrenaline and/or thyroxine. The associated mobilisation of free fatty acids suggests the possibility of using winter sport as a pleasant method of treating obesity. In men, a combination of moderate exercise and facial cooling induces a substantial fat loss over a 1- to 2-week period, with an associated ketonuria, proteinuria, and increase of body mass. Possible factors contributing to this fat loss include: (a) a small energy deficit; (b) the energy cost of synthesising new lean tissue; (c) energy loss through the storage and excretion of ketone bodies; (d) catecholamine-induced 'futile' metabolic cycles with increased resting metabolism; and (e) a specific reaction to cold dehydration. Current limitations for the clinical application of such treatment include uncertainty regarding optimal environmental conditions, concern over possible pathological reactions to cold, and suggestions of a less satisfactory fat mobilisation in female patients. Possible interactions between physical fitness and metabolic reactions to cold remain controversial.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Adaptation to exercise in the cold. 388 60

1. Imposed sinusoids were used to assess the resistance to movement at the thumb interphalangeal joint.2. The resistance to high-frequency movements (> 12 Hz) increased when the subject exerted a large voluntary flexing force; this increase was attributable to a greater non-reflex resistance of the contracting flexor muscles. This resistance was essentially ;visco-elastic', and the force was phase-advanced on joint position. At moderately large forces (up to half maximal), however, the resistance changed with changing frequency, and over a range 4-12 Hz the vectors which represented joint stiffness described the wide path that is characteristic of an active stretch reflex (Brown, Rack & Ross, 1982a). At frequencies between about 4 and 6 Hz the force was sometimes phase-delayed on position, and the joint exhibited a negative viscous stiffness. When the voluntary flexing force was very large the reflex contributed less to the resisting force, which was then phase-advanced on position at all frequencies of movement.3. Large amplitude movements did not generate correspondingly large reflex responses; as the amplitude of movement was increased, the reflex component of the resisting force became relatively smaller and the total resisting force was then phase-advanced on joint position at all frequencies.4. The reflex component of the resisting force (as indicated by the excursion of the joint stiffness vectors) varied from subject to subject and from time to time; the reflex usually became more active late in an experiment when the subject had exerted flexing forces against the imposed movement for some minutes. Extreme fatigue, however, diminished the amount of reflex force.5. In some subjects the joint-stiffness records indicated a particularly vigorous reflex response at 8-11 Hz, in contrast to a rather feeble response at 6 or 7 Hz. It is suggested that the reflex pathways then had a relatively low impedance to afferent signals that were modulated at 8-11 Hz, related perhaps to the firing patterns of the most recently recruited motoneurones.6. Under the conditions of these experiments, it appears that the stretch reflex has too small a gain to function as a very effective error-controlled position servo-mechanism.
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PMID:A range of different stretch reflex responses in the human thumb. 715 22

The mechanisms underlying skeletal muscle functional impairment and structural changes with advanced age are only partially understood. In the present study, we support and expand our theory about alterations in sarcolemmal excitation-sarcoplasmic reticulum Ca2+ release-contraction uncoupling as a primary skeletal muscle alteration and major determinant of weakness and fatigue in mammalian species including humans. To test the hypothesis that the number of RYR1 (ryanodine receptor) uncoupled to DHPR (dihydropyridine receptor) increases with age, we performed high-affinity ligand binding studies in soleus, extensor digitorum longus (EDL) and in a pool of several skeletal muscles consisting of a mixture of fast- and slow-twitch muscle fibers in middle-aged (14-month) and old (28-months) Fisher 344 Brown Norway F1 hybrids rats. The number of DHPR, RYR1, the coupling between both receptors expressed as the DHPR/RYR1 maximum binding capacity, and their dissociation constant for high-affinity ligands were measured. The DHPR/RYR1 ratio was significantly reduced in the three groups of muscles (pool: 1.03 +/- 0.15 and 0.80 +/- 0.11, soleus: 0.44 +/- 0. 12 and 0.26 +/- 0.10, and EDL: 0.95 +/- 0.14 and 0.68 +/- 0.10, for middle-aged and old muscles, respectively). These data support the concept that DHPR-RYR1 uncoupling results in alterations in the voltage-gated sarcoplasmic reticulum Ca2+ release mechanism, decreases in myoplasmic Ca2+ elevation in response to sarcolemmal depolarization, reduced Ca2+ supply to contractile proteins and reduced contraction force with aging.
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PMID:Dihydropyridine receptor-ryanodine receptor uncoupling in aged skeletal muscle. 917 12

Brown adipose tissue (BAT) has the capacity for uncoupled mitochondrial respiration and is proposed to be a key site for regulating energy expenditure in rodents. To better define the role of BAT in energy homeostasis, we previously created a line of transgenic mice with deficiency of BAT (UCP promoter-driven diphtheria toxin A transgenic mice [UCP-DTA]) mice. These mice develop obesity that initially is due to decreased energy expenditure and later accompanied by hyperphagia despite increased levels of circulating leptin. In addition, the obesity of these mice is accompanied by severe insulin-resistant diabetes and hyperlipidemia. To better define the basis for leptin resistance in this model, we treated UCP-DTA mice with leptin (300 microg i.p., b.i.d.) and compared their response with that of leptin-treated ob/ob and FVB control mice (30 microg i.p., b.i.d.). Leptin treatment of FVB and ob/ob mice decreased their body weight and food intake and improved their glucose homeostasis. In contrast, tenfold higher dosages of leptin had no effect on body weight, food intake, or circulating insulin or glucose concentrations of UCP-DTA mice. Hypothalamic neuropeptide Y (NPY) mRNA expression was lower in UCP-DTA mice than in littermate control FVB mice in the fed state, and increased progressively in response to food restriction as leptin levels fell. In parallel to the levels of hypothalamic NPY, corticosterone levels were initially suppressed and rose with food restriction. Thus food intake, body weight, and insulin and glucose homeostasis of UCP-DTA mice are all extraordinarily resistant to leptin, whereas hypothalamic NPY and the hypothalamopituitary adrenal (HPA) axis may remain under leptin control. Further elucidation of the mechanisms underlying leptin resistance in UCP-DTA mice may provide valuable insights into the basis for leptin resistance in human obesity.
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PMID:Severe leptin resistance in brown fat-deficient uncoupling protein promoter-driven diphtheria toxin A mice despite suppression of hypothalamic neuropeptide Y and circulating corticosterone concentrations. 951 18

Brown adipose tissue-deficient [uncoupling protein (UCP)-promoter-driven diphtheria toxin A (DTA)] mice develop obesity as a result of both decreased energy expenditure and hyperphagia. The hyperphagia occurs despite high serum leptin levels. Hence, this is a model of leptin-resistant obesity in which the mechanism driving hyperphagia is unknown. Leptin is a regulator of a number of hypothalamic neuropeptides involved in energy homeostasis. In ob/ob mice, leptin deficiency results in increased expression of neuropeptide Y (NPY), agouti-related protein (AGRP), and melanin-concentrating hormone (MCH), and decreased expression of POMC. We have previously shown that NPY is reduced in the UCP-DTA mouse, suggesting a normal NPY response to leptin. To define other potential sites of leptin resistance, we used in situ hybridization to evaluate the expression of messenger RNAs (mRNAs) encoding a number of peptides, including NPY, AGRP, MCH, and POMC. We confirmed that the decrease in NPY expression previously detected by Northern blots reflects a decrease in NPY expression in the arcuate nucleus. AGRP mRNA was also decreased, whereas POMC mRNA levels in the arcuate nucleus were the same as control. MCH mRNA levels in the lateral hypothalamic area were also decreased. In contrast, there was induction of NPY expression in the dorsomedial hypothalamic nucleus in the UCP-DTA animals but not in the controls. The results indicate that these neuropeptides generally respond to leptin and that the hyperphagia seen in the UCP-DTA mice is likely the result of dysregulated expression of other, as yet unexamined, hypothalamic peptides, or lies at sites distal to the hypothalamus.
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PMID:Characterization of expression of hypothalamic appetite-regulating peptides in obese hyperleptinemic brown adipose tissue-deficient (uncoupling protein-promoter-driven diphtheria toxin A) mice. 979 75

Aviation medicine came into existence as a recognized entity when certain standards were established during and shortly after World War I. During this time, accident rates were high. In fact, a larger number of pilots were dying in accidents than in combat. Figures from Great Britain's casualty list at the close of the first year of World War I indicated that for every 100 aviators killed, 60 died as a result of some individual physical defect, 30 from some form of recklessness or careless behavior, 8 as a result of some mechanical defect in the airplane, and only 2 at the hands of the enemy. Aviators were found to be in poor physical condition. Because there were no established regulations with regard to workloads, aviators were frequently found to have been flying to a point beyond exhaustion. Because of workload, chronic fatigue, and emotional stress, aviators were constantly called upon to perform superhuman feats when not in peak physical condition. Errors in judgement were common. The majority of pilots lost weight as a somatic sign of stress. This was recognized by Theodore Lyster [corrected] who had recently been appointed as the Chief Surgeon, Aviation Section of the U.S. Army. Such problems were not diagnosed by medical officers because they were not trained to recognize them. Theodore Charles Lyster [corrected] was the son of Captain William J. and Martha Doughty Lyster [corrected]. He was an Army "brat" who entered the world on July 10, 1875. His childhood was spent in various posts around the country. At the age of 7, Lyster [corrected] contracted yellow fever while living in Fort Brown, TX. The boy was treated by William Gorgas, a young post surgeon. Gorgas was credited with the young boy's recovery. Later, Gorgas was to marry Lyster's [corrected] aunt making Lyster [corrected] his nephew by marriage. Having survived the yellow fever infection, young Lyster [corrected] had a lifelong immunity to the disease.
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PMID:Brigadier General Theodore C Lyster [correction of Lister], MD: father of American aviation medicine. 1091 89

The SHIRPA protocol was proposed as a rapid, comprehensive screening method for qualitatively abnormal phenotypes in the mouse (Rogers et al., Mamm Genome 8, 711, 1997). This screening technique is currently being used to identify mutants induced by N-ethylnitrosourea (ENU) mutagenesis (Brown and Nolan, Hum Mol Genet 7, 1627, 1998). SHIRPA can be used to identify mutants with neuromuscular abnormalities, but the sensitivity of the protocol is unknown. We tested two dystrophin-deficient mutants Dmd(mdx) and Dmd(mdx3cv), both of which are indistinguishable from wild-type by a simple visual assessment, at different ages, using the primary screen of the SHIRPA protocol. The most dramatic observation was that both Dmd(mdx) and Dmd(mdx3cv) mice showed extreme fatigue after testing, while mice from the same C57BL strains appeared unaffected. Each strain of dystrophin-deficient mice showed a different profile in locomotor activity and deficiencies in the wire maneuver, righting reflex, and negative geotaxis tests. Furthermore, the wire maneuver test indicated an earlier onset of muscular impairment in Dmd(mdx) than Dmd(mdx3cv) mice. These data suggest that the SHIRPA primary screen is effective not only in identifying subtle neuromuscular mutants, but also in distinguishing qualitative differences between mutants with neuromuscular abnormalities.
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PMID:Testing of SHIRPA, a mouse phenotypic assessment protocol, on Dmd(mdx) and Dmd(mdx3cv) dystrophin-deficient mice. 1096 29

Muscle loss occurs during aging. To investigate whether the hypertrophic response is attenuated at old age, we used male Fischer 344 (26 months old; n = 5) and Fischer 344 x Brown Norway rats (6, 9, and 33 months old; n = 8, 10, and 6, respectively). Hypertrophy of the left plantaris muscle was induced by surgical denervation of its agonists. The right leg served as control. The mass and maximal tetanic force (P(0)) of control muscles declined by approximately 30% between 9 and 26 months (P < 0.05). Fatigue resistance during intermittent isometric contractions was reduced by approximately 60% at 33 months. At 33 months, the attenuated hypertrophy was accompanied by a decrease rather than an increase in P(0). Yet, hypertrophy was accompanied by a 25% rise in fatigue resistance at all ages (P = 0.001). Thus, aging is associated with a decline in muscle mass and function. In addition, at advanced age, the hypertrophic response is reduced and a hypertrophic stimulus even aggravates the age-associated muscle weakening.
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PMID:Skeletal muscle function and hypertrophy are diminished in old age. 1263 21

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