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A Jakobsson

Publications and source records attributed to A Jakobsson.

At least 19 recordsLinked to original sources
PubMed1994

Mast-cell histamine is angiogenic through receptors for histamine1 and histamine2.

The activation of mast-cells in situ induces angiogenesis in normally vascularized, adult mammalian tissue. Since the secreting mast-cell characteristically releases histamine, we studied the possible role of histamine in the outcome of mast-cell mediated angiogenesis using the rat mesenteric window assay. One H1-receptor antagonist, brompheniramine maleate (BPA), and one H2-receptor antagonist, metiamide, were separately administered systemically (s.c.) at non-toxic doses during the period of angiogenesis induction. Angiogenesis was effected by i.p. injections of the mast-cell secretagogue compound 48/80 for 5 consecutive days. The animals were killed 14 days after the start of the i.p. and s.c. treatment, close to the middle of the expanding angiogenic phase of the angiogenic reaction studied. Angiogenesis was quantified in terms of (a) the number of vessel profiles per unit tissue length (No/UL), which reflects mainly the degree of branching and/or tortuosity, (b) the relative vascularized area (VA), which is a measure of spatial extension, and (c) the vascular density (VD), a measure of vessel density per unit area of vascularized tissue. Whereas BPA significantly suppressed No/UL, metiamide significantly reduced No/UL and VD in statistical terms suggesting that endogenous mast-cell histamine is angiogenic through both H1- and H2-receptors. This appears to be the first paper to report that the occupancy of H2-receptors is angiogenic.

Animals↗
PubMed1994

Endotoxin is angiogenic.

The formation of new blood vessels, angiogenesis, is an important event in inflammation, wound healing and tumour growth. Mediators produced by various cells when exposed to endotoxin include cytokines (tumour necrosis factor, interleukins 1 and 6, and basic fibroblast growth factor) which, it has been suggested, stimulate angiogenesis. The angiogenic effect of endotoxin (lipopolysaccharide, LPS) was studied in rats using the quantitative mesenteric window assay. Adult rats were injected intraperitoneally with Escherichia coli LPS (5 pg/ml-20,000 ng/ml) twice daily for 4.5 consecutive days and were sacrificed 14 days after the start of this treatment. An angiogenic response was observed at concentrations of > 2 ng/ml in a dose-dependent manner. No inflammatory cellular exudate was seen in the test tissue at the time of angiogenesis analysis. Suppressed body-weight gain, a marker of the systemic effect of LPS in the rat, was significant only at the highest dose tested. The data suggest that endotoxin-mediated neovascularization could be a component of inflammation and wound healing.

Animals↗
PubMed1993

Two potentially angiostatic factors, a steroid and L-azetidine-2-carboxylic acid, antagonize one another.

The proline analogue L-azetidine-2-carboxylic acid (LACA) systemically suppressed mast-cell-mediated angiogenesis, as measured by the rat mesenteric-window method. Dexamethasone and methylprednisolone at very low and non-toxic s.c. doses also somewhat inhibited the angiogenesis. Most interestingly, the co-administration of either of these steroids with LACA paradoxically stimulated angiogenesis. These findings suggest that in the future search for candidates for clinically-useful systemic angiostatic remedies, one may have to focus not only on the effect of individual drugs or agents, but also on the effect of such putative anti-angiogenic agents when co-administered. The fact that two potentially angiostatic agents can antagonize one another has not previously been reported.

Animals↗
PubMed1992

Characteristics of the 'metabolic syndrome X' in a cardiovascular low risk population in Crete.

We have studied hypertension, obesity, diabetes and hypercholesterolaemia in those aged 45-79 years in the Cretan low risk population of Spili (n = 249; attendance 82%) to see if these conditions interacted in the same way as previously described for high risk populations. Hypertension, diabetes, obesity, and hypercholesterolaemia were found to be at least as prevalent in Spili as in Sweden. Furthermore, the previously described 'Metabolic Syndrome X', with insulin resistance and hyperinsulinaemia as a common denominator also seemed to exist in the Spili population where patients with these conditions had higher insulin and C-peptide levels than normals. Our finding should be viewed against the low prevalence of past myocardial infarction in Cretan men from Spili reported by us and confirming the results of the Seven Countries Study.

Aged↗
PubMed1991

Regeneration of CALLA (CD10+), TdT+ and double-positive cells in the bone marrow and blood after autologous bone marrow transplantation.

In this prospective study we investigated the frequency of CD10+, TdT+ and CD10+TdT+ mononuclear cells in the bone marrow (BM) and peripheral blood (PB) before and after autologous bone marrow transplantation (ABMT). 49 patients treated for acute lymphoblastic or myeloblastic leukaemia, malignant lymphoma or multiple myeloma were included. A significant increase in CD10+ cells occurred in BM in both children and adults after ABMT. In children, we also found a significant increase in CD10+ cells in PB. In individual patients remaining in remission, up to 34% CD10+ cells having a normal Ig kappa/lambda light chain ratio were recorded after ABMT. In children, the percentage of TdT+ and CD10+ TdT+ cells increased significantly in BM. In most cases the CD10/TdT-ratio was greater than 1.0, but during early regeneration after ABMT this ratio was less than 1.0 in several patients remaining in complete remission. In patients remaining in remission, CD10+TdT+ cells were detected in the blood in only 2 out of 140 samples tested, and the proportion of these cells never exceeded 0.03%. We conclude that quantitation of CD10+TdT+ cells in peripheral blood is helpful in the evaluation of complete remission in patients treated for pre-B-ALL.

Adult↗
PubMed1991

Influence of fibre diameter and probe geometry on the measuring depth of laser Doppler flowmetry in the gastrointestinal application.

The measuring depth of laser Doppler flowmetry (LDF) was studied in isolated segments of feline small intestine, using five probes having different fibre geometry, fibre core diameter and fibre centre separation. Recordings were made on the mucosal side at constant systemic blood pressure and venous outflow from the bowel segment. The insertion of a layer of unperfused intestine (average thickness 2.4 mm), between the probe and the perfused bowel wall, reduced the output signal from the flowmeter to an average of 42% of the initial value when a probe with large diameter fibres (700 microns) was used. No LD-signal was obtained through the unperfused tissue layer using the probes with small core diameter fibres (120 microns). Application of a mirror at the serosal surface opposite to the probe, resulted in an average increase of the output signal by 50% using the large fibre diameter probe, whereas no increase was observed with the small fibre probe. Probes based on intermediate fibre diameter and fibre centre separations, gave intermediate results in both experiments. It is concluded that the measuring depth of laser Doppler flowmetry in the gastrointestinal application is highly dependent on the fibre diameter and geometry of the probe. It is possible that, by taking into account these factors, probes may be constructed that are suitable for superficial and transmural measurements.

Animals↗
PubMed1990

Metabolism of fatty acids and their incorporation into phospholipids of the mitochondria and endoplasmic reticulum in isolated hepatocytes determined by isolation of fluorescence derivatives.

Isolated hepatocytes were incubated in the presence of [14C]palmitic, [14C]linoleic or [14C]linolenic acid and the time-courses of incorporation of radioactivity into phosphatidylcholine and phosphatidylethanolamine of microsomes and mitochondria were followed. For this purpose a procedure was developed for HPLC separation of 9-diazomethylanthracene (ADAM) derivatives of fatty acids. When [14C]palmitic acid was used, the major product of elongation and desaturation was octadecadienoic acid, which accounted for 35-65% of the total radioactivity. Labeled palmitoleic, stearic and oleic acids could also be isolated. In fatty acids which do not participate to any large extent in deacylation-reacylation reactions, the pattern of incorporation was characteristic: a high rate of incorporation into microsomal and a low rate of incorporation into mitochondrial phospholipids during the first 40 min, followed by a decrease in the former and an increase in mitochondrial labeling. This pattern is consistent with the fact that de novo synthesis of these two phospholipids occurs in the endoplasmic reticulum in vivo. When cells were incubated in the presence of [14C]linoleic acid, 70-90% of the radioactivity recovered in phospholipids was in this same form, whereas the remaining label was mainly in arachidonic acid and, to some extent, in eicosatrienoic acid. When hepatocytes were incubated in the presence of [14C]linolenic acid, 70-85% of the radioactivity in isolated phospholipids was associated with linolenic acid. As much as 20% of the label was recovered in docosahexanoic acid and 5-10% in arachidonic acid. In the case of the two latter labeled substrates the exchange reactions seem to dominate over de novo synthesis. For phospholipids synthesized de novo the transfer from the endoplasmic reticulum to mitochondria requires about 3 h.

Animals↗
PubMed1990

Increased angiogenesis in diabetes.

Rats with streptozotocin-induced diabetes mellitus showed a 3.4-4.5 times increased angiogenic response following mast-cell activation in situ as compared with age-matched normal controls. The test tissue used was the mesenteric window, which we have previously exploited as a quantitative angiogenesis assay. In the present study two independent techniques for quantifying the angiogenic response showed essentially the same result. The finding of a pathologically increased angiogenic reaction in the diabetic animals is noteworthy since some of the most harmful complications of diabetes in man relate to proliferative vascular lesions.

Animals↗
PubMed1990

On mast-cell-mediated angiogenesis in the rat mesenteric-window assay.

Testosterone propionate injected s.c. significantly reduced the mast-cell mediated angiogenic response occurring in prepubescent rats, thereby indicating that this angiogenic reaction can be influenced by hormonal stimuli. Since the newly-formed vessels are very small, one could expect that microscopic examination would be needed to quantify the vasculature. When studying the discernment of vessels at optical magnifications of between x 100 and x 1000 in sections of methacrylate-embedded mesenteric window, we found that the number of discernible vessels increased dramatically as the magnification increased. This not only underlines the genuine microvascular character of the reaction but also demonstrates the need for high-power magnification when truly quantifying an angiogenic reaction by optical means.

Animals↗
PubMed1990

Quantitative angiogenesis in spreads of intact rat mesenteric windows.

By introducing a new mode of the recently described mesenteric-window angiogenesis assay (K. Norrby, A. Jakobsson, and J. Sörbo, 1986, Virchows Arch. B. Cell Pathol. 52, 195-206) we measured the entire vascular tree in terms of the vascularized area and the vascular density in spreads of intact mesenteric windows in rats receiving a terminal iv infusion of an ink-gelatin solution to visualize the vessels. Adult and prepubescent rats given ip injections of the mast-cell secretagogue Compound 48/80 or the saline vehicle, as well as untreated litter mates, were used. Following mast-cell activation, both prepubescent and adult rats showed a significant angiogenesis taken as the vascularized area and the vascular density in spreads compared with those of the vehicle-treated animals. In fact the 48/80-treatment increased the vasculature 100-fold compared with the untreated controls. The finding of experimentally induced angiogenesis occurring in rats of all ages should make the assay useful in a wide range of angiogenesis experiments.

Aging↗
PubMed1990

Protamine and mast-cell-mediated angiogenesis in the rat.

Different doses of protamine sulphate (PS) given s.c. (at 12-h intervals) were tested for signs of non-specific toxicity measured as effect on body weight and small-gut proliferation as well as on mast-cell secretion and mast-cell-mediated mitogenesis in the mesenteric windows following i.p. injection of Compound 48/80, a potent mast cell secretagogue, in normal rats. In a non-toxic dose range, the effect of PS on mast-cell-mediated angiogenesis, effected by 48/80, was quantified as the number of vessels per mm of mesenteric window in histological sections at x 400. No intelligible dose-effect relationship was discernible between the dose of PS given and the effect on angiogenesis. Only in a tight interval, at 40 mg PS/kg but not at 20 or 60 mg PS/kg, was the angiogenesis statistically significantly suppressed. Hence, it was concluded that PS can be angiostatic but does not exert a more general angiostatic effect in the autogenous systems used.

Animals↗
PubMed1989

Uptake and modification of dietary polyprenols and dolichols in rat liver.

Short and long dolichols and polyprenols in free form or esterified with fatty acids were incorporated into liposomes and administered to rats through a gastric tube. The free alcohols were taken up by the liver to different extents. While uptake in other organs was less, it also involved the fatty acid esters. The use of systems other than liposomes did not increase the efficiency of uptake. Most of the administered lipids were recovered in the lysosomes. Exogenous dolichols and polyprenols were both partly esterified in the liver and, to some extent, also phosphorylated; a portion of the polyprenols was also alpha-saturated. These results indicate that various polyisoprenes are taken up, to a small extent, from the diet by tissues under normal conditions and in liver these dietary lipids undergo terminal modifications.

Animals↗
PubMed1989

Mast-cell secretion and angiogenesis, a quantitative study in rats and mice.

The activation of the autogenous mast cells (MCs) in situ in intact mesenterial windows was elicited by the intraperitoneal injection of the MC secretagogue Compound 48/80 over a period of 1, 3 and 5 days in Sprague-Dawley rats and in C57 BL/6 and CBA/Ca mice. As a probe of MC secretion, the release of histamine was quantified fluorometrically at predetermined intervals during the treatment. Fourteen days after the start of the treatment, the angiogenic response was quantified histologically as the number of vessel profiles per unit length of mesenteric window. Both the MC-activating and the angiogenic effect of the 48/80-treatment was greater in the rats than in the mice. The occurrence of MC-mediated angiogenesis in the mouse is demonstrated here for the first time. In the rat, 48/80-induced MC mediated angiogenesis increased in a distinctly dose-dependent manner. Two daily doses of 48/80 was the most efficient angiogenic protocol tested; a single day's treatment increased the number of vessels almost fivefold. The remarkable potency of the angiogenic reaction following MC secretion supports our previous notion that MC-mediated angiogenesis may have therapeutic implications in poorly vascularized tissues.

Animals↗
PubMed1989

On the consistency of ECG reports from two different computer-based ECG recorders.

Four consecutive computer-based ECG recordings/interpretations were made on each of 100 patients. Two of the recordings were made with the MAC II recorder (Marquette Electronics Inc., Milwaukee, USA) and two with the Cardisuny IC503FA (Fukuda M-E Kogyo Co. Ltd, Tokyo, Japan). Computer measurements of PQ interval, Q-width in III, R-amplitude in V5 and QRS axis in the frontal plane were compared between recordings, as also were diagnostic statements pertaining to the presence of atrial fibrillation and myocardial infarction. The MAC II was found to be more consistent than the Cardisuny as regards the measurements. There was a tendency that the MAC II was more specific than the Cardisuny and the Cardisuny more sensitive than the MAC II. The MAC II gave no false positive reports of atrial fibrillation and only one false positive report of myocardial infarction.

Atrial Fibrillation↗
PubMed1988

Age-dependent mast-cell-mediated angiogenesis.

In maturing male rats of approximately 5.5,10.5, and 15 weeks of age (groups I, II, and III), the mast-cell-mediated angiogenesis in the mesenterial windows was quantitatively assessed on days 14,21,28, and 35 after the start of intraperitoneal treatment using the mast-cell secretagogue 48/80, and using the saline vehicle. The number of blood vessels per unit length of the central part of the mesenterial window was virtually unaffected by age as well as by the saline treatment. The number of vessels at the mesenterial-window circumference was, however, increased in the older, untreated animals. The postpubescent animals in groups II and III showed a marked mast-cell-mediated angiogenic response lasting until day 28. The relative angiogenic response over the period of 14-28 days clearly increased with advancing age. The highest mean value in group II was about 8 times (p less than 0.001), whereas the highest mean value observed in group III was about 24 times (p less than 0.001) greater than in corresponding saline-treated controls. In contrast, no statistically significant mast-cell-mediated angiogenesis appeared in the prepubescent rats of group I.

Aging↗
PubMed1988

The lipid composition of highly differentiated human hepatomas, with special reference to fatty acids.

The lipid compositions of homogenates and microsomal fractions derived from surgical samples of highly differentiated human hepatoma, morphologically normal regions outside the tumours and from normal livers were analysed. A few enzyme activities were also assayed. Hepatoma microsomes demonstrated considerably lowered levels of cytochromes P-450 and b5. Hepatoma homogenates exhibited increased levels of cholesterol, normal amounts of dolichyl-P and slightly lowered levels of total phospholipid. The levels of dolichol, dolichol ester and ubiquinone in hepatoma homogenates were prominently decreased. In tumour microsomes the levels of cholesterol and dolichyl phosphate were increased considerably while the levels of phospholipid and dolichol were lowered. The phospholipid composition of tumour homogenates was roughly similar to that of control tissue. In tumour microsomes the relative amounts of phosphatidylserine and phosphatidylinositol were about 30% decreased, whereas the major phospholipids showed minor increases in amount. The rate and pattern of incorporation of [3H]glycerol into individual phospholipids in liver slices from control and hepatoma tissue did not differ to any larger extent. The fatty acid composition of tumour homogenates exhibited minor differences in comparison to the control with the greatest changes in the sphingomyelin fraction. In hepatoma microsomes the fatty acid compositions of the major phospholipids were altered moderately, with evident decreases in the relative amounts of the long-chain polyunsaturated fatty acids. In hepatoma homogenates the fatty acid composition of dolichol esters differed only slightly from the control pattern. These results indicate that the major disturbance in the lipid metabolism of highly differentiated hepatomas is localized to the mevalonate pathway, thus affecting mainly the levels of cholesterol, dolichol and ubiquinone.

Carcinoma, Hepatocellular↗
PubMed1988

Functional recovery after fractures of the distal forearm. Analysis of radiographic and other factors affecting the outcome.

Functional recovery of the wrist and hand after a fracture of the distal forearm in 207 consecutive patients was analysed. A good or excellent result was achieved in 77 percent, fair in 22.5 percent and poor in 0.5 percent of cases. The result in 14 unstable fractures treated with external fixation was as good as that of the whole series. Good functional results were associated with extra-articular fractures, good anatomical results, male sex and low age. Comminuted intra-articular fractures of the radiocarpal joint, fracture line into the distal radio-ulnar joint, fracture of the ulnar styloid and a poor anatomical result in addition to high age contributed to a poor result.

Adolescent↗