The effects of fasting for 7 days were investigated in 13 patients with rheumatoid arthritis (RA)... more The effects of fasting for 7 days were investigated in 13 patients with rheumatoid arthritis (RA) in comparison with a control regimen in a cross-over trial. The effects of fasting on clinical performance and blood neutrophil functions were studied. During fasting, with a mean weight loss of 5.1 kg, clinical inflammation in the joints and the erythrocyte sedimentation rate (ESR)
Total parentenal nutrition (TPN) has been associated with an increased incidence of infection. To... more Total parentenal nutrition (TPN) has been associated with an increased incidence of infection. To assess the hypothesis that TPN, and in particular one of its constituents, the fat emulsion Intralipid, might impair host defense, we investigated in vitro migration, bactericidal functions, and chemiluminescence of the neutnophil granulocyte in four patients with Crohn's disease, given TPN for up to 12 wk.
Scandinavian Journal of Clinical & Laboratory Investigation, 2002
ABSTRACT Endometrial regrowth is associated with intense angiogenesis, for which vascular endothe... more ABSTRACT Endometrial regrowth is associated with intense angiogenesis, for which vascular endothelial growth factor-A (VEGF-A) is an important regulator. However, the expression of other members of the VEGF family is less well documented. The aim of this study was to localize members of the VEGF family (VEGF-A, -B and -C), and their receptors (VEGFR1, 2 and 3) in human endometrial blood vessels. Endometrial biopsies collected from four healthy and fertile women were used for immunohistochemistry assessments. Co-localization of VEGF-family proteins with CD34 stained endothelial structures was determined by image analysis. We demonstrate here the marked expression of VEGF-A as well as VEGFR2 and 3 in capillaries. Arterioles expressed VEGF-B, VEGFR1, 2, and 3 moderately and VEGF-A variably. Venules expressed only VEGFR3 markedly. In contrast, VEGF-C was not expressed in the arterioles, but moderately in the capillaries and weakly in the venules. VEGF-B was expressed in all blood vessels; however, VEGF-B was weakly expressed in capillaries and arterioles and moderately expressed in venules and arterioles. Thus, expression of VEGF-A. B and C and VEGF receptors 1-3 in endometrial blood vessels indicates a highly structured involvement of VEGF in the regulation of angiogenesis in the human endometrium.
Medical oncology (Northwood, London, England), 2002
We conducted a nonrandomized prospective phase II study of thalidomide in anemic patients with my... more We conducted a nonrandomized prospective phase II study of thalidomide in anemic patients with myelofibrosis with myeloid metaplasia (MMM), with or without preceding polycythemia vera or essential thrombocythemia, with a primary aim to improve anemia. Thalidomide was given in escalating doses with a target dose of 800 mg daily, but the median dose of thalidomide that was actually tolerated was 400 mg daily. Fifteen patients were entered into the study and 14 were evaluable for response. Five of 14 (36%) patients discontinued thalidomide before 3 mo because of side effects, and none of these five patients had a response at the time when thalidomide was stopped. When evaluated after 3 mo of therapy, none of the remaining nine patients exhibited a discernible clinical response. Three patients showed progressive disease defined as > 50% increase in the need for red cell transfusions. Treatment was poorly tolerated, with all patients reporting side effects of thalidomide, the most pro...
The superoxide-forming nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase of hum... more The superoxide-forming nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase of human phagocytes comprises membrane-bound and cytosolic proteins, which, upon cell activation, assemble on the plasma membrane to form the active enzyme. Patients with chronic granulomatous disease (CGD) are defective in one of the phagocyte oxidase (phox) components, p47-phox or p67-phox, which reside in the cytosol of resting phagocytes, or gp91-phox or p22-phox, which constitute the membrane-bound cytochrome b(558). In four X-linked CGD patients we have identified novel missense mutations in CYBB, the gene encoding gp91-phox. These mutations were associated with normal amounts of nonfunctional cytochrome b(558) in the patients' neutrophils. In phorbol-myristate-stimulated neutrophils and in a cell-free translocation assay with neutrophil membranes and cytosol, the association of p47-phox and p67-phox with the membrane fraction of the cells with Cys369-->Arg, Gly408-->Glu, and G...
... Drug-Induced Neutropenia-A Survey for Stockholm 1973-1978 Per Arneborn and Jan Palmblad From ... more ... Drug-Induced Neutropenia-A Survey for Stockholm 1973-1978 Per Arneborn and Jan Palmblad From the Department of Infectious Diseases, Roslugstull's Hospital, and Department of Medicine IV, Siidersjukhuset, Stockholm, Sweden ... In earlier Arta Med Scand 212 Page 4. ...
We studied the effects of leukotrienes on in vitro functions of neutrophil polymorphonuclear (PMN... more We studied the effects of leukotrienes on in vitro functions of neutrophil polymorphonuclear (PMN) granulocytes. Leukotriene B4 (LTB4) evoked a stimulated and directed migration of neutrophils under agarose with an optimum concentration of 10(-6)M, whereas two nonenzymatically formed isomers (compounds I and II) induced this response at 10(-5)M. Leukotriene C4 (LTC4) and 5-hydroxyeicosate-traenoic acid (5-HETE) did not affect this PMN migration. At the same optimum concentrations, LTB4 and compounds I and II augmented PMN adherence to nylon fibers. The chemotactic and adherence responses were of the same magnitude as with formal-Met-Leu-Phe (fMLP) at 10(-7)M. None of the leukotrienes influenced the spontaneous or phagocytosis-associated chemiluminescence or the ability to kill Staphylococcus aures. The cyclooxygenase inhibitor, indomethacin, inhibited only partly the fMLP-induced migration at high concentrations and stimulated migration at 2.5 x 10(-7)M, suggesting that arachidonic ...
77 unselected adult patients with acute myeloblastic leukaemia (AML), including practically all A... more 77 unselected adult patients with acute myeloblastic leukaemia (AML), including practically all AML patients from an area with 1.9 million inhabitants, were randomized for either (1) 5 days pretreatment with 1-asparaginase and prednisolone followed by a combination of rubidomycin and cytosine arabinoside (ARAP), or (2) treatment with a combination of rubidomycin, cytosine arabinoside and prednisolone without 1-asparaginase pretreatment (RAP). Complete remission was induced with ARAP in 12 patients (31%) and with RAP in 13 patients (34%). Thus pretreatment with 1-asparaginase did not improve the therapeutic response. The overall remission frequency was significantly higher below the age of 60; 50% compared to 13% above this age. Side-effects such as liver dysfunction, nausea and vomiting were more common in patients pretreated with 1-asparaginase. Sterilization of the gut did not improve the remission frequency with either regime.
A case of visceral leishmaniasis is presented, where a pre-existing polycythemia vera obscured si... more A case of visceral leishmaniasis is presented, where a pre-existing polycythemia vera obscured signs of the infection.
We have studied effects of two partially purified human leukocyte (alpha) interferon (IFN) prepar... more We have studied effects of two partially purified human leukocyte (alpha) interferon (IFN) preparations (PIF-A and PIF-B) and a highly purified fibroblast (beta) IFN on the functional activity of normal human neutrophils (PMNs). In vitro, PIF-B conferred a significant and dose-dependent enhancement of chemiluminescence (CL) induced both by phagocytosis and a soluble stimulus, f-Met-Leu-Phe, and decreased killing of Staph. aureus. In contrast, PIF-A caused only a slight inhibition of bactericidal activity and had no effects on CL. beta-IFN had no effects on either bactericidal activity or CL. Migration under agarose was decreased with all of the IFN but phagocytosis and release of enzymes was not affected. PMNs from seven patients treated with PIF-A for multiple myeloma exhibited increased CL responses but no other PMN functions were affected. The findings that human IFN preparations affect PMN functions indicate that high-dose IFN therapy of immunocompromised patients should be carefully evaluated for the possibility of increased infectious complications.
The various clinical manifestations of the recently characterized immotile-cilia syndrome can be ... more The various clinical manifestations of the recently characterized immotile-cilia syndrome can be traced to one cause--a structural defect of the cilia, making them immotile. It was regarded of interest to examine whether other aspects of cell motility may also be involved. For this reason the functions and structure of the neutrophil leukocytes were examined. Cells from eight patients with the immotile-cilia syndrome and healthy controls were investigated with regard to random and stimulated locomotion under agarose, orientation during migration, adherence, bactericidal capacity, and chemoluminescence. Four patients showed abnormally short migration distances of the leading front neutrophils after stimulation with serum and/or an E. coli bacterial factor (BF). Ascorbic acid did not restore the defective migration. Migrating neutrophils were significantly less oriented towards the serum-containing agarose well compared with the controls (p < 0.01). Adherence, bactericidal capacity for Staphylococcus aureus, chemoluminescence, random migration, and orientation during BF-induced migration were all normal. The number of microtubules in the pericentriolar region of the neutrophil granulocytes was unusually low in four of the eight patients. We conclude that the increased frequency of respiratory tract infections in patients with this syndrome is possibly due to defects in the granulocyte locomotory system, as well as to the defective mucociliary clearance of the airways.
The effects of fasting for 7 days were investigated in 13 patients with rheumatoid arthritis (RA)... more The effects of fasting for 7 days were investigated in 13 patients with rheumatoid arthritis (RA) in comparison with a control regimen in a cross-over trial. The effects of fasting on clinical performance and blood neutrophil functions were studied. During fasting, with a mean weight loss of 5.1 kg, clinical inflammation in the joints and the erythrocyte sedimentation rate (ESR)
Total parentenal nutrition (TPN) has been associated with an increased incidence of infection. To... more Total parentenal nutrition (TPN) has been associated with an increased incidence of infection. To assess the hypothesis that TPN, and in particular one of its constituents, the fat emulsion Intralipid, might impair host defense, we investigated in vitro migration, bactericidal functions, and chemiluminescence of the neutnophil granulocyte in four patients with Crohn's disease, given TPN for up to 12 wk.
Scandinavian Journal of Clinical & Laboratory Investigation, 2002
ABSTRACT Endometrial regrowth is associated with intense angiogenesis, for which vascular endothe... more ABSTRACT Endometrial regrowth is associated with intense angiogenesis, for which vascular endothelial growth factor-A (VEGF-A) is an important regulator. However, the expression of other members of the VEGF family is less well documented. The aim of this study was to localize members of the VEGF family (VEGF-A, -B and -C), and their receptors (VEGFR1, 2 and 3) in human endometrial blood vessels. Endometrial biopsies collected from four healthy and fertile women were used for immunohistochemistry assessments. Co-localization of VEGF-family proteins with CD34 stained endothelial structures was determined by image analysis. We demonstrate here the marked expression of VEGF-A as well as VEGFR2 and 3 in capillaries. Arterioles expressed VEGF-B, VEGFR1, 2, and 3 moderately and VEGF-A variably. Venules expressed only VEGFR3 markedly. In contrast, VEGF-C was not expressed in the arterioles, but moderately in the capillaries and weakly in the venules. VEGF-B was expressed in all blood vessels; however, VEGF-B was weakly expressed in capillaries and arterioles and moderately expressed in venules and arterioles. Thus, expression of VEGF-A. B and C and VEGF receptors 1-3 in endometrial blood vessels indicates a highly structured involvement of VEGF in the regulation of angiogenesis in the human endometrium.
Medical oncology (Northwood, London, England), 2002
We conducted a nonrandomized prospective phase II study of thalidomide in anemic patients with my... more We conducted a nonrandomized prospective phase II study of thalidomide in anemic patients with myelofibrosis with myeloid metaplasia (MMM), with or without preceding polycythemia vera or essential thrombocythemia, with a primary aim to improve anemia. Thalidomide was given in escalating doses with a target dose of 800 mg daily, but the median dose of thalidomide that was actually tolerated was 400 mg daily. Fifteen patients were entered into the study and 14 were evaluable for response. Five of 14 (36%) patients discontinued thalidomide before 3 mo because of side effects, and none of these five patients had a response at the time when thalidomide was stopped. When evaluated after 3 mo of therapy, none of the remaining nine patients exhibited a discernible clinical response. Three patients showed progressive disease defined as > 50% increase in the need for red cell transfusions. Treatment was poorly tolerated, with all patients reporting side effects of thalidomide, the most pro...
The superoxide-forming nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase of hum... more The superoxide-forming nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase of human phagocytes comprises membrane-bound and cytosolic proteins, which, upon cell activation, assemble on the plasma membrane to form the active enzyme. Patients with chronic granulomatous disease (CGD) are defective in one of the phagocyte oxidase (phox) components, p47-phox or p67-phox, which reside in the cytosol of resting phagocytes, or gp91-phox or p22-phox, which constitute the membrane-bound cytochrome b(558). In four X-linked CGD patients we have identified novel missense mutations in CYBB, the gene encoding gp91-phox. These mutations were associated with normal amounts of nonfunctional cytochrome b(558) in the patients' neutrophils. In phorbol-myristate-stimulated neutrophils and in a cell-free translocation assay with neutrophil membranes and cytosol, the association of p47-phox and p67-phox with the membrane fraction of the cells with Cys369-->Arg, Gly408-->Glu, and G...
... Drug-Induced Neutropenia-A Survey for Stockholm 1973-1978 Per Arneborn and Jan Palmblad From ... more ... Drug-Induced Neutropenia-A Survey for Stockholm 1973-1978 Per Arneborn and Jan Palmblad From the Department of Infectious Diseases, Roslugstull's Hospital, and Department of Medicine IV, Siidersjukhuset, Stockholm, Sweden ... In earlier Arta Med Scand 212 Page 4. ...
We studied the effects of leukotrienes on in vitro functions of neutrophil polymorphonuclear (PMN... more We studied the effects of leukotrienes on in vitro functions of neutrophil polymorphonuclear (PMN) granulocytes. Leukotriene B4 (LTB4) evoked a stimulated and directed migration of neutrophils under agarose with an optimum concentration of 10(-6)M, whereas two nonenzymatically formed isomers (compounds I and II) induced this response at 10(-5)M. Leukotriene C4 (LTC4) and 5-hydroxyeicosate-traenoic acid (5-HETE) did not affect this PMN migration. At the same optimum concentrations, LTB4 and compounds I and II augmented PMN adherence to nylon fibers. The chemotactic and adherence responses were of the same magnitude as with formal-Met-Leu-Phe (fMLP) at 10(-7)M. None of the leukotrienes influenced the spontaneous or phagocytosis-associated chemiluminescence or the ability to kill Staphylococcus aures. The cyclooxygenase inhibitor, indomethacin, inhibited only partly the fMLP-induced migration at high concentrations and stimulated migration at 2.5 x 10(-7)M, suggesting that arachidonic ...
77 unselected adult patients with acute myeloblastic leukaemia (AML), including practically all A... more 77 unselected adult patients with acute myeloblastic leukaemia (AML), including practically all AML patients from an area with 1.9 million inhabitants, were randomized for either (1) 5 days pretreatment with 1-asparaginase and prednisolone followed by a combination of rubidomycin and cytosine arabinoside (ARAP), or (2) treatment with a combination of rubidomycin, cytosine arabinoside and prednisolone without 1-asparaginase pretreatment (RAP). Complete remission was induced with ARAP in 12 patients (31%) and with RAP in 13 patients (34%). Thus pretreatment with 1-asparaginase did not improve the therapeutic response. The overall remission frequency was significantly higher below the age of 60; 50% compared to 13% above this age. Side-effects such as liver dysfunction, nausea and vomiting were more common in patients pretreated with 1-asparaginase. Sterilization of the gut did not improve the remission frequency with either regime.
A case of visceral leishmaniasis is presented, where a pre-existing polycythemia vera obscured si... more A case of visceral leishmaniasis is presented, where a pre-existing polycythemia vera obscured signs of the infection.
We have studied effects of two partially purified human leukocyte (alpha) interferon (IFN) prepar... more We have studied effects of two partially purified human leukocyte (alpha) interferon (IFN) preparations (PIF-A and PIF-B) and a highly purified fibroblast (beta) IFN on the functional activity of normal human neutrophils (PMNs). In vitro, PIF-B conferred a significant and dose-dependent enhancement of chemiluminescence (CL) induced both by phagocytosis and a soluble stimulus, f-Met-Leu-Phe, and decreased killing of Staph. aureus. In contrast, PIF-A caused only a slight inhibition of bactericidal activity and had no effects on CL. beta-IFN had no effects on either bactericidal activity or CL. Migration under agarose was decreased with all of the IFN but phagocytosis and release of enzymes was not affected. PMNs from seven patients treated with PIF-A for multiple myeloma exhibited increased CL responses but no other PMN functions were affected. The findings that human IFN preparations affect PMN functions indicate that high-dose IFN therapy of immunocompromised patients should be carefully evaluated for the possibility of increased infectious complications.
The various clinical manifestations of the recently characterized immotile-cilia syndrome can be ... more The various clinical manifestations of the recently characterized immotile-cilia syndrome can be traced to one cause--a structural defect of the cilia, making them immotile. It was regarded of interest to examine whether other aspects of cell motility may also be involved. For this reason the functions and structure of the neutrophil leukocytes were examined. Cells from eight patients with the immotile-cilia syndrome and healthy controls were investigated with regard to random and stimulated locomotion under agarose, orientation during migration, adherence, bactericidal capacity, and chemoluminescence. Four patients showed abnormally short migration distances of the leading front neutrophils after stimulation with serum and/or an E. coli bacterial factor (BF). Ascorbic acid did not restore the defective migration. Migrating neutrophils were significantly less oriented towards the serum-containing agarose well compared with the controls (p < 0.01). Adherence, bactericidal capacity for Staphylococcus aureus, chemoluminescence, random migration, and orientation during BF-induced migration were all normal. The number of microtubules in the pericentriolar region of the neutrophil granulocytes was unusually low in four of the eight patients. We conclude that the increased frequency of respiratory tract infections in patients with this syndrome is possibly due to defects in the granulocyte locomotory system, as well as to the defective mucociliary clearance of the airways.
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