| 61. |
- Hellstrand, Kristoffer, 1956, et al.
(författare)
-
Histamine in immunotherapy of advanced melanoma: a pilot study.
- 1994
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Ingår i: Cancer immunology, immunotherapy : CII. - 0340-7004. ; 39:6, s. 416-9
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Tidskriftsartikel (refereegranskat)abstract
- Sixteen patients with advanced metastatic malignant melanoma were treated with a high-dose infusion of interleukin-2 (IL-2; 18 x 10(6) IU/m-2 day-1) together with daily subcutaneous (s.c.) injections of interferon alpha (IFN alpha; 3 x 10(6) U/m-2 day-1) in 5-day cycles. Nine of these patients were given histamine (1 mg s.c.) twice daily during treatment with IL-2 and IFN alpha. In the seven patients who did not receive histamine, one partial response (that is a reduction of more than 50% in the total tumour burden) was observed in a patient with skin and lymph node melanoma. In the eight histamine-treated patients evaluable for response, four partial responses were observed. Two other patients showed regression at one site of metastasis but tumours remained unchanged at other sites. Two histamine-treated patients showed complete resolution of extensive liver metastasis. Sites of response in histamine-treated patients also included the subcutis, lymph nodes, skeleton, spleen and muscle. Lung melanoma did not respond to histamine/IL-2/IFN alpha. Three patients with lung tumours responded with significant (more than 50%) reduction of the volume of soft-tissue tumours, suggesting that the response to histamine may be organotropic. Survival was significantly prolonged in patients receiving histamine. Our data suggest that treatment with histamine may improve the antitumour efficacy of immunotherapy in metastatic melanoma.
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| 62. |
- Hellstrand, Per, et al.
(författare)
-
Analysis of the length response to a force step in smooth muscle from rabbit urinary bladder
- 1979
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 106:2, s. 221-238
-
Tidskriftsartikel (refereegranskat)abstract
- Responses to isotonic quick release of AC-stimulated smooth muscle strips from rabbit urinary bladder were analysed. Releases were performed at the peak of contraction and at a preset tension level in the contraction and relaxation phase. In other expts. responses at 37 degrees C and 27 degrees C were compared. The length response always consisted of 3 parts: (1) elastic recoil, (2) rapid length change (isotonic transient), (3) steady length change. Qualitatively, phases (1)-(3) could be distinguished also in responses to isotonic quick stretch. The immediate elastic recoils, phase (1), were described by exponential stress-strain relations. Stiffness was found to be somewhat lower during relaxation than during contraction. No effect of temperature on the elastic recoil was seen. The initial velocity in phase (2) was 2-3 times greater than the velocity 100 ms after release. By means of computer analysis of the length records during phases (2) and (3) two decaying exponential processes with widely different time constants could be separated. The time constant of the faster process was of the order of 15-30 ms at 37 degrees C. It decreased with increasing force steps and with increasing temperature. The amount of shortening associated with this process was correlated with the size of the force step, reaching a maximum of about 1.2% of the muscle length. The shortening velocities in phase (3), measured 100 ms after release, were described by Hill's equation. Vmax in the rising part and at the peak of contraction were 0.7 and 0.6 L/s respectively at 37 degrees C. Lower values were found during relaxation and at 27 degrees C. We suggest that part of the elastic recoil in phase (1) occurs in structures associated with the individual cross-bridges, that phase (2) is dominated by a change in the distribution of conformations of bridges in the attached position and that the shortening rate in phase (3) is determined by the entire cycle of events during turnover of bridges after the muscle has adapted to the new load. Observations on the force response to length steps and on shifts from isometric to afterloaded isotonic contraction and vice versa are consistent with this interpretation.
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| 63. |
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| 64. |
- Hellstrand, Per
(författare)
-
Cross-bridge kinetics and shortening in smooth muscle
- 1994
-
Ingår i: Canadian Journal of Physiology and Pharmacology. - 0008-4212. ; 72:11, s. 1334-1337
-
Tidskriftsartikel (refereegranskat)abstract
- Stiffness measurements were performed on smooth muscle preparations from guinea-pig taenia coli to obtain information on the number of attached cross bridges under varying contractile conditions. The normalized stiffness of the cross-bridge system in smooth muscle may be of a magnitude similar to that assumed in skeletal muscle. Transition from isometric contraction to unloaded shortening was associated with a decrease in stiffness to 50% or less of the isometric value, slightly higher than that found in skeletal muscle fibers. Comparison of phasic (5 s) and tonic (5 min) contractions showed lower Vmax, intracellular [Ca2+], and myosin 20 kDa light chain phosphorylation at 5 min, indicating development of a latch state. Isometric force and stiffness were identical in the two types of contraction. However, stiffness during unloaded shortening was greater in the latch state, which may be the result of the presence of a population of cross bridges with a low rate constant for detachment.
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| 65. |
- Hellstrand, Per, et al.
(författare)
-
Cross-bridge kinetics during shortening in early and sustained contraction of intestinal smooth muscle
- 1993
-
Ingår i: American Journal of Physiology: Cell Physiology. - 1522-1563. ; 265:3 Pt 1, s. 695-703
-
Tidskriftsartikel (refereegranskat)abstract
- Mechanisms responsible for the decrease in shortening velocity after prolonged contraction ("latch" state) were investigated at identical force during early (20 s, "phasic") and sustained (5 min, "tonic") phases of high-K+ (25-30 mM) contractions in smooth muscle of guinea pig taenia coli. Cytoplasmic Ca2+ concentration, myosin light-chain phosphorylation, and maximum shortening velocity all declined from 20 s to 5 min of contraction. The time course of shortening following isotonic quick release was biexponential, with a fastest rate constant of approximately 80 s-1 in both phasic and tonic contractions. Stiffness was identical in phasic and tonic contraction; however, after a release to slack length and unloaded shortening, stiffness during restretch was greater in tonic contraction (51 vs. 43% of isometric stiffness after 16 ms of unloaded shortening). Stiffness decreased after release with a rate constant of approximately 200 s-1, slightly greater in phasic than in tonic contraction. The results indicate that the number of attached cross bridges during unloaded shortening, while substantially reduced relative to the isometric value, is higher in latch than in nonlatch, consistent with a lower detachment relative to attachment rate.
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| 66. |
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| 67. |
- Hellstrand, Per, et al.
(författare)
-
Effects of nine different gastrointestinal polypeptides on vascular smooth muscle in vitro
- 1980
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 110:1, s. 89-94
-
Tidskriftsartikel (refereegranskat)abstract
- Nine polypeptides of gastrointestinal origin were tested for their possible effect on vascular smooth muscle of the rat portal vein. The substances tested were bombesin, caerulein, glucagon, insulin, pentagastrin, secretin, somatostatin, substance P and vasoactive intestinal polypeptide (VIP). Cumulative dose-response relations of integrated mechanical activity (mean tension) were obtained with maximal concentrations of the various peptides of 1-10 microgram/ml. Within this concentration range, only substance P and VIP showed clearcut effects; substance P causing contraction and VIP relaxation. The dose of substance P needed to produce contraction was high (ED50 greater than 1 microM) so that the physiological importance of this response is doubtful. On the other hand, ED50 for the relaxing effect of VIP was about 15 nM, which is in accordance with concentrations reported to produce significant vasodilatation in vivo. The results support the view that vascular effects which have been reported to occur in response to the other 7 peptides are mainly of indirect origin and not mediated via direct action on vascular smooth muscle.
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| 68. |
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| 69. |
- Hellstrand, Per
(författare)
-
Long-term effects of intracellular calcium and growth factors on excitation and contraction in smooth muscle
- 1998
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 164:4, s. 637-644
-
Tidskriftsartikel (refereegranskat)abstract
- Modulation of vascular smooth muscle cells from a contractile to a synthetic phenotype is thought to be important in the development of the atherosclerotic lesion. Such modulation depends on growth factors and is influenced by cell-cell and cell-matrix interactions. Whereas smooth muscle cells in the vessel wall are contractile, dispersed cells in culture rapidly modulate to synthetic phenotype, which complicates long-term in vitro studies. In contrast, vascular segments or smooth muscle strips in organ culture can maintain contractility for at least a week, sufficient for studies involving altered metabolism or protein expression. Examples are effects of endogenous polyamines on membrane ion channels and excitation-contraction coupling. While smooth muscle tissue is well preserved in serum-free culture, growth stimulation with fetal calf serum (FCS) causes multiple effects, including decreased contractility, ultrastructural changes, decreased expression of L-type Ca2+ channels, and increased SR release of Ca2+ via ryanodine receptors. These are all consequences of increased basal [Ca2+]i caused by FCS, as they are reversed by culture with verapamil in a concentration (1 microM) that does not inhibit stimulation of DNA and protein synthesis by FCS. The effects of FCS on contractility and Ca2+ channel expression are mimicked in serum-free culture with increased [Ca2+]i. Contractile protein patterns, including myosin isoform composition, are unaffected by FCS, suggesting that reversal to synthetic phenotype is limited and not the immediate cause of decreased contractility.
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| 70. |
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