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Immune changes induced by exercise in an adverse environment.

Both physical activity and exposure to environmental stressors such as cold, heat, and high altitudes modify various components of immune function: T cell counts, natural killer (NK) cell counts, and cytolytic activity, cytokine secretion, lymphocyte proliferation and immunoglobulin levels. Light physical activity or a moderate level of environmental stress stimulate the immune response, but exhausting physical activity or more severe environmental stress have a suppressant effect, manifested by a temporary increase in susceptibility to viral infections. Combinations of physical activity and environmental stress generally have at least an additive effect. Thus, an intensity of physical activity or of environmental stress that is beneficial in itself can readily cause immunosuppression if the body is challenged by the two stimuli simultaneously.

Altitude↗

RecD plays an essential function during growth at low temperature in the antarctic bacterium Pseudomonas syringae Lz4W.

The Antarctic psychrotrophic bacterium Pseudomonas syringae Lz4W has been used as a model system to identify genes that are required for growth at low temperature. Transposon mutagenesis was carried out to isolate mutant(s) of the bacterium that are defective for growth at 4 degrees but normal at 22 degrees . In one such cold-sensitive mutant (CS1), the transposon-disrupted gene was identified to be a homolog of the recD gene of several bacteria. Trans-complementation and freshly targeted gene disruption studies reconfirmed that the inactivation of the recD gene leads to a cold-sensitive phenotype. We cloned, sequenced, and analyzed approximately 11.2 kbp of DNA from recD and its flanking region from the bacterium. recD was the last gene of a putative recCBD operon. The RecD ORF was 694 amino acids long and 40% identical (52% similar) to the Escherichia coli protein, and it could complement the E. coli recD mutation. The recD gene of E. coli, however, could not complement the cold-sensitive phenotype of the CS1 mutant. Interestingly, the CS1 strain showed greater sensitivity toward the DNA-damaging agents, mitomycin C and UV. The inactivation of recD in P. syringae also led to cell death and accumulation of DNA fragments of approximately 25-30 kbp in size at low temperature (4 degrees ). We propose that during growth at a very low temperature the Antarctic P. syringae is subjected to DNA damage, which requires direct participation of a unique RecD function. Additional results suggest that a truncated recD encoding the N-terminal segment of (1-576) amino acids is sufficient to support growth of P. syringae at low temperature.

Alkylating Agents↗

Triiodothyronine treatment for Raynaud's phenomenon: a controlled trial.

The effects of 80 micrograms triiodothyronine (T3) daily were compared with placebo in a double blind controlled crossover trial in 18 patients with Raynaud's phenomenon. Reductions in the frequency, duration and severity of attacks while taking T3 were gradual but highly significant. Four of 6 subjects had skin ulcer healing. Skin temperatures in the hands increased significantly. The skin temperature recovery times after cold exposure were significantly shorter during T3 therapy compared with placebo. Although large dosages of T3 were well tolerated, 6 patients experienced episodic palpitations, and slight but significant increases in heart rate and pulse pressure were observed. Evaluation of the use of physiological doses of T3 (60 micrograms daily or less) in the treatment of Raynaud's phenomenon is suggested.

Adolescent↗

Heat- and cold-stress suppresses in vivo and in vitro cellular immune responses of chickens.

The influence of hot and cold ambient temperatures on cellular immune responses of chickens was assessed, utilizing dinitrofluorobenzene-induced contact sensitivity, phytohemagglutinin (PHA) skin test, and PHA-stimulated, whole blood lymphocyte transformation assays. Dinitrofluorobenzene- and PHA-induced wattle swelling were reduced (P less than 0.05) in birds exposed to air temperatures of 36 degrees C for 1 C for 5 days when compared with wattle swelling in chickens maintained at 26 C. The PHA-induced lymphocyte transformation, as measured by tritiated thymidine uptake, was also suppressed (P less than 0.05) in chickens exposed to either heat or cold stress for 5 days. Some breed differences were observed. These data demonstrated that chronic heat and cold stress impaired expression of contact sensitivity in vivo and proliferation of T lymphocytes in vitro in the avian species. Synthesis of antibodies to sheep RBC on day 5 after antigen injection was not altered (P greater than 0.05) when birds were vaccinated 24 hours before the start of thermal stress. This indicated that B cell and T-helper cell functions were not compromised by chronic thermal stress. However, New Hampshire birds that were heat-stressed had higher (P less than 0.05) antibody titers than control birds 10 days after vaccination.

Animals↗

[Life threatening anaphylaxis after repeated cisplatin administration: case report and neu therapy concepts].

The present case reports of a 58-year-old female patient presenting with severe (III degrees) anaphylactic reaction due to repeated chemotherapy with Cisplatin. After resection of the advanced ovarian carcinoma the patient was presented with complaints of itching, angioneurotic edema and dyspnea in 1990 when Cisplatin had been infused for the first time. Due to relapse after four years a further operation was performed and as much of the tumour as possible was resected. Then again, Cisplatin was applied. Cortisone, H1- and H2-blockers were given prior to its application increasing the tolerance of treatment. Subsequent treatment with further Cisplatin infusion, however, resulted in severe anaphylactic shock with dyspnea and cold sweat. Emergency treatment included application of pure oxygen, two large i.v. cannulas, and 1.5 l of crystalloid, and 0.5 l of colloids (Gelafundin). Additionally, a potent vasoconstrictor (Akrinor) and 750 mg Methylprednisolone were given. Symptoms improved as blood pressure normalised, and the patient felt much better 20 minutes later. In summary, the present case report proves that anaphylactic shock induced by Cisplatin demands interdisciplinary action. This particularly applies to the interval between occurrence of the first shock signs and arrival of the emergency team.

Anaphylaxis↗

The effect of cold stress on lymphocyte proliferation in fetal ethanol-exposed rats.

Prenatal ethanol exposure and stress have each been shown to have significant effects on the immune system. This study examined the possible interactive effects of prenatal ethanol exposure and exposure to stress later in life on the immune system. Differential vulnerability to these challenges in female and male offspring was assessed. At 5 to 6 months of age, female and male offspring from prenatal ethanol-exposed (E), pair-red (PF), and ad libitum-fed control (C) conditions were exposed to 0, 1 or 3 days of cold (4 degrees C). At the end of the cold period, the proliferative response of splenic lymphocytes to the mitogens concanavalin A (Con A) and pokeweed mitogen (PWM) was assessed. The data demonstrate a significant interactive effect between prenatal ethanol exposure and cold stress in female offspring. After 1 day of cold stress, E females had significantly increased PWM-induced lymphocyte proliferation compared with PF and C females, and significantly increased Con A-induced lymphocyte proliferation compared with PF females. There were no differences in PWM or Con A-induced lymphocyte proliferation among E, PF, and C females after 0 or 3 days of cold stress, nor among E, PF, and C males on any test day. Regardless of prenatal treatment, females exposed to 1 or 3 days of cold had significantly greater basal plasma corticosterone levels than females not exposed to cold. In contrast, only E males exposed to 1 or 3 days of cold had significantly increased basal plasma corticosterone levels, compared with E males not exposed to cold; PF and C males showed no significant change in basal corticosterone after cold stress. These data demonstrate that, in response to the challenge of cold stress, changes in lymphocyte proliferation to PWM and Con A may occur selectively in E females. Moreover, the interactive effects of prenatal ethanol and cold stress may result in enhanced rather than suppressed immune responsiveness.

Acclimatization↗

Low-Temperature Effects on Photosynthesis and Correlation with Freezing Tolerance in Spring and Winter Cultivars of Wheat and Rye.

Winter cultivars of rye (Secale cereale L., cv Musketeer) and wheat (Triticum aestivum L. cvs Kharkov and Monopol), but not a spring cultivar of wheat (Glenlea), grown at cold-hardening temperatures showed, at high irradiances, a higher proportion of oxidized to reduced primary, stable quinone receptor (QA) than did the same cultivars grown under nonhardening conditions. In addition, there was a positive correlation between the effects of low-growth temperature on this increased proportion of oxidized QA, and a concomitant increase in the capacity for photosynthesis, and LT50, the temperature at which 50% of the seedlings are killed, in cultivars showing different freezing tolerances. This suggests that low-temperature modulation of the photosynthetic apparatus may be an important factor during the induction of freezing resistance in cereals. Finally, the control of photosystem II photochemistry by nonphotochemical quenching of excitation energy was identical for nonhardened and cold-hardened winter rye. However, examination of measuring temperature effects per se revealed that, irrespective of growth temperature, nonphotochemical quenching exerted a stronger control on photosystem II photochemistry at 10[deg] C rather than at 20[deg] C.

Journal Article↗

CTLA4Ig gene transfer prolongs survival and induces donor-specific tolerance in a rat renal allograft.

Organ transplantation requires lifelong antirejection therapy, which carries the risk of infection and cancer. A revolutionary approach is to transduce the organ graft with immunomodulatory genes to render them tolerated with no need of systemic immunosuppression. Prolonged allograft survival was achieved by adenovirus-mediated transduction of the cold-preserved kidney with sequences encoding CTLA4Ig, a recombinant fusion protein that blocks T cell activation. Organ expression of the transgene was achieved associated with mild infiltration of mononuclear cells in the transfected kidney. Mixed lymphocyte reaction as well as the production of both Thl and Th2 cytokines were reduced. Thus, the gene transfer technique to prolong graft survival is indeed effective and safe and can induce donor-specific unresponsiveness. Pending appropriate large animal testing, ex vivo genetic manipulation of the organ before surgery may hopefully represent a major step forward in human transplant medicine.

Abatacept↗

The effect of overexpression of two Brassica CBF/DREB1-like transcription factors on photosynthetic capacity and freezing tolerance in Brassica napus.

The effects of overexpression of two Brassica CBF/DREB1-like transcription factors (BNCBF5 and 17) in Brassica napus cv. Westar were studied. In addition to developing constitutive freezing tolerance and constitutively accumulating COR gene mRNAs, BNCBF5- and 17-overexpressing plants also accumulate moderate transcript levels of genes involved in photosynthesis and chloroplast development as identified by microarray and Northern analyses. These include GLK1- and GLK2-like transcription factors involved in chloroplast photosynthetic development, chloroplast stroma cyclophilin ROC4 (AtCYP20-3), beta-amylase and triose-P/Pi translocator. In parallel with these changes, increases in photosynthetic efficiency and capacity, pigment pool sizes, increased capacities of the Calvin cycle enzymes, and enzymes of starch and sucrose biosynthesis, as well as glycolysis and oxaloacetate/malate exchange are seen, suggesting that BNCBF overexpression has partially mimicked cold-induced photosynthetic acclimation constitutively. Taken together, these results suggest that BNCBF/DREB1 overexpression in Brassica not only resulted in increased constitutive freezing tolerance but also partially regulated chloroplast development to increase photochemical efficiency and photosynthetic capacity.

Adaptation, Physiological↗

The Irving-Scholander legacy in polar physiology.

The pioneer arctic and cold environment studies of Laurence Irving and Per Scholander, undertaken during the middle decades of the 20th century, have had a wide ranging and major influence on the direction and character of experimental research on polar species. Their investigations included comparative studies of metabolism, insulation, and acclimatization of mammals and birds in arctic Alaska and the tropics. Freezing, supercooling, and antifreeze research included fishes, insects, and plants. They examined the special problems of cooling in appendages of mammals and birds and the potential for acclimatization of these structures by repeated cold exposure. Studies of cold exposure in human populations considered possible adaptive reactions. Their research on diving mammals opened a vast new area for studies with attention to asphyxial tolerance and temperature regulation. A lesser-known accomplishment was an innovative approach to recovery of ancient atmospheric gases from polar ice fields, an approach that was stimulated by original investigations of frozen insect larvae and gas permeability through ice.

Adaptation, Physiological↗

Quantitative sensory testing for spinal cord stimulation in patients with chronic neuropathic pain.

OBJECTIVE: A prospective pilot study was conducted, attempting to identify objective tests that would help clinicians to assess the efficacy of spinal cord stimulation (SCS) trial preceding permanent device implantation. SETTING: Four university hospitals in the United States and Israel. PARTICIPANTS: Thirteen patients with radicular leg pain due to failed back surgery syndrome (FBSS) or leg pain due to complex regional pain syndrome (CRPS) who were candidates for SCS. METHODS: PARTICIPANTS underwent a series of quantitative sensory tests prior to, and seven days after the initiation of SCS trial. These tests included: vibration threshold (conducted using the VSA 3000; Medoc Inc., Ramat Ishay, Israel), cold threshold, warm threshold, heat pain threshold, phasic heat pain threshold, tonic heat pain threshold (conducted using the TSA 2001; Medoc Inc.), and electrical pain tolerance at 5, 250 and 2000 Hz (administered using the NerveScan 2000; Neurotron, Inc., Baltimore, MD, USA). RESULTS: Useful data were obtained from 12 patients. The results of the vibration threshold and the tolerance to electrical stimulation at 5 and 250 Hz changed with an SCS trial. These results also correlated with the decision regarding the permanent implantation, which was made independently of them. In contrast, the results of thermal thresholds and tolerance to electrical stimulation at 2000 Hz tests did not change with the SCS trial. CONCLUSIONS: Our findings, which agree with those of a few other studies, suggest that the vibration threshold and the tolerance to electrical stimulation at 5 and 250 Hz tests can assist the clinician to select the right patients for permanent stimulation.

Adolescent↗

Metabolic causes of equine exercise intolerance.

Metabolic causes of exercise intolerance can be subtle and difficult to document in horses. Because of increased metabolic rate in exercising muscle, most metabolic causes of exercise intolerance are clinically manifested by muscle abnormalities such as ER. Newer causes of ER are being documented by current research and are summarized in the article on muscular causes of equine exercise intolerance. Endocrine causes of exercise intolerance have been poorly documented, but recent work has shown the detrimental effects of hypothyroidism on exercise tolerance in horses. Many metabolic manifestations of exercise intolerance are cumulative in heat exhaustion; prevention by veterinary monitoring is the best treatment, followed by cold water bathing and oral or intravenous fluid and electrolyte replacement. Several ergogenic aids have been proposed and marketed for use in horses, but each has its own problems and few have been shown clearly to have positive effects on performance.

Acid-Base Equilibrium↗

Interferon alfa 2a in superficial bladder cancer prophylaxis: toleration and long-term follow-up. A phase I-II study.

Twenty patients (17 M., 3F., -mean age 61.5 yrs) affected by superficial bladder tumors (TINOMO) were included in the study. All patients had cold mucosa biopsy to exclude the presence of dysplasia or CIS; the histopathological grade was G1 in 19 cases and G2 in 1. The treatment was started between 3 to 7 days after radical TUR with intravesical instillations of recombinant Interferon alfa 2a, at the daily dose of 54 million/Units for 5 days for 2 consecutive weeks. No systemic adverse effects were observed. Local toleration and efficacy were assessed by cystoscopy, performed at the end of treatment after 6 weeks and then at three month intervals. At the first control 15% of patients showed an early local reaction with bollous oedema surrounding the resected area (with spontaneously disappeared after few days). No other abnormal findings were observed at the 6-week control. After a median follow-up of 98 weeks, 15 of the 19 evaluable patients (79%, C.I. 60-91) were disease-free. The median relapse time was 39.9 weeks, while clinical and local tolerance were optimal. These preliminary data confirm the complete absence of toxicity of Interferon alfa 2a administered at relatively high doses intravesically and indicate that this compound has some effect on superficial bladder cancer.

Adolescent↗

Genetic engineering of glycinebetaine synthesis in plants: current status and implications for enhancement of stress tolerance.

Metabolic acclimation via the accumulation of compatible solutes is regarded as a basic strategy for the protection and survival of plants in extreme environments. Certain plants accumulate significant amounts of glycinebetaine (betaine), a compatible quaternary amine, in response to high salinity, cold and drought. It is likely that betaine is involved in the protection of macrocomponents of plant cells, such as protein complexes and membranes, under stress conditions. Genetic engineering of the biosynthesis of betaine from choline has been the focus of considerable attention as a potential strategy for increasing stress tolerance in stress-sensitive plants that are incapable of synthesizing this compatible/protective solute. Three distinct pathways for the synthesis of betaine have been identified in spinach, Escherichia coli and Arthrobacter globiformis, and various genes and cDNAs for the proteins involved are available. Moreover, each of the pathways has been exploited to a greater or lesser extent in efforts to convert betaine-deficient plants to betaine accumulators. In this review, the potential of several recent examples of transgenic approaches to the enhancement of stress tolerance in plants is summarized and discussed.

Adaptation, Physiological↗