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- Trainer, P J, et al.
(författare)
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Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant.
- 2000
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Ingår i: The New England journal of medicine. - 0028-4793. ; 342:16, s. 1171-7
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Tidskriftsartikel (refereegranskat)abstract
- Patients with acromegaly are currently treated with surgery, radiation therapy, and drugs to reduce hypersecretion of growth hormone, but the treatments may be ineffective and have adverse effects. Pegvisomant is a genetically engineered growth hormone-receptor antagonist that blocks the action of growth hormone.We conducted a 12-week, randomized, double-blind study of three daily doses of pegvisomant (10 mg, 15 mg, and 20 mg) and placebo, given subcutaneously, in 112 patients with acromegaly.The mean (+/-SD) serum concentration of insulin-like growth factor I (IGF-I) decreased from base line by 4.0+/-16.8 percent in the placebo group, 26.7+/-27.9 percent in the group that received 10 mg of pegvisomant per day, 50.1+/-26.7 percent in the group that received 15 mg of pegvisomant per day, and 62.5+/-21.3 percent in the group that received 20 mg of pegvisomant per day (P<0.001 for the comparison of each pegvisomant group with placebo), and the concentrations became normal in 10 percent, 54 percent, 81 percent, and 89 percent of patients, respectively (P<0.001 for each comparison with placebo). Among patients treated with 15 mg or 20 mg of pegvisomant per day, there were significant decreases in ring size, soft-tissue swelling, the degree of excessive perspiration, and fatigue. The score fortotal symptoms and signs of acromegaly decreased significantly in all groups receiving pegvisomant (P< or =0.05). The incidence of adverse effects was similar in all groups.On the basis of these preliminary results, treatment of patients who have acromegaly with a growth hormone-receptor antagonist results in a reduction in serum IGF-I concentrations and in clinical improvement.
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| 4. |
- Andersson, C., et al.
(författare)
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Improved systems for hydrophobic tagging of recombinant immunogens for efficient iscom incorporation
- 2000
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Ingår i: JIM - Journal of Immunological Methods. - 0022-1759 .- 1872-7905. ; 238:02-jan, s. 181-193
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Tidskriftsartikel (refereegranskat)abstract
- We have previously reported a strategy for production in Escherichia coli of recombinant immunogens fused to a hydrophobic tag to improve their capacity to associate with an adjuvant formulation [Andersson et al., J. Immunol. Methods 222 (1999) 171]. Here, we describe a further development of the previous strategy and present significant improvements. In the novel system, the target immunogen is produced with an N-terminal affinity tag suitable for affinity purification, and a C-terminal hydrophobic tag, which should enable association through hydrophobic interactions of the immunogen with an adjuvant system, here being immunostimulating complexes (iscoms). Two different hydrophobic tags were evaluated: (i) a tag denoted M, derived from the membrane-spanning region of Staphylococcus aureus protein A (SpA), and (ii) a tag denoted MI consisting of the transmembrane region of hemagglutinin from influenza A virus. Furthermore, two alternative affinity tags were evaluated; the serum albumin-binding protein ABP, derived from streptococcal protein G, and the divalent IgG-binding ZZ-domains derived from SpA. A malaria peptide M5, derived from the central repeat region of the Plasmodium falciparum blood-stage antigen Pf155/RESA, served as model immunogen in this study. Four different fusion proteins, ABP-MS-M, ABP-MS-MI, ZZ-MS-M and ZZ-MS-MI, were thus produced, affinity purified and evaluated in iscom-incorporation experiments. All of the fusion proteins were found in the iscom fractions in analytical ultracentrifugation, indicating iscom incorporation. This was further supported by electron microscopy analysis showing that iscoms were formed. In addition, these iscom preparations were demonstrated to induce MS-specific antibody responses upon immunisation of mice, confirming the successful incorporation into iscoms. The novel system for hydrophobic tagging of immunogens, with optional affinity and hydrophobic tags, gave expression levels that were increased ten to fifty-fold, as compared to the earlier reported system. We believe that the presented strategy would be a convenient way to achieve efficient adjuvant association for recombinant immunogens.
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| 5. |
- Bengtsson, B A, et al.
(författare)
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Treatment of growth hormone deficiency in adults.
- 2000
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 85:3, s. 933-42
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Tidskriftsartikel (refereegranskat)abstract
- In analogy with other hormonal replacement therapy GH treatment should be commenced with a low starting dose, independent of body weight or body surface area. Hormonal replacement should mimic the normal physiology to minimize the risk of side effects in the life-long replacement of adults. We should, therefore, consider individual responsiveness and also be aware of the difference between pattern of GH under normal condition and during s.c. administration. The safety and monitoring of GH replacement therapy in adults have been addressed in the Growth Hormone Research Society Consensus Guidelines for Diagnosis and Treatment of Adults with GH Deficiency from the Port Stephens Workshop, April 1997. Besides finding better and more accurate biochemical markers for choosing correct GH replacement dose, future research should address the long-term benefits and safety with GH replacement in adults, with special emphasize on incipient risks in terms of cardiovascular disease and of neoplasia, in particular.
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| 6. |
- Bengtsson, M, et al.
(författare)
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A DSP controlled data acquisition system for CELSIUS
- 2000
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Ingår i: NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT. - : ELSEVIER SCIENCE BV. - 0168-9002. ; 441:1-2, s. 76-80
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Tidskriftsartikel (refereegranskat)abstract
- We describe a data acquisition system based on two 10 MHz A/D-converters, a SHARC Digital Signal Processor (DSP), and a digital synthesizer used for triggering the A/D-converters. The temporal macrostructure of the data acquisition can be determined by ex
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| 8. |
- Bäckman, A. C., et al.
(författare)
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Antennal response of codling moth males, Cydia pomonella L. (Lepidoptera: Tortricidae), to the geometric isomers of codlemone and codlemone acetate
- 2000
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Ingår i: Journal of Comparative Physiology A. Sensory, neural, and behavioral physiology. - : Springer. - 0340-7594 .- 1432-1351. ; 186:6, s. 513-519
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Tidskriftsartikel (refereegranskat)abstract
- Single sensillum recordings from Cydia pomonella male antennae showed three different types of receptor neurons. The most abundant type was most sensitive to the main pheromone compound (E,E)-8,10-dodecadienol, while its response to the geometric isomers E,Z, Z,E and Z,Z was comparable to a tenfold lower dose of (E,E)-8,10-dodecadienol. This neuron type also responded to the four behaviorally antagonistic isomers of (Delta,Delta)-8,10-dodecadienyl acetate, among which it was most sensitive to the E,E isomer. Cross-adaptation studies showed that these compounds were all detected by the same receptor neuron type. Receptor neurons specifically tuned to (E,Z) or (Z,Z)-8,10-dodecadienol were not found, although these two compounds are behaviorally active. A second type of receptor neuron responded to all isomers of (Delta,Delta)-8,10-dodecadienyl acetate and was most sensitive to the E,E isomer. This neuron type did not respond to any of the isomers of (Delta,Delta)-8,10-dodecadienol. A third receptor neuron type was highly sensitive to the plant compound alpha-farnesene. The finding that the receptor neuron type tuned to the main pheromone compound responded even to strong behavioral antagonists aids the interpretation of ongoing behavioral studies for the development of the mating disruption technique in codling moth.
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| 10. |
- Graven-Nilsen, T, et al.
(författare)
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Ketamine reduces muscle pain, temporal summation, and referred pain in fibromyalgia patients
- 2000
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Ingår i: Pain. - 0304-3959 .- 1872-6623. ; 85:3, s. 483-491
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Tidskriftsartikel (refereegranskat)abstract
- Central mechanisms related to referred muscle pain and temporal summation of muscular nociceptive activity are facilitated in fibromyalgia syndrome (FMS) patients. The present study assessed the effects of an NMDA-antagonist (ketamine) on these central mechanisms. FMS patients received either i.v. placebo or ketamine (0.3 mg/kg, Ketalar(«)) given over 30 min on two separate occasions. Habitual pain intensity was assessed on a visual analogue scale (VAS). Initially, 29 FMS patients received ketamine or isotonic saline to determine which patients were ketamine responders (>50% decrease in pain intensity at rest by active drug on two consecutive VAS assessments). Fifteen out of 17 ketamine-responders were included in the second part of the study. Before and after ketamine or placebo, experimental local and referred pain was induced by intramuscular (i.m.) infusion of hypertonic saline (0.7 ml, 5%) into the tibialis anterior (TA) muscle. The saline-induced pain intensity was assessed on an electronic VAS, and the distribution of pain drawn by the subject. In addition, the pain threshold (PT) to i.m. electrical stimulation was determined for single stimulus and five repeated (2 Hz, temporal summation) stimuli. The pressure PT of the TA muscle was determined, and the pressure PT and pressure pain tolerance threshold were determined at three bilaterally located tenderpoints (knee, epicondyle, and mid upper trapezius). VAS scores of pain at rest were progressively reduced during ketamine infusion compared with placebo infusion. Pain intensity (area under the VAS curve) to the post-drug infusion of hypertonic saline was reduced by ketamine (-18.4▒0.3% of pre-drug VAS area) compared with placebo (29.9▒18.8%, P<0.02). Local and referred pain areas were reduced by ketamine (-12.0▒14.6% of pre-drug pain areas) compared with placebo (126.3▒83.2%, P<0.03). Ketamine had no significant effect on the PT to single i.m. electrical stimulation. However, the span between the PT to single and repeated i.m. stimuli was significantly decreased by the ketamine (-42.3▒15.0% of pre-drug PT) compared with placebo (50.5▒49.2%, P<0.03) indicating a predominant effect on temporal summation. Mean pressure pain tolerance from the three paired tenderpoints was increased by ketamine (16.6▒6.2% of pre-drug thresholds) compared with placebo (-2.3▒4.9%, P<0.009). The pressure PT at the TA muscle was increased after ketamine (42.4▒9.2% of pre-drug PT) compared with placebo (7.0▒6.6%, P<0.011). The present study showed that mechanisms involved in referred pain, temporal summation, muscular hyperalgesia, and muscle pain at rest were attenuated by the NMDA-antagonist in FMS patients. It suggested a link between central hyperexcitability and the mechanisms for facilitated referred pain and temporal summation in a sub-group of the fibromyalgia syndrome patients. Whether this is specific for FMS patients or a general phenomena in painful musculoskeletal disorders is not known. Copyright (C) 2000 International Association for the Study of Pain. Published by Elsevier Science B.V.
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